Skip to main content
Top
Published in: Digestive Diseases and Sciences 6/2022

18-05-2021 | Hepatitis B | Original Article

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

Authors: Mei-Hong Lin, Hai-Qiong Li, Lin Zhu, Hai-Ying Su, Li-Shan Peng, Chuang-Yuan Wang, Cai-Ping He, Xie-Er Liang, Yan Wang

Published in: Digestive Diseases and Sciences | Issue 6/2022

Login to get access

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.
Appendix
Available only for authorised users
Literature
1.
go back to reference James SL, Abate D, Abate KH et al. Global, regional, and national incidence, prevalence, and years lived with disability for 354 diseases and injuries for 195 countries and territories, 1990–2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet 2018;392:1789–1858.CrossRef James SL, Abate D, Abate KH et al. Global, regional, and national incidence, prevalence, and years lived with disability for 354 diseases and injuries for 195 countries and territories, 1990–2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet 2018;392:1789–1858.CrossRef
2.
go back to reference Sarin SK, Kumar M, Lau GK et al. Asian-Pacific clinical practice guidelines on the management of hepatitis B: a 2015 update. Hepatol Int 2016;10:1–98.PubMedCrossRef Sarin SK, Kumar M, Lau GK et al. Asian-Pacific clinical practice guidelines on the management of hepatitis B: a 2015 update. Hepatol Int 2016;10:1–98.PubMedCrossRef
3.
go back to reference Terrault NA, Bzowej NH, Chang KM et al. AASLD guidelines for treatment of chronic hepatitis B. Hepatology 2016;63:261–283.PubMedCrossRef Terrault NA, Bzowej NH, Chang KM et al. AASLD guidelines for treatment of chronic hepatitis B. Hepatology 2016;63:261–283.PubMedCrossRef
4.
go back to reference European Association for the Study of the Liver. EASL 2017 Clinical Practice Guidelines on the management of hepatitis B virus infection. J Hepatol 2017;67:370–398.CrossRef European Association for the Study of the Liver. EASL 2017 Clinical Practice Guidelines on the management of hepatitis B virus infection. J Hepatol 2017;67:370–398.CrossRef
5.
go back to reference Stroup DF, Berlin JA, Morton SC et al. Meta-analysis of observational studies in epidemiology: a proposal for reporting. Meta-analysis Of Observational Studies in Epidemiology (MOOSE) group. JAMA 2000;283:2008–2012.PubMedCrossRef Stroup DF, Berlin JA, Morton SC et al. Meta-analysis of observational studies in epidemiology: a proposal for reporting. Meta-analysis Of Observational Studies in Epidemiology (MOOSE) group. JAMA 2000;283:2008–2012.PubMedCrossRef
6.
go back to reference Ferre F. Quantitative or semi-quantitative PCR: reality versus myth. PCR Methods Appl 1992;2:1–9.PubMedCrossRef Ferre F. Quantitative or semi-quantitative PCR: reality versus myth. PCR Methods Appl 1992;2:1–9.PubMedCrossRef
7.
go back to reference Knodell RG, Ishak KG, Black WC et al. Formulation and application of a numerical scoring system for assessing histological activity in asymptomatic chronic active hepatitis. Hepatology 1981;1:431–435.PubMedCrossRef Knodell RG, Ishak KG, Black WC et al. Formulation and application of a numerical scoring system for assessing histological activity in asymptomatic chronic active hepatitis. Hepatology 1981;1:431–435.PubMedCrossRef
8.
go back to reference Ishak K, Baptista A, Bianchi L et al. Histological grading and staging of chronic hepatitis. J Hepatol 1995;22:696–699.PubMedCrossRef Ishak K, Baptista A, Bianchi L et al. Histological grading and staging of chronic hepatitis. J Hepatol 1995;22:696–699.PubMedCrossRef
9.
go back to reference Bedossa P, Poynard T. An algorithm for the grading of activity in chronic hepatitis C The METAVIR Cooperative Study Group. Hepatology 1996;24:289–293.PubMedCrossRef Bedossa P, Poynard T. An algorithm for the grading of activity in chronic hepatitis C The METAVIR Cooperative Study Group. Hepatology 1996;24:289–293.PubMedCrossRef
10.
go back to reference Desmet VJ, Gerber M, Hoofnagle JH, Manns M, Scheuer PJ. Classification of chronic hepatitis: diagnosis, grading and staging. Hepatology 1994;19:1513–1520.PubMedCrossRef Desmet VJ, Gerber M, Hoofnagle JH, Manns M, Scheuer PJ. Classification of chronic hepatitis: diagnosis, grading and staging. Hepatology 1994;19:1513–1520.PubMedCrossRef
11.
go back to reference Batts KP, Ludwig J. Chronic hepatitis. An update on terminology and reporting. Am J Surg Pathol 1995;19:1409–1417.PubMedCrossRef Batts KP, Ludwig J. Chronic hepatitis. An update on terminology and reporting. Am J Surg Pathol 1995;19:1409–1417.PubMedCrossRef
12.
go back to reference Scheuer PJ. Classification of chronic viral hepatitis: a need for reassessment. J Hepatol 1991;13:372–374.PubMedCrossRef Scheuer PJ. Classification of chronic viral hepatitis: a need for reassessment. J Hepatol 1991;13:372–374.PubMedCrossRef
13.
go back to reference Stang A. Critical evaluation of the Newcastle-Ottawa scale for the assessment of the quality of nonrandomized studies in meta-analyses. Eur J Epidemiol 2010;25:603–605.PubMedCrossRef Stang A. Critical evaluation of the Newcastle-Ottawa scale for the assessment of the quality of nonrandomized studies in meta-analyses. Eur J Epidemiol 2010;25:603–605.PubMedCrossRef
14.
go back to reference Rostom A DC, Cranney A, et al. Appendix D. Quality Assessment Forms—Celiac Disease—NCBI Bookshelf In; 2004. Rostom A DC, Cranney A, et al. Appendix D. Quality Assessment Forms—Celiac Disease—NCBI Bookshelf In; 2004.
15.
go back to reference Ahn SH, Park YN, Park JY et al. Long-term clinical and histological outcomes in patients with spontaneous hepatitis B surface antigen seroclearance. J Hepatol 2005;42:188–194.PubMedCrossRef Ahn SH, Park YN, Park JY et al. Long-term clinical and histological outcomes in patients with spontaneous hepatitis B surface antigen seroclearance. J Hepatol 2005;42:188–194.PubMedCrossRef
16.
go back to reference Alam S, Ahmad N, Mustafa G et al. Evaluation of normal or minimally elevated alanine transaminase, age and DNA level in predicting liver histological changes in chronic hepatitis B. Liver Int 2011;31:824–830.PubMedCrossRef Alam S, Ahmad N, Mustafa G et al. Evaluation of normal or minimally elevated alanine transaminase, age and DNA level in predicting liver histological changes in chronic hepatitis B. Liver Int 2011;31:824–830.PubMedCrossRef
17.
go back to reference Bae SK, Yatsuhashi H, Hashimoto S et al. Prediction of early HBeAg seroconversion by decreased titers of HBeAg in the serum combined with increased grades of lobular inflammation in the liver. Med Sci Monit 2012;18:Cr698-705.PubMedPubMedCentralCrossRef Bae SK, Yatsuhashi H, Hashimoto S et al. Prediction of early HBeAg seroconversion by decreased titers of HBeAg in the serum combined with increased grades of lobular inflammation in the liver. Med Sci Monit 2012;18:Cr698-705.PubMedPubMedCentralCrossRef
18.
go back to reference Balkan A, Namiduru M, Balkan Y et al. Are serum quantitative hepatitis b surface antigen levels, liver histopathology and viral loads related in chronic hepatitis b-infected patients? Saudi J Gastroenterol 2016;22:208–214.PubMedPubMedCentralCrossRef Balkan A, Namiduru M, Balkan Y et al. Are serum quantitative hepatitis b surface antigen levels, liver histopathology and viral loads related in chronic hepatitis b-infected patients? Saudi J Gastroenterol 2016;22:208–214.PubMedPubMedCentralCrossRef
19.
go back to reference Barut S, Gemici U, Gunes F, Demir O, Duygu F. Predictors of histological indication for treatment in HBeAg negative chronic HBV infection. J Med Virol 2017;89:1952–1957.PubMedCrossRef Barut S, Gemici U, Gunes F, Demir O, Duygu F. Predictors of histological indication for treatment in HBeAg negative chronic HBV infection. J Med Virol 2017;89:1952–1957.PubMedCrossRef
20.
go back to reference Bayram A, Erkilic S, Ozkur A, Bayram M, Sari I. Quantification of intrahepatic total hepatitis B virus DNA in chronic hepatitis B patients and its relationship with liver histology. J Clin Pathol 2008;61:338–342.PubMedCrossRef Bayram A, Erkilic S, Ozkur A, Bayram M, Sari I. Quantification of intrahepatic total hepatitis B virus DNA in chronic hepatitis B patients and its relationship with liver histology. J Clin Pathol 2008;61:338–342.PubMedCrossRef
21.
go back to reference Charatcharoenwitthaya P, Phisalprapa P, Pausawasdi N et al. Alanine aminotransferase course, serum hepatitis B virus DNA, and liver stiffness measurement for therapeutic decisions in hepatitis B e antigen-negative chronic hepatitis B. Hepatol Res 2016;46:1347–1357.PubMedCrossRef Charatcharoenwitthaya P, Phisalprapa P, Pausawasdi N et al. Alanine aminotransferase course, serum hepatitis B virus DNA, and liver stiffness measurement for therapeutic decisions in hepatitis B e antigen-negative chronic hepatitis B. Hepatol Res 2016;46:1347–1357.PubMedCrossRef
22.
go back to reference Chen YC, Huang SF, Chu CM, Liaw YF. Serial HBV DNA levels in patients with persistently normal transaminase over 10 years following spontaneous HBeAg seroconversion. J Viral Hepat 2012;19:138–146.PubMedCrossRef Chen YC, Huang SF, Chu CM, Liaw YF. Serial HBV DNA levels in patients with persistently normal transaminase over 10 years following spontaneous HBeAg seroconversion. J Viral Hepat 2012;19:138–146.PubMedCrossRef
23.
go back to reference Hong MZ, Huang WQ, Min F et al. Enhanced HBsAg Synthesis Correlates with Increased Severity of Fibrosis in Chronic Hepatitis B Patients. Plos One 2014;9:e87344.PubMedPubMedCentralCrossRef Hong MZ, Huang WQ, Min F et al. Enhanced HBsAg Synthesis Correlates with Increased Severity of Fibrosis in Chronic Hepatitis B Patients. Plos One 2014;9:e87344.PubMedPubMedCentralCrossRef
24.
go back to reference Hui CK, Leung N, Shek TW et al. Sustained disease remission after spontaneous HBeAg seroconversion is associated with reduction in fibrosis progression in chronic hepatitis B Chinese patients. Hepatology 2007;46:690–698.PubMedCrossRef Hui CK, Leung N, Shek TW et al. Sustained disease remission after spontaneous HBeAg seroconversion is associated with reduction in fibrosis progression in chronic hepatitis B Chinese patients. Hepatology 2007;46:690–698.PubMedCrossRef
25.
go back to reference Hui CK, Leung N, Yuen ST et al. Natural history and disease progression in Chinese chronic hepatitis B patients in immune-tolerant phase. Hepatology 2007;46:395–401.PubMedCrossRef Hui CK, Leung N, Yuen ST et al. Natural history and disease progression in Chinese chronic hepatitis B patients in immune-tolerant phase. Hepatology 2007;46:395–401.PubMedCrossRef
26.
go back to reference Ikeda K, Arase Y, Saitoh S et al. Long-term outcome of HBV carriers with negative HBe antigen and normal aminotransferase. Am J Med 2006;119:977–985.PubMedCrossRef Ikeda K, Arase Y, Saitoh S et al. Long-term outcome of HBV carriers with negative HBe antigen and normal aminotransferase. Am J Med 2006;119:977–985.PubMedCrossRef
27.
go back to reference Ke WM, Xie SB, Li XJ et al. There were no differences in serum HBV DNA level between HBeAg-positive and HBeAg-negative chronic hepatitis B with same liver histological necroinflammation grade but differences among grades 1, 2, 3 and 4 apportioned by the same hepatic parenchyma cell volume. J Viral Hepat 2011;18:637–645.PubMedCrossRef Ke WM, Xie SB, Li XJ et al. There were no differences in serum HBV DNA level between HBeAg-positive and HBeAg-negative chronic hepatitis B with same liver histological necroinflammation grade but differences among grades 1, 2, 3 and 4 apportioned by the same hepatic parenchyma cell volume. J Viral Hepat 2011;18:637–645.PubMedCrossRef
28.
go back to reference Li MR, Zheng HW, Ma SM et al. Correlations between serum hepatitis B surface antigen and hepatitis B core antibody titers and liver fibrosis in treatment-naive CHB patients. J Chin Med Assoc 2018;81:1052–1059.PubMedCrossRef Li MR, Zheng HW, Ma SM et al. Correlations between serum hepatitis B surface antigen and hepatitis B core antibody titers and liver fibrosis in treatment-naive CHB patients. J Chin Med Assoc 2018;81:1052–1059.PubMedCrossRef
29.
go back to reference Li Q, Li W, Huang Y, Chen L. The gamma-glutamyl transpeptidase-to-platelet ratio predicts liver fibrosis and cirrhosis in HBeAg-positive chronic HBV infection patients with high HBV DNA and normal or mildly elevated alanine transaminase levels in China. J Viral Hepat 2016;23:912–919.PubMedCrossRef Li Q, Li W, Huang Y, Chen L. The gamma-glutamyl transpeptidase-to-platelet ratio predicts liver fibrosis and cirrhosis in HBeAg-positive chronic HBV infection patients with high HBV DNA and normal or mildly elevated alanine transaminase levels in China. J Viral Hepat 2016;23:912–919.PubMedCrossRef
30.
go back to reference Liang LB, Zhu X, Yan LB et al. Quantitative intrahepatic HBV cccDNA correlates with histological liver inflammation in chronic hepatitis B virus infection. Int J Infect Dis 2016;52:77–82.PubMedCrossRef Liang LB, Zhu X, Yan LB et al. Quantitative intrahepatic HBV cccDNA correlates with histological liver inflammation in chronic hepatitis B virus infection. Int J Infect Dis 2016;52:77–82.PubMedCrossRef
31.
go back to reference Liao B, Wang Z, Lin S et al. Significant fibrosis is not rare in Chinese chronic hepatitis B patients with persistent normal ALT. PLoS One 2013;8:e78672.PubMedPubMedCentralCrossRef Liao B, Wang Z, Lin S et al. Significant fibrosis is not rare in Chinese chronic hepatitis B patients with persistent normal ALT. PLoS One 2013;8:e78672.PubMedPubMedCentralCrossRef
32.
go back to reference Liu D, Li J, Lu W et al. Gamma-glutamyl transpeptidase to cholinesterase and platelet ratio in predicting significant liver fibrosis and cirrhosis of chronic hepatitis B. Clin Microbiol Infect 2019;25:514-e1.PubMedCrossRef Liu D, Li J, Lu W et al. Gamma-glutamyl transpeptidase to cholinesterase and platelet ratio in predicting significant liver fibrosis and cirrhosis of chronic hepatitis B. Clin Microbiol Infect 2019;25:514-e1.PubMedCrossRef
33.
go back to reference Mohamadnejad M, Montazeri G, Fazlollahi A et al. Noninvasive markers of liver fibrosis and inflammation in chronic hepatitis B-virus related liver disease. Am J Gastroenterol 2006;101:2537–2545.PubMedCrossRef Mohamadnejad M, Montazeri G, Fazlollahi A et al. Noninvasive markers of liver fibrosis and inflammation in chronic hepatitis B-virus related liver disease. Am J Gastroenterol 2006;101:2537–2545.PubMedCrossRef
34.
go back to reference Murata M, Matsuzaki K, Yoshida K et al. Hepatitis B virus X protein shifts human hepatic transforming growth factor (TGF)-beta signaling from tumor suppression to oncogenesis in early chronic hepatitis B. Hepatology 2009;49:1203–1217.PubMedCrossRef Murata M, Matsuzaki K, Yoshida K et al. Hepatitis B virus X protein shifts human hepatic transforming growth factor (TGF)-beta signaling from tumor suppression to oncogenesis in early chronic hepatitis B. Hepatology 2009;49:1203–1217.PubMedCrossRef
35.
go back to reference Park JY, Park YN, Kim DY et al. High prevalence of significant histology in asymptomatic chronic hepatitis B patients with genotype C and high serum HBV DNA levels. J Viral Hepat 2008;15:615–621.PubMedCrossRef Park JY, Park YN, Kim DY et al. High prevalence of significant histology in asymptomatic chronic hepatitis B patients with genotype C and high serum HBV DNA levels. J Viral Hepat 2008;15:615–621.PubMedCrossRef
36.
go back to reference Seto WK, Lai CL, Ip PP et al. A large population histology study showing the lack of association between ALT elevation and significant fibrosis in chronic hepatitis B. PLoS One 2012;7:e32622.PubMedPubMedCentralCrossRef Seto WK, Lai CL, Ip PP et al. A large population histology study showing the lack of association between ALT elevation and significant fibrosis in chronic hepatitis B. PLoS One 2012;7:e32622.PubMedPubMedCentralCrossRef
37.
go back to reference Yim SY, Kim TH, Jun SS et al. Expression of hepatocyte hepatitis B core antigen and hepatitis B surface antigen as a marker in the management of chronic hepatitis B patients. Gut Liver 2017;11:417–425.PubMedPubMedCentralCrossRef Yim SY, Kim TH, Jun SS et al. Expression of hepatocyte hepatitis B core antigen and hepatitis B surface antigen as a marker in the management of chronic hepatitis B patients. Gut Liver 2017;11:417–425.PubMedPubMedCentralCrossRef
38.
go back to reference Yuen MF, Ng IO, Fan ST et al. Significance of HBV DNA levels in liver histology of HBeAg and Anti-HBe positive patients with chronic hepatitis B. Am J Gastroenterol 2004;99:2032–2037.PubMedCrossRef Yuen MF, Ng IO, Fan ST et al. Significance of HBV DNA levels in liver histology of HBeAg and Anti-HBe positive patients with chronic hepatitis B. Am J Gastroenterol 2004;99:2032–2037.PubMedCrossRef
39.
go back to reference Zeng DW, Liu YR, Dong J et al. Serum HBsAg and HBeAg levels are associated with liver pathological stages in the immune clearance phase of hepatitis B virus chronic infection. Mol Med Rep 2015;11:3465–3472.PubMedCrossRef Zeng DW, Liu YR, Dong J et al. Serum HBsAg and HBeAg levels are associated with liver pathological stages in the immune clearance phase of hepatitis B virus chronic infection. Mol Med Rep 2015;11:3465–3472.PubMedCrossRef
40.
go back to reference Zhou J, Song L, Zhao H et al. Serum hepatitis B core antibody as a biomarker of hepatic inflammation in chronic hepatitis B patients with normal alanine aminotransferase. Sci Rep 2017;7:2747.PubMedPubMedCentralCrossRef Zhou J, Song L, Zhao H et al. Serum hepatitis B core antibody as a biomarker of hepatic inflammation in chronic hepatitis B patients with normal alanine aminotransferase. Sci Rep 2017;7:2747.PubMedPubMedCentralCrossRef
41.
go back to reference Andreani T, Serfaty L, Mohand D et al. Chronic hepatitis B virus carriers in the immunotolerant phase of infection: histologic findings and outcome. Clin Gastroenterol Hepatol 2007;5:636–641.PubMedCrossRef Andreani T, Serfaty L, Mohand D et al. Chronic hepatitis B virus carriers in the immunotolerant phase of infection: histologic findings and outcome. Clin Gastroenterol Hepatol 2007;5:636–641.PubMedCrossRef
42.
go back to reference Di Marco V, Lo Iacono O, Camma C et al. The long-term course of chronic hepatitis B. Hepatology 1999;30:257–264.PubMedCrossRef Di Marco V, Lo Iacono O, Camma C et al. The long-term course of chronic hepatitis B. Hepatology 1999;30:257–264.PubMedCrossRef
43.
go back to reference Martinot-Peignoux M, Carvalho-Filho R, Lapalus M et al. Hepatitis B surface antigen serum level is associated with fibrosis severity in treatment-naive, e antigen-positive patients. J Hepatol 2013;58:1089–1095.PubMedCrossRef Martinot-Peignoux M, Carvalho-Filho R, Lapalus M et al. Hepatitis B surface antigen serum level is associated with fibrosis severity in treatment-naive, e antigen-positive patients. J Hepatol 2013;58:1089–1095.PubMedCrossRef
44.
go back to reference Zacharakis GH, Koskinas J, Kotsiou S et al. Natural history of chronic HBV infection: a cohort study with up to 12 years follow-up in North Greece (part of the Interreg I-II/EC-project). J Med Virol 2005;77:173–179.PubMedCrossRef Zacharakis GH, Koskinas J, Kotsiou S et al. Natural history of chronic HBV infection: a cohort study with up to 12 years follow-up in North Greece (part of the Interreg I-II/EC-project). J Med Virol 2005;77:173–179.PubMedCrossRef
45.
go back to reference Nguyen MH, Garcia RT, Trinh HN et al. Histological disease in Asian-Americans with chronic hepatitis B, high hepatitis B virus DNA, and normal alanine aminotransferase levels. Am J Gastroenterol 2009;104:2206–2213.PubMedCrossRef Nguyen MH, Garcia RT, Trinh HN et al. Histological disease in Asian-Americans with chronic hepatitis B, high hepatitis B virus DNA, and normal alanine aminotransferase levels. Am J Gastroenterol 2009;104:2206–2213.PubMedCrossRef
46.
go back to reference Wang CC, Lim LY, Deubner H et al. Factors predictive of significant hepatic fibrosis in adults with chronic hepatitis B and normal serum ALT. J Clin Gastroenterol 2008;42:820–826.PubMedCrossRef Wang CC, Lim LY, Deubner H et al. Factors predictive of significant hepatic fibrosis in adults with chronic hepatitis B and normal serum ALT. J Clin Gastroenterol 2008;42:820–826.PubMedCrossRef
47.
go back to reference El-Zayadi AR, Badran HM, Saied A et al. Evaluation of liver biopsy in Egyptian HBeAg-negative chronic hepatitis B patients at initial presentation: implications for therapy. Am J Gastroenterol 2009;104:906–911.PubMedCrossRef El-Zayadi AR, Badran HM, Saied A et al. Evaluation of liver biopsy in Egyptian HBeAg-negative chronic hepatitis B patients at initial presentation: implications for therapy. Am J Gastroenterol 2009;104:906–911.PubMedCrossRef
48.
go back to reference Chao DT, Lim JK, Ayoub WS, Nguyen LH, Nguyen MH. Systematic review with meta-analysis: the proportion of chronic hepatitis B patients with normal alanine transaminase ≤ 40 IU/L and significant hepatic fibrosis. Aliment Pharmacol Ther 2014;39:349–358.PubMedCrossRef Chao DT, Lim JK, Ayoub WS, Nguyen LH, Nguyen MH. Systematic review with meta-analysis: the proportion of chronic hepatitis B patients with normal alanine transaminase ≤ 40 IU/L and significant hepatic fibrosis. Aliment Pharmacol Ther 2014;39:349–358.PubMedCrossRef
49.
go back to reference Wu JF, Song SH, Lee CS et al. Clinical predictors of liver fibrosis in patients with chronic hepatitis B virus infection from children to adults. J Infect Dis 2018;217:1408–1416.PubMedCrossRef Wu JF, Song SH, Lee CS et al. Clinical predictors of liver fibrosis in patients with chronic hepatitis B virus infection from children to adults. J Infect Dis 2018;217:1408–1416.PubMedCrossRef
Metadata
Title
Liver Fibrosis in the Natural Course of Chronic Hepatitis B Viral Infection: A Systematic Review with Meta-Analysis
Authors
Mei-Hong Lin
Hai-Qiong Li
Lin Zhu
Hai-Ying Su
Li-Shan Peng
Chuang-Yuan Wang
Cai-Ping He
Xie-Er Liang
Yan Wang
Publication date
18-05-2021
Publisher
Springer US
Keyword
Hepatitis B
Published in
Digestive Diseases and Sciences / Issue 6/2022
Print ISSN: 0163-2116
Electronic ISSN: 1573-2568
DOI
https://doi.org/10.1007/s10620-021-07009-y

Other articles of this Issue 6/2022

Digestive Diseases and Sciences 6/2022 Go to the issue