Introduction: Chronic hepatitis B (CHB) is a significant global health problem, being a predominant cause of liver cancer and death. Evidence is required to assess the long-term impact of antiviral treatment for CHB on these adverse outcomes. However, much of the existing evidence relies on observational data subject to bias in the provision of treatment to at-risk individuals.
Methods: A systematic review was conducted. Studies were identified on people living with CHB, comparing first-line treatment (entecavir or tenofovir) to no treatment. The main outcomes were hepatocellular carcinoma (HCC) and all-cause mortality. Crude and propensity/risk score adjusted estimates were used to conduct random effects meta-analyses on this association.
Results: 10 cohort studies were included in the meta-analysis. All studies used entecavir treatment. Meta-analysis of crude results showed no impact of treatment on adverse outcomes. However, using adjusted estimates, entecavir substantially reduced the risk of HCC (hazard ratio: 0.48 95% CI (0.32, 0.64)) and all-cause mortality (hazard ratio: 0.42 95% CI (0.23,0.61)).
Conclusions: This analysis provides evidence that treatment with entecavir reduces the risk of both HCC and all-cause mortality in people living with CHB, and supports increased use of treatment to prevent adverse outcomes. The disparity between crude and adjusted rates demonstrates the importance of these methods in analysis of cohort studies where bias is unavoidable.The increased use of adjustment techniques and data from registry/linkage-based systems is essential for future research on tenofovir treatment on the outcomes of HCC and all-cause mortality.
PROSPERO Trial registration: CRD42018088356