The Different Prognoses of Hepatocellular Carcinoma with Previous Tenofovir versus Entecavir Treatment for Chronic Hepatitis B Virus: Analysis Based on 15 Propensity Score-Matched Studies.

Background: Currently, enough studies with aggregated study-level data have demonstrated that there was no clinically meaningful difference in the risk of hepatocellular carcinoma (HCC) between patients who received entecavir and patients who received tenofovir treatment for chronic hepatitis B virus (CHBV). However, many studies found many differences in prognosis of these HCC patients. This meta-analysis of high-quality propensity score-matched (PSM) studies was designed to provide robust estimates for comparative HCC prognosis between groups receiving tenofovir or entecavir.

Methods: PubMed, Embase, Cochrane Library, and Web of Science were searched from inception to July 10, 2022, for relevant studies that compare the different prognoses of HCC between tenofovir and entecavir treatment. The primary outcomes were the difference of overall death or liver transplantation between tenofovir and entecavir treatment. The secondary outcomes included risk factors of overall death or liver transplantation and different treatment responses between tenofovir and entecavir treatment for CHBV. All statistical analyses were performed using the standard statistical procedures provided in Review Manager 5.2.

Results: A total of 15 PSM studies were identified, with 24,035 sample sizes in tenofovir group and 61,410 sample sizes in entecavir group, respectively. Pooled data indicated that, compared with entecavir, patients receiving tenofovir experienced significantly lower overall death or liver transplantation, with a pooled OR of 0.55 (95% CI: 0.45-0.68; p < 0.00001). Subgroup analysis by population also found similar results with pooled ORs of 0.52 (95% CI: 0.38-0.70; p < 0.0001) in entire cohort and 0.62 (95% CI: 0.50-0.77; p < 0.0001) in PSM cohort. Similarly, the subgroup analysis also found that HCC patients without cirrhosis receiving tenofovir experienced significantly lower overall death or liver transplantation than entecavir (OR: 0.56; 95% CI: 0.49-0.66), but no significant result was found in HCC patients with cirrhosis. In addition, both univariate (OR: 0.46; 95% CI: 0.31-0.69) and multivariable analyses (OR: 0.86; 95% CI: 0.82-0.91) also indicated significant reduction of overall death or liver transplantation in tenofovir group than entecavir group.

Conclusion: Our analysis indicated that there was clinically meaningful difference in prognosis of HCC between patients who received entecavir and patients who received tenofovir. Patients who received tenofovir experienced much lower overall death or liver transplantation than patients who received entecavir. Tenofovir treatment may be one of independent favorable factors of prognosis for HCC patients with CHBV.