Poster Presentations

Session Title: Category 5g. VIRAL HEPATITIS: g. HEPATITIS C - CLINICAL (THERAPY)
Presentation Date: Apr 15, 2010

REDUCING ALPHA-FETOPROTEIN WITH INTERFERON THERAPY SUPPRESSES HEPATOCARCINOGENESIS IN HEPATITIS C VIRUS-INFECTED PATIENTS WHO ARE VIROLOGICAL RESPONDERS AND NON-RESPONDERS

Y. Asahina*, K. Tsuchiya, N. Tamaki, M. Sato, T. Tanaka, I. Hirayama, Y. Yasui, K. Ueda, T. Kuzuya, H. Nakanishi, J. Itakura, M. Kurosaki, N. Izumi
Division of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan. *asahina@musashino.jrc.or.jp

Background: Chronic hepatitis C (CH-C) patients without hepatocellular carcinoma (HCC) have occasionally elevated serum alpha-fetoprotein (AFP). The effects of interferon (IFN) on post-treatment AFP levels and hepatocarcinogenesis are unclear.
Aims: To determine the change in AFP production after IFN treatment and the benefit of reducing AFP by IFN against hepatocarcinogenesis.
Methods: Biopsy-proven 2,166 CH-C patients treated with IFN were studied. The absence of HCC before IFN treatment was carefully confirmed. The cumulative incidence of HCC after IFN treatment was analyzed by the Kaplan-Meier method for an average follow-up of 7.5 years. Factors associated with HCC risk were determined with Cox proportional hazard analysis. Serum AFP levels were measured every 1-2 months, and HCC was screened radiographically every 3-6 months. Patients in whom HCC developed within 1 year after IFN treatment were excluded.
Results: HCC developed in 177 IFN-treated patients. Overall, the mean AFP level was significantly reduced from 13.7 to 6.9 ng/ml by IFN (p < 0.001). The cumulative incidence of HCC after IFN treatment depended on post-treatment AFP levels (15-year HCC rate: mean AFP < 5 ng/ml, 6%; 5-9, 15%; 10-19, 62%; 20-39, 85%; ≥40, 90%; logrank test, p < 0.001), and the risk ratio of HCC was 13-fold lower in patients with an AFP level less than 10 ng/ml as compared to that in other patients (95% CI: 9.1-16.9). Even in non-sustained virological responders (non-SVR), AFP levels were normalized in 58% of patients after IFN treatment, and the cumulative rate of HCC was equivalent to that observed in SVR (7.8% and 7.2% at 15 years, respectively). In contrast, cumulative rates of HCC were significantly higher in patients whose post-treatment AFP level was unchanged or increased (27% and 72% at 10 years, respectively). Although pre-treatment AFP levels were significantly correlated with age, liver fibrosis, and steatosis, a multivariate analysis confirmed that post-treatment AFP level, age, gender, liver fibrosis, and steatosis were independent risk factors associated with HCC.
Conclusion: AFP level after IFN treatment is an independent predictor for hepatocarcinogenesis. Suppressing AFP levels with IFN treatment significantly reduces the risk of HCC even in non-SVR.