Treatment Discontinuation and Adherence in Patients With Chronic Hepatitis B Infection Newly Initiating Nucleos(t)ide Analogues in Japan: A Retrospective Cohort Study

Nucleos(t)ide analogue (NA) therapy is the current standard of care for chronic hepatitis B (CHB) virus infection but rarely achieves functional cure, necessitating long-term therapy, which often leads to nonadherence and increased treatment burden. This retrospective cohort study was designed to describe treatment discontinuation and adherence to second-generation NAs among patients with CHB in Japan. We used the Japanese Medical Data Center Claims Database (JMDC Inc.) to identify adults with CHB who were newly initiated on a single-agent, second-generation NA between January 2007 and August 2023. Outcomes included treatment discontinuation and adherence, treatment restart after discontinuation, NA switching and factors associated with treatment discontinuation/adherence. Of the 2473 patients included in this study (mean age 49.9 years), 65.6% were male. The most common index NAs were entecavir (55.5%) and tenofovir alafenamide fumarate (TAF, 36.2%). Treatment discontinuation was observed in 20.3% of patients; mean time to discontinuation was 20.4 months. Of the patients who discontinued, 50.7% restarted NAs. Mean adherence (proportion of days covered [PDC]) was 0.87, and 81.2% of participants had PDC ≥ 80%. Age group 35-64 years, index treatment TAF and baseline hepatocellular carcinoma diagnosis were significantly associated with a decreased probability of treatment discontinuation and nonadherence. Although a high proportion of patients were persistent and adherent to NA treatment, there is a subgroup of patients whose needs are not met while receiving NA treatment, particularly in younger age groups. The results emphasise the need for alternative therapies with shorter, finite treatment durations to improve patient persistence, adherence and outcomes.