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Bringing HCC Patients Hope Through Trials, Advanced Treatments
For Reena Salgia, MD, the most rewarding part about working with patients with hepatocellular carcinoma is being there for their entire journey, thanks to advancements in treatment. “It brings a smile to my face just to think about it,” says Dr. Salgia, medical director of Henry Ford Health’s Liver Cancer Clinic in Detroit.
Hepatocellular carcinoma accounts for 80% of all liver cancer. When she first entered the field, Dr. Salgia often heard that survival rates 5 years after diagnosis were less than 10%. Over the last decade however, “I’ve seen an expansion in the procedural options that we offer these patients. We have an array of options both surgically as well as procedurally,” she said.
Especially over the last three to four years, “we’ve seen meaningful responses for patients with medications that we previously didn’t have in our toolbox. That’s really been exciting, along with continued involvement in clinical trials and being able to offer patients a number of different approaches to their care of liver cancer,” said Dr. Salgia.
A regular attendee and presenter at national GI meetings, Dr. Salgia participated in AGA’s Women’s Executive Leadership Conference in 2023. Her academic resume includes a long list of clinical trials to assess treatments for patients at different stages of hepatocellular carcinoma.
In an interview, she discussed the highlights of her career as a researcher and mentor of fellows, and how she guides and supports her transplant patients.
What drove you to pursue the field of hepatology and transplant hepatology?
I came across this field during my fourth year of medical school. I didn’t know anything about hepatology when I reached that stage and had the opportunity to do an elective. I just fell in love with the specialty. I liked the complex pathophysiology of liver disease, the long-term follow-up and care of patients. It appealed to the type of science that I had enjoyed back in college.
As I went into my GI fellowship training, I got to learn more about the field of transplant medicine. For instance, how you can take these patients who are incredibly ill, really at a very vulnerable point of their illness, and then offer them great hope and see their lives turn around afterwards. When I had the opportunity to see patients go from end stage liver disease to such significant improvement in their quality of life, and restoring their physical functioning beyond what we would’ve ever imagined when they were ill, it reaffirmed my interest in both hepatology as well as in transplant medicine.
How do you help those patients waiting on transplant lists for a liver?
We are intimately involved in their care all the way through their journey with liver disease, up until the time of physically getting the liver transplant, which is performed by our colleagues in transplant surgery. From the time they are transplanted, we are involved in their inpatient and outpatient post-transplant care. We’ve helped to get them on the transplant list with the work of the multidisciplinary team. If there are opportunities to help them understand their position on the list or obtaining exceptions—though that is done in a very objective fashion through the regulatory system—we help to guide them through that journey.
You’ve worked on many studies that involve treatments for hepatocellular carcinoma. Can you highlight a paper that yielded clinically significant benefits?
What really stands out the most to me was our site’s involvement in the IMbrave150 trial, which was published in 2020. This multicenter study made a big difference in the outcomes and treatments for patients, as it brought the adoption of first-line immunotherapy (atezolizumab plus bevacizumab) for patients with advanced hepatocellular carcinoma. I remember vividly the patients we had the opportunity to enroll in that trial – some who we continue to care for today. This stands out as one of the trials that I was involved in that had a lasting impact.
What were the clinical endpoints and key results of that trial?
The endpoint was to see an improvement in overall survival utilizing immunotherapy, compared with the prior standard of care then available, oral therapy. The results led to the adoption and FDA approval of immunotherapy in the first line setting for advanced unresectable hepatocellular carcinoma patients.
What are some of the highlights of serving as director of Henry Ford’s fellowship program?
Education is my passion. I went into medical training feeling that at some point I would love to blend in teaching in a formal role. Becoming program director of the gastroenterology and hepatology fellowship at Henry Ford in 2018 was one of the most meaningful things that I’ve had the opportunity to do in my career. I get to see trainees who are at a very impressionable point of their journey go on to become gastroenterologists and then launch into their first job and really develop in this field. Seeing them come in day one, not knowing how to hold a scope or do a procedure on a patient of this nature, then quickly evolve over the first year and grow over three years to achieve this specialty training [is rewarding]. I’ve learned a lot from the fellows along the way. I think of them as an extension of my family. We have 15 fellows currently in our program and we’ll be growing this summer. So that’s really been a highlight of my career thus far.
What fears did you have to push past to get to where you are in your career?
I think that there have been a few. One is certainly the fear of making the wrong choice with your first career opportunity. I did choose to leave my comfort zone from where I had done my training. I met that with some fear, but also excitement for new opportunities of personal and professional growth.
Another fear is: Am I going to be able to be ambitious in this field? Can I pursue research, become a program director, and do things that my role models and mentors were able to achieve? There’s also the fear of being able to balance a busy work life with a busy home life and figuring out how to do both well and minimize the guilt on both sides. I have a family with two girls. They are definitely a top priority.
What teacher or mentor had the greatest impact on you?
Helen Te, MD, a hepatologist at the University of Chicago. When I was a medical student there, I had the opportunity to work with her and saw her passion for this field. She really had so much enthusiasm for teaching and was a big part of why I started to fall in love with liver disease.
Karen Kim, MD, now the dean of Penn State College of Medicine, was one of my assigned mentors as a medical student. She helped me explore the fields where there were opportunities for residency and helped me make the decision to go into internal medicine, which often is a key deciding point for medical students. She was also a very influential teacher. The other individual who stands out is my fellowship program director, Hari Sree Conjeevaram, MD, MSc, at University of Michigan Health. He exhibited the qualities as an educator and program director that helped me recognize that education was something that I wanted to pursue in a formal fashion once I moved on in my career.
Describe how you would spend a free Saturday afternoon.
Likely taking a hike or go to a park with my family, enjoying the outdoors and spending time with them.
Lightning Round
If you weren’t a gastroenterologist, what would you be?
Philanthropist
Favorite city in U.S. besides the one you live in?
Chicago
Place you most want to travel?
New Zealand
Favorite breakfast?
Avocado toast
Favorite ice cream flavor?
Cookies and cream
How many cups of coffee do you drink per day?
Two…or more
Cat person or dog person?
Dog
Texting or talking?
Talk
Favorite season?
Autumn
Favorite type of music?
Pop
Favorite movie genre?
Action
For Reena Salgia, MD, the most rewarding part about working with patients with hepatocellular carcinoma is being there for their entire journey, thanks to advancements in treatment. “It brings a smile to my face just to think about it,” says Dr. Salgia, medical director of Henry Ford Health’s Liver Cancer Clinic in Detroit.
Hepatocellular carcinoma accounts for 80% of all liver cancer. When she first entered the field, Dr. Salgia often heard that survival rates 5 years after diagnosis were less than 10%. Over the last decade however, “I’ve seen an expansion in the procedural options that we offer these patients. We have an array of options both surgically as well as procedurally,” she said.
Especially over the last three to four years, “we’ve seen meaningful responses for patients with medications that we previously didn’t have in our toolbox. That’s really been exciting, along with continued involvement in clinical trials and being able to offer patients a number of different approaches to their care of liver cancer,” said Dr. Salgia.
A regular attendee and presenter at national GI meetings, Dr. Salgia participated in AGA’s Women’s Executive Leadership Conference in 2023. Her academic resume includes a long list of clinical trials to assess treatments for patients at different stages of hepatocellular carcinoma.
In an interview, she discussed the highlights of her career as a researcher and mentor of fellows, and how she guides and supports her transplant patients.
What drove you to pursue the field of hepatology and transplant hepatology?
I came across this field during my fourth year of medical school. I didn’t know anything about hepatology when I reached that stage and had the opportunity to do an elective. I just fell in love with the specialty. I liked the complex pathophysiology of liver disease, the long-term follow-up and care of patients. It appealed to the type of science that I had enjoyed back in college.
As I went into my GI fellowship training, I got to learn more about the field of transplant medicine. For instance, how you can take these patients who are incredibly ill, really at a very vulnerable point of their illness, and then offer them great hope and see their lives turn around afterwards. When I had the opportunity to see patients go from end stage liver disease to such significant improvement in their quality of life, and restoring their physical functioning beyond what we would’ve ever imagined when they were ill, it reaffirmed my interest in both hepatology as well as in transplant medicine.
How do you help those patients waiting on transplant lists for a liver?
We are intimately involved in their care all the way through their journey with liver disease, up until the time of physically getting the liver transplant, which is performed by our colleagues in transplant surgery. From the time they are transplanted, we are involved in their inpatient and outpatient post-transplant care. We’ve helped to get them on the transplant list with the work of the multidisciplinary team. If there are opportunities to help them understand their position on the list or obtaining exceptions—though that is done in a very objective fashion through the regulatory system—we help to guide them through that journey.
You’ve worked on many studies that involve treatments for hepatocellular carcinoma. Can you highlight a paper that yielded clinically significant benefits?
What really stands out the most to me was our site’s involvement in the IMbrave150 trial, which was published in 2020. This multicenter study made a big difference in the outcomes and treatments for patients, as it brought the adoption of first-line immunotherapy (atezolizumab plus bevacizumab) for patients with advanced hepatocellular carcinoma. I remember vividly the patients we had the opportunity to enroll in that trial – some who we continue to care for today. This stands out as one of the trials that I was involved in that had a lasting impact.
What were the clinical endpoints and key results of that trial?
The endpoint was to see an improvement in overall survival utilizing immunotherapy, compared with the prior standard of care then available, oral therapy. The results led to the adoption and FDA approval of immunotherapy in the first line setting for advanced unresectable hepatocellular carcinoma patients.
What are some of the highlights of serving as director of Henry Ford’s fellowship program?
Education is my passion. I went into medical training feeling that at some point I would love to blend in teaching in a formal role. Becoming program director of the gastroenterology and hepatology fellowship at Henry Ford in 2018 was one of the most meaningful things that I’ve had the opportunity to do in my career. I get to see trainees who are at a very impressionable point of their journey go on to become gastroenterologists and then launch into their first job and really develop in this field. Seeing them come in day one, not knowing how to hold a scope or do a procedure on a patient of this nature, then quickly evolve over the first year and grow over three years to achieve this specialty training [is rewarding]. I’ve learned a lot from the fellows along the way. I think of them as an extension of my family. We have 15 fellows currently in our program and we’ll be growing this summer. So that’s really been a highlight of my career thus far.
What fears did you have to push past to get to where you are in your career?
I think that there have been a few. One is certainly the fear of making the wrong choice with your first career opportunity. I did choose to leave my comfort zone from where I had done my training. I met that with some fear, but also excitement for new opportunities of personal and professional growth.
Another fear is: Am I going to be able to be ambitious in this field? Can I pursue research, become a program director, and do things that my role models and mentors were able to achieve? There’s also the fear of being able to balance a busy work life with a busy home life and figuring out how to do both well and minimize the guilt on both sides. I have a family with two girls. They are definitely a top priority.
What teacher or mentor had the greatest impact on you?
Helen Te, MD, a hepatologist at the University of Chicago. When I was a medical student there, I had the opportunity to work with her and saw her passion for this field. She really had so much enthusiasm for teaching and was a big part of why I started to fall in love with liver disease.
Karen Kim, MD, now the dean of Penn State College of Medicine, was one of my assigned mentors as a medical student. She helped me explore the fields where there were opportunities for residency and helped me make the decision to go into internal medicine, which often is a key deciding point for medical students. She was also a very influential teacher. The other individual who stands out is my fellowship program director, Hari Sree Conjeevaram, MD, MSc, at University of Michigan Health. He exhibited the qualities as an educator and program director that helped me recognize that education was something that I wanted to pursue in a formal fashion once I moved on in my career.
Describe how you would spend a free Saturday afternoon.
Likely taking a hike or go to a park with my family, enjoying the outdoors and spending time with them.
Lightning Round
If you weren’t a gastroenterologist, what would you be?
Philanthropist
Favorite city in U.S. besides the one you live in?
Chicago
Place you most want to travel?
New Zealand
Favorite breakfast?
Avocado toast
Favorite ice cream flavor?
Cookies and cream
How many cups of coffee do you drink per day?
Two…or more
Cat person or dog person?
Dog
Texting or talking?
Talk
Favorite season?
Autumn
Favorite type of music?
Pop
Favorite movie genre?
Action
For Reena Salgia, MD, the most rewarding part about working with patients with hepatocellular carcinoma is being there for their entire journey, thanks to advancements in treatment. “It brings a smile to my face just to think about it,” says Dr. Salgia, medical director of Henry Ford Health’s Liver Cancer Clinic in Detroit.
Hepatocellular carcinoma accounts for 80% of all liver cancer. When she first entered the field, Dr. Salgia often heard that survival rates 5 years after diagnosis were less than 10%. Over the last decade however, “I’ve seen an expansion in the procedural options that we offer these patients. We have an array of options both surgically as well as procedurally,” she said.
Especially over the last three to four years, “we’ve seen meaningful responses for patients with medications that we previously didn’t have in our toolbox. That’s really been exciting, along with continued involvement in clinical trials and being able to offer patients a number of different approaches to their care of liver cancer,” said Dr. Salgia.
A regular attendee and presenter at national GI meetings, Dr. Salgia participated in AGA’s Women’s Executive Leadership Conference in 2023. Her academic resume includes a long list of clinical trials to assess treatments for patients at different stages of hepatocellular carcinoma.
In an interview, she discussed the highlights of her career as a researcher and mentor of fellows, and how she guides and supports her transplant patients.
What drove you to pursue the field of hepatology and transplant hepatology?
I came across this field during my fourth year of medical school. I didn’t know anything about hepatology when I reached that stage and had the opportunity to do an elective. I just fell in love with the specialty. I liked the complex pathophysiology of liver disease, the long-term follow-up and care of patients. It appealed to the type of science that I had enjoyed back in college.
As I went into my GI fellowship training, I got to learn more about the field of transplant medicine. For instance, how you can take these patients who are incredibly ill, really at a very vulnerable point of their illness, and then offer them great hope and see their lives turn around afterwards. When I had the opportunity to see patients go from end stage liver disease to such significant improvement in their quality of life, and restoring their physical functioning beyond what we would’ve ever imagined when they were ill, it reaffirmed my interest in both hepatology as well as in transplant medicine.
How do you help those patients waiting on transplant lists for a liver?
We are intimately involved in their care all the way through their journey with liver disease, up until the time of physically getting the liver transplant, which is performed by our colleagues in transplant surgery. From the time they are transplanted, we are involved in their inpatient and outpatient post-transplant care. We’ve helped to get them on the transplant list with the work of the multidisciplinary team. If there are opportunities to help them understand their position on the list or obtaining exceptions—though that is done in a very objective fashion through the regulatory system—we help to guide them through that journey.
You’ve worked on many studies that involve treatments for hepatocellular carcinoma. Can you highlight a paper that yielded clinically significant benefits?
What really stands out the most to me was our site’s involvement in the IMbrave150 trial, which was published in 2020. This multicenter study made a big difference in the outcomes and treatments for patients, as it brought the adoption of first-line immunotherapy (atezolizumab plus bevacizumab) for patients with advanced hepatocellular carcinoma. I remember vividly the patients we had the opportunity to enroll in that trial – some who we continue to care for today. This stands out as one of the trials that I was involved in that had a lasting impact.
What were the clinical endpoints and key results of that trial?
The endpoint was to see an improvement in overall survival utilizing immunotherapy, compared with the prior standard of care then available, oral therapy. The results led to the adoption and FDA approval of immunotherapy in the first line setting for advanced unresectable hepatocellular carcinoma patients.
What are some of the highlights of serving as director of Henry Ford’s fellowship program?
Education is my passion. I went into medical training feeling that at some point I would love to blend in teaching in a formal role. Becoming program director of the gastroenterology and hepatology fellowship at Henry Ford in 2018 was one of the most meaningful things that I’ve had the opportunity to do in my career. I get to see trainees who are at a very impressionable point of their journey go on to become gastroenterologists and then launch into their first job and really develop in this field. Seeing them come in day one, not knowing how to hold a scope or do a procedure on a patient of this nature, then quickly evolve over the first year and grow over three years to achieve this specialty training [is rewarding]. I’ve learned a lot from the fellows along the way. I think of them as an extension of my family. We have 15 fellows currently in our program and we’ll be growing this summer. So that’s really been a highlight of my career thus far.
What fears did you have to push past to get to where you are in your career?
I think that there have been a few. One is certainly the fear of making the wrong choice with your first career opportunity. I did choose to leave my comfort zone from where I had done my training. I met that with some fear, but also excitement for new opportunities of personal and professional growth.
Another fear is: Am I going to be able to be ambitious in this field? Can I pursue research, become a program director, and do things that my role models and mentors were able to achieve? There’s also the fear of being able to balance a busy work life with a busy home life and figuring out how to do both well and minimize the guilt on both sides. I have a family with two girls. They are definitely a top priority.
What teacher or mentor had the greatest impact on you?
Helen Te, MD, a hepatologist at the University of Chicago. When I was a medical student there, I had the opportunity to work with her and saw her passion for this field. She really had so much enthusiasm for teaching and was a big part of why I started to fall in love with liver disease.
Karen Kim, MD, now the dean of Penn State College of Medicine, was one of my assigned mentors as a medical student. She helped me explore the fields where there were opportunities for residency and helped me make the decision to go into internal medicine, which often is a key deciding point for medical students. She was also a very influential teacher. The other individual who stands out is my fellowship program director, Hari Sree Conjeevaram, MD, MSc, at University of Michigan Health. He exhibited the qualities as an educator and program director that helped me recognize that education was something that I wanted to pursue in a formal fashion once I moved on in my career.
Describe how you would spend a free Saturday afternoon.
Likely taking a hike or go to a park with my family, enjoying the outdoors and spending time with them.
Lightning Round
If you weren’t a gastroenterologist, what would you be?
Philanthropist
Favorite city in U.S. besides the one you live in?
Chicago
Place you most want to travel?
New Zealand
Favorite breakfast?
Avocado toast
Favorite ice cream flavor?
Cookies and cream
How many cups of coffee do you drink per day?
Two…or more
Cat person or dog person?
Dog
Texting or talking?
Talk
Favorite season?
Autumn
Favorite type of music?
Pop
Favorite movie genre?
Action

Giving the Smallest GI Transplant Patients a New Lease On Life
The best part about working with kids is that “I get to laugh every day,” said Ke-You (Yoyo) Zhang, MD, clinical assistant professor for pediatrics–gastroenterology and hepatology at Stanford Medicine in California.
Dealing with sick children is difficult. “But I think the difference between pediatrics and adults is despite how hard things get, children are the single most resilient people you’re ever going to meet,” she said.
Kids don’t always know they’re sick and they don’t act sick, even when they are. “Every day, I literally get on the floor, I get to play, I get to run around. And truly, I have fun every single day. I get excited to go to work. And I think that’s what makes work not feel like work,” said Dr. Zhang.
In an interview, she discussed the satisfaction of following patients throughout their care continuum and her research to reduce the likelihood of transplant rejection.
She also shared an inspirational story of one young patient who spent his life tied to an IV, and how a transplant exposed him to the normal joys of life, like swimming, going to camp and getting on a plane for the first time.
Q: Why did you choose this subspecialty of pediatric GI?
I think it’s the best subspecialty because I think it combines a lot of the things that I enjoy, which is long-term continuity of care. It’s about growing up with your patients and seeing them through all the various stages of their life, often meeting patients when they’re babies. I get pictures of high school graduations and life milestones and even see some of my patients have families of their own. Becoming a part of their family is very meaningful to me. I also like complexity and acuity, and gastroenterology and hepatology provide those things.
And then lastly, it’s great to be able to exercise procedural skills and constantly learn new procedural skills.
Q: How did you become interested in the field of pediatric intestinal and liver transplantation?
I did all my training here at Stanford. We have one of the largest pediatric transplant centers and we also have a very large intestinal rehabilitation population.
Coming through residency and fellowship, I had a lot of exposure to transplant and intestinal failure, intestinal rehabilitation. I really liked the longitudinal relationship I got to form with my patients. Sometimes they’re in the neonatal ICU, where you’re meeting them in their very first days of life. You follow them through their chronic illness, through transplant and after transplant for many years. You become not just their GI, but the center of their care.
Q: What challenges are unique to this type of transplant work?
Pediatric intestinal failure and intestinal transplant represents an incredibly small subset of children. Oftentimes, they do not get the resources and recognition on a national policy level or even at the hospital level that other gastrointestinal diseases receive. What’s difficult is they are such a small subset but their complexity and their needs are probably in the highest percentile. So that’s a really challenging combination to start with. And there’s only a few centers that specialize in doing intestinal rehabilitation and intestinal transplantation for children in the country.
Developing expertise has been slow. But I think in the last decade or so, our understanding and success with intestinal rehabilitation and intestinal transplantation has really improved, especially at large centers like Stanford. We’ve had a lot of success stories and have not had any graft loss since 2014.
Q: Are these transplants hard to acquire?
Yes, especially when you’re transplanting not just the intestines but the liver as well. You’re waiting for two organs, not just one organ. And on top of that, you’re waiting for an appropriately sized donor; usually a child who’s around the same size or same age who’s passed away. Those organs would have to be a good match. Children can wait multiple years for a transplant.
Q: Is there a success story you’d like to share?
One patient I met in the neonatal ICU had congenital short bowel syndrome. He was born with hardly any intestines. He developed complications of being on long-term intravenous nutrition, which included recurrent central line infections and liver disease. He was never able to eat because he really didn’t have a digestive system that could adequately absorb anything. He had a central line in one of his large veins, so he couldn’t go swimming.
He had to have special adaptive wear to even shower or bathe and couldn’t travel. It’s these types of patients that benefit so much from transplant. Putting any kid through transplant is a massive undertaking and it certainly has risks. But he underwent a successful transplant at the age of 8—not just an intestinal transplant, but a multi-visceral transplant of the liver, intestine, and pancreas. He’s 9 years old now, and no longer needs intravenous nutrition. He ate by mouth for the very first time after transplant. He’s trying all sorts of new foods and he was able to go to a special transplant camp for children. Getting on a plane to Los Angeles, which is where our transplant camp is, was a huge deal.
He was able to swim in the lake. He’s never been able to do that. And he wants to start doing sports this fall. This was really a life-changing story for him.
Q: What advancements lie ahead for this field of work? Have you work on any notable research?
I think our understanding of transplant immunology has really progressed, especially recently. That’s what part of my research is about—using novel therapies to modulate the immune system of pediatric transplant recipients. The No. 1 complication that occurs after intestinal transplant is rejection because obviously you’re implanting somebody else’s organs into a patient.
I am involved in a clinical trial that’s looking at the use of extracellular vesicles that are isolated from hematopoietic stem cells. These vesicles contain various growth factors, anti-inflammatory proteins and tissue repair factors that we are infusing into intestinal transplant patients with the aim to repair the intestinal tissue patients are rejecting.
Q: When you’re not being a GI, how do you spend your free weekend afternoons?
My husband and I have an almost 2-year-old little girl. She keeps us busy and I spend my afternoons chasing after a crazy toddler.
Lightning Round
Texting or talking?
Huge texter
Favorite junk food?
French fries
Cat or dog person?
Dog
Favorite ice cream?
Strawberry
If you weren’t a gastroenterologist, what would you be?Florist
Best place you’ve traveled to?
Thailand
Number of cups of coffee you drink per day?
Too many
Favorite city in the US besides the one you live in?
New York City
Favorite sport?
Tennis
Optimist or pessimist?
Optimist
The best part about working with kids is that “I get to laugh every day,” said Ke-You (Yoyo) Zhang, MD, clinical assistant professor for pediatrics–gastroenterology and hepatology at Stanford Medicine in California.
Dealing with sick children is difficult. “But I think the difference between pediatrics and adults is despite how hard things get, children are the single most resilient people you’re ever going to meet,” she said.
Kids don’t always know they’re sick and they don’t act sick, even when they are. “Every day, I literally get on the floor, I get to play, I get to run around. And truly, I have fun every single day. I get excited to go to work. And I think that’s what makes work not feel like work,” said Dr. Zhang.
In an interview, she discussed the satisfaction of following patients throughout their care continuum and her research to reduce the likelihood of transplant rejection.
She also shared an inspirational story of one young patient who spent his life tied to an IV, and how a transplant exposed him to the normal joys of life, like swimming, going to camp and getting on a plane for the first time.
Q: Why did you choose this subspecialty of pediatric GI?
I think it’s the best subspecialty because I think it combines a lot of the things that I enjoy, which is long-term continuity of care. It’s about growing up with your patients and seeing them through all the various stages of their life, often meeting patients when they’re babies. I get pictures of high school graduations and life milestones and even see some of my patients have families of their own. Becoming a part of their family is very meaningful to me. I also like complexity and acuity, and gastroenterology and hepatology provide those things.
And then lastly, it’s great to be able to exercise procedural skills and constantly learn new procedural skills.
Q: How did you become interested in the field of pediatric intestinal and liver transplantation?
I did all my training here at Stanford. We have one of the largest pediatric transplant centers and we also have a very large intestinal rehabilitation population.
Coming through residency and fellowship, I had a lot of exposure to transplant and intestinal failure, intestinal rehabilitation. I really liked the longitudinal relationship I got to form with my patients. Sometimes they’re in the neonatal ICU, where you’re meeting them in their very first days of life. You follow them through their chronic illness, through transplant and after transplant for many years. You become not just their GI, but the center of their care.
Q: What challenges are unique to this type of transplant work?
Pediatric intestinal failure and intestinal transplant represents an incredibly small subset of children. Oftentimes, they do not get the resources and recognition on a national policy level or even at the hospital level that other gastrointestinal diseases receive. What’s difficult is they are such a small subset but their complexity and their needs are probably in the highest percentile. So that’s a really challenging combination to start with. And there’s only a few centers that specialize in doing intestinal rehabilitation and intestinal transplantation for children in the country.
Developing expertise has been slow. But I think in the last decade or so, our understanding and success with intestinal rehabilitation and intestinal transplantation has really improved, especially at large centers like Stanford. We’ve had a lot of success stories and have not had any graft loss since 2014.
Q: Are these transplants hard to acquire?
Yes, especially when you’re transplanting not just the intestines but the liver as well. You’re waiting for two organs, not just one organ. And on top of that, you’re waiting for an appropriately sized donor; usually a child who’s around the same size or same age who’s passed away. Those organs would have to be a good match. Children can wait multiple years for a transplant.
Q: Is there a success story you’d like to share?
One patient I met in the neonatal ICU had congenital short bowel syndrome. He was born with hardly any intestines. He developed complications of being on long-term intravenous nutrition, which included recurrent central line infections and liver disease. He was never able to eat because he really didn’t have a digestive system that could adequately absorb anything. He had a central line in one of his large veins, so he couldn’t go swimming.
He had to have special adaptive wear to even shower or bathe and couldn’t travel. It’s these types of patients that benefit so much from transplant. Putting any kid through transplant is a massive undertaking and it certainly has risks. But he underwent a successful transplant at the age of 8—not just an intestinal transplant, but a multi-visceral transplant of the liver, intestine, and pancreas. He’s 9 years old now, and no longer needs intravenous nutrition. He ate by mouth for the very first time after transplant. He’s trying all sorts of new foods and he was able to go to a special transplant camp for children. Getting on a plane to Los Angeles, which is where our transplant camp is, was a huge deal.
He was able to swim in the lake. He’s never been able to do that. And he wants to start doing sports this fall. This was really a life-changing story for him.
Q: What advancements lie ahead for this field of work? Have you work on any notable research?
I think our understanding of transplant immunology has really progressed, especially recently. That’s what part of my research is about—using novel therapies to modulate the immune system of pediatric transplant recipients. The No. 1 complication that occurs after intestinal transplant is rejection because obviously you’re implanting somebody else’s organs into a patient.
I am involved in a clinical trial that’s looking at the use of extracellular vesicles that are isolated from hematopoietic stem cells. These vesicles contain various growth factors, anti-inflammatory proteins and tissue repair factors that we are infusing into intestinal transplant patients with the aim to repair the intestinal tissue patients are rejecting.
Q: When you’re not being a GI, how do you spend your free weekend afternoons?
My husband and I have an almost 2-year-old little girl. She keeps us busy and I spend my afternoons chasing after a crazy toddler.
Lightning Round
Texting or talking?
Huge texter
Favorite junk food?
French fries
Cat or dog person?
Dog
Favorite ice cream?
Strawberry
If you weren’t a gastroenterologist, what would you be?Florist
Best place you’ve traveled to?
Thailand
Number of cups of coffee you drink per day?
Too many
Favorite city in the US besides the one you live in?
New York City
Favorite sport?
Tennis
Optimist or pessimist?
Optimist
The best part about working with kids is that “I get to laugh every day,” said Ke-You (Yoyo) Zhang, MD, clinical assistant professor for pediatrics–gastroenterology and hepatology at Stanford Medicine in California.
Dealing with sick children is difficult. “But I think the difference between pediatrics and adults is despite how hard things get, children are the single most resilient people you’re ever going to meet,” she said.
Kids don’t always know they’re sick and they don’t act sick, even when they are. “Every day, I literally get on the floor, I get to play, I get to run around. And truly, I have fun every single day. I get excited to go to work. And I think that’s what makes work not feel like work,” said Dr. Zhang.
In an interview, she discussed the satisfaction of following patients throughout their care continuum and her research to reduce the likelihood of transplant rejection.
She also shared an inspirational story of one young patient who spent his life tied to an IV, and how a transplant exposed him to the normal joys of life, like swimming, going to camp and getting on a plane for the first time.
Q: Why did you choose this subspecialty of pediatric GI?
I think it’s the best subspecialty because I think it combines a lot of the things that I enjoy, which is long-term continuity of care. It’s about growing up with your patients and seeing them through all the various stages of their life, often meeting patients when they’re babies. I get pictures of high school graduations and life milestones and even see some of my patients have families of their own. Becoming a part of their family is very meaningful to me. I also like complexity and acuity, and gastroenterology and hepatology provide those things.
And then lastly, it’s great to be able to exercise procedural skills and constantly learn new procedural skills.
Q: How did you become interested in the field of pediatric intestinal and liver transplantation?
I did all my training here at Stanford. We have one of the largest pediatric transplant centers and we also have a very large intestinal rehabilitation population.
Coming through residency and fellowship, I had a lot of exposure to transplant and intestinal failure, intestinal rehabilitation. I really liked the longitudinal relationship I got to form with my patients. Sometimes they’re in the neonatal ICU, where you’re meeting them in their very first days of life. You follow them through their chronic illness, through transplant and after transplant for many years. You become not just their GI, but the center of their care.
Q: What challenges are unique to this type of transplant work?
Pediatric intestinal failure and intestinal transplant represents an incredibly small subset of children. Oftentimes, they do not get the resources and recognition on a national policy level or even at the hospital level that other gastrointestinal diseases receive. What’s difficult is they are such a small subset but their complexity and their needs are probably in the highest percentile. So that’s a really challenging combination to start with. And there’s only a few centers that specialize in doing intestinal rehabilitation and intestinal transplantation for children in the country.
Developing expertise has been slow. But I think in the last decade or so, our understanding and success with intestinal rehabilitation and intestinal transplantation has really improved, especially at large centers like Stanford. We’ve had a lot of success stories and have not had any graft loss since 2014.
Q: Are these transplants hard to acquire?
Yes, especially when you’re transplanting not just the intestines but the liver as well. You’re waiting for two organs, not just one organ. And on top of that, you’re waiting for an appropriately sized donor; usually a child who’s around the same size or same age who’s passed away. Those organs would have to be a good match. Children can wait multiple years for a transplant.
Q: Is there a success story you’d like to share?
One patient I met in the neonatal ICU had congenital short bowel syndrome. He was born with hardly any intestines. He developed complications of being on long-term intravenous nutrition, which included recurrent central line infections and liver disease. He was never able to eat because he really didn’t have a digestive system that could adequately absorb anything. He had a central line in one of his large veins, so he couldn’t go swimming.
He had to have special adaptive wear to even shower or bathe and couldn’t travel. It’s these types of patients that benefit so much from transplant. Putting any kid through transplant is a massive undertaking and it certainly has risks. But he underwent a successful transplant at the age of 8—not just an intestinal transplant, but a multi-visceral transplant of the liver, intestine, and pancreas. He’s 9 years old now, and no longer needs intravenous nutrition. He ate by mouth for the very first time after transplant. He’s trying all sorts of new foods and he was able to go to a special transplant camp for children. Getting on a plane to Los Angeles, which is where our transplant camp is, was a huge deal.
He was able to swim in the lake. He’s never been able to do that. And he wants to start doing sports this fall. This was really a life-changing story for him.
Q: What advancements lie ahead for this field of work? Have you work on any notable research?
I think our understanding of transplant immunology has really progressed, especially recently. That’s what part of my research is about—using novel therapies to modulate the immune system of pediatric transplant recipients. The No. 1 complication that occurs after intestinal transplant is rejection because obviously you’re implanting somebody else’s organs into a patient.
I am involved in a clinical trial that’s looking at the use of extracellular vesicles that are isolated from hematopoietic stem cells. These vesicles contain various growth factors, anti-inflammatory proteins and tissue repair factors that we are infusing into intestinal transplant patients with the aim to repair the intestinal tissue patients are rejecting.
Q: When you’re not being a GI, how do you spend your free weekend afternoons?
My husband and I have an almost 2-year-old little girl. She keeps us busy and I spend my afternoons chasing after a crazy toddler.
Lightning Round
Texting or talking?
Huge texter
Favorite junk food?
French fries
Cat or dog person?
Dog
Favorite ice cream?
Strawberry
If you weren’t a gastroenterologist, what would you be?Florist
Best place you’ve traveled to?
Thailand
Number of cups of coffee you drink per day?
Too many
Favorite city in the US besides the one you live in?
New York City
Favorite sport?
Tennis
Optimist or pessimist?
Optimist

Diet Drinks Harder on the Liver Than Sugary Drinks?
BERLIN — Diet drinks may not be “healthier” than sugary drinks when it comes to liver health.
In fact, low- or artificially sweetened beverages were actually linked to a higher risk for MASLD than sugar-laden drinks, even at modest intake levels such as a single can per day.
“These findings challenge the common perception that these drinks are harmless and highlight the need to reconsider their role in diet and liver health, especially as MASLD emerges as a global health concern,” lead author Lihe Liu, a graduate student in the Department of Gastroenterology at The First Affiliated Hospital of Soochow University in Suzhou, China, said in a news release.
She presented her research at the United European Gastroenterology (UEG) Week 2025 in Berlin, Germany.
Stick With Water
MASLD affects 38% of the global population and has become a leading cause of cirrhosis, liver cancer, and liver-related death. Lifestyle modification remains “a cornerstone” of MASLD management. Current guidelines advise against SSBs, but the evidence regarding LNSSBs remains “limited,” Liu explained in her presentation.
To investigate, the researchers analyzed data of 123,788 UK Biobank participants without liver disease at baseline who were followed for an average of 10.3 years. Beverage consumption was assessed through repeated 24-hour dietary questionnaires using the question: “How many glasses, cans, or cartons containing 250 mL (roughly 250 g) of SSBs or LNSSBs did you drink yesterday?”
Intake was averaged across at least two recalls, and participants were grouped into three intake categories: none, more than 0 to one serving per day, or more than one serving per day.
The primary outcome was incident MASLD, and secondary outcomes included liver-related mortality and liver fat content measured using MRI-derived proton density fat fraction.
In the fully adjusted multivariable Cox model, compared with no consumption, consuming more than one serving of LNSSBs daily was associated with a 60% higher risk for MASLD (hazard ratio [HR], 1.599). The level of consumption of SSBs was associated with a 50% higher risk (HR, 1.469).
Consuming more than one serving of LNSSBs daily was also associated with a higher risk for severe liver outcomes (HR, 1.555), while SSBs showed no significant association after adjustment.
Neither SSBs nor LNSSBs showed significant associations with all-cause mortality in fully adjusted models.
Substituting either beverage with water reduced the risk for MASLD by 12.8% for SSBs and 15.2% for LNSSBs, Liu reported.
Both beverage types were positively associated with higher liver fat content. Consumption of more than one serving of SSBs and LNSSBs daily was associated with about 5% and 7% higher liver fat levels, respectively, than nonconsumption.
“The higher sugar content in SSBs can cause rapid spikes in blood glucose and insulin, promote weight gain, and increase uric acid levels, all of which contribute to liver fat accumulation. LNSSBs, on the other hand, may affect liver health by altering the gut microbiome, disrupting the feeling of fullness, driving sweet cravings, and even stimulating insulin secretion,” Liu said.
“The safest approach is to limit both sugar-sweetened and artificially sweetened drinks. Water remains the best choice as it removes the metabolic burden and prevents fat accumulation in the liver, whilst hydrating the body,” she concluded.
More Study Needed
Reached for comment, Sujit V. Janardhan, MD, PhD, director of the steatotic liver disease program, Rush University Medical Center, Chicago, said the findings “certainly should cause one to take pause from the popular notion that diet or non-sugar-sweetened beverages are healthier than their sugar-sweetened alternatives.”
He cautioned, however, that it would be “important to confirm confounders are adequately addressed in this large population-based study.”
“We must better understand what other exposure and characteristics were present in patients who had increased intake of non-sugar-sweetened beverages,” Janardhan told GI & Hepatology News.
“For example, it’s possible people who drank more non-sugar-sweetened beverages had more cardiovascular or metabolic risk factors (which prompted them to switch to the ‘diet’ alternative) and that it is these comorbidities that drove an association with increased MASLD incidence and liver-related mortality,” Janardhan noted.
“If there is one finding that seems easy to take away from this study, it’s that people who drank more water in place of sweetened beverages had reduced risk of MASLD,” he told GI & Hepatology News.
Therefore, while awaiting results of mechanistic studies and careful confounder analysis, “plain old boring water is your best bet,” Janardhan said.
The study had no specific funding. Liu and Janardhan had no relevant disclosures.
A version of this article appeared on Medscape.com.
BERLIN — Diet drinks may not be “healthier” than sugary drinks when it comes to liver health.
In fact, low- or artificially sweetened beverages were actually linked to a higher risk for MASLD than sugar-laden drinks, even at modest intake levels such as a single can per day.
“These findings challenge the common perception that these drinks are harmless and highlight the need to reconsider their role in diet and liver health, especially as MASLD emerges as a global health concern,” lead author Lihe Liu, a graduate student in the Department of Gastroenterology at The First Affiliated Hospital of Soochow University in Suzhou, China, said in a news release.
She presented her research at the United European Gastroenterology (UEG) Week 2025 in Berlin, Germany.
Stick With Water
MASLD affects 38% of the global population and has become a leading cause of cirrhosis, liver cancer, and liver-related death. Lifestyle modification remains “a cornerstone” of MASLD management. Current guidelines advise against SSBs, but the evidence regarding LNSSBs remains “limited,” Liu explained in her presentation.
To investigate, the researchers analyzed data of 123,788 UK Biobank participants without liver disease at baseline who were followed for an average of 10.3 years. Beverage consumption was assessed through repeated 24-hour dietary questionnaires using the question: “How many glasses, cans, or cartons containing 250 mL (roughly 250 g) of SSBs or LNSSBs did you drink yesterday?”
Intake was averaged across at least two recalls, and participants were grouped into three intake categories: none, more than 0 to one serving per day, or more than one serving per day.
The primary outcome was incident MASLD, and secondary outcomes included liver-related mortality and liver fat content measured using MRI-derived proton density fat fraction.
In the fully adjusted multivariable Cox model, compared with no consumption, consuming more than one serving of LNSSBs daily was associated with a 60% higher risk for MASLD (hazard ratio [HR], 1.599). The level of consumption of SSBs was associated with a 50% higher risk (HR, 1.469).
Consuming more than one serving of LNSSBs daily was also associated with a higher risk for severe liver outcomes (HR, 1.555), while SSBs showed no significant association after adjustment.
Neither SSBs nor LNSSBs showed significant associations with all-cause mortality in fully adjusted models.
Substituting either beverage with water reduced the risk for MASLD by 12.8% for SSBs and 15.2% for LNSSBs, Liu reported.
Both beverage types were positively associated with higher liver fat content. Consumption of more than one serving of SSBs and LNSSBs daily was associated with about 5% and 7% higher liver fat levels, respectively, than nonconsumption.
“The higher sugar content in SSBs can cause rapid spikes in blood glucose and insulin, promote weight gain, and increase uric acid levels, all of which contribute to liver fat accumulation. LNSSBs, on the other hand, may affect liver health by altering the gut microbiome, disrupting the feeling of fullness, driving sweet cravings, and even stimulating insulin secretion,” Liu said.
“The safest approach is to limit both sugar-sweetened and artificially sweetened drinks. Water remains the best choice as it removes the metabolic burden and prevents fat accumulation in the liver, whilst hydrating the body,” she concluded.
More Study Needed
Reached for comment, Sujit V. Janardhan, MD, PhD, director of the steatotic liver disease program, Rush University Medical Center, Chicago, said the findings “certainly should cause one to take pause from the popular notion that diet or non-sugar-sweetened beverages are healthier than their sugar-sweetened alternatives.”
He cautioned, however, that it would be “important to confirm confounders are adequately addressed in this large population-based study.”
“We must better understand what other exposure and characteristics were present in patients who had increased intake of non-sugar-sweetened beverages,” Janardhan told GI & Hepatology News.
“For example, it’s possible people who drank more non-sugar-sweetened beverages had more cardiovascular or metabolic risk factors (which prompted them to switch to the ‘diet’ alternative) and that it is these comorbidities that drove an association with increased MASLD incidence and liver-related mortality,” Janardhan noted.
“If there is one finding that seems easy to take away from this study, it’s that people who drank more water in place of sweetened beverages had reduced risk of MASLD,” he told GI & Hepatology News.
Therefore, while awaiting results of mechanistic studies and careful confounder analysis, “plain old boring water is your best bet,” Janardhan said.
The study had no specific funding. Liu and Janardhan had no relevant disclosures.
A version of this article appeared on Medscape.com.
BERLIN — Diet drinks may not be “healthier” than sugary drinks when it comes to liver health.
In fact, low- or artificially sweetened beverages were actually linked to a higher risk for MASLD than sugar-laden drinks, even at modest intake levels such as a single can per day.
“These findings challenge the common perception that these drinks are harmless and highlight the need to reconsider their role in diet and liver health, especially as MASLD emerges as a global health concern,” lead author Lihe Liu, a graduate student in the Department of Gastroenterology at The First Affiliated Hospital of Soochow University in Suzhou, China, said in a news release.
She presented her research at the United European Gastroenterology (UEG) Week 2025 in Berlin, Germany.
Stick With Water
MASLD affects 38% of the global population and has become a leading cause of cirrhosis, liver cancer, and liver-related death. Lifestyle modification remains “a cornerstone” of MASLD management. Current guidelines advise against SSBs, but the evidence regarding LNSSBs remains “limited,” Liu explained in her presentation.
To investigate, the researchers analyzed data of 123,788 UK Biobank participants without liver disease at baseline who were followed for an average of 10.3 years. Beverage consumption was assessed through repeated 24-hour dietary questionnaires using the question: “How many glasses, cans, or cartons containing 250 mL (roughly 250 g) of SSBs or LNSSBs did you drink yesterday?”
Intake was averaged across at least two recalls, and participants were grouped into three intake categories: none, more than 0 to one serving per day, or more than one serving per day.
The primary outcome was incident MASLD, and secondary outcomes included liver-related mortality and liver fat content measured using MRI-derived proton density fat fraction.
In the fully adjusted multivariable Cox model, compared with no consumption, consuming more than one serving of LNSSBs daily was associated with a 60% higher risk for MASLD (hazard ratio [HR], 1.599). The level of consumption of SSBs was associated with a 50% higher risk (HR, 1.469).
Consuming more than one serving of LNSSBs daily was also associated with a higher risk for severe liver outcomes (HR, 1.555), while SSBs showed no significant association after adjustment.
Neither SSBs nor LNSSBs showed significant associations with all-cause mortality in fully adjusted models.
Substituting either beverage with water reduced the risk for MASLD by 12.8% for SSBs and 15.2% for LNSSBs, Liu reported.
Both beverage types were positively associated with higher liver fat content. Consumption of more than one serving of SSBs and LNSSBs daily was associated with about 5% and 7% higher liver fat levels, respectively, than nonconsumption.
“The higher sugar content in SSBs can cause rapid spikes in blood glucose and insulin, promote weight gain, and increase uric acid levels, all of which contribute to liver fat accumulation. LNSSBs, on the other hand, may affect liver health by altering the gut microbiome, disrupting the feeling of fullness, driving sweet cravings, and even stimulating insulin secretion,” Liu said.
“The safest approach is to limit both sugar-sweetened and artificially sweetened drinks. Water remains the best choice as it removes the metabolic burden and prevents fat accumulation in the liver, whilst hydrating the body,” she concluded.
More Study Needed
Reached for comment, Sujit V. Janardhan, MD, PhD, director of the steatotic liver disease program, Rush University Medical Center, Chicago, said the findings “certainly should cause one to take pause from the popular notion that diet or non-sugar-sweetened beverages are healthier than their sugar-sweetened alternatives.”
He cautioned, however, that it would be “important to confirm confounders are adequately addressed in this large population-based study.”
“We must better understand what other exposure and characteristics were present in patients who had increased intake of non-sugar-sweetened beverages,” Janardhan told GI & Hepatology News.
“For example, it’s possible people who drank more non-sugar-sweetened beverages had more cardiovascular or metabolic risk factors (which prompted them to switch to the ‘diet’ alternative) and that it is these comorbidities that drove an association with increased MASLD incidence and liver-related mortality,” Janardhan noted.
“If there is one finding that seems easy to take away from this study, it’s that people who drank more water in place of sweetened beverages had reduced risk of MASLD,” he told GI & Hepatology News.
Therefore, while awaiting results of mechanistic studies and careful confounder analysis, “plain old boring water is your best bet,” Janardhan said.
The study had no specific funding. Liu and Janardhan had no relevant disclosures.
A version of this article appeared on Medscape.com.
Real-World Pros & Cons of the New Liver Disease Nomenclature
VIENNA –United European Gastroenterology (UEG) Week 2025 in Vienna, Austria.
Maria Effenberger, MD, Medical University of Innsbruck, Berlin, Germany, told attendees atIn her presentation, “Sense and Nonsense of the New Nomenclature,” Effenberger highlighted the clinical implications of the new liver-disease terminology and pointed to a few factors still needing to be sorted out.
Both NAFLD and MASLD are steatotic liver diseasesand, notably, there are few differences between the two in clinical studies, which makes the terminology shift easier, said Effenberger. She cited a recent study showing demographic and clinical profiles of individuals classified as NAFLD and MASLD in the US were “strikingly similar,” as were the accuracy of the noninvasive tests and all-cause and cause-specific mortality rates for both conditions.
However, “the important thing about MASLD is that the term is really connected to metabolic dysfunction,” said Effenberger. To be diagnosed with MASLD, patients with liver disease need to have at least one of five cardiometabolic abnormalities: a high BMI — over 25 in White people and over 23 in Asian people; type 2 diabetes (T2D) or prediabetes; arterial hypertension; high levels of triglycerides; or a low level of high-density lipoprotein cholesterol.
“MASLD is a systemic disease, and that term represents it much better than only looking at it as a hepatological disease,” Effenberger said. “Many factors, especially inflammatory ones, influence steatosis, inflammation, and fibrosis.” These include influences from adipose tissue, the gut microbiome, the brain, a hypocaloric diet, and from steatosis of the liver itself. Proinflammatory cytokines induced by the disease can lead to inflammation throughout the body, with clinical outcomes such as stroke, heart failure, arrhythmias, myocardial infarction, chronic kidney disease.
MASLD, MetALD, or ALD?
“What is important now,” said Effenberger, is that “every patient who has liver disease should be asked two questions.” The first question is whether the patient has any of the cardiometabolic criteria outlined above. Second, is the patient consuming alcohol?
If the patient has one of the cardiometabolic criteria but doesn’t consume alcohol, “we are straight at the diagnosis of MASLD,” she explained. If the patient does consume alcohol, it depends on how much.
Patients who have at least one cardiometabolic risk factor and consume 140-350 g for men and 210-420 g for women are considered to have Metabolic and Alcohol-Associated Liver Disease (MetALD). And those with steatotic liver disease who drink alcohol above the MetALD thresholds are considered to have ALD.
Effenberger pointed to two “cons” of the new nomenclature that need to be clarified. Although MetALD has poorer outcomes than MASLD, “it’s really hard to differentiate between ALD and MASLD,” she said. Yet the distinction is important because risks for cirrhosis, hepatocellular carcinoma (HCC), and overall mortality increase more for patients diagnosed with ALD vs MASLD.
“Do MASLD patients drink alcohol? Yes they do,” Effenberger said. “And if you have MASLD and another trigger factor like alcohol, the rates of mortality, morbidity and cancer go up.”
Moderator Laurent Castera, MD, PhD, Université Paris-Cité, Paris, France, noted that a “pro” of the new nomenclature is that it is “shedding light on the importance of alcohol because when we discuss steatotic liver disease or MASLD, alcohol is always the elephant in the room,” he said. “We need to increase the awareness that even in the absence of alcohol, you can still develop cirrhosis if you have severe metabolic risk factors.”
On the other hand, he said, “We desperately need more statistics on the true prevalence of alcohol consumption. While studies suggest the prevalence is low, at around 4% or 5%, that does not match the reality, in my opinion.”
Effenberger agreed. There’s a problem in trying to zero in on alcohol consumption because of the stigma attached to it, she said. She pointed to an Austrian study assessing patients who are diagnosed with MASLD. The researchers asked them, “Do you drink alcohol?” and all the participants said “no.” However, after completing a questionnaire designed to identify alcohol use disorders, and undergoing glucuronide tests in the urine and hair, it became clear that 25%-30% of these patients actually drank alcohol on a regular basis.
Cancer, Cirrhosis, CVD
MASLD is a trigger for cancer, especially HCC, Effenberger said. A recent review affirmed that MASLD is strongly associated with HCC, especially in Southeast Asia and India. The same study showed that many patients with MASLD are getting HCC without cirrhosis, and their cancer is often detected at a later stage, however, it’s not yet clear why they are getting HCC, and further study is needed.
In addition, MASLD is also associated with higher rates of extrahepatic cancers, including cancers of the skin and androgenic cancers. This, too, requires further investigation.
Regarding cardiovascular disease (CVD) risk, Effenberger emphasized that cardiometabolic diseases are strongly linked to each other. “Therefore, if you have diabetes and MASLD, the rates of atherosclerosis and of heart insufficiency and arteriosclerotic events like stroke and heart attacks go up, leading to the question of whether a CVD risk assessment is necessary in patients with MASLD.”
One recent study suggests that yes, it is, she reported. “If a patient has MASLD and cardiometabolic risk factors, and a risk score that suggests the patient is at increased risk of CVD for 10 years, then a CT scan of the arteries of the heart is important. The increased risk could also lead to intensified medical therapy, including GLP-1s or SGLT2s.”
During the Q&A, one attendee asked whether all patients with noncirrhotic MASLD should be screened for HCC, given the increased risk. Effenberger agreed that would be the best way to identify those at high risk; however, she said, “I think science is not in a state where you can clearly define which patients will be at high risk, and so we don’t have any guidelines for that.”
Another attendee asked why HCC is more common in Indians and Asians. Effenberger said, “We don’t know, but it is likely that there is an HCC-driven genetic risk factor.”
Remaining Questions
And finally, there’s the question of “what do we do with burnt-out MASLD?” Effenberger asked. “We know the fat content of the liver decreases when liver severity goes up. Therefore, we have a lot of patients with cirrhosis whose disease is not defined as steatotic liver because the liver fat content is no longer more than 5%.”
The decrease in fat is an ongoing process, and therefore, these patients with MASLD and advanced hepatic disease need to be better represented in the nomenclature, she suggested.
No funding information was provided. Effenberger declared working with Ipsen as a potential conflict.
A version of this article first appeared on Medscape.com.
VIENNA –United European Gastroenterology (UEG) Week 2025 in Vienna, Austria.
Maria Effenberger, MD, Medical University of Innsbruck, Berlin, Germany, told attendees atIn her presentation, “Sense and Nonsense of the New Nomenclature,” Effenberger highlighted the clinical implications of the new liver-disease terminology and pointed to a few factors still needing to be sorted out.
Both NAFLD and MASLD are steatotic liver diseasesand, notably, there are few differences between the two in clinical studies, which makes the terminology shift easier, said Effenberger. She cited a recent study showing demographic and clinical profiles of individuals classified as NAFLD and MASLD in the US were “strikingly similar,” as were the accuracy of the noninvasive tests and all-cause and cause-specific mortality rates for both conditions.
However, “the important thing about MASLD is that the term is really connected to metabolic dysfunction,” said Effenberger. To be diagnosed with MASLD, patients with liver disease need to have at least one of five cardiometabolic abnormalities: a high BMI — over 25 in White people and over 23 in Asian people; type 2 diabetes (T2D) or prediabetes; arterial hypertension; high levels of triglycerides; or a low level of high-density lipoprotein cholesterol.
“MASLD is a systemic disease, and that term represents it much better than only looking at it as a hepatological disease,” Effenberger said. “Many factors, especially inflammatory ones, influence steatosis, inflammation, and fibrosis.” These include influences from adipose tissue, the gut microbiome, the brain, a hypocaloric diet, and from steatosis of the liver itself. Proinflammatory cytokines induced by the disease can lead to inflammation throughout the body, with clinical outcomes such as stroke, heart failure, arrhythmias, myocardial infarction, chronic kidney disease.
MASLD, MetALD, or ALD?
“What is important now,” said Effenberger, is that “every patient who has liver disease should be asked two questions.” The first question is whether the patient has any of the cardiometabolic criteria outlined above. Second, is the patient consuming alcohol?
If the patient has one of the cardiometabolic criteria but doesn’t consume alcohol, “we are straight at the diagnosis of MASLD,” she explained. If the patient does consume alcohol, it depends on how much.
Patients who have at least one cardiometabolic risk factor and consume 140-350 g for men and 210-420 g for women are considered to have Metabolic and Alcohol-Associated Liver Disease (MetALD). And those with steatotic liver disease who drink alcohol above the MetALD thresholds are considered to have ALD.
Effenberger pointed to two “cons” of the new nomenclature that need to be clarified. Although MetALD has poorer outcomes than MASLD, “it’s really hard to differentiate between ALD and MASLD,” she said. Yet the distinction is important because risks for cirrhosis, hepatocellular carcinoma (HCC), and overall mortality increase more for patients diagnosed with ALD vs MASLD.
“Do MASLD patients drink alcohol? Yes they do,” Effenberger said. “And if you have MASLD and another trigger factor like alcohol, the rates of mortality, morbidity and cancer go up.”
Moderator Laurent Castera, MD, PhD, Université Paris-Cité, Paris, France, noted that a “pro” of the new nomenclature is that it is “shedding light on the importance of alcohol because when we discuss steatotic liver disease or MASLD, alcohol is always the elephant in the room,” he said. “We need to increase the awareness that even in the absence of alcohol, you can still develop cirrhosis if you have severe metabolic risk factors.”
On the other hand, he said, “We desperately need more statistics on the true prevalence of alcohol consumption. While studies suggest the prevalence is low, at around 4% or 5%, that does not match the reality, in my opinion.”
Effenberger agreed. There’s a problem in trying to zero in on alcohol consumption because of the stigma attached to it, she said. She pointed to an Austrian study assessing patients who are diagnosed with MASLD. The researchers asked them, “Do you drink alcohol?” and all the participants said “no.” However, after completing a questionnaire designed to identify alcohol use disorders, and undergoing glucuronide tests in the urine and hair, it became clear that 25%-30% of these patients actually drank alcohol on a regular basis.
Cancer, Cirrhosis, CVD
MASLD is a trigger for cancer, especially HCC, Effenberger said. A recent review affirmed that MASLD is strongly associated with HCC, especially in Southeast Asia and India. The same study showed that many patients with MASLD are getting HCC without cirrhosis, and their cancer is often detected at a later stage, however, it’s not yet clear why they are getting HCC, and further study is needed.
In addition, MASLD is also associated with higher rates of extrahepatic cancers, including cancers of the skin and androgenic cancers. This, too, requires further investigation.
Regarding cardiovascular disease (CVD) risk, Effenberger emphasized that cardiometabolic diseases are strongly linked to each other. “Therefore, if you have diabetes and MASLD, the rates of atherosclerosis and of heart insufficiency and arteriosclerotic events like stroke and heart attacks go up, leading to the question of whether a CVD risk assessment is necessary in patients with MASLD.”
One recent study suggests that yes, it is, she reported. “If a patient has MASLD and cardiometabolic risk factors, and a risk score that suggests the patient is at increased risk of CVD for 10 years, then a CT scan of the arteries of the heart is important. The increased risk could also lead to intensified medical therapy, including GLP-1s or SGLT2s.”
During the Q&A, one attendee asked whether all patients with noncirrhotic MASLD should be screened for HCC, given the increased risk. Effenberger agreed that would be the best way to identify those at high risk; however, she said, “I think science is not in a state where you can clearly define which patients will be at high risk, and so we don’t have any guidelines for that.”
Another attendee asked why HCC is more common in Indians and Asians. Effenberger said, “We don’t know, but it is likely that there is an HCC-driven genetic risk factor.”
Remaining Questions
And finally, there’s the question of “what do we do with burnt-out MASLD?” Effenberger asked. “We know the fat content of the liver decreases when liver severity goes up. Therefore, we have a lot of patients with cirrhosis whose disease is not defined as steatotic liver because the liver fat content is no longer more than 5%.”
The decrease in fat is an ongoing process, and therefore, these patients with MASLD and advanced hepatic disease need to be better represented in the nomenclature, she suggested.
No funding information was provided. Effenberger declared working with Ipsen as a potential conflict.
A version of this article first appeared on Medscape.com.
VIENNA –United European Gastroenterology (UEG) Week 2025 in Vienna, Austria.
Maria Effenberger, MD, Medical University of Innsbruck, Berlin, Germany, told attendees atIn her presentation, “Sense and Nonsense of the New Nomenclature,” Effenberger highlighted the clinical implications of the new liver-disease terminology and pointed to a few factors still needing to be sorted out.
Both NAFLD and MASLD are steatotic liver diseasesand, notably, there are few differences between the two in clinical studies, which makes the terminology shift easier, said Effenberger. She cited a recent study showing demographic and clinical profiles of individuals classified as NAFLD and MASLD in the US were “strikingly similar,” as were the accuracy of the noninvasive tests and all-cause and cause-specific mortality rates for both conditions.
However, “the important thing about MASLD is that the term is really connected to metabolic dysfunction,” said Effenberger. To be diagnosed with MASLD, patients with liver disease need to have at least one of five cardiometabolic abnormalities: a high BMI — over 25 in White people and over 23 in Asian people; type 2 diabetes (T2D) or prediabetes; arterial hypertension; high levels of triglycerides; or a low level of high-density lipoprotein cholesterol.
“MASLD is a systemic disease, and that term represents it much better than only looking at it as a hepatological disease,” Effenberger said. “Many factors, especially inflammatory ones, influence steatosis, inflammation, and fibrosis.” These include influences from adipose tissue, the gut microbiome, the brain, a hypocaloric diet, and from steatosis of the liver itself. Proinflammatory cytokines induced by the disease can lead to inflammation throughout the body, with clinical outcomes such as stroke, heart failure, arrhythmias, myocardial infarction, chronic kidney disease.
MASLD, MetALD, or ALD?
“What is important now,” said Effenberger, is that “every patient who has liver disease should be asked two questions.” The first question is whether the patient has any of the cardiometabolic criteria outlined above. Second, is the patient consuming alcohol?
If the patient has one of the cardiometabolic criteria but doesn’t consume alcohol, “we are straight at the diagnosis of MASLD,” she explained. If the patient does consume alcohol, it depends on how much.
Patients who have at least one cardiometabolic risk factor and consume 140-350 g for men and 210-420 g for women are considered to have Metabolic and Alcohol-Associated Liver Disease (MetALD). And those with steatotic liver disease who drink alcohol above the MetALD thresholds are considered to have ALD.
Effenberger pointed to two “cons” of the new nomenclature that need to be clarified. Although MetALD has poorer outcomes than MASLD, “it’s really hard to differentiate between ALD and MASLD,” she said. Yet the distinction is important because risks for cirrhosis, hepatocellular carcinoma (HCC), and overall mortality increase more for patients diagnosed with ALD vs MASLD.
“Do MASLD patients drink alcohol? Yes they do,” Effenberger said. “And if you have MASLD and another trigger factor like alcohol, the rates of mortality, morbidity and cancer go up.”
Moderator Laurent Castera, MD, PhD, Université Paris-Cité, Paris, France, noted that a “pro” of the new nomenclature is that it is “shedding light on the importance of alcohol because when we discuss steatotic liver disease or MASLD, alcohol is always the elephant in the room,” he said. “We need to increase the awareness that even in the absence of alcohol, you can still develop cirrhosis if you have severe metabolic risk factors.”
On the other hand, he said, “We desperately need more statistics on the true prevalence of alcohol consumption. While studies suggest the prevalence is low, at around 4% or 5%, that does not match the reality, in my opinion.”
Effenberger agreed. There’s a problem in trying to zero in on alcohol consumption because of the stigma attached to it, she said. She pointed to an Austrian study assessing patients who are diagnosed with MASLD. The researchers asked them, “Do you drink alcohol?” and all the participants said “no.” However, after completing a questionnaire designed to identify alcohol use disorders, and undergoing glucuronide tests in the urine and hair, it became clear that 25%-30% of these patients actually drank alcohol on a regular basis.
Cancer, Cirrhosis, CVD
MASLD is a trigger for cancer, especially HCC, Effenberger said. A recent review affirmed that MASLD is strongly associated with HCC, especially in Southeast Asia and India. The same study showed that many patients with MASLD are getting HCC without cirrhosis, and their cancer is often detected at a later stage, however, it’s not yet clear why they are getting HCC, and further study is needed.
In addition, MASLD is also associated with higher rates of extrahepatic cancers, including cancers of the skin and androgenic cancers. This, too, requires further investigation.
Regarding cardiovascular disease (CVD) risk, Effenberger emphasized that cardiometabolic diseases are strongly linked to each other. “Therefore, if you have diabetes and MASLD, the rates of atherosclerosis and of heart insufficiency and arteriosclerotic events like stroke and heart attacks go up, leading to the question of whether a CVD risk assessment is necessary in patients with MASLD.”
One recent study suggests that yes, it is, she reported. “If a patient has MASLD and cardiometabolic risk factors, and a risk score that suggests the patient is at increased risk of CVD for 10 years, then a CT scan of the arteries of the heart is important. The increased risk could also lead to intensified medical therapy, including GLP-1s or SGLT2s.”
During the Q&A, one attendee asked whether all patients with noncirrhotic MASLD should be screened for HCC, given the increased risk. Effenberger agreed that would be the best way to identify those at high risk; however, she said, “I think science is not in a state where you can clearly define which patients will be at high risk, and so we don’t have any guidelines for that.”
Another attendee asked why HCC is more common in Indians and Asians. Effenberger said, “We don’t know, but it is likely that there is an HCC-driven genetic risk factor.”
Remaining Questions
And finally, there’s the question of “what do we do with burnt-out MASLD?” Effenberger asked. “We know the fat content of the liver decreases when liver severity goes up. Therefore, we have a lot of patients with cirrhosis whose disease is not defined as steatotic liver because the liver fat content is no longer more than 5%.”
The decrease in fat is an ongoing process, and therefore, these patients with MASLD and advanced hepatic disease need to be better represented in the nomenclature, she suggested.
No funding information was provided. Effenberger declared working with Ipsen as a potential conflict.
A version of this article first appeared on Medscape.com.
Making Surgery Safer for Patients With Cirrhosis
guideline from the American College of Gastroenterology.
, according to an updatedProcedures such as cholecystectomy and hernia repair can be safely performed if precautions are taken, but surgical decision-making in patients with cirrhosis calls for a nuanced approach that takes into account several factors, including severity of liver disease, nonhepatic comorbidities, and procedure-specific considerations, wrote lead author Nadim Mahmud, MD, assistant professor of medicine and epidemiology at the Perelman School of Medicine, University of Pennsylvania, Philadelphia, and colleagues, in the American Journal of Gastroenterology.
“Patients with cirrhosis face substantially higher risks from surgery than those without liver disease, and careful guidance and risk stratification are essential,” Mahmud told GI & Hepatology News.
“At the same time, more patients are living longer with cirrhosis and increasingly require nonhepatic surgeries. Clinicians need up-to-date, practical recommendations that go beyond liver scores alone by integrating liver disease severity, comorbidities, and procedure-specific risk,” Mahmud said. The new guideline provides a comprehensive framework to help ensure that patients with cirrhosis undergo necessary operations, while managing preventable complications, he explained.
The guideline includes four recommendations for preoperative care, of which three are conditional and one is strong. The strong recommendation calls for the use of thrombopoietin receptor agonists, dosed according to baseline platelet count, in patients with cirrhosis and severe thrombocytopenia who are undergoing invasive procedures to reduce the need for perioperative transfusions and potentially reduce the risk for periprocedural bleeding.
Three conditional recommendations:
- For patients with compensated cirrhosis and unclear presence of clinically significant portal hypertension (CSPH), preoperative liver stiffness measurement and platelet count assessment are recommended to determine whether CSPH is present due to increased perioperative risks associated with the condition. Cross-sectional imaging should be conducted to identify portosystemic collaterals and complications of portal hypertension.
- For patients with cirrhosis and CSPH with alternative indications for transjugular intrahepatic portosystemic shunt (TIPS), such as large varices or refractory ascites, preoperative TIPS is suggested to reduce postoperative morbidity and mortality attributable to portal hypertension.
- For patients with cirrhosis undergoing major hepatic surgery, referral to a high-volume liver surgery or transplant center, when feasible, is recommended.
The guideline also advises on 26 key concepts, including nutrition, alcohol and tobacco use, comorbidities such as frailty and sarcopenia, and preoperative treatment of liver disease drivers such as hepatitis B, hepatitis C, and autoimmune hepatitis.
What’s New and Notable?
New elements of the guideline include use of cirrhosis-specific risk calculators, especially the Veterans Outcomes and Costs Associated with Liver disease (VOCAL)-Penn Score, to estimate operative risk and facilitate shared decision-making regarding surgery. The VOCAL-Penn Score, developed by Mahmud and colleagues at the University of Pennsylvania, incorporates surgery type and has shown superiority to older tools that often overestimate risk, Mahmud told GI & Hepatology News.
The guideline highlights standardized assessment of portal hypertension using noninvasive liver stiffness measurement plus platelet count and imaging, Mahmud said. “The guideline also underscores the importance of considering liver transplant evaluation before surgery in higher-risk patients,” he noted.
Clinicians will find clear recommendations on optimizing the perioperative period through nutritional support and structured prehabilitation, as well as the use of viscoelastic testing to guide transfusion decisions and the use of thrombopoietin-receptor agonists for severe thrombocytopenia, he added.
“Importantly, in carefully selected patients with significant portal hypertension, a preoperative transjugular intrahepatic portosystemic shunt may be reasonable, though it is not recommended broadly,” Mahmud said. “Finally, procedure-specific guidance, such as elective hernia repair after ascites control, laparoscopic cholecystectomy in well-compensated cirrhosis, and sleeve gastrectomy as the bariatric procedure of choice, helps translate risk into action,” he said.
These elements address key challenges in managing perioperative risk in patients with cirrhosis, namely miscalibrated risk estimates, inconsistent portal hypertension assessment, hemostasis management, and wide variation in practice, Mahmud noted.
Tackling Clinical Challenges
The new guideline collates the latest evidence and assessment tools to provide practical advice for clinicians to not only estimate risk but also better prepare patients with cirrhosis for surgical procedures, Peter D. Block, MD, assistant professor of medicine in the section of digestive diseases at the Yale School of Medicine, New Haven, Connecticut, told GI & Hepatology News.
“The larger and more invasive the operation, the higher the risk,” said Block, who was not involved in writing the guideline. Surgeries associated with the highest risk for patients with cirrhosis include major open abdominal operations, chest or cardiothoracic surgery, and major vascular surgeries, as well as emergency operations, for which there is less time to optimize any liver-related problems in advance, he said.
“Cirrhosis affects clotting, fluid balance, immunity, kidney function, and medication clearance, and each of these factors influence surgical risk,” Block said. “The guideline recommends combining liver-specific risk assessment scores with surgery-specific factors and clinical judgement, rather than relying on a single test,” he noted.
For elective surgeries, “the guideline provides practical pathways for when and how to optimize first, and when surgery must proceed despite higher risk,” he said.
The guideline was supported by the American College of Gastroenterology. Mahmud disclosed receiving research support from the National Institute of Diabetes and Digestive and Kidney Diseases and investigator-initiated research funding from Grifols, unrelated to the guideline. Block had no financial conflicts to disclose.
A version of this article appeared on Medscape.com
guideline from the American College of Gastroenterology.
, according to an updatedProcedures such as cholecystectomy and hernia repair can be safely performed if precautions are taken, but surgical decision-making in patients with cirrhosis calls for a nuanced approach that takes into account several factors, including severity of liver disease, nonhepatic comorbidities, and procedure-specific considerations, wrote lead author Nadim Mahmud, MD, assistant professor of medicine and epidemiology at the Perelman School of Medicine, University of Pennsylvania, Philadelphia, and colleagues, in the American Journal of Gastroenterology.
“Patients with cirrhosis face substantially higher risks from surgery than those without liver disease, and careful guidance and risk stratification are essential,” Mahmud told GI & Hepatology News.
“At the same time, more patients are living longer with cirrhosis and increasingly require nonhepatic surgeries. Clinicians need up-to-date, practical recommendations that go beyond liver scores alone by integrating liver disease severity, comorbidities, and procedure-specific risk,” Mahmud said. The new guideline provides a comprehensive framework to help ensure that patients with cirrhosis undergo necessary operations, while managing preventable complications, he explained.
The guideline includes four recommendations for preoperative care, of which three are conditional and one is strong. The strong recommendation calls for the use of thrombopoietin receptor agonists, dosed according to baseline platelet count, in patients with cirrhosis and severe thrombocytopenia who are undergoing invasive procedures to reduce the need for perioperative transfusions and potentially reduce the risk for periprocedural bleeding.
Three conditional recommendations:
- For patients with compensated cirrhosis and unclear presence of clinically significant portal hypertension (CSPH), preoperative liver stiffness measurement and platelet count assessment are recommended to determine whether CSPH is present due to increased perioperative risks associated with the condition. Cross-sectional imaging should be conducted to identify portosystemic collaterals and complications of portal hypertension.
- For patients with cirrhosis and CSPH with alternative indications for transjugular intrahepatic portosystemic shunt (TIPS), such as large varices or refractory ascites, preoperative TIPS is suggested to reduce postoperative morbidity and mortality attributable to portal hypertension.
- For patients with cirrhosis undergoing major hepatic surgery, referral to a high-volume liver surgery or transplant center, when feasible, is recommended.
The guideline also advises on 26 key concepts, including nutrition, alcohol and tobacco use, comorbidities such as frailty and sarcopenia, and preoperative treatment of liver disease drivers such as hepatitis B, hepatitis C, and autoimmune hepatitis.
What’s New and Notable?
New elements of the guideline include use of cirrhosis-specific risk calculators, especially the Veterans Outcomes and Costs Associated with Liver disease (VOCAL)-Penn Score, to estimate operative risk and facilitate shared decision-making regarding surgery. The VOCAL-Penn Score, developed by Mahmud and colleagues at the University of Pennsylvania, incorporates surgery type and has shown superiority to older tools that often overestimate risk, Mahmud told GI & Hepatology News.
The guideline highlights standardized assessment of portal hypertension using noninvasive liver stiffness measurement plus platelet count and imaging, Mahmud said. “The guideline also underscores the importance of considering liver transplant evaluation before surgery in higher-risk patients,” he noted.
Clinicians will find clear recommendations on optimizing the perioperative period through nutritional support and structured prehabilitation, as well as the use of viscoelastic testing to guide transfusion decisions and the use of thrombopoietin-receptor agonists for severe thrombocytopenia, he added.
“Importantly, in carefully selected patients with significant portal hypertension, a preoperative transjugular intrahepatic portosystemic shunt may be reasonable, though it is not recommended broadly,” Mahmud said. “Finally, procedure-specific guidance, such as elective hernia repair after ascites control, laparoscopic cholecystectomy in well-compensated cirrhosis, and sleeve gastrectomy as the bariatric procedure of choice, helps translate risk into action,” he said.
These elements address key challenges in managing perioperative risk in patients with cirrhosis, namely miscalibrated risk estimates, inconsistent portal hypertension assessment, hemostasis management, and wide variation in practice, Mahmud noted.
Tackling Clinical Challenges
The new guideline collates the latest evidence and assessment tools to provide practical advice for clinicians to not only estimate risk but also better prepare patients with cirrhosis for surgical procedures, Peter D. Block, MD, assistant professor of medicine in the section of digestive diseases at the Yale School of Medicine, New Haven, Connecticut, told GI & Hepatology News.
“The larger and more invasive the operation, the higher the risk,” said Block, who was not involved in writing the guideline. Surgeries associated with the highest risk for patients with cirrhosis include major open abdominal operations, chest or cardiothoracic surgery, and major vascular surgeries, as well as emergency operations, for which there is less time to optimize any liver-related problems in advance, he said.
“Cirrhosis affects clotting, fluid balance, immunity, kidney function, and medication clearance, and each of these factors influence surgical risk,” Block said. “The guideline recommends combining liver-specific risk assessment scores with surgery-specific factors and clinical judgement, rather than relying on a single test,” he noted.
For elective surgeries, “the guideline provides practical pathways for when and how to optimize first, and when surgery must proceed despite higher risk,” he said.
The guideline was supported by the American College of Gastroenterology. Mahmud disclosed receiving research support from the National Institute of Diabetes and Digestive and Kidney Diseases and investigator-initiated research funding from Grifols, unrelated to the guideline. Block had no financial conflicts to disclose.
A version of this article appeared on Medscape.com
guideline from the American College of Gastroenterology.
, according to an updatedProcedures such as cholecystectomy and hernia repair can be safely performed if precautions are taken, but surgical decision-making in patients with cirrhosis calls for a nuanced approach that takes into account several factors, including severity of liver disease, nonhepatic comorbidities, and procedure-specific considerations, wrote lead author Nadim Mahmud, MD, assistant professor of medicine and epidemiology at the Perelman School of Medicine, University of Pennsylvania, Philadelphia, and colleagues, in the American Journal of Gastroenterology.
“Patients with cirrhosis face substantially higher risks from surgery than those without liver disease, and careful guidance and risk stratification are essential,” Mahmud told GI & Hepatology News.
“At the same time, more patients are living longer with cirrhosis and increasingly require nonhepatic surgeries. Clinicians need up-to-date, practical recommendations that go beyond liver scores alone by integrating liver disease severity, comorbidities, and procedure-specific risk,” Mahmud said. The new guideline provides a comprehensive framework to help ensure that patients with cirrhosis undergo necessary operations, while managing preventable complications, he explained.
The guideline includes four recommendations for preoperative care, of which three are conditional and one is strong. The strong recommendation calls for the use of thrombopoietin receptor agonists, dosed according to baseline platelet count, in patients with cirrhosis and severe thrombocytopenia who are undergoing invasive procedures to reduce the need for perioperative transfusions and potentially reduce the risk for periprocedural bleeding.
Three conditional recommendations:
- For patients with compensated cirrhosis and unclear presence of clinically significant portal hypertension (CSPH), preoperative liver stiffness measurement and platelet count assessment are recommended to determine whether CSPH is present due to increased perioperative risks associated with the condition. Cross-sectional imaging should be conducted to identify portosystemic collaterals and complications of portal hypertension.
- For patients with cirrhosis and CSPH with alternative indications for transjugular intrahepatic portosystemic shunt (TIPS), such as large varices or refractory ascites, preoperative TIPS is suggested to reduce postoperative morbidity and mortality attributable to portal hypertension.
- For patients with cirrhosis undergoing major hepatic surgery, referral to a high-volume liver surgery or transplant center, when feasible, is recommended.
The guideline also advises on 26 key concepts, including nutrition, alcohol and tobacco use, comorbidities such as frailty and sarcopenia, and preoperative treatment of liver disease drivers such as hepatitis B, hepatitis C, and autoimmune hepatitis.
What’s New and Notable?
New elements of the guideline include use of cirrhosis-specific risk calculators, especially the Veterans Outcomes and Costs Associated with Liver disease (VOCAL)-Penn Score, to estimate operative risk and facilitate shared decision-making regarding surgery. The VOCAL-Penn Score, developed by Mahmud and colleagues at the University of Pennsylvania, incorporates surgery type and has shown superiority to older tools that often overestimate risk, Mahmud told GI & Hepatology News.
The guideline highlights standardized assessment of portal hypertension using noninvasive liver stiffness measurement plus platelet count and imaging, Mahmud said. “The guideline also underscores the importance of considering liver transplant evaluation before surgery in higher-risk patients,” he noted.
Clinicians will find clear recommendations on optimizing the perioperative period through nutritional support and structured prehabilitation, as well as the use of viscoelastic testing to guide transfusion decisions and the use of thrombopoietin-receptor agonists for severe thrombocytopenia, he added.
“Importantly, in carefully selected patients with significant portal hypertension, a preoperative transjugular intrahepatic portosystemic shunt may be reasonable, though it is not recommended broadly,” Mahmud said. “Finally, procedure-specific guidance, such as elective hernia repair after ascites control, laparoscopic cholecystectomy in well-compensated cirrhosis, and sleeve gastrectomy as the bariatric procedure of choice, helps translate risk into action,” he said.
These elements address key challenges in managing perioperative risk in patients with cirrhosis, namely miscalibrated risk estimates, inconsistent portal hypertension assessment, hemostasis management, and wide variation in practice, Mahmud noted.
Tackling Clinical Challenges
The new guideline collates the latest evidence and assessment tools to provide practical advice for clinicians to not only estimate risk but also better prepare patients with cirrhosis for surgical procedures, Peter D. Block, MD, assistant professor of medicine in the section of digestive diseases at the Yale School of Medicine, New Haven, Connecticut, told GI & Hepatology News.
“The larger and more invasive the operation, the higher the risk,” said Block, who was not involved in writing the guideline. Surgeries associated with the highest risk for patients with cirrhosis include major open abdominal operations, chest or cardiothoracic surgery, and major vascular surgeries, as well as emergency operations, for which there is less time to optimize any liver-related problems in advance, he said.
“Cirrhosis affects clotting, fluid balance, immunity, kidney function, and medication clearance, and each of these factors influence surgical risk,” Block said. “The guideline recommends combining liver-specific risk assessment scores with surgery-specific factors and clinical judgement, rather than relying on a single test,” he noted.
For elective surgeries, “the guideline provides practical pathways for when and how to optimize first, and when surgery must proceed despite higher risk,” he said.
The guideline was supported by the American College of Gastroenterology. Mahmud disclosed receiving research support from the National Institute of Diabetes and Digestive and Kidney Diseases and investigator-initiated research funding from Grifols, unrelated to the guideline. Block had no financial conflicts to disclose.
A version of this article appeared on Medscape.com
Prevention and Risk-Based Surveillance Key to Curbing HCC
BERLIN —
according to a joint statement from United European Gastroenterology (UEG) and the German Society for Gastroenterology, Digestive and Metabolic Diseases (DGVS).The statement calls on EU and national policymakers to embed a twofold approach into healthcare systems that combines surveillance and prevention, rather than relying on voluntary participation. It also encourages stronger prevention measures, such as improved food labeling and restrictions on marketing unhealthy foods to children. The statement — which was also endorsed by the European Association for the Study of the Liver (EASL) — was presented at UEG Week 2025 .
“Curing HCC in early stages rather than treating the disease in a palliative setting should be the goal for all liver doctors and carers, and this is certainly the goal for patients,” said Thomas Seufferlein, MD, professor of gastroenterology at Ulm University, Germany, and one of the members of the DGVS who initiated the statement.
“We have to take HCC screening seriously which means setting up a structured, nationwide, well-documented, and evaluated program for HCC screening in Germany,” he said in an interview.
HCC is mainly curable in the early stages by local ablation, resection, or liver transplantation, “so early diagnosis is of the utmost importance for improving survival,” added Patrick Michl, MD, gastroenterologist, University of Heidelberg, Germany, DGVS member and co-initiator of the statement.
Risk-Stratified HCC Surveillance
In the face of rising rates worldwide, the UEG/DGVS call on policymakers to recognize liver cancer as a preventable and growing public health priority and to implement structured surveillance programs guided by risk thresholds. In particular, they support the recent policy statement from EASL recommending risk-based screening.
EASL’s key recommendations include:
- Targeted surveillance for individuals with an annual HCC risk exceeding 1.5%, where it is both clinically beneficial and cost-effective
- Risk scoring tools such as the age-male-albumin-bilirubin-platelets score that incorporates age, sex, platelet count, albumin, and bilirubin, to stratify patients by HCC risk, including those without established cirrhosis
- Enhanced surveillance for very high-risk groups, where MRI-based surveillance may be warranted despite higher costs, given its superior sensitivity for early-stage disease
- A de-escalation in low-risk individuals
- Patients with an annual HCC risk < 0.5% may be safely spared surveillance, avoiding unnecessary interventions
Evidence from France, Italy, and the UK showed that structured surveillance in high-risk groups is both clinically beneficial and cost-effective. National models in France have demonstrated higher curative treatment rates and fewer costly late-stage cases with structured surveillance. In the UK, health technology assessments indicate targeted surveillance is an efficient use of National Health Services resources, particularly when uptake is optimized. Italian models show that earlier diagnosis in well-defined high-risk groups can offset downstream treatment costs.
Seufferlein noted that Germany needs a “structured program to be implemented and there is currently little public awareness regarding this surveillance strategy.” However, he added there is a structured hepatitis B vaccination program in Germany, which has been successful. “Studies show that the inclusion of hep B vaccination in infancy and childhood has led to good uptake among young age groups.”
Germany, however, has yet to conduct national studies. “Prospective data on HCC surveillance benefits in Germany are lacking,” said Michl, “but multi-country models incorporating Germany’s cost structures suggest similar benefits would accrue if there were greater adherence to guideline-based recommendations and if publicly funded screening programs were implemented.”
Current recommendations in Germany for surveillance are based on evidence-based guidelines of the DGVS with stronger (‘should’) or weaker (‘may’) evidence-based recommendations. For example, patients with chronic hepatitis B virus infection should be offered regular surveillance once their platelet age gender–hepatitis B risk score is ≥ 10. In patients with advanced fibrosis because of chronic hepatitis C virus infection, regular surveillance should also be offered.
Barriers to Screening Uptake
HCC remains one of the most lethal cancers in Europe, largely because it is often diagnosed too late. Underdiagnosis of chronic liver disease, limited access to imaging, and reimbursement gaps prevent timely intervention.
Maria Buti, MD, consultant hepatologist, Hospital Vall d’Hebron, Barcelona, Spain, who was not involved in drafting the statement, remarked that “Patients with liver cirrhosis, or with advanced fibrosis, and also some high-risk noncirrhotic patients such as those with hepatitis B, clearly benefit from surveillance. Surveillance can change life expectancy and also reduce morbidity.”
However, structural barriers continue to impede uptake. “It is not always easy to identify patients with liver cirrhosis because the majority are completely asymptomatic in the early stages,” she said.
Even when risk factors are identified, adherence to 6-monthly surveillance remains patchy. “Sometimes physicians forget to request ultrasounds, or patients don’t understand the importance of it because they feel well,” Buti told GI & Hepatology News.
Expanded Training and Public Health Measures
The joint statement also advocates for expanded physician training in nutrition and hepatology, equitable access to diagnostic tools including MRI, and EU-wide nutrition labeling systems such as Nutri-Score.
The authors also called for strengthened public health measures to tackle obesity, alcohol misuse, and hepatitis transmission, and fiscal and regulatory measures such as taxation of obesogenic foods, and reducing the cost burden of healthier foods.
“If we decrease the percentage of people with liver cirrhosis through prevention, fewer people will need surveillance,” Buti stated.
Seufferlein, Michl, and Buti all declared no relevant disclosures. All three experts are members of the UEG Public Affairs Group.
A version of this article appeared on Medscape.com.
BERLIN —
according to a joint statement from United European Gastroenterology (UEG) and the German Society for Gastroenterology, Digestive and Metabolic Diseases (DGVS).The statement calls on EU and national policymakers to embed a twofold approach into healthcare systems that combines surveillance and prevention, rather than relying on voluntary participation. It also encourages stronger prevention measures, such as improved food labeling and restrictions on marketing unhealthy foods to children. The statement — which was also endorsed by the European Association for the Study of the Liver (EASL) — was presented at UEG Week 2025 .
“Curing HCC in early stages rather than treating the disease in a palliative setting should be the goal for all liver doctors and carers, and this is certainly the goal for patients,” said Thomas Seufferlein, MD, professor of gastroenterology at Ulm University, Germany, and one of the members of the DGVS who initiated the statement.
“We have to take HCC screening seriously which means setting up a structured, nationwide, well-documented, and evaluated program for HCC screening in Germany,” he said in an interview.
HCC is mainly curable in the early stages by local ablation, resection, or liver transplantation, “so early diagnosis is of the utmost importance for improving survival,” added Patrick Michl, MD, gastroenterologist, University of Heidelberg, Germany, DGVS member and co-initiator of the statement.
Risk-Stratified HCC Surveillance
In the face of rising rates worldwide, the UEG/DGVS call on policymakers to recognize liver cancer as a preventable and growing public health priority and to implement structured surveillance programs guided by risk thresholds. In particular, they support the recent policy statement from EASL recommending risk-based screening.
EASL’s key recommendations include:
- Targeted surveillance for individuals with an annual HCC risk exceeding 1.5%, where it is both clinically beneficial and cost-effective
- Risk scoring tools such as the age-male-albumin-bilirubin-platelets score that incorporates age, sex, platelet count, albumin, and bilirubin, to stratify patients by HCC risk, including those without established cirrhosis
- Enhanced surveillance for very high-risk groups, where MRI-based surveillance may be warranted despite higher costs, given its superior sensitivity for early-stage disease
- A de-escalation in low-risk individuals
- Patients with an annual HCC risk < 0.5% may be safely spared surveillance, avoiding unnecessary interventions
Evidence from France, Italy, and the UK showed that structured surveillance in high-risk groups is both clinically beneficial and cost-effective. National models in France have demonstrated higher curative treatment rates and fewer costly late-stage cases with structured surveillance. In the UK, health technology assessments indicate targeted surveillance is an efficient use of National Health Services resources, particularly when uptake is optimized. Italian models show that earlier diagnosis in well-defined high-risk groups can offset downstream treatment costs.
Seufferlein noted that Germany needs a “structured program to be implemented and there is currently little public awareness regarding this surveillance strategy.” However, he added there is a structured hepatitis B vaccination program in Germany, which has been successful. “Studies show that the inclusion of hep B vaccination in infancy and childhood has led to good uptake among young age groups.”
Germany, however, has yet to conduct national studies. “Prospective data on HCC surveillance benefits in Germany are lacking,” said Michl, “but multi-country models incorporating Germany’s cost structures suggest similar benefits would accrue if there were greater adherence to guideline-based recommendations and if publicly funded screening programs were implemented.”
Current recommendations in Germany for surveillance are based on evidence-based guidelines of the DGVS with stronger (‘should’) or weaker (‘may’) evidence-based recommendations. For example, patients with chronic hepatitis B virus infection should be offered regular surveillance once their platelet age gender–hepatitis B risk score is ≥ 10. In patients with advanced fibrosis because of chronic hepatitis C virus infection, regular surveillance should also be offered.
Barriers to Screening Uptake
HCC remains one of the most lethal cancers in Europe, largely because it is often diagnosed too late. Underdiagnosis of chronic liver disease, limited access to imaging, and reimbursement gaps prevent timely intervention.
Maria Buti, MD, consultant hepatologist, Hospital Vall d’Hebron, Barcelona, Spain, who was not involved in drafting the statement, remarked that “Patients with liver cirrhosis, or with advanced fibrosis, and also some high-risk noncirrhotic patients such as those with hepatitis B, clearly benefit from surveillance. Surveillance can change life expectancy and also reduce morbidity.”
However, structural barriers continue to impede uptake. “It is not always easy to identify patients with liver cirrhosis because the majority are completely asymptomatic in the early stages,” she said.
Even when risk factors are identified, adherence to 6-monthly surveillance remains patchy. “Sometimes physicians forget to request ultrasounds, or patients don’t understand the importance of it because they feel well,” Buti told GI & Hepatology News.
Expanded Training and Public Health Measures
The joint statement also advocates for expanded physician training in nutrition and hepatology, equitable access to diagnostic tools including MRI, and EU-wide nutrition labeling systems such as Nutri-Score.
The authors also called for strengthened public health measures to tackle obesity, alcohol misuse, and hepatitis transmission, and fiscal and regulatory measures such as taxation of obesogenic foods, and reducing the cost burden of healthier foods.
“If we decrease the percentage of people with liver cirrhosis through prevention, fewer people will need surveillance,” Buti stated.
Seufferlein, Michl, and Buti all declared no relevant disclosures. All three experts are members of the UEG Public Affairs Group.
A version of this article appeared on Medscape.com.
BERLIN —
according to a joint statement from United European Gastroenterology (UEG) and the German Society for Gastroenterology, Digestive and Metabolic Diseases (DGVS).The statement calls on EU and national policymakers to embed a twofold approach into healthcare systems that combines surveillance and prevention, rather than relying on voluntary participation. It also encourages stronger prevention measures, such as improved food labeling and restrictions on marketing unhealthy foods to children. The statement — which was also endorsed by the European Association for the Study of the Liver (EASL) — was presented at UEG Week 2025 .
“Curing HCC in early stages rather than treating the disease in a palliative setting should be the goal for all liver doctors and carers, and this is certainly the goal for patients,” said Thomas Seufferlein, MD, professor of gastroenterology at Ulm University, Germany, and one of the members of the DGVS who initiated the statement.
“We have to take HCC screening seriously which means setting up a structured, nationwide, well-documented, and evaluated program for HCC screening in Germany,” he said in an interview.
HCC is mainly curable in the early stages by local ablation, resection, or liver transplantation, “so early diagnosis is of the utmost importance for improving survival,” added Patrick Michl, MD, gastroenterologist, University of Heidelberg, Germany, DGVS member and co-initiator of the statement.
Risk-Stratified HCC Surveillance
In the face of rising rates worldwide, the UEG/DGVS call on policymakers to recognize liver cancer as a preventable and growing public health priority and to implement structured surveillance programs guided by risk thresholds. In particular, they support the recent policy statement from EASL recommending risk-based screening.
EASL’s key recommendations include:
- Targeted surveillance for individuals with an annual HCC risk exceeding 1.5%, where it is both clinically beneficial and cost-effective
- Risk scoring tools such as the age-male-albumin-bilirubin-platelets score that incorporates age, sex, platelet count, albumin, and bilirubin, to stratify patients by HCC risk, including those without established cirrhosis
- Enhanced surveillance for very high-risk groups, where MRI-based surveillance may be warranted despite higher costs, given its superior sensitivity for early-stage disease
- A de-escalation in low-risk individuals
- Patients with an annual HCC risk < 0.5% may be safely spared surveillance, avoiding unnecessary interventions
Evidence from France, Italy, and the UK showed that structured surveillance in high-risk groups is both clinically beneficial and cost-effective. National models in France have demonstrated higher curative treatment rates and fewer costly late-stage cases with structured surveillance. In the UK, health technology assessments indicate targeted surveillance is an efficient use of National Health Services resources, particularly when uptake is optimized. Italian models show that earlier diagnosis in well-defined high-risk groups can offset downstream treatment costs.
Seufferlein noted that Germany needs a “structured program to be implemented and there is currently little public awareness regarding this surveillance strategy.” However, he added there is a structured hepatitis B vaccination program in Germany, which has been successful. “Studies show that the inclusion of hep B vaccination in infancy and childhood has led to good uptake among young age groups.”
Germany, however, has yet to conduct national studies. “Prospective data on HCC surveillance benefits in Germany are lacking,” said Michl, “but multi-country models incorporating Germany’s cost structures suggest similar benefits would accrue if there were greater adherence to guideline-based recommendations and if publicly funded screening programs were implemented.”
Current recommendations in Germany for surveillance are based on evidence-based guidelines of the DGVS with stronger (‘should’) or weaker (‘may’) evidence-based recommendations. For example, patients with chronic hepatitis B virus infection should be offered regular surveillance once their platelet age gender–hepatitis B risk score is ≥ 10. In patients with advanced fibrosis because of chronic hepatitis C virus infection, regular surveillance should also be offered.
Barriers to Screening Uptake
HCC remains one of the most lethal cancers in Europe, largely because it is often diagnosed too late. Underdiagnosis of chronic liver disease, limited access to imaging, and reimbursement gaps prevent timely intervention.
Maria Buti, MD, consultant hepatologist, Hospital Vall d’Hebron, Barcelona, Spain, who was not involved in drafting the statement, remarked that “Patients with liver cirrhosis, or with advanced fibrosis, and also some high-risk noncirrhotic patients such as those with hepatitis B, clearly benefit from surveillance. Surveillance can change life expectancy and also reduce morbidity.”
However, structural barriers continue to impede uptake. “It is not always easy to identify patients with liver cirrhosis because the majority are completely asymptomatic in the early stages,” she said.
Even when risk factors are identified, adherence to 6-monthly surveillance remains patchy. “Sometimes physicians forget to request ultrasounds, or patients don’t understand the importance of it because they feel well,” Buti told GI & Hepatology News.
Expanded Training and Public Health Measures
The joint statement also advocates for expanded physician training in nutrition and hepatology, equitable access to diagnostic tools including MRI, and EU-wide nutrition labeling systems such as Nutri-Score.
The authors also called for strengthened public health measures to tackle obesity, alcohol misuse, and hepatitis transmission, and fiscal and regulatory measures such as taxation of obesogenic foods, and reducing the cost burden of healthier foods.
“If we decrease the percentage of people with liver cirrhosis through prevention, fewer people will need surveillance,” Buti stated.
Seufferlein, Michl, and Buti all declared no relevant disclosures. All three experts are members of the UEG Public Affairs Group.
A version of this article appeared on Medscape.com.
FROM UEG WEEK 2025
Linerixibat Reduces Itching in PBC
BERLIN —
, according to phase 3 results from the GLISTEN trial.The therapy also improved sleep interference associated with itching and was generally well-tolerated, offering hope for patients who do not respond to existing treatments.
“Linerixibat has the potential to be the first global therapy indicated for pruritus,” asserted Andreas E. Kremer, MD, Department of Gastroenterology and Hepatology, University Hospital Zürich, Switzerland, who presented the findings at United European Gastroenterology (UEG) Week 2025.
Cholestatic pruritus is one of the most distressing and disabling symptoms of PBC, often unrelieved by existing first-line therapies such as ursodeoxycholic acid.
Up to 70% of patients with PBC experience cholestatic pruritus which can seriously impair quality of life, comparable to that seen in severe Parkinson’s disease or heart failure, said Kremer. With the limitations of existing treatments, symptom control remains a major unmet clinical need.
The GLISTEN Trial
Linerixibat is a minimally absorbed oral IBAT inhibitor that inhibits bile acid reuptake and reduces key mediators of pruritus.
Participants in the double-blind, placebo-controlled trial were randomized to oral linerixibat 40 mg twice daily (n = 119) or to placebo (n = 119) for 24 weeks. Patients had PBC and moderate-to-severe pruritus (Worst Itch Numerical Rating Scale [WI-NRS] ≥ 4).
The primary endpoint was change from baseline in monthly worst-itch score over 24 weeks. Key secondary endpoints included change in itch at week 2, change in sleep interference over 24 weeks, responder rates (≥ 2-, ≥ 3-, and ≥ 4-point reduction), and patient-reported global impression of severity and change.
The majority of participants (95%) were women and had a mean WI-NRS of 7.3 at baseline. After 24 weeks of twice daily dosing of linerixibat or placebo, participants entered a blinded crossover period for 8 weeks.
24-Week Data
Linerixibat produced a significant improvement in pruritus vs placebo, with a least-squares mean change in WI-NRS of -2.86 compared with -2.15, respectively, resulting in an adjusted mean difference of -0.72 (P = .001). The benefit appeared rapid, with superiority already evident at 2 weeks (P < .001), noted Kremer, adding this is important for patients.
Pruritus-related sleep interference NRS also improved significantly (-2.77 vs -2.24; difference, -0.53; P = .024). By week 24, 56% of patients with linerixibat achieved a ≥ 3-point reduction compared with 43% of those treated with placebo (nominal P = .043).
“A three-point reduction for a patient with pruritus is a clearly meaningful benefit,” said Kremer.
In addition, a greater proportion of patients with linerixibat rated their itch as “absent” (21% vs 9%) on the patient global impression of severity scales. The ideal goal for these patients is complete relief, “and here we saw that every fifth patient on linerixibat achieved such relief,” he pointed out.
Linerixibat was generally well-tolerated, and the most frequent on-treatment adverse event was diarrhea, which occurred in 61% of patients compared with 18% of those on placebo. There were five (4%) discontinuations on linerixibat vs one (< 1%) on placebo. Abdominal pain was experienced by 18% on linerixibat and 3% on placebo. There was also a slight elevation of alanine aminotransferase in 11 (9%) vs three patients (3%).
“In summary, it is a safe drug from our perspective,” said Kremer.
Focusing on Symptoms, Not Biochemical Response
Commenting for GI & Hepatology News, Frank Tacke, MD, head of the Department of Hepatology and Gastroenterology at Charité Medical University Berlin, Germany, explained that so far drugs for the treatment of PBC focused on the biochemical response. These treatments have shown a reduction in liver enzymes and in disease activity, but less of a reduction in symptoms, he explained. “This is the first drug at phase 3 that focuses on itching, which is one of the major symptoms in people with PBC. As such, this is a major breakthrough.”
Sabine Weber, MD, gastroenterologist at the University Hospital of Munich, Germany, said that the data suggested particular potential for patients whose pruritus doesn’t respond to first-line treatment, even if the treatment is otherwise effective.
“This is so important for patients who — due to their extreme itching — experience serious lifestyle effects such as isolation because they can’t go out socially,” she said. “We desperately need drugs to help these patients, and here we have one drug that seems to do this.”
Weber noted that linerixibat works differently from other PBC treatments. It is licensed in pediatric medicine for a number of diseases, but “this is the first time we’ve seen it for use in adults,” she added.
Kremer disclosed receiving research support from Gilead, Intercept Pharmaceuticals, and Roche; consulting for AbbVie, Advanz, Alentis, Alphasigma, AstraZeneca, Avior, Bayer, CymaBay Therapeutics, Eisai, Escient, Falk, Gilead, GSK, Intercept Pharmaceuticals, Ipsen, Mirum, MSD, Roche, Takeda, and Vifor; and receiving payment or honoraria from AbbVie, Advanz, Alphasigma, Falk, Gilead, GSK, Intercept Pharmaceuticals, Ipsen, Mirum, MSD, Roche, Takeda, and Vifor. Tache declared that he previously gave lectures for GSK. Weber declared no relevant conflicts of interest.
The GLISTEN study was funded by GSK.
A version of this article appeared on Medscape.com.
BERLIN —
, according to phase 3 results from the GLISTEN trial.The therapy also improved sleep interference associated with itching and was generally well-tolerated, offering hope for patients who do not respond to existing treatments.
“Linerixibat has the potential to be the first global therapy indicated for pruritus,” asserted Andreas E. Kremer, MD, Department of Gastroenterology and Hepatology, University Hospital Zürich, Switzerland, who presented the findings at United European Gastroenterology (UEG) Week 2025.
Cholestatic pruritus is one of the most distressing and disabling symptoms of PBC, often unrelieved by existing first-line therapies such as ursodeoxycholic acid.
Up to 70% of patients with PBC experience cholestatic pruritus which can seriously impair quality of life, comparable to that seen in severe Parkinson’s disease or heart failure, said Kremer. With the limitations of existing treatments, symptom control remains a major unmet clinical need.
The GLISTEN Trial
Linerixibat is a minimally absorbed oral IBAT inhibitor that inhibits bile acid reuptake and reduces key mediators of pruritus.
Participants in the double-blind, placebo-controlled trial were randomized to oral linerixibat 40 mg twice daily (n = 119) or to placebo (n = 119) for 24 weeks. Patients had PBC and moderate-to-severe pruritus (Worst Itch Numerical Rating Scale [WI-NRS] ≥ 4).
The primary endpoint was change from baseline in monthly worst-itch score over 24 weeks. Key secondary endpoints included change in itch at week 2, change in sleep interference over 24 weeks, responder rates (≥ 2-, ≥ 3-, and ≥ 4-point reduction), and patient-reported global impression of severity and change.
The majority of participants (95%) were women and had a mean WI-NRS of 7.3 at baseline. After 24 weeks of twice daily dosing of linerixibat or placebo, participants entered a blinded crossover period for 8 weeks.
24-Week Data
Linerixibat produced a significant improvement in pruritus vs placebo, with a least-squares mean change in WI-NRS of -2.86 compared with -2.15, respectively, resulting in an adjusted mean difference of -0.72 (P = .001). The benefit appeared rapid, with superiority already evident at 2 weeks (P < .001), noted Kremer, adding this is important for patients.
Pruritus-related sleep interference NRS also improved significantly (-2.77 vs -2.24; difference, -0.53; P = .024). By week 24, 56% of patients with linerixibat achieved a ≥ 3-point reduction compared with 43% of those treated with placebo (nominal P = .043).
“A three-point reduction for a patient with pruritus is a clearly meaningful benefit,” said Kremer.
In addition, a greater proportion of patients with linerixibat rated their itch as “absent” (21% vs 9%) on the patient global impression of severity scales. The ideal goal for these patients is complete relief, “and here we saw that every fifth patient on linerixibat achieved such relief,” he pointed out.
Linerixibat was generally well-tolerated, and the most frequent on-treatment adverse event was diarrhea, which occurred in 61% of patients compared with 18% of those on placebo. There were five (4%) discontinuations on linerixibat vs one (< 1%) on placebo. Abdominal pain was experienced by 18% on linerixibat and 3% on placebo. There was also a slight elevation of alanine aminotransferase in 11 (9%) vs three patients (3%).
“In summary, it is a safe drug from our perspective,” said Kremer.
Focusing on Symptoms, Not Biochemical Response
Commenting for GI & Hepatology News, Frank Tacke, MD, head of the Department of Hepatology and Gastroenterology at Charité Medical University Berlin, Germany, explained that so far drugs for the treatment of PBC focused on the biochemical response. These treatments have shown a reduction in liver enzymes and in disease activity, but less of a reduction in symptoms, he explained. “This is the first drug at phase 3 that focuses on itching, which is one of the major symptoms in people with PBC. As such, this is a major breakthrough.”
Sabine Weber, MD, gastroenterologist at the University Hospital of Munich, Germany, said that the data suggested particular potential for patients whose pruritus doesn’t respond to first-line treatment, even if the treatment is otherwise effective.
“This is so important for patients who — due to their extreme itching — experience serious lifestyle effects such as isolation because they can’t go out socially,” she said. “We desperately need drugs to help these patients, and here we have one drug that seems to do this.”
Weber noted that linerixibat works differently from other PBC treatments. It is licensed in pediatric medicine for a number of diseases, but “this is the first time we’ve seen it for use in adults,” she added.
Kremer disclosed receiving research support from Gilead, Intercept Pharmaceuticals, and Roche; consulting for AbbVie, Advanz, Alentis, Alphasigma, AstraZeneca, Avior, Bayer, CymaBay Therapeutics, Eisai, Escient, Falk, Gilead, GSK, Intercept Pharmaceuticals, Ipsen, Mirum, MSD, Roche, Takeda, and Vifor; and receiving payment or honoraria from AbbVie, Advanz, Alphasigma, Falk, Gilead, GSK, Intercept Pharmaceuticals, Ipsen, Mirum, MSD, Roche, Takeda, and Vifor. Tache declared that he previously gave lectures for GSK. Weber declared no relevant conflicts of interest.
The GLISTEN study was funded by GSK.
A version of this article appeared on Medscape.com.
BERLIN —
, according to phase 3 results from the GLISTEN trial.The therapy also improved sleep interference associated with itching and was generally well-tolerated, offering hope for patients who do not respond to existing treatments.
“Linerixibat has the potential to be the first global therapy indicated for pruritus,” asserted Andreas E. Kremer, MD, Department of Gastroenterology and Hepatology, University Hospital Zürich, Switzerland, who presented the findings at United European Gastroenterology (UEG) Week 2025.
Cholestatic pruritus is one of the most distressing and disabling symptoms of PBC, often unrelieved by existing first-line therapies such as ursodeoxycholic acid.
Up to 70% of patients with PBC experience cholestatic pruritus which can seriously impair quality of life, comparable to that seen in severe Parkinson’s disease or heart failure, said Kremer. With the limitations of existing treatments, symptom control remains a major unmet clinical need.
The GLISTEN Trial
Linerixibat is a minimally absorbed oral IBAT inhibitor that inhibits bile acid reuptake and reduces key mediators of pruritus.
Participants in the double-blind, placebo-controlled trial were randomized to oral linerixibat 40 mg twice daily (n = 119) or to placebo (n = 119) for 24 weeks. Patients had PBC and moderate-to-severe pruritus (Worst Itch Numerical Rating Scale [WI-NRS] ≥ 4).
The primary endpoint was change from baseline in monthly worst-itch score over 24 weeks. Key secondary endpoints included change in itch at week 2, change in sleep interference over 24 weeks, responder rates (≥ 2-, ≥ 3-, and ≥ 4-point reduction), and patient-reported global impression of severity and change.
The majority of participants (95%) were women and had a mean WI-NRS of 7.3 at baseline. After 24 weeks of twice daily dosing of linerixibat or placebo, participants entered a blinded crossover period for 8 weeks.
24-Week Data
Linerixibat produced a significant improvement in pruritus vs placebo, with a least-squares mean change in WI-NRS of -2.86 compared with -2.15, respectively, resulting in an adjusted mean difference of -0.72 (P = .001). The benefit appeared rapid, with superiority already evident at 2 weeks (P < .001), noted Kremer, adding this is important for patients.
Pruritus-related sleep interference NRS also improved significantly (-2.77 vs -2.24; difference, -0.53; P = .024). By week 24, 56% of patients with linerixibat achieved a ≥ 3-point reduction compared with 43% of those treated with placebo (nominal P = .043).
“A three-point reduction for a patient with pruritus is a clearly meaningful benefit,” said Kremer.
In addition, a greater proportion of patients with linerixibat rated their itch as “absent” (21% vs 9%) on the patient global impression of severity scales. The ideal goal for these patients is complete relief, “and here we saw that every fifth patient on linerixibat achieved such relief,” he pointed out.
Linerixibat was generally well-tolerated, and the most frequent on-treatment adverse event was diarrhea, which occurred in 61% of patients compared with 18% of those on placebo. There were five (4%) discontinuations on linerixibat vs one (< 1%) on placebo. Abdominal pain was experienced by 18% on linerixibat and 3% on placebo. There was also a slight elevation of alanine aminotransferase in 11 (9%) vs three patients (3%).
“In summary, it is a safe drug from our perspective,” said Kremer.
Focusing on Symptoms, Not Biochemical Response
Commenting for GI & Hepatology News, Frank Tacke, MD, head of the Department of Hepatology and Gastroenterology at Charité Medical University Berlin, Germany, explained that so far drugs for the treatment of PBC focused on the biochemical response. These treatments have shown a reduction in liver enzymes and in disease activity, but less of a reduction in symptoms, he explained. “This is the first drug at phase 3 that focuses on itching, which is one of the major symptoms in people with PBC. As such, this is a major breakthrough.”
Sabine Weber, MD, gastroenterologist at the University Hospital of Munich, Germany, said that the data suggested particular potential for patients whose pruritus doesn’t respond to first-line treatment, even if the treatment is otherwise effective.
“This is so important for patients who — due to their extreme itching — experience serious lifestyle effects such as isolation because they can’t go out socially,” she said. “We desperately need drugs to help these patients, and here we have one drug that seems to do this.”
Weber noted that linerixibat works differently from other PBC treatments. It is licensed in pediatric medicine for a number of diseases, but “this is the first time we’ve seen it for use in adults,” she added.
Kremer disclosed receiving research support from Gilead, Intercept Pharmaceuticals, and Roche; consulting for AbbVie, Advanz, Alentis, Alphasigma, AstraZeneca, Avior, Bayer, CymaBay Therapeutics, Eisai, Escient, Falk, Gilead, GSK, Intercept Pharmaceuticals, Ipsen, Mirum, MSD, Roche, Takeda, and Vifor; and receiving payment or honoraria from AbbVie, Advanz, Alphasigma, Falk, Gilead, GSK, Intercept Pharmaceuticals, Ipsen, Mirum, MSD, Roche, Takeda, and Vifor. Tache declared that he previously gave lectures for GSK. Weber declared no relevant conflicts of interest.
The GLISTEN study was funded by GSK.
A version of this article appeared on Medscape.com.
MASLD/MASH Global Consensus Recommendations Address Guideline Discordance
These recommendations aim to boost guideline adherence and disease awareness, which have lagged despite a surge of national and international guidance in recent years, lead author Zobair M. Younossi, MD, of the Global NASH/MASH Council, Washington, DC, and colleagues, reported.
“Although these documents are similar in many ways, there are important differences in their recommendations, which have created some confusion within the field,” the panel wrote in Gastroenterology. “Areas of discordance among guidelines can be partly responsible for their low rate of implementation and the suboptimal awareness about this liver disease. Furthermore, these guidelines can be long and complex, making it challenging for busy clinicians to access the appropriate information quickly and efficiently.”
To address these gaps, more than 40 experts from around the world collaborated on the consensus project. The team reviewed 61 eligible documents published between 2018 and January 2025. Each guideline was evaluated across eight domains: epidemiology; screening; risk stratification using noninvasive tests (NITs); lifestyle management; treatment with existing medications; treatment with future medications; hepatocellular carcinoma (HCC) and preventive guidance; and pregnancy and pediatric populations.
Areas of discordance were advanced to a Delphi process using iterative online surveys, with a supermajority threshold of 67% required for acceptance. Four Delphi rounds were conducted, and by the end, all statements had achieved more than 90% agreement. The final recommendations were then summarized into practical algorithms for clinical use.
The results cover the full spectrum of MASLD care. For screening and diagnosis, experts agreed that individuals with type 2 diabetes, obesity plus cardiometabolic risk factors, or persistently elevated aminotransferases should be considered high risk. Alcohol thresholds were standardized, clarifying when to classify disease as MASLD, alcohol-related liver disease, or the hybrid “Met-ALD.”
For risk stratification, the panel endorsed a two-step algorithm beginning with the Fibrosis-4 (FIB-4) index, followed by vibration-controlled transient elastography (VCTE) or other NITs in patients above the threshold. This approach, the authors noted, was designed to be feasible in both primary care and specialty settings.
Lifestyle intervention remains the cornerstone of treatment, with weight-loss goals of 5% to reduce steatosis, 7%–10% to reduce inflammation, and at least 10% to improve fibrosis. To this end, the panel recommended a Mediterranean-style diet, increased physical activity, and reductions in sedentary time.
Drug therapy recommendations prioritized glucagon-like peptide-1 receptor agonists (GLP-1RAs) and sodium-glucose cotransporter-2 (SGLT2) inhibitors for patients with diabetes or obesity, though these were not considered MASH-specific agents. Pioglitazone was noted as an option for diabetes management but not as direct MASH therapy. The panel did not recommend vitamin E, ursodeoxycholic acid, or omega-3 fatty acids, citing insufficient evidence.
The document also provides structured guidance on resmetirom, the first FDA-approved therapy for MASH. Its use was endorsed in patients with F2–F3 fibrosis confirmed by NITs, with safety checks at 3, 6, and 12 months, and efficacy evaluation after 1 year. Treatment futility was defined as concordant worsening across two NITs.
Preventive recommendations included hepatitis A and B vaccination and HCC surveillance every 6 months in patients with cirrhosis. Surveillance in noncirrhotic MASH was left to clinician judgment, based on individualized risk factors. Special considerations were outlined for pediatric and pregnant populations, although the evidence base in these groups remains sparse.
“Further research is required to determine the effectiveness of this algorithm in raising awareness of MASLD and its treatment,” Dr. Younossi and colleagues concluded.
The study was supported by the Global NASH/MASH Council, Inova Health System, and an unrestricted educational grant from Madrigal Pharmaceuticals. The investigators disclosed relationships with Sanofi, Gilead, AstraZeneca, and others.
The new consensus MASLD recommendations should help reconcile the “important differences” between guidelines from around the world, said Dr. Jaideep Behari, of the the University of Pittsburgh Medical Center.
Behari highlighted several points that may be underappreciated in clinical practice. “While many clinicians associate MASLD with obesity and type 2 diabetes, approximately a fifth of people living with MASLD are lean,” he said. “It may also come as a surprise to non-liver specialists that cardiovascular disease is the most common cause of mortality in patients with MASLD.”
He underscored the consensus recommendation to screen patients with type 2 diabetes, those with obesity and at least one cardiometabolic risk factor, and individuals with persistently elevated liver enzymes.
“Since many patients in the first two groups are mainly seen in primary care or endocrinology practices, physicians in these specialties need to be cognizant of these global consensus recommendations,” Behari said.
Turning to therapeutics, he described resmetirom as “a major milestone in the management of MASLD since it is the first drug approved in the US for treatment of MASH with F2 (moderate) or F3 (advanced) fibrosis.”
He noted that treatment requires careful patient selection and monitoring, including VCTE in the 8–20 kPa range, followed by serial liver injury testing. Efficacy should be assessed at 12 months, he noted, since “resmetirom was found to be effective in approximately a quarter of all treated patients in the pivotal clinical trial.”
“These limitations highlight the gaps in the treatment of MASLD/MASH and the need to continue development of other therapies,” Behari said.
Jaideep Behari, MD, PhD, AGAF, is director of the liver steatosis and metabolic wellness program at the University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania. He reported research grant support from AstraZeneca, Madrigal, and recently completed research grant support from Gilead and Pfizer.
The new consensus MASLD recommendations should help reconcile the “important differences” between guidelines from around the world, said Dr. Jaideep Behari, of the the University of Pittsburgh Medical Center.
Behari highlighted several points that may be underappreciated in clinical practice. “While many clinicians associate MASLD with obesity and type 2 diabetes, approximately a fifth of people living with MASLD are lean,” he said. “It may also come as a surprise to non-liver specialists that cardiovascular disease is the most common cause of mortality in patients with MASLD.”
He underscored the consensus recommendation to screen patients with type 2 diabetes, those with obesity and at least one cardiometabolic risk factor, and individuals with persistently elevated liver enzymes.
“Since many patients in the first two groups are mainly seen in primary care or endocrinology practices, physicians in these specialties need to be cognizant of these global consensus recommendations,” Behari said.
Turning to therapeutics, he described resmetirom as “a major milestone in the management of MASLD since it is the first drug approved in the US for treatment of MASH with F2 (moderate) or F3 (advanced) fibrosis.”
He noted that treatment requires careful patient selection and monitoring, including VCTE in the 8–20 kPa range, followed by serial liver injury testing. Efficacy should be assessed at 12 months, he noted, since “resmetirom was found to be effective in approximately a quarter of all treated patients in the pivotal clinical trial.”
“These limitations highlight the gaps in the treatment of MASLD/MASH and the need to continue development of other therapies,” Behari said.
Jaideep Behari, MD, PhD, AGAF, is director of the liver steatosis and metabolic wellness program at the University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania. He reported research grant support from AstraZeneca, Madrigal, and recently completed research grant support from Gilead and Pfizer.
The new consensus MASLD recommendations should help reconcile the “important differences” between guidelines from around the world, said Dr. Jaideep Behari, of the the University of Pittsburgh Medical Center.
Behari highlighted several points that may be underappreciated in clinical practice. “While many clinicians associate MASLD with obesity and type 2 diabetes, approximately a fifth of people living with MASLD are lean,” he said. “It may also come as a surprise to non-liver specialists that cardiovascular disease is the most common cause of mortality in patients with MASLD.”
He underscored the consensus recommendation to screen patients with type 2 diabetes, those with obesity and at least one cardiometabolic risk factor, and individuals with persistently elevated liver enzymes.
“Since many patients in the first two groups are mainly seen in primary care or endocrinology practices, physicians in these specialties need to be cognizant of these global consensus recommendations,” Behari said.
Turning to therapeutics, he described resmetirom as “a major milestone in the management of MASLD since it is the first drug approved in the US for treatment of MASH with F2 (moderate) or F3 (advanced) fibrosis.”
He noted that treatment requires careful patient selection and monitoring, including VCTE in the 8–20 kPa range, followed by serial liver injury testing. Efficacy should be assessed at 12 months, he noted, since “resmetirom was found to be effective in approximately a quarter of all treated patients in the pivotal clinical trial.”
“These limitations highlight the gaps in the treatment of MASLD/MASH and the need to continue development of other therapies,” Behari said.
Jaideep Behari, MD, PhD, AGAF, is director of the liver steatosis and metabolic wellness program at the University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania. He reported research grant support from AstraZeneca, Madrigal, and recently completed research grant support from Gilead and Pfizer.
These recommendations aim to boost guideline adherence and disease awareness, which have lagged despite a surge of national and international guidance in recent years, lead author Zobair M. Younossi, MD, of the Global NASH/MASH Council, Washington, DC, and colleagues, reported.
“Although these documents are similar in many ways, there are important differences in their recommendations, which have created some confusion within the field,” the panel wrote in Gastroenterology. “Areas of discordance among guidelines can be partly responsible for their low rate of implementation and the suboptimal awareness about this liver disease. Furthermore, these guidelines can be long and complex, making it challenging for busy clinicians to access the appropriate information quickly and efficiently.”
To address these gaps, more than 40 experts from around the world collaborated on the consensus project. The team reviewed 61 eligible documents published between 2018 and January 2025. Each guideline was evaluated across eight domains: epidemiology; screening; risk stratification using noninvasive tests (NITs); lifestyle management; treatment with existing medications; treatment with future medications; hepatocellular carcinoma (HCC) and preventive guidance; and pregnancy and pediatric populations.
Areas of discordance were advanced to a Delphi process using iterative online surveys, with a supermajority threshold of 67% required for acceptance. Four Delphi rounds were conducted, and by the end, all statements had achieved more than 90% agreement. The final recommendations were then summarized into practical algorithms for clinical use.
The results cover the full spectrum of MASLD care. For screening and diagnosis, experts agreed that individuals with type 2 diabetes, obesity plus cardiometabolic risk factors, or persistently elevated aminotransferases should be considered high risk. Alcohol thresholds were standardized, clarifying when to classify disease as MASLD, alcohol-related liver disease, or the hybrid “Met-ALD.”
For risk stratification, the panel endorsed a two-step algorithm beginning with the Fibrosis-4 (FIB-4) index, followed by vibration-controlled transient elastography (VCTE) or other NITs in patients above the threshold. This approach, the authors noted, was designed to be feasible in both primary care and specialty settings.
Lifestyle intervention remains the cornerstone of treatment, with weight-loss goals of 5% to reduce steatosis, 7%–10% to reduce inflammation, and at least 10% to improve fibrosis. To this end, the panel recommended a Mediterranean-style diet, increased physical activity, and reductions in sedentary time.
Drug therapy recommendations prioritized glucagon-like peptide-1 receptor agonists (GLP-1RAs) and sodium-glucose cotransporter-2 (SGLT2) inhibitors for patients with diabetes or obesity, though these were not considered MASH-specific agents. Pioglitazone was noted as an option for diabetes management but not as direct MASH therapy. The panel did not recommend vitamin E, ursodeoxycholic acid, or omega-3 fatty acids, citing insufficient evidence.
The document also provides structured guidance on resmetirom, the first FDA-approved therapy for MASH. Its use was endorsed in patients with F2–F3 fibrosis confirmed by NITs, with safety checks at 3, 6, and 12 months, and efficacy evaluation after 1 year. Treatment futility was defined as concordant worsening across two NITs.
Preventive recommendations included hepatitis A and B vaccination and HCC surveillance every 6 months in patients with cirrhosis. Surveillance in noncirrhotic MASH was left to clinician judgment, based on individualized risk factors. Special considerations were outlined for pediatric and pregnant populations, although the evidence base in these groups remains sparse.
“Further research is required to determine the effectiveness of this algorithm in raising awareness of MASLD and its treatment,” Dr. Younossi and colleagues concluded.
The study was supported by the Global NASH/MASH Council, Inova Health System, and an unrestricted educational grant from Madrigal Pharmaceuticals. The investigators disclosed relationships with Sanofi, Gilead, AstraZeneca, and others.
These recommendations aim to boost guideline adherence and disease awareness, which have lagged despite a surge of national and international guidance in recent years, lead author Zobair M. Younossi, MD, of the Global NASH/MASH Council, Washington, DC, and colleagues, reported.
“Although these documents are similar in many ways, there are important differences in their recommendations, which have created some confusion within the field,” the panel wrote in Gastroenterology. “Areas of discordance among guidelines can be partly responsible for their low rate of implementation and the suboptimal awareness about this liver disease. Furthermore, these guidelines can be long and complex, making it challenging for busy clinicians to access the appropriate information quickly and efficiently.”
To address these gaps, more than 40 experts from around the world collaborated on the consensus project. The team reviewed 61 eligible documents published between 2018 and January 2025. Each guideline was evaluated across eight domains: epidemiology; screening; risk stratification using noninvasive tests (NITs); lifestyle management; treatment with existing medications; treatment with future medications; hepatocellular carcinoma (HCC) and preventive guidance; and pregnancy and pediatric populations.
Areas of discordance were advanced to a Delphi process using iterative online surveys, with a supermajority threshold of 67% required for acceptance. Four Delphi rounds were conducted, and by the end, all statements had achieved more than 90% agreement. The final recommendations were then summarized into practical algorithms for clinical use.
The results cover the full spectrum of MASLD care. For screening and diagnosis, experts agreed that individuals with type 2 diabetes, obesity plus cardiometabolic risk factors, or persistently elevated aminotransferases should be considered high risk. Alcohol thresholds were standardized, clarifying when to classify disease as MASLD, alcohol-related liver disease, or the hybrid “Met-ALD.”
For risk stratification, the panel endorsed a two-step algorithm beginning with the Fibrosis-4 (FIB-4) index, followed by vibration-controlled transient elastography (VCTE) or other NITs in patients above the threshold. This approach, the authors noted, was designed to be feasible in both primary care and specialty settings.
Lifestyle intervention remains the cornerstone of treatment, with weight-loss goals of 5% to reduce steatosis, 7%–10% to reduce inflammation, and at least 10% to improve fibrosis. To this end, the panel recommended a Mediterranean-style diet, increased physical activity, and reductions in sedentary time.
Drug therapy recommendations prioritized glucagon-like peptide-1 receptor agonists (GLP-1RAs) and sodium-glucose cotransporter-2 (SGLT2) inhibitors for patients with diabetes or obesity, though these were not considered MASH-specific agents. Pioglitazone was noted as an option for diabetes management but not as direct MASH therapy. The panel did not recommend vitamin E, ursodeoxycholic acid, or omega-3 fatty acids, citing insufficient evidence.
The document also provides structured guidance on resmetirom, the first FDA-approved therapy for MASH. Its use was endorsed in patients with F2–F3 fibrosis confirmed by NITs, with safety checks at 3, 6, and 12 months, and efficacy evaluation after 1 year. Treatment futility was defined as concordant worsening across two NITs.
Preventive recommendations included hepatitis A and B vaccination and HCC surveillance every 6 months in patients with cirrhosis. Surveillance in noncirrhotic MASH was left to clinician judgment, based on individualized risk factors. Special considerations were outlined for pediatric and pregnant populations, although the evidence base in these groups remains sparse.
“Further research is required to determine the effectiveness of this algorithm in raising awareness of MASLD and its treatment,” Dr. Younossi and colleagues concluded.
The study was supported by the Global NASH/MASH Council, Inova Health System, and an unrestricted educational grant from Madrigal Pharmaceuticals. The investigators disclosed relationships with Sanofi, Gilead, AstraZeneca, and others.
FROM GASTROENTEROLOGY
Healthy Diet, Exercise Cut Liver Death Risk in Drinkers
Following a healthy diet and engaging in a high level of physical activity can significantly lower the risk for alcohol-related liver mortality, even among all drinking patterns, including heavy and binge drinking, according to a new study from Indiana University researchers.
Notably, any amount of daily alcohol intake or binge drinking increases the liver mortality risk, the researchers found. However, that risk can be reduced somewhat with healthy dietary patterns and increased physical activity.
Although previous studies suggested that one or two drinks per day could be associated with lower risks for cardiovascular disease, cancer, or liver-related outcomes, other confounders and unmeasured lifestyle behaviors could vary significantly between consumers and influence their health risks, the researchers said.
“A significant knowledge gap exists regarding the interplay of dietary patterns and physical activity with alcohol-attributable liver-specific mortality,” said senior author Naga Chalasani, MD, AGAF, professor of gastroenterology and hepatology at the Indiana University School of Medicine in Indianapolis.
“It is not well understood whether healthy diets or increased physical activity levels explain differences in liver-specific mortality risks between lifetime abstainers and light-to-moderate alcohol consumers,” he said. “More importantly, it remains unclear whether a healthy diet and physical activity can lower liver-specific mortality in individuals engaging in high-risk alcohol consumption, such as heavy or binge drinking.”
The study was published online in the Journal of Hepatology.
Analyzing Alcohol-Related Effects
Chalasani and colleagues analyzed data from more than 60,000 adults in the National Health and Nutrition Examination Surveys for 1984-2018 and linked data in the National Death Index through December 2019.
The research team looked at self-reported alcohol use, diet quality based on the Healthy Eating Index, and physical activity levels. Heavy drinking was defined as more than three drinks per day for women and more than four drinks per day for men, while binge drinking was defined as four or more drinks per day for women and five or more drinks per day for men.
Physically active participants had at least 150 minutes of moderate-intensity physical activity or 75 minutes of vigorous-intensity physical activity per week. Participants with healthier diets were in the top quartile of the Healthy Eating Index, which included diets high in vegetables, fruits, whole grains, seafood, plant-based proteins, and unsaturated fats, as well as diets low in solid fats, alcohol, and added sugars.
During a 12-year follow-up period, 12,881 deaths were reported, including 252 related to liver disease. An increased risk for liver-related death was associated with older age, smoking, diabetes, higher BMI, waist circumference, average daily alcohol intake, and binge drinking.
Compared to nondrinkers, those with daily alcohol intake had an increased liver-specific mortality risk, with an adjusted subdistribution hazard ratio (aSHR) of 1.04 for men and 1.08 for women.
Binge drinking had an even greater liver mortality risk, with an aSHR of 1.52 for men and 2.52 for women, than nonbinge drinking.
In contrast, a healthier diet — among those at the top quartile of the Healthy Eating Index — had a lower liver mortality risk in nonheavy drinkers (aSHR, 0.35), heavy drinkers (aSHR, 0.14), and binge drinkers (aSHR, 0.16).
In addition, physically active participants had a lower liver mortality risk for nonheavy drinkers (aSHR, 0.52), heavy drinkers (aSHR, 0.64), and binge drinkers (aSHR, 0.31).
Overall, the benefits of higher diet quality and physical activity were substantially greater in women than in men, the researchers found.
“The uniqueness of our study lies in its ability to simultaneously assess the moderating effects of two important lifestyle behaviors on liver mortality risk across different levels and patterns of alcohol consumption in a representative US population, offering a more nuanced and complete view of the risks of drinking,” Chalasani said.
Messaging From Clinicians to Patients
Despite some attenuation from a healthy diet and physical activity, alcohol consumption still carries an increased liver mortality risk, the researchers noted. Economically disadvantaged groups face higher exposure to high-risk alcohol use, unhealthy diets, and physical activity — and as a result, increased liver mortality.
“This study challenges the long-held belief that light-to-moderate drinking might be safe for the liver. It shows that any level of alcohol raises risk, but healthy diet and exercise can meaningfully reduce that harm,” said Joseph Ahn, MD, AGAF, assistant professor of medicine in the Division of Gastroenterology and Hepatology at the Mayo Clinic in Rochester, Minnesota.
“The results should change how we think about alcohol — not as something potentially protective, but as a risk factor that can be partly mitigated by lifestyle,” he said.
“The key takeaway is that there is no safe level of alcohol for liver health. Clinicians should move away from reassuring patients about ‘moderate’ drinking and instead stress both alcohol reduction and the protective role of diet and physical activity,” Ahn added. “The next step is bringing these insights into guidelines and patient counseling, especially for populations at higher risk.”
The study was funded by departmental internal funding. Chalasani declared having no conflicts of interest for this paper, but he disclosed paid consulting agreements with numerous pharmaceutical companies. Ahn reported having no disclosures.
A version of this article appeared on Medscape.com.
Following a healthy diet and engaging in a high level of physical activity can significantly lower the risk for alcohol-related liver mortality, even among all drinking patterns, including heavy and binge drinking, according to a new study from Indiana University researchers.
Notably, any amount of daily alcohol intake or binge drinking increases the liver mortality risk, the researchers found. However, that risk can be reduced somewhat with healthy dietary patterns and increased physical activity.
Although previous studies suggested that one or two drinks per day could be associated with lower risks for cardiovascular disease, cancer, or liver-related outcomes, other confounders and unmeasured lifestyle behaviors could vary significantly between consumers and influence their health risks, the researchers said.
“A significant knowledge gap exists regarding the interplay of dietary patterns and physical activity with alcohol-attributable liver-specific mortality,” said senior author Naga Chalasani, MD, AGAF, professor of gastroenterology and hepatology at the Indiana University School of Medicine in Indianapolis.
“It is not well understood whether healthy diets or increased physical activity levels explain differences in liver-specific mortality risks between lifetime abstainers and light-to-moderate alcohol consumers,” he said. “More importantly, it remains unclear whether a healthy diet and physical activity can lower liver-specific mortality in individuals engaging in high-risk alcohol consumption, such as heavy or binge drinking.”
The study was published online in the Journal of Hepatology.
Analyzing Alcohol-Related Effects
Chalasani and colleagues analyzed data from more than 60,000 adults in the National Health and Nutrition Examination Surveys for 1984-2018 and linked data in the National Death Index through December 2019.
The research team looked at self-reported alcohol use, diet quality based on the Healthy Eating Index, and physical activity levels. Heavy drinking was defined as more than three drinks per day for women and more than four drinks per day for men, while binge drinking was defined as four or more drinks per day for women and five or more drinks per day for men.
Physically active participants had at least 150 minutes of moderate-intensity physical activity or 75 minutes of vigorous-intensity physical activity per week. Participants with healthier diets were in the top quartile of the Healthy Eating Index, which included diets high in vegetables, fruits, whole grains, seafood, plant-based proteins, and unsaturated fats, as well as diets low in solid fats, alcohol, and added sugars.
During a 12-year follow-up period, 12,881 deaths were reported, including 252 related to liver disease. An increased risk for liver-related death was associated with older age, smoking, diabetes, higher BMI, waist circumference, average daily alcohol intake, and binge drinking.
Compared to nondrinkers, those with daily alcohol intake had an increased liver-specific mortality risk, with an adjusted subdistribution hazard ratio (aSHR) of 1.04 for men and 1.08 for women.
Binge drinking had an even greater liver mortality risk, with an aSHR of 1.52 for men and 2.52 for women, than nonbinge drinking.
In contrast, a healthier diet — among those at the top quartile of the Healthy Eating Index — had a lower liver mortality risk in nonheavy drinkers (aSHR, 0.35), heavy drinkers (aSHR, 0.14), and binge drinkers (aSHR, 0.16).
In addition, physically active participants had a lower liver mortality risk for nonheavy drinkers (aSHR, 0.52), heavy drinkers (aSHR, 0.64), and binge drinkers (aSHR, 0.31).
Overall, the benefits of higher diet quality and physical activity were substantially greater in women than in men, the researchers found.
“The uniqueness of our study lies in its ability to simultaneously assess the moderating effects of two important lifestyle behaviors on liver mortality risk across different levels and patterns of alcohol consumption in a representative US population, offering a more nuanced and complete view of the risks of drinking,” Chalasani said.
Messaging From Clinicians to Patients
Despite some attenuation from a healthy diet and physical activity, alcohol consumption still carries an increased liver mortality risk, the researchers noted. Economically disadvantaged groups face higher exposure to high-risk alcohol use, unhealthy diets, and physical activity — and as a result, increased liver mortality.
“This study challenges the long-held belief that light-to-moderate drinking might be safe for the liver. It shows that any level of alcohol raises risk, but healthy diet and exercise can meaningfully reduce that harm,” said Joseph Ahn, MD, AGAF, assistant professor of medicine in the Division of Gastroenterology and Hepatology at the Mayo Clinic in Rochester, Minnesota.
“The results should change how we think about alcohol — not as something potentially protective, but as a risk factor that can be partly mitigated by lifestyle,” he said.
“The key takeaway is that there is no safe level of alcohol for liver health. Clinicians should move away from reassuring patients about ‘moderate’ drinking and instead stress both alcohol reduction and the protective role of diet and physical activity,” Ahn added. “The next step is bringing these insights into guidelines and patient counseling, especially for populations at higher risk.”
The study was funded by departmental internal funding. Chalasani declared having no conflicts of interest for this paper, but he disclosed paid consulting agreements with numerous pharmaceutical companies. Ahn reported having no disclosures.
A version of this article appeared on Medscape.com.
Following a healthy diet and engaging in a high level of physical activity can significantly lower the risk for alcohol-related liver mortality, even among all drinking patterns, including heavy and binge drinking, according to a new study from Indiana University researchers.
Notably, any amount of daily alcohol intake or binge drinking increases the liver mortality risk, the researchers found. However, that risk can be reduced somewhat with healthy dietary patterns and increased physical activity.
Although previous studies suggested that one or two drinks per day could be associated with lower risks for cardiovascular disease, cancer, or liver-related outcomes, other confounders and unmeasured lifestyle behaviors could vary significantly between consumers and influence their health risks, the researchers said.
“A significant knowledge gap exists regarding the interplay of dietary patterns and physical activity with alcohol-attributable liver-specific mortality,” said senior author Naga Chalasani, MD, AGAF, professor of gastroenterology and hepatology at the Indiana University School of Medicine in Indianapolis.
“It is not well understood whether healthy diets or increased physical activity levels explain differences in liver-specific mortality risks between lifetime abstainers and light-to-moderate alcohol consumers,” he said. “More importantly, it remains unclear whether a healthy diet and physical activity can lower liver-specific mortality in individuals engaging in high-risk alcohol consumption, such as heavy or binge drinking.”
The study was published online in the Journal of Hepatology.
Analyzing Alcohol-Related Effects
Chalasani and colleagues analyzed data from more than 60,000 adults in the National Health and Nutrition Examination Surveys for 1984-2018 and linked data in the National Death Index through December 2019.
The research team looked at self-reported alcohol use, diet quality based on the Healthy Eating Index, and physical activity levels. Heavy drinking was defined as more than three drinks per day for women and more than four drinks per day for men, while binge drinking was defined as four or more drinks per day for women and five or more drinks per day for men.
Physically active participants had at least 150 minutes of moderate-intensity physical activity or 75 minutes of vigorous-intensity physical activity per week. Participants with healthier diets were in the top quartile of the Healthy Eating Index, which included diets high in vegetables, fruits, whole grains, seafood, plant-based proteins, and unsaturated fats, as well as diets low in solid fats, alcohol, and added sugars.
During a 12-year follow-up period, 12,881 deaths were reported, including 252 related to liver disease. An increased risk for liver-related death was associated with older age, smoking, diabetes, higher BMI, waist circumference, average daily alcohol intake, and binge drinking.
Compared to nondrinkers, those with daily alcohol intake had an increased liver-specific mortality risk, with an adjusted subdistribution hazard ratio (aSHR) of 1.04 for men and 1.08 for women.
Binge drinking had an even greater liver mortality risk, with an aSHR of 1.52 for men and 2.52 for women, than nonbinge drinking.
In contrast, a healthier diet — among those at the top quartile of the Healthy Eating Index — had a lower liver mortality risk in nonheavy drinkers (aSHR, 0.35), heavy drinkers (aSHR, 0.14), and binge drinkers (aSHR, 0.16).
In addition, physically active participants had a lower liver mortality risk for nonheavy drinkers (aSHR, 0.52), heavy drinkers (aSHR, 0.64), and binge drinkers (aSHR, 0.31).
Overall, the benefits of higher diet quality and physical activity were substantially greater in women than in men, the researchers found.
“The uniqueness of our study lies in its ability to simultaneously assess the moderating effects of two important lifestyle behaviors on liver mortality risk across different levels and patterns of alcohol consumption in a representative US population, offering a more nuanced and complete view of the risks of drinking,” Chalasani said.
Messaging From Clinicians to Patients
Despite some attenuation from a healthy diet and physical activity, alcohol consumption still carries an increased liver mortality risk, the researchers noted. Economically disadvantaged groups face higher exposure to high-risk alcohol use, unhealthy diets, and physical activity — and as a result, increased liver mortality.
“This study challenges the long-held belief that light-to-moderate drinking might be safe for the liver. It shows that any level of alcohol raises risk, but healthy diet and exercise can meaningfully reduce that harm,” said Joseph Ahn, MD, AGAF, assistant professor of medicine in the Division of Gastroenterology and Hepatology at the Mayo Clinic in Rochester, Minnesota.
“The results should change how we think about alcohol — not as something potentially protective, but as a risk factor that can be partly mitigated by lifestyle,” he said.
“The key takeaway is that there is no safe level of alcohol for liver health. Clinicians should move away from reassuring patients about ‘moderate’ drinking and instead stress both alcohol reduction and the protective role of diet and physical activity,” Ahn added. “The next step is bringing these insights into guidelines and patient counseling, especially for populations at higher risk.”
The study was funded by departmental internal funding. Chalasani declared having no conflicts of interest for this paper, but he disclosed paid consulting agreements with numerous pharmaceutical companies. Ahn reported having no disclosures.
A version of this article appeared on Medscape.com.
Ocaliva for Primary Biliary Cholangitis Withdrawn From US Market
The decision follows a request from the FDA. The FDA has also placed a clinical hold on all of Intercept’s clinical trials involving obeticholic acid.
PBC is a rare, progressive, and chronic autoimmune disease that affects the bile ducts in the liver and is most prevalent in women older than 40 years of age. PBC causes a buildup of bile acid in the liver, resulting in inflammation and fibrosis, which — if not treated — can lead to cirrhosis, a liver transplant, or death.
Ocaliva, a farnesoid X receptor agonist, received accelerated FDA approval in 2016 for the treatment of PBC in adults with an inadequate response to or intolerance of ursodeoxycholic acid.
Yet, in September 2024, staff reviewers at the FDA said a confirmatory trial did not show that the drug was effective for PBC.
Ocaliva has also been linked to an increased risk of serious liver injury in patients with PBC with and without cirrhosis.
The company has advised patients currently taking Ocaliva for PBC to consult their healthcare provider before making any changes.
Intercept will provide additional information to support healthcare professionals and patients as it works with the FDA on the transition process.
Healthcare professionals who have questions about this development can contact Intercept Medical Information at [email protected] or call 1-844-782-4278.
A version of this article appeared on Medscape.com.
The decision follows a request from the FDA. The FDA has also placed a clinical hold on all of Intercept’s clinical trials involving obeticholic acid.
PBC is a rare, progressive, and chronic autoimmune disease that affects the bile ducts in the liver and is most prevalent in women older than 40 years of age. PBC causes a buildup of bile acid in the liver, resulting in inflammation and fibrosis, which — if not treated — can lead to cirrhosis, a liver transplant, or death.
Ocaliva, a farnesoid X receptor agonist, received accelerated FDA approval in 2016 for the treatment of PBC in adults with an inadequate response to or intolerance of ursodeoxycholic acid.
Yet, in September 2024, staff reviewers at the FDA said a confirmatory trial did not show that the drug was effective for PBC.
Ocaliva has also been linked to an increased risk of serious liver injury in patients with PBC with and without cirrhosis.
The company has advised patients currently taking Ocaliva for PBC to consult their healthcare provider before making any changes.
Intercept will provide additional information to support healthcare professionals and patients as it works with the FDA on the transition process.
Healthcare professionals who have questions about this development can contact Intercept Medical Information at [email protected] or call 1-844-782-4278.
A version of this article appeared on Medscape.com.
The decision follows a request from the FDA. The FDA has also placed a clinical hold on all of Intercept’s clinical trials involving obeticholic acid.
PBC is a rare, progressive, and chronic autoimmune disease that affects the bile ducts in the liver and is most prevalent in women older than 40 years of age. PBC causes a buildup of bile acid in the liver, resulting in inflammation and fibrosis, which — if not treated — can lead to cirrhosis, a liver transplant, or death.
Ocaliva, a farnesoid X receptor agonist, received accelerated FDA approval in 2016 for the treatment of PBC in adults with an inadequate response to or intolerance of ursodeoxycholic acid.
Yet, in September 2024, staff reviewers at the FDA said a confirmatory trial did not show that the drug was effective for PBC.
Ocaliva has also been linked to an increased risk of serious liver injury in patients with PBC with and without cirrhosis.
The company has advised patients currently taking Ocaliva for PBC to consult their healthcare provider before making any changes.
Intercept will provide additional information to support healthcare professionals and patients as it works with the FDA on the transition process.
Healthcare professionals who have questions about this development can contact Intercept Medical Information at [email protected] or call 1-844-782-4278.
A version of this article appeared on Medscape.com.