A Small Proportion of Hepatitis C Patients Develop Liver Cancer despite Sustained Response to Interferon-based Therapy

Over years or decades, chronic hepatitis C virus (HCV) infection can lead to advanced liver disease, including cirrhosis and hepatocellular carcinoma (HCC). Sustained response to interferon-based therapy dramatically reduces the risk of liver disease progression, but does not eliminate it completely, according to 2 recently published studies.

5-year Outcomes

Sustained virological response (SVR), defined as continued undetectable HCV RNA 6 months after completion of therapy, is the usual endpoint of clinical trials for hepatitis C treatment, but longer-term outcomes have been less extensively studied.

As described in the March 2009 issue of Hepatology, Sarah George from St. Louis University and colleagues enrolled 150 patients who achieved SVR after interferon-based therapy in a long-term follow-up study conducted between June 1997 and April 2002. About half the participants were men, almost all (98%) were white, and the average age at enrollment was 49 years old.

Most patients (87%) had been treated with conventional interferon plus ribavirin (the study period began before pegylated interferon was widely used). A majority of participants (65%) were treated for 12 months, while the remainder were treated for 6 months.

Participants underwent long-term follow-up to assess liver-related clinical outcomes and evidence of biochemical (liver enzyme elevation) or virological relapse. Of the initial enrollees, 128 patients (85%) were followed through their fourth year after achieving SVR, with 108 patients (72%) followed for 5 or more years.

Participants with a pre-treatment liver biopsy showing stage 2 (moderate) or higher fibrosis were offered a follow-up biopsy after 4 years; 60 patients underwent a second biopsy, and 49 patients had their paired pre-treatment and long-term follow-up biopsies blindly rescored.


"In a cohort of 150 patients with SVR followed for 5 years, the majority of patients had good outcomes," the study investigators stated.

"Serum virologic relapse was not seen, but 2 patients with pretreatment cirrhosis developed HCC, and one died," they continued. "In a blind rescoring of 49 paired pretreatment and long-term follow-up biopsies, 82% improved fibrosis scores and 92% improved at least 1 component of inflammation."

"A minority of patients had normal or nearly normal liver tissue on long-term follow-up biopsy," they concluded. "Patients with cirrhosis pretreatment are at a low but real risk of HCC after SVR."

HCC despite SVR

In a related report published in the February 2009 European Journal of Gastroenterology and Hepatology, Justin Sewell from the University of California at San Francisco and colleagues described 5 chronic hepatitis C patients without cirrhosis at baseline who developed HCC despite achieving SVR.

Multiple cases of non-cirrhotic patients developing liver cancer despite sustained response to hepatitis C treatment have been reported in Japan, but this has only rarely been documented outside of Asia, the study authors noted as background.

At the time of HCC diagnosis, 2 of the 5 patients were still non-cirrhotic, 1 had clearly progressed to cirrhosis, and 2 did not have repeat liver histology data.

"Physicians often base screening and treatment decisions on an initial liver biopsy performed years earlier," the researchers wrote. "As fibrosis may advance, and because SVR and lack of cirrhosis do not fully protect against HCC, future study should further evaluate the risk of HCC among hepatitis C patients after sustained virologic response."



SL George, BR Bacon, EM Brunt, and others. Clinical, virologic, histologic, and biochemical outcomes after successful HCV therapy: A 5-year follow-up of 150 patients. Hepatology 49(3): 729-738. March 2009. (Abstract).

JL Sewell, KM Stick, and A Monto. Hepatocellular carcinoma after sustained virologic response in hepatitis C patients without cirrhosis on a pretreatment liver biopsy. European Journal of Gastroenterology and Hepatology. 21(2): 225-229. February 2009. (Abstract).