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Liver Fibrosis in the Natural Course of Chronic Hepatitis B Viral Infection: A Systematic Review with Meta-Analysis

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Abstract

Background

Quantitative data are limited on the natural course of liver fibrosis in patients with chronic HBV infection (CHB).

Aims

To estimate the prevalence of fibrosis status including non-fibrosis, significant fibrosis, advanced fibrosis, and cirrhosis throughout the natural course of CHB.

Methods

We searched Cochrane library, EMBASE, PubMed, SCOPUS, Web of Science, and ScienceDirect from January 1993 to November 2019 for studies with histologic data on liver fibrosis in CHB natural course. CHB course was defined based on current criteria for identifying infection phases as recommended by international clinical practice guidelines, including the HBeAg-positive immune-tolerant, HBeAg-positive immune-active, HBeAg-negative immune-inactive, HBeAg-negative immune-reactive, and HBsAg-negative phases. Pooled prevalence rate of fibrosis status at each phase was obtained from random-effect meta-analyses.

Results

Thirty-three studies with 9,377 adult participants (23.8–49.0 age years; 45.5–88.6% males) were eligible and finally included. The estimated prevalence of non-fibrosis, significant fibrosis, advanced fibrosis, and cirrhosis was, for HBeAg-positive immune-tolerant phase: 31.2% (95%CI 15.6–46.7), 16.9% (95%CI 7.8–26.1), 5.4% (95%CI 0.0–11.2), and 0.0% (95%CI 0.0–1.5); HBeAg-positive immune-active phase: 6.9% (95%CI 3.6–10.2), 50.6% (95%CI 39.2–61.9), 32.1% (95%CI 24.2–40.0), and 12.8% (95%CI 8.6–17.0); HBeAg-negative immune-inactive phase: 32.4% (95%CI 0.0–100.0), 24.8% (95%CI 4.5–45.1), 3.0% (95%CI 0.0–8.3), and 0.0% (95%CI 0.0–1.0); and HBeAg-negative immune-reactive phase: 6.3% (95%CI 3.5–9.2), 50.3% (95%CI 38.9–61.7), 30.3% (95%CI 20.9–39.6), and 10.0% (95%CI 6.6–13.5), respectively. There was only one study for HBsAg-negative phase, thus not allowing further meta-analyses.

Conclusions

Fibrosis risk persists through CHB natural course. These data can support risk estimation in clinical practice and provide reference for noninvasive investigation.

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Abbreviations

ALT:

Alanine aminotransferase

BMI:

Body mass index

CHB:

Chronic hepatitis B viral infection

CPGs:

Clinical practice guidelines

HBeAg:

Hepatitis B virus e antigen

HBV:

Hepatitis B virus

MOOSE:

Meta-analyses Of Observational Studies in Epidemiology

PNALT:

Persistently normal ALT

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Funding

This study was partly supported by the National Natural Science Foundation of China (81670522, 82070589), President Foundation of Southern Medical University Nanfang Hospital (2018Z016), and Sanming Project of Medicine in Shenzhen (SZSM201911001).

Author information

Authors and Affiliations

  1. Department of Infectious Disease and Hepatology Unit, Nanfang Hospital, Southern Medical University, Guangzhou, China

    Mei-Hong Lin, Hai-Qiong Li, Lin Zhu, Hai-Ying Su, Li-Shan Peng, Chuang-Yuan Wang, Xie-Er Liang & Yan Wang

  2. The Second School of Clinical Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou, China

    Mei-Hong Lin, Hai-Qiong Li, Lin Zhu, Hai-Ying Su, Li-Shan Peng & Chuang-Yuan Wang

  3. Biomedical Research Center, Southern Medical University, Guangzhou, China

    Cai-Ping He & Yan Wang

  4. School of Pharmaceutical Science, Southern Medical University, Guangzhou, China

    Cai-Ping He

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  1. Mei-Hong Lin
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Contributions

MHL, HQL, LZ, HYS, LSP, CYW, and YW screened the studies, identified the studies, and extracted data. MHL, HQL, and LZ conducted data analyses and prepared the manuscript data. CPH provided technical support. XEL critically revised the manuscript. YW acquired the funding, designed and supervised the project, and drafted the manuscript. All authors approved the final version of the article and agreed on the order of their names in the author list.

Corresponding author

Correspondence to Yan Wang.

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Lin, MH., Li, HQ., Zhu, L. et al. Liver Fibrosis in the Natural Course of Chronic Hepatitis B Viral Infection: A Systematic Review with Meta-Analysis. Dig Dis Sci 67, 2608–2626 (2022). https://doi.org/10.1007/s10620-021-07009-y

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