Liver Disease

The newly proposed consensus definition of acute kidney injury in patients with cirrhosis accurately predicts 30-day mortality and other adverse outcomes in this patient population much better than the current, more rigid definition would, according to a report in the December issue of Gastroenterology (doi:10.1053/j.gastro.2013.08.051).

In what they described as the largest prospective study of this topic to date, researchers found that the recently proposed, broader redefinition of acute kidney injury (AKI) correctly identified which patients were likely to die, develop severe complications such as organ failure, or require longer hospitalization, even when the AKI was transient and resolved completely after treatment.

Courtesy American Gastroenterological Association

More than half of the patients in this study who had episodes of AKI according to the new definition did not meet the criteria of the old definition. So using the new definition will help identify these high-risk patients at an earlier stage of renal dysfunction, "well before the stringent diagnostic criteria of [the old definition] are reached," when they will have a better treatment response, said Dr. Florence Wong of the division of gastroenterology, University of Toronto, and her associates.

The old definition of AKI required the presence of hepatorenal syndrome, with a serum creatinine level of greater than 2.5 mg/dL. This meant that patients with less severe renal dysfunction didn’t qualify and weren’t treated. But emerging evidence indicates that even mild degrees of renal dysfunction signal a poor prognosis, and that serum creatinine alone doesn’t accurately reflect renal dysfunction in advanced cirrhosis.

So the International Ascites Club and the Acute Dialysis Quality Initiative (ADQI) group proposed that acute kidney injury in cirrhosis should be redefined as an increase in serum creatinine level of 0.3 mg/dL or greater within 48 hours, or a 50% increase in serum creatinine level from a stable baseline reading within the previous 6 months, regardless of final serum creatinine level.

Dr. Wong and her colleagues assessed the new definition in a cohort of 337 cirrhotic patients treated during a 2-year period at 12 North American medical centers who were admitted with a bacterial infection (287 subjects) or who developed a bacterial infection during hospitalization (50 subjects). The most common infections were urinary tract infection (27% of patients), spontaneous bacterial peritonitis (21%), skin infection (14%), pneumonia (10%), and spontaneous bacteremia with no clear source of infection (9%).

Approximately half of these patients (49%) developed at least one episode of AKI during hospitalization. The 30-day mortality was significantly higher for those who developed AKI according to the new definition (34% mortality) than in those who did not (7% mortality), the investigators said.

Most patients who developed AKI had only a transient case, and their renal function completely recovered. Yet their subsequent mortality within 30 days was twice as high as that for patients who didn’t have any AKI.

The negative predictive value of the new definition of AKI was 93%, and the positive predictive value was 34%.

This study was supported in part by the National Institutes of Health, the National Institute of Diabetes and Digestive and Kidney Diseases, and the National Center for Research Resources. No financial conflicts of interest were reported.

The newly proposed consensus definition of acute kidney injury in patients with cirrhosis accurately predicts 30-day mortality and other adverse outcomes in this patient population much better than the current, more rigid definition would, according to a report in the December issue of Gastroenterology (doi:10.1053/j.gastro.2013.08.051).

In what they described as the largest prospective study of this topic to date, researchers found that the recently proposed, broader redefinition of acute kidney injury (AKI) correctly identified which patients were likely to die, develop severe complications such as organ failure, or require longer hospitalization, even when the AKI was transient and resolved completely after treatment.

Courtesy American Gastroenterological Association

More than half of the patients in this study who had episodes of AKI according to the new definition did not meet the criteria of the old definition. So using the new definition will help identify these high-risk patients at an earlier stage of renal dysfunction, "well before the stringent diagnostic criteria of [the old definition] are reached," when they will have a better treatment response, said Dr. Florence Wong of the division of gastroenterology, University of Toronto, and her associates.

The old definition of AKI required the presence of hepatorenal syndrome, with a serum creatinine level of greater than 2.5 mg/dL. This meant that patients with less severe renal dysfunction didn’t qualify and weren’t treated. But emerging evidence indicates that even mild degrees of renal dysfunction signal a poor prognosis, and that serum creatinine alone doesn’t accurately reflect renal dysfunction in advanced cirrhosis.

So the International Ascites Club and the Acute Dialysis Quality Initiative (ADQI) group proposed that acute kidney injury in cirrhosis should be redefined as an increase in serum creatinine level of 0.3 mg/dL or greater within 48 hours, or a 50% increase in serum creatinine level from a stable baseline reading within the previous 6 months, regardless of final serum creatinine level.

Dr. Wong and her colleagues assessed the new definition in a cohort of 337 cirrhotic patients treated during a 2-year period at 12 North American medical centers who were admitted with a bacterial infection (287 subjects) or who developed a bacterial infection during hospitalization (50 subjects). The most common infections were urinary tract infection (27% of patients), spontaneous bacterial peritonitis (21%), skin infection (14%), pneumonia (10%), and spontaneous bacteremia with no clear source of infection (9%).

Approximately half of these patients (49%) developed at least one episode of AKI during hospitalization. The 30-day mortality was significantly higher for those who developed AKI according to the new definition (34% mortality) than in those who did not (7% mortality), the investigators said.

Most patients who developed AKI had only a transient case, and their renal function completely recovered. Yet their subsequent mortality within 30 days was twice as high as that for patients who didn’t have any AKI.

The negative predictive value of the new definition of AKI was 93%, and the positive predictive value was 34%.

This study was supported in part by the National Institutes of Health, the National Institute of Diabetes and Digestive and Kidney Diseases, and the National Center for Research Resources. No financial conflicts of interest were reported.

The newly proposed consensus definition of acute kidney injury in patients with cirrhosis accurately predicts 30-day mortality and other adverse outcomes in this patient population much better than the current, more rigid definition would, according to a report in the December issue of Gastroenterology (doi:10.1053/j.gastro.2013.08.051).

In what they described as the largest prospective study of this topic to date, researchers found that the recently proposed, broader redefinition of acute kidney injury (AKI) correctly identified which patients were likely to die, develop severe complications such as organ failure, or require longer hospitalization, even when the AKI was transient and resolved completely after treatment.

Courtesy American Gastroenterological Association

More than half of the patients in this study who had episodes of AKI according to the new definition did not meet the criteria of the old definition. So using the new definition will help identify these high-risk patients at an earlier stage of renal dysfunction, "well before the stringent diagnostic criteria of [the old definition] are reached," when they will have a better treatment response, said Dr. Florence Wong of the division of gastroenterology, University of Toronto, and her associates.

The old definition of AKI required the presence of hepatorenal syndrome, with a serum creatinine level of greater than 2.5 mg/dL. This meant that patients with less severe renal dysfunction didn’t qualify and weren’t treated. But emerging evidence indicates that even mild degrees of renal dysfunction signal a poor prognosis, and that serum creatinine alone doesn’t accurately reflect renal dysfunction in advanced cirrhosis.

So the International Ascites Club and the Acute Dialysis Quality Initiative (ADQI) group proposed that acute kidney injury in cirrhosis should be redefined as an increase in serum creatinine level of 0.3 mg/dL or greater within 48 hours, or a 50% increase in serum creatinine level from a stable baseline reading within the previous 6 months, regardless of final serum creatinine level.

Dr. Wong and her colleagues assessed the new definition in a cohort of 337 cirrhotic patients treated during a 2-year period at 12 North American medical centers who were admitted with a bacterial infection (287 subjects) or who developed a bacterial infection during hospitalization (50 subjects). The most common infections were urinary tract infection (27% of patients), spontaneous bacterial peritonitis (21%), skin infection (14%), pneumonia (10%), and spontaneous bacteremia with no clear source of infection (9%).

Approximately half of these patients (49%) developed at least one episode of AKI during hospitalization. The 30-day mortality was significantly higher for those who developed AKI according to the new definition (34% mortality) than in those who did not (7% mortality), the investigators said.

Most patients who developed AKI had only a transient case, and their renal function completely recovered. Yet their subsequent mortality within 30 days was twice as high as that for patients who didn’t have any AKI.

The negative predictive value of the new definition of AKI was 93%, and the positive predictive value was 34%.

This study was supported in part by the National Institutes of Health, the National Institute of Diabetes and Digestive and Kidney Diseases, and the National Center for Research Resources. No financial conflicts of interest were reported.

WASHINGTON – Treatment with nonselective beta-blockers was not associated with an increased mortality risk in patients with decompensated cirrhosis, judging from findings from a retrospective longitudinal cohort study using Danish registry data presented by Dr. Ulrich Bang at the annual meeting of the American Association for the Study of Liver Diseases.

However, dose played a role in the mortality risk, with low-dose beta-blocker treatment (40 mg/day or less) reducing the risk of death "in all patients independent of severity of cirrhosis," said Dr. Bang of the department of gastroenterology, University Hospital of Hvidovre, Denmark. High-dose beta-blockers (more than 40 mg/day) were associated with increased mortality among patients with diuretic-resistant ascites as a feature of decompensated cirrhosis, he said. Using data on patients with alcoholic or biliary cirrhosis from the Danish national patient registry and medication use from the country’s national prescription registry, the study addressed the possibility that treatment with beta-blockers may have a negative impact on survival in severely ill cirrhotic patients. Although treatment with beta-blockers reduces the risk of mortality and repeat bleeding in patients with cirrhosis and varices, there has been concern about the possibility that beta-blockers have detrimental effects in patients with diuretic-refractory ascites because of a negative effect on cardiac output, he noted.

The primary outcome was mortality, adjusted for age, comorbidities, sex, and socioeconomic status.

Between 1995 and 2010, there were 1,576 people in the registry with mild decompensated cirrhosis (defined as those who had undergone one to four paracentesis procedures) and 239 people with severe decompensated cirrhosis (they had had more than four paracenteses). There were also 16,828 people with nonresistant "cirrhosis," who had not undergone a paracentesis procedure. Of the total of 18,643 patients, almost 90% had alcoholic cirrhosis, about 21% used a beta-blocker, and 64% used diuretics.

The median beta-blocker dose among the patients with mild cirrhosis was 30 mg/day (range 20-264 mg), and 24 mg/day (16-58 mg) among those with severe cirrhosis.

Among the patients with mild decompensated cirrhosis, mortality was 43% among those on a beta-blocker vs. 58% among those not on a beta-blocker, a significantly decreased risk of death. Among those on a beta-blocker, mortality was 38% among those on 40 mg or less per day vs. 51% among those on higher daily doses.

Mortality was also lower among those treated with a beta-blocker among the 239 patients with severe decompensated cirrhosis, Dr. Bang said. In this group, mortality was 47% among those not on a beta-blocker, compared with 41% of those on a beta-blocker. Of those on a beta-blocker, mortality was 36% among those on a dose of 40 mg or less a day but was 52% among those on more than 40 mg/day. The same patterns were seen in a subgroup of patients with diuretic-resistant decompensated cirrhosis.

The use of a beta-blocker was associated with a lower risk of spontaneous bacterial peritonitis in patients with decompensated cirrhosis, he said.

Dr. Bang had no disclosures.

emechcatie@frontlinemedcom.com

WASHINGTON – Treatment with nonselective beta-blockers was not associated with an increased mortality risk in patients with decompensated cirrhosis, judging from findings from a retrospective longitudinal cohort study using Danish registry data presented by Dr. Ulrich Bang at the annual meeting of the American Association for the Study of Liver Diseases.

However, dose played a role in the mortality risk, with low-dose beta-blocker treatment (40 mg/day or less) reducing the risk of death "in all patients independent of severity of cirrhosis," said Dr. Bang of the department of gastroenterology, University Hospital of Hvidovre, Denmark. High-dose beta-blockers (more than 40 mg/day) were associated with increased mortality among patients with diuretic-resistant ascites as a feature of decompensated cirrhosis, he said. Using data on patients with alcoholic or biliary cirrhosis from the Danish national patient registry and medication use from the country’s national prescription registry, the study addressed the possibility that treatment with beta-blockers may have a negative impact on survival in severely ill cirrhotic patients. Although treatment with beta-blockers reduces the risk of mortality and repeat bleeding in patients with cirrhosis and varices, there has been concern about the possibility that beta-blockers have detrimental effects in patients with diuretic-refractory ascites because of a negative effect on cardiac output, he noted.

The primary outcome was mortality, adjusted for age, comorbidities, sex, and socioeconomic status.

Between 1995 and 2010, there were 1,576 people in the registry with mild decompensated cirrhosis (defined as those who had undergone one to four paracentesis procedures) and 239 people with severe decompensated cirrhosis (they had had more than four paracenteses). There were also 16,828 people with nonresistant "cirrhosis," who had not undergone a paracentesis procedure. Of the total of 18,643 patients, almost 90% had alcoholic cirrhosis, about 21% used a beta-blocker, and 64% used diuretics.

The median beta-blocker dose among the patients with mild cirrhosis was 30 mg/day (range 20-264 mg), and 24 mg/day (16-58 mg) among those with severe cirrhosis.

Among the patients with mild decompensated cirrhosis, mortality was 43% among those on a beta-blocker vs. 58% among those not on a beta-blocker, a significantly decreased risk of death. Among those on a beta-blocker, mortality was 38% among those on 40 mg or less per day vs. 51% among those on higher daily doses.

Mortality was also lower among those treated with a beta-blocker among the 239 patients with severe decompensated cirrhosis, Dr. Bang said. In this group, mortality was 47% among those not on a beta-blocker, compared with 41% of those on a beta-blocker. Of those on a beta-blocker, mortality was 36% among those on a dose of 40 mg or less a day but was 52% among those on more than 40 mg/day. The same patterns were seen in a subgroup of patients with diuretic-resistant decompensated cirrhosis.

The use of a beta-blocker was associated with a lower risk of spontaneous bacterial peritonitis in patients with decompensated cirrhosis, he said.

Dr. Bang had no disclosures.

emechcatie@frontlinemedcom.com

WASHINGTON – Treatment with nonselective beta-blockers was not associated with an increased mortality risk in patients with decompensated cirrhosis, judging from findings from a retrospective longitudinal cohort study using Danish registry data presented by Dr. Ulrich Bang at the annual meeting of the American Association for the Study of Liver Diseases.

However, dose played a role in the mortality risk, with low-dose beta-blocker treatment (40 mg/day or less) reducing the risk of death "in all patients independent of severity of cirrhosis," said Dr. Bang of the department of gastroenterology, University Hospital of Hvidovre, Denmark. High-dose beta-blockers (more than 40 mg/day) were associated with increased mortality among patients with diuretic-resistant ascites as a feature of decompensated cirrhosis, he said. Using data on patients with alcoholic or biliary cirrhosis from the Danish national patient registry and medication use from the country’s national prescription registry, the study addressed the possibility that treatment with beta-blockers may have a negative impact on survival in severely ill cirrhotic patients. Although treatment with beta-blockers reduces the risk of mortality and repeat bleeding in patients with cirrhosis and varices, there has been concern about the possibility that beta-blockers have detrimental effects in patients with diuretic-refractory ascites because of a negative effect on cardiac output, he noted.

The primary outcome was mortality, adjusted for age, comorbidities, sex, and socioeconomic status.

Between 1995 and 2010, there were 1,576 people in the registry with mild decompensated cirrhosis (defined as those who had undergone one to four paracentesis procedures) and 239 people with severe decompensated cirrhosis (they had had more than four paracenteses). There were also 16,828 people with nonresistant "cirrhosis," who had not undergone a paracentesis procedure. Of the total of 18,643 patients, almost 90% had alcoholic cirrhosis, about 21% used a beta-blocker, and 64% used diuretics.

The median beta-blocker dose among the patients with mild cirrhosis was 30 mg/day (range 20-264 mg), and 24 mg/day (16-58 mg) among those with severe cirrhosis.

Among the patients with mild decompensated cirrhosis, mortality was 43% among those on a beta-blocker vs. 58% among those not on a beta-blocker, a significantly decreased risk of death. Among those on a beta-blocker, mortality was 38% among those on 40 mg or less per day vs. 51% among those on higher daily doses.

Mortality was also lower among those treated with a beta-blocker among the 239 patients with severe decompensated cirrhosis, Dr. Bang said. In this group, mortality was 47% among those not on a beta-blocker, compared with 41% of those on a beta-blocker. Of those on a beta-blocker, mortality was 36% among those on a dose of 40 mg or less a day but was 52% among those on more than 40 mg/day. The same patterns were seen in a subgroup of patients with diuretic-resistant decompensated cirrhosis.

The use of a beta-blocker was associated with a lower risk of spontaneous bacterial peritonitis in patients with decompensated cirrhosis, he said.

Dr. Bang had no disclosures.

emechcatie@frontlinemedcom.com

WASHINGTON – Signals for several hematologic toxicities and for hepatic failure were identified in an analysis of serious adverse drug reactions associated with boceprevir treatment, according to an analysis of Food and Drug Administration data.

Signals for anemia, thrombocytopenia, and neutropenia – adverse events that were also reported in clinical trials of boceprevir before approval – were statistically significant, while the signal for hepatic failure approached significance, Bryan Love, Pharm.D., reported at the annual meeting of the American Association for the Study of Liver Diseases.

Reports of hepatic failure were unexpected, and should be investigated to provide insight into a possible causal association, he said.

Boceprevir (Victrelis) is one of two hepatitis C virus (HCV) protease inhibitors that were approved for treating chronic hepatitis C (genotype 1) in 2011, in combination with peginterferon and ribavirin, for both treatment-naive and treatment-experienced patients. Boceprevir, and the second drug, telaprevir, ushered in a new era for HCV treatments, with improved sustained virologic response rates, but their trade-offs included additional side effects, drug-drug interactions, as well as increased cost, he pointed out.

Dr. Love of the South Carolina College of Pharmacy, Columbia, and his coinvestigators searched for boceprevir-associated serious adverse drug reactions in the FDA Adverse Event Reporting System (FAERS) database between May 13, 2011 (the day of U.S. approval), and June 30, 2012, looking for those of special interest: thromboembolic events, severe cutaneous reactions, hematologic toxicities, and hepatic failure.

After duplicate reports were excluded, they identified 334 events in about 300 patients. The most frequent were neutropenia (168 reports), thrombocytopenia (80), and anemia (46). They also identified 13 severe cutaneous reactions, including one case of Stevens-Johnson syndrome.

There were 11 cases of hepatic failure in patients treated for a median of 111 days. Most (nine cases) were in women and most were outside of the United States; three reports specified that the patients had cirrhosis. Of the 11 patients, 7 died (6 women and 1 man).

On analysis, the investigators determined that the highest risk was for anemia, followed by neutropenia and thrombocytopenia, all statistically significant. The finding for hepatic failure approached statistical significance.

There were no new signals identified for other serious adverse events, including Stevens-Johnson syndrome, which he called "comforting."

Further investigation into the hepatic failure signal could include evaluation of patients in real world treatment settings, Dr. Love suggested. He pointed out that the adverse events are significantly underreported to the FDA and that the quality of those reports is unknown, making it difficult to determine causality.

Dr. Love reported no relevant financial conflicts of interest. The study was not funded.

emechcatie@frontlinemedcom.com

WASHINGTON – Signals for several hematologic toxicities and for hepatic failure were identified in an analysis of serious adverse drug reactions associated with boceprevir treatment, according to an analysis of Food and Drug Administration data.

Signals for anemia, thrombocytopenia, and neutropenia – adverse events that were also reported in clinical trials of boceprevir before approval – were statistically significant, while the signal for hepatic failure approached significance, Bryan Love, Pharm.D., reported at the annual meeting of the American Association for the Study of Liver Diseases.

Reports of hepatic failure were unexpected, and should be investigated to provide insight into a possible causal association, he said.

Boceprevir (Victrelis) is one of two hepatitis C virus (HCV) protease inhibitors that were approved for treating chronic hepatitis C (genotype 1) in 2011, in combination with peginterferon and ribavirin, for both treatment-naive and treatment-experienced patients. Boceprevir, and the second drug, telaprevir, ushered in a new era for HCV treatments, with improved sustained virologic response rates, but their trade-offs included additional side effects, drug-drug interactions, as well as increased cost, he pointed out.

Dr. Love of the South Carolina College of Pharmacy, Columbia, and his coinvestigators searched for boceprevir-associated serious adverse drug reactions in the FDA Adverse Event Reporting System (FAERS) database between May 13, 2011 (the day of U.S. approval), and June 30, 2012, looking for those of special interest: thromboembolic events, severe cutaneous reactions, hematologic toxicities, and hepatic failure.

After duplicate reports were excluded, they identified 334 events in about 300 patients. The most frequent were neutropenia (168 reports), thrombocytopenia (80), and anemia (46). They also identified 13 severe cutaneous reactions, including one case of Stevens-Johnson syndrome.

There were 11 cases of hepatic failure in patients treated for a median of 111 days. Most (nine cases) were in women and most were outside of the United States; three reports specified that the patients had cirrhosis. Of the 11 patients, 7 died (6 women and 1 man).

On analysis, the investigators determined that the highest risk was for anemia, followed by neutropenia and thrombocytopenia, all statistically significant. The finding for hepatic failure approached statistical significance.

There were no new signals identified for other serious adverse events, including Stevens-Johnson syndrome, which he called "comforting."

Further investigation into the hepatic failure signal could include evaluation of patients in real world treatment settings, Dr. Love suggested. He pointed out that the adverse events are significantly underreported to the FDA and that the quality of those reports is unknown, making it difficult to determine causality.

Dr. Love reported no relevant financial conflicts of interest. The study was not funded.

emechcatie@frontlinemedcom.com

WASHINGTON – Signals for several hematologic toxicities and for hepatic failure were identified in an analysis of serious adverse drug reactions associated with boceprevir treatment, according to an analysis of Food and Drug Administration data.

Signals for anemia, thrombocytopenia, and neutropenia – adverse events that were also reported in clinical trials of boceprevir before approval – were statistically significant, while the signal for hepatic failure approached significance, Bryan Love, Pharm.D., reported at the annual meeting of the American Association for the Study of Liver Diseases.

Reports of hepatic failure were unexpected, and should be investigated to provide insight into a possible causal association, he said.

Boceprevir (Victrelis) is one of two hepatitis C virus (HCV) protease inhibitors that were approved for treating chronic hepatitis C (genotype 1) in 2011, in combination with peginterferon and ribavirin, for both treatment-naive and treatment-experienced patients. Boceprevir, and the second drug, telaprevir, ushered in a new era for HCV treatments, with improved sustained virologic response rates, but their trade-offs included additional side effects, drug-drug interactions, as well as increased cost, he pointed out.

Dr. Love of the South Carolina College of Pharmacy, Columbia, and his coinvestigators searched for boceprevir-associated serious adverse drug reactions in the FDA Adverse Event Reporting System (FAERS) database between May 13, 2011 (the day of U.S. approval), and June 30, 2012, looking for those of special interest: thromboembolic events, severe cutaneous reactions, hematologic toxicities, and hepatic failure.

After duplicate reports were excluded, they identified 334 events in about 300 patients. The most frequent were neutropenia (168 reports), thrombocytopenia (80), and anemia (46). They also identified 13 severe cutaneous reactions, including one case of Stevens-Johnson syndrome.

There were 11 cases of hepatic failure in patients treated for a median of 111 days. Most (nine cases) were in women and most were outside of the United States; three reports specified that the patients had cirrhosis. Of the 11 patients, 7 died (6 women and 1 man).

On analysis, the investigators determined that the highest risk was for anemia, followed by neutropenia and thrombocytopenia, all statistically significant. The finding for hepatic failure approached statistical significance.

There were no new signals identified for other serious adverse events, including Stevens-Johnson syndrome, which he called "comforting."

Further investigation into the hepatic failure signal could include evaluation of patients in real world treatment settings, Dr. Love suggested. He pointed out that the adverse events are significantly underreported to the FDA and that the quality of those reports is unknown, making it difficult to determine causality.

Dr. Love reported no relevant financial conflicts of interest. The study was not funded.

emechcatie@frontlinemedcom.com

The results of a randomized, open-label study suggest that reducing the ribavirin dose should be the "primary approach" for managing anemia associated with peginterferon, ribavirin, and boceprevir therapy in patients with chronic hepatitis C, the authors of the study concluded.

In the study, the effects of two anemia-management strategies, ribavirin (RBV) dose reduction and erythropoietin (EPO) treatment, on the sustained virologic response (SVR) were similar – there was less than 1% difference between the two groups, according to the investigators, Dr. Fred F. Poordad of the Texas Liver Institute, at the University of Texas Health Science Center, San Antonio, and his associates. They also found that SVR rates were significantly lower among those who received less than half of the total ribavirin dose during the entire treatment period, compared with those who received a greater proportion of the total dosage.

"There appears to be no apparent benefit of using EPO as a first-line anemia-management strategy to enhance SVR rate or minimize relapse," the authors concluded. "EPO can be used as a secondary management strategy to prevent treatment interruption if RBV dosage reduction alone is inadequate, but the safety of EPO use in this setting has not been clearly established," they added. The study was published in the November issue of Gastroenterology (2013 [doi:10.1053/j.gastro.2013.07.051]).

The study includes an algorithm for managing boceprevir-related anemia, based on the results of this and other clinical studies, and the authors’ expertise.

The study, conducted between December 2009 and October 2011, compared the two regimens in 500 of 687 previously untreated patients with chronic HCV genotype-1 infections, who became anemic (hemoglobin levels dropping to 10 g/dL or lower) during treatment with the three drugs: peginterferon alfa-2b (PegIntron) at a dose of 1.5 mcg/kg per week; ribavirin at a dose of 600-1400 mg per day depending on weight; and boceprevir (Victrelis) at a dose of 800 mg three times a day. (After 4 weeks of treatment with peginterferon and RBV, boceprevir was added for 24 or 44 weeks). Their mean age was about 50 years, 33% were men, 77% were white, and 18% were black; 91% had a baseline viral load of more than 400,000 IU/mL. Almost 90% were in the United States, the rest were in Canada and Europe.

The 500 patients were randomized to treatment with EPO (a subcutaneous infusion of 40,000 IU a week) or a reduction in the ribavirin dose (200 mg/day or, for those on the 1,400 mg daily dose, a 400-mg reduction). If hemoglobin levels dropped to 7.5 g/dL or lower, the patients were dropped from the study.

The SVR rate (undetectable HCV RNA 24 weeks after the end of treatment) was 71.5% among those whose ribavirin dosage was reduced and 70.9% among those treated with EPO. Among the 187 patients who did not develop anemia, the SVR rate was 40.1%; this group included a large number of patients who discontinued treatment because of adverse events. But of the 64 who completed treatment, the SVR rate was 89%. The overall SVR rate – among all 687 patients, those randomized and not randomized – was 63%.

Common adverse events were similar in the two randomized treatment groups, with anemia, fatigue, nausea, and headache being the most commonly reported. The rates of serious adverse events were 16% among those in the RBV dose-reduction arm and 13% of those on EPO. There were more thromboembolic events among the patients treated with EPO. There was one death in a patient in the RBV arm, a sudden cardiac death 3 weeks after stopping treatment.

The algorithm proposed by the authors, which has different hemoglobin monitoring recommendations for those with and without advanced fibrosis and cirrhosis, recommends that the primary intervention for managing anemia should be to reduce the RBV dosage. But if hemoglobin levels remain below 10 g/dL, "secondary interventions, such as administration of EPO, red cell transfusions, and reducing the dosage of peginterferon can be considered," the authors wrote. In addition, "it is important that the patient receives at least 50% of the total milligrams of RBV calculated from the initial RBV dosage (mg/d) and the assigned duration" defined by the response-guided therapy algorithm, they added.

The open-label design was one of the study’s limitations, and whether these results apply to other HCV treatment regimens is unclear, the authors noted. However, the results "would most likely be applicable to all RBV- and peginterferon/RBV-based regimens" for hepatitis C, they added.

The study was funded by Schering-Plough, the manufacturer of PegIntron and combination packs of PegIntron with ribavirin, which is now part of Merck. The investigator disclosures included having served as consultants and speakers, and/or having received grants from multiple pharmaceutical companies; the investigators include several current and former employees of Merck Sharp & Dohme Corp. (a subsidiary of Merck & Co.), the manufacturer of Victrelis.

emechcatie@frontlinemedcom.com

The results of a randomized, open-label study suggest that reducing the ribavirin dose should be the "primary approach" for managing anemia associated with peginterferon, ribavirin, and boceprevir therapy in patients with chronic hepatitis C, the authors of the study concluded.

In the study, the effects of two anemia-management strategies, ribavirin (RBV) dose reduction and erythropoietin (EPO) treatment, on the sustained virologic response (SVR) were similar – there was less than 1% difference between the two groups, according to the investigators, Dr. Fred F. Poordad of the Texas Liver Institute, at the University of Texas Health Science Center, San Antonio, and his associates. They also found that SVR rates were significantly lower among those who received less than half of the total ribavirin dose during the entire treatment period, compared with those who received a greater proportion of the total dosage.

"There appears to be no apparent benefit of using EPO as a first-line anemia-management strategy to enhance SVR rate or minimize relapse," the authors concluded. "EPO can be used as a secondary management strategy to prevent treatment interruption if RBV dosage reduction alone is inadequate, but the safety of EPO use in this setting has not been clearly established," they added. The study was published in the November issue of Gastroenterology (2013 [doi:10.1053/j.gastro.2013.07.051]).

The study includes an algorithm for managing boceprevir-related anemia, based on the results of this and other clinical studies, and the authors’ expertise.

The study, conducted between December 2009 and October 2011, compared the two regimens in 500 of 687 previously untreated patients with chronic HCV genotype-1 infections, who became anemic (hemoglobin levels dropping to 10 g/dL or lower) during treatment with the three drugs: peginterferon alfa-2b (PegIntron) at a dose of 1.5 mcg/kg per week; ribavirin at a dose of 600-1400 mg per day depending on weight; and boceprevir (Victrelis) at a dose of 800 mg three times a day. (After 4 weeks of treatment with peginterferon and RBV, boceprevir was added for 24 or 44 weeks). Their mean age was about 50 years, 33% were men, 77% were white, and 18% were black; 91% had a baseline viral load of more than 400,000 IU/mL. Almost 90% were in the United States, the rest were in Canada and Europe.

The 500 patients were randomized to treatment with EPO (a subcutaneous infusion of 40,000 IU a week) or a reduction in the ribavirin dose (200 mg/day or, for those on the 1,400 mg daily dose, a 400-mg reduction). If hemoglobin levels dropped to 7.5 g/dL or lower, the patients were dropped from the study.

The SVR rate (undetectable HCV RNA 24 weeks after the end of treatment) was 71.5% among those whose ribavirin dosage was reduced and 70.9% among those treated with EPO. Among the 187 patients who did not develop anemia, the SVR rate was 40.1%; this group included a large number of patients who discontinued treatment because of adverse events. But of the 64 who completed treatment, the SVR rate was 89%. The overall SVR rate – among all 687 patients, those randomized and not randomized – was 63%.

Common adverse events were similar in the two randomized treatment groups, with anemia, fatigue, nausea, and headache being the most commonly reported. The rates of serious adverse events were 16% among those in the RBV dose-reduction arm and 13% of those on EPO. There were more thromboembolic events among the patients treated with EPO. There was one death in a patient in the RBV arm, a sudden cardiac death 3 weeks after stopping treatment.

The algorithm proposed by the authors, which has different hemoglobin monitoring recommendations for those with and without advanced fibrosis and cirrhosis, recommends that the primary intervention for managing anemia should be to reduce the RBV dosage. But if hemoglobin levels remain below 10 g/dL, "secondary interventions, such as administration of EPO, red cell transfusions, and reducing the dosage of peginterferon can be considered," the authors wrote. In addition, "it is important that the patient receives at least 50% of the total milligrams of RBV calculated from the initial RBV dosage (mg/d) and the assigned duration" defined by the response-guided therapy algorithm, they added.

The open-label design was one of the study’s limitations, and whether these results apply to other HCV treatment regimens is unclear, the authors noted. However, the results "would most likely be applicable to all RBV- and peginterferon/RBV-based regimens" for hepatitis C, they added.

The study was funded by Schering-Plough, the manufacturer of PegIntron and combination packs of PegIntron with ribavirin, which is now part of Merck. The investigator disclosures included having served as consultants and speakers, and/or having received grants from multiple pharmaceutical companies; the investigators include several current and former employees of Merck Sharp & Dohme Corp. (a subsidiary of Merck & Co.), the manufacturer of Victrelis.

emechcatie@frontlinemedcom.com

The results of a randomized, open-label study suggest that reducing the ribavirin dose should be the "primary approach" for managing anemia associated with peginterferon, ribavirin, and boceprevir therapy in patients with chronic hepatitis C, the authors of the study concluded.

In the study, the effects of two anemia-management strategies, ribavirin (RBV) dose reduction and erythropoietin (EPO) treatment, on the sustained virologic response (SVR) were similar – there was less than 1% difference between the two groups, according to the investigators, Dr. Fred F. Poordad of the Texas Liver Institute, at the University of Texas Health Science Center, San Antonio, and his associates. They also found that SVR rates were significantly lower among those who received less than half of the total ribavirin dose during the entire treatment period, compared with those who received a greater proportion of the total dosage.

"There appears to be no apparent benefit of using EPO as a first-line anemia-management strategy to enhance SVR rate or minimize relapse," the authors concluded. "EPO can be used as a secondary management strategy to prevent treatment interruption if RBV dosage reduction alone is inadequate, but the safety of EPO use in this setting has not been clearly established," they added. The study was published in the November issue of Gastroenterology (2013 [doi:10.1053/j.gastro.2013.07.051]).

The study includes an algorithm for managing boceprevir-related anemia, based on the results of this and other clinical studies, and the authors’ expertise.

The study, conducted between December 2009 and October 2011, compared the two regimens in 500 of 687 previously untreated patients with chronic HCV genotype-1 infections, who became anemic (hemoglobin levels dropping to 10 g/dL or lower) during treatment with the three drugs: peginterferon alfa-2b (PegIntron) at a dose of 1.5 mcg/kg per week; ribavirin at a dose of 600-1400 mg per day depending on weight; and boceprevir (Victrelis) at a dose of 800 mg three times a day. (After 4 weeks of treatment with peginterferon and RBV, boceprevir was added for 24 or 44 weeks). Their mean age was about 50 years, 33% were men, 77% were white, and 18% were black; 91% had a baseline viral load of more than 400,000 IU/mL. Almost 90% were in the United States, the rest were in Canada and Europe.

The 500 patients were randomized to treatment with EPO (a subcutaneous infusion of 40,000 IU a week) or a reduction in the ribavirin dose (200 mg/day or, for those on the 1,400 mg daily dose, a 400-mg reduction). If hemoglobin levels dropped to 7.5 g/dL or lower, the patients were dropped from the study.

The SVR rate (undetectable HCV RNA 24 weeks after the end of treatment) was 71.5% among those whose ribavirin dosage was reduced and 70.9% among those treated with EPO. Among the 187 patients who did not develop anemia, the SVR rate was 40.1%; this group included a large number of patients who discontinued treatment because of adverse events. But of the 64 who completed treatment, the SVR rate was 89%. The overall SVR rate – among all 687 patients, those randomized and not randomized – was 63%.

Common adverse events were similar in the two randomized treatment groups, with anemia, fatigue, nausea, and headache being the most commonly reported. The rates of serious adverse events were 16% among those in the RBV dose-reduction arm and 13% of those on EPO. There were more thromboembolic events among the patients treated with EPO. There was one death in a patient in the RBV arm, a sudden cardiac death 3 weeks after stopping treatment.

The algorithm proposed by the authors, which has different hemoglobin monitoring recommendations for those with and without advanced fibrosis and cirrhosis, recommends that the primary intervention for managing anemia should be to reduce the RBV dosage. But if hemoglobin levels remain below 10 g/dL, "secondary interventions, such as administration of EPO, red cell transfusions, and reducing the dosage of peginterferon can be considered," the authors wrote. In addition, "it is important that the patient receives at least 50% of the total milligrams of RBV calculated from the initial RBV dosage (mg/d) and the assigned duration" defined by the response-guided therapy algorithm, they added.

The open-label design was one of the study’s limitations, and whether these results apply to other HCV treatment regimens is unclear, the authors noted. However, the results "would most likely be applicable to all RBV- and peginterferon/RBV-based regimens" for hepatitis C, they added.

The study was funded by Schering-Plough, the manufacturer of PegIntron and combination packs of PegIntron with ribavirin, which is now part of Merck. The investigator disclosures included having served as consultants and speakers, and/or having received grants from multiple pharmaceutical companies; the investigators include several current and former employees of Merck Sharp & Dohme Corp. (a subsidiary of Merck & Co.), the manufacturer of Victrelis.

emechcatie@frontlinemedcom.com

SILVER SPRING, MD. – A Food and Drug Administration advisory panel has unanimously recommended the approval of sofosbuvir, a new antiviral drug, for treating adults with chronic hepatitis C infection, with several panelists describing the votes to approve the drug as historic.

At a meeting on Oct. 25, the FDA’s Antiviral Drugs Advisory Committee voted 15-0 to recommend approval of sofosbuvir for the treatment of two different chronic hepatitis C indications: In combination with pegylated interferon and ribavirin for treatment-naive adults with genotype 1 and 4 infections; and in combination with ribavirin for adults with genotype 2 and 3 infections.

If approved – which is expected – the second indication will mark the first approval of a treatment for chronic hepatitis C with an interferon-free regimen, and it will be the first drug in its class to be approved. Sofosbuvir is a nucleotide analogue inhibitor of the hepatitis C virus (HCV) NS5B polymerase enzyme, which plays an important role in HCV replication and is active against HCV genotypes 1 (the most common genotype in the United States), 2, 3, 4, 5, and 6. It is taken orally once a day at a 400-mg dose.

This is "truly a historic moment," said panelist Dr. Demetre Daskalakis, medical director of the HIV program at Mt. Sinai School of Medicine, New York. "I can’t wait to get this drug into the clinic. We are all excited," he added. The consumer representative on the panel, Daniel Raymond, policy director at the Harm Reduction Coalition, New York City, said that the company had "pulled off the hat trick" of superior efficacy, safety, and convenience over current treatments.

"I voted yes because, quite simply, this is a game changer," said Dr. Marc Ghany, staff physician in the liver diseases branch at the National Institute of Diabetes, Digestive and Kidney Diseases, Bethesda, Md.

The manufacturer, Gilead Sciences, has proposed that sofosbuvir be approved for treating chronic hepatitis C infection in combination with other agents in adults with genotypes 1-6 and/or adults waiting for a liver transplant, with different regimens of ribavirin, with or without pegylated interferon. The data on patients with genotypes 5 and 6 and on pretransplant patients are limited, and the panel was not asked to vote on approval for patients with those genotypes, or on approval for the pretransplant population.

The company presented the results of four phase III trials in patients with genotypes 2 and 3, which included an open-label study and randomized double-blind studies. The primary endpoint in all studies was the sustained virologic response rate (undetectable HCV) 12 weeks after active treatment was stopped (SVR12). In the studies, more than 1,000 patients received sofosbuvir.

The SVR12 rates of genotype 2 patients treated with sofosbuvir plus ribavirin for 12 weeks ranged from 93% to 97% among those who were treatment naive, and from 82% to 90% among those who were treatment experienced. For those with genotype 3 treated with sofosbuvir plus ribavirin for 24 weeks, the SVR12 rates were 93% among those who were treatment naive and 77% for those who were treatment experienced.

In an open-label study of 327 treatment-naive patients with genotypes 1, 4, 5, and 6, patients were treated with sofosbuvir plus pegylated interferon and ribavirin (PR) for 12 weeks. Most (292) of the patients had genotype 1, followed by genotype 4 (28 patients). The SVR12 rates were 89% among those with genotype 1 and 96% among those with genotype 4. The one patient with genotype 5 and all 6 patients with genotype 6 achieved an SVR12.

Gilead is also conducting a phase II study of patients on a liver transplant list who have hepatocellular carcinoma and genotypes 1-6 and were treated with sofosbuvir plus ribavirin for a maximum of 24 weeks (which was extended to 48 weeks) or until transplant. HCV almost always recurs after liver transplantation, and there are no approved treatments to prevent recurrence of HCV after liver transplantation. In the study, 64% of the patients met the primary efficacy endpoint – HCV RNA below detectable levels 12 weeks after transplant.

Panelists said there is a need to treat this group of patients, who are increasing in numbers and are very challenging to treat, and they should be studied further.

Summarizing the FDA’s view of the sofosbuvir data, Dr. Poonan Mishra, a medical officer in the FDA’s division of antiviral products, said that, for patients with chronic hepatitis C infection, sofosbuvir, in combination with ribavirin, provides the first "all oral interferon-free regimen" for patients with genotype 2 or 3 infections. Combined with pegylated interferon and ribavirin, sofosbuvir "provides improved efficacy and shorter treatment duration for patients with genotype 1 or 4 HCV infection," she added. The results in the liver transplant population were "encouraging," and address an unmet need for these patients, she said.

The regimens of sofosbuvir combined with ribavirin or PR in the study were well tolerated in the different groups of patients, including those waiting for liver transplant, and there were no clusters or trends of any specific types of adverse events identified. An evaluation of cardiac disorders in treated patients found no obvious safety issues related to cardiac toxicity, according to the FDA. A drug in development in the same class was associated with cardiac toxicity.

The FDA is expected to make a decision by Dec. 8. Sofosbuvir also is under review in the European Union, Australia, Canada, New Zealand, Switzerland and Turkey, according to Gilead.

The FDA usually follows the recommendations of its advisory panels. Members of FDA panels have usually been cleared of conflicts related to the product under review; occasionally, a panelist is given a waiver, but not at this meeting.

emechcatie@frontlinemedcom.com

SILVER SPRING, MD. – A Food and Drug Administration advisory panel has unanimously recommended the approval of sofosbuvir, a new antiviral drug, for treating adults with chronic hepatitis C infection, with several panelists describing the votes to approve the drug as historic.

At a meeting on Oct. 25, the FDA’s Antiviral Drugs Advisory Committee voted 15-0 to recommend approval of sofosbuvir for the treatment of two different chronic hepatitis C indications: In combination with pegylated interferon and ribavirin for treatment-naive adults with genotype 1 and 4 infections; and in combination with ribavirin for adults with genotype 2 and 3 infections.

If approved – which is expected – the second indication will mark the first approval of a treatment for chronic hepatitis C with an interferon-free regimen, and it will be the first drug in its class to be approved. Sofosbuvir is a nucleotide analogue inhibitor of the hepatitis C virus (HCV) NS5B polymerase enzyme, which plays an important role in HCV replication and is active against HCV genotypes 1 (the most common genotype in the United States), 2, 3, 4, 5, and 6. It is taken orally once a day at a 400-mg dose.

This is "truly a historic moment," said panelist Dr. Demetre Daskalakis, medical director of the HIV program at Mt. Sinai School of Medicine, New York. "I can’t wait to get this drug into the clinic. We are all excited," he added. The consumer representative on the panel, Daniel Raymond, policy director at the Harm Reduction Coalition, New York City, said that the company had "pulled off the hat trick" of superior efficacy, safety, and convenience over current treatments.

"I voted yes because, quite simply, this is a game changer," said Dr. Marc Ghany, staff physician in the liver diseases branch at the National Institute of Diabetes, Digestive and Kidney Diseases, Bethesda, Md.

The manufacturer, Gilead Sciences, has proposed that sofosbuvir be approved for treating chronic hepatitis C infection in combination with other agents in adults with genotypes 1-6 and/or adults waiting for a liver transplant, with different regimens of ribavirin, with or without pegylated interferon. The data on patients with genotypes 5 and 6 and on pretransplant patients are limited, and the panel was not asked to vote on approval for patients with those genotypes, or on approval for the pretransplant population.

The company presented the results of four phase III trials in patients with genotypes 2 and 3, which included an open-label study and randomized double-blind studies. The primary endpoint in all studies was the sustained virologic response rate (undetectable HCV) 12 weeks after active treatment was stopped (SVR12). In the studies, more than 1,000 patients received sofosbuvir.

The SVR12 rates of genotype 2 patients treated with sofosbuvir plus ribavirin for 12 weeks ranged from 93% to 97% among those who were treatment naive, and from 82% to 90% among those who were treatment experienced. For those with genotype 3 treated with sofosbuvir plus ribavirin for 24 weeks, the SVR12 rates were 93% among those who were treatment naive and 77% for those who were treatment experienced.

In an open-label study of 327 treatment-naive patients with genotypes 1, 4, 5, and 6, patients were treated with sofosbuvir plus pegylated interferon and ribavirin (PR) for 12 weeks. Most (292) of the patients had genotype 1, followed by genotype 4 (28 patients). The SVR12 rates were 89% among those with genotype 1 and 96% among those with genotype 4. The one patient with genotype 5 and all 6 patients with genotype 6 achieved an SVR12.

Gilead is also conducting a phase II study of patients on a liver transplant list who have hepatocellular carcinoma and genotypes 1-6 and were treated with sofosbuvir plus ribavirin for a maximum of 24 weeks (which was extended to 48 weeks) or until transplant. HCV almost always recurs after liver transplantation, and there are no approved treatments to prevent recurrence of HCV after liver transplantation. In the study, 64% of the patients met the primary efficacy endpoint – HCV RNA below detectable levels 12 weeks after transplant.

Panelists said there is a need to treat this group of patients, who are increasing in numbers and are very challenging to treat, and they should be studied further.

Summarizing the FDA’s view of the sofosbuvir data, Dr. Poonan Mishra, a medical officer in the FDA’s division of antiviral products, said that, for patients with chronic hepatitis C infection, sofosbuvir, in combination with ribavirin, provides the first "all oral interferon-free regimen" for patients with genotype 2 or 3 infections. Combined with pegylated interferon and ribavirin, sofosbuvir "provides improved efficacy and shorter treatment duration for patients with genotype 1 or 4 HCV infection," she added. The results in the liver transplant population were "encouraging," and address an unmet need for these patients, she said.

The regimens of sofosbuvir combined with ribavirin or PR in the study were well tolerated in the different groups of patients, including those waiting for liver transplant, and there were no clusters or trends of any specific types of adverse events identified. An evaluation of cardiac disorders in treated patients found no obvious safety issues related to cardiac toxicity, according to the FDA. A drug in development in the same class was associated with cardiac toxicity.

The FDA is expected to make a decision by Dec. 8. Sofosbuvir also is under review in the European Union, Australia, Canada, New Zealand, Switzerland and Turkey, according to Gilead.

The FDA usually follows the recommendations of its advisory panels. Members of FDA panels have usually been cleared of conflicts related to the product under review; occasionally, a panelist is given a waiver, but not at this meeting.

emechcatie@frontlinemedcom.com

SILVER SPRING, MD. – A Food and Drug Administration advisory panel has unanimously recommended the approval of sofosbuvir, a new antiviral drug, for treating adults with chronic hepatitis C infection, with several panelists describing the votes to approve the drug as historic.

At a meeting on Oct. 25, the FDA’s Antiviral Drugs Advisory Committee voted 15-0 to recommend approval of sofosbuvir for the treatment of two different chronic hepatitis C indications: In combination with pegylated interferon and ribavirin for treatment-naive adults with genotype 1 and 4 infections; and in combination with ribavirin for adults with genotype 2 and 3 infections.

If approved – which is expected – the second indication will mark the first approval of a treatment for chronic hepatitis C with an interferon-free regimen, and it will be the first drug in its class to be approved. Sofosbuvir is a nucleotide analogue inhibitor of the hepatitis C virus (HCV) NS5B polymerase enzyme, which plays an important role in HCV replication and is active against HCV genotypes 1 (the most common genotype in the United States), 2, 3, 4, 5, and 6. It is taken orally once a day at a 400-mg dose.

This is "truly a historic moment," said panelist Dr. Demetre Daskalakis, medical director of the HIV program at Mt. Sinai School of Medicine, New York. "I can’t wait to get this drug into the clinic. We are all excited," he added. The consumer representative on the panel, Daniel Raymond, policy director at the Harm Reduction Coalition, New York City, said that the company had "pulled off the hat trick" of superior efficacy, safety, and convenience over current treatments.

"I voted yes because, quite simply, this is a game changer," said Dr. Marc Ghany, staff physician in the liver diseases branch at the National Institute of Diabetes, Digestive and Kidney Diseases, Bethesda, Md.

The manufacturer, Gilead Sciences, has proposed that sofosbuvir be approved for treating chronic hepatitis C infection in combination with other agents in adults with genotypes 1-6 and/or adults waiting for a liver transplant, with different regimens of ribavirin, with or without pegylated interferon. The data on patients with genotypes 5 and 6 and on pretransplant patients are limited, and the panel was not asked to vote on approval for patients with those genotypes, or on approval for the pretransplant population.

The company presented the results of four phase III trials in patients with genotypes 2 and 3, which included an open-label study and randomized double-blind studies. The primary endpoint in all studies was the sustained virologic response rate (undetectable HCV) 12 weeks after active treatment was stopped (SVR12). In the studies, more than 1,000 patients received sofosbuvir.

The SVR12 rates of genotype 2 patients treated with sofosbuvir plus ribavirin for 12 weeks ranged from 93% to 97% among those who were treatment naive, and from 82% to 90% among those who were treatment experienced. For those with genotype 3 treated with sofosbuvir plus ribavirin for 24 weeks, the SVR12 rates were 93% among those who were treatment naive and 77% for those who were treatment experienced.

In an open-label study of 327 treatment-naive patients with genotypes 1, 4, 5, and 6, patients were treated with sofosbuvir plus pegylated interferon and ribavirin (PR) for 12 weeks. Most (292) of the patients had genotype 1, followed by genotype 4 (28 patients). The SVR12 rates were 89% among those with genotype 1 and 96% among those with genotype 4. The one patient with genotype 5 and all 6 patients with genotype 6 achieved an SVR12.

Gilead is also conducting a phase II study of patients on a liver transplant list who have hepatocellular carcinoma and genotypes 1-6 and were treated with sofosbuvir plus ribavirin for a maximum of 24 weeks (which was extended to 48 weeks) or until transplant. HCV almost always recurs after liver transplantation, and there are no approved treatments to prevent recurrence of HCV after liver transplantation. In the study, 64% of the patients met the primary efficacy endpoint – HCV RNA below detectable levels 12 weeks after transplant.

Panelists said there is a need to treat this group of patients, who are increasing in numbers and are very challenging to treat, and they should be studied further.

Summarizing the FDA’s view of the sofosbuvir data, Dr. Poonan Mishra, a medical officer in the FDA’s division of antiviral products, said that, for patients with chronic hepatitis C infection, sofosbuvir, in combination with ribavirin, provides the first "all oral interferon-free regimen" for patients with genotype 2 or 3 infections. Combined with pegylated interferon and ribavirin, sofosbuvir "provides improved efficacy and shorter treatment duration for patients with genotype 1 or 4 HCV infection," she added. The results in the liver transplant population were "encouraging," and address an unmet need for these patients, she said.

The regimens of sofosbuvir combined with ribavirin or PR in the study were well tolerated in the different groups of patients, including those waiting for liver transplant, and there were no clusters or trends of any specific types of adverse events identified. An evaluation of cardiac disorders in treated patients found no obvious safety issues related to cardiac toxicity, according to the FDA. A drug in development in the same class was associated with cardiac toxicity.

The FDA is expected to make a decision by Dec. 8. Sofosbuvir also is under review in the European Union, Australia, Canada, New Zealand, Switzerland and Turkey, according to Gilead.

The FDA usually follows the recommendations of its advisory panels. Members of FDA panels have usually been cleared of conflicts related to the product under review; occasionally, a panelist is given a waiver, but not at this meeting.

emechcatie@frontlinemedcom.com

Patients with chronic liver disease who are hospitalized for spontaneous bacterial peritonitis were more likely to be treated according to evidence-based guidelines if their care was comanaged by a hospitalist and a hepatologist, rather than the traditional approach, according to a report in the Journal of Clinical Gastroenterology.

In a study comparing outcomes before the implementation of a hospitalist/hepatologist comanagement program with those afterward at one medical center, the comanaged care improved adherence to a variety of recommendations, such as performing diagnostic paracentesis within 24 hours, administering albumin appropriately, and providing ongoing peritonitis prophylaxis at discharge, said Dr. Archita P. Desai of the section of gastroenterology, hepatology, and nutrition, University of Chicago Medical Center, and her associates.

"No study to date has evaluated the quality of comanaged hospitalist care for complex medical subspecialty patients," they noted.

Dr. Desai and her colleagues performed a chart review of 56 adults with chronic liver disease (CLD) who were admitted either during the 2 years before the comanagement program was implemented (January 2004 through June 2006) or the 4 years afterward (July 2006 through December 2010). A total of 26 patients received conventional care during the earlier period, and 30 received joint care under the new comanagement program during the latter.

The two study groups were similar regarding patient age, sex, race, etiology of cirrhosis, serum bilirubin levels, serum INR (international normalized ratio), end-stage liver disease scores, and percentage with bacteremia and/or variceal hemorrhage.

With the comanagement program, patients were admitted to a hepatology unit by a hospitalist team comprising an academic hospitalist and several nurse practitioners and physician assistants. The hepatology team included a hepatologist, a gastroenterology fellow, and internal medicine residents and medical students rotating through the unit.

Both teams evaluated patients separately but met for daily "sit-down" rounds in the early afternoon to discuss the cases.

Patients in the new program were significantly more likely to undergo paracentesis within 24 hours (100% vs. 79%), to receive albumin appropriately while hospitalized (97% vs. 65%), and to receive at discharge medication to prevent further peritonitis (91% vs. 32%).

Patients under comanagement also were less likely to receive fresh-frozen plasma, which is contraindicated, and more likely to have antibiotic therapy initiated within 6 hours of presentation (J. Clin. Gastroenterol. 2013 [doi:10.1097/MCG.0b013e3182a87f70]).

The two groups were similar regarding other processes of care such as the choice of appropriate antibiotics, the use of DVT prophylaxis while confined to bed, and the offer of pneumococcal vaccination at discharge.

There was a statistical trend, which did not reach significance, for comanaged patients to have a lower rate of transfer to an ICU (27% vs 17%). Similarly, there was a nonsignificant trend toward a lower inpatient mortality with comanaged 13%) than with conventional (27%) care.

Mortality at 30 days after discharge also was lower after comanagement than conventional care (0% vs 5.3%). However, this trend also didn’t reach statistical significance because 30-day mortality data were missing for a substantial number of patients in both study groups.

"We speculate that the close interactions between the primary inpatient team and the hepatology team during formal daily rounds facilitated structured communication between the hospitalist and the hepatology teams, and likely played a significant role in the intervention," Dr. Desai and her associates said.

In addition, comanagement allowed the hepatology team to be more involved with detailed discharge planning specifically related to liver disease, "which in turn improves transition to outpatient care, a time of vulnerability for these complex patients," they said.

Both the length of stay and the total cost of hospitalization tended to be higher under the comanagement program. However, "overall care may be more cost-effective after considering variables such as improved access to specialty-specific resources in the short term and the prospect of increasing transplantation rates earlier in the course of disease, which in the long term leads to the prevention of costly complications," the investigators noted.

This study was supported by the University of Chicago’s Liver Research Fund. No financial conflicts of interest were reported.

hospitalistnews@frontlinemedcom.com

Patients with chronic liver disease who are hospitalized for spontaneous bacterial peritonitis were more likely to be treated according to evidence-based guidelines if their care was comanaged by a hospitalist and a hepatologist, rather than the traditional approach, according to a report in the Journal of Clinical Gastroenterology.

In a study comparing outcomes before the implementation of a hospitalist/hepatologist comanagement program with those afterward at one medical center, the comanaged care improved adherence to a variety of recommendations, such as performing diagnostic paracentesis within 24 hours, administering albumin appropriately, and providing ongoing peritonitis prophylaxis at discharge, said Dr. Archita P. Desai of the section of gastroenterology, hepatology, and nutrition, University of Chicago Medical Center, and her associates.

"No study to date has evaluated the quality of comanaged hospitalist care for complex medical subspecialty patients," they noted.

Dr. Desai and her colleagues performed a chart review of 56 adults with chronic liver disease (CLD) who were admitted either during the 2 years before the comanagement program was implemented (January 2004 through June 2006) or the 4 years afterward (July 2006 through December 2010). A total of 26 patients received conventional care during the earlier period, and 30 received joint care under the new comanagement program during the latter.

The two study groups were similar regarding patient age, sex, race, etiology of cirrhosis, serum bilirubin levels, serum INR (international normalized ratio), end-stage liver disease scores, and percentage with bacteremia and/or variceal hemorrhage.

With the comanagement program, patients were admitted to a hepatology unit by a hospitalist team comprising an academic hospitalist and several nurse practitioners and physician assistants. The hepatology team included a hepatologist, a gastroenterology fellow, and internal medicine residents and medical students rotating through the unit.

Both teams evaluated patients separately but met for daily "sit-down" rounds in the early afternoon to discuss the cases.

Patients in the new program were significantly more likely to undergo paracentesis within 24 hours (100% vs. 79%), to receive albumin appropriately while hospitalized (97% vs. 65%), and to receive at discharge medication to prevent further peritonitis (91% vs. 32%).

Patients under comanagement also were less likely to receive fresh-frozen plasma, which is contraindicated, and more likely to have antibiotic therapy initiated within 6 hours of presentation (J. Clin. Gastroenterol. 2013 [doi:10.1097/MCG.0b013e3182a87f70]).

The two groups were similar regarding other processes of care such as the choice of appropriate antibiotics, the use of DVT prophylaxis while confined to bed, and the offer of pneumococcal vaccination at discharge.

There was a statistical trend, which did not reach significance, for comanaged patients to have a lower rate of transfer to an ICU (27% vs 17%). Similarly, there was a nonsignificant trend toward a lower inpatient mortality with comanaged 13%) than with conventional (27%) care.

Mortality at 30 days after discharge also was lower after comanagement than conventional care (0% vs 5.3%). However, this trend also didn’t reach statistical significance because 30-day mortality data were missing for a substantial number of patients in both study groups.

"We speculate that the close interactions between the primary inpatient team and the hepatology team during formal daily rounds facilitated structured communication between the hospitalist and the hepatology teams, and likely played a significant role in the intervention," Dr. Desai and her associates said.

In addition, comanagement allowed the hepatology team to be more involved with detailed discharge planning specifically related to liver disease, "which in turn improves transition to outpatient care, a time of vulnerability for these complex patients," they said.

Both the length of stay and the total cost of hospitalization tended to be higher under the comanagement program. However, "overall care may be more cost-effective after considering variables such as improved access to specialty-specific resources in the short term and the prospect of increasing transplantation rates earlier in the course of disease, which in the long term leads to the prevention of costly complications," the investigators noted.

This study was supported by the University of Chicago’s Liver Research Fund. No financial conflicts of interest were reported.

hospitalistnews@frontlinemedcom.com

Patients with chronic liver disease who are hospitalized for spontaneous bacterial peritonitis were more likely to be treated according to evidence-based guidelines if their care was comanaged by a hospitalist and a hepatologist, rather than the traditional approach, according to a report in the Journal of Clinical Gastroenterology.

In a study comparing outcomes before the implementation of a hospitalist/hepatologist comanagement program with those afterward at one medical center, the comanaged care improved adherence to a variety of recommendations, such as performing diagnostic paracentesis within 24 hours, administering albumin appropriately, and providing ongoing peritonitis prophylaxis at discharge, said Dr. Archita P. Desai of the section of gastroenterology, hepatology, and nutrition, University of Chicago Medical Center, and her associates.

"No study to date has evaluated the quality of comanaged hospitalist care for complex medical subspecialty patients," they noted.

Dr. Desai and her colleagues performed a chart review of 56 adults with chronic liver disease (CLD) who were admitted either during the 2 years before the comanagement program was implemented (January 2004 through June 2006) or the 4 years afterward (July 2006 through December 2010). A total of 26 patients received conventional care during the earlier period, and 30 received joint care under the new comanagement program during the latter.

The two study groups were similar regarding patient age, sex, race, etiology of cirrhosis, serum bilirubin levels, serum INR (international normalized ratio), end-stage liver disease scores, and percentage with bacteremia and/or variceal hemorrhage.

With the comanagement program, patients were admitted to a hepatology unit by a hospitalist team comprising an academic hospitalist and several nurse practitioners and physician assistants. The hepatology team included a hepatologist, a gastroenterology fellow, and internal medicine residents and medical students rotating through the unit.

Both teams evaluated patients separately but met for daily "sit-down" rounds in the early afternoon to discuss the cases.

Patients in the new program were significantly more likely to undergo paracentesis within 24 hours (100% vs. 79%), to receive albumin appropriately while hospitalized (97% vs. 65%), and to receive at discharge medication to prevent further peritonitis (91% vs. 32%).

Patients under comanagement also were less likely to receive fresh-frozen plasma, which is contraindicated, and more likely to have antibiotic therapy initiated within 6 hours of presentation (J. Clin. Gastroenterol. 2013 [doi:10.1097/MCG.0b013e3182a87f70]).

The two groups were similar regarding other processes of care such as the choice of appropriate antibiotics, the use of DVT prophylaxis while confined to bed, and the offer of pneumococcal vaccination at discharge.

There was a statistical trend, which did not reach significance, for comanaged patients to have a lower rate of transfer to an ICU (27% vs 17%). Similarly, there was a nonsignificant trend toward a lower inpatient mortality with comanaged 13%) than with conventional (27%) care.

Mortality at 30 days after discharge also was lower after comanagement than conventional care (0% vs 5.3%). However, this trend also didn’t reach statistical significance because 30-day mortality data were missing for a substantial number of patients in both study groups.

"We speculate that the close interactions between the primary inpatient team and the hepatology team during formal daily rounds facilitated structured communication between the hospitalist and the hepatology teams, and likely played a significant role in the intervention," Dr. Desai and her associates said.

In addition, comanagement allowed the hepatology team to be more involved with detailed discharge planning specifically related to liver disease, "which in turn improves transition to outpatient care, a time of vulnerability for these complex patients," they said.

Both the length of stay and the total cost of hospitalization tended to be higher under the comanagement program. However, "overall care may be more cost-effective after considering variables such as improved access to specialty-specific resources in the short term and the prospect of increasing transplantation rates earlier in the course of disease, which in the long term leads to the prevention of costly complications," the investigators noted.

This study was supported by the University of Chicago’s Liver Research Fund. No financial conflicts of interest were reported.

hospitalistnews@frontlinemedcom.com

Combination therapy with the second-generation protease inhibitor danoprevir yielded high rates of sustained virologic response in hepatitis C.

Moreover, a large portion of patients also demonstrated an extended rapid virologic response up to 20 weeks, reported Dr. Patrick Marcellin and his colleagues in the October issue of Gastroenterology.

Dr. Marcellin, of the Hôpital Beaujon in Clichy, France, and his coinvestigators looked at 225 treatment-naive adults with hepatitis C virus (HCV) genotype 1 infection, including those who had a serum RNA level of 50,000 IU/mL or more.

Exclusion criteria included advanced fibrosis or cirrhosis, anemia, poorly controlled diabetes, or body mass index less than 18 kg/m² or greater than 36 kg/m².

The goal of this phase II, randomized, placebo-controlled study (ATLAS) was to evaluate the efficacy of treatment with danoprevir plus peginterferon alfa-2a/ribavirin for 12 weeks, compared with peginterferon alfa-2a/ribavirin alone.

Patients were randomized to one of three doses of oral danoprevir or placebo: 300 mg every 8 hours, 600 mg every 12 hours, or 900 mg every 12 hours.

All doses and placebo were given with standard combination HCV therapy, including subcutaneous peginterferon alfa-2a 180 mg/week plus oral ribavirin (1,000 mg/day for patients with a body weight less than 75 kg or 1,200 mg/day for patients weighing 75 kg or more).

At week 12, treatment with danoprevir or placebo was stopped, and peginterferon alfa-2a/ribavirin was continued for a total duration of 24 or 48 weeks, according to patient response.

Dr. Marcellin found that by week 1, mean decreases in HCV RNA ranged from 3.95 to 4.28 log₁₀ IU/mL in the danoprevir groups, compared with 0.77 log₁₀ IU/mL in the placebo group.

By week 2, according to the investigators, more than half of the danoprevir patients and none of the placebo recipients had achieved undetectable HCV RNA levels.

Indeed, broken down by dose, the researchers calculated that 74% of the danoprevir 300-mg group achieved a rapid virologic response (undetectable serum HCV RNA at week 4), with 65% maintaining an extended rapid virologic response (eRVR), defined as an undetectable HCV RNA that lasted from weeks 4 through 20.

Among the patients taking 600-mg doses, 88% achieved an RVR, with 79% maintaining an eRVR at week 20.

Finally, 86% of patients in the 900-mg treatment group achieved an RVR, although only 18% reached an eRVR.

Patients with an eRVR stopped all treatment at 24 weeks.

"Relapse occurred in 18%, 8%, and 11% of patients treated with danoprevir 300 mg, 600 mg, and 900 mg, respectively, versus 38% in the placebo group," the authors wrote.

Looking at the side-effect profile, Dr. Marcellin reported that fatigue, headache, nausea, insomnia, myalgia, and chills were the most common adverse events for both the treatment and placebo groups.

They also observed reversible, grade 4 elevations in alanine aminotransferase (ALT) levels between weeks 6 and 12 in 2% of danoprevir-treated patients, including three in the 900-mg cohort and one in the 600-mg cohort.

Treatment was discontinued, and serum ALT levels returned to within 1.5 times the upper limit of normal within a month for all four patients, the authors added.

"Notwithstanding the low incidence of reversible ALT elevations observed with high-dose danoprevir in this trial, danoprevir also appears to have a better tolerability profile than either boceprevir or telaprevir, as evidenced by the lower incidence of rash and anemia among danoprevir-treated patients compared with placebo recipients," concluded the investigators.

Indeed, they pointed to other studies showing that coadministration of low-dose ritonavir, another protease inhibitor, "significantly inhibits danoprevir reactive metabolite formation, proposed to be associated with ALT elevations."

"Studies to further evaluate the efficacy and safety of danoprevir in different patient groups are ongoing," the researchers said.

Dr. Marcellin and his fellow investigators reported financial relationships with numerous pharmaceutical companies, including Roche, the maker of danoprevir, which also funded this study.

Combination therapy with the second-generation protease inhibitor danoprevir yielded high rates of sustained virologic response in hepatitis C.

Moreover, a large portion of patients also demonstrated an extended rapid virologic response up to 20 weeks, reported Dr. Patrick Marcellin and his colleagues in the October issue of Gastroenterology.

Dr. Marcellin, of the Hôpital Beaujon in Clichy, France, and his coinvestigators looked at 225 treatment-naive adults with hepatitis C virus (HCV) genotype 1 infection, including those who had a serum RNA level of 50,000 IU/mL or more.

Exclusion criteria included advanced fibrosis or cirrhosis, anemia, poorly controlled diabetes, or body mass index less than 18 kg/m² or greater than 36 kg/m².

The goal of this phase II, randomized, placebo-controlled study (ATLAS) was to evaluate the efficacy of treatment with danoprevir plus peginterferon alfa-2a/ribavirin for 12 weeks, compared with peginterferon alfa-2a/ribavirin alone.

Patients were randomized to one of three doses of oral danoprevir or placebo: 300 mg every 8 hours, 600 mg every 12 hours, or 900 mg every 12 hours.

All doses and placebo were given with standard combination HCV therapy, including subcutaneous peginterferon alfa-2a 180 mg/week plus oral ribavirin (1,000 mg/day for patients with a body weight less than 75 kg or 1,200 mg/day for patients weighing 75 kg or more).

At week 12, treatment with danoprevir or placebo was stopped, and peginterferon alfa-2a/ribavirin was continued for a total duration of 24 or 48 weeks, according to patient response.

Dr. Marcellin found that by week 1, mean decreases in HCV RNA ranged from 3.95 to 4.28 log₁₀ IU/mL in the danoprevir groups, compared with 0.77 log₁₀ IU/mL in the placebo group.

By week 2, according to the investigators, more than half of the danoprevir patients and none of the placebo recipients had achieved undetectable HCV RNA levels.

Indeed, broken down by dose, the researchers calculated that 74% of the danoprevir 300-mg group achieved a rapid virologic response (undetectable serum HCV RNA at week 4), with 65% maintaining an extended rapid virologic response (eRVR), defined as an undetectable HCV RNA that lasted from weeks 4 through 20.

Among the patients taking 600-mg doses, 88% achieved an RVR, with 79% maintaining an eRVR at week 20.

Finally, 86% of patients in the 900-mg treatment group achieved an RVR, although only 18% reached an eRVR.

Patients with an eRVR stopped all treatment at 24 weeks.

"Relapse occurred in 18%, 8%, and 11% of patients treated with danoprevir 300 mg, 600 mg, and 900 mg, respectively, versus 38% in the placebo group," the authors wrote.

Looking at the side-effect profile, Dr. Marcellin reported that fatigue, headache, nausea, insomnia, myalgia, and chills were the most common adverse events for both the treatment and placebo groups.

They also observed reversible, grade 4 elevations in alanine aminotransferase (ALT) levels between weeks 6 and 12 in 2% of danoprevir-treated patients, including three in the 900-mg cohort and one in the 600-mg cohort.

Treatment was discontinued, and serum ALT levels returned to within 1.5 times the upper limit of normal within a month for all four patients, the authors added.

"Notwithstanding the low incidence of reversible ALT elevations observed with high-dose danoprevir in this trial, danoprevir also appears to have a better tolerability profile than either boceprevir or telaprevir, as evidenced by the lower incidence of rash and anemia among danoprevir-treated patients compared with placebo recipients," concluded the investigators.

Indeed, they pointed to other studies showing that coadministration of low-dose ritonavir, another protease inhibitor, "significantly inhibits danoprevir reactive metabolite formation, proposed to be associated with ALT elevations."

"Studies to further evaluate the efficacy and safety of danoprevir in different patient groups are ongoing," the researchers said.

Dr. Marcellin and his fellow investigators reported financial relationships with numerous pharmaceutical companies, including Roche, the maker of danoprevir, which also funded this study.

Combination therapy with the second-generation protease inhibitor danoprevir yielded high rates of sustained virologic response in hepatitis C.

Moreover, a large portion of patients also demonstrated an extended rapid virologic response up to 20 weeks, reported Dr. Patrick Marcellin and his colleagues in the October issue of Gastroenterology.

Dr. Marcellin, of the Hôpital Beaujon in Clichy, France, and his coinvestigators looked at 225 treatment-naive adults with hepatitis C virus (HCV) genotype 1 infection, including those who had a serum RNA level of 50,000 IU/mL or more.

Exclusion criteria included advanced fibrosis or cirrhosis, anemia, poorly controlled diabetes, or body mass index less than 18 kg/m² or greater than 36 kg/m².

The goal of this phase II, randomized, placebo-controlled study (ATLAS) was to evaluate the efficacy of treatment with danoprevir plus peginterferon alfa-2a/ribavirin for 12 weeks, compared with peginterferon alfa-2a/ribavirin alone.

Patients were randomized to one of three doses of oral danoprevir or placebo: 300 mg every 8 hours, 600 mg every 12 hours, or 900 mg every 12 hours.

All doses and placebo were given with standard combination HCV therapy, including subcutaneous peginterferon alfa-2a 180 mg/week plus oral ribavirin (1,000 mg/day for patients with a body weight less than 75 kg or 1,200 mg/day for patients weighing 75 kg or more).

At week 12, treatment with danoprevir or placebo was stopped, and peginterferon alfa-2a/ribavirin was continued for a total duration of 24 or 48 weeks, according to patient response.

Dr. Marcellin found that by week 1, mean decreases in HCV RNA ranged from 3.95 to 4.28 log₁₀ IU/mL in the danoprevir groups, compared with 0.77 log₁₀ IU/mL in the placebo group.

By week 2, according to the investigators, more than half of the danoprevir patients and none of the placebo recipients had achieved undetectable HCV RNA levels.

Indeed, broken down by dose, the researchers calculated that 74% of the danoprevir 300-mg group achieved a rapid virologic response (undetectable serum HCV RNA at week 4), with 65% maintaining an extended rapid virologic response (eRVR), defined as an undetectable HCV RNA that lasted from weeks 4 through 20.

Among the patients taking 600-mg doses, 88% achieved an RVR, with 79% maintaining an eRVR at week 20.

Finally, 86% of patients in the 900-mg treatment group achieved an RVR, although only 18% reached an eRVR.

Patients with an eRVR stopped all treatment at 24 weeks.

"Relapse occurred in 18%, 8%, and 11% of patients treated with danoprevir 300 mg, 600 mg, and 900 mg, respectively, versus 38% in the placebo group," the authors wrote.

Looking at the side-effect profile, Dr. Marcellin reported that fatigue, headache, nausea, insomnia, myalgia, and chills were the most common adverse events for both the treatment and placebo groups.

They also observed reversible, grade 4 elevations in alanine aminotransferase (ALT) levels between weeks 6 and 12 in 2% of danoprevir-treated patients, including three in the 900-mg cohort and one in the 600-mg cohort.

Treatment was discontinued, and serum ALT levels returned to within 1.5 times the upper limit of normal within a month for all four patients, the authors added.

"Notwithstanding the low incidence of reversible ALT elevations observed with high-dose danoprevir in this trial, danoprevir also appears to have a better tolerability profile than either boceprevir or telaprevir, as evidenced by the lower incidence of rash and anemia among danoprevir-treated patients compared with placebo recipients," concluded the investigators.

Indeed, they pointed to other studies showing that coadministration of low-dose ritonavir, another protease inhibitor, "significantly inhibits danoprevir reactive metabolite formation, proposed to be associated with ALT elevations."

"Studies to further evaluate the efficacy and safety of danoprevir in different patient groups are ongoing," the researchers said.

Dr. Marcellin and his fellow investigators reported financial relationships with numerous pharmaceutical companies, including Roche, the maker of danoprevir, which also funded this study.

Dr. Guadalupe Garcia-Tsao reviewed the evidence supporting treatment recommendation for patients with variceal hemorrhage at the 2013 AGA Spring Postgraduate Course. Early resuscitation (transfusion with hemoglobin in 7-9-g/L range, antibiotic prophylaxis, and vasoactive drugs) remains the cornerstone in the management of patients with variceal hemorrhage. Patients should undergo an upper endoscopy within 12 hours of presentation; those confirmed to have bled from esophageal varices should then undergo endoscopic variceal ligation, whereas those with bleeding gastric varices can be considered for early transjugular intrahepatic portosystemic shunt (TIPS). Early TIPS (ideally done within 24 hours) should also be considered for patients at high risk for rebleeding. These include patients with Child class C cirrhosis or those with Child class B but with active bleeding during endoscopy.

Dr. Bruce Runyon provided an overview of management of patients with ascites. The first-line strategies in the treatment of ascites include complete cessation of alcohol consumption, sodium restriction (2-g/d salt diet), diuretics, and consideration for liver transplantation. Second-line treatments include discontinuation of beta blockers, angiotensin-converting enzyme inhibitors, and angiotensin receptor blockers; consideration to add midodrine, especially in the profoundly hypotensive patients; serial therapeutic paracenteses; and TIPS. TIPS can be considered in patients with refractory ascites who are younger than 65 year old, those with a caregiver at home, Child-Pugh score less than 12, MELD score less than 18, no evidence of alcoholic hepatitis, no severe spontaneous hepatic encephalopathy, and an ejection fraction greater than 60%.

Dr. Alan Barkun provided evidence-based recommendations to guide imaging and treatment decisions in patients with biliary obstruction. High-quality abdominal ultrasound remains the most cost-effective initial test in patients with biliary obstruction. Choice of subsequent imaging is based on the likelihood of benign versus malignant obstruction.

In patients with symptomatic cholelithiasis, presence of common bile duct (CBD) stones on ultrasound, ascending cholangitis, or bilirubin greater than 4 mg/dL should prompt preoperative endoscopic retrograde cholangiopancreaticography (ERCP). Preoperative ERCP is also warranted in patients who have a dilated CBD in the presence of a mildly elevated bilirubin level (1.8-4 mg/dL). Patients who do not meet these criteria but who are still suspected to have CBD stones (gallstone pancreatitis, abnormal liver tests other than bilirubin) should undergo a preoperative magnetic resonance cholangiopancreaticograph (MRCP), endoscopic ultrasound (EUS), or intraoperative cholangiogram to rule out CBD stones. Remaining patients are at low risk for CBD stones and can be managed with laparoscopic cholecystectomy alone. In patients suspected to have malignant biliary obstruction, the next imaging modality should be selected based on the level of biliary obstruction. If the lesion is suspected to involve the upper or middle third of CBD, then the best test is an MRCP or a helical CT cholangiography (although an EUS may be used for lesions in the mid third). Either an ERCP or EUS can be used for lesions involving lower third of CBD. A PET CT in a locally advanced lesion may help rule out distant metastasis. In patients with advanced disease, palliative treatment may include an EUS (with fine-needle aspiration) and an ERCP with stenting or percutaneous transhepatic cholangiograpy.

Dr. William Brugge discussed the management of intraductal papillary mucinous neoplasms (IPMNs). IPMN is a common yet slowly progressive neoplasm. Resection should be considered only in the presence of high-risk stigmata: obstructive jaundice, enhancing solid component in the cyst, or with pancreatic duct dilation grater than 10 mm. Other worrisome features that need evaluation with EUS/FNA include cysts greater than 3cm, main duct 5-9 mm, and suspicion for a mural nodule. Surgery is recommended if EUS/FNA confirms main duct involvement, presence of a mural nodule, or if the cytology is positive for malignancy. Patients who do not have any of these alarm signs can be monitored. However, the type and frequency of follow-up imaging depends on the size of the largest cyst: Cysts greater than 3 cm need MRI alternating with EUS every 3 months; 2-3-cm cysts require EUS every 3-6 months; 1-2-cm cysts require annual CT or MRI. Patients with small cysts (less than 1 cm) can be imaged every 2-3 years with a CT or an MRI.

Dr. Bruce Bacon discussed the current and future treatment options for patients with hepatitis C virus infection. With the advent of direct-acting antiviral agents, hepatitis C treatment will become shorter, safer, and more effective in the near term. Given this changing landscape, the most important decision that patients and clinicians face today is whether to treat now or wait for new treatment. Although each decision has to be tailored to a given patient’s clinical condition and wishes, patients with mild fibrosis (F0-F2), those with prior nonresponse to pegylated interferon–based treatment, and patients with cirrhosis (particularly those with portal hypertension) may benefit from waiting for these new treatments.

Dr. Kanwal is associate professor of medicine at Michael E. DeBakey Veterans Affairs Medical Center, Baylor College of Medicine, Houston.

Dr. Guadalupe Garcia-Tsao reviewed the evidence supporting treatment recommendation for patients with variceal hemorrhage at the 2013 AGA Spring Postgraduate Course. Early resuscitation (transfusion with hemoglobin in 7-9-g/L range, antibiotic prophylaxis, and vasoactive drugs) remains the cornerstone in the management of patients with variceal hemorrhage. Patients should undergo an upper endoscopy within 12 hours of presentation; those confirmed to have bled from esophageal varices should then undergo endoscopic variceal ligation, whereas those with bleeding gastric varices can be considered for early transjugular intrahepatic portosystemic shunt (TIPS). Early TIPS (ideally done within 24 hours) should also be considered for patients at high risk for rebleeding. These include patients with Child class C cirrhosis or those with Child class B but with active bleeding during endoscopy.

Dr. Bruce Runyon provided an overview of management of patients with ascites. The first-line strategies in the treatment of ascites include complete cessation of alcohol consumption, sodium restriction (2-g/d salt diet), diuretics, and consideration for liver transplantation. Second-line treatments include discontinuation of beta blockers, angiotensin-converting enzyme inhibitors, and angiotensin receptor blockers; consideration to add midodrine, especially in the profoundly hypotensive patients; serial therapeutic paracenteses; and TIPS. TIPS can be considered in patients with refractory ascites who are younger than 65 year old, those with a caregiver at home, Child-Pugh score less than 12, MELD score less than 18, no evidence of alcoholic hepatitis, no severe spontaneous hepatic encephalopathy, and an ejection fraction greater than 60%.

Dr. Alan Barkun provided evidence-based recommendations to guide imaging and treatment decisions in patients with biliary obstruction. High-quality abdominal ultrasound remains the most cost-effective initial test in patients with biliary obstruction. Choice of subsequent imaging is based on the likelihood of benign versus malignant obstruction.

In patients with symptomatic cholelithiasis, presence of common bile duct (CBD) stones on ultrasound, ascending cholangitis, or bilirubin greater than 4 mg/dL should prompt preoperative endoscopic retrograde cholangiopancreaticography (ERCP). Preoperative ERCP is also warranted in patients who have a dilated CBD in the presence of a mildly elevated bilirubin level (1.8-4 mg/dL). Patients who do not meet these criteria but who are still suspected to have CBD stones (gallstone pancreatitis, abnormal liver tests other than bilirubin) should undergo a preoperative magnetic resonance cholangiopancreaticograph (MRCP), endoscopic ultrasound (EUS), or intraoperative cholangiogram to rule out CBD stones. Remaining patients are at low risk for CBD stones and can be managed with laparoscopic cholecystectomy alone. In patients suspected to have malignant biliary obstruction, the next imaging modality should be selected based on the level of biliary obstruction. If the lesion is suspected to involve the upper or middle third of CBD, then the best test is an MRCP or a helical CT cholangiography (although an EUS may be used for lesions in the mid third). Either an ERCP or EUS can be used for lesions involving lower third of CBD. A PET CT in a locally advanced lesion may help rule out distant metastasis. In patients with advanced disease, palliative treatment may include an EUS (with fine-needle aspiration) and an ERCP with stenting or percutaneous transhepatic cholangiograpy.

Dr. William Brugge discussed the management of intraductal papillary mucinous neoplasms (IPMNs). IPMN is a common yet slowly progressive neoplasm. Resection should be considered only in the presence of high-risk stigmata: obstructive jaundice, enhancing solid component in the cyst, or with pancreatic duct dilation grater than 10 mm. Other worrisome features that need evaluation with EUS/FNA include cysts greater than 3cm, main duct 5-9 mm, and suspicion for a mural nodule. Surgery is recommended if EUS/FNA confirms main duct involvement, presence of a mural nodule, or if the cytology is positive for malignancy. Patients who do not have any of these alarm signs can be monitored. However, the type and frequency of follow-up imaging depends on the size of the largest cyst: Cysts greater than 3 cm need MRI alternating with EUS every 3 months; 2-3-cm cysts require EUS every 3-6 months; 1-2-cm cysts require annual CT or MRI. Patients with small cysts (less than 1 cm) can be imaged every 2-3 years with a CT or an MRI.

Dr. Bruce Bacon discussed the current and future treatment options for patients with hepatitis C virus infection. With the advent of direct-acting antiviral agents, hepatitis C treatment will become shorter, safer, and more effective in the near term. Given this changing landscape, the most important decision that patients and clinicians face today is whether to treat now or wait for new treatment. Although each decision has to be tailored to a given patient’s clinical condition and wishes, patients with mild fibrosis (F0-F2), those with prior nonresponse to pegylated interferon–based treatment, and patients with cirrhosis (particularly those with portal hypertension) may benefit from waiting for these new treatments.

Dr. Kanwal is associate professor of medicine at Michael E. DeBakey Veterans Affairs Medical Center, Baylor College of Medicine, Houston.

Dr. Guadalupe Garcia-Tsao reviewed the evidence supporting treatment recommendation for patients with variceal hemorrhage at the 2013 AGA Spring Postgraduate Course. Early resuscitation (transfusion with hemoglobin in 7-9-g/L range, antibiotic prophylaxis, and vasoactive drugs) remains the cornerstone in the management of patients with variceal hemorrhage. Patients should undergo an upper endoscopy within 12 hours of presentation; those confirmed to have bled from esophageal varices should then undergo endoscopic variceal ligation, whereas those with bleeding gastric varices can be considered for early transjugular intrahepatic portosystemic shunt (TIPS). Early TIPS (ideally done within 24 hours) should also be considered for patients at high risk for rebleeding. These include patients with Child class C cirrhosis or those with Child class B but with active bleeding during endoscopy.

Dr. Bruce Runyon provided an overview of management of patients with ascites. The first-line strategies in the treatment of ascites include complete cessation of alcohol consumption, sodium restriction (2-g/d salt diet), diuretics, and consideration for liver transplantation. Second-line treatments include discontinuation of beta blockers, angiotensin-converting enzyme inhibitors, and angiotensin receptor blockers; consideration to add midodrine, especially in the profoundly hypotensive patients; serial therapeutic paracenteses; and TIPS. TIPS can be considered in patients with refractory ascites who are younger than 65 year old, those with a caregiver at home, Child-Pugh score less than 12, MELD score less than 18, no evidence of alcoholic hepatitis, no severe spontaneous hepatic encephalopathy, and an ejection fraction greater than 60%.

Dr. Alan Barkun provided evidence-based recommendations to guide imaging and treatment decisions in patients with biliary obstruction. High-quality abdominal ultrasound remains the most cost-effective initial test in patients with biliary obstruction. Choice of subsequent imaging is based on the likelihood of benign versus malignant obstruction.

In patients with symptomatic cholelithiasis, presence of common bile duct (CBD) stones on ultrasound, ascending cholangitis, or bilirubin greater than 4 mg/dL should prompt preoperative endoscopic retrograde cholangiopancreaticography (ERCP). Preoperative ERCP is also warranted in patients who have a dilated CBD in the presence of a mildly elevated bilirubin level (1.8-4 mg/dL). Patients who do not meet these criteria but who are still suspected to have CBD stones (gallstone pancreatitis, abnormal liver tests other than bilirubin) should undergo a preoperative magnetic resonance cholangiopancreaticograph (MRCP), endoscopic ultrasound (EUS), or intraoperative cholangiogram to rule out CBD stones. Remaining patients are at low risk for CBD stones and can be managed with laparoscopic cholecystectomy alone. In patients suspected to have malignant biliary obstruction, the next imaging modality should be selected based on the level of biliary obstruction. If the lesion is suspected to involve the upper or middle third of CBD, then the best test is an MRCP or a helical CT cholangiography (although an EUS may be used for lesions in the mid third). Either an ERCP or EUS can be used for lesions involving lower third of CBD. A PET CT in a locally advanced lesion may help rule out distant metastasis. In patients with advanced disease, palliative treatment may include an EUS (with fine-needle aspiration) and an ERCP with stenting or percutaneous transhepatic cholangiograpy.

Dr. William Brugge discussed the management of intraductal papillary mucinous neoplasms (IPMNs). IPMN is a common yet slowly progressive neoplasm. Resection should be considered only in the presence of high-risk stigmata: obstructive jaundice, enhancing solid component in the cyst, or with pancreatic duct dilation grater than 10 mm. Other worrisome features that need evaluation with EUS/FNA include cysts greater than 3cm, main duct 5-9 mm, and suspicion for a mural nodule. Surgery is recommended if EUS/FNA confirms main duct involvement, presence of a mural nodule, or if the cytology is positive for malignancy. Patients who do not have any of these alarm signs can be monitored. However, the type and frequency of follow-up imaging depends on the size of the largest cyst: Cysts greater than 3 cm need MRI alternating with EUS every 3 months; 2-3-cm cysts require EUS every 3-6 months; 1-2-cm cysts require annual CT or MRI. Patients with small cysts (less than 1 cm) can be imaged every 2-3 years with a CT or an MRI.

Dr. Bruce Bacon discussed the current and future treatment options for patients with hepatitis C virus infection. With the advent of direct-acting antiviral agents, hepatitis C treatment will become shorter, safer, and more effective in the near term. Given this changing landscape, the most important decision that patients and clinicians face today is whether to treat now or wait for new treatment. Although each decision has to be tailored to a given patient’s clinical condition and wishes, patients with mild fibrosis (F0-F2), those with prior nonresponse to pegylated interferon–based treatment, and patients with cirrhosis (particularly those with portal hypertension) may benefit from waiting for these new treatments.

Dr. Kanwal is associate professor of medicine at Michael E. DeBakey Veterans Affairs Medical Center, Baylor College of Medicine, Houston.

Combined therapy with pentoxifylline and prednisolone failed to improve 6-month survival in patients with severe alcoholic hepatitis, compared with prednisolone alone, according to a report published online Sept. 10 in JAMA.

In the largest and the only double-blind randomized clinical trial of this combination therapy performed to date, overall survival at 6 months was 69.9% for pentoxifylline plus prednisolone, compared with 69.2% for placebo plus prednisolone. "Our study does not support the use of a combination of pentoxifylline and prednisolone for severe alcoholic hepatitis," said Dr. Philippe Mathurin of Hopital Huriez, Lille (France), and his associates in their report (JAMA. 2013;310:1033-41. doi:10.1001/jama.2013.276300).

The two agents are believed to have two different and perhaps complementary mechanisms of action, so it was thought that combining them might have a synergistic therapeutic effect. Pentoxifylline appears to protect against the hepatorenal syndrome without exerting any significant effect on inflammatory cytokines or liver tests, while prednisolone improves liver function, inhibits inflammatory cytokines, and interferes with the activation of polymorphonuclear neutrophils.

Dr. Mathurin and his colleagues compared the combination therapy against prednisolone alone in 270 patients treated at 23 French and 1 Belgian hospital during a 3-year period. The study subjects were heavy drinkers with biopsy-proven alcoholic hepatitis whose disease was judged to be severe based on the recent onset of jaundice and a Maddrey score of at least 32.

The 163 men and 107 women were assigned randomly to receive either 40 mg prednisolone once daily plus 400 mg pentoxifylline three times daily (133 patients) or 40 mg prednisolone once daily plus a placebo three times daily (137 patients), for 28 days. If adverse effects developed, treatment could be reduced or interrupted at the discretion of the treating physician.

The primary endpoint was survival 6 months after initiating treatment.

There was no significant difference in this outcome between the combination-therapy group (69.9%) and the single-therapy group (69.2%) in the intention-to-treat analysis nor in the per-protocol analysis (72.4% and 70%, respectively).

The mean length of time until death also was not significantly different: 49.7 days with combination therapy and 51.4 days with single therapy, the investigators said.

Causes of death also were similar between the two study groups. Complications of liver failure were cited in approximately 82% of the entire study population and gastrointestinal bleeding in the remaining 18%.

Overall, 26% of the study subjects relapsed and began drinking alcohol again during 6-month follow-up. However, survival did not differ between patients who relapsed and those who did not.

Patients deemed to be treatment responders had markedly better 6-month survival (85%) than did nonresponders (46%), but the treatment response rate did not differ between the two study groups. Similarly, in an analysis restricted only to complete responders and null responders, survival did not differ significantly between patients who received the combination therapy and those who received prednisolone alone.

At the beginning of the study, it was thought that the combination of pentoxifylline plus prednisolone would improve survival chiefly by reducing the incidence of hepatorenal syndrome, relative to prednisolone alone. And at the conclusion of the 1-month course of treatment, the risk of hepatorenal syndrome was significantly lower with combination therapy (3.1%) than with prednisolone alone (11.7%). However, this difference disappeared by the end of follow-up.

But it is important to note that this study was only powered to detect a difference in survival, the primary outcome, and was likely underpowered to detect differences in secondary outcomes such as the rate of the hepatorenal syndrome. "Therefore, the difference in the incidence of hepatorenal syndrome in our study should not be interpreted as being null, and a larger study is necessary to evaluate this issue," according to Dr. Mathurin and his associates.

Regarding the adverse effects of treatment, 13 patients in each study group required temporary withdrawal from therapy. And the rate of complete withdrawal due to adverse treatment effects was not significantly different between the two study groups.

Adverse effects included infections, pruritus, diarrhea, and nausea.

The study findings do not support the use of combination therapy for severe alcoholic hepatitis, and suggest that other agents that target different pathways, such as those involved in liver regeneration, should be explored, the researchers said.

This study was supported by a grant from the French Ministry of Health to the Hospital-Based Clinical Research Program. Pentoxifylline and its matching placebo were supplied by Sanofi-Aventis. No financial conflicts of interest were reported.

Combined therapy with pentoxifylline and prednisolone failed to improve 6-month survival in patients with severe alcoholic hepatitis, compared with prednisolone alone, according to a report published online Sept. 10 in JAMA.

In the largest and the only double-blind randomized clinical trial of this combination therapy performed to date, overall survival at 6 months was 69.9% for pentoxifylline plus prednisolone, compared with 69.2% for placebo plus prednisolone. "Our study does not support the use of a combination of pentoxifylline and prednisolone for severe alcoholic hepatitis," said Dr. Philippe Mathurin of Hopital Huriez, Lille (France), and his associates in their report (JAMA. 2013;310:1033-41. doi:10.1001/jama.2013.276300).

The two agents are believed to have two different and perhaps complementary mechanisms of action, so it was thought that combining them might have a synergistic therapeutic effect. Pentoxifylline appears to protect against the hepatorenal syndrome without exerting any significant effect on inflammatory cytokines or liver tests, while prednisolone improves liver function, inhibits inflammatory cytokines, and interferes with the activation of polymorphonuclear neutrophils.

Dr. Mathurin and his colleagues compared the combination therapy against prednisolone alone in 270 patients treated at 23 French and 1 Belgian hospital during a 3-year period. The study subjects were heavy drinkers with biopsy-proven alcoholic hepatitis whose disease was judged to be severe based on the recent onset of jaundice and a Maddrey score of at least 32.

The 163 men and 107 women were assigned randomly to receive either 40 mg prednisolone once daily plus 400 mg pentoxifylline three times daily (133 patients) or 40 mg prednisolone once daily plus a placebo three times daily (137 patients), for 28 days. If adverse effects developed, treatment could be reduced or interrupted at the discretion of the treating physician.

The primary endpoint was survival 6 months after initiating treatment.

There was no significant difference in this outcome between the combination-therapy group (69.9%) and the single-therapy group (69.2%) in the intention-to-treat analysis nor in the per-protocol analysis (72.4% and 70%, respectively).

The mean length of time until death also was not significantly different: 49.7 days with combination therapy and 51.4 days with single therapy, the investigators said.

Causes of death also were similar between the two study groups. Complications of liver failure were cited in approximately 82% of the entire study population and gastrointestinal bleeding in the remaining 18%.

Overall, 26% of the study subjects relapsed and began drinking alcohol again during 6-month follow-up. However, survival did not differ between patients who relapsed and those who did not.

Patients deemed to be treatment responders had markedly better 6-month survival (85%) than did nonresponders (46%), but the treatment response rate did not differ between the two study groups. Similarly, in an analysis restricted only to complete responders and null responders, survival did not differ significantly between patients who received the combination therapy and those who received prednisolone alone.

At the beginning of the study, it was thought that the combination of pentoxifylline plus prednisolone would improve survival chiefly by reducing the incidence of hepatorenal syndrome, relative to prednisolone alone. And at the conclusion of the 1-month course of treatment, the risk of hepatorenal syndrome was significantly lower with combination therapy (3.1%) than with prednisolone alone (11.7%). However, this difference disappeared by the end of follow-up.

But it is important to note that this study was only powered to detect a difference in survival, the primary outcome, and was likely underpowered to detect differences in secondary outcomes such as the rate of the hepatorenal syndrome. "Therefore, the difference in the incidence of hepatorenal syndrome in our study should not be interpreted as being null, and a larger study is necessary to evaluate this issue," according to Dr. Mathurin and his associates.

Regarding the adverse effects of treatment, 13 patients in each study group required temporary withdrawal from therapy. And the rate of complete withdrawal due to adverse treatment effects was not significantly different between the two study groups.

Adverse effects included infections, pruritus, diarrhea, and nausea.

The study findings do not support the use of combination therapy for severe alcoholic hepatitis, and suggest that other agents that target different pathways, such as those involved in liver regeneration, should be explored, the researchers said.

This study was supported by a grant from the French Ministry of Health to the Hospital-Based Clinical Research Program. Pentoxifylline and its matching placebo were supplied by Sanofi-Aventis. No financial conflicts of interest were reported.

Combined therapy with pentoxifylline and prednisolone failed to improve 6-month survival in patients with severe alcoholic hepatitis, compared with prednisolone alone, according to a report published online Sept. 10 in JAMA.

In the largest and the only double-blind randomized clinical trial of this combination therapy performed to date, overall survival at 6 months was 69.9% for pentoxifylline plus prednisolone, compared with 69.2% for placebo plus prednisolone. "Our study does not support the use of a combination of pentoxifylline and prednisolone for severe alcoholic hepatitis," said Dr. Philippe Mathurin of Hopital Huriez, Lille (France), and his associates in their report (JAMA. 2013;310:1033-41. doi:10.1001/jama.2013.276300).

The two agents are believed to have two different and perhaps complementary mechanisms of action, so it was thought that combining them might have a synergistic therapeutic effect. Pentoxifylline appears to protect against the hepatorenal syndrome without exerting any significant effect on inflammatory cytokines or liver tests, while prednisolone improves liver function, inhibits inflammatory cytokines, and interferes with the activation of polymorphonuclear neutrophils.

Dr. Mathurin and his colleagues compared the combination therapy against prednisolone alone in 270 patients treated at 23 French and 1 Belgian hospital during a 3-year period. The study subjects were heavy drinkers with biopsy-proven alcoholic hepatitis whose disease was judged to be severe based on the recent onset of jaundice and a Maddrey score of at least 32.

The 163 men and 107 women were assigned randomly to receive either 40 mg prednisolone once daily plus 400 mg pentoxifylline three times daily (133 patients) or 40 mg prednisolone once daily plus a placebo three times daily (137 patients), for 28 days. If adverse effects developed, treatment could be reduced or interrupted at the discretion of the treating physician.

The primary endpoint was survival 6 months after initiating treatment.

There was no significant difference in this outcome between the combination-therapy group (69.9%) and the single-therapy group (69.2%) in the intention-to-treat analysis nor in the per-protocol analysis (72.4% and 70%, respectively).

The mean length of time until death also was not significantly different: 49.7 days with combination therapy and 51.4 days with single therapy, the investigators said.

Causes of death also were similar between the two study groups. Complications of liver failure were cited in approximately 82% of the entire study population and gastrointestinal bleeding in the remaining 18%.

Overall, 26% of the study subjects relapsed and began drinking alcohol again during 6-month follow-up. However, survival did not differ between patients who relapsed and those who did not.

Patients deemed to be treatment responders had markedly better 6-month survival (85%) than did nonresponders (46%), but the treatment response rate did not differ between the two study groups. Similarly, in an analysis restricted only to complete responders and null responders, survival did not differ significantly between patients who received the combination therapy and those who received prednisolone alone.

At the beginning of the study, it was thought that the combination of pentoxifylline plus prednisolone would improve survival chiefly by reducing the incidence of hepatorenal syndrome, relative to prednisolone alone. And at the conclusion of the 1-month course of treatment, the risk of hepatorenal syndrome was significantly lower with combination therapy (3.1%) than with prednisolone alone (11.7%). However, this difference disappeared by the end of follow-up.

But it is important to note that this study was only powered to detect a difference in survival, the primary outcome, and was likely underpowered to detect differences in secondary outcomes such as the rate of the hepatorenal syndrome. "Therefore, the difference in the incidence of hepatorenal syndrome in our study should not be interpreted as being null, and a larger study is necessary to evaluate this issue," according to Dr. Mathurin and his associates.

Regarding the adverse effects of treatment, 13 patients in each study group required temporary withdrawal from therapy. And the rate of complete withdrawal due to adverse treatment effects was not significantly different between the two study groups.

Adverse effects included infections, pruritus, diarrhea, and nausea.

The study findings do not support the use of combination therapy for severe alcoholic hepatitis, and suggest that other agents that target different pathways, such as those involved in liver regeneration, should be explored, the researchers said.

This study was supported by a grant from the French Ministry of Health to the Hospital-Based Clinical Research Program. Pentoxifylline and its matching placebo were supplied by Sanofi-Aventis. No financial conflicts of interest were reported.

Medicare officials will spend the next several months deciding whether to cover screening for hepatitis C, after other public health agencies recommended one-time screening for baby boomers.

The agency is scheduled to issue a formal proposal for possible screening coverage in March 2014 and make a final decision in June 2014.

In a memo issued Sept. 5, officials at the Centers for Medicare and Medicaid Services (CMS) asked the public for input. Agency officials are specifically interested in clinical studies and other evidence showing that screening leads to an improvement in either short- or long-term outcomes.

Initial public comments from physicians and other health care providers were supportive of coverage. The commenters wrote that they favored screening because the condition is often asymptomatic and because there are effective treatments available.

Earlier this year, the United States Preventive Services Task Force (USPSTF) recommended that physicians offer one-time screening for hepatitis C virus (HCV) to baby boomers born between 1945 and 1965. The task force pointed to recent data showing that about three-fourths of HCV patients in the United States were born between 1945 and 1965.

A risk-based approach alone could miss a substantial number of HCV cases in the birth cohort because of lack of patient disclosure of or knowledge about risks. The one-time screening offers a chance to identify infected patients at the early stage of disease before they develop complications from liver damage, according to the USPSTF.

While age-based screening is less efficient than risk-based screening, the number of Americans who would likely benefit is greater than the number who would potentially benefit from risk-based screening, the USPSTF concluded. The task force gave the evidence associated with the recommendation a Grade B.

The Centers for Disease Control and Prevention has also endorsed universal, one-time screening of baby boomers for HCV. In August 2012, the CDC recommended an age-based approach to screening, citing the limited effectiveness of risk-based screening alone, the rising morbidity and mortality associated with HCV, and advances in treatment (MMWR 2012;61:1-18).

Comments to the national coverage analysis can be made until Oct. 5.

mschneider@frontlinemedcom.com

On Twitter @MaryEllenNY

Medicare officials will spend the next several months deciding whether to cover screening for hepatitis C, after other public health agencies recommended one-time screening for baby boomers.

The agency is scheduled to issue a formal proposal for possible screening coverage in March 2014 and make a final decision in June 2014.

In a memo issued Sept. 5, officials at the Centers for Medicare and Medicaid Services (CMS) asked the public for input. Agency officials are specifically interested in clinical studies and other evidence showing that screening leads to an improvement in either short- or long-term outcomes.

Initial public comments from physicians and other health care providers were supportive of coverage. The commenters wrote that they favored screening because the condition is often asymptomatic and because there are effective treatments available.

Earlier this year, the United States Preventive Services Task Force (USPSTF) recommended that physicians offer one-time screening for hepatitis C virus (HCV) to baby boomers born between 1945 and 1965. The task force pointed to recent data showing that about three-fourths of HCV patients in the United States were born between 1945 and 1965.

A risk-based approach alone could miss a substantial number of HCV cases in the birth cohort because of lack of patient disclosure of or knowledge about risks. The one-time screening offers a chance to identify infected patients at the early stage of disease before they develop complications from liver damage, according to the USPSTF.

While age-based screening is less efficient than risk-based screening, the number of Americans who would likely benefit is greater than the number who would potentially benefit from risk-based screening, the USPSTF concluded. The task force gave the evidence associated with the recommendation a Grade B.

The Centers for Disease Control and Prevention has also endorsed universal, one-time screening of baby boomers for HCV. In August 2012, the CDC recommended an age-based approach to screening, citing the limited effectiveness of risk-based screening alone, the rising morbidity and mortality associated with HCV, and advances in treatment (MMWR 2012;61:1-18).

Comments to the national coverage analysis can be made until Oct. 5.

mschneider@frontlinemedcom.com

On Twitter @MaryEllenNY

Medicare officials will spend the next several months deciding whether to cover screening for hepatitis C, after other public health agencies recommended one-time screening for baby boomers.

The agency is scheduled to issue a formal proposal for possible screening coverage in March 2014 and make a final decision in June 2014.

In a memo issued Sept. 5, officials at the Centers for Medicare and Medicaid Services (CMS) asked the public for input. Agency officials are specifically interested in clinical studies and other evidence showing that screening leads to an improvement in either short- or long-term outcomes.

Initial public comments from physicians and other health care providers were supportive of coverage. The commenters wrote that they favored screening because the condition is often asymptomatic and because there are effective treatments available.

Earlier this year, the United States Preventive Services Task Force (USPSTF) recommended that physicians offer one-time screening for hepatitis C virus (HCV) to baby boomers born between 1945 and 1965. The task force pointed to recent data showing that about three-fourths of HCV patients in the United States were born between 1945 and 1965.

A risk-based approach alone could miss a substantial number of HCV cases in the birth cohort because of lack of patient disclosure of or knowledge about risks. The one-time screening offers a chance to identify infected patients at the early stage of disease before they develop complications from liver damage, according to the USPSTF.

While age-based screening is less efficient than risk-based screening, the number of Americans who would likely benefit is greater than the number who would potentially benefit from risk-based screening, the USPSTF concluded. The task force gave the evidence associated with the recommendation a Grade B.

The Centers for Disease Control and Prevention has also endorsed universal, one-time screening of baby boomers for HCV. In August 2012, the CDC recommended an age-based approach to screening, citing the limited effectiveness of risk-based screening alone, the rising morbidity and mortality associated with HCV, and advances in treatment (MMWR 2012;61:1-18).

Comments to the national coverage analysis can be made until Oct. 5.

mschneider@frontlinemedcom.com

On Twitter @MaryEllenNY