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Published in: Hepatology International 5/2019

01-09-2019 | Original Article

The prognostic role of liver stiffness in patients with chronic liver disease: a systematic review and dose–response meta-analysis

Authors: Yue Shen, Sheng-Di Wu, Ling Wu, Si-Qi Wang, Yao Chen, Li-Li Liu, Jing Li, Chang-Qing Yang, Ji-Yao Wang, Wei Jiang

Published in: Hepatology International | Issue 5/2019

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Abstract

Background and aims

Liver stiffness measurement (LSM) by transient elastography (TE) has been assessed for the evaluation of clinically relevant outcomes in patients with chronic liver diseases (CLDs) while with variable results. This systematic review and meta–analysis aims to investigate the relationship between baseline LSM by TE and the development of clinically relevant outcomes.

Methods

The systematic review identified eligible cohorts reporting the association between baseline LSM by TE and risk of hepatic carcinoma (HCC), hepatic decompensation (HD), all–cause and/or liver–related mortality and liver–related events (LREs) in CLD patients. Summary relative risks (RRs) with 95% confidence intervals (CIs) were estimated using a random–effect model. The dose–response association was evaluated by generalized least squares trend (Glst) estimation and restricted cubic splines. Commands of GLST, MKSPLINE, MVMETA were applied for statistical analysis.

Results

62 cohort studies were finally included, reporting on 43,817 participants. For one kPa (kilopascal) increment in baseline liver stiffness (LS), the pooled RR (95% CI) was 1.08 (1.05–1.11) for HCC, 1.08 (1.06–1.11) for all–cause mortality, 1.11 (1.05–1.17) for liver-related mortality, 1.08 (1.06–1.10) for HD and 1.07 (1.04–1.09) for LREs. Furthermore, the nonlinear dose–response analysis indicated that the significant increase in the risk of corresponding clinically relevant outcomes turned to a stable increase or a slight decrease with increasing baseline LS changing primarily in the magnitude of effect rather than the direction.

Conclusions

The dose–response meta-analysis presents a combination between the levels of baseline LS and RRs for each clinically relevant outcome. TE, which is noninvasive, might be a novel strategy for risk stratification and identification of patients at high risk of developing these outcomes.
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Literature
2.
go back to reference Pungpapong S, Kim WR, Poterucha JJ. Natural history of hepatitis B virus infection: an update for clinicians. Mayo Clin Proc. 2007;82:967–75.CrossRefPubMed Pungpapong S, Kim WR, Poterucha JJ. Natural history of hepatitis B virus infection: an update for clinicians. Mayo Clin Proc. 2007;82:967–75.CrossRefPubMed
3.
go back to reference Maharaj B, Maharaj RJ, Leary WP, et al. Sampling variability and its influence on the diagnostic yield of percutaneous needle biopsy of the liver. Lancet. 1986;1:523–5.CrossRefPubMed Maharaj B, Maharaj RJ, Leary WP, et al. Sampling variability and its influence on the diagnostic yield of percutaneous needle biopsy of the liver. Lancet. 1986;1:523–5.CrossRefPubMed
4.
go back to reference Regev A, Berho M, Jeffers LJ, et al. Sampling error and intraobserver variation in liver biopsy in patients with chronic HCV infection. Am J Gastroenterol. 2002;97:2614–8.CrossRefPubMed Regev A, Berho M, Jeffers LJ, et al. Sampling error and intraobserver variation in liver biopsy in patients with chronic HCV infection. Am J Gastroenterol. 2002;97:2614–8.CrossRefPubMed
5.
go back to reference Martinez SM, Crespo G, Navasa M, et al. Noninvasive assessment of liver fibrosis. Hepatology. 2011;53:325–35.CrossRefPubMed Martinez SM, Crespo G, Navasa M, et al. Noninvasive assessment of liver fibrosis. Hepatology. 2011;53:325–35.CrossRefPubMed
6.
go back to reference Ziol M, Handra-Luca A, Kettaneh A, et al. Noninvasive assessment of liver fibrosis by measurement of stiffness in patients with chronic hepatitis C. Hepatology. 2005;41:48–54.CrossRefPubMed Ziol M, Handra-Luca A, Kettaneh A, et al. Noninvasive assessment of liver fibrosis by measurement of stiffness in patients with chronic hepatitis C. Hepatology. 2005;41:48–54.CrossRefPubMed
7.
go back to reference Castera L, Pinzani M, Bosch J. Non invasive evaluation of portal hypertension using transient elastography. J Hepatol. 2012;56:696–703.CrossRefPubMed Castera L, Pinzani M, Bosch J. Non invasive evaluation of portal hypertension using transient elastography. J Hepatol. 2012;56:696–703.CrossRefPubMed
8.
go back to reference Masuzaki R, Tateishi R, Yoshida H, et al. Prospective risk assessment for hepatocellular carcinoma development in patients with chronic hepatitis C by transient elastography. Hepatology. 2009;49:1954–61.CrossRefPubMed Masuzaki R, Tateishi R, Yoshida H, et al. Prospective risk assessment for hepatocellular carcinoma development in patients with chronic hepatitis C by transient elastography. Hepatology. 2009;49:1954–61.CrossRefPubMed
9.
go back to reference Calvaruso V, Bronte F, Simone F, et al. Liver stiffness at baseline predicts decompensation and hepatocellular carcinoma in patients with compensated HCV cirrhosis. Hepatology. 2012;56:930A–1A. Calvaruso V, Bronte F, Simone F, et al. Liver stiffness at baseline predicts decompensation and hepatocellular carcinoma in patients with compensated HCV cirrhosis. Hepatology. 2012;56:930A–1A.
10.
go back to reference Vicente FJ, Barreiro P, Vispo E, et al. Baseline liver stiffness and achievement of sustained virological response predict liver complications and death in HIV/HCV coinfected patients receiving peginterferon/ribavirin therapy. Hepatology. 2012;56:650A–1A. Vicente FJ, Barreiro P, Vispo E, et al. Baseline liver stiffness and achievement of sustained virological response predict liver complications and death in HIV/HCV coinfected patients receiving peginterferon/ribavirin therapy. Hepatology. 2012;56:650A–1A.
11.
go back to reference Klibansky DA, Mehta SH, Curry M, et al. Transient elastography for predicting clinical outcomes in patients with chronic liver disease. J Viral Hepatitis. 2012;19:e184–93.CrossRef Klibansky DA, Mehta SH, Curry M, et al. Transient elastography for predicting clinical outcomes in patients with chronic liver disease. J Viral Hepatitis. 2012;19:e184–93.CrossRef
12.
go back to reference Wong GLH, Chan HLY, Wong CKY, et al. Liver stiffness–based optimization of hepatocellular carcinoma risk score in patients with chronic hepatitis B. J Hepatol. 2014;60:339–45.CrossRefPubMed Wong GLH, Chan HLY, Wong CKY, et al. Liver stiffness–based optimization of hepatocellular carcinoma risk score in patients with chronic hepatitis B. J Hepatol. 2014;60:339–45.CrossRefPubMed
13.
go back to reference Singh S, Fujii LL, Murad MH, et al. Liver stiffness is associated with risk of decompensation, liver cancer, and death in patients with chronic liver diseases: a systematic review and meta–analysis. Clin Gastroenterol H. 2013;11:1573–84.CrossRef Singh S, Fujii LL, Murad MH, et al. Liver stiffness is associated with risk of decompensation, liver cancer, and death in patients with chronic liver diseases: a systematic review and meta–analysis. Clin Gastroenterol H. 2013;11:1573–84.CrossRef
14.
go back to reference Higgins JPT, Green S (eds) Cochrane Handbook for systematic reviews of interventions version 5.1.0 [updated March 2011]. The Cochrane Collaboration, 2011. Available from http://handbook.cochrane.org. Accessed 16 May 2013. Higgins JPT, Green S (eds) Cochrane Handbook for systematic reviews of interventions version 5.1.0 [updated March 2011]. The Cochrane Collaboration, 2011. Available from http://​handbook.​cochrane.​org. Accessed 16 May 2013.
15.
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;283:2008–12.CrossRefPubMed 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;283:2008–12.CrossRefPubMed
16.
go back to reference Hayden JA, van der Windt DA, Cartwright JL, et al. Assessing bias in studies of prognostic factors. Ann Intern Med. 2013;158:280–6.CrossRefPubMed Hayden JA, van der Windt DA, Cartwright JL, et al. Assessing bias in studies of prognostic factors. Ann Intern Med. 2013;158:280–6.CrossRefPubMed
17.
18.
go back to reference Berlin JA, Longnecker MP, Greenland S. Meta-analysis of epidemiologic dose-response data. Epidemiology. 1993;4:218–28.CrossRefPubMed Berlin JA, Longnecker MP, Greenland S. Meta-analysis of epidemiologic dose-response data. Epidemiology. 1993;4:218–28.CrossRefPubMed
19.
go back to reference Orsini N, Bellocco R, Greenland S. Generalized least squares for trend estimation of summarized dose–response data. Stata J. 2006;6:40–57.CrossRef Orsini N, Bellocco R, Greenland S. Generalized least squares for trend estimation of summarized dose–response data. Stata J. 2006;6:40–57.CrossRef
20.
go back to reference Orsini N, Li R, Wolk A, et al. Meta-analysis for linear and nonlinear dose-response relations: examples, an evaluation of approximations, and software. Am J Epidemiol. 2012;175:66–73.CrossRefPubMed Orsini N, Li R, Wolk A, et al. Meta-analysis for linear and nonlinear dose-response relations: examples, an evaluation of approximations, and software. Am J Epidemiol. 2012;175:66–73.CrossRefPubMed
23.
go back to reference Begg CB, Mazumdar M. Operating characteristics of a rank correlation test for publication bias. Biometrics. 1994;50:1088–101.CrossRefPubMed Begg CB, Mazumdar M. Operating characteristics of a rank correlation test for publication bias. Biometrics. 1994;50:1088–101.CrossRefPubMed
24.
go back to reference Song ZZ. Acute viral hepatitis increases liver stiffness values measured by transient elastography. Hepatology. 2008;48(349–350):350. Song ZZ. Acute viral hepatitis increases liver stiffness values measured by transient elastography. Hepatology. 2008;48(349–350):350.
25.
go back to reference Zeuzem S, Feinman SV, Rasenack J, et al. Peginterferon alfa–2a in patients with chronic hepatitis C. N Engl J Med. 2000;343:1666–72.CrossRefPubMed Zeuzem S, Feinman SV, Rasenack J, et al. Peginterferon alfa–2a in patients with chronic hepatitis C. N Engl J Med. 2000;343:1666–72.CrossRefPubMed
26.
go back to reference Chang TT, Liaw YF, Wu SS, et al. Long-term entecavir therapy results in the reversal of fibrosis/cirrhosis and continued histological improvement in patients with chronic hepatitis B. Hepatology. 2010;52:886–93.CrossRefPubMed Chang TT, Liaw YF, Wu SS, et al. Long-term entecavir therapy results in the reversal of fibrosis/cirrhosis and continued histological improvement in patients with chronic hepatitis B. Hepatology. 2010;52:886–93.CrossRefPubMed
27.
go back to reference Fattovich G, Giustina G, Schalm SW, et al. Occurrence of hepatocellular carcinoma and decompensation in western European patients with cirrhosis type B. The EUROHEP Study Group on Hepatitis B Virus and Cirrhosis. Hepatology. 1995;21:77–82.PubMed Fattovich G, Giustina G, Schalm SW, et al. Occurrence of hepatocellular carcinoma and decompensation in western European patients with cirrhosis type B. The EUROHEP Study Group on Hepatitis B Virus and Cirrhosis. Hepatology. 1995;21:77–82.PubMed
28.
go back to reference Fernández-Montero JV, Barreiro P, Vispo E, et al. Liver stiffness predicts liver-related complications and mortality in HIV patients with chronic hepatitis C on antiretroviral therapy. Aids. 2013;27:1129–34.CrossRefPubMed Fernández-Montero JV, Barreiro P, Vispo E, et al. Liver stiffness predicts liver-related complications and mortality in HIV patients with chronic hepatitis C on antiretroviral therapy. Aids. 2013;27:1129–34.CrossRefPubMed
29.
go back to reference Wong VW, Chan HL. Prevention of hepatocellular carcinoma: a concise review of contemporary issues. Ann Hepatol. 2012;11:284.CrossRefPubMed Wong VW, Chan HL. Prevention of hepatocellular carcinoma: a concise review of contemporary issues. Ann Hepatol. 2012;11:284.CrossRefPubMed
31.
go back to reference Roulot D, Czernichow S, Le Clésiau H, et al. Liver stiffness values in apparently healthy subjects: Influence of gender and metabolic syndrome. J Hepatol. 2008;48:606–13.CrossRefPubMed Roulot D, Czernichow S, Le Clésiau H, et al. Liver stiffness values in apparently healthy subjects: Influence of gender and metabolic syndrome. J Hepatol. 2008;48:606–13.CrossRefPubMed
32.
go back to reference Wang J, Li J, Zhou Q, et al. Liver stiffness measurement predicted liver-related events and all-cause mortality: a systematic review and nonlinear dose-response meta-analysis. Hepatol Commun. 2018;2:467–76.CrossRefPubMedPubMedCentral Wang J, Li J, Zhou Q, et al. Liver stiffness measurement predicted liver-related events and all-cause mortality: a systematic review and nonlinear dose-response meta-analysis. Hepatol Commun. 2018;2:467–76.CrossRefPubMedPubMedCentral
33.
go back to reference Vergniol J, Boursier J, Coutzac C, et al. Evolution of noninvasive tests of liver fibrosis is associated with prognosis in patients with chronic hepatitis C. Hepatology. 2014;60:65–76.CrossRefPubMed Vergniol J, Boursier J, Coutzac C, et al. Evolution of noninvasive tests of liver fibrosis is associated with prognosis in patients with chronic hepatitis C. Hepatology. 2014;60:65–76.CrossRefPubMed
Metadata
Title
The prognostic role of liver stiffness in patients with chronic liver disease: a systematic review and dose–response meta-analysis
Authors
Yue Shen
Sheng-Di Wu
Ling Wu
Si-Qi Wang
Yao Chen
Li-Li Liu
Jing Li
Chang-Qing Yang
Ji-Yao Wang
Wei Jiang
Publication date
01-09-2019
Publisher
Springer India
Published in
Hepatology International / Issue 5/2019
Print ISSN: 1936-0533
Electronic ISSN: 1936-0541
DOI
https://doi.org/10.1007/s12072-019-09952-5

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