Reply

We thank Bao-Hong Yuan and colleagues for their interest in our meta-analysis, which showed that tenofovir disoproxil fumarate treatment is more effective in preventing hepatitis B–associated hepatocellular carcinoma development compared with entecavir.1Choi W.M. et al.Clin Gastroenterol Hepatol. 2021; 19: 246-258Abstract Full Text Full Text PDF PubMed Scopus (61) Google Scholar Appreciating their incisive comments, we are sharing our opinion on their concerns as follows. First of all, the unadjusted hazard ratio of the 3 studies that were indicated by Bao-Hong Yuan and colleagues were estimated by Poisson regression under the assumption of constant hazards in each group during the follow-up period.2Hernán M.A. Epidemiology. 2010; 21: 13-15Crossref PubMed Scopus (681) Google Scholar,3Vonesh E.F. et al.Kidney Int. 2000; 57: S19-S27Abstract Full Text Full Text PDF PubMed Scopus (49) Google Scholar We also considered that many other meta-analyses on the same topic included those studies.4Zhang Z. et al.BMC Cancer. 2019; 19: 511Crossref PubMed Scopus (50) Google Scholar, 5Wang X. et al.Gut Liver. 2020; 14: 232-247Crossref PubMed Scopus (33) Google Scholar, 6Gu L. et al.J Gastroenterol Hepatol. 2020; 35: 1467-1476Crossref PubMed Scopus (20) Google Scholar When we excluded those 3 studies, our meta-analysis yielded very similar results showing a significantly lower risk of hepatocellular carcinoma in tenofovir disoproxil fumarate than entecavir (hazard ratio, 0.80; 95% confidence interval, 0.68–0.95). Second, the study “Huang et al 2019” listed as the 25th reference in our meta-analysis was actually presented by Huang YH as a poster during the Liver Meeting 2019 of the American Association for the Study of Liver Diseases, although the first author of the corresponding abstract was Lee CJ. We regret causing the confusion; however, we wanted to appreciate the actual presenter based on the most updated information at the time of our analysis. Third, we intentionally excluded the results from the Korean nationwide cohort7Choi J. et al.JAMA Oncol. 2019; 5: 30-36Crossref PubMed Scopus (198) Google Scholar for our pooled analysis, because of the concern that many patients in the nationwide cohort may overlap with the patients from other Korean hospital cohort studies. Lastly, we chose subgroup analyses based on the results from the meta-regression analysis. When we conducted the subgroup analysis of studies that included only treatment-naive patients, tenofovir disoproxil fumarate was consistently associated with a significantly lower incidence of hepatocellular carcinoma (hazard ratio, 0.75; 95% confidence interval, 0.61–0.92) compared with entecavir. Again, we are grateful for their interest in our meta-analysis, and hope our reply could allay their concerns. Effects of Tenofovir vs Entecavir on Risk of Hepatocellular Carcinoma in Patients With CHB: A Comment for Moving ForwardClinical Gastroenterology and HepatologyVol. 20Issue 2PreviewWe read with interest the meta-analysis by Choi et al.1 Their meta-analysis pooled the hazard ratios and 95% confidence intervals for incidences of hepatocellular carcinoma. They found tenofovir treatment was associated with a significantly lower risk of hepatocellular carcinoma than entecavir in patients with chronic hepatitis B virus infection. Moreover, sensitivity analysis with propensity score–matched cohorts and subgroup analysis with cirrhosis subcohorts confirmed the findings. We applaud Choi et al1 for providing this interesting study that seems to settle a very controversial and hot issue. Full-Text PDF