Hepatology

Rates of hepatocellular carcinoma (HCC) continue to rise in the United States, but unevenly so given how the incidence has become highest in the Hispanic population, which is reflected in increased rates in the southern and western states, Hashem B. El-Serag, MD, of Baylor College of Medicine, Houston, said in a virtual presentation at the annual Digestive Diseases: New Advances, which is jointly provided by Rutgers and Global Academy for Medical Education.

In addition to this demographic shift, the risk factors for HCC are shifting, he said. Hepatitis C virus (HCV) has been the dominant risk factor for HCC; for patients with active HCV, the factors historically associated with increased HCC risk have included alcohol consumption, obesity, diabetes, coinfection, and genetics, he said.

This pattern is starting to change. In fact, for patients with active HCV, antiviral treatment with a sustained virologic response has surfaced as the most significant risk factor in the development of HCC, said Dr. El-Serag: Among these patients, sustained virologic response from direct-acting antivirals is associated with a significant reduction in HCC risk. However, it is important to recognize that a residual risk of HCC remains that doesn’t go away for several years, he noted.

“Who are those people who got treated, got cured, and still developed HCC? Those with cirrhosis at the time of treatment,” he said. Those with cirrhosis have cumulative incidence of 1.8% per year, but those without cirrhosis had very low risk, he said.

Some good news in HCC is that rates appear to be declining among young men, and this is thought to be one of the groups who are achieving a cure of HCV, he said.

“One would hope, if goals for HCV elimination are met, that will translate into massive reduction of HCC,” he said.

“The issue now for hepatitis is finding infected patients and curing them,” he noted.

Dr. El-Serag touched on hepatitis B (HBV), which continues to be the driving force of hepatitis infections globally. However, in patients who receive and respond to antiviral treatment “there is a significant and considerable reduction in HCC in the context of hepatitis B” similar to that seen with hepatitis C. Vaccination programs for HBV have started to make the desired impact of reducing HCC in HBV-endemic areas, he noted.

However, current risk factors for HCC are related less to HCV and HBV and more to metabolic syndrome because more people are treated for HCV and HBV, Dr. El-Serag said. He went on to address the new dominant global risk factor for HCC: obesity. Based on data from multiple studies, those who are obese, defined as a body mass index greater than 30 kg/m², carry a twofold increased risk of developing HCC, he said.

To reduce this risk, treatment targets might address intermediate factors such as abdominal obesity, said Dr. El-Serag. He cited a study published in Hepatology in which individuals in the highest tertile for waist-hip ratio had a threefold higher risk of HCC, compared with those in the lowest tertile.

In addition, consideration of obesity must include type 2 diabetes, which is often linked to obesity and occurs in approximately one-third of adults in the United States, Dr. El-Serag said.

Treatment of type 2 diabetes may make a difference in HCC risk reduction, Dr. El-Serag noted. “The impact of treatment of diabetes on HCC risk is an area of intense interest,” he said. Based on the latest research, “the bottom line is that those treated with metformin experience a 50% reduction in the risk of HCC,” he said

Dr. El-Serag also acknowledged the impact of other risk factors for HCC: the use of statins and the presence of nonalcoholic fatty liver disease (NAFLD).

Dr. El-Serag noted that, among NAFLD patients, subgroups at even greater risk for HCC include those with diabetes, those older than 65 years, Hispanic race, and those with cirrhosis. These patients should be candidates for surveillance. Metabolic dysfunction traits such as obesity and diabetes are very common conditions, so it’s important to look at other, more specific factors, he added. “I hope that there will be tools to help clinicians classify or risk-stratify patients into different buckets,” he said.

Areas for further research on HCC continue to include risk stratification, mechanisms of action, and HCC prevention related to treatment of metabolic syndrome, he emphasized.

Dr. El-Serag had no financial conflicts to disclose. Global Academy for Medical Education and this news organization are owned by the same parent company.

*This story was updated on Oct. 28, 2020. 

SOURCE: El-Serag HB. Digestive Diseases: New Advances 2020.

Rates of hepatocellular carcinoma (HCC) continue to rise in the United States, but unevenly so given how the incidence has become highest in the Hispanic population, which is reflected in increased rates in the southern and western states, Hashem B. El-Serag, MD, of Baylor College of Medicine, Houston, said in a virtual presentation at the annual Digestive Diseases: New Advances, which is jointly provided by Rutgers and Global Academy for Medical Education.

In addition to this demographic shift, the risk factors for HCC are shifting, he said. Hepatitis C virus (HCV) has been the dominant risk factor for HCC; for patients with active HCV, the factors historically associated with increased HCC risk have included alcohol consumption, obesity, diabetes, coinfection, and genetics, he said.

This pattern is starting to change. In fact, for patients with active HCV, antiviral treatment with a sustained virologic response has surfaced as the most significant risk factor in the development of HCC, said Dr. El-Serag: Among these patients, sustained virologic response from direct-acting antivirals is associated with a significant reduction in HCC risk. However, it is important to recognize that a residual risk of HCC remains that doesn’t go away for several years, he noted.

“Who are those people who got treated, got cured, and still developed HCC? Those with cirrhosis at the time of treatment,” he said. Those with cirrhosis have cumulative incidence of 1.8% per year, but those without cirrhosis had very low risk, he said.

Some good news in HCC is that rates appear to be declining among young men, and this is thought to be one of the groups who are achieving a cure of HCV, he said.

“One would hope, if goals for HCV elimination are met, that will translate into massive reduction of HCC,” he said.

“The issue now for hepatitis is finding infected patients and curing them,” he noted.

Dr. El-Serag touched on hepatitis B (HBV), which continues to be the driving force of hepatitis infections globally. However, in patients who receive and respond to antiviral treatment “there is a significant and considerable reduction in HCC in the context of hepatitis B” similar to that seen with hepatitis C. Vaccination programs for HBV have started to make the desired impact of reducing HCC in HBV-endemic areas, he noted.

However, current risk factors for HCC are related less to HCV and HBV and more to metabolic syndrome because more people are treated for HCV and HBV, Dr. El-Serag said. He went on to address the new dominant global risk factor for HCC: obesity. Based on data from multiple studies, those who are obese, defined as a body mass index greater than 30 kg/m², carry a twofold increased risk of developing HCC, he said.

To reduce this risk, treatment targets might address intermediate factors such as abdominal obesity, said Dr. El-Serag. He cited a study published in Hepatology in which individuals in the highest tertile for waist-hip ratio had a threefold higher risk of HCC, compared with those in the lowest tertile.

In addition, consideration of obesity must include type 2 diabetes, which is often linked to obesity and occurs in approximately one-third of adults in the United States, Dr. El-Serag said.

Treatment of type 2 diabetes may make a difference in HCC risk reduction, Dr. El-Serag noted. “The impact of treatment of diabetes on HCC risk is an area of intense interest,” he said. Based on the latest research, “the bottom line is that those treated with metformin experience a 50% reduction in the risk of HCC,” he said

Dr. El-Serag also acknowledged the impact of other risk factors for HCC: the use of statins and the presence of nonalcoholic fatty liver disease (NAFLD).

Dr. El-Serag noted that, among NAFLD patients, subgroups at even greater risk for HCC include those with diabetes, those older than 65 years, Hispanic race, and those with cirrhosis. These patients should be candidates for surveillance. Metabolic dysfunction traits such as obesity and diabetes are very common conditions, so it’s important to look at other, more specific factors, he added. “I hope that there will be tools to help clinicians classify or risk-stratify patients into different buckets,” he said.

Areas for further research on HCC continue to include risk stratification, mechanisms of action, and HCC prevention related to treatment of metabolic syndrome, he emphasized.

Dr. El-Serag had no financial conflicts to disclose. Global Academy for Medical Education and this news organization are owned by the same parent company.

*This story was updated on Oct. 28, 2020. 

SOURCE: El-Serag HB. Digestive Diseases: New Advances 2020.

Rates of hepatocellular carcinoma (HCC) continue to rise in the United States, but unevenly so given how the incidence has become highest in the Hispanic population, which is reflected in increased rates in the southern and western states, Hashem B. El-Serag, MD, of Baylor College of Medicine, Houston, said in a virtual presentation at the annual Digestive Diseases: New Advances, which is jointly provided by Rutgers and Global Academy for Medical Education.

In addition to this demographic shift, the risk factors for HCC are shifting, he said. Hepatitis C virus (HCV) has been the dominant risk factor for HCC; for patients with active HCV, the factors historically associated with increased HCC risk have included alcohol consumption, obesity, diabetes, coinfection, and genetics, he said.

This pattern is starting to change. In fact, for patients with active HCV, antiviral treatment with a sustained virologic response has surfaced as the most significant risk factor in the development of HCC, said Dr. El-Serag: Among these patients, sustained virologic response from direct-acting antivirals is associated with a significant reduction in HCC risk. However, it is important to recognize that a residual risk of HCC remains that doesn’t go away for several years, he noted.

“Who are those people who got treated, got cured, and still developed HCC? Those with cirrhosis at the time of treatment,” he said. Those with cirrhosis have cumulative incidence of 1.8% per year, but those without cirrhosis had very low risk, he said.

Some good news in HCC is that rates appear to be declining among young men, and this is thought to be one of the groups who are achieving a cure of HCV, he said.

“One would hope, if goals for HCV elimination are met, that will translate into massive reduction of HCC,” he said.

“The issue now for hepatitis is finding infected patients and curing them,” he noted.

Dr. El-Serag touched on hepatitis B (HBV), which continues to be the driving force of hepatitis infections globally. However, in patients who receive and respond to antiviral treatment “there is a significant and considerable reduction in HCC in the context of hepatitis B” similar to that seen with hepatitis C. Vaccination programs for HBV have started to make the desired impact of reducing HCC in HBV-endemic areas, he noted.

However, current risk factors for HCC are related less to HCV and HBV and more to metabolic syndrome because more people are treated for HCV and HBV, Dr. El-Serag said. He went on to address the new dominant global risk factor for HCC: obesity. Based on data from multiple studies, those who are obese, defined as a body mass index greater than 30 kg/m², carry a twofold increased risk of developing HCC, he said.

To reduce this risk, treatment targets might address intermediate factors such as abdominal obesity, said Dr. El-Serag. He cited a study published in Hepatology in which individuals in the highest tertile for waist-hip ratio had a threefold higher risk of HCC, compared with those in the lowest tertile.

In addition, consideration of obesity must include type 2 diabetes, which is often linked to obesity and occurs in approximately one-third of adults in the United States, Dr. El-Serag said.

Treatment of type 2 diabetes may make a difference in HCC risk reduction, Dr. El-Serag noted. “The impact of treatment of diabetes on HCC risk is an area of intense interest,” he said. Based on the latest research, “the bottom line is that those treated with metformin experience a 50% reduction in the risk of HCC,” he said

Dr. El-Serag also acknowledged the impact of other risk factors for HCC: the use of statins and the presence of nonalcoholic fatty liver disease (NAFLD).

Dr. El-Serag noted that, among NAFLD patients, subgroups at even greater risk for HCC include those with diabetes, those older than 65 years, Hispanic race, and those with cirrhosis. These patients should be candidates for surveillance. Metabolic dysfunction traits such as obesity and diabetes are very common conditions, so it’s important to look at other, more specific factors, he added. “I hope that there will be tools to help clinicians classify or risk-stratify patients into different buckets,” he said.

Areas for further research on HCC continue to include risk stratification, mechanisms of action, and HCC prevention related to treatment of metabolic syndrome, he emphasized.

Dr. El-Serag had no financial conflicts to disclose. Global Academy for Medical Education and this news organization are owned by the same parent company.

*This story was updated on Oct. 28, 2020. 

SOURCE: El-Serag HB. Digestive Diseases: New Advances 2020.

Not only the prevalence, but the impact of nonalcoholic fatty liver disease (NAFLD) is increasing in much of the world, Arun J. Sanyal, MD, said in a virtual presentation at the meeting jointly provided by Rutgers and Global Academy for Medical Education. “It is currently estimated that the number of people living with cirrhosis or with decompensated cirrhosis will increase two- to threefold from 2015 to 2030,” which underlines the public health impact and the need for improved treatment paradigms, he emphasized.

“The thing to remember about NAFLD is that it does not exist in a vacuum,” Dr. Sanyal said. NAFLD is a multisystem disorder. Most patients have concomitant cardiovascular disease, but others may have type 2 diabetes, hypertension, and dyslipidemia, all of which are now accepted as risk factors for nonalcoholic steatohepatitis (NASH), he said.

“What ties these conditions together is metabolic stress leading to systemic inflammation and fibrosis. This is primarily due to diet-induced obesity. If you think about treating all of these competing risks to the patient’s life, the optimal way is to treat the root cause,” he said.

Various options exist to manage the conditions that can lead to NASH, but several of these also appear promising as a treatment of NASH, Dr. Sanyal said. Glucagonlike peptide–1 agonists and sodium-glucose transporter 2 inhibitors have been shown to improve multiple outcomes of interest in type 2 diabetes. However, insulin can cause weight gain at the expense of controlling HbA1C levels, he said.

Bariatric surgery can improve histology, but many patients with advanced fibrosis do not demonstrate improvement in fibrosis. Also, bariatric surgery has its own associated morbidity, including an increased suicide rate across multiple studies, Dr. Sanyal noted.

A new and interesting option is duodenal mucosal resurfacing (DMR) “a novel, minimally invasive outpatient upper-endoscopic procedure,” said Dr. Sanyal. DMR involves use of a catheter to perform a submucosal lift and hydrothermal mucosal ablation, prompting healthy epithelial regrowth, he explained. “The mucosa sloughs off, fresh epithelium grows in, and the hormonal signal from the gut to the rest of the body is restored to a more normal pattern,” he noted.

In the REVITA-2 study of patients with diabetes and NAFLD, the average fat loss was 5.4% in those randomized to DMR vs. 2.4% in sham-procedure patients and represented “quite significant defatting of the liver,” Dr. Sanyal said.

Dr. Sanyal then focused on fatty liver disease. “The first step when you see a patient with fatty liver disease is to see how scarred is the liver, and whether the patient has silent cirrhosis. The more scarred the liver, the greater risk of liver-related outcomes,” he said. The goal of therapy for these patients is to reduce the risk of progression to cirrhosis, he added. Dr. Sanyal recommended evaluating fibrosis using the Fibrosis 4 score (Fib4). “If the Fib4 is less than 1.3, the likelihood of significant scarring in the liver is less than 10%,” he said. On the other hand, a Fib4 greater than 2.67 suggests advanced fibrosis, he noted.

Overall, the goals of treatment for NASH patients are to prevent cirrhosis, reduce decompensation, and prevent hepatocellular carcinoma, said Dr. Sanyal.

“The ideal drug for NASH should also help other end organs, or at least be neutral,” said Dr. Sanyal.

Current frontline therapies for precirrhotic NASH include thiazolidinediones (TZD), farnesoid X receptor (FXR)/fibroblast growth factor 19 (FGF-19), FGF21, thyroxine B-R, and glucagonlike peptide-1. Clinical evidence varies based on different populations, endpoints, assessment methods, and treatment duration, he said.

Looking ahead to the next decade, a NASH management paradigm will likely play out that can be applied in the clinic today, Dr. Sanyal said. First, make an initial assessment of the status of the end organs. Start with a weight-loss regimen; use statins and GLP-1 and SGLT2 inhibitors as needed. Follow and reassess, and if the patient still has disease, progress to targeted therapy for active NASH while continuing to encourage weight loss and healthy living, he said.

“The ultimate proof that what we are doing is working is that we are improving mortality, reducing health care costs, and improving patients’ function and quality of life,” he concluded.

Dr. Sanyal is president of Sanyal Biotechnologies. He also disclosed stock options for Durect, Exhalenz, Galmed, Genfit, Immuton, Indalo, and Tiziana, as well as various relationships with Allergan, AMRA, Astra Zeneca-Medimmune, Birdrock, Boehringer Ingelheim, Bristol Myers, Echosense, GE, Genentech, Gilead, Hemoshear, IFMO, Innovate, Intercept, Lilly, Lipocine, Merck, Novartis, Novo Nordisk, OWL, Pfizer, RedX, Sundise, Tern, and Zydus.

Global Academy for Medical Education and this news organization are owned by the same parent company.

Not only the prevalence, but the impact of nonalcoholic fatty liver disease (NAFLD) is increasing in much of the world, Arun J. Sanyal, MD, said in a virtual presentation at the meeting jointly provided by Rutgers and Global Academy for Medical Education. “It is currently estimated that the number of people living with cirrhosis or with decompensated cirrhosis will increase two- to threefold from 2015 to 2030,” which underlines the public health impact and the need for improved treatment paradigms, he emphasized.

“The thing to remember about NAFLD is that it does not exist in a vacuum,” Dr. Sanyal said. NAFLD is a multisystem disorder. Most patients have concomitant cardiovascular disease, but others may have type 2 diabetes, hypertension, and dyslipidemia, all of which are now accepted as risk factors for nonalcoholic steatohepatitis (NASH), he said.

“What ties these conditions together is metabolic stress leading to systemic inflammation and fibrosis. This is primarily due to diet-induced obesity. If you think about treating all of these competing risks to the patient’s life, the optimal way is to treat the root cause,” he said.

Various options exist to manage the conditions that can lead to NASH, but several of these also appear promising as a treatment of NASH, Dr. Sanyal said. Glucagonlike peptide–1 agonists and sodium-glucose transporter 2 inhibitors have been shown to improve multiple outcomes of interest in type 2 diabetes. However, insulin can cause weight gain at the expense of controlling HbA1C levels, he said.

Bariatric surgery can improve histology, but many patients with advanced fibrosis do not demonstrate improvement in fibrosis. Also, bariatric surgery has its own associated morbidity, including an increased suicide rate across multiple studies, Dr. Sanyal noted.

A new and interesting option is duodenal mucosal resurfacing (DMR) “a novel, minimally invasive outpatient upper-endoscopic procedure,” said Dr. Sanyal. DMR involves use of a catheter to perform a submucosal lift and hydrothermal mucosal ablation, prompting healthy epithelial regrowth, he explained. “The mucosa sloughs off, fresh epithelium grows in, and the hormonal signal from the gut to the rest of the body is restored to a more normal pattern,” he noted.

In the REVITA-2 study of patients with diabetes and NAFLD, the average fat loss was 5.4% in those randomized to DMR vs. 2.4% in sham-procedure patients and represented “quite significant defatting of the liver,” Dr. Sanyal said.

Dr. Sanyal then focused on fatty liver disease. “The first step when you see a patient with fatty liver disease is to see how scarred is the liver, and whether the patient has silent cirrhosis. The more scarred the liver, the greater risk of liver-related outcomes,” he said. The goal of therapy for these patients is to reduce the risk of progression to cirrhosis, he added. Dr. Sanyal recommended evaluating fibrosis using the Fibrosis 4 score (Fib4). “If the Fib4 is less than 1.3, the likelihood of significant scarring in the liver is less than 10%,” he said. On the other hand, a Fib4 greater than 2.67 suggests advanced fibrosis, he noted.

Overall, the goals of treatment for NASH patients are to prevent cirrhosis, reduce decompensation, and prevent hepatocellular carcinoma, said Dr. Sanyal.

“The ideal drug for NASH should also help other end organs, or at least be neutral,” said Dr. Sanyal.

Current frontline therapies for precirrhotic NASH include thiazolidinediones (TZD), farnesoid X receptor (FXR)/fibroblast growth factor 19 (FGF-19), FGF21, thyroxine B-R, and glucagonlike peptide-1. Clinical evidence varies based on different populations, endpoints, assessment methods, and treatment duration, he said.

Looking ahead to the next decade, a NASH management paradigm will likely play out that can be applied in the clinic today, Dr. Sanyal said. First, make an initial assessment of the status of the end organs. Start with a weight-loss regimen; use statins and GLP-1 and SGLT2 inhibitors as needed. Follow and reassess, and if the patient still has disease, progress to targeted therapy for active NASH while continuing to encourage weight loss and healthy living, he said.

“The ultimate proof that what we are doing is working is that we are improving mortality, reducing health care costs, and improving patients’ function and quality of life,” he concluded.

Dr. Sanyal is president of Sanyal Biotechnologies. He also disclosed stock options for Durect, Exhalenz, Galmed, Genfit, Immuton, Indalo, and Tiziana, as well as various relationships with Allergan, AMRA, Astra Zeneca-Medimmune, Birdrock, Boehringer Ingelheim, Bristol Myers, Echosense, GE, Genentech, Gilead, Hemoshear, IFMO, Innovate, Intercept, Lilly, Lipocine, Merck, Novartis, Novo Nordisk, OWL, Pfizer, RedX, Sundise, Tern, and Zydus.

Global Academy for Medical Education and this news organization are owned by the same parent company.

Not only the prevalence, but the impact of nonalcoholic fatty liver disease (NAFLD) is increasing in much of the world, Arun J. Sanyal, MD, said in a virtual presentation at the meeting jointly provided by Rutgers and Global Academy for Medical Education. “It is currently estimated that the number of people living with cirrhosis or with decompensated cirrhosis will increase two- to threefold from 2015 to 2030,” which underlines the public health impact and the need for improved treatment paradigms, he emphasized.

“The thing to remember about NAFLD is that it does not exist in a vacuum,” Dr. Sanyal said. NAFLD is a multisystem disorder. Most patients have concomitant cardiovascular disease, but others may have type 2 diabetes, hypertension, and dyslipidemia, all of which are now accepted as risk factors for nonalcoholic steatohepatitis (NASH), he said.

“What ties these conditions together is metabolic stress leading to systemic inflammation and fibrosis. This is primarily due to diet-induced obesity. If you think about treating all of these competing risks to the patient’s life, the optimal way is to treat the root cause,” he said.

Various options exist to manage the conditions that can lead to NASH, but several of these also appear promising as a treatment of NASH, Dr. Sanyal said. Glucagonlike peptide–1 agonists and sodium-glucose transporter 2 inhibitors have been shown to improve multiple outcomes of interest in type 2 diabetes. However, insulin can cause weight gain at the expense of controlling HbA1C levels, he said.

Bariatric surgery can improve histology, but many patients with advanced fibrosis do not demonstrate improvement in fibrosis. Also, bariatric surgery has its own associated morbidity, including an increased suicide rate across multiple studies, Dr. Sanyal noted.

A new and interesting option is duodenal mucosal resurfacing (DMR) “a novel, minimally invasive outpatient upper-endoscopic procedure,” said Dr. Sanyal. DMR involves use of a catheter to perform a submucosal lift and hydrothermal mucosal ablation, prompting healthy epithelial regrowth, he explained. “The mucosa sloughs off, fresh epithelium grows in, and the hormonal signal from the gut to the rest of the body is restored to a more normal pattern,” he noted.

In the REVITA-2 study of patients with diabetes and NAFLD, the average fat loss was 5.4% in those randomized to DMR vs. 2.4% in sham-procedure patients and represented “quite significant defatting of the liver,” Dr. Sanyal said.

Dr. Sanyal then focused on fatty liver disease. “The first step when you see a patient with fatty liver disease is to see how scarred is the liver, and whether the patient has silent cirrhosis. The more scarred the liver, the greater risk of liver-related outcomes,” he said. The goal of therapy for these patients is to reduce the risk of progression to cirrhosis, he added. Dr. Sanyal recommended evaluating fibrosis using the Fibrosis 4 score (Fib4). “If the Fib4 is less than 1.3, the likelihood of significant scarring in the liver is less than 10%,” he said. On the other hand, a Fib4 greater than 2.67 suggests advanced fibrosis, he noted.

Overall, the goals of treatment for NASH patients are to prevent cirrhosis, reduce decompensation, and prevent hepatocellular carcinoma, said Dr. Sanyal.

“The ideal drug for NASH should also help other end organs, or at least be neutral,” said Dr. Sanyal.

Current frontline therapies for precirrhotic NASH include thiazolidinediones (TZD), farnesoid X receptor (FXR)/fibroblast growth factor 19 (FGF-19), FGF21, thyroxine B-R, and glucagonlike peptide-1. Clinical evidence varies based on different populations, endpoints, assessment methods, and treatment duration, he said.

Looking ahead to the next decade, a NASH management paradigm will likely play out that can be applied in the clinic today, Dr. Sanyal said. First, make an initial assessment of the status of the end organs. Start with a weight-loss regimen; use statins and GLP-1 and SGLT2 inhibitors as needed. Follow and reassess, and if the patient still has disease, progress to targeted therapy for active NASH while continuing to encourage weight loss and healthy living, he said.

“The ultimate proof that what we are doing is working is that we are improving mortality, reducing health care costs, and improving patients’ function and quality of life,” he concluded.

Dr. Sanyal is president of Sanyal Biotechnologies. He also disclosed stock options for Durect, Exhalenz, Galmed, Genfit, Immuton, Indalo, and Tiziana, as well as various relationships with Allergan, AMRA, Astra Zeneca-Medimmune, Birdrock, Boehringer Ingelheim, Bristol Myers, Echosense, GE, Genentech, Gilead, Hemoshear, IFMO, Innovate, Intercept, Lilly, Lipocine, Merck, Novartis, Novo Nordisk, OWL, Pfizer, RedX, Sundise, Tern, and Zydus.

Global Academy for Medical Education and this news organization are owned by the same parent company.

For patients with severe thrombocytopenia and chronic liver diseases, including hepatocellular carcinoma, treatment with lusutrombopag prior to invasive procedures significantly decreased the need for platelet transfusions without increasing the need for rescue treatment for bleeding or the rate of thromboembolic events.

In a post hoc analysis of data from 270 patients in two manufacturer-sponsored, multicenter, randomized, double-blind, placebo-controlled, phase 3 trials, significantly more lusutrombopag recipients met the primary efficacy endpoint, including patients with hepatocellular carcinoma (68.0% vs. 8.9% in the placebo group; P < .0001) and those without it (77.0% vs. 21.6%; P < .0001). Rates of treatment-emergent adverse events were similar between the lusutrombopag and placebo groups, and patients with hepatocellular carcinoma were not at increased risk for thrombosis, Naim Alkhouri, MD, of Texas Liver Institute in San Antonio, and associates wrote in Clinical Gastroenterology and Hepatology.

Platelet transfusion is the treatment mainstay for patients with thrombocytopenia related to cirrhosis who are undergoing invasive procedures, but its effects are short-lived, and at least one in five transfusions fails. Thrombopoietin agonists such as lusutrombopag are efficacious and approved in this setting, but they can be prothrombotic, particularly in patients with hepatocellular carcinoma, who already are at heightened risk for portal vein thrombosis.

Dr. Alkhouri and associates performed an integrated analysis of the PLUS 1 trial (Japan, October 2013–May 2014) and the L-PLUS 2 (global, June 2015–April 2017). Participants were adults with Child-Pugh Class A or B chronic liver disease and baseline platelet counts under 50 x 10⁹ per L who were scheduled for invasive procedures. Of the 270 patients, 95 had hepatocellular carcinoma. Patients were randomly assigned on a one-to-one basis to receive either lusutrombopag (3 mg) or placebo daily for up to 7 days before procedures. The primary endpoint was the percentage of patients in the per-protocol population who did not need a platelet transfusion before the invasive procedure or rescue therapy within 7 days afterward.

The treatment and placebo arms were similar except that patients with hepatocellular carcinoma were about 10 years older on average. In patients with hepatocellular carcinoma, 60.5% more lusutrombopag recipients than placebo recipients met the primary endpoint, and rates of bleeding-related adverse events were 9.1% and 15.7%, respectively. In patients with other chronic liver diseases, 52.6% more lusutrombopag recipients met the primary endpoint. Rates of bleeding-related adverse events were 5% and 10.6%.

“Approximately 88% of patients with hepatocellular carcinoma underwent a liver-related procedure, compared with approximately 10% of patients without hepatocellular carcinoma,” the investigators wrote. “This is significant because ablations or transcatheter arterial chemoembolizations can be associated with serious bleeding complications. It is clinically important that, given the greater number of liver-related procedures, the incidence of bleeding-related adverse events was lower in patients treated with lusutrombopag than placebo.”

Imaging after the procedures confirmed low rates of thromboses in both groups and subgroups. Four patients developed portal vein thromboses, including two lusutrombopag recipients (one of whom had hepatocellular carcinoma) and two placebo recipients without hepatocellular carcinoma.

These trials excluded patients undergoing major surgical procedures and those with decompensated cirrhosis; portal vein thrombosis; hematopoietic tumors; aplastic anemia; myelodysplastic syndrome; myelofibrosis; liver transplantation; splenectomy; and thrombocytopenia that was congenital, autoimmune, or drug induced. “A limitation of this study was the high rate of protocol violations related to platelet transfusions,” the researchers noted. “A number of patients [42 in all] were excluded from the per-protocol population owing to receipt of unnecessary platelet transfusions, or because they did not receive a needed platelet transfusion.”Shionogi makes lusutrombopag and sponsored the study. Dr. Alkhouri reported an advisory relationship with Shionogi and Dova Pharma. Two coinvestigators reported being employed by Shionogi. Three coinvestigators also disclosed ties to Shionogi and to several other pharmaceutical companies.

SOURCE: Alkhouri N et al. Clin Gastroenterol Hepatol. 2020 Mar 20. doi: 10.1016/j.cgh.2020.03.032.

For patients with severe thrombocytopenia and chronic liver diseases, including hepatocellular carcinoma, treatment with lusutrombopag prior to invasive procedures significantly decreased the need for platelet transfusions without increasing the need for rescue treatment for bleeding or the rate of thromboembolic events.

In a post hoc analysis of data from 270 patients in two manufacturer-sponsored, multicenter, randomized, double-blind, placebo-controlled, phase 3 trials, significantly more lusutrombopag recipients met the primary efficacy endpoint, including patients with hepatocellular carcinoma (68.0% vs. 8.9% in the placebo group; P < .0001) and those without it (77.0% vs. 21.6%; P < .0001). Rates of treatment-emergent adverse events were similar between the lusutrombopag and placebo groups, and patients with hepatocellular carcinoma were not at increased risk for thrombosis, Naim Alkhouri, MD, of Texas Liver Institute in San Antonio, and associates wrote in Clinical Gastroenterology and Hepatology.

Platelet transfusion is the treatment mainstay for patients with thrombocytopenia related to cirrhosis who are undergoing invasive procedures, but its effects are short-lived, and at least one in five transfusions fails. Thrombopoietin agonists such as lusutrombopag are efficacious and approved in this setting, but they can be prothrombotic, particularly in patients with hepatocellular carcinoma, who already are at heightened risk for portal vein thrombosis.

Dr. Alkhouri and associates performed an integrated analysis of the PLUS 1 trial (Japan, October 2013–May 2014) and the L-PLUS 2 (global, June 2015–April 2017). Participants were adults with Child-Pugh Class A or B chronic liver disease and baseline platelet counts under 50 x 10⁹ per L who were scheduled for invasive procedures. Of the 270 patients, 95 had hepatocellular carcinoma. Patients were randomly assigned on a one-to-one basis to receive either lusutrombopag (3 mg) or placebo daily for up to 7 days before procedures. The primary endpoint was the percentage of patients in the per-protocol population who did not need a platelet transfusion before the invasive procedure or rescue therapy within 7 days afterward.

The treatment and placebo arms were similar except that patients with hepatocellular carcinoma were about 10 years older on average. In patients with hepatocellular carcinoma, 60.5% more lusutrombopag recipients than placebo recipients met the primary endpoint, and rates of bleeding-related adverse events were 9.1% and 15.7%, respectively. In patients with other chronic liver diseases, 52.6% more lusutrombopag recipients met the primary endpoint. Rates of bleeding-related adverse events were 5% and 10.6%.

“Approximately 88% of patients with hepatocellular carcinoma underwent a liver-related procedure, compared with approximately 10% of patients without hepatocellular carcinoma,” the investigators wrote. “This is significant because ablations or transcatheter arterial chemoembolizations can be associated with serious bleeding complications. It is clinically important that, given the greater number of liver-related procedures, the incidence of bleeding-related adverse events was lower in patients treated with lusutrombopag than placebo.”

Imaging after the procedures confirmed low rates of thromboses in both groups and subgroups. Four patients developed portal vein thromboses, including two lusutrombopag recipients (one of whom had hepatocellular carcinoma) and two placebo recipients without hepatocellular carcinoma.

These trials excluded patients undergoing major surgical procedures and those with decompensated cirrhosis; portal vein thrombosis; hematopoietic tumors; aplastic anemia; myelodysplastic syndrome; myelofibrosis; liver transplantation; splenectomy; and thrombocytopenia that was congenital, autoimmune, or drug induced. “A limitation of this study was the high rate of protocol violations related to platelet transfusions,” the researchers noted. “A number of patients [42 in all] were excluded from the per-protocol population owing to receipt of unnecessary platelet transfusions, or because they did not receive a needed platelet transfusion.”Shionogi makes lusutrombopag and sponsored the study. Dr. Alkhouri reported an advisory relationship with Shionogi and Dova Pharma. Two coinvestigators reported being employed by Shionogi. Three coinvestigators also disclosed ties to Shionogi and to several other pharmaceutical companies.

SOURCE: Alkhouri N et al. Clin Gastroenterol Hepatol. 2020 Mar 20. doi: 10.1016/j.cgh.2020.03.032.

For patients with severe thrombocytopenia and chronic liver diseases, including hepatocellular carcinoma, treatment with lusutrombopag prior to invasive procedures significantly decreased the need for platelet transfusions without increasing the need for rescue treatment for bleeding or the rate of thromboembolic events.

In a post hoc analysis of data from 270 patients in two manufacturer-sponsored, multicenter, randomized, double-blind, placebo-controlled, phase 3 trials, significantly more lusutrombopag recipients met the primary efficacy endpoint, including patients with hepatocellular carcinoma (68.0% vs. 8.9% in the placebo group; P < .0001) and those without it (77.0% vs. 21.6%; P < .0001). Rates of treatment-emergent adverse events were similar between the lusutrombopag and placebo groups, and patients with hepatocellular carcinoma were not at increased risk for thrombosis, Naim Alkhouri, MD, of Texas Liver Institute in San Antonio, and associates wrote in Clinical Gastroenterology and Hepatology.

Platelet transfusion is the treatment mainstay for patients with thrombocytopenia related to cirrhosis who are undergoing invasive procedures, but its effects are short-lived, and at least one in five transfusions fails. Thrombopoietin agonists such as lusutrombopag are efficacious and approved in this setting, but they can be prothrombotic, particularly in patients with hepatocellular carcinoma, who already are at heightened risk for portal vein thrombosis.

Dr. Alkhouri and associates performed an integrated analysis of the PLUS 1 trial (Japan, October 2013–May 2014) and the L-PLUS 2 (global, June 2015–April 2017). Participants were adults with Child-Pugh Class A or B chronic liver disease and baseline platelet counts under 50 x 10⁹ per L who were scheduled for invasive procedures. Of the 270 patients, 95 had hepatocellular carcinoma. Patients were randomly assigned on a one-to-one basis to receive either lusutrombopag (3 mg) or placebo daily for up to 7 days before procedures. The primary endpoint was the percentage of patients in the per-protocol population who did not need a platelet transfusion before the invasive procedure or rescue therapy within 7 days afterward.

The treatment and placebo arms were similar except that patients with hepatocellular carcinoma were about 10 years older on average. In patients with hepatocellular carcinoma, 60.5% more lusutrombopag recipients than placebo recipients met the primary endpoint, and rates of bleeding-related adverse events were 9.1% and 15.7%, respectively. In patients with other chronic liver diseases, 52.6% more lusutrombopag recipients met the primary endpoint. Rates of bleeding-related adverse events were 5% and 10.6%.

“Approximately 88% of patients with hepatocellular carcinoma underwent a liver-related procedure, compared with approximately 10% of patients without hepatocellular carcinoma,” the investigators wrote. “This is significant because ablations or transcatheter arterial chemoembolizations can be associated with serious bleeding complications. It is clinically important that, given the greater number of liver-related procedures, the incidence of bleeding-related adverse events was lower in patients treated with lusutrombopag than placebo.”

Imaging after the procedures confirmed low rates of thromboses in both groups and subgroups. Four patients developed portal vein thromboses, including two lusutrombopag recipients (one of whom had hepatocellular carcinoma) and two placebo recipients without hepatocellular carcinoma.

These trials excluded patients undergoing major surgical procedures and those with decompensated cirrhosis; portal vein thrombosis; hematopoietic tumors; aplastic anemia; myelodysplastic syndrome; myelofibrosis; liver transplantation; splenectomy; and thrombocytopenia that was congenital, autoimmune, or drug induced. “A limitation of this study was the high rate of protocol violations related to platelet transfusions,” the researchers noted. “A number of patients [42 in all] were excluded from the per-protocol population owing to receipt of unnecessary platelet transfusions, or because they did not receive a needed platelet transfusion.”Shionogi makes lusutrombopag and sponsored the study. Dr. Alkhouri reported an advisory relationship with Shionogi and Dova Pharma. Two coinvestigators reported being employed by Shionogi. Three coinvestigators also disclosed ties to Shionogi and to several other pharmaceutical companies.

SOURCE: Alkhouri N et al. Clin Gastroenterol Hepatol. 2020 Mar 20. doi: 10.1016/j.cgh.2020.03.032.

Bariatric surgery resolved nonalcoholic steatohepatitis (NASH) without worsening fibrosis in 84% of patients with evaluable biopsies, according to the findings of a prospective study.

The study included 180 severely or morbidly obese adults (body mass index >35 kg/m²) with NASH who underwent bariatric surgery at a center in France. Among 94 patients evaluated 5 years later, 68% had follow-up liver biopsies, of whom 84% (95% confidence interval, 73.1%-92.2%) met the primary endpoint of resolution of NASH without worsening of fibrosis. All histologic aspects of NASH had improved, median nonalcoholic fatty liver disease scores (NAS) fell from 5 (interquartile range, 4 to 5) to 1 (IQR, 0-2; P < .001), and 90% of patients achieved at least a 2-point NAS improvement. Hepatocellular ballooning also improved in 87.5% of patients. Baseline severity of NASH did not affect the chances of it resolving at 5 years. “The reduction of fibrosis [was] progressive, beginning during the first year and continuing through 5 years,” Guillaume Lassailly, MD, and associates wrote in Gastroenterology.

NASH is a priority for clinical research because of the substantial risk for subsequent cirrhosis, added Dr. Lassailly of CHU Lille (France). For NASH to resolve, most patients need to lose at least 7%-10% of their body weight, but “only 10% of patients reach this objective with lifestyle therapy at 1 year, and less than half maintain the weight loss 5 years later.” Despite ongoing drug development efforts, no medications have been approved for treating NASH. Although weight loss after bariatric surgery has been reported to resolve NASH in approximately 80% of patients at 1 year, longer-term data have been unavailable, and it has remained unclear whether bariatric surgery can slow or halt fibrosis progression.

All patients in this study had biopsy-confirmed NASH and at least a 5-year history of severe or morbid obesity as well as at least one comorbidity, such as diabetes mellitus or arterial hypertension. Patients were not heavy drinkers, and none had detectable markers of chronic liver disease.

Bariatric surgery produced a median 12-kg/m² drop in body mass index. At 5-year follow-up, 93% of patients meeting or exceeding this threshold who had biopsies performed showed resolution of NASH without worsening of fibrosis. Furthermore, 56% of patients (95% CI, 42.4%-69.3%) had no histologic evidence of fibrosis, including 45.5% of patients who had bridging fibrosis at baseline.

Participants in this study received intensive preoperative support, including evaluations by numerous specialists, a nutrition plan, and a 6- to 12-month therapeutic education program. Bariatric surgery techniques included Roux-en-Y gastric bypass, gastric banding, and sleeve gastrectomy. A subgroup analysis linked gastric bypass to a significantly higher probability of meeting the primary endpoint, compared with gastric banding. Refusal was the most common reason for not having a follow-up biopsy, the researchers said. “Patients without liver biopsy after bariatric surgery were not significantly different from those with a histological follow-up except for a lower BMI at 1 year. Baseline fibrosis did not influence the probability of undergoing histological reevaluation at 5 years.”

Two study participants died from surgical complications within 1 month after surgery, and one patient died from cardiac dysfunction 4 years later. No fatality was deemed liver related.

The study was funded by the French Ministry of Health, Conseil Régional Nord-Pas de Calais, National de la Recherche, and the European commission (FEDER). The researchers reported having no conflicts of interest.

SOURCE: Lassailly G et al. Gastroenterology. 2020 Jun 15. doi: 10.1053/j.gastro.2020.06.006.

Bariatric surgery resolved nonalcoholic steatohepatitis (NASH) without worsening fibrosis in 84% of patients with evaluable biopsies, according to the findings of a prospective study.

The study included 180 severely or morbidly obese adults (body mass index >35 kg/m²) with NASH who underwent bariatric surgery at a center in France. Among 94 patients evaluated 5 years later, 68% had follow-up liver biopsies, of whom 84% (95% confidence interval, 73.1%-92.2%) met the primary endpoint of resolution of NASH without worsening of fibrosis. All histologic aspects of NASH had improved, median nonalcoholic fatty liver disease scores (NAS) fell from 5 (interquartile range, 4 to 5) to 1 (IQR, 0-2; P < .001), and 90% of patients achieved at least a 2-point NAS improvement. Hepatocellular ballooning also improved in 87.5% of patients. Baseline severity of NASH did not affect the chances of it resolving at 5 years. “The reduction of fibrosis [was] progressive, beginning during the first year and continuing through 5 years,” Guillaume Lassailly, MD, and associates wrote in Gastroenterology.

NASH is a priority for clinical research because of the substantial risk for subsequent cirrhosis, added Dr. Lassailly of CHU Lille (France). For NASH to resolve, most patients need to lose at least 7%-10% of their body weight, but “only 10% of patients reach this objective with lifestyle therapy at 1 year, and less than half maintain the weight loss 5 years later.” Despite ongoing drug development efforts, no medications have been approved for treating NASH. Although weight loss after bariatric surgery has been reported to resolve NASH in approximately 80% of patients at 1 year, longer-term data have been unavailable, and it has remained unclear whether bariatric surgery can slow or halt fibrosis progression.

All patients in this study had biopsy-confirmed NASH and at least a 5-year history of severe or morbid obesity as well as at least one comorbidity, such as diabetes mellitus or arterial hypertension. Patients were not heavy drinkers, and none had detectable markers of chronic liver disease.

Bariatric surgery produced a median 12-kg/m² drop in body mass index. At 5-year follow-up, 93% of patients meeting or exceeding this threshold who had biopsies performed showed resolution of NASH without worsening of fibrosis. Furthermore, 56% of patients (95% CI, 42.4%-69.3%) had no histologic evidence of fibrosis, including 45.5% of patients who had bridging fibrosis at baseline.

Participants in this study received intensive preoperative support, including evaluations by numerous specialists, a nutrition plan, and a 6- to 12-month therapeutic education program. Bariatric surgery techniques included Roux-en-Y gastric bypass, gastric banding, and sleeve gastrectomy. A subgroup analysis linked gastric bypass to a significantly higher probability of meeting the primary endpoint, compared with gastric banding. Refusal was the most common reason for not having a follow-up biopsy, the researchers said. “Patients without liver biopsy after bariatric surgery were not significantly different from those with a histological follow-up except for a lower BMI at 1 year. Baseline fibrosis did not influence the probability of undergoing histological reevaluation at 5 years.”

Two study participants died from surgical complications within 1 month after surgery, and one patient died from cardiac dysfunction 4 years later. No fatality was deemed liver related.

The study was funded by the French Ministry of Health, Conseil Régional Nord-Pas de Calais, National de la Recherche, and the European commission (FEDER). The researchers reported having no conflicts of interest.

SOURCE: Lassailly G et al. Gastroenterology. 2020 Jun 15. doi: 10.1053/j.gastro.2020.06.006.

Bariatric surgery resolved nonalcoholic steatohepatitis (NASH) without worsening fibrosis in 84% of patients with evaluable biopsies, according to the findings of a prospective study.

The study included 180 severely or morbidly obese adults (body mass index >35 kg/m²) with NASH who underwent bariatric surgery at a center in France. Among 94 patients evaluated 5 years later, 68% had follow-up liver biopsies, of whom 84% (95% confidence interval, 73.1%-92.2%) met the primary endpoint of resolution of NASH without worsening of fibrosis. All histologic aspects of NASH had improved, median nonalcoholic fatty liver disease scores (NAS) fell from 5 (interquartile range, 4 to 5) to 1 (IQR, 0-2; P < .001), and 90% of patients achieved at least a 2-point NAS improvement. Hepatocellular ballooning also improved in 87.5% of patients. Baseline severity of NASH did not affect the chances of it resolving at 5 years. “The reduction of fibrosis [was] progressive, beginning during the first year and continuing through 5 years,” Guillaume Lassailly, MD, and associates wrote in Gastroenterology.

NASH is a priority for clinical research because of the substantial risk for subsequent cirrhosis, added Dr. Lassailly of CHU Lille (France). For NASH to resolve, most patients need to lose at least 7%-10% of their body weight, but “only 10% of patients reach this objective with lifestyle therapy at 1 year, and less than half maintain the weight loss 5 years later.” Despite ongoing drug development efforts, no medications have been approved for treating NASH. Although weight loss after bariatric surgery has been reported to resolve NASH in approximately 80% of patients at 1 year, longer-term data have been unavailable, and it has remained unclear whether bariatric surgery can slow or halt fibrosis progression.

All patients in this study had biopsy-confirmed NASH and at least a 5-year history of severe or morbid obesity as well as at least one comorbidity, such as diabetes mellitus or arterial hypertension. Patients were not heavy drinkers, and none had detectable markers of chronic liver disease.

Bariatric surgery produced a median 12-kg/m² drop in body mass index. At 5-year follow-up, 93% of patients meeting or exceeding this threshold who had biopsies performed showed resolution of NASH without worsening of fibrosis. Furthermore, 56% of patients (95% CI, 42.4%-69.3%) had no histologic evidence of fibrosis, including 45.5% of patients who had bridging fibrosis at baseline.

Participants in this study received intensive preoperative support, including evaluations by numerous specialists, a nutrition plan, and a 6- to 12-month therapeutic education program. Bariatric surgery techniques included Roux-en-Y gastric bypass, gastric banding, and sleeve gastrectomy. A subgroup analysis linked gastric bypass to a significantly higher probability of meeting the primary endpoint, compared with gastric banding. Refusal was the most common reason for not having a follow-up biopsy, the researchers said. “Patients without liver biopsy after bariatric surgery were not significantly different from those with a histological follow-up except for a lower BMI at 1 year. Baseline fibrosis did not influence the probability of undergoing histological reevaluation at 5 years.”

Two study participants died from surgical complications within 1 month after surgery, and one patient died from cardiac dysfunction 4 years later. No fatality was deemed liver related.

The study was funded by the French Ministry of Health, Conseil Régional Nord-Pas de Calais, National de la Recherche, and the European commission (FEDER). The researchers reported having no conflicts of interest.

SOURCE: Lassailly G et al. Gastroenterology. 2020 Jun 15. doi: 10.1053/j.gastro.2020.06.006.

Widespread treatment of hepatitis C virus significantly reduced the risk of hepatocellular carcinoma, based on 18 years of data from patients in Veterans Health Administration hospitals.

Although eradication of hepatitis C virus (HCV) infections has been shown to reduce the risk of hepatocellular carcinoma (HCC), effective direct-acting antiviral therapies available since 2013 appear underused in the United States, with a 14% cure rate for HCV patients as of 2016, wrote Lauren A. Beste, MD, of Veterans Affairs Puget Sound Health Care System, Seattle, and colleagues.

However, “the Veterans Health Administration, the largest integrated health care system in the U.S., provides unrestricted access to HCV treatments and approximately 85% of its case load has achieved cure,” the researchers said.

In a letter published in JAMA, the researchers identified all patients in the VHA diagnosed with HCC based on electronic health records for each year between 2002 and 2018. HCV infection was based on any history of detectable viral load, and HCV cure was defined as a negative viral load at least 12 weeks following completion of antiviral treatment, the researchers said.

“We categorized patients into 3 groups as of the time of HCC diagnosis: HCC/HCV viremic (latest HCV RNA before HCC diagnosis was positive), HCC/HCV cured (HCV eradicated before HCC diagnosis), and HCC/non-HCV (no positive lifetime HCV RNA),” they explained.

The sum of HCC/HCV viremic plus HCC/HCV cured made up the HCC/HCV total. Overall, the incidence of HCC/HCV total increased from 2000 to 2015, peaked at 31.0 per 100,000 patients in 2015, and decreased to 21.8 per 100,000 in 2018 after the introduction of viral eradication efforts from 2014 to 2016.
 

HCV treatment shows value despite lack of causality

Although the study could not prove causality, “the timing of HCV eradication and declining HCC incidence, lack of decline in non–HCV-related HCC, and prior studies demonstrating that HCV eradication reduces HCC risk, provide indirect evidence that this decline may be related to widespread HCV treatment,” the researchers said.

The findings were limited by several factors including the observational study design, use of the International Classification of Diseases to define HCC, use of a VA population that might limit generalizability, and lack of data on the severity of disease prior to treatment, the researchers noted. However, “HCC incidence trends should continue to be monitored closely because patients cured of HCV may have yet to experience the full potential of risk reduction,” and the study results support large-scale campaigns to eliminate HCV as well as monitoring for HCC and HCV patients who achieve disease eradication, they concluded.

The study was supported in part by grants from the National Institutes of Health/National Cancer Institute and the Veterans Affairs Clinical Science Research and Development. The researchers had no financial conflicts to disclose.

SOURCE: Beste LA et al. JAMA. 2020 Sep 8;324(10):1003-5.

Widespread treatment of hepatitis C virus significantly reduced the risk of hepatocellular carcinoma, based on 18 years of data from patients in Veterans Health Administration hospitals.

Although eradication of hepatitis C virus (HCV) infections has been shown to reduce the risk of hepatocellular carcinoma (HCC), effective direct-acting antiviral therapies available since 2013 appear underused in the United States, with a 14% cure rate for HCV patients as of 2016, wrote Lauren A. Beste, MD, of Veterans Affairs Puget Sound Health Care System, Seattle, and colleagues.

However, “the Veterans Health Administration, the largest integrated health care system in the U.S., provides unrestricted access to HCV treatments and approximately 85% of its case load has achieved cure,” the researchers said.

In a letter published in JAMA, the researchers identified all patients in the VHA diagnosed with HCC based on electronic health records for each year between 2002 and 2018. HCV infection was based on any history of detectable viral load, and HCV cure was defined as a negative viral load at least 12 weeks following completion of antiviral treatment, the researchers said.

“We categorized patients into 3 groups as of the time of HCC diagnosis: HCC/HCV viremic (latest HCV RNA before HCC diagnosis was positive), HCC/HCV cured (HCV eradicated before HCC diagnosis), and HCC/non-HCV (no positive lifetime HCV RNA),” they explained.

The sum of HCC/HCV viremic plus HCC/HCV cured made up the HCC/HCV total. Overall, the incidence of HCC/HCV total increased from 2000 to 2015, peaked at 31.0 per 100,000 patients in 2015, and decreased to 21.8 per 100,000 in 2018 after the introduction of viral eradication efforts from 2014 to 2016.
 

HCV treatment shows value despite lack of causality

Although the study could not prove causality, “the timing of HCV eradication and declining HCC incidence, lack of decline in non–HCV-related HCC, and prior studies demonstrating that HCV eradication reduces HCC risk, provide indirect evidence that this decline may be related to widespread HCV treatment,” the researchers said.

The findings were limited by several factors including the observational study design, use of the International Classification of Diseases to define HCC, use of a VA population that might limit generalizability, and lack of data on the severity of disease prior to treatment, the researchers noted. However, “HCC incidence trends should continue to be monitored closely because patients cured of HCV may have yet to experience the full potential of risk reduction,” and the study results support large-scale campaigns to eliminate HCV as well as monitoring for HCC and HCV patients who achieve disease eradication, they concluded.

The study was supported in part by grants from the National Institutes of Health/National Cancer Institute and the Veterans Affairs Clinical Science Research and Development. The researchers had no financial conflicts to disclose.

SOURCE: Beste LA et al. JAMA. 2020 Sep 8;324(10):1003-5.

Widespread treatment of hepatitis C virus significantly reduced the risk of hepatocellular carcinoma, based on 18 years of data from patients in Veterans Health Administration hospitals.

Although eradication of hepatitis C virus (HCV) infections has been shown to reduce the risk of hepatocellular carcinoma (HCC), effective direct-acting antiviral therapies available since 2013 appear underused in the United States, with a 14% cure rate for HCV patients as of 2016, wrote Lauren A. Beste, MD, of Veterans Affairs Puget Sound Health Care System, Seattle, and colleagues.

However, “the Veterans Health Administration, the largest integrated health care system in the U.S., provides unrestricted access to HCV treatments and approximately 85% of its case load has achieved cure,” the researchers said.

In a letter published in JAMA, the researchers identified all patients in the VHA diagnosed with HCC based on electronic health records for each year between 2002 and 2018. HCV infection was based on any history of detectable viral load, and HCV cure was defined as a negative viral load at least 12 weeks following completion of antiviral treatment, the researchers said.

“We categorized patients into 3 groups as of the time of HCC diagnosis: HCC/HCV viremic (latest HCV RNA before HCC diagnosis was positive), HCC/HCV cured (HCV eradicated before HCC diagnosis), and HCC/non-HCV (no positive lifetime HCV RNA),” they explained.

The sum of HCC/HCV viremic plus HCC/HCV cured made up the HCC/HCV total. Overall, the incidence of HCC/HCV total increased from 2000 to 2015, peaked at 31.0 per 100,000 patients in 2015, and decreased to 21.8 per 100,000 in 2018 after the introduction of viral eradication efforts from 2014 to 2016.
 

HCV treatment shows value despite lack of causality

Although the study could not prove causality, “the timing of HCV eradication and declining HCC incidence, lack of decline in non–HCV-related HCC, and prior studies demonstrating that HCV eradication reduces HCC risk, provide indirect evidence that this decline may be related to widespread HCV treatment,” the researchers said.

The findings were limited by several factors including the observational study design, use of the International Classification of Diseases to define HCC, use of a VA population that might limit generalizability, and lack of data on the severity of disease prior to treatment, the researchers noted. However, “HCC incidence trends should continue to be monitored closely because patients cured of HCV may have yet to experience the full potential of risk reduction,” and the study results support large-scale campaigns to eliminate HCV as well as monitoring for HCC and HCV patients who achieve disease eradication, they concluded.

The study was supported in part by grants from the National Institutes of Health/National Cancer Institute and the Veterans Affairs Clinical Science Research and Development. The researchers had no financial conflicts to disclose.

SOURCE: Beste LA et al. JAMA. 2020 Sep 8;324(10):1003-5.

Systemic inflammation and portal hypertension are key predictors of acute-on-chronic liver failure (ACLF) in the 3 months after a hospital stay for acute decompensated cirrhosis and also of death after 12 months, a preliminary analysis of data from the PREDICT study shows.

“Before this, we never had any patient signatures to identify ACLF,” said Jonel Trebicka, MD, PhD, from the JW Goethe University Hospital in Frankfurt, Germany.

Now, Dr. Trebicka’s team has “characterized the phenotypes in pre-ACLF that will progress within 3 months,” he said in an interview. “Those with high levels of inflammatory proteins, white blood cell count, are more likely to develop ACLF.”

ACLF is a highly complex disorder that can lead liver, cardiovascular, renal, cerebral, pulmonary, intestinal, adrenal, and immune systems to fail, Dr. Trebicka explained when he discussed the analysis – published online in the Journal of Hepatology – during the virtual International Liver Congress (ILC) 2020.

The chance of survival after the onset of ACLF is low – the 28-day survival rate is 30% – and “the only treatment we have is liver transplant,” he said.

For their prospective observational study, Dr. Trebicka and his colleagues assessed 1071 participants from 48 European hospitals in 14 countries who were admitted for an episode of acute decompensation, defined as the development of ascites, hepatic encephalopathy, gastrointestinal hemorrhage, infection, or a combination thereof.

The researchers identified three distinct clinical courses for a patient hospitalized with acute decompensated cirrhosis that will help clinicians predict the development of ACLF.

At study enrollment, more than half of the patients at highest risk for ACLF had pre-ACLF and high-grade systemic inflammation. The patients at intermediate risk had unstable decompensated cirrhosis with low-grade systemic inflammation and complications related to severe portal hypertension. And those at lowest risk for ACLF had stable decompensated cirrhosis and no severe systemic inflammation or portal hypertension complications, and did not develop ACLF or another episode of acute decompensation in the subsequent 3 months.

More tools emerging to help predict ACLF

The Albumin-functionality-test (AFT), which uses serum albumin levels to evaluate liver and kidney function, might also be useful in the prediction of ACLF and 12-month survival, according to a separate study an Italian group presented at the virtual ILC.

“Our main results are that parameters from albumin predict the development of ACLF in acute decompensated patients with the same diagnostic performance as the CLIF-AD score,” said Katja Waterstradt, PhD, from the University of Bologna in Italy.

And when the two tests are combined, diagnostic performance is increased, she added.

Dr. Trebicka has disclosed no relevant financial relationships. Dr. Waterstrand is a researcher for MedInnovation GmbH.
 

This article first appeared on Medscape.com.

Systemic inflammation and portal hypertension are key predictors of acute-on-chronic liver failure (ACLF) in the 3 months after a hospital stay for acute decompensated cirrhosis and also of death after 12 months, a preliminary analysis of data from the PREDICT study shows.

“Before this, we never had any patient signatures to identify ACLF,” said Jonel Trebicka, MD, PhD, from the JW Goethe University Hospital in Frankfurt, Germany.

Now, Dr. Trebicka’s team has “characterized the phenotypes in pre-ACLF that will progress within 3 months,” he said in an interview. “Those with high levels of inflammatory proteins, white blood cell count, are more likely to develop ACLF.”

ACLF is a highly complex disorder that can lead liver, cardiovascular, renal, cerebral, pulmonary, intestinal, adrenal, and immune systems to fail, Dr. Trebicka explained when he discussed the analysis – published online in the Journal of Hepatology – during the virtual International Liver Congress (ILC) 2020.

The chance of survival after the onset of ACLF is low – the 28-day survival rate is 30% – and “the only treatment we have is liver transplant,” he said.

For their prospective observational study, Dr. Trebicka and his colleagues assessed 1071 participants from 48 European hospitals in 14 countries who were admitted for an episode of acute decompensation, defined as the development of ascites, hepatic encephalopathy, gastrointestinal hemorrhage, infection, or a combination thereof.

The researchers identified three distinct clinical courses for a patient hospitalized with acute decompensated cirrhosis that will help clinicians predict the development of ACLF.

At study enrollment, more than half of the patients at highest risk for ACLF had pre-ACLF and high-grade systemic inflammation. The patients at intermediate risk had unstable decompensated cirrhosis with low-grade systemic inflammation and complications related to severe portal hypertension. And those at lowest risk for ACLF had stable decompensated cirrhosis and no severe systemic inflammation or portal hypertension complications, and did not develop ACLF or another episode of acute decompensation in the subsequent 3 months.

More tools emerging to help predict ACLF

The Albumin-functionality-test (AFT), which uses serum albumin levels to evaluate liver and kidney function, might also be useful in the prediction of ACLF and 12-month survival, according to a separate study an Italian group presented at the virtual ILC.

“Our main results are that parameters from albumin predict the development of ACLF in acute decompensated patients with the same diagnostic performance as the CLIF-AD score,” said Katja Waterstradt, PhD, from the University of Bologna in Italy.

And when the two tests are combined, diagnostic performance is increased, she added.

Dr. Trebicka has disclosed no relevant financial relationships. Dr. Waterstrand is a researcher for MedInnovation GmbH.
 

This article first appeared on Medscape.com.

Systemic inflammation and portal hypertension are key predictors of acute-on-chronic liver failure (ACLF) in the 3 months after a hospital stay for acute decompensated cirrhosis and also of death after 12 months, a preliminary analysis of data from the PREDICT study shows.

“Before this, we never had any patient signatures to identify ACLF,” said Jonel Trebicka, MD, PhD, from the JW Goethe University Hospital in Frankfurt, Germany.

Now, Dr. Trebicka’s team has “characterized the phenotypes in pre-ACLF that will progress within 3 months,” he said in an interview. “Those with high levels of inflammatory proteins, white blood cell count, are more likely to develop ACLF.”

ACLF is a highly complex disorder that can lead liver, cardiovascular, renal, cerebral, pulmonary, intestinal, adrenal, and immune systems to fail, Dr. Trebicka explained when he discussed the analysis – published online in the Journal of Hepatology – during the virtual International Liver Congress (ILC) 2020.

The chance of survival after the onset of ACLF is low – the 28-day survival rate is 30% – and “the only treatment we have is liver transplant,” he said.

For their prospective observational study, Dr. Trebicka and his colleagues assessed 1071 participants from 48 European hospitals in 14 countries who were admitted for an episode of acute decompensation, defined as the development of ascites, hepatic encephalopathy, gastrointestinal hemorrhage, infection, or a combination thereof.

The researchers identified three distinct clinical courses for a patient hospitalized with acute decompensated cirrhosis that will help clinicians predict the development of ACLF.

At study enrollment, more than half of the patients at highest risk for ACLF had pre-ACLF and high-grade systemic inflammation. The patients at intermediate risk had unstable decompensated cirrhosis with low-grade systemic inflammation and complications related to severe portal hypertension. And those at lowest risk for ACLF had stable decompensated cirrhosis and no severe systemic inflammation or portal hypertension complications, and did not develop ACLF or another episode of acute decompensation in the subsequent 3 months.

More tools emerging to help predict ACLF

The Albumin-functionality-test (AFT), which uses serum albumin levels to evaluate liver and kidney function, might also be useful in the prediction of ACLF and 12-month survival, according to a separate study an Italian group presented at the virtual ILC.

“Our main results are that parameters from albumin predict the development of ACLF in acute decompensated patients with the same diagnostic performance as the CLIF-AD score,” said Katja Waterstradt, PhD, from the University of Bologna in Italy.

And when the two tests are combined, diagnostic performance is increased, she added.

Dr. Trebicka has disclosed no relevant financial relationships. Dr. Waterstrand is a researcher for MedInnovation GmbH.
 

This article first appeared on Medscape.com.

A history of liver transplant conveyed no increased risk of death from COVID-19 infections, according to data from a multicenter cohort study of 151 transplant recipients who became infected.

Although current data suggest a possible increased risk of adverse outcomes if liver transplant patients develop COVID-19 infections, the effects remain unclear, wrote Gwilym J. Webb, PhD, of the University of Oxford (England) and colleagues.

In a study published in the Lancet Gastroenterology & Hepatology, the researchers identified adults from 18 countries who had laboratory-confirmed COVID-19 infections between March 25, 2020, and June 26, 2020. The average age of the patients was 60 years, and 68% were men. A contemporaneous group of 627 consecutive adults with confirmed COVID-19 infections who had not undergone liver transplants served as controls.

Overall, 28 of the liver transplant patients and 167 of the controls died (19% vs. 27%; P = .046).

In addition, no differences appeared between infected transplant patients and infected controls in terms of hospitalization (82% vs. 76%) and the need for intensive care (31% vs. 30%), although the transplant patients were significantly more likely to require invasive ventilation (20% vs. 5%).

However, in a multivariate analysis, older age, serum creatinine concentration, and the presence of nonliver cancers were independently associated with increased risk of death in the liver transplant patients, with odds ratios of 1.06 for each year increase in age, 1.57 for each mg/dL increase in serum creatinine concentration, and 18.30 with the presence of a nonliver cancer.

The study findings were limited by several factors including the potential overreporting of severe COVID-19 cases because of reporting bias in the transplant registry, as well as the inability of the sample size to rule out mortality differences, the differences in comorbidities between the transplant patients and controls, and the impact of unmeasured confounding variables such as diet, physical activity, or fibrosis or cirrhosis in recipient grafts, the researchers noted. However, the results suggest that a history of liver transplantation does not increase the risk of death following COVID-19 infection, they wrote.

“Thus, traditional risk factors for adverse outcomes from COVID-19 should be preferentially considered when considering the risks and benefits of hospital attendance, immunosuppression, and social-distancing requirements for liver transplant recipients during the ongoing COVID-19 pandemic,” they concluded.

Focus on comorbidities and combined transplants

“Given that age and presence of comorbidities were significantly associated with risk of death in the cohorts of patients who had and had not undergone liver transplantation, greater emphasis should be placed on other coexisting comorbidities, rather than transplantation status per se, when risk-stratifying liver transplant recipients,” the researchers noted. “Indirectly, these findings suggest that liver transplantation, where indicated, should not be delayed during the COVID-19 pandemic, and that supportive care should not be limited for patients with existing liver transplants with COVID-19,” they suggested.

Given the high prevalence of COVID-19 in many countries, “it is inevitable that liver transplant patients will become infected,” said Wajahat Mehal, MD, of Yale University, New Haven, Conn., in an interview.

Going forward, “it is important to know the natural history of COVID in the immunocompromised population,” he emphasized.

One of the study limitations was the lack of data on how patients’ immunosuppression regimens were changed, if at all, while they were infected. “Since some other immunocompromised patients have had a higher rate of complications [in the wake of COVID-19 infections], I was pleasantly surprised that liver transplant recipients did so well,” Dr. Mehal said.

Dr. Mehal noted that additional research is needed to promote safety in patients with liver disease in the context of COVID-19. “It would be important to evaluate combined transplants, particularly combined liver/kidney transplants,” he said.

The study was supported by the European Association for the Study of the Liver, the National Institutes of Health, and the United Kingdom National Institute for Health Research. Lead author Dr. Webb had no financial conflicts to disclose. One coauthor disclosed unrelated fees from AbbVie and grants from the Fondation du Centre Hospitalier de l’Université de Montréal. Dr. Mehal had no financial conflicts to disclose.

SOURCE: Webb GJ et al. Lancet Gastroenterol Hepatol. 2020 Aug 28. doi: 10.1016/ S2468-1253(20)30271-5.

A history of liver transplant conveyed no increased risk of death from COVID-19 infections, according to data from a multicenter cohort study of 151 transplant recipients who became infected.

Although current data suggest a possible increased risk of adverse outcomes if liver transplant patients develop COVID-19 infections, the effects remain unclear, wrote Gwilym J. Webb, PhD, of the University of Oxford (England) and colleagues.

In a study published in the Lancet Gastroenterology & Hepatology, the researchers identified adults from 18 countries who had laboratory-confirmed COVID-19 infections between March 25, 2020, and June 26, 2020. The average age of the patients was 60 years, and 68% were men. A contemporaneous group of 627 consecutive adults with confirmed COVID-19 infections who had not undergone liver transplants served as controls.

Overall, 28 of the liver transplant patients and 167 of the controls died (19% vs. 27%; P = .046).

In addition, no differences appeared between infected transplant patients and infected controls in terms of hospitalization (82% vs. 76%) and the need for intensive care (31% vs. 30%), although the transplant patients were significantly more likely to require invasive ventilation (20% vs. 5%).

However, in a multivariate analysis, older age, serum creatinine concentration, and the presence of nonliver cancers were independently associated with increased risk of death in the liver transplant patients, with odds ratios of 1.06 for each year increase in age, 1.57 for each mg/dL increase in serum creatinine concentration, and 18.30 with the presence of a nonliver cancer.

The study findings were limited by several factors including the potential overreporting of severe COVID-19 cases because of reporting bias in the transplant registry, as well as the inability of the sample size to rule out mortality differences, the differences in comorbidities between the transplant patients and controls, and the impact of unmeasured confounding variables such as diet, physical activity, or fibrosis or cirrhosis in recipient grafts, the researchers noted. However, the results suggest that a history of liver transplantation does not increase the risk of death following COVID-19 infection, they wrote.

“Thus, traditional risk factors for adverse outcomes from COVID-19 should be preferentially considered when considering the risks and benefits of hospital attendance, immunosuppression, and social-distancing requirements for liver transplant recipients during the ongoing COVID-19 pandemic,” they concluded.

Focus on comorbidities and combined transplants

“Given that age and presence of comorbidities were significantly associated with risk of death in the cohorts of patients who had and had not undergone liver transplantation, greater emphasis should be placed on other coexisting comorbidities, rather than transplantation status per se, when risk-stratifying liver transplant recipients,” the researchers noted. “Indirectly, these findings suggest that liver transplantation, where indicated, should not be delayed during the COVID-19 pandemic, and that supportive care should not be limited for patients with existing liver transplants with COVID-19,” they suggested.

Given the high prevalence of COVID-19 in many countries, “it is inevitable that liver transplant patients will become infected,” said Wajahat Mehal, MD, of Yale University, New Haven, Conn., in an interview.

Going forward, “it is important to know the natural history of COVID in the immunocompromised population,” he emphasized.

One of the study limitations was the lack of data on how patients’ immunosuppression regimens were changed, if at all, while they were infected. “Since some other immunocompromised patients have had a higher rate of complications [in the wake of COVID-19 infections], I was pleasantly surprised that liver transplant recipients did so well,” Dr. Mehal said.

Dr. Mehal noted that additional research is needed to promote safety in patients with liver disease in the context of COVID-19. “It would be important to evaluate combined transplants, particularly combined liver/kidney transplants,” he said.

The study was supported by the European Association for the Study of the Liver, the National Institutes of Health, and the United Kingdom National Institute for Health Research. Lead author Dr. Webb had no financial conflicts to disclose. One coauthor disclosed unrelated fees from AbbVie and grants from the Fondation du Centre Hospitalier de l’Université de Montréal. Dr. Mehal had no financial conflicts to disclose.

SOURCE: Webb GJ et al. Lancet Gastroenterol Hepatol. 2020 Aug 28. doi: 10.1016/ S2468-1253(20)30271-5.

A history of liver transplant conveyed no increased risk of death from COVID-19 infections, according to data from a multicenter cohort study of 151 transplant recipients who became infected.

Although current data suggest a possible increased risk of adverse outcomes if liver transplant patients develop COVID-19 infections, the effects remain unclear, wrote Gwilym J. Webb, PhD, of the University of Oxford (England) and colleagues.

In a study published in the Lancet Gastroenterology & Hepatology, the researchers identified adults from 18 countries who had laboratory-confirmed COVID-19 infections between March 25, 2020, and June 26, 2020. The average age of the patients was 60 years, and 68% were men. A contemporaneous group of 627 consecutive adults with confirmed COVID-19 infections who had not undergone liver transplants served as controls.

Overall, 28 of the liver transplant patients and 167 of the controls died (19% vs. 27%; P = .046).

In addition, no differences appeared between infected transplant patients and infected controls in terms of hospitalization (82% vs. 76%) and the need for intensive care (31% vs. 30%), although the transplant patients were significantly more likely to require invasive ventilation (20% vs. 5%).

However, in a multivariate analysis, older age, serum creatinine concentration, and the presence of nonliver cancers were independently associated with increased risk of death in the liver transplant patients, with odds ratios of 1.06 for each year increase in age, 1.57 for each mg/dL increase in serum creatinine concentration, and 18.30 with the presence of a nonliver cancer.

The study findings were limited by several factors including the potential overreporting of severe COVID-19 cases because of reporting bias in the transplant registry, as well as the inability of the sample size to rule out mortality differences, the differences in comorbidities between the transplant patients and controls, and the impact of unmeasured confounding variables such as diet, physical activity, or fibrosis or cirrhosis in recipient grafts, the researchers noted. However, the results suggest that a history of liver transplantation does not increase the risk of death following COVID-19 infection, they wrote.

“Thus, traditional risk factors for adverse outcomes from COVID-19 should be preferentially considered when considering the risks and benefits of hospital attendance, immunosuppression, and social-distancing requirements for liver transplant recipients during the ongoing COVID-19 pandemic,” they concluded.

Focus on comorbidities and combined transplants

“Given that age and presence of comorbidities were significantly associated with risk of death in the cohorts of patients who had and had not undergone liver transplantation, greater emphasis should be placed on other coexisting comorbidities, rather than transplantation status per se, when risk-stratifying liver transplant recipients,” the researchers noted. “Indirectly, these findings suggest that liver transplantation, where indicated, should not be delayed during the COVID-19 pandemic, and that supportive care should not be limited for patients with existing liver transplants with COVID-19,” they suggested.

Given the high prevalence of COVID-19 in many countries, “it is inevitable that liver transplant patients will become infected,” said Wajahat Mehal, MD, of Yale University, New Haven, Conn., in an interview.

Going forward, “it is important to know the natural history of COVID in the immunocompromised population,” he emphasized.

One of the study limitations was the lack of data on how patients’ immunosuppression regimens were changed, if at all, while they were infected. “Since some other immunocompromised patients have had a higher rate of complications [in the wake of COVID-19 infections], I was pleasantly surprised that liver transplant recipients did so well,” Dr. Mehal said.

Dr. Mehal noted that additional research is needed to promote safety in patients with liver disease in the context of COVID-19. “It would be important to evaluate combined transplants, particularly combined liver/kidney transplants,” he said.

The study was supported by the European Association for the Study of the Liver, the National Institutes of Health, and the United Kingdom National Institute for Health Research. Lead author Dr. Webb had no financial conflicts to disclose. One coauthor disclosed unrelated fees from AbbVie and grants from the Fondation du Centre Hospitalier de l’Université de Montréal. Dr. Mehal had no financial conflicts to disclose.

SOURCE: Webb GJ et al. Lancet Gastroenterol Hepatol. 2020 Aug 28. doi: 10.1016/ S2468-1253(20)30271-5.

Eleven high-income countries are on track to meet World Health Organization targets to eliminate hepatitis C infection by 2030, compared with 9 countries 2 years ago, researchers reported. But 28 countries, including the United States, are not expected to eliminate HCV until 2050.

“In the countries making progress, the common elements are political will, a clear national plan, and easing of restrictions on the cascade of care and testing,” Yuri Sanchez Gonzalez, PhD, director of health economics and outcomes research for biopharmaceutical company AbbVie said in an interview. That would include offering hepatitis C treatment to individuals who have liver fibrosis and those struggling with sobriety, he said. “We can’t overstate how much this is a massive driver of the hepatitis C epidemic.”

His research, presented at the digital edition of the International Liver Congress this week, showed more countries on target than in a study published 2 years ago in Liver International . “But it’s not enough,” Dr. Sanchez Gonzalez said. “We know that more than 80% of infections are in people who inject drugs. Stigmatization of drug use is still a very major issue.” Despite data clearly showing that countries who have harm-reduction programs make progress, “in many countries these programs are still illegal.”

To evaluate which countries are on target to eliminate hepatitis C by 2030, researchers performed Markov disease progression models of HCV infection in 45 high-income countries. The results showed that Australia, Canada, France, Germany, Iceland, Italy, Japan, Spain, Sweden, Switzerland, and the United Kingdom are “in the green” (on target for 2030).

Austria, Malta, the Netherlands, New Zealand, and South Korea are “in the yellow” (on target for 2040), and 28 remaining countries, including the United States, are “in the red,” with targets estimated to be met by 2050.

Compared with an analysis performed 2 years ago, South Korea moved from green to yellow, while Canada, Germany, and Sweden moved from red to green. 

Researchers say that the countries moving the needle are the ones addressing barriers to care.
 

EASL: Eliminate barriers to treatment

During this week’s Congress, the European Association for the Study of the Liver (EASL) launched a policy statement recommending breaking down all barriers that prevent people who inject drugs from getting access to hepatitis C treatment, including encouragement of laws and policies that “decriminalize drug use, drug possession and drug users themselves,” said statement coauthor Mojca Maticic, MD, PhD, University of Ljubljana, Slovenia.

“To reach the desired WHO goal, combining decriminalization of personal drug consumption and integrated interventions that include hepatitis C testing and treatment should be implemented,” she added. We need to adopt “an approach based on public health promotion, respect for human rights, and evidence.”

Although harm reduction is the top strategy for making 2030 targets, having precision data also helps a lot.

“High-quality data and harm-reduction innovation to curb the overdose crisis has moved us out of the red and into the green,” Canadian researcher Jordan Feld, MD, MPH, University of Toronto, said in an interview. He points to British Columbia, Canada’s third-most populous province, putting harm reduction programs in place as key to Canadian progress.

“Given the increasing opioid epidemic, you’re creating yourself a bigger problem if you don’t treat this population,” Dr. Feld said. When a person needs 6 months to get sober in order to be treated for HCV, that’s more potential time to pass the infection to others. His study, also presented at ILC this week, outlines anticipated timing of hepatitis C in Canada’s four most populous provinces (Ontario, Quebec, British Columbia, and Alberta), and shows British Columbia will reach targets by 2028.

Lifting all restrictions clearly helps, Dr. Sanchez Gonzalez reported. He pointed to Sweden as a good example, a country that recently lifted HCV treatment restrictions for individuals living with fibrosis. Sweden moved from a red to a green spot in this analysis and is now on target for 2030.

“As long as everyone who needs treatment gets treatment, you can make tremendous progress,” he said.

Keeping track is also essential to moving the needle. Since the WHO has no enforcement power, “these studies, which offer a report card of progress, really matter,” Dr. Sanchez Gonzalez explained. When a country knows where they stand, they are more likely to take action to change. “Nobody likes to be shown in the red.”

Still, “it’s not a shaming exercise,” he said. It’s about starting a conversation, showing who’s on track, and sharing how to get on track. “Knowing that there is something in your power to move the needle toward elimination by learning from your neighbors is powerful – often, it just takes political will.”

Dr. Feld has received consulting fees from AbbVie. Dr. Sanchez Gonzalez is on staff as the Director of Economics at AbbVie. Dr. Maticic has disclosed no relevant financial relationships.

A version of this article originally appeared on Medscape.com.

Eleven high-income countries are on track to meet World Health Organization targets to eliminate hepatitis C infection by 2030, compared with 9 countries 2 years ago, researchers reported. But 28 countries, including the United States, are not expected to eliminate HCV until 2050.

“In the countries making progress, the common elements are political will, a clear national plan, and easing of restrictions on the cascade of care and testing,” Yuri Sanchez Gonzalez, PhD, director of health economics and outcomes research for biopharmaceutical company AbbVie said in an interview. That would include offering hepatitis C treatment to individuals who have liver fibrosis and those struggling with sobriety, he said. “We can’t overstate how much this is a massive driver of the hepatitis C epidemic.”

His research, presented at the digital edition of the International Liver Congress this week, showed more countries on target than in a study published 2 years ago in Liver International . “But it’s not enough,” Dr. Sanchez Gonzalez said. “We know that more than 80% of infections are in people who inject drugs. Stigmatization of drug use is still a very major issue.” Despite data clearly showing that countries who have harm-reduction programs make progress, “in many countries these programs are still illegal.”

To evaluate which countries are on target to eliminate hepatitis C by 2030, researchers performed Markov disease progression models of HCV infection in 45 high-income countries. The results showed that Australia, Canada, France, Germany, Iceland, Italy, Japan, Spain, Sweden, Switzerland, and the United Kingdom are “in the green” (on target for 2030).

Austria, Malta, the Netherlands, New Zealand, and South Korea are “in the yellow” (on target for 2040), and 28 remaining countries, including the United States, are “in the red,” with targets estimated to be met by 2050.

Compared with an analysis performed 2 years ago, South Korea moved from green to yellow, while Canada, Germany, and Sweden moved from red to green. 

Researchers say that the countries moving the needle are the ones addressing barriers to care.
 

EASL: Eliminate barriers to treatment

During this week’s Congress, the European Association for the Study of the Liver (EASL) launched a policy statement recommending breaking down all barriers that prevent people who inject drugs from getting access to hepatitis C treatment, including encouragement of laws and policies that “decriminalize drug use, drug possession and drug users themselves,” said statement coauthor Mojca Maticic, MD, PhD, University of Ljubljana, Slovenia.

“To reach the desired WHO goal, combining decriminalization of personal drug consumption and integrated interventions that include hepatitis C testing and treatment should be implemented,” she added. We need to adopt “an approach based on public health promotion, respect for human rights, and evidence.”

Although harm reduction is the top strategy for making 2030 targets, having precision data also helps a lot.

“High-quality data and harm-reduction innovation to curb the overdose crisis has moved us out of the red and into the green,” Canadian researcher Jordan Feld, MD, MPH, University of Toronto, said in an interview. He points to British Columbia, Canada’s third-most populous province, putting harm reduction programs in place as key to Canadian progress.

“Given the increasing opioid epidemic, you’re creating yourself a bigger problem if you don’t treat this population,” Dr. Feld said. When a person needs 6 months to get sober in order to be treated for HCV, that’s more potential time to pass the infection to others. His study, also presented at ILC this week, outlines anticipated timing of hepatitis C in Canada’s four most populous provinces (Ontario, Quebec, British Columbia, and Alberta), and shows British Columbia will reach targets by 2028.

Lifting all restrictions clearly helps, Dr. Sanchez Gonzalez reported. He pointed to Sweden as a good example, a country that recently lifted HCV treatment restrictions for individuals living with fibrosis. Sweden moved from a red to a green spot in this analysis and is now on target for 2030.

“As long as everyone who needs treatment gets treatment, you can make tremendous progress,” he said.

Keeping track is also essential to moving the needle. Since the WHO has no enforcement power, “these studies, which offer a report card of progress, really matter,” Dr. Sanchez Gonzalez explained. When a country knows where they stand, they are more likely to take action to change. “Nobody likes to be shown in the red.”

Still, “it’s not a shaming exercise,” he said. It’s about starting a conversation, showing who’s on track, and sharing how to get on track. “Knowing that there is something in your power to move the needle toward elimination by learning from your neighbors is powerful – often, it just takes political will.”

Dr. Feld has received consulting fees from AbbVie. Dr. Sanchez Gonzalez is on staff as the Director of Economics at AbbVie. Dr. Maticic has disclosed no relevant financial relationships.

A version of this article originally appeared on Medscape.com.

Eleven high-income countries are on track to meet World Health Organization targets to eliminate hepatitis C infection by 2030, compared with 9 countries 2 years ago, researchers reported. But 28 countries, including the United States, are not expected to eliminate HCV until 2050.

“In the countries making progress, the common elements are political will, a clear national plan, and easing of restrictions on the cascade of care and testing,” Yuri Sanchez Gonzalez, PhD, director of health economics and outcomes research for biopharmaceutical company AbbVie said in an interview. That would include offering hepatitis C treatment to individuals who have liver fibrosis and those struggling with sobriety, he said. “We can’t overstate how much this is a massive driver of the hepatitis C epidemic.”

His research, presented at the digital edition of the International Liver Congress this week, showed more countries on target than in a study published 2 years ago in Liver International . “But it’s not enough,” Dr. Sanchez Gonzalez said. “We know that more than 80% of infections are in people who inject drugs. Stigmatization of drug use is still a very major issue.” Despite data clearly showing that countries who have harm-reduction programs make progress, “in many countries these programs are still illegal.”

To evaluate which countries are on target to eliminate hepatitis C by 2030, researchers performed Markov disease progression models of HCV infection in 45 high-income countries. The results showed that Australia, Canada, France, Germany, Iceland, Italy, Japan, Spain, Sweden, Switzerland, and the United Kingdom are “in the green” (on target for 2030).

Austria, Malta, the Netherlands, New Zealand, and South Korea are “in the yellow” (on target for 2040), and 28 remaining countries, including the United States, are “in the red,” with targets estimated to be met by 2050.

Compared with an analysis performed 2 years ago, South Korea moved from green to yellow, while Canada, Germany, and Sweden moved from red to green. 

Researchers say that the countries moving the needle are the ones addressing barriers to care.
 

EASL: Eliminate barriers to treatment

During this week’s Congress, the European Association for the Study of the Liver (EASL) launched a policy statement recommending breaking down all barriers that prevent people who inject drugs from getting access to hepatitis C treatment, including encouragement of laws and policies that “decriminalize drug use, drug possession and drug users themselves,” said statement coauthor Mojca Maticic, MD, PhD, University of Ljubljana, Slovenia.

“To reach the desired WHO goal, combining decriminalization of personal drug consumption and integrated interventions that include hepatitis C testing and treatment should be implemented,” she added. We need to adopt “an approach based on public health promotion, respect for human rights, and evidence.”

Although harm reduction is the top strategy for making 2030 targets, having precision data also helps a lot.

“High-quality data and harm-reduction innovation to curb the overdose crisis has moved us out of the red and into the green,” Canadian researcher Jordan Feld, MD, MPH, University of Toronto, said in an interview. He points to British Columbia, Canada’s third-most populous province, putting harm reduction programs in place as key to Canadian progress.

“Given the increasing opioid epidemic, you’re creating yourself a bigger problem if you don’t treat this population,” Dr. Feld said. When a person needs 6 months to get sober in order to be treated for HCV, that’s more potential time to pass the infection to others. His study, also presented at ILC this week, outlines anticipated timing of hepatitis C in Canada’s four most populous provinces (Ontario, Quebec, British Columbia, and Alberta), and shows British Columbia will reach targets by 2028.

Lifting all restrictions clearly helps, Dr. Sanchez Gonzalez reported. He pointed to Sweden as a good example, a country that recently lifted HCV treatment restrictions for individuals living with fibrosis. Sweden moved from a red to a green spot in this analysis and is now on target for 2030.

“As long as everyone who needs treatment gets treatment, you can make tremendous progress,” he said.

Keeping track is also essential to moving the needle. Since the WHO has no enforcement power, “these studies, which offer a report card of progress, really matter,” Dr. Sanchez Gonzalez explained. When a country knows where they stand, they are more likely to take action to change. “Nobody likes to be shown in the red.”

Still, “it’s not a shaming exercise,” he said. It’s about starting a conversation, showing who’s on track, and sharing how to get on track. “Knowing that there is something in your power to move the needle toward elimination by learning from your neighbors is powerful – often, it just takes political will.”

Dr. Feld has received consulting fees from AbbVie. Dr. Sanchez Gonzalez is on staff as the Director of Economics at AbbVie. Dr. Maticic has disclosed no relevant financial relationships.

A version of this article originally appeared on Medscape.com.

Repeat Fibrosis-4 (FIB-4) scores can be used to identify people at greatest risk for cirrhosis of the liver, new research shows.

“Done repeatedly, this test can improve prediction capacity to identify who will develop cirrhosis of the liver later in life,” said lead researcher Hannes Hagström, MD, from the Karolinska University Hospital in Stockholm.

A FIB-4 score that rises from one test to the next indicates that a person is at increased risk for severe liver disease, whereas a score that drops indicates a decreased risk, he told Medscape Medical News. The study results — published online July 1 in the Journal of Hepatology, was presented at the Digital International Liver Congress 2020.

The noninvasive, widely available, cheap FIB-4 test — which is calculated on the basis of age, transaminase level, and platelet count — is commonly used to identify the risk for advanced fibrosis in liver disease, but it has not been used to predict future risk.

To evaluate risk for cirrhosis, Hagström and his colleagues looked at 812,073 blood tests performed from 1985 to 1996 on people enrolled in the Swedish Apolipoprotein Mortality Risk (AMORIS) study.

They excluded people younger than 35 years and older than 79 years and anyone with a diagnosis of any liver disease at baseline.

The 40,729 people who had two FIB-4 measurements taken less than 5 years apart were included in the analysis. Test results were categorized into three risk groups: low (<1.30), intermediate (1.30 - 2.67), and high (>2.67).

After a median of 16.2 years, 11,929 people in the study cohort had died and 581 had a severe liver disease event.

Severe liver disease events were more common in people who had both tests categorized as high risk than in people who had both tests categorized as low risk (13.2% vs 1.0%; aHR, 17.04; 95% CI, 11.67 - 24.88).

The researchers found that a one-unit increase between the two test results was continuously predictive of a severe liver disease event (aHR, 1.81; 95% CI, 1.67 - 1.96).
 

One test not enough

The absolute risk for severe liver disease in the general population is 2%, but the FIB-4 score is elevated in about one-third of people in the general population.

“A lot of people who have increased levels of this biomarker will never develop cirrhosis,” Hagström told Medscape Medical News.

Although two FIB-4 scores might not identify everyone who will get cirrhosis, comparing scores provides insight into who is at greatest risk, he explained.

This information can be useful, particularly for primary care doctors. If you know that someone is at higher risk, “you can send that patient for a FibroScan, which is a much more sensitive measurement,” but also much more expensive. “Now we can better know who to send,” he said.

However, “the main problem is that these tests are not widely known” or used enough by primary care doctors, Hagström said.

A lack of knowledge about the utility of this test is a problem, agreed Jérôme Boursier, MD, PhD, from Angers University in France.

“The younger doctors are using these tests more often,” he told Medscape Medical News, but “the older doctors are not aware they exist.”

This study supports repeating the tests. “One test offers quite poor prediction,” Boursier said. But “when you have a higher score on a second one, this can help the conversation with the patient.”

Hagström and Boursier have disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

Repeat Fibrosis-4 (FIB-4) scores can be used to identify people at greatest risk for cirrhosis of the liver, new research shows.

“Done repeatedly, this test can improve prediction capacity to identify who will develop cirrhosis of the liver later in life,” said lead researcher Hannes Hagström, MD, from the Karolinska University Hospital in Stockholm.

A FIB-4 score that rises from one test to the next indicates that a person is at increased risk for severe liver disease, whereas a score that drops indicates a decreased risk, he told Medscape Medical News. The study results — published online July 1 in the Journal of Hepatology, was presented at the Digital International Liver Congress 2020.

The noninvasive, widely available, cheap FIB-4 test — which is calculated on the basis of age, transaminase level, and platelet count — is commonly used to identify the risk for advanced fibrosis in liver disease, but it has not been used to predict future risk.

To evaluate risk for cirrhosis, Hagström and his colleagues looked at 812,073 blood tests performed from 1985 to 1996 on people enrolled in the Swedish Apolipoprotein Mortality Risk (AMORIS) study.

They excluded people younger than 35 years and older than 79 years and anyone with a diagnosis of any liver disease at baseline.

The 40,729 people who had two FIB-4 measurements taken less than 5 years apart were included in the analysis. Test results were categorized into three risk groups: low (<1.30), intermediate (1.30 - 2.67), and high (>2.67).

After a median of 16.2 years, 11,929 people in the study cohort had died and 581 had a severe liver disease event.

Severe liver disease events were more common in people who had both tests categorized as high risk than in people who had both tests categorized as low risk (13.2% vs 1.0%; aHR, 17.04; 95% CI, 11.67 - 24.88).

The researchers found that a one-unit increase between the two test results was continuously predictive of a severe liver disease event (aHR, 1.81; 95% CI, 1.67 - 1.96).
 

One test not enough

The absolute risk for severe liver disease in the general population is 2%, but the FIB-4 score is elevated in about one-third of people in the general population.

“A lot of people who have increased levels of this biomarker will never develop cirrhosis,” Hagström told Medscape Medical News.

Although two FIB-4 scores might not identify everyone who will get cirrhosis, comparing scores provides insight into who is at greatest risk, he explained.

This information can be useful, particularly for primary care doctors. If you know that someone is at higher risk, “you can send that patient for a FibroScan, which is a much more sensitive measurement,” but also much more expensive. “Now we can better know who to send,” he said.

However, “the main problem is that these tests are not widely known” or used enough by primary care doctors, Hagström said.

A lack of knowledge about the utility of this test is a problem, agreed Jérôme Boursier, MD, PhD, from Angers University in France.

“The younger doctors are using these tests more often,” he told Medscape Medical News, but “the older doctors are not aware they exist.”

This study supports repeating the tests. “One test offers quite poor prediction,” Boursier said. But “when you have a higher score on a second one, this can help the conversation with the patient.”

Hagström and Boursier have disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

Repeat Fibrosis-4 (FIB-4) scores can be used to identify people at greatest risk for cirrhosis of the liver, new research shows.

“Done repeatedly, this test can improve prediction capacity to identify who will develop cirrhosis of the liver later in life,” said lead researcher Hannes Hagström, MD, from the Karolinska University Hospital in Stockholm.

A FIB-4 score that rises from one test to the next indicates that a person is at increased risk for severe liver disease, whereas a score that drops indicates a decreased risk, he told Medscape Medical News. The study results — published online July 1 in the Journal of Hepatology, was presented at the Digital International Liver Congress 2020.

The noninvasive, widely available, cheap FIB-4 test — which is calculated on the basis of age, transaminase level, and platelet count — is commonly used to identify the risk for advanced fibrosis in liver disease, but it has not been used to predict future risk.

To evaluate risk for cirrhosis, Hagström and his colleagues looked at 812,073 blood tests performed from 1985 to 1996 on people enrolled in the Swedish Apolipoprotein Mortality Risk (AMORIS) study.

They excluded people younger than 35 years and older than 79 years and anyone with a diagnosis of any liver disease at baseline.

The 40,729 people who had two FIB-4 measurements taken less than 5 years apart were included in the analysis. Test results were categorized into three risk groups: low (<1.30), intermediate (1.30 - 2.67), and high (>2.67).

After a median of 16.2 years, 11,929 people in the study cohort had died and 581 had a severe liver disease event.

Severe liver disease events were more common in people who had both tests categorized as high risk than in people who had both tests categorized as low risk (13.2% vs 1.0%; aHR, 17.04; 95% CI, 11.67 - 24.88).

The researchers found that a one-unit increase between the two test results was continuously predictive of a severe liver disease event (aHR, 1.81; 95% CI, 1.67 - 1.96).
 

One test not enough

The absolute risk for severe liver disease in the general population is 2%, but the FIB-4 score is elevated in about one-third of people in the general population.

“A lot of people who have increased levels of this biomarker will never develop cirrhosis,” Hagström told Medscape Medical News.

Although two FIB-4 scores might not identify everyone who will get cirrhosis, comparing scores provides insight into who is at greatest risk, he explained.

This information can be useful, particularly for primary care doctors. If you know that someone is at higher risk, “you can send that patient for a FibroScan, which is a much more sensitive measurement,” but also much more expensive. “Now we can better know who to send,” he said.

However, “the main problem is that these tests are not widely known” or used enough by primary care doctors, Hagström said.

A lack of knowledge about the utility of this test is a problem, agreed Jérôme Boursier, MD, PhD, from Angers University in France.

“The younger doctors are using these tests more often,” he told Medscape Medical News, but “the older doctors are not aware they exist.”

This study supports repeating the tests. “One test offers quite poor prediction,” Boursier said. But “when you have a higher score on a second one, this can help the conversation with the patient.”

Hagström and Boursier have disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

Fecal microbiota transplantation results in a short-term reduction in alcohol craving in patients with alcohol-induced cirrhosis who can’t stop drinking, results from a new study show.

And that reduction could lead to a better psychosocial quality of life for patients with cirrhosis and alcohol use disorder, said investigator Jasmohan Bajaj, MD, from Virginia Commonwealth University, Richmond.

“This is the most common addiction disorder worldwide, but we have nothing to treat these patients with,” he said.

Cirrhosis is associated with an altered gut-brain axis. It leads to organ damage in several parts of the body, including the brain, gut, pancreas, and liver. This makes changing the gut microbes “an attractive target,” Dr. Bajaj said at the Digital International Liver Congress 2020.

For their phase 1, double-blind study, he and his colleagues assessed 20 men from a Virginia veteran’s hospital with untreatable alcohol use disorder who were not eligible for liver transplantation.

All had failed behavioral or pharmacologic therapy and were unwilling to try again. “That’s what made them good candidates to try something new,” Dr. Bajaj said during a press briefing.

Mean age in the study cohort was 65 years, mean Model for End-Stage Liver disease score was 8.9, and demographic characteristics were similar between the 10 men randomly assigned to fecal transplantation and the 10 assigned to placebo. One man in each group dropped out of the study.

The investigators evaluated cravings, microbiota, and quality of life during the 30-day study period.

At day 15, significantly more men in the transplant group than in the placebo group experienced a reduction in alcohol cravings (90% vs. 30%).

At 30 days, levels of creatinine, serum interleukin-6, and lipopolysaccharide-binding protein were lower in the transplant group than in the placebo group. In addition, levels of butyrate and isobutyrate increased, as did cognition and quality of life scores.

There was also a decrease in urinary ethyl glucuronide in the transplant group, which “is the objective criteria for alcohol intake,” Dr. Bajaj reported, noting that there was no change in ethyl glucuronide in the placebo group.

The increase in microbiota diversity was significant in the transplant group but not in the placebo group. Alistipes, Odoribacter, and Roseburia were more abundant in the transplant group than in the placebo group.

During the 30-day study period, two men in the placebo group required medical attention, one for hyponatremia and the other for atrial fibrillation. However, no adverse events were seen in any men in the transplant group. “This was the No. 1 result,” Dr. Bajaj said.
 

Liver disease and the microbiome

“Understanding of interactions between the human and microbiome genome [metagenome] in health and disease has represented one of the major areas of progress in the last few years,” said Luca Valenti, MD, from the University of Milan, who is a member of the scientific committee of the European Association the Study of the Liver, which organized the congress.

“These studies lay the groundwork for the exploitation of this new knowledge for the treatment of liver disease,” he said.

“We are [now] diagnosing liver disease and the stages of liver disease based on microbiome changes,” said Jonel Trebicka, MD, PhD, from University Hospital Frankfurt (Germany), who chaired a session at the congress on the role of the microbiome in liver disease.

“This and other studies have shown us that the microbiome itself may influence liver disease,” he added.

Dr. Bajaj is considered one of the world’s experts on cirrhosis and the microbiome, Dr. Trebicka explained. Last year, Dr. Bajaj and his team demonstrated that fecal microbiota transplantation can reduce the incidence of recurrent hepatic encephalopathy, as reported by Medscape Medical News.

The current study also “shows clearly that the microbiome plays a role in craving. FMT reduces the desire for alcohol,” said Dr. Trebicka.

“The way to the brain is through the gut,” Dr. Bajaj said.

Dr. Bajaj, Dr. Trebicka, and Dr. Valenti disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

Fecal microbiota transplantation results in a short-term reduction in alcohol craving in patients with alcohol-induced cirrhosis who can’t stop drinking, results from a new study show.

And that reduction could lead to a better psychosocial quality of life for patients with cirrhosis and alcohol use disorder, said investigator Jasmohan Bajaj, MD, from Virginia Commonwealth University, Richmond.

“This is the most common addiction disorder worldwide, but we have nothing to treat these patients with,” he said.

Cirrhosis is associated with an altered gut-brain axis. It leads to organ damage in several parts of the body, including the brain, gut, pancreas, and liver. This makes changing the gut microbes “an attractive target,” Dr. Bajaj said at the Digital International Liver Congress 2020.

For their phase 1, double-blind study, he and his colleagues assessed 20 men from a Virginia veteran’s hospital with untreatable alcohol use disorder who were not eligible for liver transplantation.

All had failed behavioral or pharmacologic therapy and were unwilling to try again. “That’s what made them good candidates to try something new,” Dr. Bajaj said during a press briefing.

Mean age in the study cohort was 65 years, mean Model for End-Stage Liver disease score was 8.9, and demographic characteristics were similar between the 10 men randomly assigned to fecal transplantation and the 10 assigned to placebo. One man in each group dropped out of the study.

The investigators evaluated cravings, microbiota, and quality of life during the 30-day study period.

At day 15, significantly more men in the transplant group than in the placebo group experienced a reduction in alcohol cravings (90% vs. 30%).

At 30 days, levels of creatinine, serum interleukin-6, and lipopolysaccharide-binding protein were lower in the transplant group than in the placebo group. In addition, levels of butyrate and isobutyrate increased, as did cognition and quality of life scores.

There was also a decrease in urinary ethyl glucuronide in the transplant group, which “is the objective criteria for alcohol intake,” Dr. Bajaj reported, noting that there was no change in ethyl glucuronide in the placebo group.

The increase in microbiota diversity was significant in the transplant group but not in the placebo group. Alistipes, Odoribacter, and Roseburia were more abundant in the transplant group than in the placebo group.

During the 30-day study period, two men in the placebo group required medical attention, one for hyponatremia and the other for atrial fibrillation. However, no adverse events were seen in any men in the transplant group. “This was the No. 1 result,” Dr. Bajaj said.
 

Liver disease and the microbiome

“Understanding of interactions between the human and microbiome genome [metagenome] in health and disease has represented one of the major areas of progress in the last few years,” said Luca Valenti, MD, from the University of Milan, who is a member of the scientific committee of the European Association the Study of the Liver, which organized the congress.

“These studies lay the groundwork for the exploitation of this new knowledge for the treatment of liver disease,” he said.

“We are [now] diagnosing liver disease and the stages of liver disease based on microbiome changes,” said Jonel Trebicka, MD, PhD, from University Hospital Frankfurt (Germany), who chaired a session at the congress on the role of the microbiome in liver disease.

“This and other studies have shown us that the microbiome itself may influence liver disease,” he added.

Dr. Bajaj is considered one of the world’s experts on cirrhosis and the microbiome, Dr. Trebicka explained. Last year, Dr. Bajaj and his team demonstrated that fecal microbiota transplantation can reduce the incidence of recurrent hepatic encephalopathy, as reported by Medscape Medical News.

The current study also “shows clearly that the microbiome plays a role in craving. FMT reduces the desire for alcohol,” said Dr. Trebicka.

“The way to the brain is through the gut,” Dr. Bajaj said.

Dr. Bajaj, Dr. Trebicka, and Dr. Valenti disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

Fecal microbiota transplantation results in a short-term reduction in alcohol craving in patients with alcohol-induced cirrhosis who can’t stop drinking, results from a new study show.

And that reduction could lead to a better psychosocial quality of life for patients with cirrhosis and alcohol use disorder, said investigator Jasmohan Bajaj, MD, from Virginia Commonwealth University, Richmond.

“This is the most common addiction disorder worldwide, but we have nothing to treat these patients with,” he said.

Cirrhosis is associated with an altered gut-brain axis. It leads to organ damage in several parts of the body, including the brain, gut, pancreas, and liver. This makes changing the gut microbes “an attractive target,” Dr. Bajaj said at the Digital International Liver Congress 2020.

For their phase 1, double-blind study, he and his colleagues assessed 20 men from a Virginia veteran’s hospital with untreatable alcohol use disorder who were not eligible for liver transplantation.

All had failed behavioral or pharmacologic therapy and were unwilling to try again. “That’s what made them good candidates to try something new,” Dr. Bajaj said during a press briefing.

Mean age in the study cohort was 65 years, mean Model for End-Stage Liver disease score was 8.9, and demographic characteristics were similar between the 10 men randomly assigned to fecal transplantation and the 10 assigned to placebo. One man in each group dropped out of the study.

The investigators evaluated cravings, microbiota, and quality of life during the 30-day study period.

At day 15, significantly more men in the transplant group than in the placebo group experienced a reduction in alcohol cravings (90% vs. 30%).

At 30 days, levels of creatinine, serum interleukin-6, and lipopolysaccharide-binding protein were lower in the transplant group than in the placebo group. In addition, levels of butyrate and isobutyrate increased, as did cognition and quality of life scores.

There was also a decrease in urinary ethyl glucuronide in the transplant group, which “is the objective criteria for alcohol intake,” Dr. Bajaj reported, noting that there was no change in ethyl glucuronide in the placebo group.

The increase in microbiota diversity was significant in the transplant group but not in the placebo group. Alistipes, Odoribacter, and Roseburia were more abundant in the transplant group than in the placebo group.

During the 30-day study period, two men in the placebo group required medical attention, one for hyponatremia and the other for atrial fibrillation. However, no adverse events were seen in any men in the transplant group. “This was the No. 1 result,” Dr. Bajaj said.
 

Liver disease and the microbiome

“Understanding of interactions between the human and microbiome genome [metagenome] in health and disease has represented one of the major areas of progress in the last few years,” said Luca Valenti, MD, from the University of Milan, who is a member of the scientific committee of the European Association the Study of the Liver, which organized the congress.

“These studies lay the groundwork for the exploitation of this new knowledge for the treatment of liver disease,” he said.

“We are [now] diagnosing liver disease and the stages of liver disease based on microbiome changes,” said Jonel Trebicka, MD, PhD, from University Hospital Frankfurt (Germany), who chaired a session at the congress on the role of the microbiome in liver disease.

“This and other studies have shown us that the microbiome itself may influence liver disease,” he added.

Dr. Bajaj is considered one of the world’s experts on cirrhosis and the microbiome, Dr. Trebicka explained. Last year, Dr. Bajaj and his team demonstrated that fecal microbiota transplantation can reduce the incidence of recurrent hepatic encephalopathy, as reported by Medscape Medical News.

The current study also “shows clearly that the microbiome plays a role in craving. FMT reduces the desire for alcohol,” said Dr. Trebicka.

“The way to the brain is through the gut,” Dr. Bajaj said.

Dr. Bajaj, Dr. Trebicka, and Dr. Valenti disclosed no relevant financial relationships.

This article first appeared on Medscape.com.