J Viral Hepat. 2020 May 8. doi: 10.1111/jvh.13315. [Epub ahead of print]
Clinical Features of Hepatitis B Patients at Immune-tolerance Phase with Basal Core Promoter and/or Precore Mutations.
Li MR1,2, Xu ZG2, Lu JH2, Zheng HW2, Ye LH2, Liu YY2, Liu ZQ2, Zhang HC2, Huang Y2, Dai EH2, Pan CQ3,4.
Author information
1
Division of Infectious Disease, The First Affiliated Hospital of Jinan University, Guangzhou, China.
2
Division of Liver Disease, The Fifth Hospital of Shijiazhuang, Hebei Medical University, Shijiazhuang, China.
3
Center of Liver Diseases, Beijing Ditan Hospital, Capital Medical Univerisity, Beijing, China.
4
Division of Gastroenterology and Hepatology, Department of Medicine, NYU Langone Health, New York University School of Medicine, New York, NY, USA.
Abstract
Little data exists on basal core promoter/precore (BCP/PC) mutations in chronic hepatitis B (CHB) patients at the immune-tolerance (IT) phase. We studied consecutive treatment-naïve, CHBe-antigen (HBeAg) positive patients who had undergone liver biopsy and genotyping. Those in the IT phase or immune-clearance (IC) phase were enrolled for comparison of the frequency of BCP/PC mutations and their clinical presentations. Subgroup analyses for the IT group were also performed between patients with and without mutations, and IC patients between fibrosis stages≤2 vs fibrosis>2.Among 301 patients enrolled, 88/301 (29.24%) and 213/301 (70.76%) were at the IT and IC phase, respectively. The frequency of BCP/PC mutations in IT phase was significantly lower than those in IC phase (15.91% vs 64.79 %, P<0.001). The BCP mutation only was significantly more frequent than the PC mutation in both groups and also in all IC subgroups. IT patients with BCP/PC mutations had significantly higher quantitative anti-HBc levels compared with those of patients with wild-type virus (P<0.05). They also had significantly lower mean levels of alanine transaminase, aspartate transaminase, total bilirubin, and qAnti-HBc compared with those of IC patients (all P<0.05). Additionally, they were significantly younger in mean age; had higher platelet count, higher levels of HBV DNA and surface antigen, as well as higher frequency of genotype B than those of IC patients with fibrosis>2 (all P<0.05). BCP/PC mutations were found in IT patients with CHB. They had distinct clinical characteristics when compared with patients with wild-type or at IC phase. Further studies are needed to understand their natural history and treatment outcomes.
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KEYWORDS:
Hepatitis B virus; basal core promoter; hepatitis B e antigen; immune-tolerance; mutation; pre-core