Bob Roehr

November 07, 2010

November 7, 2010 (Boston, Massachusetts) — The utility of maintenance pegylated interferon (PegIFN) therapy to prevent hepatocellular carcinoma (HCC) in patients with advanced chronic hepatitis has been a contentious matter for some time.

The pendulum has swung from support for the idea to early evidence of a lack of efficacy. Now, here at The Liver Meeting 2010: American Association for the Study of Liver Diseases 61st Annual Meeting, longer-term data suggest marginal, limited support for its use. Most surprisingly, data opposing its use — and now for its support — have come from the same study, the ongoing Hepatitis C Antiviral Long-term Treatment against Cirrhosis (HALT-C) trial.

Anna S. Lok, MD, from the University of Michigan Medical Center in Ann Arbor, presented the latest iteration of data on extended follow-up. "In an earlier report, which included a median follow-up of up to 4.6 years, with a total of 53 HCC cases, we found no difference between the treated and the control groups. The 2 lines basically were identical."

The newer analysis was based on a median of 6.1 years of follow-up. There were "almost double the number of HCC cases, with a total of 88," Dr. Lok reported. The cumulative incidence of HCC at 3, 5, and 7 years for the treated group was 2.3%, 6%, and 8.1%, respectively. Incidence in the control group was 2.5%, 6.2%, and 13.8% at 3, 5, and 7 years, respectively.

"The 2 lines of the Kaplan-Meier Curve completely overlap until the end of year 6, when there is a divergence in the 2 lines, and the P value was not significant," Dr. Lok said.

"However, when we analyzed the data separately, for the fibrosis substratum and the cirrhosis substratum, we saw that the treated group had a significantly lower incidence of HCC compared with the untreated group, with a hazard ratio of 0.45 and a P value of .01."

Subsequent analysis showed that incidence of HCC was significantly lower in patients who had completed at least 2 years of treatment. "They had less advanced liver disease, more normal platelet counts, and normal [aspartate aminotransferase] levels."

Dr. Lok concluded, "Extended follow-up of the HALT-C cohort showed a modest effect of long-term low-dose PegIFN in reducing the incidence of HCC in patients with hepatitis C and cirrhosis, but not in those with advanced fibrosis.

"Given the marginal benefit on HCC, the lack of overall benefit on disease progression, and the side effects of PegIFN, the utility of maintenance PegIFN to prevent HCC in patients with HCV-related cirrhosis who failed to achieve SVR is limited," she acknowledged.

Arun J. Sanyal, MD, American Association for the Study of Liver Diseases president and head of the division of gastroenterology at Virginia Commonwealth University, in Richmond, said, "This, potentially, could be very important."

During the question session, treatment activist Jules Levin said 4 years ago the initial analysis and strong recommendations not to treat "did a lot of damage to patients and to the field. I took issue with the investigators over that" at the time, Mr. Levin said.

Subsequent research and analysis of this trial have shown that they were wrong. "It has done irreparable damage to patients. It is important to take note of this." Mr. Levin said. "Patients and their own clinicians should be able to make their own decision for what benefits them based on a clear understanding of the data."

The National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Diseases is funding the HALT-C trial. The speakers have disclosed no relevant financial relationships.

The Liver Meeting 2010: American Association for the Study of Liver Diseases 61st Annual Meeting: Abstract 214. Presented November 2, 2010.

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