Clinical Features of Chronic Hepatitis B in Treatment-naive Asian Patients With Positive HBeAg and Coexisting Precore and/or Basal Core Promoter Mutations

Background: Precore or/and basal core promoter ( PC/BCP)mutations are frequently detected in hepatitis B e antigen ( HBeAg)negative patients, but little is known about their clinical significance in HBeAg-positive patients. Aim: To characterize and report the clinical features of treatmentnaive chronic hepatitis B patients who are HBeAg positive and harbor PC and/or BCP mutations. Patients and Methods: Consecutive treatment-naive patients with chronic hepatitis B between 2004 and 2014 were enrolled. Clinical characteristics were compared based on the stratification of HBeAg status and the presence of PC/BCP mutations. In addition, subset analysis in HBeAg-positive cohort was performed to compare clinical features of patients with and without PC/BCP mutations Results: Of the 267 patients enrolled from 3 centers, 177 were HBeAg positive and 90 HBeAg negative. When compared with HBeAg-negative patients, HBeAg-positive patients were significantly younger in mean age ( 37.93 vs. 44.40; P < 0.001), had higher levels of median ALT ( 51 vs. 30.5U/mL; P < 0.001), higher levels of mean HBV DNA ( 7.50 +/- 1.48 vs. 5.10 +/- 1.44 log(10) copies/mL; P < 0.001), and lower frequency of detectable PC/BCP mutations ( 60.45% vs. 93.33%; P < 0.001), but had significantly higher frequency of BCP when mutations were detected ( 37.85% vs. 22.22%; P = 0.013). Among HBeAg-positive patients, when compared with patients with wild type, those with PC/BCP mutations were significantly older ( 30.63 vs. 42.71; P < 0.001), had higher median ALT levels ( 29.5 vs. 73U/mL; P < 0.001), but there was no significant association with mean HBV DNA levels ( 7.96 vs. 7.20 log(10) copies/mL; P = 0.865) or HBV genotype ( P = 1.000). In the multivariate analysis, only age and ALT were independently associated with PC/BCP mutations in HBeAg-positive patients, but there was no association with HBV genotype or DNA. Conclusions: PC/BCP mutants were frequent (up to 60%) in treatment-naive HBeAg-positive patients and were associated with distinct clinical characteristics when compared with patients with wild type or HBeAg negative. Future large studies are needed to substantiate the long-term clinical outcomes when PC/BCP mutations are detected in HBeAg-positive patients as it may impact the natural history or treatment response in such patients.