α-fetoprotein levels after interferon therapy and risk of hepatocarcinogenesis in chronic hepatitis C


  • Potential conflict of interest: Dr. Asahina is on the speakers' bureau of Chugai Pharma and MSD, and received research funding from Daiichi-Sankyo and Chugai Pharma. Dr. Asahina and Dr. Kakinuma belong to a donation-funded department funded by Chugai Pharma, Toray, Bristol-Myers Squibb, Dainippon-Sumitomo Pharma, and MSD.

  • Supported by grants from the Japanese Ministry of Education, Culture, Sports, Science, and Technology, and the Japanese Ministry of Welfare, Health, and Labor.

Address reprint requests to: Yasuhiro Asahina, M.D., Ph.D., Professor, Department of Liver Disease Control, Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japan. E-mail:; fax: +81-3-5803-0268.


The effects of interferon (IFN) treatment and the post-IFN treatment α-fetoprotein (AFP) levels on risk of hepatocellular carcinoma (HCC) in patients with chronic hepatitis C (CHC) are unknown. To determine the relationship between AFP and alanine transaminase (ALT) levels and HCC risk, a cohort consisting of 1,818 patients histologically proven to have CHC treated with IFN were studied. Cumulative incidence and HCC risk were analyzed over a mean follow-up period of 6.1 years using the Kaplan-Meier method and Cox proportional hazard analysis. HCC developed in 179 study subjects. According to multivariate analysis, older age, male gender, advanced fibrosis, severe steatosis, lower serum albumin levels, non sustained virological response (non-SVR), and higher post-IFN treatment ALT or AFP levels were identified as independent factors significantly associated with HCC development. Cutoff values for ALT and AFP for prediction of future HCC were determined as 40 IU/L and 6.0 ng/mL, respectively, and negative predictive values of these cutoffs were high at 0.960 in each value. The cumulative incidence of HCC was significantly lower in patients whose post-IFN treatment ALT and AFP levels were suppressed to less than the cutoff values even in non-SVR patients. This suppressive effect was also found in patients whose post-IFN treatment ALT and AFP levels were reduced to less than the cutoff values despite abnormal pretreatment levels. Conclusion: Post-IFN treatment ALT and AFP levels are significantly associated with hepatocarcinogenesis. Measurement of these values is useful for predicting future HCC risk after IFN treatment. Suppression of these values after IFN therapy reduces HCC risk even in patients without HCV eradication. (Hepatology 2013;58:1253–1262)