By Liz Highleyman

Over years or decades, people with chronic hepatitis C virus (HCV) infection may develop advanced liver disease, including severe cirrhosis and hepatocellular carcinoma (HCC).

Individuals who achieve a sustained virological response (SVR) to treatment with interferon-based therapy, or continued undetectable HCV RNA 6 months after completion of treatment, are widely considered to be cured. This occurs in approximately 50%-75% of patients treated with pegylated interferon (Pegasys or PegIntron) plus ribavirin, with higher response rates for genotypes 2 or 3 compared with 1 or 4. Long-term follow-up studies have shown that the overwhelming majority of such patients maintain HCV suppression.

Several studies have indicated that people who respond to treatment reduce their risk of liver fibrosis progressing to cirrhosis or HCC. In fact, some data suggest that even therapy that does not completely and permanently clear HCV may still reduce the risk of disease progression -- although the recent HALT-C trial of pegylated interferon maintenance therapy demonstrated minimal benefit.

But a small proportion of patients who achieve SVR may nevertheless develop liver cancer, according to a report in the September 2008 Journal of Viral Hepatitis.

Peter Ferenci and colleagues described 5 patients -- 3 from Austria, 2 from the U.S. -- who developed hepatocellular carcinoma during 3-6 years of follow-up after achieving SVR. All remained HCV RNA negative during follow-up and at the time of HCC diagnosis. Three patients did not have cirrhosis, either at the start of treatment or at the time of liver cancer diagnosis. None had any other type of liver diseases besides hepatitis C. One patient presented with bilateral adrenal metastasis, while the remaining 4 had large liver tumors.

"Successful antiviral treatment in HCV patients does not prevent development of hepatocellular carcinoma even in non-cirrhotic livers," the investigators concluded. "Long-term follow up of patients with SVR is mandatory and should include surveillance for hepatocellular carcinoma."

Department of Internal Medicine III, Division of Gastroenterology and Hepatology, Medical University of Vienna, Vienna, Austria ; 2 Division of Gastroenterology, Department of Medicine, University of Pennsylvania, Philadelphia, PA, USA ; and 3 Department of Clinical Pathology, Medical University of Vienna, Vienna, Austria

10/10/08

Reference
TM Scherzer, KR Reddy, F Wrba, and others. Hepatocellular carcinoma in long-term sustained virological responders following antiviral combination therapy for chronic hepatitis C. Journal of Viral Hepatitis 15(9): 659-665. (Abstract).