Liver Disease

Gilead Sciences Inc. and Aetna Inc. have announced a partnership wherein the drug company will offer Aetna’s approximately 20 million health plan members a discounted rate on its hepatitis C drugs, Sovaldi (sofosbuvir) and Harvoni (ledipasvir and sofosbuvir).

The amount of the discount has not yet been announced, although it should be significantly less than the current rate: Sovaldi costs $84,000 for a 12-week course of treatment, and Harvoni costs $94,500 for 12 weeks.

For more information, go to www.reuters.com.

mbock@frontlinemedcom.com

Gilead Sciences Inc. and Aetna Inc. have announced a partnership wherein the drug company will offer Aetna’s approximately 20 million health plan members a discounted rate on its hepatitis C drugs, Sovaldi (sofosbuvir) and Harvoni (ledipasvir and sofosbuvir).

The amount of the discount has not yet been announced, although it should be significantly less than the current rate: Sovaldi costs $84,000 for a 12-week course of treatment, and Harvoni costs $94,500 for 12 weeks.

For more information, go to www.reuters.com.

mbock@frontlinemedcom.com

Gilead Sciences Inc. and Aetna Inc. have announced a partnership wherein the drug company will offer Aetna’s approximately 20 million health plan members a discounted rate on its hepatitis C drugs, Sovaldi (sofosbuvir) and Harvoni (ledipasvir and sofosbuvir).

The amount of the discount has not yet been announced, although it should be significantly less than the current rate: Sovaldi costs $84,000 for a 12-week course of treatment, and Harvoni costs $94,500 for 12 weeks.

For more information, go to www.reuters.com.

mbock@frontlinemedcom.com

The recent advent of new treatments for hepatitis C prompted organizations including the Centers for Disease Control and Prevention, the U.S. Preventive Services Task Force, and the World Health Organization to recommend expanded hepatitis C screening, but such screening may be premature, according to a subject analysis.

Too much uncertainty exists regarding the validity of surrogate markers for treatment efficacy that were used in trials, and evidence regarding clinical outcomes and screening strategies is lacking, according to Dr. Ronald L. Koretz of the University of California, Los Angeles, and his colleagues, who evaluated the current understanding of the incidence and natural course of hepatitis C infection, treatment efficacy, and potential harms of treatment for their analysis.

Courtesy NIH

The best available data suggest that 80%-85% of patients with chronic hepatitis C will die of nonhepatic causes; thus screening could lead to unnecessary treatment. This is important, as safety data for newer drugs are limited, and the existing data suggest a small but concerning rate of serious adverse events associated with the use of some treatments and treatment regimens; the risk-benefit profile of treatment cannot be adequately evaluated because of the lack of data regarding treatment benefits, the investigators reported online Jan. 13 in the British Medical Journal ([doi:10.10036/bmj.g7809]).

Clinical trials to determine the outcomes of treatment in screen-detected patients, as well as the long-term hazards of treatment, are needed, they said, noting that currently available trials included small numbers of patients and/or only short-term follow-up. Until data from such trials are available, physicians should not be pressured to enforce recommended screening strategies “out of enthusiasm for new treatments that have not yet been shown to cause long-term clinical improvement,” they concluded.

Dr. Koretz is a member of the editorial board of the Cochrane Hepato-Biliary Group. The authors reported having no other financial conflicts.

The recent advent of new treatments for hepatitis C prompted organizations including the Centers for Disease Control and Prevention, the U.S. Preventive Services Task Force, and the World Health Organization to recommend expanded hepatitis C screening, but such screening may be premature, according to a subject analysis.

Too much uncertainty exists regarding the validity of surrogate markers for treatment efficacy that were used in trials, and evidence regarding clinical outcomes and screening strategies is lacking, according to Dr. Ronald L. Koretz of the University of California, Los Angeles, and his colleagues, who evaluated the current understanding of the incidence and natural course of hepatitis C infection, treatment efficacy, and potential harms of treatment for their analysis.

Courtesy NIH

The best available data suggest that 80%-85% of patients with chronic hepatitis C will die of nonhepatic causes; thus screening could lead to unnecessary treatment. This is important, as safety data for newer drugs are limited, and the existing data suggest a small but concerning rate of serious adverse events associated with the use of some treatments and treatment regimens; the risk-benefit profile of treatment cannot be adequately evaluated because of the lack of data regarding treatment benefits, the investigators reported online Jan. 13 in the British Medical Journal ([doi:10.10036/bmj.g7809]).

Clinical trials to determine the outcomes of treatment in screen-detected patients, as well as the long-term hazards of treatment, are needed, they said, noting that currently available trials included small numbers of patients and/or only short-term follow-up. Until data from such trials are available, physicians should not be pressured to enforce recommended screening strategies “out of enthusiasm for new treatments that have not yet been shown to cause long-term clinical improvement,” they concluded.

Dr. Koretz is a member of the editorial board of the Cochrane Hepato-Biliary Group. The authors reported having no other financial conflicts.

The recent advent of new treatments for hepatitis C prompted organizations including the Centers for Disease Control and Prevention, the U.S. Preventive Services Task Force, and the World Health Organization to recommend expanded hepatitis C screening, but such screening may be premature, according to a subject analysis.

Too much uncertainty exists regarding the validity of surrogate markers for treatment efficacy that were used in trials, and evidence regarding clinical outcomes and screening strategies is lacking, according to Dr. Ronald L. Koretz of the University of California, Los Angeles, and his colleagues, who evaluated the current understanding of the incidence and natural course of hepatitis C infection, treatment efficacy, and potential harms of treatment for their analysis.

Courtesy NIH

The best available data suggest that 80%-85% of patients with chronic hepatitis C will die of nonhepatic causes; thus screening could lead to unnecessary treatment. This is important, as safety data for newer drugs are limited, and the existing data suggest a small but concerning rate of serious adverse events associated with the use of some treatments and treatment regimens; the risk-benefit profile of treatment cannot be adequately evaluated because of the lack of data regarding treatment benefits, the investigators reported online Jan. 13 in the British Medical Journal ([doi:10.10036/bmj.g7809]).

Clinical trials to determine the outcomes of treatment in screen-detected patients, as well as the long-term hazards of treatment, are needed, they said, noting that currently available trials included small numbers of patients and/or only short-term follow-up. Until data from such trials are available, physicians should not be pressured to enforce recommended screening strategies “out of enthusiasm for new treatments that have not yet been shown to cause long-term clinical improvement,” they concluded.

Dr. Koretz is a member of the editorial board of the Cochrane Hepato-Biliary Group. The authors reported having no other financial conflicts.

BOSTON – Screening all adults born between 1945 and 1965 for hepatitis C and then treating all infected patients with oral drug regimens is the most cost effective strategy for society, because better outcomes more than offset the higher costs of wider screening and newer drugs, Dr. Zobair Younossi said.

A computer simulation analysis that compared four strategies for screening and treatment (plus the option of no screening or treatment) found that birth cohort screening and treatment of all hepatitis C virus–positive patients would save more than 4 million life-years at an incremental cost of $36,585 per quality-adjusted life-year (QALY), he reported at the annual meeting of the American Association for the Study of Liver Diseases.

That strategy produced an incremental cost-effectiveness ratio well below the widely accepted threshold of $50,000 per QALY used to define cost effectiveness in health care, said Dr. Younossi, professor of medicine at Virginia Commonwealth University’s Inova Campus and chair of Liver Disease Services for Inova, Falls Church, Va.

In first-generation treatment with direct-acting antivirals – namely, triple therapy with protease inhibitors – the mean cost to achieve a sustained virologic response was $172,889, he said, “and we did not get a lot of pushback from the payers at that point.”

Risk-based screening for HCV has been recommended, and the Centers for Disease Control and Prevention recently recommended birth cohort screening of people born between 1945 and 1965, the so-called baby boomers, Dr. Younossi said.

Still, studies suggest that less than 10% of patients with chronic HCV have been treated successfully, because of the failure of risk-based screening to identify all infected patients and the low efficacy and high rate of side effects from regimens based on interferon and ribavirin, he said.

Higher costs, lower risks

Dr. Younossi’s study used computer simulations to analyze the economic impact of various screening strategies followed by treatment with oral anti-HCV regimens.

The four strategies involved either risk-based screening or birth cohort screening, followed by treatment that either gave all HCV-infected patients oral regimens or that based treatment on staging, giving oral medications only to patients with significant fibrosis. The investigators also considered a fifth strategy: no screening and no treatment.

Birth cohort screening would lead to 1,162,323 patients being diagnosed with previously unknown chronic HCV, they estimated.

To estimate treatment costs, the investigators began with risk-based screening probabilities from a previous study: They assumed that 98% of patients would be medically eligible for treatment and have no contraindications to all-oral treatment regimens, and 98% of those treated would achieve a sustained virologic response for 12 weeks (SVR12), based on results of published trials.

The cost of oral direct-acting antiviral therapy was based on the cost of sofosbuvir – around $1,000 per day for 12 weeks, Dr. Younossi said. Costs for testing, staging, monitoring, and other data were taken from previous treatment models. The investigators calculated QALY from patients’ health utility reports in clinical trials.

Costs averaged approximately $88,000 per patient with birth cohort screening and treating all positive patients, $72,000 per patient with birth cohort screening and treatment based on staging, $60,000-$61,000 per patient for the risk-based screening strategies, and $53,000 per patient with no screening and no treatment.

The probabilities of cirrhosis, hepatocellular carcinoma, or liver transplant were much lower with either birth cohort screening strategy, however, compared with the risk-based strategies or no screening. The probability of cirrhosis was approximately 1% with birth cohort screening and treating all positive patients, 7% with birth cohort screening and treatment based on staging, 55%-60% with the risk-based strategies, and 67% with no screening.

The risk of hepatocellular carcinoma was 4% with birth cohort screening and treating all positive patients, 5% with birth cohort screening and treatment based on staging, 15% with either risk-based screening strategy, and 20% with no screening. The risk of liver transplant was 0.6% with either birth cohort screening strategy, 3% with either risk-based screening strategy, and nearly 4% with no screening.

A total of 4% of patients would be expected to die of liver-related causes after birth cohort screening and treating all positive patients, compared with 7% liver-related mortality after birth cohort screening and staging-based treatment, 25% liver-related mortality in either of the risk-based screening groups, and 34% liver-related mortality with no screening.

HCV costlier than other conditions?

When considering governmental health policy and budgetary issues, Dr. Younossi explained, the cost of curing HCV is not very different from lifetime treatment costs for type 2 diabetes, rheumatoid arthritis, or breast cancer with metastases – and it’s significantly lower than lifetime treatment costs for HIV or relapsing-remitting multiple sclerosis.

As advocates for patients, physicians need to lobby officials so that “as they are dividing the pie, hepatology and HCV are represented,” he said. “These regimens are cost effective.”

The study was an underestimation of savings from birth cohort screening and treating all HCV positives, Dr. Younossi noted, because it did not incorporate an estimated $3 billion per year in savings from work productivity in the United States by curing HCV.

A physician in the audience countered Dr. Younossi’s call for more enlightened health policy supporting funding for HCV treatment, noting that drug companies also need to be pressured to lower the price of the newer drugs.

“The biggest bridge we have to cross is the cost of the drugs,” he said. “This is like denying somebody treatment for tuberculosis by making the cost of the drug too high.”

“I agree,” Dr. Younossi said. “We have to focus on our colleagues in the industry. But we also have to focus on our colleagues in Congress and the policymakers to make sure that, even if we get help from the industry side, we also get help from the policymakers to provide us” with the funding for access to HCV screening and treatment.

Dr. Younossi reported having no financial disclosures. One of his coinvestigators reported financial associations with Gilead and Bristol-Myers Squibb.

sboschert@frontlinemedcom.com

On Twitter @sherryboschert

AGA RESOURCE

View the technical review, guideline and clinical decision support tool at www.gastro.org/guideline. Join the guideline authors for a webinar about the guidelines on Jan. 29, 2015, at noon ET. Register at http://ow.ly/FWcsx.

BOSTON – Screening all adults born between 1945 and 1965 for hepatitis C and then treating all infected patients with oral drug regimens is the most cost effective strategy for society, because better outcomes more than offset the higher costs of wider screening and newer drugs, Dr. Zobair Younossi said.

A computer simulation analysis that compared four strategies for screening and treatment (plus the option of no screening or treatment) found that birth cohort screening and treatment of all hepatitis C virus–positive patients would save more than 4 million life-years at an incremental cost of $36,585 per quality-adjusted life-year (QALY), he reported at the annual meeting of the American Association for the Study of Liver Diseases.

That strategy produced an incremental cost-effectiveness ratio well below the widely accepted threshold of $50,000 per QALY used to define cost effectiveness in health care, said Dr. Younossi, professor of medicine at Virginia Commonwealth University’s Inova Campus and chair of Liver Disease Services for Inova, Falls Church, Va.

In first-generation treatment with direct-acting antivirals – namely, triple therapy with protease inhibitors – the mean cost to achieve a sustained virologic response was $172,889, he said, “and we did not get a lot of pushback from the payers at that point.”

Risk-based screening for HCV has been recommended, and the Centers for Disease Control and Prevention recently recommended birth cohort screening of people born between 1945 and 1965, the so-called baby boomers, Dr. Younossi said.

Still, studies suggest that less than 10% of patients with chronic HCV have been treated successfully, because of the failure of risk-based screening to identify all infected patients and the low efficacy and high rate of side effects from regimens based on interferon and ribavirin, he said.

Higher costs, lower risks

Dr. Younossi’s study used computer simulations to analyze the economic impact of various screening strategies followed by treatment with oral anti-HCV regimens.

The four strategies involved either risk-based screening or birth cohort screening, followed by treatment that either gave all HCV-infected patients oral regimens or that based treatment on staging, giving oral medications only to patients with significant fibrosis. The investigators also considered a fifth strategy: no screening and no treatment.

Birth cohort screening would lead to 1,162,323 patients being diagnosed with previously unknown chronic HCV, they estimated.

To estimate treatment costs, the investigators began with risk-based screening probabilities from a previous study: They assumed that 98% of patients would be medically eligible for treatment and have no contraindications to all-oral treatment regimens, and 98% of those treated would achieve a sustained virologic response for 12 weeks (SVR12), based on results of published trials.

The cost of oral direct-acting antiviral therapy was based on the cost of sofosbuvir – around $1,000 per day for 12 weeks, Dr. Younossi said. Costs for testing, staging, monitoring, and other data were taken from previous treatment models. The investigators calculated QALY from patients’ health utility reports in clinical trials.

Costs averaged approximately $88,000 per patient with birth cohort screening and treating all positive patients, $72,000 per patient with birth cohort screening and treatment based on staging, $60,000-$61,000 per patient for the risk-based screening strategies, and $53,000 per patient with no screening and no treatment.

The probabilities of cirrhosis, hepatocellular carcinoma, or liver transplant were much lower with either birth cohort screening strategy, however, compared with the risk-based strategies or no screening. The probability of cirrhosis was approximately 1% with birth cohort screening and treating all positive patients, 7% with birth cohort screening and treatment based on staging, 55%-60% with the risk-based strategies, and 67% with no screening.

The risk of hepatocellular carcinoma was 4% with birth cohort screening and treating all positive patients, 5% with birth cohort screening and treatment based on staging, 15% with either risk-based screening strategy, and 20% with no screening. The risk of liver transplant was 0.6% with either birth cohort screening strategy, 3% with either risk-based screening strategy, and nearly 4% with no screening.

A total of 4% of patients would be expected to die of liver-related causes after birth cohort screening and treating all positive patients, compared with 7% liver-related mortality after birth cohort screening and staging-based treatment, 25% liver-related mortality in either of the risk-based screening groups, and 34% liver-related mortality with no screening.

HCV costlier than other conditions?

When considering governmental health policy and budgetary issues, Dr. Younossi explained, the cost of curing HCV is not very different from lifetime treatment costs for type 2 diabetes, rheumatoid arthritis, or breast cancer with metastases – and it’s significantly lower than lifetime treatment costs for HIV or relapsing-remitting multiple sclerosis.

As advocates for patients, physicians need to lobby officials so that “as they are dividing the pie, hepatology and HCV are represented,” he said. “These regimens are cost effective.”

The study was an underestimation of savings from birth cohort screening and treating all HCV positives, Dr. Younossi noted, because it did not incorporate an estimated $3 billion per year in savings from work productivity in the United States by curing HCV.

A physician in the audience countered Dr. Younossi’s call for more enlightened health policy supporting funding for HCV treatment, noting that drug companies also need to be pressured to lower the price of the newer drugs.

“The biggest bridge we have to cross is the cost of the drugs,” he said. “This is like denying somebody treatment for tuberculosis by making the cost of the drug too high.”

“I agree,” Dr. Younossi said. “We have to focus on our colleagues in the industry. But we also have to focus on our colleagues in Congress and the policymakers to make sure that, even if we get help from the industry side, we also get help from the policymakers to provide us” with the funding for access to HCV screening and treatment.

Dr. Younossi reported having no financial disclosures. One of his coinvestigators reported financial associations with Gilead and Bristol-Myers Squibb.

sboschert@frontlinemedcom.com

On Twitter @sherryboschert

AGA RESOURCE

View the technical review, guideline and clinical decision support tool at www.gastro.org/guideline. Join the guideline authors for a webinar about the guidelines on Jan. 29, 2015, at noon ET. Register at http://ow.ly/FWcsx.

BOSTON – Screening all adults born between 1945 and 1965 for hepatitis C and then treating all infected patients with oral drug regimens is the most cost effective strategy for society, because better outcomes more than offset the higher costs of wider screening and newer drugs, Dr. Zobair Younossi said.

A computer simulation analysis that compared four strategies for screening and treatment (plus the option of no screening or treatment) found that birth cohort screening and treatment of all hepatitis C virus–positive patients would save more than 4 million life-years at an incremental cost of $36,585 per quality-adjusted life-year (QALY), he reported at the annual meeting of the American Association for the Study of Liver Diseases.

That strategy produced an incremental cost-effectiveness ratio well below the widely accepted threshold of $50,000 per QALY used to define cost effectiveness in health care, said Dr. Younossi, professor of medicine at Virginia Commonwealth University’s Inova Campus and chair of Liver Disease Services for Inova, Falls Church, Va.

In first-generation treatment with direct-acting antivirals – namely, triple therapy with protease inhibitors – the mean cost to achieve a sustained virologic response was $172,889, he said, “and we did not get a lot of pushback from the payers at that point.”

Risk-based screening for HCV has been recommended, and the Centers for Disease Control and Prevention recently recommended birth cohort screening of people born between 1945 and 1965, the so-called baby boomers, Dr. Younossi said.

Still, studies suggest that less than 10% of patients with chronic HCV have been treated successfully, because of the failure of risk-based screening to identify all infected patients and the low efficacy and high rate of side effects from regimens based on interferon and ribavirin, he said.

Higher costs, lower risks

Dr. Younossi’s study used computer simulations to analyze the economic impact of various screening strategies followed by treatment with oral anti-HCV regimens.

The four strategies involved either risk-based screening or birth cohort screening, followed by treatment that either gave all HCV-infected patients oral regimens or that based treatment on staging, giving oral medications only to patients with significant fibrosis. The investigators also considered a fifth strategy: no screening and no treatment.

Birth cohort screening would lead to 1,162,323 patients being diagnosed with previously unknown chronic HCV, they estimated.

To estimate treatment costs, the investigators began with risk-based screening probabilities from a previous study: They assumed that 98% of patients would be medically eligible for treatment and have no contraindications to all-oral treatment regimens, and 98% of those treated would achieve a sustained virologic response for 12 weeks (SVR12), based on results of published trials.

The cost of oral direct-acting antiviral therapy was based on the cost of sofosbuvir – around $1,000 per day for 12 weeks, Dr. Younossi said. Costs for testing, staging, monitoring, and other data were taken from previous treatment models. The investigators calculated QALY from patients’ health utility reports in clinical trials.

Costs averaged approximately $88,000 per patient with birth cohort screening and treating all positive patients, $72,000 per patient with birth cohort screening and treatment based on staging, $60,000-$61,000 per patient for the risk-based screening strategies, and $53,000 per patient with no screening and no treatment.

The probabilities of cirrhosis, hepatocellular carcinoma, or liver transplant were much lower with either birth cohort screening strategy, however, compared with the risk-based strategies or no screening. The probability of cirrhosis was approximately 1% with birth cohort screening and treating all positive patients, 7% with birth cohort screening and treatment based on staging, 55%-60% with the risk-based strategies, and 67% with no screening.

The risk of hepatocellular carcinoma was 4% with birth cohort screening and treating all positive patients, 5% with birth cohort screening and treatment based on staging, 15% with either risk-based screening strategy, and 20% with no screening. The risk of liver transplant was 0.6% with either birth cohort screening strategy, 3% with either risk-based screening strategy, and nearly 4% with no screening.

A total of 4% of patients would be expected to die of liver-related causes after birth cohort screening and treating all positive patients, compared with 7% liver-related mortality after birth cohort screening and staging-based treatment, 25% liver-related mortality in either of the risk-based screening groups, and 34% liver-related mortality with no screening.

HCV costlier than other conditions?

When considering governmental health policy and budgetary issues, Dr. Younossi explained, the cost of curing HCV is not very different from lifetime treatment costs for type 2 diabetes, rheumatoid arthritis, or breast cancer with metastases – and it’s significantly lower than lifetime treatment costs for HIV or relapsing-remitting multiple sclerosis.

As advocates for patients, physicians need to lobby officials so that “as they are dividing the pie, hepatology and HCV are represented,” he said. “These regimens are cost effective.”

The study was an underestimation of savings from birth cohort screening and treating all HCV positives, Dr. Younossi noted, because it did not incorporate an estimated $3 billion per year in savings from work productivity in the United States by curing HCV.

A physician in the audience countered Dr. Younossi’s call for more enlightened health policy supporting funding for HCV treatment, noting that drug companies also need to be pressured to lower the price of the newer drugs.

“The biggest bridge we have to cross is the cost of the drugs,” he said. “This is like denying somebody treatment for tuberculosis by making the cost of the drug too high.”

“I agree,” Dr. Younossi said. “We have to focus on our colleagues in the industry. But we also have to focus on our colleagues in Congress and the policymakers to make sure that, even if we get help from the industry side, we also get help from the policymakers to provide us” with the funding for access to HCV screening and treatment.

Dr. Younossi reported having no financial disclosures. One of his coinvestigators reported financial associations with Gilead and Bristol-Myers Squibb.

sboschert@frontlinemedcom.com

On Twitter @sherryboschert

AGA RESOURCE

View the technical review, guideline and clinical decision support tool at www.gastro.org/guideline. Join the guideline authors for a webinar about the guidelines on Jan. 29, 2015, at noon ET. Register at http://ow.ly/FWcsx.

BOSTON – A 16-week diet and exercise program reduced body weight and portal pressure in a prospective pilot study of 50 obese patients with cirrhosis and portal hypertension.

Twenty-six patients achieved a clinically relevant weight loss of at least 5%, compared with baseline weight (52% of the cohort). The hepatic venous pressure gradient (HVPG) decreased by at least 10% in 21 patients (42%), compared with baseline, Dr. Annalisa Berzigotti and her associates reported at the annual meeting of the American Association for the Study of Liver Diseases.

Sherry Boschert/Frontline Medical News

Obesity has been shown to increase the risk of clinical decompensation in patients with compensated cirrhosis and portal hypertension, possibly by increasing portal hypertension, said Dr. Berzigotti of the Networked Research Center for Hepatic and Digestive Diseases (CIBERehd), Barcelona.

“An intensive 16-week program of tailored diet and moderate exercise can be safely recommended to obtain weight loss,” she said.

Dr. Berzigotti and her associates at two Spanish centers put patients through a 16-week program of a normoproteic, hypocaloric diet supervised by nutritionists. It followed a personalized decrease of 500-1,000 kcal/day, with 20%-25% of the diet consisting of proteins. The exercise intervention consisted of 60 minutes per week of supervised, moderately-intense physical activity in small groups plus personalized advice and use of a daily physical activity log.

Patients had a baseline HVPG of at least 6 mm Hg with or without esophageal varices and regardless of whether they were receiving nonselective beta-blocker medications.

The investigators recruited 60 patients, 50 of whom completed the study and were included in the analysis.

The lifestyle intervention decreased the mean body weight by 5 kg and the median body weight by 5%, which was associated with significant decreases in waist circumference and percentage body fat. Eight patients achieved at least a 10% reduction in body weight (16%), she reported.

The mean HVPG decreased significantly from 13.9 mm Hg at baseline to 12.3 mm Hg after treatment, with an average 11% reduction. The HVPG decreased by at least 20% in 12 patients (24%).

Four patients who lost at least 5% of their body weight reduced their HVPG to below 10 mm Hg. Patients who lost at least 10% of body weight reduced their HVPG to a greater degree than did patients who lost less than 10% of body weight, with 24% and 8% reductions in HVPG, respectively.

Changes in body weight and HVPG were more subtle in patients with diabetes than in those without diabetes. Results did not differ significantly across other subgroups based on cirrhosis etiology, clinically significant portal hypertension and esophageal varices, treatment with nonselective beta-blockers, history of variceal bleeding, or medical center.

No patients clinically decompensated during the study. Patients’ Child-Pugh scores and Model for End-Stage Liver Disease scores did not change.

Patients who lost weight kept it off for 6 months, with average weights of 86 kg at 16 weeks and 85 kg at a 6-month follow-up.

Patients had a mean age of 56 years and 62% were male. The etiologies of cirrhosis were viral in 36% of patients, alcoholic in 38%, and nonalcoholic steatohepatitis in 26%. Patients had an average body mass index of 33 kg/m², and 72% had an HVPG of at least 10 mm Hg at baseline. Thirty percent of patients had a previous variceal hemorrhage but currently were compensated. Sixty-two percent of patients had a history of esophageal varices and 60% were on nonselective beta-blockers.

Dr. Berzigotti reported having no financial disclosures. One of her associates reported financial associations with Falk, Gilead, Norgine, Ono Pharma USA, Intercept Pharmaceuticals, Exalenz Bioscience, Almirall, and Conatus Pharmaceuticals.

sboschert@frontlinemedcom.com

On Twitter @sherryboschert

BOSTON – A 16-week diet and exercise program reduced body weight and portal pressure in a prospective pilot study of 50 obese patients with cirrhosis and portal hypertension.

Twenty-six patients achieved a clinically relevant weight loss of at least 5%, compared with baseline weight (52% of the cohort). The hepatic venous pressure gradient (HVPG) decreased by at least 10% in 21 patients (42%), compared with baseline, Dr. Annalisa Berzigotti and her associates reported at the annual meeting of the American Association for the Study of Liver Diseases.

Sherry Boschert/Frontline Medical News

Obesity has been shown to increase the risk of clinical decompensation in patients with compensated cirrhosis and portal hypertension, possibly by increasing portal hypertension, said Dr. Berzigotti of the Networked Research Center for Hepatic and Digestive Diseases (CIBERehd), Barcelona.

“An intensive 16-week program of tailored diet and moderate exercise can be safely recommended to obtain weight loss,” she said.

Dr. Berzigotti and her associates at two Spanish centers put patients through a 16-week program of a normoproteic, hypocaloric diet supervised by nutritionists. It followed a personalized decrease of 500-1,000 kcal/day, with 20%-25% of the diet consisting of proteins. The exercise intervention consisted of 60 minutes per week of supervised, moderately-intense physical activity in small groups plus personalized advice and use of a daily physical activity log.

Patients had a baseline HVPG of at least 6 mm Hg with or without esophageal varices and regardless of whether they were receiving nonselective beta-blocker medications.

The investigators recruited 60 patients, 50 of whom completed the study and were included in the analysis.

The lifestyle intervention decreased the mean body weight by 5 kg and the median body weight by 5%, which was associated with significant decreases in waist circumference and percentage body fat. Eight patients achieved at least a 10% reduction in body weight (16%), she reported.

The mean HVPG decreased significantly from 13.9 mm Hg at baseline to 12.3 mm Hg after treatment, with an average 11% reduction. The HVPG decreased by at least 20% in 12 patients (24%).

Four patients who lost at least 5% of their body weight reduced their HVPG to below 10 mm Hg. Patients who lost at least 10% of body weight reduced their HVPG to a greater degree than did patients who lost less than 10% of body weight, with 24% and 8% reductions in HVPG, respectively.

Changes in body weight and HVPG were more subtle in patients with diabetes than in those without diabetes. Results did not differ significantly across other subgroups based on cirrhosis etiology, clinically significant portal hypertension and esophageal varices, treatment with nonselective beta-blockers, history of variceal bleeding, or medical center.

No patients clinically decompensated during the study. Patients’ Child-Pugh scores and Model for End-Stage Liver Disease scores did not change.

Patients who lost weight kept it off for 6 months, with average weights of 86 kg at 16 weeks and 85 kg at a 6-month follow-up.

Patients had a mean age of 56 years and 62% were male. The etiologies of cirrhosis were viral in 36% of patients, alcoholic in 38%, and nonalcoholic steatohepatitis in 26%. Patients had an average body mass index of 33 kg/m², and 72% had an HVPG of at least 10 mm Hg at baseline. Thirty percent of patients had a previous variceal hemorrhage but currently were compensated. Sixty-two percent of patients had a history of esophageal varices and 60% were on nonselective beta-blockers.

Dr. Berzigotti reported having no financial disclosures. One of her associates reported financial associations with Falk, Gilead, Norgine, Ono Pharma USA, Intercept Pharmaceuticals, Exalenz Bioscience, Almirall, and Conatus Pharmaceuticals.

sboschert@frontlinemedcom.com

On Twitter @sherryboschert

BOSTON – A 16-week diet and exercise program reduced body weight and portal pressure in a prospective pilot study of 50 obese patients with cirrhosis and portal hypertension.

Twenty-six patients achieved a clinically relevant weight loss of at least 5%, compared with baseline weight (52% of the cohort). The hepatic venous pressure gradient (HVPG) decreased by at least 10% in 21 patients (42%), compared with baseline, Dr. Annalisa Berzigotti and her associates reported at the annual meeting of the American Association for the Study of Liver Diseases.

Sherry Boschert/Frontline Medical News

Obesity has been shown to increase the risk of clinical decompensation in patients with compensated cirrhosis and portal hypertension, possibly by increasing portal hypertension, said Dr. Berzigotti of the Networked Research Center for Hepatic and Digestive Diseases (CIBERehd), Barcelona.

“An intensive 16-week program of tailored diet and moderate exercise can be safely recommended to obtain weight loss,” she said.

Dr. Berzigotti and her associates at two Spanish centers put patients through a 16-week program of a normoproteic, hypocaloric diet supervised by nutritionists. It followed a personalized decrease of 500-1,000 kcal/day, with 20%-25% of the diet consisting of proteins. The exercise intervention consisted of 60 minutes per week of supervised, moderately-intense physical activity in small groups plus personalized advice and use of a daily physical activity log.

Patients had a baseline HVPG of at least 6 mm Hg with or without esophageal varices and regardless of whether they were receiving nonselective beta-blocker medications.

The investigators recruited 60 patients, 50 of whom completed the study and were included in the analysis.

The lifestyle intervention decreased the mean body weight by 5 kg and the median body weight by 5%, which was associated with significant decreases in waist circumference and percentage body fat. Eight patients achieved at least a 10% reduction in body weight (16%), she reported.

The mean HVPG decreased significantly from 13.9 mm Hg at baseline to 12.3 mm Hg after treatment, with an average 11% reduction. The HVPG decreased by at least 20% in 12 patients (24%).

Four patients who lost at least 5% of their body weight reduced their HVPG to below 10 mm Hg. Patients who lost at least 10% of body weight reduced their HVPG to a greater degree than did patients who lost less than 10% of body weight, with 24% and 8% reductions in HVPG, respectively.

Changes in body weight and HVPG were more subtle in patients with diabetes than in those without diabetes. Results did not differ significantly across other subgroups based on cirrhosis etiology, clinically significant portal hypertension and esophageal varices, treatment with nonselective beta-blockers, history of variceal bleeding, or medical center.

No patients clinically decompensated during the study. Patients’ Child-Pugh scores and Model for End-Stage Liver Disease scores did not change.

Patients who lost weight kept it off for 6 months, with average weights of 86 kg at 16 weeks and 85 kg at a 6-month follow-up.

Patients had a mean age of 56 years and 62% were male. The etiologies of cirrhosis were viral in 36% of patients, alcoholic in 38%, and nonalcoholic steatohepatitis in 26%. Patients had an average body mass index of 33 kg/m², and 72% had an HVPG of at least 10 mm Hg at baseline. Thirty percent of patients had a previous variceal hemorrhage but currently were compensated. Sixty-two percent of patients had a history of esophageal varices and 60% were on nonselective beta-blockers.

Dr. Berzigotti reported having no financial disclosures. One of her associates reported financial associations with Falk, Gilead, Norgine, Ono Pharma USA, Intercept Pharmaceuticals, Exalenz Bioscience, Almirall, and Conatus Pharmaceuticals.

sboschert@frontlinemedcom.com

On Twitter @sherryboschert

BOSTON – Terlipressin proved noninferior to noradrenaline as a vasopressor for patients with cirrhosis and septic shock in an open-label study that randomized 84 patients.

Terlipressin also seemed to provide advantages over noradrenaline by contributing to greater hemodynamic stability, improved urine output, reduced variceal bleeding, a lower risk of spontaneous bacterial peritonitis, and reduced mortality in the first 48 hours but not at 28 days, Dr. Ashok K. Choudhury and his associates reported.

“Terlipressin is noninferior to noradrenaline as a vasopressor,” he said at the annual meeting of the American Association for the Study of Liver Diseases.

The investigators randomized consecutive, matched adults with cirrhosis and septic shock not responding to fluid resuscitation for 2 hours. They aimed to achieve a mean arterial pressure (MAP) > 65 mm Hg at 6 hours by treating 42 patients with a continuous infusion of terlipressin 1.3-5.2 mcg/min, stepped up every 15 minutes, and 42 patients with noradrenaline 7.5-6 mcg/min, stepped up every 15 minutes. Both groups received standard medical care of intravenous fluids, antibiotics, and ICU care.

The target MAP was reached within 6 hours in 28 patients on terlipressin (67%) and 23 patients on noradrenaline (55%), a difference that was not statistically significant, said Dr. Choudhury of the Institute of Liver and Biliary Sciences, New Delhi. He won a research award from the Association.

Patients in the two groups were matched by age, sex, etiology and severity of cirrhosis, and scores on the Model for End-Stage Liver Disease and the Sequential Organ Failure Assessment.

Spontaneous bacterial peritonitis was the main cause of sepsis at admission, followed by pneumonia, but pneumonia was the main cause of “second hit” pneumonia, he said.

Terlipressin therapy was associated with a lower failure rate at 6 hours, a greater likelihood of MAP maintenance with cessation of vasopressor requirements at 48 hours, and improved urine output at 24 hours, compared with noradrenaline treatment. At 48 hours, 19 of 40 patients on terlipressin (48%) and 11 of 30 patients on noradrenaline (36%) had an MAP > 65 mm Hg.

No patients on terlipressin developed a variceal bleed, compared with seven patients in the noradrenaline group (10%). Overall rates of adverse events did not differ significantly between groups, but were higher in the terlipressin group than in the noradrenaline group.

Better rates of lactate clearance, central venous oxygen saturation, and carbon dioxide gradient in venous-arterial blood gases in the terlipressin group were not statistically different from rates in the noradrenaline group.

Significantly more patients on terlipressin survived the first 48 hours than patients on noradrenaline, but by day 28 of follow-up survival rates did not differ significantly between groups.

On the whole, septic shock in these patients with cirrhosis was associated with a high mortality rate (80%). Twelve percent of patients were responsive to fluids in 2 hours.

Dr. Choudhury reported having no financial disclosures.

sboschert@frontlinemedcom.com

On Twitter @sherryboschert

BOSTON – Terlipressin proved noninferior to noradrenaline as a vasopressor for patients with cirrhosis and septic shock in an open-label study that randomized 84 patients.

Terlipressin also seemed to provide advantages over noradrenaline by contributing to greater hemodynamic stability, improved urine output, reduced variceal bleeding, a lower risk of spontaneous bacterial peritonitis, and reduced mortality in the first 48 hours but not at 28 days, Dr. Ashok K. Choudhury and his associates reported.

“Terlipressin is noninferior to noradrenaline as a vasopressor,” he said at the annual meeting of the American Association for the Study of Liver Diseases.

The investigators randomized consecutive, matched adults with cirrhosis and septic shock not responding to fluid resuscitation for 2 hours. They aimed to achieve a mean arterial pressure (MAP) > 65 mm Hg at 6 hours by treating 42 patients with a continuous infusion of terlipressin 1.3-5.2 mcg/min, stepped up every 15 minutes, and 42 patients with noradrenaline 7.5-6 mcg/min, stepped up every 15 minutes. Both groups received standard medical care of intravenous fluids, antibiotics, and ICU care.

The target MAP was reached within 6 hours in 28 patients on terlipressin (67%) and 23 patients on noradrenaline (55%), a difference that was not statistically significant, said Dr. Choudhury of the Institute of Liver and Biliary Sciences, New Delhi. He won a research award from the Association.

Patients in the two groups were matched by age, sex, etiology and severity of cirrhosis, and scores on the Model for End-Stage Liver Disease and the Sequential Organ Failure Assessment.

Spontaneous bacterial peritonitis was the main cause of sepsis at admission, followed by pneumonia, but pneumonia was the main cause of “second hit” pneumonia, he said.

Terlipressin therapy was associated with a lower failure rate at 6 hours, a greater likelihood of MAP maintenance with cessation of vasopressor requirements at 48 hours, and improved urine output at 24 hours, compared with noradrenaline treatment. At 48 hours, 19 of 40 patients on terlipressin (48%) and 11 of 30 patients on noradrenaline (36%) had an MAP > 65 mm Hg.

No patients on terlipressin developed a variceal bleed, compared with seven patients in the noradrenaline group (10%). Overall rates of adverse events did not differ significantly between groups, but were higher in the terlipressin group than in the noradrenaline group.

Better rates of lactate clearance, central venous oxygen saturation, and carbon dioxide gradient in venous-arterial blood gases in the terlipressin group were not statistically different from rates in the noradrenaline group.

Significantly more patients on terlipressin survived the first 48 hours than patients on noradrenaline, but by day 28 of follow-up survival rates did not differ significantly between groups.

On the whole, septic shock in these patients with cirrhosis was associated with a high mortality rate (80%). Twelve percent of patients were responsive to fluids in 2 hours.

Dr. Choudhury reported having no financial disclosures.

sboschert@frontlinemedcom.com

On Twitter @sherryboschert

BOSTON – Terlipressin proved noninferior to noradrenaline as a vasopressor for patients with cirrhosis and septic shock in an open-label study that randomized 84 patients.

Terlipressin also seemed to provide advantages over noradrenaline by contributing to greater hemodynamic stability, improved urine output, reduced variceal bleeding, a lower risk of spontaneous bacterial peritonitis, and reduced mortality in the first 48 hours but not at 28 days, Dr. Ashok K. Choudhury and his associates reported.

“Terlipressin is noninferior to noradrenaline as a vasopressor,” he said at the annual meeting of the American Association for the Study of Liver Diseases.

The investigators randomized consecutive, matched adults with cirrhosis and septic shock not responding to fluid resuscitation for 2 hours. They aimed to achieve a mean arterial pressure (MAP) > 65 mm Hg at 6 hours by treating 42 patients with a continuous infusion of terlipressin 1.3-5.2 mcg/min, stepped up every 15 minutes, and 42 patients with noradrenaline 7.5-6 mcg/min, stepped up every 15 minutes. Both groups received standard medical care of intravenous fluids, antibiotics, and ICU care.

The target MAP was reached within 6 hours in 28 patients on terlipressin (67%) and 23 patients on noradrenaline (55%), a difference that was not statistically significant, said Dr. Choudhury of the Institute of Liver and Biliary Sciences, New Delhi. He won a research award from the Association.

Patients in the two groups were matched by age, sex, etiology and severity of cirrhosis, and scores on the Model for End-Stage Liver Disease and the Sequential Organ Failure Assessment.

Spontaneous bacterial peritonitis was the main cause of sepsis at admission, followed by pneumonia, but pneumonia was the main cause of “second hit” pneumonia, he said.

Terlipressin therapy was associated with a lower failure rate at 6 hours, a greater likelihood of MAP maintenance with cessation of vasopressor requirements at 48 hours, and improved urine output at 24 hours, compared with noradrenaline treatment. At 48 hours, 19 of 40 patients on terlipressin (48%) and 11 of 30 patients on noradrenaline (36%) had an MAP > 65 mm Hg.

No patients on terlipressin developed a variceal bleed, compared with seven patients in the noradrenaline group (10%). Overall rates of adverse events did not differ significantly between groups, but were higher in the terlipressin group than in the noradrenaline group.

Better rates of lactate clearance, central venous oxygen saturation, and carbon dioxide gradient in venous-arterial blood gases in the terlipressin group were not statistically different from rates in the noradrenaline group.

Significantly more patients on terlipressin survived the first 48 hours than patients on noradrenaline, but by day 28 of follow-up survival rates did not differ significantly between groups.

On the whole, septic shock in these patients with cirrhosis was associated with a high mortality rate (80%). Twelve percent of patients were responsive to fluids in 2 hours.

Dr. Choudhury reported having no financial disclosures.

sboschert@frontlinemedcom.com

On Twitter @sherryboschert

Administration of a novel fatty acid–bile acid conjugate safely and significantly reduced liver fat content in patients with nonalcoholic fatty liver disease in a phase II trial.

Administration of resveratrol for 8 weeks, however, failed to improve any features of the disease in a separate placebo-controlled study.

Courtesy of Wikimedia /Nephron / Creative Commons License

In 60 patients aged 18-75 years in a randomized, double-blind, placebo-controlled study of the fatty acid–bile acid conjugate aramchol (Trima Israel Pharmaceutical Products Ltd. Maabarot), 3 months of treatment was associated with a decrease in liver fat content by a mean of 12.57% as measured by magnetic resonance spectroscopy, compared with an increase in liver fat by a mean of 6.39% in patients who received placebo, Dr. Rifaat Safadi of Hadassah University Medical Center, Jerusalem and colleagues reported in the DEcember issue of Clinical Gastroenterology and Hepatology.

The difference between the treatment and placebo groups was significant, even after age, sex, and body mass index were adjusted for.

Liver fat content also decreased in patients who received treatment with a 100-mg dose of aramchol, but the difference compared with placebo was not statistically significant, indicating a dose-response relationship in treated patients, the investigators said (Clin Gastroenterol Hepatol 2014[doi:10.1016/j.cgh.2014.04.038]).

A trend was seen for improvements over time in endothelial function and levels of alanine aminotransferase and adiponectin.

Patients in the study were from 10 centers in Israel, and all had biopsy-confirmed NAFLD (54 patients) or nonalcoholic steatohepatitis (NASH, 6 patients). They were randomized to receive 100 or 300 mg of aramchol or placebo once daily for 3 months.

No serious or drug-related adverse events occurred in the treated patients, the investigators said.

The findings suggest that aramchol is a candidate for the treatment of fatty liver–related diseases, which are “an increasingly relevant public health issue because of their association with the worldwide epidemics of diabetes and obesity,” and for which treatments are lacking, they said, concluding that longer trials in patients with NASH and metabolic complications are warranted to evaluate metabolic and histologic benefits of treatment.

Findings from the resveratrol study were less encouraging.

Eight weeks of treatment at 3,000 mg daily in overweight or obese men with NAFLD who were recruited from clinics in Brisbane from 2011 through 2012 was no better than placebo for improving insulin resistance, hepatic steatosis, or abdominal fat distribution, Dr. Veronique S. Chachay of the University of Queensland, Brisbane, Australia and her colleagues also reported in the December issue of Clinical Gastroenterology and Hepatology.

No changes were observed in plasma lipids or antioxidant activity, and levels of alanine and aspartate aminotransferases increased significantly (from 45 to 63 U/L and from 35 to 45 U/L, respectively) until week 6 in the 10 treated patients, compared with the 10 who received placebo (40 to 48 U/L and 36 to 38 U/L, respectively). Resveratrol did not significantly alter transcription of NQ01, PTP1B, IL6, or H01, the investigators said (Clin Gastroenterol Hepatol 2014[doi:10.106/j.cgh.2014.02.024]).

NAFLD is associated with abdominal obesity, insulin resistance, and inflammation, and while weight loss via calorie restriction is known to reduce features of the disease, there is no pharmacologic therapy available to achieve this end.

The investigators sought to determine if resveratrol – a polyphenol that has been shown to prevent high-energy diet-induced steatosis and insulin resistance in animals – might be beneficial in patients with NAFLD.

“The present study demonstrates that the preventive role of resveratrol observed in diet-induced preclinical models of NAFLD does not translate into a therapeutic role in clinically established NAFLD,” they said, adding that clinical dose-finding studies are “paramount to elucidate the dose-response relationship” and that “the purported calorie-restriction mimicking of resveratrol may require investigation in combination with dietary prescription, standard care, and lifestyle modifications to target adequately the complexity of dysregulation in obesity-related chronic disease.”

The aramchol study was supported by Galmed Medical Research, Ltd. Dr. Safadi reported having no disclosures. The resveratrol study was supported by the Princess Alexandra Research Foundation, the Lions Medical Research Foundation, and the National Health and Medical Research Council of Australia. The authors reported having no disclosures.

Administration of a novel fatty acid–bile acid conjugate safely and significantly reduced liver fat content in patients with nonalcoholic fatty liver disease in a phase II trial.

Administration of resveratrol for 8 weeks, however, failed to improve any features of the disease in a separate placebo-controlled study.

Courtesy of Wikimedia /Nephron / Creative Commons License

In 60 patients aged 18-75 years in a randomized, double-blind, placebo-controlled study of the fatty acid–bile acid conjugate aramchol (Trima Israel Pharmaceutical Products Ltd. Maabarot), 3 months of treatment was associated with a decrease in liver fat content by a mean of 12.57% as measured by magnetic resonance spectroscopy, compared with an increase in liver fat by a mean of 6.39% in patients who received placebo, Dr. Rifaat Safadi of Hadassah University Medical Center, Jerusalem and colleagues reported in the DEcember issue of Clinical Gastroenterology and Hepatology.

The difference between the treatment and placebo groups was significant, even after age, sex, and body mass index were adjusted for.

Liver fat content also decreased in patients who received treatment with a 100-mg dose of aramchol, but the difference compared with placebo was not statistically significant, indicating a dose-response relationship in treated patients, the investigators said (Clin Gastroenterol Hepatol 2014[doi:10.1016/j.cgh.2014.04.038]).

A trend was seen for improvements over time in endothelial function and levels of alanine aminotransferase and adiponectin.

Patients in the study were from 10 centers in Israel, and all had biopsy-confirmed NAFLD (54 patients) or nonalcoholic steatohepatitis (NASH, 6 patients). They were randomized to receive 100 or 300 mg of aramchol or placebo once daily for 3 months.

No serious or drug-related adverse events occurred in the treated patients, the investigators said.

The findings suggest that aramchol is a candidate for the treatment of fatty liver–related diseases, which are “an increasingly relevant public health issue because of their association with the worldwide epidemics of diabetes and obesity,” and for which treatments are lacking, they said, concluding that longer trials in patients with NASH and metabolic complications are warranted to evaluate metabolic and histologic benefits of treatment.

Findings from the resveratrol study were less encouraging.

Eight weeks of treatment at 3,000 mg daily in overweight or obese men with NAFLD who were recruited from clinics in Brisbane from 2011 through 2012 was no better than placebo for improving insulin resistance, hepatic steatosis, or abdominal fat distribution, Dr. Veronique S. Chachay of the University of Queensland, Brisbane, Australia and her colleagues also reported in the December issue of Clinical Gastroenterology and Hepatology.

No changes were observed in plasma lipids or antioxidant activity, and levels of alanine and aspartate aminotransferases increased significantly (from 45 to 63 U/L and from 35 to 45 U/L, respectively) until week 6 in the 10 treated patients, compared with the 10 who received placebo (40 to 48 U/L and 36 to 38 U/L, respectively). Resveratrol did not significantly alter transcription of NQ01, PTP1B, IL6, or H01, the investigators said (Clin Gastroenterol Hepatol 2014[doi:10.106/j.cgh.2014.02.024]).

NAFLD is associated with abdominal obesity, insulin resistance, and inflammation, and while weight loss via calorie restriction is known to reduce features of the disease, there is no pharmacologic therapy available to achieve this end.

The investigators sought to determine if resveratrol – a polyphenol that has been shown to prevent high-energy diet-induced steatosis and insulin resistance in animals – might be beneficial in patients with NAFLD.

“The present study demonstrates that the preventive role of resveratrol observed in diet-induced preclinical models of NAFLD does not translate into a therapeutic role in clinically established NAFLD,” they said, adding that clinical dose-finding studies are “paramount to elucidate the dose-response relationship” and that “the purported calorie-restriction mimicking of resveratrol may require investigation in combination with dietary prescription, standard care, and lifestyle modifications to target adequately the complexity of dysregulation in obesity-related chronic disease.”

The aramchol study was supported by Galmed Medical Research, Ltd. Dr. Safadi reported having no disclosures. The resveratrol study was supported by the Princess Alexandra Research Foundation, the Lions Medical Research Foundation, and the National Health and Medical Research Council of Australia. The authors reported having no disclosures.

Administration of a novel fatty acid–bile acid conjugate safely and significantly reduced liver fat content in patients with nonalcoholic fatty liver disease in a phase II trial.

Administration of resveratrol for 8 weeks, however, failed to improve any features of the disease in a separate placebo-controlled study.

Courtesy of Wikimedia /Nephron / Creative Commons License

In 60 patients aged 18-75 years in a randomized, double-blind, placebo-controlled study of the fatty acid–bile acid conjugate aramchol (Trima Israel Pharmaceutical Products Ltd. Maabarot), 3 months of treatment was associated with a decrease in liver fat content by a mean of 12.57% as measured by magnetic resonance spectroscopy, compared with an increase in liver fat by a mean of 6.39% in patients who received placebo, Dr. Rifaat Safadi of Hadassah University Medical Center, Jerusalem and colleagues reported in the DEcember issue of Clinical Gastroenterology and Hepatology.

The difference between the treatment and placebo groups was significant, even after age, sex, and body mass index were adjusted for.

Liver fat content also decreased in patients who received treatment with a 100-mg dose of aramchol, but the difference compared with placebo was not statistically significant, indicating a dose-response relationship in treated patients, the investigators said (Clin Gastroenterol Hepatol 2014[doi:10.1016/j.cgh.2014.04.038]).

A trend was seen for improvements over time in endothelial function and levels of alanine aminotransferase and adiponectin.

Patients in the study were from 10 centers in Israel, and all had biopsy-confirmed NAFLD (54 patients) or nonalcoholic steatohepatitis (NASH, 6 patients). They were randomized to receive 100 or 300 mg of aramchol or placebo once daily for 3 months.

No serious or drug-related adverse events occurred in the treated patients, the investigators said.

The findings suggest that aramchol is a candidate for the treatment of fatty liver–related diseases, which are “an increasingly relevant public health issue because of their association with the worldwide epidemics of diabetes and obesity,” and for which treatments are lacking, they said, concluding that longer trials in patients with NASH and metabolic complications are warranted to evaluate metabolic and histologic benefits of treatment.

Findings from the resveratrol study were less encouraging.

Eight weeks of treatment at 3,000 mg daily in overweight or obese men with NAFLD who were recruited from clinics in Brisbane from 2011 through 2012 was no better than placebo for improving insulin resistance, hepatic steatosis, or abdominal fat distribution, Dr. Veronique S. Chachay of the University of Queensland, Brisbane, Australia and her colleagues also reported in the December issue of Clinical Gastroenterology and Hepatology.

No changes were observed in plasma lipids or antioxidant activity, and levels of alanine and aspartate aminotransferases increased significantly (from 45 to 63 U/L and from 35 to 45 U/L, respectively) until week 6 in the 10 treated patients, compared with the 10 who received placebo (40 to 48 U/L and 36 to 38 U/L, respectively). Resveratrol did not significantly alter transcription of NQ01, PTP1B, IL6, or H01, the investigators said (Clin Gastroenterol Hepatol 2014[doi:10.106/j.cgh.2014.02.024]).

NAFLD is associated with abdominal obesity, insulin resistance, and inflammation, and while weight loss via calorie restriction is known to reduce features of the disease, there is no pharmacologic therapy available to achieve this end.

The investigators sought to determine if resveratrol – a polyphenol that has been shown to prevent high-energy diet-induced steatosis and insulin resistance in animals – might be beneficial in patients with NAFLD.

“The present study demonstrates that the preventive role of resveratrol observed in diet-induced preclinical models of NAFLD does not translate into a therapeutic role in clinically established NAFLD,” they said, adding that clinical dose-finding studies are “paramount to elucidate the dose-response relationship” and that “the purported calorie-restriction mimicking of resveratrol may require investigation in combination with dietary prescription, standard care, and lifestyle modifications to target adequately the complexity of dysregulation in obesity-related chronic disease.”

The aramchol study was supported by Galmed Medical Research, Ltd. Dr. Safadi reported having no disclosures. The resveratrol study was supported by the Princess Alexandra Research Foundation, the Lions Medical Research Foundation, and the National Health and Medical Research Council of Australia. The authors reported having no disclosures.

BOSTON – Pediatric nonalcoholic fatty liver disease progresses as children age to a more adult pattern of disease, a paired-biopsy study shows.

“As they grow older, they are facing liver transplant and potentially hepatocellular carcinoma, just as the adults do,” Dr. Elizabeth M. Brunt said during an interview at the annual meeting of the American Association for the Study of Liver Diseases.

Among 102 children studied, the zone 1 (borderline 1b) diagnostic pattern decreased from 27.5% to 9.8%, while the more “adult” NAFLD zone 3 (borderline 1a) pattern and definite steatohepatitis patterns both increased from 14.7% and 28.4% to 18.6% and 29.4%.

Moreover, cirrhosis was seen in nearly 3% of children at first biopsy, but by the second biopsy, nearly 20% of children had advanced fibrosis or cirrhosis, she said.

The findings are troubling because the United States is in the midst of an obesity epidemic, and obesity is associated with high rates of fatty liver disease, said Dr. Brunt of Washington University, St. Louis.

The National Institutes of Health supported the study. Dr. Brunt reported consulting for Synageva, serving as an independent contractor for Rottapharm and Kadmon, and speaking and teaching for the Geneva Foundation.

BOSTON – Pediatric nonalcoholic fatty liver disease progresses as children age to a more adult pattern of disease, a paired-biopsy study shows.

“As they grow older, they are facing liver transplant and potentially hepatocellular carcinoma, just as the adults do,” Dr. Elizabeth M. Brunt said during an interview at the annual meeting of the American Association for the Study of Liver Diseases.

Among 102 children studied, the zone 1 (borderline 1b) diagnostic pattern decreased from 27.5% to 9.8%, while the more “adult” NAFLD zone 3 (borderline 1a) pattern and definite steatohepatitis patterns both increased from 14.7% and 28.4% to 18.6% and 29.4%.

Moreover, cirrhosis was seen in nearly 3% of children at first biopsy, but by the second biopsy, nearly 20% of children had advanced fibrosis or cirrhosis, she said.

The findings are troubling because the United States is in the midst of an obesity epidemic, and obesity is associated with high rates of fatty liver disease, said Dr. Brunt of Washington University, St. Louis.

The National Institutes of Health supported the study. Dr. Brunt reported consulting for Synageva, serving as an independent contractor for Rottapharm and Kadmon, and speaking and teaching for the Geneva Foundation.

BOSTON – Pediatric nonalcoholic fatty liver disease progresses as children age to a more adult pattern of disease, a paired-biopsy study shows.

“As they grow older, they are facing liver transplant and potentially hepatocellular carcinoma, just as the adults do,” Dr. Elizabeth M. Brunt said during an interview at the annual meeting of the American Association for the Study of Liver Diseases.

Among 102 children studied, the zone 1 (borderline 1b) diagnostic pattern decreased from 27.5% to 9.8%, while the more “adult” NAFLD zone 3 (borderline 1a) pattern and definite steatohepatitis patterns both increased from 14.7% and 28.4% to 18.6% and 29.4%.

Moreover, cirrhosis was seen in nearly 3% of children at first biopsy, but by the second biopsy, nearly 20% of children had advanced fibrosis or cirrhosis, she said.

The findings are troubling because the United States is in the midst of an obesity epidemic, and obesity is associated with high rates of fatty liver disease, said Dr. Brunt of Washington University, St. Louis.

The National Institutes of Health supported the study. Dr. Brunt reported consulting for Synageva, serving as an independent contractor for Rottapharm and Kadmon, and speaking and teaching for the Geneva Foundation.