Medication Nonadherence Increases Hepatocellular Carcinoma, Cirrhotic Complications, and Mortality in Chronic Hepatitis B Patients Treated With Entecavir

Abstract

OBJECTIVES: Optimal adherence to nucleoside analogue treatment is necessary to achieve undetectable levels of hepatitis B virus (HBV) DNA in patients with chronic hepatitis B (CHB), and to prevent cirrhotic complications. However, any large long-term follow-up study has not been investigated the effect of adherence to entecavir (ETV) treatment on specific liver-related events (LREs), namely, hepatocellular carcinoma (HCC), cirrhotic complications, and mortality. METHODS: This was a 10-year longitudinal observational study of treatment-naïve patients with CHB who received ETV treatment. The primary outcome was the cumulative probability of LREs. The cumulative level of adherence to medication was categorized as good (≥90%) or poor (<90%). RESULTS: Data from 894 treatment-naïve CHB patients who received ETV were analyzed. Overall mean adherence rates were 89.1%. Patients with poor adherence had a higher risk of virologic breakthrough (VBT) (HR, 22.42; 95% CI, 19.57-52.52; P < 0.001) than those with good adherence. Multivariate analyses showed a higher risk of liver-related (HR, 14.29; 95% CI, 3.49-58.47; P < 0.001) or all-cause (HR, 4.96; 95% CI, 2.19-11.27; P < 0.001) mortality, HCC (HR, 2.86; 95% CI, 1.76-4.64; P < 0.001), and cirrhotic complications (HR, 2.86; 95% CI, 1.93-4.25; P < 0.001) with poor adherence. Medication adherence was further stratified into three groups according to adherence rates of <70%, ≥70 to <90%, and ≥90%. The dose-response analyses of adherence rates showed that the risk of LREs increased progressively as medication adherence declined. In particular, the unfavorable effects of nonadherence were more pronounced in patients with cirrhosis. CONCLUSIONS: Poor adherence to medication was associated with a higher mortality and greater risk of HCC and cirrhotic complications, particularly among patients with liver cirrhosis.