Liver and Bile
Hepatology. 2024;79(3):690–703
Hepatocellular carcinoma reduced, HBsAg loss increased, and survival improved after finite therapy in hepatitis B patients with cirrhosis
Background and aims: Long-term nucleos(t)ide analogue (NA) treatment can reduce hepatocellular carcinoma (HCC) in patients with hepatitis B virus-related liver cirrhosis (HBV-LC). Earlier small cohort studies showed a comparable 5-year incidence of HCC in hepatitis B e antigen (HBeAg)-negative patients with HBV-LC who stopped and those continued NA therapy. This study aimed to validate these findings using a large cohort with 10-year follow-up.
Approach and results: From 2 centers, 494 HBeAg-negative patients with HBV-LC who stopped (finite group) and 593 who continued (continuous group) NA therapy were recruited. HCC, hepatitis B surface antigen (HBsAg) loss, liver-related mortality/transplantation, and overall survival rates were compared between 2 groups with 1:1 propensity score matching of sex, treatment history, types of NA, age, transaminases, platelet count, and HBsAg levels at end of therapy in finite group or 3-year on-therapy in continuous groups. During a median follow-up of 6.2 (3.4–8.9) years, the annual and 10-year HCC incidence were lower in finite group (1.6% vs. 3.3%/year and 10-year 15.7% vs. 26.8%, respectively; log-rank test, p < 0.0001). The finite group showed greater HBsAg decline/year (-0.116 vs. -0.095 log10 IU/ml, p = 0.0026) and 7.6 times higher 10-year incidence of HBsAg loss (22.7% vs. 3%, p < 0.0001). Multivariate Cox regression showed finite therapy an independent factor for HBsAg loss (adjusted hazard ratio [aHR] = 11.79) but protective against HCC (aHR = 0.593), liver-related mortality/transplantation (aHR = 0.312), and overall mortality (aHR = 0.382).
Conclusions: Finite nucleos(t)ide analogue therapy in hepatitis B e antigen-negative hepatitis B virus-related liver cirrhosis may reduce incidence of hepatocellular carcinoma, increase hepatitis B surface antigen (HBsAg) loss, and improve survival. Greater HBsAg decline/loss may reflect enhanced immunity and contribute to the reduction of hepatic carcinogenesis.