Hepatology

Probiotics appear to be beneficial for patients with cirrhosis, showing a reversal of hepatic encephalopathy (HE), improvement in liver function measures, and regulation of gut dysbiosis, according to a systematic review and meta-analysis.

They also improve quality of life and have a favorable safety profile, adding to their potential as a promising intervention for treating cirrhosis, the study authors wrote.

“As currently one of the top 10 leading causes of death globally, cirrhosis imposes a great health burden in many countries,” wrote lead author Xing Yang of the Health Management Research Institute at the People’s Hospital of Guangxi Zhuang Autonomous Region and Guangxi Academy of Medical Sciences in Nanning, China, and colleagues.

“The burden has escalated at the worldwide level since 1990, partly because of population growth and aging,” the authors wrote. “Thus, it is meaningful to explore effective treatments for reversing cirrhosis and preventing severe liver function and even systemic damage.”

The study was published online in Frontiers in Medicine .
 

Analyzing Probiotic Trials

The researchers conducted a systematic review and meta-analysis of 30 randomized controlled trials among 2084 adults with cirrhosis, comparing the effects of probiotic intervention and control treatments, including placebo, no treatment, standard care, or active controls such as lactulose and rifaximin. The studies spanned 14 countries and included 1049 patients in the probiotic groups and 1035 in the control groups.

The research team calculated risk ratios (RRs) or standardized mean difference (SMD) for outcomes such as HE reversal, Model for End-Stage Liver Disease (MELD) scores, safety and tolerability of probiotics, liver function, and quality of life.

Among 17 studies involving patients with different stages of HE, as compared with the control group, probiotics significantly reversed minimal HE (RR, 1.54) and improved HE (RR, 1.94). In particular, the probiotic VSL#3 — which contains Streptococcus, Bifidobacterium, and Lactobacillus — produced more significant HE improvement (RR, 1.44) compared with other types of probiotics.

In addition, probiotics appeared to improve liver function by reducing MELD scores (SMD, −0.57) but didn’t show a difference in other liver function parameters. There were numerical but not significant reductions in mortality and serum inflammatory cytokine expression, including endotoxin, interleukin-6, and tumor necrosis factor-alpha.

Probiotics also improved quality-of-life scores (SMD, 0.51) and gut flora (SMD, 1.67). For gut flora, the numbers of the Lactobacillus group were significantly higher after probiotic treatment, but there wasn’t a significant difference for Bifidobacterium, Enterococcus, Bacteroidaceae, and Fusobacterium.

Finally, compared with control treatments, including placebo, standard therapy, and active controls such as lactulose and rifaximin, probiotics showed higher safety and tolerability profiles, causing a significantly lower incidence of serious adverse events (RR, 0.71).

Longer intervention times reduced the risk for overt HE development, hospitalization, and infections compared with shorter intervention times.

“Probiotics contribute to the reduction of ammonia levels and the improvement of neuropsychometric or neurophysiological status, leading to the reversal of HE associated with cirrhosis,” the study authors wrote. “Moreover, they induce favorable changes in gut flora and quality of life. Therefore, probiotics emerge as a promising intervention for reversing the onset of cirrhosis and preventing disease progression.”
 

Considering Variables

The authors noted several limitations, including a high or unclear risk for bias in 28 studies and the lack of data on the intervention effect for various types of probiotics or treatment durations.

“Overall, despite a number of methodological concerns, the study shows that probiotics can improve some disease markers in cirrhosis,” Phillipp Hartmann, MD, assistant professor of pediatric gastroenterology, hepatology, and nutrition at the University of California, San Diego, said in an interview.

“One of the methodological concerns is that the authors compared probiotics with a multitude of different treatments, including fiber and lactulose (which are both prebiotics), rifaximin (which is an antibiotic), standard of care, placebo, or no therapy,” he said. “This might contribute to the sometimes-contradictory findings between the different studies. The ideal comparison would be a specific probiotic formulation versus a placebo to understand what the probiotic actually does.”

Dr. Hartmann, who wasn’t involved with this study, has published a review on the potential of probiotics, prebiotics, and synbiotics in liver disease. He and colleagues noted the mechanisms that improve a disrupted intestinal barrier, microbial translocation, and altered gut microbiome metabolism.

“Over the last few years, we and others have studied the intestinal microbiota in various liver diseases, including alcohol-associated liver disease and metabolic dysfunction-associated steatotic liver disease,” he said. “Essentially, all studies support the notion that probiotics improve the microbial structure in the gut by increasing the beneficial and decreasing the potentially pathogenic microbes.”

However, probiotics and supplements are unregulated, Dr. Hartmann noted. Many different probiotic mixes and dosages have been tested in clinical trials, and additional studies are needed to determine the best formulations and dosages.

“Usually, the best outcomes can be achieved with a higher number of strains included in the probiotic formulation (10-30+) and a higher number of colony-forming units at 30-50+ billion per day,” he said.

The study was supported by funds from the Science and Technology Major Project of Guangxi, Guangxi Key Research and Development Program, and Natural Science Foundation of Guangxi Zhuang Autonomous Region. The authors declared no conflicts of interest. Dr. Hartmann reported no relevant disclosures.

A version of this article appeared on Medscape.com .

Probiotics appear to be beneficial for patients with cirrhosis, showing a reversal of hepatic encephalopathy (HE), improvement in liver function measures, and regulation of gut dysbiosis, according to a systematic review and meta-analysis.

They also improve quality of life and have a favorable safety profile, adding to their potential as a promising intervention for treating cirrhosis, the study authors wrote.

“As currently one of the top 10 leading causes of death globally, cirrhosis imposes a great health burden in many countries,” wrote lead author Xing Yang of the Health Management Research Institute at the People’s Hospital of Guangxi Zhuang Autonomous Region and Guangxi Academy of Medical Sciences in Nanning, China, and colleagues.

“The burden has escalated at the worldwide level since 1990, partly because of population growth and aging,” the authors wrote. “Thus, it is meaningful to explore effective treatments for reversing cirrhosis and preventing severe liver function and even systemic damage.”

The study was published online in Frontiers in Medicine .
 

Analyzing Probiotic Trials

The researchers conducted a systematic review and meta-analysis of 30 randomized controlled trials among 2084 adults with cirrhosis, comparing the effects of probiotic intervention and control treatments, including placebo, no treatment, standard care, or active controls such as lactulose and rifaximin. The studies spanned 14 countries and included 1049 patients in the probiotic groups and 1035 in the control groups.

The research team calculated risk ratios (RRs) or standardized mean difference (SMD) for outcomes such as HE reversal, Model for End-Stage Liver Disease (MELD) scores, safety and tolerability of probiotics, liver function, and quality of life.

Among 17 studies involving patients with different stages of HE, as compared with the control group, probiotics significantly reversed minimal HE (RR, 1.54) and improved HE (RR, 1.94). In particular, the probiotic VSL#3 — which contains Streptococcus, Bifidobacterium, and Lactobacillus — produced more significant HE improvement (RR, 1.44) compared with other types of probiotics.

In addition, probiotics appeared to improve liver function by reducing MELD scores (SMD, −0.57) but didn’t show a difference in other liver function parameters. There were numerical but not significant reductions in mortality and serum inflammatory cytokine expression, including endotoxin, interleukin-6, and tumor necrosis factor-alpha.

Probiotics also improved quality-of-life scores (SMD, 0.51) and gut flora (SMD, 1.67). For gut flora, the numbers of the Lactobacillus group were significantly higher after probiotic treatment, but there wasn’t a significant difference for Bifidobacterium, Enterococcus, Bacteroidaceae, and Fusobacterium.

Finally, compared with control treatments, including placebo, standard therapy, and active controls such as lactulose and rifaximin, probiotics showed higher safety and tolerability profiles, causing a significantly lower incidence of serious adverse events (RR, 0.71).

Longer intervention times reduced the risk for overt HE development, hospitalization, and infections compared with shorter intervention times.

“Probiotics contribute to the reduction of ammonia levels and the improvement of neuropsychometric or neurophysiological status, leading to the reversal of HE associated with cirrhosis,” the study authors wrote. “Moreover, they induce favorable changes in gut flora and quality of life. Therefore, probiotics emerge as a promising intervention for reversing the onset of cirrhosis and preventing disease progression.”
 

Considering Variables

The authors noted several limitations, including a high or unclear risk for bias in 28 studies and the lack of data on the intervention effect for various types of probiotics or treatment durations.

“Overall, despite a number of methodological concerns, the study shows that probiotics can improve some disease markers in cirrhosis,” Phillipp Hartmann, MD, assistant professor of pediatric gastroenterology, hepatology, and nutrition at the University of California, San Diego, said in an interview.

“One of the methodological concerns is that the authors compared probiotics with a multitude of different treatments, including fiber and lactulose (which are both prebiotics), rifaximin (which is an antibiotic), standard of care, placebo, or no therapy,” he said. “This might contribute to the sometimes-contradictory findings between the different studies. The ideal comparison would be a specific probiotic formulation versus a placebo to understand what the probiotic actually does.”

Dr. Hartmann, who wasn’t involved with this study, has published a review on the potential of probiotics, prebiotics, and synbiotics in liver disease. He and colleagues noted the mechanisms that improve a disrupted intestinal barrier, microbial translocation, and altered gut microbiome metabolism.

“Over the last few years, we and others have studied the intestinal microbiota in various liver diseases, including alcohol-associated liver disease and metabolic dysfunction-associated steatotic liver disease,” he said. “Essentially, all studies support the notion that probiotics improve the microbial structure in the gut by increasing the beneficial and decreasing the potentially pathogenic microbes.”

However, probiotics and supplements are unregulated, Dr. Hartmann noted. Many different probiotic mixes and dosages have been tested in clinical trials, and additional studies are needed to determine the best formulations and dosages.

“Usually, the best outcomes can be achieved with a higher number of strains included in the probiotic formulation (10-30+) and a higher number of colony-forming units at 30-50+ billion per day,” he said.

The study was supported by funds from the Science and Technology Major Project of Guangxi, Guangxi Key Research and Development Program, and Natural Science Foundation of Guangxi Zhuang Autonomous Region. The authors declared no conflicts of interest. Dr. Hartmann reported no relevant disclosures.

A version of this article appeared on Medscape.com .

Probiotics appear to be beneficial for patients with cirrhosis, showing a reversal of hepatic encephalopathy (HE), improvement in liver function measures, and regulation of gut dysbiosis, according to a systematic review and meta-analysis.

They also improve quality of life and have a favorable safety profile, adding to their potential as a promising intervention for treating cirrhosis, the study authors wrote.

“As currently one of the top 10 leading causes of death globally, cirrhosis imposes a great health burden in many countries,” wrote lead author Xing Yang of the Health Management Research Institute at the People’s Hospital of Guangxi Zhuang Autonomous Region and Guangxi Academy of Medical Sciences in Nanning, China, and colleagues.

“The burden has escalated at the worldwide level since 1990, partly because of population growth and aging,” the authors wrote. “Thus, it is meaningful to explore effective treatments for reversing cirrhosis and preventing severe liver function and even systemic damage.”

The study was published online in Frontiers in Medicine .
 

Analyzing Probiotic Trials

The researchers conducted a systematic review and meta-analysis of 30 randomized controlled trials among 2084 adults with cirrhosis, comparing the effects of probiotic intervention and control treatments, including placebo, no treatment, standard care, or active controls such as lactulose and rifaximin. The studies spanned 14 countries and included 1049 patients in the probiotic groups and 1035 in the control groups.

The research team calculated risk ratios (RRs) or standardized mean difference (SMD) for outcomes such as HE reversal, Model for End-Stage Liver Disease (MELD) scores, safety and tolerability of probiotics, liver function, and quality of life.

Among 17 studies involving patients with different stages of HE, as compared with the control group, probiotics significantly reversed minimal HE (RR, 1.54) and improved HE (RR, 1.94). In particular, the probiotic VSL#3 — which contains Streptococcus, Bifidobacterium, and Lactobacillus — produced more significant HE improvement (RR, 1.44) compared with other types of probiotics.

In addition, probiotics appeared to improve liver function by reducing MELD scores (SMD, −0.57) but didn’t show a difference in other liver function parameters. There were numerical but not significant reductions in mortality and serum inflammatory cytokine expression, including endotoxin, interleukin-6, and tumor necrosis factor-alpha.

Probiotics also improved quality-of-life scores (SMD, 0.51) and gut flora (SMD, 1.67). For gut flora, the numbers of the Lactobacillus group were significantly higher after probiotic treatment, but there wasn’t a significant difference for Bifidobacterium, Enterococcus, Bacteroidaceae, and Fusobacterium.

Finally, compared with control treatments, including placebo, standard therapy, and active controls such as lactulose and rifaximin, probiotics showed higher safety and tolerability profiles, causing a significantly lower incidence of serious adverse events (RR, 0.71).

Longer intervention times reduced the risk for overt HE development, hospitalization, and infections compared with shorter intervention times.

“Probiotics contribute to the reduction of ammonia levels and the improvement of neuropsychometric or neurophysiological status, leading to the reversal of HE associated with cirrhosis,” the study authors wrote. “Moreover, they induce favorable changes in gut flora and quality of life. Therefore, probiotics emerge as a promising intervention for reversing the onset of cirrhosis and preventing disease progression.”
 

Considering Variables

The authors noted several limitations, including a high or unclear risk for bias in 28 studies and the lack of data on the intervention effect for various types of probiotics or treatment durations.

“Overall, despite a number of methodological concerns, the study shows that probiotics can improve some disease markers in cirrhosis,” Phillipp Hartmann, MD, assistant professor of pediatric gastroenterology, hepatology, and nutrition at the University of California, San Diego, said in an interview.

“One of the methodological concerns is that the authors compared probiotics with a multitude of different treatments, including fiber and lactulose (which are both prebiotics), rifaximin (which is an antibiotic), standard of care, placebo, or no therapy,” he said. “This might contribute to the sometimes-contradictory findings between the different studies. The ideal comparison would be a specific probiotic formulation versus a placebo to understand what the probiotic actually does.”

Dr. Hartmann, who wasn’t involved with this study, has published a review on the potential of probiotics, prebiotics, and synbiotics in liver disease. He and colleagues noted the mechanisms that improve a disrupted intestinal barrier, microbial translocation, and altered gut microbiome metabolism.

“Over the last few years, we and others have studied the intestinal microbiota in various liver diseases, including alcohol-associated liver disease and metabolic dysfunction-associated steatotic liver disease,” he said. “Essentially, all studies support the notion that probiotics improve the microbial structure in the gut by increasing the beneficial and decreasing the potentially pathogenic microbes.”

However, probiotics and supplements are unregulated, Dr. Hartmann noted. Many different probiotic mixes and dosages have been tested in clinical trials, and additional studies are needed to determine the best formulations and dosages.

“Usually, the best outcomes can be achieved with a higher number of strains included in the probiotic formulation (10-30+) and a higher number of colony-forming units at 30-50+ billion per day,” he said.

The study was supported by funds from the Science and Technology Major Project of Guangxi, Guangxi Key Research and Development Program, and Natural Science Foundation of Guangxi Zhuang Autonomous Region. The authors declared no conflicts of interest. Dr. Hartmann reported no relevant disclosures.

A version of this article appeared on Medscape.com .

TOPLINE:

Metabolic dysfunction-associated steatotic liver disease (MASLD) co-occurring with HIV infection does not appear to increase the risk for cirrhosis or hepatocellular carcinoma (HCC) compared with MASLD alone. However, the incidence of major adverse cardiovascular events (MACE) is significantly increased among patients with MASLD and HIV, a large study suggested.

METHODOLOGY:

• MASLD is highly prevalent in people living with HIV, but the impact of HIV on liver and cardiovascular disease (CVD) outcomes in people with MASLD remains unclear.
• To investigate, researchers created a propensity score-matched cohort of veterans with noncirrhotic MASLD, with and without HIV (920 patients in each group).
• They evaluated the incidence of cirrhosis, HCC, and MACE, as well as overall survival, among the two groups. They also assessed these outcomes in MASLD patients with HIV on the basis of whether they were on antiretroviral therapy (ART).

TAKEAWAY:

• During a median follow-up of 10.4 years in the MASLD with HIV group and 11.8 years in the MASLD-only group, the overall incidence of cirrhosis and HCC was similar in MASLD with vs without HIV (cirrhosis: 0.97 vs 1.06 per 100 person-years, P = .54; HCC: 0.26 vs 0.17 per 100,000 person-years, P = .23), regardless of ART use.

• In contrast, the incidence of MACE was significantly higher in MASLD with vs without HIV (5.18 vs 4.48 per 100 person-years, P = .03). The incidence also was higher in patients with MASLD and HIV who were not on ART compared with those on ART (5.83 vs 4.7 per 100 person-years, P = .07).

• Compared with MASLD without HIV, the overall 5-year survival was significantly lower in MASLD with HIV (91.3% vs 85.7%). In MASLD with HIV, receipt of ART was associated with a significantly higher 5-year survival than no ART (87.4% vs 81.6%).

IN PRACTICE:

“Ensuring timely and appropriate initiation of HIV treatment is critical in patients with MASLD who have concurrent HIV infection, as well as optimizing metabolic comorbidities that may also contribute to increased risks of CVD and increased mortality,” the authors wrote.

SOURCE:

The study, led by Robert J. Wong, MD, Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Palo Alto, California, was published online in the American Journal of Gastroenterology.

LIMITATIONS:

The study cohort consisted predominantly of older men, which may limit generalizability to women and younger populations. Metabolic comorbidities are more common in veterans compared with the general population, potentially affecting the generalizability of the CVD risk findings.

DISCLOSURES:

The study was supported by an investigator-initiated research grant from Theratechnologies. Wong has received funding for his institution from Gilead Sciences, Exact Sciences, and Durect Corporation and has served as a consultant for Gilead Sciences.
 

A version of this article appeared on Medscape.com.

TOPLINE:

Metabolic dysfunction-associated steatotic liver disease (MASLD) co-occurring with HIV infection does not appear to increase the risk for cirrhosis or hepatocellular carcinoma (HCC) compared with MASLD alone. However, the incidence of major adverse cardiovascular events (MACE) is significantly increased among patients with MASLD and HIV, a large study suggested.

METHODOLOGY:

• MASLD is highly prevalent in people living with HIV, but the impact of HIV on liver and cardiovascular disease (CVD) outcomes in people with MASLD remains unclear.
• To investigate, researchers created a propensity score-matched cohort of veterans with noncirrhotic MASLD, with and without HIV (920 patients in each group).
• They evaluated the incidence of cirrhosis, HCC, and MACE, as well as overall survival, among the two groups. They also assessed these outcomes in MASLD patients with HIV on the basis of whether they were on antiretroviral therapy (ART).

TAKEAWAY:

• During a median follow-up of 10.4 years in the MASLD with HIV group and 11.8 years in the MASLD-only group, the overall incidence of cirrhosis and HCC was similar in MASLD with vs without HIV (cirrhosis: 0.97 vs 1.06 per 100 person-years, P = .54; HCC: 0.26 vs 0.17 per 100,000 person-years, P = .23), regardless of ART use.

• In contrast, the incidence of MACE was significantly higher in MASLD with vs without HIV (5.18 vs 4.48 per 100 person-years, P = .03). The incidence also was higher in patients with MASLD and HIV who were not on ART compared with those on ART (5.83 vs 4.7 per 100 person-years, P = .07).

• Compared with MASLD without HIV, the overall 5-year survival was significantly lower in MASLD with HIV (91.3% vs 85.7%). In MASLD with HIV, receipt of ART was associated with a significantly higher 5-year survival than no ART (87.4% vs 81.6%).

IN PRACTICE:

“Ensuring timely and appropriate initiation of HIV treatment is critical in patients with MASLD who have concurrent HIV infection, as well as optimizing metabolic comorbidities that may also contribute to increased risks of CVD and increased mortality,” the authors wrote.

SOURCE:

The study, led by Robert J. Wong, MD, Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Palo Alto, California, was published online in the American Journal of Gastroenterology.

LIMITATIONS:

The study cohort consisted predominantly of older men, which may limit generalizability to women and younger populations. Metabolic comorbidities are more common in veterans compared with the general population, potentially affecting the generalizability of the CVD risk findings.

DISCLOSURES:

The study was supported by an investigator-initiated research grant from Theratechnologies. Wong has received funding for his institution from Gilead Sciences, Exact Sciences, and Durect Corporation and has served as a consultant for Gilead Sciences.
 

A version of this article appeared on Medscape.com.

TOPLINE:

Metabolic dysfunction-associated steatotic liver disease (MASLD) co-occurring with HIV infection does not appear to increase the risk for cirrhosis or hepatocellular carcinoma (HCC) compared with MASLD alone. However, the incidence of major adverse cardiovascular events (MACE) is significantly increased among patients with MASLD and HIV, a large study suggested.

METHODOLOGY:

• MASLD is highly prevalent in people living with HIV, but the impact of HIV on liver and cardiovascular disease (CVD) outcomes in people with MASLD remains unclear.
• To investigate, researchers created a propensity score-matched cohort of veterans with noncirrhotic MASLD, with and without HIV (920 patients in each group).
• They evaluated the incidence of cirrhosis, HCC, and MACE, as well as overall survival, among the two groups. They also assessed these outcomes in MASLD patients with HIV on the basis of whether they were on antiretroviral therapy (ART).

TAKEAWAY:

• During a median follow-up of 10.4 years in the MASLD with HIV group and 11.8 years in the MASLD-only group, the overall incidence of cirrhosis and HCC was similar in MASLD with vs without HIV (cirrhosis: 0.97 vs 1.06 per 100 person-years, P = .54; HCC: 0.26 vs 0.17 per 100,000 person-years, P = .23), regardless of ART use.

• In contrast, the incidence of MACE was significantly higher in MASLD with vs without HIV (5.18 vs 4.48 per 100 person-years, P = .03). The incidence also was higher in patients with MASLD and HIV who were not on ART compared with those on ART (5.83 vs 4.7 per 100 person-years, P = .07).

• Compared with MASLD without HIV, the overall 5-year survival was significantly lower in MASLD with HIV (91.3% vs 85.7%). In MASLD with HIV, receipt of ART was associated with a significantly higher 5-year survival than no ART (87.4% vs 81.6%).

IN PRACTICE:

“Ensuring timely and appropriate initiation of HIV treatment is critical in patients with MASLD who have concurrent HIV infection, as well as optimizing metabolic comorbidities that may also contribute to increased risks of CVD and increased mortality,” the authors wrote.

SOURCE:

The study, led by Robert J. Wong, MD, Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Palo Alto, California, was published online in the American Journal of Gastroenterology.

LIMITATIONS:

The study cohort consisted predominantly of older men, which may limit generalizability to women and younger populations. Metabolic comorbidities are more common in veterans compared with the general population, potentially affecting the generalizability of the CVD risk findings.

DISCLOSURES:

The study was supported by an investigator-initiated research grant from Theratechnologies. Wong has received funding for his institution from Gilead Sciences, Exact Sciences, and Durect Corporation and has served as a consultant for Gilead Sciences.
 

A version of this article appeared on Medscape.com.

People with opioid use disorder (OUD) who have hepatitis C virus (HCV) were twice as likely to be treated and cured of HCV if they received facilitated telemedicine treatment within their opioid treatment program than if they were referred for off-site treatment, the results of a new study showed.

In addition, among cured patients, illicit drug use fell significantly, and there were few reinfections, reported the researchers, led by Andrew Talal, MD, MPH, with the University at Buffalo, State University of New York, Buffalo.

The study was published online in JAMA.

HCV is a major public health concern, especially among people with OUD. Geographic and logistical barriers often prevent this underserved population from accessing treatment; however, telemedicine has the potential to overcome these obstacles.

In a prospective cluster randomized clinical trial, Dr. Talal and colleagues assessed the impact of embedding facilitated telemedicine for HCV care into 12 opioid treatment programs in New York State.

They studied 602 HCV-infected adults (61% male; 51% White) with OUD. Of these, 290 (mean age, 47.1 years) were enrolled in facilitated telemedicine programs onsite, and 312 (mean age, 48.9 years) received an off-site referral (usual care).

Telemedicine participants had an initial telemedicine encounter facilitated by study case managers onsite who also administered a blood test. The telemedicine clinician subsequently evaluated participants and ordered direct-acting antiviral (DAA) medication that was delivered to the opioid treatment program monthly (as refills required) and dispensed along with methadone.

In the telemedicine group, 268 of 290 individuals (92.4%) initiated HCV treatment compared with 126 of 312 (40.4%) in the referral group.

Participants in the telemedicine group were also seen sooner and started treatment faster.

The interval between screening and initial appointments was 14 days with telemedicine vs 18 days with a referral (P = .04). The time between the initial visit and DAA initiation was 49.9 days with telemedicine vs 123.5 days with a referral (P < .001).

Intention-to-treat analysis showed significantly higher HCV cure rates with telemedicine than with referral (90.3% vs 39.4%, respectively). Similarly, the observed cure rates were also higher in the telemedicine group (84.8% vs 34.0%).

Sustained virologic response was durable, with only 13 reinfections (incidence, 2.5 per 100 person-years) occurring during the 2-year follow-up period, the researchers reported.

In addition, illicit drug use decreased significantly among cured patients in both the telemedicine group (P < .001) and the referral group (P = .001). Adults in both groups rated healthcare delivery satisfaction as high or very high.

“Our study demonstrates how telemedicine successfully integrates medical and behavioral treatment,” Dr. Talal said in a statement.

The intervention “builds patient-clinician trust across the screen, and significant decreases in substance use were observed in cured participants with minimal HCV reinfections,” the study team wrote.

Support for this research was provided by the Patient-Centered Outcomes Research Institute and by the Troup Fund of the Kaleida Health Foundation.

A version of this article appeared on Medscape.com .

People with opioid use disorder (OUD) who have hepatitis C virus (HCV) were twice as likely to be treated and cured of HCV if they received facilitated telemedicine treatment within their opioid treatment program than if they were referred for off-site treatment, the results of a new study showed.

In addition, among cured patients, illicit drug use fell significantly, and there were few reinfections, reported the researchers, led by Andrew Talal, MD, MPH, with the University at Buffalo, State University of New York, Buffalo.

The study was published online in JAMA.

HCV is a major public health concern, especially among people with OUD. Geographic and logistical barriers often prevent this underserved population from accessing treatment; however, telemedicine has the potential to overcome these obstacles.

In a prospective cluster randomized clinical trial, Dr. Talal and colleagues assessed the impact of embedding facilitated telemedicine for HCV care into 12 opioid treatment programs in New York State.

They studied 602 HCV-infected adults (61% male; 51% White) with OUD. Of these, 290 (mean age, 47.1 years) were enrolled in facilitated telemedicine programs onsite, and 312 (mean age, 48.9 years) received an off-site referral (usual care).

Telemedicine participants had an initial telemedicine encounter facilitated by study case managers onsite who also administered a blood test. The telemedicine clinician subsequently evaluated participants and ordered direct-acting antiviral (DAA) medication that was delivered to the opioid treatment program monthly (as refills required) and dispensed along with methadone.

In the telemedicine group, 268 of 290 individuals (92.4%) initiated HCV treatment compared with 126 of 312 (40.4%) in the referral group.

Participants in the telemedicine group were also seen sooner and started treatment faster.

The interval between screening and initial appointments was 14 days with telemedicine vs 18 days with a referral (P = .04). The time between the initial visit and DAA initiation was 49.9 days with telemedicine vs 123.5 days with a referral (P < .001).

Intention-to-treat analysis showed significantly higher HCV cure rates with telemedicine than with referral (90.3% vs 39.4%, respectively). Similarly, the observed cure rates were also higher in the telemedicine group (84.8% vs 34.0%).

Sustained virologic response was durable, with only 13 reinfections (incidence, 2.5 per 100 person-years) occurring during the 2-year follow-up period, the researchers reported.

In addition, illicit drug use decreased significantly among cured patients in both the telemedicine group (P < .001) and the referral group (P = .001). Adults in both groups rated healthcare delivery satisfaction as high or very high.

“Our study demonstrates how telemedicine successfully integrates medical and behavioral treatment,” Dr. Talal said in a statement.

The intervention “builds patient-clinician trust across the screen, and significant decreases in substance use were observed in cured participants with minimal HCV reinfections,” the study team wrote.

Support for this research was provided by the Patient-Centered Outcomes Research Institute and by the Troup Fund of the Kaleida Health Foundation.

A version of this article appeared on Medscape.com .

People with opioid use disorder (OUD) who have hepatitis C virus (HCV) were twice as likely to be treated and cured of HCV if they received facilitated telemedicine treatment within their opioid treatment program than if they were referred for off-site treatment, the results of a new study showed.

In addition, among cured patients, illicit drug use fell significantly, and there were few reinfections, reported the researchers, led by Andrew Talal, MD, MPH, with the University at Buffalo, State University of New York, Buffalo.

The study was published online in JAMA.

HCV is a major public health concern, especially among people with OUD. Geographic and logistical barriers often prevent this underserved population from accessing treatment; however, telemedicine has the potential to overcome these obstacles.

In a prospective cluster randomized clinical trial, Dr. Talal and colleagues assessed the impact of embedding facilitated telemedicine for HCV care into 12 opioid treatment programs in New York State.

They studied 602 HCV-infected adults (61% male; 51% White) with OUD. Of these, 290 (mean age, 47.1 years) were enrolled in facilitated telemedicine programs onsite, and 312 (mean age, 48.9 years) received an off-site referral (usual care).

Telemedicine participants had an initial telemedicine encounter facilitated by study case managers onsite who also administered a blood test. The telemedicine clinician subsequently evaluated participants and ordered direct-acting antiviral (DAA) medication that was delivered to the opioid treatment program monthly (as refills required) and dispensed along with methadone.

In the telemedicine group, 268 of 290 individuals (92.4%) initiated HCV treatment compared with 126 of 312 (40.4%) in the referral group.

Participants in the telemedicine group were also seen sooner and started treatment faster.

The interval between screening and initial appointments was 14 days with telemedicine vs 18 days with a referral (P = .04). The time between the initial visit and DAA initiation was 49.9 days with telemedicine vs 123.5 days with a referral (P < .001).

Intention-to-treat analysis showed significantly higher HCV cure rates with telemedicine than with referral (90.3% vs 39.4%, respectively). Similarly, the observed cure rates were also higher in the telemedicine group (84.8% vs 34.0%).

Sustained virologic response was durable, with only 13 reinfections (incidence, 2.5 per 100 person-years) occurring during the 2-year follow-up period, the researchers reported.

In addition, illicit drug use decreased significantly among cured patients in both the telemedicine group (P < .001) and the referral group (P = .001). Adults in both groups rated healthcare delivery satisfaction as high or very high.

“Our study demonstrates how telemedicine successfully integrates medical and behavioral treatment,” Dr. Talal said in a statement.

The intervention “builds patient-clinician trust across the screen, and significant decreases in substance use were observed in cured participants with minimal HCV reinfections,” the study team wrote.

Support for this research was provided by the Patient-Centered Outcomes Research Institute and by the Troup Fund of the Kaleida Health Foundation.

A version of this article appeared on Medscape.com .

The hepatitis E virus (HEV) is among the leading global causes of acute viral hepatitis. Molecular studies of HEV strains have identified four main genotypes. Genotypes 1 and 2 are limited to humans and are transmitted through contaminated water in resource-limited countries, mainly in Asia. Genotypes 3 and 4 are zoonotic, causing sporadic indigenous hepatitis E in nearly all countries.

Each year, approximately 20 million HEV infections occur worldwide, resulting in around 3.3 million symptomatic infections and 70,000 deaths. Despite this toll, HEV infection remains underestimated, and Western countries are likely not immune to the virus. To date, two recombinant vaccines against hepatitis E, based on genotype 1, have been developed and approved in China, but further studies are needed to determine the duration of vaccination protection.
 

Ten-Year Results

This study is an extension of a randomized, double-blind, placebo-controlled phase 3 clinical trial of the Hecolin hepatitis E vaccine that was conducted in Dongtai County, Jiangsu, China. In the initial trial, healthy adults aged 16-65 years were recruited, stratified by age and sex, and randomly assigned in a 1:1 ratio to receive three doses of intramuscular hepatitis E vaccine or placebo at months 0, 1, and 6.

A hepatitis E surveillance system, including 205 clinical sentinels covering the entire study region, was established before the study began and maintained for 10 years after vaccination to identify individuals with suspected hepatitis. In addition, an external control cohort was formed to assess vaccine efficacy. The primary endpoint was the vaccine’s efficacy in preventing confirmed hepatitis E occurring at least 30 days after the administration of the third vaccine dose.

Follow-up occurred every 3 months. Participants with hepatitis symptoms for 3 days or more underwent alanine aminotransferase (ALT) concentration measurement. Patients with ALT concentrations ≥ 2.5 times the upper limit of normal were considered to have acute hepatitis. A diagnosis of HEV-confirmed infection was made for patients with acute hepatitis presenting with at least two of the following markers: Presence of HEV RNA, presence of positive anti-HEV immunoglobulin (Ig) M antibodies, and at least fourfold increase in anti-HEV IgG concentrations.

For the efficacy analysis, a Poisson regression model was used to estimate the relative risk and its 95% CI of incidence between groups. Incidence was reported as the number of patients with hepatitis E per 10,000 person-years.

Immunogenicity persistence was assessed by measuring anti-HEV IgG in participants. Serum samples were collected at months 0, 7, 13, 19, 31, 43, 55, 79, and 103 for Qingdao district participants and at months 0, 7, 19, 31, 43, 67, and 91 for Anfeng district participants.
 

Efficacy and Duration

The follow-up period extended from 2007 to 2017. In total, 97,356 participants completed the three-dose regimen and were included in the per-protocol population (48,693 in the vaccine group and 48,663 in the placebo group), and 178,236 residents from the study region participated in the external control cohort. During the study period, 90 cases of hepatitis E were identified, with 13 in the vaccine group (0.2 per 10,000 person-years) and 77 in the placebo group (1.4 per 10,000 person-years). This indicated a vaccine efficacy of 86.6% in the per-protocol analysis.

In the subgroups evaluated for immunogenicity persistence, among those who were initially seronegative and received three doses of hepatitis E vaccine, 254 out of 291 vaccinated participants (87.3%) in Qingdao after 8.5 years and 1270 (73.0%) out of 1740 vaccinated participants in Anfeng after 7.5 years maintained detectable antibody concentrations.

The identification of infections despite vaccination is notable, especially with eight cases occurring beyond the fourth year following the last dose. This information is crucial for understanding potential immunity decline over time and highlights the importance of exploring various vaccination strategies to optimize protection.

An ongoing phase 4 clinical trial in Bangladesh, exploring different administration schedules and target populations, could help optimize vaccination strategies. The remarkable efficacy (100%) observed over a 30-month period for the two-dose schedule (doses are administered 1 month apart) is promising.

The observation of higher IgG antibody avidity in participants with infections despite vaccination underscores the importance of robust antibody responses to mitigate disease severity and duration. Several study limitations, such as lack of data on deaths and emigrations, a single-center study design, predominance of genotype 4 infections, and the risk for bias in the external control cohort, should be acknowledged.

In conclusion, this study provides compelling evidence of sustained protection of the hepatitis E vaccine over a decade. The observed persistence of induced antibodies for at least 8.5 years supports the long-term efficacy of the vaccine. Diverse global trials, further investigation into the impact of natural infections on vaccine-induced antibodies, and confirmation of inter-genotypic protection are needed.

This story was translated from JIM, which is part of the Medscape professional network, using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

The hepatitis E virus (HEV) is among the leading global causes of acute viral hepatitis. Molecular studies of HEV strains have identified four main genotypes. Genotypes 1 and 2 are limited to humans and are transmitted through contaminated water in resource-limited countries, mainly in Asia. Genotypes 3 and 4 are zoonotic, causing sporadic indigenous hepatitis E in nearly all countries.

Each year, approximately 20 million HEV infections occur worldwide, resulting in around 3.3 million symptomatic infections and 70,000 deaths. Despite this toll, HEV infection remains underestimated, and Western countries are likely not immune to the virus. To date, two recombinant vaccines against hepatitis E, based on genotype 1, have been developed and approved in China, but further studies are needed to determine the duration of vaccination protection.
 

Ten-Year Results

This study is an extension of a randomized, double-blind, placebo-controlled phase 3 clinical trial of the Hecolin hepatitis E vaccine that was conducted in Dongtai County, Jiangsu, China. In the initial trial, healthy adults aged 16-65 years were recruited, stratified by age and sex, and randomly assigned in a 1:1 ratio to receive three doses of intramuscular hepatitis E vaccine or placebo at months 0, 1, and 6.

A hepatitis E surveillance system, including 205 clinical sentinels covering the entire study region, was established before the study began and maintained for 10 years after vaccination to identify individuals with suspected hepatitis. In addition, an external control cohort was formed to assess vaccine efficacy. The primary endpoint was the vaccine’s efficacy in preventing confirmed hepatitis E occurring at least 30 days after the administration of the third vaccine dose.

Follow-up occurred every 3 months. Participants with hepatitis symptoms for 3 days or more underwent alanine aminotransferase (ALT) concentration measurement. Patients with ALT concentrations ≥ 2.5 times the upper limit of normal were considered to have acute hepatitis. A diagnosis of HEV-confirmed infection was made for patients with acute hepatitis presenting with at least two of the following markers: Presence of HEV RNA, presence of positive anti-HEV immunoglobulin (Ig) M antibodies, and at least fourfold increase in anti-HEV IgG concentrations.

For the efficacy analysis, a Poisson regression model was used to estimate the relative risk and its 95% CI of incidence between groups. Incidence was reported as the number of patients with hepatitis E per 10,000 person-years.

Immunogenicity persistence was assessed by measuring anti-HEV IgG in participants. Serum samples were collected at months 0, 7, 13, 19, 31, 43, 55, 79, and 103 for Qingdao district participants and at months 0, 7, 19, 31, 43, 67, and 91 for Anfeng district participants.
 

Efficacy and Duration

The follow-up period extended from 2007 to 2017. In total, 97,356 participants completed the three-dose regimen and were included in the per-protocol population (48,693 in the vaccine group and 48,663 in the placebo group), and 178,236 residents from the study region participated in the external control cohort. During the study period, 90 cases of hepatitis E were identified, with 13 in the vaccine group (0.2 per 10,000 person-years) and 77 in the placebo group (1.4 per 10,000 person-years). This indicated a vaccine efficacy of 86.6% in the per-protocol analysis.

In the subgroups evaluated for immunogenicity persistence, among those who were initially seronegative and received three doses of hepatitis E vaccine, 254 out of 291 vaccinated participants (87.3%) in Qingdao after 8.5 years and 1270 (73.0%) out of 1740 vaccinated participants in Anfeng after 7.5 years maintained detectable antibody concentrations.

The identification of infections despite vaccination is notable, especially with eight cases occurring beyond the fourth year following the last dose. This information is crucial for understanding potential immunity decline over time and highlights the importance of exploring various vaccination strategies to optimize protection.

An ongoing phase 4 clinical trial in Bangladesh, exploring different administration schedules and target populations, could help optimize vaccination strategies. The remarkable efficacy (100%) observed over a 30-month period for the two-dose schedule (doses are administered 1 month apart) is promising.

The observation of higher IgG antibody avidity in participants with infections despite vaccination underscores the importance of robust antibody responses to mitigate disease severity and duration. Several study limitations, such as lack of data on deaths and emigrations, a single-center study design, predominance of genotype 4 infections, and the risk for bias in the external control cohort, should be acknowledged.

In conclusion, this study provides compelling evidence of sustained protection of the hepatitis E vaccine over a decade. The observed persistence of induced antibodies for at least 8.5 years supports the long-term efficacy of the vaccine. Diverse global trials, further investigation into the impact of natural infections on vaccine-induced antibodies, and confirmation of inter-genotypic protection are needed.

This story was translated from JIM, which is part of the Medscape professional network, using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

The hepatitis E virus (HEV) is among the leading global causes of acute viral hepatitis. Molecular studies of HEV strains have identified four main genotypes. Genotypes 1 and 2 are limited to humans and are transmitted through contaminated water in resource-limited countries, mainly in Asia. Genotypes 3 and 4 are zoonotic, causing sporadic indigenous hepatitis E in nearly all countries.

Each year, approximately 20 million HEV infections occur worldwide, resulting in around 3.3 million symptomatic infections and 70,000 deaths. Despite this toll, HEV infection remains underestimated, and Western countries are likely not immune to the virus. To date, two recombinant vaccines against hepatitis E, based on genotype 1, have been developed and approved in China, but further studies are needed to determine the duration of vaccination protection.
 

Ten-Year Results

This study is an extension of a randomized, double-blind, placebo-controlled phase 3 clinical trial of the Hecolin hepatitis E vaccine that was conducted in Dongtai County, Jiangsu, China. In the initial trial, healthy adults aged 16-65 years were recruited, stratified by age and sex, and randomly assigned in a 1:1 ratio to receive three doses of intramuscular hepatitis E vaccine or placebo at months 0, 1, and 6.

A hepatitis E surveillance system, including 205 clinical sentinels covering the entire study region, was established before the study began and maintained for 10 years after vaccination to identify individuals with suspected hepatitis. In addition, an external control cohort was formed to assess vaccine efficacy. The primary endpoint was the vaccine’s efficacy in preventing confirmed hepatitis E occurring at least 30 days after the administration of the third vaccine dose.

Follow-up occurred every 3 months. Participants with hepatitis symptoms for 3 days or more underwent alanine aminotransferase (ALT) concentration measurement. Patients with ALT concentrations ≥ 2.5 times the upper limit of normal were considered to have acute hepatitis. A diagnosis of HEV-confirmed infection was made for patients with acute hepatitis presenting with at least two of the following markers: Presence of HEV RNA, presence of positive anti-HEV immunoglobulin (Ig) M antibodies, and at least fourfold increase in anti-HEV IgG concentrations.

For the efficacy analysis, a Poisson regression model was used to estimate the relative risk and its 95% CI of incidence between groups. Incidence was reported as the number of patients with hepatitis E per 10,000 person-years.

Immunogenicity persistence was assessed by measuring anti-HEV IgG in participants. Serum samples were collected at months 0, 7, 13, 19, 31, 43, 55, 79, and 103 for Qingdao district participants and at months 0, 7, 19, 31, 43, 67, and 91 for Anfeng district participants.
 

Efficacy and Duration

The follow-up period extended from 2007 to 2017. In total, 97,356 participants completed the three-dose regimen and were included in the per-protocol population (48,693 in the vaccine group and 48,663 in the placebo group), and 178,236 residents from the study region participated in the external control cohort. During the study period, 90 cases of hepatitis E were identified, with 13 in the vaccine group (0.2 per 10,000 person-years) and 77 in the placebo group (1.4 per 10,000 person-years). This indicated a vaccine efficacy of 86.6% in the per-protocol analysis.

In the subgroups evaluated for immunogenicity persistence, among those who were initially seronegative and received three doses of hepatitis E vaccine, 254 out of 291 vaccinated participants (87.3%) in Qingdao after 8.5 years and 1270 (73.0%) out of 1740 vaccinated participants in Anfeng after 7.5 years maintained detectable antibody concentrations.

The identification of infections despite vaccination is notable, especially with eight cases occurring beyond the fourth year following the last dose. This information is crucial for understanding potential immunity decline over time and highlights the importance of exploring various vaccination strategies to optimize protection.

An ongoing phase 4 clinical trial in Bangladesh, exploring different administration schedules and target populations, could help optimize vaccination strategies. The remarkable efficacy (100%) observed over a 30-month period for the two-dose schedule (doses are administered 1 month apart) is promising.

The observation of higher IgG antibody avidity in participants with infections despite vaccination underscores the importance of robust antibody responses to mitigate disease severity and duration. Several study limitations, such as lack of data on deaths and emigrations, a single-center study design, predominance of genotype 4 infections, and the risk for bias in the external control cohort, should be acknowledged.

In conclusion, this study provides compelling evidence of sustained protection of the hepatitis E vaccine over a decade. The observed persistence of induced antibodies for at least 8.5 years supports the long-term efficacy of the vaccine. Diverse global trials, further investigation into the impact of natural infections on vaccine-induced antibodies, and confirmation of inter-genotypic protection are needed.

This story was translated from JIM, which is part of the Medscape professional network, using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

The US Food and Drug Administration (FDA) has approved resmetirom (Rezdiffra, Madrigal Pharmaceuticals), the first drug to treat patients with metabolic dysfunction–associated steatohepatitis (MASH) and moderate to advanced liver fibrosis (consistent with stage F2 and F3 disease), along with diet and exercise. 

Resmetirom is a once-daily, oral thyroid hormone receptor beta-selective agonist. The FDA granted the drug breakthrough therapy designation and priority review.

The approval is based on the phase 3 MAESTRO-NASH trial, in which resmetirom was superior to placebo at achieving resolution of nonalcoholic steatohepatitis (NASH) and improving liver fibrosis in both 80-mg and 100-mg doses. 

The trial used the earlier nomenclature of NASH and nonalcoholic fatty liver disease (NAFLD). An international consensus group has since changed these terms to MASH and metabolic dysfunction–associated steatotic liver disease (MASLD), respectively. (Note that the terms NASH and NAFLD will be used to discuss the trial results in this article to align with the trial’s original language.) 

The results were published online February 6 in The New England Journal of Medicine. 

“The approval of the first medication for NASH is a true game-changer for healthcare providers, the research community and, most importantly, patients living with this serious liver condition,” lead MAESTRO-NASH investigator Stephen Harrison, MD, gastroenterologist, hepatologist, and chairman of Pinnacle Clinical Research and Summit Clinical Research, San Antonio, Texas, said in a news release. 

“Based on the robust efficacy and safety data generated in two large Phase 3 MAESTRO studies, I believe Rezdiffra will become the foundational therapy for patients with NASH with moderate to advanced liver fibrosis. Importantly, we continue to study Rezdiffra to determine if the positive results observed in the MAESTRO studies will lead to reduced risk of progression to cirrhosis, liver failure, need for liver transplant and premature mortality,” Dr. Harrison added.

 

Addressing an Unmet Need 

MASH is a progressive liver disease and the leading cause of liver-related mortality. The disease affects an estimated 1.5 million adults in the United States, of which, roughly 525,000 have MASH with significant fibrosis. Until now, there was no FDA-approved medication. 

In the ongoing MAESTRO-NASH, 996 adults with biopsy-confirmed NASH and significant stage 2-3 fibrosis were randomly assigned to receive oral once-daily resmetirom (80 mg or 100 mg) or placebo. 

Patients were followed for 52 weeks, at which point, they were assessed for the dual primary endpoints of NASH resolution (including a reduction in the NAFLD activity score by ≥ 2 points) with no worsening of fibrosis and an improvement (reduction) in fibrosis by at least one stage with no worsening of the NAFLD activity score.

Patients receiving resmetirom had a significant improvement across both doses and both primary endpoints. 

At 52 weeks, NASH resolution with no worsening of fibrosis was achieved in 25.9% and 29.9% of the patients in the 80-mg and 100-mg groups, respectively, compared with 9.7% on placebo.

Fibrosis improved by at least one stage with no worsening of the NAFLD activity score in 24.2% and 25.9% of patients in the 80-mg and 100-mg groups, respectively, compared with 14.2% on placebo. 

The trial also met multiple secondary endpoints, including statistically significant reduction from baseline in liver enzymes (alanine transaminase, aspartate aminotransferase, and gamma-glutamyl transferase) and low-density lipoprotein cholesterol with resmetirom compared with placebo. 

Improvement in fibrosis biomarkers and relevant imaging tests were also observed in resmetirom treatment groups compared with placebo. 

The most common adverse events included diarrhea and nausea, which typically began early in treatment and were mild to moderate in severity. Pruritus, abdominal pain, vomiting, constipation, and dizziness were also reported.

Resmetirom is expected to be available to patients in the United States in April and will be distributed through a limited specialty pharmacy network.

Full prescribing information is available online. Prescribing information does not include a liver biopsy requirement for diagnosis.

A version of this article appeared on Medscape.com.

The US Food and Drug Administration (FDA) has approved resmetirom (Rezdiffra, Madrigal Pharmaceuticals), the first drug to treat patients with metabolic dysfunction–associated steatohepatitis (MASH) and moderate to advanced liver fibrosis (consistent with stage F2 and F3 disease), along with diet and exercise. 

Resmetirom is a once-daily, oral thyroid hormone receptor beta-selective agonist. The FDA granted the drug breakthrough therapy designation and priority review.

The approval is based on the phase 3 MAESTRO-NASH trial, in which resmetirom was superior to placebo at achieving resolution of nonalcoholic steatohepatitis (NASH) and improving liver fibrosis in both 80-mg and 100-mg doses. 

The trial used the earlier nomenclature of NASH and nonalcoholic fatty liver disease (NAFLD). An international consensus group has since changed these terms to MASH and metabolic dysfunction–associated steatotic liver disease (MASLD), respectively. (Note that the terms NASH and NAFLD will be used to discuss the trial results in this article to align with the trial’s original language.) 

The results were published online February 6 in The New England Journal of Medicine. 

“The approval of the first medication for NASH is a true game-changer for healthcare providers, the research community and, most importantly, patients living with this serious liver condition,” lead MAESTRO-NASH investigator Stephen Harrison, MD, gastroenterologist, hepatologist, and chairman of Pinnacle Clinical Research and Summit Clinical Research, San Antonio, Texas, said in a news release. 

“Based on the robust efficacy and safety data generated in two large Phase 3 MAESTRO studies, I believe Rezdiffra will become the foundational therapy for patients with NASH with moderate to advanced liver fibrosis. Importantly, we continue to study Rezdiffra to determine if the positive results observed in the MAESTRO studies will lead to reduced risk of progression to cirrhosis, liver failure, need for liver transplant and premature mortality,” Dr. Harrison added.

 

Addressing an Unmet Need 

MASH is a progressive liver disease and the leading cause of liver-related mortality. The disease affects an estimated 1.5 million adults in the United States, of which, roughly 525,000 have MASH with significant fibrosis. Until now, there was no FDA-approved medication. 

In the ongoing MAESTRO-NASH, 996 adults with biopsy-confirmed NASH and significant stage 2-3 fibrosis were randomly assigned to receive oral once-daily resmetirom (80 mg or 100 mg) or placebo. 

Patients were followed for 52 weeks, at which point, they were assessed for the dual primary endpoints of NASH resolution (including a reduction in the NAFLD activity score by ≥ 2 points) with no worsening of fibrosis and an improvement (reduction) in fibrosis by at least one stage with no worsening of the NAFLD activity score.

Patients receiving resmetirom had a significant improvement across both doses and both primary endpoints. 

At 52 weeks, NASH resolution with no worsening of fibrosis was achieved in 25.9% and 29.9% of the patients in the 80-mg and 100-mg groups, respectively, compared with 9.7% on placebo.

Fibrosis improved by at least one stage with no worsening of the NAFLD activity score in 24.2% and 25.9% of patients in the 80-mg and 100-mg groups, respectively, compared with 14.2% on placebo. 

The trial also met multiple secondary endpoints, including statistically significant reduction from baseline in liver enzymes (alanine transaminase, aspartate aminotransferase, and gamma-glutamyl transferase) and low-density lipoprotein cholesterol with resmetirom compared with placebo. 

Improvement in fibrosis biomarkers and relevant imaging tests were also observed in resmetirom treatment groups compared with placebo. 

The most common adverse events included diarrhea and nausea, which typically began early in treatment and were mild to moderate in severity. Pruritus, abdominal pain, vomiting, constipation, and dizziness were also reported.

Resmetirom is expected to be available to patients in the United States in April and will be distributed through a limited specialty pharmacy network.

Full prescribing information is available online. Prescribing information does not include a liver biopsy requirement for diagnosis.

A version of this article appeared on Medscape.com.

The US Food and Drug Administration (FDA) has approved resmetirom (Rezdiffra, Madrigal Pharmaceuticals), the first drug to treat patients with metabolic dysfunction–associated steatohepatitis (MASH) and moderate to advanced liver fibrosis (consistent with stage F2 and F3 disease), along with diet and exercise. 

Resmetirom is a once-daily, oral thyroid hormone receptor beta-selective agonist. The FDA granted the drug breakthrough therapy designation and priority review.

The approval is based on the phase 3 MAESTRO-NASH trial, in which resmetirom was superior to placebo at achieving resolution of nonalcoholic steatohepatitis (NASH) and improving liver fibrosis in both 80-mg and 100-mg doses. 

The trial used the earlier nomenclature of NASH and nonalcoholic fatty liver disease (NAFLD). An international consensus group has since changed these terms to MASH and metabolic dysfunction–associated steatotic liver disease (MASLD), respectively. (Note that the terms NASH and NAFLD will be used to discuss the trial results in this article to align with the trial’s original language.) 

The results were published online February 6 in The New England Journal of Medicine. 

“The approval of the first medication for NASH is a true game-changer for healthcare providers, the research community and, most importantly, patients living with this serious liver condition,” lead MAESTRO-NASH investigator Stephen Harrison, MD, gastroenterologist, hepatologist, and chairman of Pinnacle Clinical Research and Summit Clinical Research, San Antonio, Texas, said in a news release. 

“Based on the robust efficacy and safety data generated in two large Phase 3 MAESTRO studies, I believe Rezdiffra will become the foundational therapy for patients with NASH with moderate to advanced liver fibrosis. Importantly, we continue to study Rezdiffra to determine if the positive results observed in the MAESTRO studies will lead to reduced risk of progression to cirrhosis, liver failure, need for liver transplant and premature mortality,” Dr. Harrison added.

 

Addressing an Unmet Need 

MASH is a progressive liver disease and the leading cause of liver-related mortality. The disease affects an estimated 1.5 million adults in the United States, of which, roughly 525,000 have MASH with significant fibrosis. Until now, there was no FDA-approved medication. 

In the ongoing MAESTRO-NASH, 996 adults with biopsy-confirmed NASH and significant stage 2-3 fibrosis were randomly assigned to receive oral once-daily resmetirom (80 mg or 100 mg) or placebo. 

Patients were followed for 52 weeks, at which point, they were assessed for the dual primary endpoints of NASH resolution (including a reduction in the NAFLD activity score by ≥ 2 points) with no worsening of fibrosis and an improvement (reduction) in fibrosis by at least one stage with no worsening of the NAFLD activity score.

Patients receiving resmetirom had a significant improvement across both doses and both primary endpoints. 

At 52 weeks, NASH resolution with no worsening of fibrosis was achieved in 25.9% and 29.9% of the patients in the 80-mg and 100-mg groups, respectively, compared with 9.7% on placebo.

Fibrosis improved by at least one stage with no worsening of the NAFLD activity score in 24.2% and 25.9% of patients in the 80-mg and 100-mg groups, respectively, compared with 14.2% on placebo. 

The trial also met multiple secondary endpoints, including statistically significant reduction from baseline in liver enzymes (alanine transaminase, aspartate aminotransferase, and gamma-glutamyl transferase) and low-density lipoprotein cholesterol with resmetirom compared with placebo. 

Improvement in fibrosis biomarkers and relevant imaging tests were also observed in resmetirom treatment groups compared with placebo. 

The most common adverse events included diarrhea and nausea, which typically began early in treatment and were mild to moderate in severity. Pruritus, abdominal pain, vomiting, constipation, and dizziness were also reported.

Resmetirom is expected to be available to patients in the United States in April and will be distributed through a limited specialty pharmacy network.

Full prescribing information is available online. Prescribing information does not include a liver biopsy requirement for diagnosis.

A version of this article appeared on Medscape.com.

Semaglutide improved metabolic dysfunction–associated steatotic liver disease (MASLD) among people living with HIV, and in some cases resolved it completely, according to results from the SLIM LIVER study presented by the AIDS Clinical Trials Group (ACTG) at this year’s Conference on Retroviruses and Opportunistic Infections (CROI) 2024 Annual Meeting in Denver.

Furthermore, although muscle volume decreased with weight loss, participants did not experience significant changes in muscle quality or physical function.
 

‘A First’

SLIM LIVER is the first study evaluating semaglutide as a treatment of MASLD among people living with HIV.

The phase 2b, single-arm pilot study enrolled adults living with HIV who were virally suppressed and had central adiposity, insulin resistance or prediabetes, and steatotic liver disease.

Participants self-injected semaglutide weekly at increasing doses until they reached a 1-mg dose at week 4. At 24 weeks, the study team assessed changes in participants’ intra-hepatic triglyceride content using magnetic resonance imaging-proton density fat fraction.

The primary analysis results from SLIM LIVER were reported in an oral presentation, “Semaglutide Reduces Metabolic-Associated Steatotic Liver Disease in People With HIV: The SLIM LIVER Study,” on March 5 by Jordan E. Lake, MD, MSc, of UTHealth Houston.

A subgroup analysis of the study was provided in a poster, “Effects of Semaglutide on Muscle Structure and Function in the SLIM LIVER Study,” presented on March 4 by Grace L. Ditzenberger, PT, DPT, of the University of Colorado Anschutz Medical Campus in Aurora.

In the primary analysis, the median age of the 49 participants was 52 years, 43% were women (cisgender and transgender), the mean body mass index was 35, 39% were Hispanic and 33% were Black/African American, and 82% were taking antiretroviral therapy that included an integrase inhibitor.

Liver fat was reduced by an average of 31%, with 29% of participants experiencing a complete resolution (5% or less liver fat) of MASLD. They also experienced weight loss, reduced fasting blood glucose, and reduced fasting triglycerides, consistent with effects observed in studies of semaglutide in people without HIV.

The sub-analysis of the 46 participants for whom muscle measurements were available showed that muscle volume (measured in the psoas) decreased but with no significant change in physical function.

Semaglutide was generally well tolerated, with an adverse event profile similar to that seen in individuals without HIV.

The most common adverse events were gastrointestinal (ie, nausea, diarrhea, vomiting, and abdominal pain). Two participants experienced more significant adverse events possibly related to semaglutide but were able to continue in the study.

All participants completed the full 24 weeks of therapy at the originally prescribed dose.
 

Potential Impact

“Even at the low dose of 1 mg every week, most participants lost significant weight, and weight loss was closely associated with improvements in MASLD,” Dr. Lake said. “Additional research will assess the secondary effects of semaglutide on systemic inflammation and metabolism and determine whether semaglutide may have unique risks or benefits for people living with HIV.”

“These findings have the potential to have a significant impact on the health and quality of life of people living with HIV,” added ACTG Chair Judith Currier, MD, MSc, University of California Los Angeles.

The SLIM LIVER study was sponsored by the US National Institute of Allergy and Infectious Diseases (NIAID), with additional funding from UTHealth Houston McGovern School of Medicine. ACTG is a clinical trials network focused on HIV and other infectious diseases, funded by NIAID and collaborating institutes of the US National Institutes of Health.

No conflicts of interest were reported.
 

A version of this article appeared on Medscape.com.

Semaglutide improved metabolic dysfunction–associated steatotic liver disease (MASLD) among people living with HIV, and in some cases resolved it completely, according to results from the SLIM LIVER study presented by the AIDS Clinical Trials Group (ACTG) at this year’s Conference on Retroviruses and Opportunistic Infections (CROI) 2024 Annual Meeting in Denver.

Furthermore, although muscle volume decreased with weight loss, participants did not experience significant changes in muscle quality or physical function.
 

‘A First’

SLIM LIVER is the first study evaluating semaglutide as a treatment of MASLD among people living with HIV.

The phase 2b, single-arm pilot study enrolled adults living with HIV who were virally suppressed and had central adiposity, insulin resistance or prediabetes, and steatotic liver disease.

Participants self-injected semaglutide weekly at increasing doses until they reached a 1-mg dose at week 4. At 24 weeks, the study team assessed changes in participants’ intra-hepatic triglyceride content using magnetic resonance imaging-proton density fat fraction.

The primary analysis results from SLIM LIVER were reported in an oral presentation, “Semaglutide Reduces Metabolic-Associated Steatotic Liver Disease in People With HIV: The SLIM LIVER Study,” on March 5 by Jordan E. Lake, MD, MSc, of UTHealth Houston.

A subgroup analysis of the study was provided in a poster, “Effects of Semaglutide on Muscle Structure and Function in the SLIM LIVER Study,” presented on March 4 by Grace L. Ditzenberger, PT, DPT, of the University of Colorado Anschutz Medical Campus in Aurora.

In the primary analysis, the median age of the 49 participants was 52 years, 43% were women (cisgender and transgender), the mean body mass index was 35, 39% were Hispanic and 33% were Black/African American, and 82% were taking antiretroviral therapy that included an integrase inhibitor.

Liver fat was reduced by an average of 31%, with 29% of participants experiencing a complete resolution (5% or less liver fat) of MASLD. They also experienced weight loss, reduced fasting blood glucose, and reduced fasting triglycerides, consistent with effects observed in studies of semaglutide in people without HIV.

The sub-analysis of the 46 participants for whom muscle measurements were available showed that muscle volume (measured in the psoas) decreased but with no significant change in physical function.

Semaglutide was generally well tolerated, with an adverse event profile similar to that seen in individuals without HIV.

The most common adverse events were gastrointestinal (ie, nausea, diarrhea, vomiting, and abdominal pain). Two participants experienced more significant adverse events possibly related to semaglutide but were able to continue in the study.

All participants completed the full 24 weeks of therapy at the originally prescribed dose.
 

Potential Impact

“Even at the low dose of 1 mg every week, most participants lost significant weight, and weight loss was closely associated with improvements in MASLD,” Dr. Lake said. “Additional research will assess the secondary effects of semaglutide on systemic inflammation and metabolism and determine whether semaglutide may have unique risks or benefits for people living with HIV.”

“These findings have the potential to have a significant impact on the health and quality of life of people living with HIV,” added ACTG Chair Judith Currier, MD, MSc, University of California Los Angeles.

The SLIM LIVER study was sponsored by the US National Institute of Allergy and Infectious Diseases (NIAID), with additional funding from UTHealth Houston McGovern School of Medicine. ACTG is a clinical trials network focused on HIV and other infectious diseases, funded by NIAID and collaborating institutes of the US National Institutes of Health.

No conflicts of interest were reported.
 

A version of this article appeared on Medscape.com.

Semaglutide improved metabolic dysfunction–associated steatotic liver disease (MASLD) among people living with HIV, and in some cases resolved it completely, according to results from the SLIM LIVER study presented by the AIDS Clinical Trials Group (ACTG) at this year’s Conference on Retroviruses and Opportunistic Infections (CROI) 2024 Annual Meeting in Denver.

Furthermore, although muscle volume decreased with weight loss, participants did not experience significant changes in muscle quality or physical function.
 

‘A First’

SLIM LIVER is the first study evaluating semaglutide as a treatment of MASLD among people living with HIV.

The phase 2b, single-arm pilot study enrolled adults living with HIV who were virally suppressed and had central adiposity, insulin resistance or prediabetes, and steatotic liver disease.

Participants self-injected semaglutide weekly at increasing doses until they reached a 1-mg dose at week 4. At 24 weeks, the study team assessed changes in participants’ intra-hepatic triglyceride content using magnetic resonance imaging-proton density fat fraction.

The primary analysis results from SLIM LIVER were reported in an oral presentation, “Semaglutide Reduces Metabolic-Associated Steatotic Liver Disease in People With HIV: The SLIM LIVER Study,” on March 5 by Jordan E. Lake, MD, MSc, of UTHealth Houston.

A subgroup analysis of the study was provided in a poster, “Effects of Semaglutide on Muscle Structure and Function in the SLIM LIVER Study,” presented on March 4 by Grace L. Ditzenberger, PT, DPT, of the University of Colorado Anschutz Medical Campus in Aurora.

In the primary analysis, the median age of the 49 participants was 52 years, 43% were women (cisgender and transgender), the mean body mass index was 35, 39% were Hispanic and 33% were Black/African American, and 82% were taking antiretroviral therapy that included an integrase inhibitor.

Liver fat was reduced by an average of 31%, with 29% of participants experiencing a complete resolution (5% or less liver fat) of MASLD. They also experienced weight loss, reduced fasting blood glucose, and reduced fasting triglycerides, consistent with effects observed in studies of semaglutide in people without HIV.

The sub-analysis of the 46 participants for whom muscle measurements were available showed that muscle volume (measured in the psoas) decreased but with no significant change in physical function.

Semaglutide was generally well tolerated, with an adverse event profile similar to that seen in individuals without HIV.

The most common adverse events were gastrointestinal (ie, nausea, diarrhea, vomiting, and abdominal pain). Two participants experienced more significant adverse events possibly related to semaglutide but were able to continue in the study.

All participants completed the full 24 weeks of therapy at the originally prescribed dose.
 

Potential Impact

“Even at the low dose of 1 mg every week, most participants lost significant weight, and weight loss was closely associated with improvements in MASLD,” Dr. Lake said. “Additional research will assess the secondary effects of semaglutide on systemic inflammation and metabolism and determine whether semaglutide may have unique risks or benefits for people living with HIV.”

“These findings have the potential to have a significant impact on the health and quality of life of people living with HIV,” added ACTG Chair Judith Currier, MD, MSc, University of California Los Angeles.

The SLIM LIVER study was sponsored by the US National Institute of Allergy and Infectious Diseases (NIAID), with additional funding from UTHealth Houston McGovern School of Medicine. ACTG is a clinical trials network focused on HIV and other infectious diseases, funded by NIAID and collaborating institutes of the US National Institutes of Health.

No conflicts of interest were reported.
 

A version of this article appeared on Medscape.com.

TOPLINE:

A multicomponent strategy of nurse-led communication, home blood pressure monitoring, evidence-based treatment algorithms, and electronic health record tools improved systolic blood pressure (SBP) and non–high-density lipoprotein (non-HDL) cholesterol levels in people living with HIV.

METHODOLOGY:

• Investigators assessed if EXTRA-CVD, a nurse-led multicomponent intervention for preventing cardiovascular diseases (CVD), could effectively improve SBP and non-HDL cholesterol levels in people living with HIV whose viral replication has been controlled effectively using antiretroviral therapy.
• They recruited 297 individuals (median age, 59 years; 20.9% women) from three academic HIV clinics in the United States with an HIV-1 viral load < 200 copies/mL who were diagnosed with both hypertension and hypercholesterolemia.
• Participants were randomly assigned to either the EXTRA-CVD intervention group or a control group comprising individuals who received general prevention education.
• SBP (the primary outcome) was calculated as the mean of two SBP measurements obtained 1 minute apart, and non-HDL cholesterol (the secondary outcome) was calculated as total cholesterol minus HDL cholesterol.

TAKEAWAY:

• Participants in the intervention vs control group reported having significantly lower SBP as early as 4 months after the nurse-led strategy (mean difference, −6.4 mm Hg; P = .002), with the improvements sustaining until 12 months (mean difference, −4.2 mm Hg; P = .04).
• At 12 months, participants in the intervention group showed a 16.9-mg/dL (P < .001) reduction in non-HDL cholesterol levels compared with those in the control group.
• The nurse-led strategy led to a greater reduction in SBP in women with HIV vs men living with HIV (5.9 mm Hg greater SBP difference at 12 months), with the difference being clinically meaningful but not statistically significant.
• This nurse-led strategy did not increase the risk for adverse events in people living with HIV.

IN PRACTICE:

“Although the EXTRA-CVD intervention was limited to BP and cholesterol, nurse-led case management might be beneficial for a range of other primary care conditions in HIV clinics. If HIV clinics choose to implement EXTRA-CVD, they might consider adding staff trained in other chronic comorbidities and/or health promotion activities,” the authors noted.

SOURCE:

This study was led by Christopher T. Longenecker, MD, University of Washington School of Medicine, Seattle, and published online on March 5, 2024, in JAMA Network Open.

LIMITATIONS:

Because this trial was conducted at well-resourced, major academic HIV clinics, the results may not be applicable to other populations, such as smaller community-based clinics or HIV care outside the United States. The sensitivity analyses performed in this study may not have fully accounted for the bias introduced by the differential attrition in the intervention group.

DISCLOSURES:

This study was supported by grants from the National Institutes of Health (NIH). The authors declared receiving grants and personal fees from or having other ties with the NIH and other sources.

A version of this article appeared on Medscape.com.

TOPLINE:

A multicomponent strategy of nurse-led communication, home blood pressure monitoring, evidence-based treatment algorithms, and electronic health record tools improved systolic blood pressure (SBP) and non–high-density lipoprotein (non-HDL) cholesterol levels in people living with HIV.

METHODOLOGY:

• Investigators assessed if EXTRA-CVD, a nurse-led multicomponent intervention for preventing cardiovascular diseases (CVD), could effectively improve SBP and non-HDL cholesterol levels in people living with HIV whose viral replication has been controlled effectively using antiretroviral therapy.
• They recruited 297 individuals (median age, 59 years; 20.9% women) from three academic HIV clinics in the United States with an HIV-1 viral load < 200 copies/mL who were diagnosed with both hypertension and hypercholesterolemia.
• Participants were randomly assigned to either the EXTRA-CVD intervention group or a control group comprising individuals who received general prevention education.
• SBP (the primary outcome) was calculated as the mean of two SBP measurements obtained 1 minute apart, and non-HDL cholesterol (the secondary outcome) was calculated as total cholesterol minus HDL cholesterol.

TAKEAWAY:

• Participants in the intervention vs control group reported having significantly lower SBP as early as 4 months after the nurse-led strategy (mean difference, −6.4 mm Hg; P = .002), with the improvements sustaining until 12 months (mean difference, −4.2 mm Hg; P = .04).
• At 12 months, participants in the intervention group showed a 16.9-mg/dL (P < .001) reduction in non-HDL cholesterol levels compared with those in the control group.
• The nurse-led strategy led to a greater reduction in SBP in women with HIV vs men living with HIV (5.9 mm Hg greater SBP difference at 12 months), with the difference being clinically meaningful but not statistically significant.
• This nurse-led strategy did not increase the risk for adverse events in people living with HIV.

IN PRACTICE:

“Although the EXTRA-CVD intervention was limited to BP and cholesterol, nurse-led case management might be beneficial for a range of other primary care conditions in HIV clinics. If HIV clinics choose to implement EXTRA-CVD, they might consider adding staff trained in other chronic comorbidities and/or health promotion activities,” the authors noted.

SOURCE:

This study was led by Christopher T. Longenecker, MD, University of Washington School of Medicine, Seattle, and published online on March 5, 2024, in JAMA Network Open.

LIMITATIONS:

Because this trial was conducted at well-resourced, major academic HIV clinics, the results may not be applicable to other populations, such as smaller community-based clinics or HIV care outside the United States. The sensitivity analyses performed in this study may not have fully accounted for the bias introduced by the differential attrition in the intervention group.

DISCLOSURES:

This study was supported by grants from the National Institutes of Health (NIH). The authors declared receiving grants and personal fees from or having other ties with the NIH and other sources.

A version of this article appeared on Medscape.com.

TOPLINE:

A multicomponent strategy of nurse-led communication, home blood pressure monitoring, evidence-based treatment algorithms, and electronic health record tools improved systolic blood pressure (SBP) and non–high-density lipoprotein (non-HDL) cholesterol levels in people living with HIV.

METHODOLOGY:

• Investigators assessed if EXTRA-CVD, a nurse-led multicomponent intervention for preventing cardiovascular diseases (CVD), could effectively improve SBP and non-HDL cholesterol levels in people living with HIV whose viral replication has been controlled effectively using antiretroviral therapy.
• They recruited 297 individuals (median age, 59 years; 20.9% women) from three academic HIV clinics in the United States with an HIV-1 viral load < 200 copies/mL who were diagnosed with both hypertension and hypercholesterolemia.
• Participants were randomly assigned to either the EXTRA-CVD intervention group or a control group comprising individuals who received general prevention education.
• SBP (the primary outcome) was calculated as the mean of two SBP measurements obtained 1 minute apart, and non-HDL cholesterol (the secondary outcome) was calculated as total cholesterol minus HDL cholesterol.

TAKEAWAY:

• Participants in the intervention vs control group reported having significantly lower SBP as early as 4 months after the nurse-led strategy (mean difference, −6.4 mm Hg; P = .002), with the improvements sustaining until 12 months (mean difference, −4.2 mm Hg; P = .04).
• At 12 months, participants in the intervention group showed a 16.9-mg/dL (P < .001) reduction in non-HDL cholesterol levels compared with those in the control group.
• The nurse-led strategy led to a greater reduction in SBP in women with HIV vs men living with HIV (5.9 mm Hg greater SBP difference at 12 months), with the difference being clinically meaningful but not statistically significant.
• This nurse-led strategy did not increase the risk for adverse events in people living with HIV.

IN PRACTICE:

“Although the EXTRA-CVD intervention was limited to BP and cholesterol, nurse-led case management might be beneficial for a range of other primary care conditions in HIV clinics. If HIV clinics choose to implement EXTRA-CVD, they might consider adding staff trained in other chronic comorbidities and/or health promotion activities,” the authors noted.

SOURCE:

This study was led by Christopher T. Longenecker, MD, University of Washington School of Medicine, Seattle, and published online on March 5, 2024, in JAMA Network Open.

LIMITATIONS:

Because this trial was conducted at well-resourced, major academic HIV clinics, the results may not be applicable to other populations, such as smaller community-based clinics or HIV care outside the United States. The sensitivity analyses performed in this study may not have fully accounted for the bias introduced by the differential attrition in the intervention group.

DISCLOSURES:

This study was supported by grants from the National Institutes of Health (NIH). The authors declared receiving grants and personal fees from or having other ties with the NIH and other sources.

A version of this article appeared on Medscape.com.

Seladelpar, an investigational selective agonist of peroxisome proliferator–activated receptor-delta (PPAR-delta), significantly improves liver biomarkers of disease activity and bothersome symptoms of pruritus in adults with primary biliary cholangitis (PBC), according to the full results of the RESPONSE phase 3 study.

“At a dose of 10 mg daily, 1 in 4 patients normalize their alkaline phosphatase level,” chief investigator Gideon Hirschfield, PhD, BM BChir, with the Toronto Center for Liver Disease at Toronto General Hospital, Toronto, Ontario, Canada, said in an interview.

‘Unequivocal’ Progress

Up to 40% of patients with PBC have an inadequate response to first-line therapy with ursodeoxycholic acid (UDCA) and are at a high risk for disease progression. More than half of patients with the disease fail to respond to second-line therapy with obeticholic acid.

Seladelpar, and the dual PPAR-alpha and PPAR-delta agonist elafibranor, are an “unequivocal sign of progress, marking the arrival of a new era in which PBC treatment is expected to provide both biochemical benefits and amelioration of symptoms for patients,” David N. Assis, MD, with the Section of Digestive Diseases, Yale School of Medicine, New Haven, Connecticut, wrote in a linked editorial.

Significant Reduction in Pruritus

A key secondary endpoint was change in patient-reported pruritus.

At baseline, 38.3% of patients in the seladelpar group and 35.4% of those in the placebo group had moderate to severe pruritus, with a daily numerical rating scale (NRS) score of 4 or higher out of 10.

Among these patients, the reduction from baseline in the pruritus NRS score at month 6 was significantly greater with seladelpar than with placebo (change from baseline, −3.2 points vs −1.7 points). These improvements were sustained through 12 months.

Improvements on the 5-D Itch Scale in both the moderate to severe pruritus population and the overall population also favored seladelpar over placebo for itch relief, which had a positive impact on sleep. Similar results demonstrating reductions in itch and improvements in sleep were observed using the PBC-40 questionnaire.

Adverse events that led to discontinuation of seladelpar or placebo were rare, and there was no between-group difference in the incidence of serious adverse events.

“No worrisome adverse events affecting the muscles were observed, including among patients receiving statins. Certain gastrointestinal events — abdominal pain, abdominal distention, and nausea — were reported more frequently in the seladelpar group than in the placebo group,” the study authors wrote.

The most common adverse events that occurred in ≥ 5% of patients in either group were COVID-19 and pruritus. A greater percentage of patients treated with placebo reported pruritus (15.4% vs 4.7%) as an adverse event — a finding consistent with the positive effect of seladelpar on reducing pruritus.

The researchers noted that 96.4% of patients who participated in the RESPONSE trial chose to enroll in the extension trial to evaluate long-term safety and the side-effect profile of seladelpar.
 

Potential First-Line Treatment?

In Dr. Assis’ view, the RESPONSE trial, coupled with the recently reported ELATIVE trial of the dual PPAR-alpha and PPAR-delta agonist elafibranor in PBC, “cement the role of PPAR agonists as the preferred second-line treatment in primary biliary cholangitis.”

“The reduction in serum cholestatic markers and the safety profiles of elafibranor and seladelpar offer clear advantages beyond what was previously shown with obeticholic acid. These trials also cement a new treatment goal for primary biliary cholangitis in which a reduction in pruritus should be expected as part of anticholestatic treatment,” Dr. Assis wrote.

“The results of these trials suggest that the use of PPAR agonists in primary biliary cholangitis could improve treatment outcomes while also improving quality of life, which is a highly desirable alignment of clinician and patient goals,” Dr. Assis added.

Looking ahead, Dr. Hirschfield sees a potential role for seladelpar earlier in the course of PBC treatment, he said in an interview.

“Over time, the way we treat patients will not be to wait to fail. It will be treat to target and treat to success,” Dr. Hirschfield said.

Earlier this month, the US Food and Drug Administration accepted CymaBay Therapeutics’ new drug application for seladelpar for the treatment of PBC, including pruritus in adults without cirrhosis or with compensated cirrhosis (Child Pugh A) who fail to respond adequately or cannot tolerate UDCA. Seladelpar for PBC was granted breakthrough designation in October 2023.

The study was funded by CymaBay Therapeutics. Disclosures for authors and editorialist are available at NEJM.org.

A version of this article appeared on Medscape.com.

Seladelpar, an investigational selective agonist of peroxisome proliferator–activated receptor-delta (PPAR-delta), significantly improves liver biomarkers of disease activity and bothersome symptoms of pruritus in adults with primary biliary cholangitis (PBC), according to the full results of the RESPONSE phase 3 study.

“At a dose of 10 mg daily, 1 in 4 patients normalize their alkaline phosphatase level,” chief investigator Gideon Hirschfield, PhD, BM BChir, with the Toronto Center for Liver Disease at Toronto General Hospital, Toronto, Ontario, Canada, said in an interview.

‘Unequivocal’ Progress

Up to 40% of patients with PBC have an inadequate response to first-line therapy with ursodeoxycholic acid (UDCA) and are at a high risk for disease progression. More than half of patients with the disease fail to respond to second-line therapy with obeticholic acid.

Seladelpar, and the dual PPAR-alpha and PPAR-delta agonist elafibranor, are an “unequivocal sign of progress, marking the arrival of a new era in which PBC treatment is expected to provide both biochemical benefits and amelioration of symptoms for patients,” David N. Assis, MD, with the Section of Digestive Diseases, Yale School of Medicine, New Haven, Connecticut, wrote in a linked editorial.

Significant Reduction in Pruritus

A key secondary endpoint was change in patient-reported pruritus.

At baseline, 38.3% of patients in the seladelpar group and 35.4% of those in the placebo group had moderate to severe pruritus, with a daily numerical rating scale (NRS) score of 4 or higher out of 10.

Among these patients, the reduction from baseline in the pruritus NRS score at month 6 was significantly greater with seladelpar than with placebo (change from baseline, −3.2 points vs −1.7 points). These improvements were sustained through 12 months.

Improvements on the 5-D Itch Scale in both the moderate to severe pruritus population and the overall population also favored seladelpar over placebo for itch relief, which had a positive impact on sleep. Similar results demonstrating reductions in itch and improvements in sleep were observed using the PBC-40 questionnaire.

Adverse events that led to discontinuation of seladelpar or placebo were rare, and there was no between-group difference in the incidence of serious adverse events.

“No worrisome adverse events affecting the muscles were observed, including among patients receiving statins. Certain gastrointestinal events — abdominal pain, abdominal distention, and nausea — were reported more frequently in the seladelpar group than in the placebo group,” the study authors wrote.

The most common adverse events that occurred in ≥ 5% of patients in either group were COVID-19 and pruritus. A greater percentage of patients treated with placebo reported pruritus (15.4% vs 4.7%) as an adverse event — a finding consistent with the positive effect of seladelpar on reducing pruritus.

The researchers noted that 96.4% of patients who participated in the RESPONSE trial chose to enroll in the extension trial to evaluate long-term safety and the side-effect profile of seladelpar.
 

Potential First-Line Treatment?

In Dr. Assis’ view, the RESPONSE trial, coupled with the recently reported ELATIVE trial of the dual PPAR-alpha and PPAR-delta agonist elafibranor in PBC, “cement the role of PPAR agonists as the preferred second-line treatment in primary biliary cholangitis.”

“The reduction in serum cholestatic markers and the safety profiles of elafibranor and seladelpar offer clear advantages beyond what was previously shown with obeticholic acid. These trials also cement a new treatment goal for primary biliary cholangitis in which a reduction in pruritus should be expected as part of anticholestatic treatment,” Dr. Assis wrote.

“The results of these trials suggest that the use of PPAR agonists in primary biliary cholangitis could improve treatment outcomes while also improving quality of life, which is a highly desirable alignment of clinician and patient goals,” Dr. Assis added.

Looking ahead, Dr. Hirschfield sees a potential role for seladelpar earlier in the course of PBC treatment, he said in an interview.

“Over time, the way we treat patients will not be to wait to fail. It will be treat to target and treat to success,” Dr. Hirschfield said.

Earlier this month, the US Food and Drug Administration accepted CymaBay Therapeutics’ new drug application for seladelpar for the treatment of PBC, including pruritus in adults without cirrhosis or with compensated cirrhosis (Child Pugh A) who fail to respond adequately or cannot tolerate UDCA. Seladelpar for PBC was granted breakthrough designation in October 2023.

The study was funded by CymaBay Therapeutics. Disclosures for authors and editorialist are available at NEJM.org.

A version of this article appeared on Medscape.com.

Seladelpar, an investigational selective agonist of peroxisome proliferator–activated receptor-delta (PPAR-delta), significantly improves liver biomarkers of disease activity and bothersome symptoms of pruritus in adults with primary biliary cholangitis (PBC), according to the full results of the RESPONSE phase 3 study.

“At a dose of 10 mg daily, 1 in 4 patients normalize their alkaline phosphatase level,” chief investigator Gideon Hirschfield, PhD, BM BChir, with the Toronto Center for Liver Disease at Toronto General Hospital, Toronto, Ontario, Canada, said in an interview.

‘Unequivocal’ Progress

Up to 40% of patients with PBC have an inadequate response to first-line therapy with ursodeoxycholic acid (UDCA) and are at a high risk for disease progression. More than half of patients with the disease fail to respond to second-line therapy with obeticholic acid.

Seladelpar, and the dual PPAR-alpha and PPAR-delta agonist elafibranor, are an “unequivocal sign of progress, marking the arrival of a new era in which PBC treatment is expected to provide both biochemical benefits and amelioration of symptoms for patients,” David N. Assis, MD, with the Section of Digestive Diseases, Yale School of Medicine, New Haven, Connecticut, wrote in a linked editorial.

Significant Reduction in Pruritus

A key secondary endpoint was change in patient-reported pruritus.

At baseline, 38.3% of patients in the seladelpar group and 35.4% of those in the placebo group had moderate to severe pruritus, with a daily numerical rating scale (NRS) score of 4 or higher out of 10.

Among these patients, the reduction from baseline in the pruritus NRS score at month 6 was significantly greater with seladelpar than with placebo (change from baseline, −3.2 points vs −1.7 points). These improvements were sustained through 12 months.

Improvements on the 5-D Itch Scale in both the moderate to severe pruritus population and the overall population also favored seladelpar over placebo for itch relief, which had a positive impact on sleep. Similar results demonstrating reductions in itch and improvements in sleep were observed using the PBC-40 questionnaire.

Adverse events that led to discontinuation of seladelpar or placebo were rare, and there was no between-group difference in the incidence of serious adverse events.

“No worrisome adverse events affecting the muscles were observed, including among patients receiving statins. Certain gastrointestinal events — abdominal pain, abdominal distention, and nausea — were reported more frequently in the seladelpar group than in the placebo group,” the study authors wrote.

The most common adverse events that occurred in ≥ 5% of patients in either group were COVID-19 and pruritus. A greater percentage of patients treated with placebo reported pruritus (15.4% vs 4.7%) as an adverse event — a finding consistent with the positive effect of seladelpar on reducing pruritus.

The researchers noted that 96.4% of patients who participated in the RESPONSE trial chose to enroll in the extension trial to evaluate long-term safety and the side-effect profile of seladelpar.
 

Potential First-Line Treatment?

In Dr. Assis’ view, the RESPONSE trial, coupled with the recently reported ELATIVE trial of the dual PPAR-alpha and PPAR-delta agonist elafibranor in PBC, “cement the role of PPAR agonists as the preferred second-line treatment in primary biliary cholangitis.”

“The reduction in serum cholestatic markers and the safety profiles of elafibranor and seladelpar offer clear advantages beyond what was previously shown with obeticholic acid. These trials also cement a new treatment goal for primary biliary cholangitis in which a reduction in pruritus should be expected as part of anticholestatic treatment,” Dr. Assis wrote.

“The results of these trials suggest that the use of PPAR agonists in primary biliary cholangitis could improve treatment outcomes while also improving quality of life, which is a highly desirable alignment of clinician and patient goals,” Dr. Assis added.

Looking ahead, Dr. Hirschfield sees a potential role for seladelpar earlier in the course of PBC treatment, he said in an interview.

“Over time, the way we treat patients will not be to wait to fail. It will be treat to target and treat to success,” Dr. Hirschfield said.

Earlier this month, the US Food and Drug Administration accepted CymaBay Therapeutics’ new drug application for seladelpar for the treatment of PBC, including pruritus in adults without cirrhosis or with compensated cirrhosis (Child Pugh A) who fail to respond adequately or cannot tolerate UDCA. Seladelpar for PBC was granted breakthrough designation in October 2023.

The study was funded by CymaBay Therapeutics. Disclosures for authors and editorialist are available at NEJM.org.

A version of this article appeared on Medscape.com.

TOPLINE:

Augmenting an intake of vitamin E, via both diet and supplements, may help prevent metabolic dysfunction–associated steatotic liver disease (MASLD), particularly in adults without hyperlipidemia, new data showed.

METHODOLOGY:

• MASLD (formerly known as nonalcoholic fatty liver disease) is a common chronic liver disease, and its severe form — metabolic dysfunction–associated steatohepatitis (formerly nonalcoholic steatohepatitis) — is associated with oxidative stress. As an antioxidant, vitamin E may protect against MASLD.
• Researchers analyzed data for 6122 adults from the National Health and Nutrition Examination Survey from 2017 to 2020.
• Information on dietary, supplementary, and total vitamin E intake was obtained from two 24-hour dietary recall interviews.
• The extent of hepatic steatosis was measured by liver ultrasound transient elastography, with MASLD defined as a controlled attenuated parameter threshold of ≥ 288 dB/m.

TAKEAWAY:

• After adjustment for sociodemographic characteristics, adults with MASLD had lower dietary and total intake of vitamin E, and dietary and total vitamin E intake was inversely associated with MASLD outcome.
• Adults in the top quartile of dietary vitamin E intake had approximately 40% lower odds of MASLD (odds ratio [OR], 0.60; P = .0091).
• Vitamin E supplement use was associated with 34% reduced odds of MASLD (OR, 0.66; P = .0249), whereas adults in the top quartile of total vitamin E intake had a 33% lower likelihood of MASLD (OR, 0.67; P = .0538).
• The findings were robust to sensitivity analysis, and the effects were stronger in those without hyperlipidemia.

IN PRACTICE:

“Increasing dietary sources of vitamin E is beneficial for preventing [MASLD], particularly in individuals without hyperlipidemia,” the researchers concluded.

SOURCE:

The study, with first author Xiangjun Qi, Guangzhou University of Chinese Medicine, Guangzhou, China, was published online in Scientific Reports.

LIMITATIONS:

Causality cannot be determined due to the cross-sectional study design. Dietary recalls may not fully reflect the dietary status of participants, which may influence assessment of exposure to some extent.

DISCLOSURES:

The study had no specific funding. The authors declared no conflicts of interest.

A version of this article appeared on Medscape.com.

TOPLINE:

Augmenting an intake of vitamin E, via both diet and supplements, may help prevent metabolic dysfunction–associated steatotic liver disease (MASLD), particularly in adults without hyperlipidemia, new data showed.

METHODOLOGY:

• MASLD (formerly known as nonalcoholic fatty liver disease) is a common chronic liver disease, and its severe form — metabolic dysfunction–associated steatohepatitis (formerly nonalcoholic steatohepatitis) — is associated with oxidative stress. As an antioxidant, vitamin E may protect against MASLD.
• Researchers analyzed data for 6122 adults from the National Health and Nutrition Examination Survey from 2017 to 2020.
• Information on dietary, supplementary, and total vitamin E intake was obtained from two 24-hour dietary recall interviews.
• The extent of hepatic steatosis was measured by liver ultrasound transient elastography, with MASLD defined as a controlled attenuated parameter threshold of ≥ 288 dB/m.

TAKEAWAY:

• After adjustment for sociodemographic characteristics, adults with MASLD had lower dietary and total intake of vitamin E, and dietary and total vitamin E intake was inversely associated with MASLD outcome.
• Adults in the top quartile of dietary vitamin E intake had approximately 40% lower odds of MASLD (odds ratio [OR], 0.60; P = .0091).
• Vitamin E supplement use was associated with 34% reduced odds of MASLD (OR, 0.66; P = .0249), whereas adults in the top quartile of total vitamin E intake had a 33% lower likelihood of MASLD (OR, 0.67; P = .0538).
• The findings were robust to sensitivity analysis, and the effects were stronger in those without hyperlipidemia.

IN PRACTICE:

“Increasing dietary sources of vitamin E is beneficial for preventing [MASLD], particularly in individuals without hyperlipidemia,” the researchers concluded.

SOURCE:

The study, with first author Xiangjun Qi, Guangzhou University of Chinese Medicine, Guangzhou, China, was published online in Scientific Reports.

LIMITATIONS:

Causality cannot be determined due to the cross-sectional study design. Dietary recalls may not fully reflect the dietary status of participants, which may influence assessment of exposure to some extent.

DISCLOSURES:

The study had no specific funding. The authors declared no conflicts of interest.

A version of this article appeared on Medscape.com.

TOPLINE:

Augmenting an intake of vitamin E, via both diet and supplements, may help prevent metabolic dysfunction–associated steatotic liver disease (MASLD), particularly in adults without hyperlipidemia, new data showed.

METHODOLOGY:

• MASLD (formerly known as nonalcoholic fatty liver disease) is a common chronic liver disease, and its severe form — metabolic dysfunction–associated steatohepatitis (formerly nonalcoholic steatohepatitis) — is associated with oxidative stress. As an antioxidant, vitamin E may protect against MASLD.
• Researchers analyzed data for 6122 adults from the National Health and Nutrition Examination Survey from 2017 to 2020.
• Information on dietary, supplementary, and total vitamin E intake was obtained from two 24-hour dietary recall interviews.
• The extent of hepatic steatosis was measured by liver ultrasound transient elastography, with MASLD defined as a controlled attenuated parameter threshold of ≥ 288 dB/m.

TAKEAWAY:

• After adjustment for sociodemographic characteristics, adults with MASLD had lower dietary and total intake of vitamin E, and dietary and total vitamin E intake was inversely associated with MASLD outcome.
• Adults in the top quartile of dietary vitamin E intake had approximately 40% lower odds of MASLD (odds ratio [OR], 0.60; P = .0091).
• Vitamin E supplement use was associated with 34% reduced odds of MASLD (OR, 0.66; P = .0249), whereas adults in the top quartile of total vitamin E intake had a 33% lower likelihood of MASLD (OR, 0.67; P = .0538).
• The findings were robust to sensitivity analysis, and the effects were stronger in those without hyperlipidemia.

IN PRACTICE:

“Increasing dietary sources of vitamin E is beneficial for preventing [MASLD], particularly in individuals without hyperlipidemia,” the researchers concluded.

SOURCE:

The study, with first author Xiangjun Qi, Guangzhou University of Chinese Medicine, Guangzhou, China, was published online in Scientific Reports.

LIMITATIONS:

Causality cannot be determined due to the cross-sectional study design. Dietary recalls may not fully reflect the dietary status of participants, which may influence assessment of exposure to some extent.

DISCLOSURES:

The study had no specific funding. The authors declared no conflicts of interest.

A version of this article appeared on Medscape.com.

This transcript has been edited for clarity.

The American Cancer Society has just published its cancer statistics for 2024. This is an annual report, the latest version of which has some alarming news for gastroenterologists. Usually, we think of being “number one” as a positive thing, but that’s not the case this year when it comes to the projections for colorectal cancer.

But first, let’s discuss the report’s overall findings. Broadly speaking, the news is quite good in that there’s been an aversion of over 4 million deaths since 1991. That decline over the past four decades is due to reductions in smoking, earlier detection, and improved screening and treatments for localized or metastatic disease. But these gains are now threatened by some offsets that we’re seeing, with increasing rates of six of the top 10 cancers in the past several years.
 

Increasing Rates of Gastrointestinal Cancers

The incidence rate of pancreas cancer has increased from 0.6% to 1% annually.

Pancreas cancer has a 5-year relative survival rate of 13%, which ranks as one of the three worst rates for cancers. This cancer represents a real screening challenge for us, as it typically presents asymptomatically.

Women have experienced a 2%-3% annual increase in incidence rates for liver cancer.

I suspect that this is due to cases of fibrotic liver disease resulting from viral hepatitis and metabolic liver diseases with nonalcoholic fatty liver and advanced fibrosis (F3 and F4). These cases may be carried over from before, thereby contributing to the increasing incremental cancer risk.

We can’t overlook the need for risk reduction here and should focus on applying regular screening efforts in our female patients. However, it’s also true that we require better liver cancer screening tests to accomplish that goal.
 

In Those Under 50, CRC the Leading Cause of Cancer Death in Men, Second in Women

I really want to focus on the news around colorectal cancer.

To put this in perspective, in the late 1990s, colorectal cancer was the fourth leading cause of death in men and women. The current report extrapolated 2024 projections using the Surveillance, Epidemiology, and End Results (SEER) database ending in 2020, which was necessary given the incremental time it takes to develop cancers. The SEER database suggests that in 2024, colorectal cancer in those younger than 50 years of age will become the number-one leading cause of cancer death in men and number-two in women. The increasing incidence of colorectal cancer in younger people is probably the result of a number of epidemiologic and other reasons.

The current report offers evidence of racial disparities in cancer mortality rates in general, which are twofold higher in Black people compared with White people, particularly for gastric cancer. There is also an evident disparity in Native Americans, who have higher rates of gastric and liver cancer. This is a reminder of the increasing need for equity to address racial disparities across these populations.

But returning to colon cancer, it’s a marked change to go from being the fourth-leading cause of cancer death in those younger than 50 years of age to being number one for men and number two for women.

Being “number one” is supposed to make you famous. This “number one,” however, should in fact be infamous. It’s a travesty, because colorectal cancer is a potentially preventable disease.

As we move into March, which happens to be Colorectal Cancer Awareness Month, hopefully this fires up some of the conversations you have with your younger at-risk population, who may be reticent or resistant to colorectal cancer screening.

We have to do better at getting this message out to that population at large. “Number one” is not where we want to be for this potentially preventable problem.
 

Dr. Johnson is professor of medicine and chief of gastroenterology at Eastern Virginia Medical School in Norfolk, Virginia, and a past president of the American College of Gastroenterology. His primary focus is the clinical practice of gastroenterology. He has published extensively in the internal medicine/gastroenterology literature, with principal research interests in esophageal and colon disease, and more recently in sleep and microbiome effects on gastrointestinal health and disease. He has disclosed ties with ISOTHRIVE and Johnson & Johnson.

A version of this article appeared on Medscape.com.

This transcript has been edited for clarity.

The American Cancer Society has just published its cancer statistics for 2024. This is an annual report, the latest version of which has some alarming news for gastroenterologists. Usually, we think of being “number one” as a positive thing, but that’s not the case this year when it comes to the projections for colorectal cancer.

But first, let’s discuss the report’s overall findings. Broadly speaking, the news is quite good in that there’s been an aversion of over 4 million deaths since 1991. That decline over the past four decades is due to reductions in smoking, earlier detection, and improved screening and treatments for localized or metastatic disease. But these gains are now threatened by some offsets that we’re seeing, with increasing rates of six of the top 10 cancers in the past several years.
 

Increasing Rates of Gastrointestinal Cancers

The incidence rate of pancreas cancer has increased from 0.6% to 1% annually.

Pancreas cancer has a 5-year relative survival rate of 13%, which ranks as one of the three worst rates for cancers. This cancer represents a real screening challenge for us, as it typically presents asymptomatically.

Women have experienced a 2%-3% annual increase in incidence rates for liver cancer.

I suspect that this is due to cases of fibrotic liver disease resulting from viral hepatitis and metabolic liver diseases with nonalcoholic fatty liver and advanced fibrosis (F3 and F4). These cases may be carried over from before, thereby contributing to the increasing incremental cancer risk.

We can’t overlook the need for risk reduction here and should focus on applying regular screening efforts in our female patients. However, it’s also true that we require better liver cancer screening tests to accomplish that goal.
 

In Those Under 50, CRC the Leading Cause of Cancer Death in Men, Second in Women

I really want to focus on the news around colorectal cancer.

To put this in perspective, in the late 1990s, colorectal cancer was the fourth leading cause of death in men and women. The current report extrapolated 2024 projections using the Surveillance, Epidemiology, and End Results (SEER) database ending in 2020, which was necessary given the incremental time it takes to develop cancers. The SEER database suggests that in 2024, colorectal cancer in those younger than 50 years of age will become the number-one leading cause of cancer death in men and number-two in women. The increasing incidence of colorectal cancer in younger people is probably the result of a number of epidemiologic and other reasons.

The current report offers evidence of racial disparities in cancer mortality rates in general, which are twofold higher in Black people compared with White people, particularly for gastric cancer. There is also an evident disparity in Native Americans, who have higher rates of gastric and liver cancer. This is a reminder of the increasing need for equity to address racial disparities across these populations.

But returning to colon cancer, it’s a marked change to go from being the fourth-leading cause of cancer death in those younger than 50 years of age to being number one for men and number two for women.

Being “number one” is supposed to make you famous. This “number one,” however, should in fact be infamous. It’s a travesty, because colorectal cancer is a potentially preventable disease.

As we move into March, which happens to be Colorectal Cancer Awareness Month, hopefully this fires up some of the conversations you have with your younger at-risk population, who may be reticent or resistant to colorectal cancer screening.

We have to do better at getting this message out to that population at large. “Number one” is not where we want to be for this potentially preventable problem.
 

Dr. Johnson is professor of medicine and chief of gastroenterology at Eastern Virginia Medical School in Norfolk, Virginia, and a past president of the American College of Gastroenterology. His primary focus is the clinical practice of gastroenterology. He has published extensively in the internal medicine/gastroenterology literature, with principal research interests in esophageal and colon disease, and more recently in sleep and microbiome effects on gastrointestinal health and disease. He has disclosed ties with ISOTHRIVE and Johnson & Johnson.

A version of this article appeared on Medscape.com.

This transcript has been edited for clarity.

The American Cancer Society has just published its cancer statistics for 2024. This is an annual report, the latest version of which has some alarming news for gastroenterologists. Usually, we think of being “number one” as a positive thing, but that’s not the case this year when it comes to the projections for colorectal cancer.

But first, let’s discuss the report’s overall findings. Broadly speaking, the news is quite good in that there’s been an aversion of over 4 million deaths since 1991. That decline over the past four decades is due to reductions in smoking, earlier detection, and improved screening and treatments for localized or metastatic disease. But these gains are now threatened by some offsets that we’re seeing, with increasing rates of six of the top 10 cancers in the past several years.
 

Increasing Rates of Gastrointestinal Cancers

The incidence rate of pancreas cancer has increased from 0.6% to 1% annually.

Pancreas cancer has a 5-year relative survival rate of 13%, which ranks as one of the three worst rates for cancers. This cancer represents a real screening challenge for us, as it typically presents asymptomatically.

Women have experienced a 2%-3% annual increase in incidence rates for liver cancer.

I suspect that this is due to cases of fibrotic liver disease resulting from viral hepatitis and metabolic liver diseases with nonalcoholic fatty liver and advanced fibrosis (F3 and F4). These cases may be carried over from before, thereby contributing to the increasing incremental cancer risk.

We can’t overlook the need for risk reduction here and should focus on applying regular screening efforts in our female patients. However, it’s also true that we require better liver cancer screening tests to accomplish that goal.
 

In Those Under 50, CRC the Leading Cause of Cancer Death in Men, Second in Women

I really want to focus on the news around colorectal cancer.

To put this in perspective, in the late 1990s, colorectal cancer was the fourth leading cause of death in men and women. The current report extrapolated 2024 projections using the Surveillance, Epidemiology, and End Results (SEER) database ending in 2020, which was necessary given the incremental time it takes to develop cancers. The SEER database suggests that in 2024, colorectal cancer in those younger than 50 years of age will become the number-one leading cause of cancer death in men and number-two in women. The increasing incidence of colorectal cancer in younger people is probably the result of a number of epidemiologic and other reasons.

The current report offers evidence of racial disparities in cancer mortality rates in general, which are twofold higher in Black people compared with White people, particularly for gastric cancer. There is also an evident disparity in Native Americans, who have higher rates of gastric and liver cancer. This is a reminder of the increasing need for equity to address racial disparities across these populations.

But returning to colon cancer, it’s a marked change to go from being the fourth-leading cause of cancer death in those younger than 50 years of age to being number one for men and number two for women.

Being “number one” is supposed to make you famous. This “number one,” however, should in fact be infamous. It’s a travesty, because colorectal cancer is a potentially preventable disease.

As we move into March, which happens to be Colorectal Cancer Awareness Month, hopefully this fires up some of the conversations you have with your younger at-risk population, who may be reticent or resistant to colorectal cancer screening.

We have to do better at getting this message out to that population at large. “Number one” is not where we want to be for this potentially preventable problem.
 

Dr. Johnson is professor of medicine and chief of gastroenterology at Eastern Virginia Medical School in Norfolk, Virginia, and a past president of the American College of Gastroenterology. His primary focus is the clinical practice of gastroenterology. He has published extensively in the internal medicine/gastroenterology literature, with principal research interests in esophageal and colon disease, and more recently in sleep and microbiome effects on gastrointestinal health and disease. He has disclosed ties with ISOTHRIVE and Johnson & Johnson.

A version of this article appeared on Medscape.com.