Antiviral therapy substantially reduces hepatocellular carcinoma risk in chronic Hepatitis B patients in the indeterminate phase. Hepatology (Baltimore, Md.) Huang, D. Q., Tran, A., Yeh, M., Yasuda, S., Tsai, P., Huang, C., Dai, C. Y., Ogawa, E., Ishigami, M., Ito, T., Kozuka, R., Enomoto, M., Suzuki, T., Yoshimaru, Y., Preda, C. M., Marin, R. I., Sandra, I., Tran, S., Quek, S. X., Khine, H. H., Itokawa, N., Atsukawa, M., Uojima, H., Watanabe, T., Takahashi, H., Inoue, K., Maeda, M., Hoang, J. K., Trinh, L., Barnett, S., Cheung, R., Lim, S. G., Trinh, H. N., Chuang, W., Tanaka, Y., Toyoda, H., Yu, M., Nguyen, M. H. 2023


BACKGROUND AIMS: Hepatocellular carcinoma (HCC) risk in chronic hepatitis B (CHB) is higher in the indeterminate phase compared to the inactive phase. However, it is unclear if antiviral therapy reduces HCC risk in this population. We aimed to evaluate the association between antiviral therapy and HCC risk in the indeterminate phase.APPROACH RESULTS: We analyzed 855 adult (59% male), treatment-naive CHB patients without advanced fibrosis in the indeterminate phase at 14 centers (U.S., Europe, and Asia). Inverse probability of treatment weighting (IPTW) was used to balance the treated (n = 405) and untreated (n = 450) groups. The primary outcome was HCC development. The mean age was 46 ± 13 years, the median ALT was 38 (IQR, 24 - 52) U/L, the mean HBV DNA was 4.5 ± 2.1 log10 IU/mL and 20% were HBeAg positive. The two groups were similar after IPTW. After IPTW (n = 819), the 5-, 10- and 15-year cumulative HCC incidence was 3%, 4%, and 9% among treated patients (n = 394) versus 3%, 15%, and 19%, among untreated patients(n = 425), respectively (p = 0.02), with consistent findings in subgroup analyses for age > 35 years, males, HBeAg positive, HBV DNA > 1,000IU/mL, and ALT < upper limit of normal. In multivariable Cox proportional hazards analysis adjusted for age, sex, HBeAg, HBV DNA, ALT, diabetes, and platelets, antiviral therapy remained an independent predictor of reduced HCC risk (adjusted HR 0.3, 95%CI 0.1 - 0.6, p = 0.001).CONCLUSION: Antiviral therapy reduces HCC risk by 70% among indeterminate phase CHB patients. These data have important implications for the potential expansion of CHB treatment criteria.

View details for DOI 10.1097/HEP.0000000000000459

View details for PubMedID 37184202