Skip to main content

Advertisement

SpringerLink
Log in

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

  • Original Article
  • Published:
Hepatology International Aims and scope Submit manuscript

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

Abbreviations

ALT:

Alanine aminotransferase

CHB:

Chronic hepatitis B

CIs:

Confidence intervals

CLD:

Chronic liver disease

Glst:

Generalized least-squares trend

HBV:

Hepatitis B virus

HCC:

Hepatic carcinoma

HCV:

Hepatitis C virus

HD:

Hepatic decompensation

HIV:

Human immunodeficiency virus

HR:

Hazard ratio

kPa:

Kilopascal

LREs:

Liver-related events

LS:

Live stiffness

LSM:

Liver stiffness measurement

PH:

Portal hypertension

RRs:

Relative risks

TE:

Transient elastography

ULN:

Upper limit of normal

References

  1. Bataller R, Brenner DA. Liver fibrosis. J Clin Invest. 2005;115:209–18.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Pungpapong S, Kim WR, Poterucha JJ. Natural history of hepatitis B virus infection: an update for clinicians. Mayo Clin Proc. 2007;82:967–75.

    Article  CAS  PubMed  Google Scholar 

  3. 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.

    Article  CAS  PubMed  Google Scholar 

  4. 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.

    Article  PubMed  Google Scholar 

  5. Martinez SM, Crespo G, Navasa M, et al. Noninvasive assessment of liver fibrosis. Hepatology. 2011;53:325–35.

    Article  PubMed  Google Scholar 

  6. 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.

    Article  PubMed  Google Scholar 

  7. Castera L, Pinzani M, Bosch J. Non invasive evaluation of portal hypertension using transient elastography. J Hepatol. 2012;56:696–703.

    Article  PubMed  Google Scholar 

  8. 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.

    Article  PubMed  Google Scholar 

  9. 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.

    Google Scholar 

  10. 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.

    Google Scholar 

  11. 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.

    Article  CAS  Google Scholar 

  12. 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.

    Article  PubMed  Google Scholar 

  13. 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.

    Article  Google Scholar 

  14. 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. 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.

    Article  CAS  PubMed  Google Scholar 

  16. Hayden JA, van der Windt DA, Cartwright JL, et al. Assessing bias in studies of prognostic factors. Ann Intern Med. 2013;158:280–6.

    Article  PubMed  Google Scholar 

  17. DerSimonian R, Laird N. Meta-analysis in clinical trials. Control Clin Trials. 1986;7:177–88.

    Article  CAS  PubMed  Google Scholar 

  18. Berlin JA, Longnecker MP, Greenland S. Meta-analysis of epidemiologic dose-response data. Epidemiology. 1993;4:218–28.

    Article  CAS  PubMed  Google Scholar 

  19. Orsini N, Bellocco R, Greenland S. Generalized least squares for trend estimation of summarized dose–response data. Stata J. 2006;6:40–57.

    Article  Google Scholar 

  20. 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.

    Article  PubMed  Google Scholar 

  21. Higgins JP, Thompson SG, Deeks JJ, et al. Measuring inconsistency in meta-analyses. BMJ. 2003;327:557–60.

    Article  PubMed  PubMed Central  Google Scholar 

  22. Egger M, Davey SG, Schneider M, et al. Bias in meta-analysis detected by a simple, graphical test. BMJ. 1997;315:629–34.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Begg CB, Mazumdar M. Operating characteristics of a rank correlation test for publication bias. Biometrics. 1994;50:1088–101.

    Article  CAS  PubMed  Google Scholar 

  24. Song ZZ. Acute viral hepatitis increases liver stiffness values measured by transient elastography. Hepatology. 2008;48(349–350):350.

    Google Scholar 

  25. 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.

    Article  CAS  PubMed  Google Scholar 

  26. 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.

    Article  CAS  PubMed  Google Scholar 

  27. 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.

    CAS  PubMed  Google Scholar 

  28. 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.

    Article  CAS  PubMed  Google Scholar 

  29. Wong VW, Chan HL. Prevention of hepatocellular carcinoma: a concise review of contemporary issues. Ann Hepatol. 2012;11:284.

    Article  PubMed  Google Scholar 

  30. Bazerbachi F, Haffar S, Wang Z, et al. Range of normal liver stiffness and predictors of suspected advanced fibrosis in apparently healthy individuals: a pooled analysis of 16,082 participants. Clin Gastroenterol Hepatol. 2018. https://doi.org/10.1016/j.cgh.2018.08.069.

    Article  PubMed  PubMed Central  Google Scholar 

  31. 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.

    Article  PubMed  Google Scholar 

  32. 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.

    Article  PubMed  PubMed Central  Google Scholar 

  33. 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.

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

The study was supported by the National Nature Science Foundation, No. 81670541; and National Science and Technology Major Project of China, No. 2013ZX10002004 and No. 2017ZX10203202.

Author information

Authors and Affiliations

  1. Department of Gastroenterology and Hepatology, Zhongshan Hospital, Fudan University, 180 Fenglin Road, Xuhui District, Shanghai, People’s Republic of China

    Yue Shen, Sheng-Di Wu, Ling Wu, Si-Qi Wang, Li-Li Liu, Ji-Yao Wang & Wei Jiang

  2. Department of Emergency Medicine, Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of China

    Yao Chen

  3. Department of Gastroenterology, Tongji Hospital, Tongji University, Shanghai, People’s Republic of China

    Jing Li & Chang-Qing Yang

Authors
  1. Yue Shen
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Sheng-Di Wu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ling Wu
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Si-Qi Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Yao Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Li-Li Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Jing Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Chang-Qing Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Ji-Yao Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Wei Jiang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Wei Jiang.

Ethics declarations

Conflict of interest

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 declare that they have no conflict of interest.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Yue Shen and Sheng-Di Wu share co-first authorship.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary Fig. 1A1 (PDF 39 kb)

Supplementary Fig. 1A2 (PDF 40 kb)

Supplementary Fig. 1B1 (PDF 62 kb)

Supplementary Fig. 1B2 (PDF 29 kb)

Supplementary Fig. 1C1 (PDF 112 kb)

Supplementary Fig. 1C2 (PDF 180 kb)

Supplementary Fig. 1D1 (PDF 118 kb)

Supplementary Fig. 1D2 (PDF 183 kb)

Supplementary Fig. 2A1 (PDF 71 kb)

Supplementary Fig. 2A2 (PDF 76 kb)

Supplementary Fig. 2B1 (PDF 65 kb)

Supplementary Fig. 2B2 (PDF 63 kb)

Supplementary Fig. 2C1 (PDF 67 kb)

Supplementary Fig. 2C2 (PDF 71 kb)

Supplementary Fig. 2D1 (PDF 69 kb)

Supplementary Fig. 2D2 (PDF 71 kb)

Supplementary Fig. 3A1 (PDF 63 kb)

Supplementary Fig. 3A2 (PDF 60 kb)

Supplementary Fig. 3B1 (PDF 61 kb)

Supplementary Fig. 3B2 (PDF 63 kb)

Supplementary Fig. 3C1 (PDF 62 kb)

Supplementary Fig. 3C2 (PDF 62 kb)

Supplementary Table 1 (DOC 70 kb)

Supplementary Table 2 (DOC 92 kb)

Supplementary Table 3 (DOC 35 kb)

Supplementary Table 4 (DOC 32 kb)

Supplementary Table 5 (DOC 40 kb)

Supplementary Table 6 (DOC 42 kb)

Supplementary Table 7 (DOC 286 kb)

Supplementary Table 8 (DOCX 33 kb)

Supplementary Table 9 (DOC 144 kb)

Supplementary Table 10 (DOC 350 kb)

Supplementary Table 11 (DOC 76 kb)

Supplementary Table 12 (DOC 131 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Shen, Y., Wu, SD., Wu, L. et al. The prognostic role of liver stiffness in patients with chronic liver disease: a systematic review and dose–response meta-analysis. Hepatol Int 13, 560–572 (2019). https://doi.org/10.1007/s12072-019-09952-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12072-019-09952-5

Keywords

Search

Navigation