AASLD: Maintenance Therapy for Chronic Hepatitis C Found Ineffective


BOSTON, Nov. 8 -- Long-term maintenance therapy with peginterferon did not reduce the rate of chronic hepatitis C progression and advanced hepatic fibrosis for patients refractory to other treatment.The peginterferon patients had previously been treated with peginterferon-ribavirin. After 3.5 years, 34.1% of the peginterferon group and 33.8% of the control group had evidence of disease progression, (hazard ratio: 1.01, 95% CI: 0.81 to 1.26, P=0.91), said Adrian M. Di Bisceglie, M.D., of St. Louis University.
Action Points
Explain to patients with chronic hepatitis and advanced fibrosis who have not responded well to initial peginterferon-ribavirin therapy that according to this study continuing treatment with peginterferon does not appear to be beneficial.
This study was published as an abstract and presented at a conference. These data and conclusions should be considered to be preliminary as they have not yet been reviewed and published in a peer-reviewed publication.
Dr. Di Bisceglie reported results of the long-awaited 1,050-patient HALT-C (Hepatitis C Antiviral Long-Term Treatment against Cirrhosis) trial at a late-breaking trials plenary session of the American Association for the Study of Liver Diseases meeting here.
He said there was no significant difference in the rates of any of the components of the primary outcome -- death, hepatocellular carcinoma, liver decompensation, and increase in fibrosis -- between the peginterferon patients and the control patients.
Interestingly, mean serum alanine aminotransferase (ALT) and HCV RNA levels decreased significantly with treatment (both P0.0001), as did necroinflammatory changes on liver biopsy (P0.0001).
The HALT-C findings on surrogate markers mirrored results from earlier small trials of long-term peginterferon therapy -- results that led many to assume the strategy would be effective, said Ira Jacobson, M.D., chief of gastroenterology and hepatology at Cornell Weill Medical College in New York.
Dr. Jacobson, who was not involved in the trial, said, despite the suggestion of a trend toward improvement in fibrosis and less inflammation in an earlier study, "that improvement did not translate into improvement in progression of fibrosis or improvement in major clinical outcomes. I found it particularly notable that [maintenance therapy] did not seem to be associated with a reduction in hepatocellular carcinoma, the single most prevalent complication in patients with chronic HCV."
He said that the finding will not have an impact in his practice because "I was not using maintenance therapy pending the outcome of this very important trial, the findings of which have vindicated those of us who have not widely applied maintenance therapy."
Dr. Di Bisceglie agreed that the surrogate markers did not have clinical meaning in this study. He also said that eradication of HCV should continue to be the gold standard of treatment.
The trial randomized 517 patients to peginterferon alfa-2a (90 mcg per week) and 533 to placebo. All patients had chronic HCV infection with an Ishak fibrosis score of ≧3 on liver biopsy, a Child-Turcotte-Pugh score of ≦6, no history of ascites, encephalopathy or bleeding varices, and no other identifiable cause of liver disease.
Patients were stratified according to their stage of fibrosis: Ishak stage 3 or 4 (622 with fibrosis) versus stage 5 or 6 (428 with cirrhosis). In order to be monitored for disease progression, the participants were seen at three-month intervals, and underwent liver biopsy at 1.5 and 3.5 years after randomization.
For the primary outcomes, 6.6% of the treatment group died compared with 4.6% of the placebo controls; there was decompensation in 14.3% of the treatment group compared with 13.2% of controls; hepatocellular carcinoma developed in 2.8% of the treatment group compared with 3.2% of controls; and there was an increase in fibrosis in 28.2% of the treatment group compared with 31.9% of controls. None of the differences was statistically significant.
The rate of serious events was about one-third of each group. With regard to patient compliance, 53% were still on a full dose of treatment at 3.5 years, 10% were on a lower dose, and 37% stopped therapy, said Dr. Di Bisceglie.
The study was supported by the National Institute of Diabetes and Digestive and Kidney Diseases and by Roche. Dr. Di Bisceglie has a financial relationship with Roche.
Primary source: American Association for the Study of Liver DiseasesSource reference: Di Bisceglie AM, et al "Prolonged Antiviral Therapy With Peginterferon to Prevent Complications of Advanced Liver Disease Associated With Hepatitis C: Results of the Hepatitis C Antiviral Long-term Treatment against Cirrhosis (HALT-C) Trial" AASLD Meeting 2007; Abstract LB1 presented Nov. 5.