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Am Fam Physician. 2000;61(2):488

Hepatitis C virus (HCV) infection is usually a chronic disease. In patients with HCV infection, liver cirrhosis may develop after approximately 30 years, sometimes progressing to hepatocellular carcinoma. The degree of liver fibrosis is related to an increased risk of cancer. Interferon, the only effective treatment of HCV infection, induces a sustained virologic response, with biochemical and histologic improvement in 15 to 30 percent of patients with HCV infection. Yoshida and associates analyzed the effect of interferon therapy on the incidence of hepatocellular carcinoma in patients with chronic HCV infection who had undergone liver biopsy.

Of the 2,890 patients enrolled in the study, 2,400 received a partial or full course of interferon therapy, while 490 did not receive treatment. Most of the treated patients received interferon-A, while smaller groups received interferon-B or a combination of both. The average duration of therapy was 160 days. Patients were examined for hepatocellular carcinoma by abdominal ultrasonography at least every six months. Further studies were performed to confirm the diagnosis if the ultrasound results were abnormal.

Of the 2,357 patients in the treatment group who responded to interferon therapy, a sustained virologic response was achieved in 789 (33.5 percent). The response was similar regardless of the type of interferon used. A sustained biochemical response with normal serum alanine aminotransferase (ALT) levels was achieved in 984 patients (41.7 percent). During follow-up (median: 4.3 years), hepatocellular carcinoma developed in 89 of the interferon-treated patients and in 59 of the untreated patients. The incidence of hepatocellular carcinoma was lower among interferon-treated patients than among untreated patients at the same stage of liver fibrosis, although this difference was significant only in patients with stage F2 or F3 fibrosis. Interferon therapy had no effect on patients with mild liver fibrosis (stage F0 or F1); in this group, the incidence of hepatocellular carcinoma was low, even in untreated patients. The protective effect of interferon therapy in cirrhotic patients (those with stage F4 fibrosis) approached, but did not reach, statistical significance. The incidence of hepatocellular carcinoma was also low among cirrhotic patients with sustained virologic response and those with sustained biochemical response.

The authors conclude that in patients with HCV infection, the risk for hepatocellular carcinoma is strongly associated with the stage of liver fibrosis. The risk is reduced with interferon therapy in patients with stage F2 or F3 fibrosis. Sustained virologic and biochemical responses are associated with further risk reduction.

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