Effect of the Dose and Duration of Interferon-Alpha Therapy on the Incidence of Hepatocellular Carcinoma in Noncirrhotic Patients with a Nonsustained Response to Interferon for Chronic Hepatitis C

Abstract

Objective: We evaluated the effect of dose and duration of treatment with interferon (IFN)-α on the incidence of hepatocellular carcinoma (HCC) after IFN treatment in patients with chronic hepatitis C. Methods: A total of 291 noncirrhotic patients with chronic hepatitis C without hepatitis B virus coinfection in whom hepatitis C virus (HCV) was not eradicated by IFN-α therapy were retrospectively analyzed. The incidence of HCC after IFN therapy was compared according to the total dose or duration of treatment. Results: Patients were followed up for 6–117 months after the end of IFN treatment. The duration of IFN treatment (≦24 vs. >24 weeks) had no effect on the incidence of HCC. However, the incidence of HCC was significantly lower in patients who received >500 million units of IFN as a total dose than in patients who received ≦500 million units of IFN (p = 0.0480), and the total dose of IFN (>500 million units) was an independent factor affecting the incidence of HCC (p = 0.0405). In addition, when focusing on patients whose histology was F2 or F3 before IFN treatment, the suppressive effect of the total dose of IFN (>500 million units) was emphasized (p = 0.0049 in generalized Wilcoxon test and p = 0.0178 in multivariate analysis). Conclusions: Patients with chronic hepatitis C should receive more than 500 million units of IFN when IFN is used to decrease the incidence of subsequent HCC.

Management of hepatocellular carcinoma

“…97 A number of studies in Japan compared the incidence of HCC in treated patients with that in historical controls. 15,64,[98][99][100][101][102][103] These have suggested that there is a reduced incidence of HCC in treated patients. However, no data demonstrate that treating or eradicating hepatitis C completely eliminates the risk for HCC.…”

Treatment of hepatocellular carcinoma

“…Treatment of chronic hepatitis B by interferon alpha or nucleostide analogs [90][91][92][93][94][95] and chronic hepatitis C by interferon alpha and now the combination of interferon alpha or pegylated interferon alpha and ribavirin demonstrated biochemical, virological and histopathological improvement 96-100 and a lower incidence of HCC development. [101][102][103] Stage 4: Interventions at this step are aimed at interfering with the molecular events leading to HCC development, usually in a cirrhotic liver. These strategies include all treatment modalities detailed above (Stage 3) as far as they can be implemented in patients with compensated or decompensated liver cirrhosis.…”

Molecular Targets for Prevention of Hepatocellular Carcinoma

“…This includes the treatment of inherited, cholestatic or autoimmune liver diseases as well as the treatment of chronic viral hepatitis B or C. Reduction of iron overload by phlebotomy, for example, has been shown to stop the progression of hemochromatosis to liver cirrhosis and HCC. Treatment of chronic hepatitis B by interferon alpha or nucleoside analogs [93][94][95] and chronic hepatitis C by interferon alpha and more recently by its combination with the nucleoside analog ribavirin demonstrated biochemical, virological and histopathologial improvement [96][97][98][99] and a lower incidence of HCC development [100][101][102].…”