Tenofovir vs Entecavir for Hepatocellular Carcinoma Prevention in Patients With Chronic Hepatitis B

Current guidelines for the treatment of chronic hepatitis B (CHB) recommend as first-line line therapy entecavir (ETV), tenofovir disoproxil fumarate (TDF), or tenofovir alafenamide fumarate. Both ETV and TDF achieve similar rates of hepatitis B virus (HBV) DNA suppression and alanine aminotransferase normalization over time and have an excellent safety record. However, ETV and TDF have not been directly compared except in patients with decompensated cirrhosis; to our knowledge, no other head-to-head randomized trials exist. Yet, there is strong interest in understanding if one drug might be superior to the other in specific clinical settings or subpopulations. In the absence of randomized comparator trials, high-quality "real world" cohorts can be quite informative. In this issue of JAMA Oncology, Choi and colleagues report the results of 2 retrospective cohort studies of patients with CHB from Korea that evaluated the association between the type of nucleoside or nucleotide analogue and the development of hepatocellular carcinoma (HCC). Using both a large administrative data set (24 156 patients with CHB and 984 with HCC) and a tertiary hospital-based cohort (2701 patients with CHB and 154 with HCC), the authors found that the risk of HCC was consistently about 35% lower in those treated with TDF than in those treated with ETV. This association persisted even when stratified by cirrhosis status and after very thorough adjustment for available confounders. These striking findings raise the question of whether the current CHB guidelines should be updated to reflect this observed superior anticancer benefit of TDF over ETV.

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