Persistent Low Level of Hepatitis B Virus Promotes Fibrosis Progression During Therapy.

Abstract

BACKGROUND & AIMS:

Progression of liver fibrosis still occurs in some patients with chronic hepatitis B virus (HBV) infection despite antiviral therapy. We aimed to identify risk factors for fibrosis progression in patients who received antiviral therapy.

METHODS:

We conducted a longitudinal study of patients with chronic HBV infection and liver biopsies collected before and after 78 weeks of anti-HBV therapy. Fibrosis progression was defined as Ishak stage increase ≥ 1 or as predominantly progressive classified by P-I-R system (Beijing Classification). Levels of HBV DNA and HBV RNA in blood samples were measured by real-time quantitative PCR. HBV RNA in liver tissue was detected by in situ hybridization.

RESULTS:

A total of 239 patients with chronic HBV infection with paired liver biopsies were included. Among the 163 patients with significant fibrosis at baseline (Ishak ≥ stage 3), fibrosis progressed in 22 patients (13%), was indeterminate in 24 patients (15%), and regressed in 117 patients (72%). Univariate and multivariate analyses revealed that independent risk factors for fibrosis progression were higher rate of detected HBV DNA at week 78 (odds ratio, 4.84; 95% CI, 1.30-17.98; P = .019) and alcohol intake (odds ratio, 23.84; 95% CI, 2.68-212.50; P = .004). HBV DNA was detected in blood samples from a significantly higher proportion of patients with fibrosis progression (50%) at week 78 than patients with fibrosis regression (19%) or indeterminate fibrosis (26%) (P = .015), despite low viremia (20-200 IU/mL) in all groups. The decrease of serum HBV RNA from baseline in the fibrosis regression group was larger than that in the fibrosis progression group.

CONCLUSIONS:

In a longitudinal study of patients with chronic HBV infection, we associated liver fibrosis progression at week 78 of treatment with higher rates of detected HBV DNA. We propose that a low level of residual HBV may still promote fibrosis progression, and that patients' levels of HBV DNA should be carefully monitored.

• Authors: Yameng Sun, Xiaoning Wu, Jialing Zhou, Tongtong Meng, Bingqiong Wang, Shuyan Chen, Hui Liu, Tailing Wang, Xinyan Zhao, Shanshan Wu, Yuanyuan Kong, Xiaojuan Ou, Aileen Wee, Neil D Theise, Chao Qiu, Wenhong Zhang, Fengmin Lu, Jidong Jia, Hong You
• Journal: Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association (Clin Gastroenterol Hepatol) Vol. 18 Issue 11 Pg. 2582-2591.e6 (10 2020) ISSN: 1542-7714 [Electronic] United States
• PMID: 32147592 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.

Chemical References

• DNA, Viral
• Hepatitis B e Antigens

Topics

• DNA, Viral
• Hepatitis B
• Hepatitis B e Antigens
• Hepatitis B virus (genetics)
• Hepatitis B, Chronic (drug therapy)
• Humans
• Liver Cirrhosis
• Longitudinal Studies