High level of medication adherence is required to lower mortality in patients with chronic hepatitis B taking entecavir: A nationwide cohort study

It is unclear whether suboptimal adherence contributes to adverse clinical outcomes in patients with chronic hepatitis B (CHB). Moreover, there is no consensus regarding the optimal level of drug adherence. This was a population‐based historical cohort study including 51 975 adult CHB patients treated with entecavir (0.5 mg/d orally). Data were obtained from the Korean national health insurance service claims database, which covers >99% of the entire population, between 2007 and 2015. Medication adherence was categorized as high (proportion of days covered [PDC], ≥90%; n = 32 089), intermediate (PDC, 80%‐89%; n = 10 197) and low (PDC, <80%; n = 9689). During a median 4.5 years (maximal 9 years) of follow‐up in 51 975 CHB patients treated with entecavir, multivariable analyses revealed that the risk of mortality/transplantation was significantly greater in the low‐adherers (adjusted hazard ratio [HR], 1.38; P < .001) and intermediate‐adherers (adjusted HR, 1.44; P < .001) than the high‐adherers (P for trend < 0.001). The risk of renal failure in the low‐ and intermediate‐adherence groups was also significantly higher than the high‐adherence group (P for trend < 0.001). By contrast, the risk of hepatocellular carcinoma (HCC) was not significantly different between groups (P for trend = 0.70). The higher risk of mortality/transplantation and renal failure but similar risk of HCC for low‐ and intermediate‐adherers compared with high‐adherers was consistent in inverse probability treatment weighting analysis of the entire cohort and subcohorts with or without cirrhosis. In conclusion, high medication adherence (≥90%) is required to significantly lower risk of mortality and renal failure in patients with CHB during long‐term treatment with entecavir.