OBJECTIVES: With the advent of Entecavir (ENT), a nucleoside analogue with low drug resistance induction, long-term antiviral therapy (AVT) has become more widely used for chronic hepatitis B (CHB) treatment. Tenofovir disoproxil fumarate (TDF) has been reported to have lower resistance induction compared to ENT, but it is associated with bone and kidney adverse events (AEs) in some patients. Tenofovir alafenamide (TAF), a novel agent, has demonstrated reduced occurrence of these AEs. This study aimed to examine the prevalence of musculoskeletal and renal outcomes in patients receiving ENT, TDF, and TAF.

METHODS: From the 2018 national patient sample claims data, which covers the entire population of South Korea, patients prescribed ENT, TDF, or TAF were extracted. Patients prescribed more than two medications or multiple medications simultaneously within a year were excluded from the analysis. We compared the baseline characteristics of these three groups and investigated the prevalence of musculoskeletal outcomes (including bone fracture and osteoporosis) and renal outcomes (including chronic kidney disease, albuminuria, and kidney transplantation).

RESULTS: Among the 6,584 patients included, TDF usage accounted for 51%, ENT for 46%, and TAF for 3%. ENT-treated patients were generally older, while TDF and TAF-treated patients were progressively younger. Gender differences were not significant. The prevalence of musculoskeletal outcomes did not significantly differ among the treatment groups and was observed in 8.1% of the total patients. However, renal outcomes varied among medication groups, with rates of 5.5% for TAF users, 3.4% for ENT users, and 2.5% for TDF users.

CONCLUSIONS: Despite TAF users being relatively young, they exhibited a higher prevalence of renal outcomes, indicating a potentially lower renal burden compared to TDF. In the context of long-term AVT needs for patients with CHB, AVT selection should consider the AEs associated with each drug and individual characteristics.