Impact of Nucleos(t)ide Analogs on Major Clinical Outcomes in Patients With Chronic Hepatitis B: A 10-Year French Nationwide Cohort Study.

Background: Conflicting results have been reported on the impact of tenofovir versus entecavir on liver-related outcomes.

Aims: To explore trends in clinical outcomes in chronic hepatitis B virus (HBV)-infected patients and compare the impact of tenofovir versus entecavir on the risk of hepatocellular carcinoma (HCC), liver transplantation (LT) and mortality.

Methods: We used the French National Health Insurance Databases (SNDS) to identify HBV-infected patients. We quantified the excess clinical burden from 2012 to 2021 by comparing the HBV-infected cohort with a general population cohort, using 1:1 exact matching on birth date, sex, social deprivation index and follow-up start date. The risks of mortality, HCC and LT were compared between patients treated with tenofovir and entecavir using inverse probability weighting.

Results: A total of 101,740 patients were matched to the general population. From 2012 to 2021, the average annual decreases in excess mortality, incidence of HCC and LT were 3.7%, 8.0% and 11.9%, respectively (p for trend < 0.001). During the same period, the nucleos(t)ide analog (NUC) treatment coverage significantly increased, particularly after 2016 (p < 0.001). Among 14,054 treatment-naïve patients starting tenofovir (n = 7426) or entecavir (n = 6628), we observed no difference in the composite outcome of mortality, LT or HCC (HR, 1.09; 95% CI, 0.95-1.24). Tenofovir was associated with an increased risk of HCC compared with entecavir (HR, 1.31; 95% CI, 1.07-1.62).

Conclusions: Tenofovir was associated with a higher risk of HCC compared with entecavir, although no difference in the composite outcome of mortality or liver-related events was observed between the two treatments.