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Metabolic risk factors and incident advanced liver disease in non-alcoholic fatty liver disease (NAFLD): A systematic review and meta-analysis of population-based observational studies

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  • Helen Jarvis
  • Dawn Craig
  • Robert Barker
  • Gemma Spiers
  • Daniel Stow
  • Quentin M Anstee
  • Barbara Hanratty

Abstract

Background: Non-alcoholic fatty liver disease (NAFLD) is a leading cause of chronic liver disease worldwide. Many individuals have risk factors associated with NAFLD, but the majority do not develop advanced liver disease: cirrhosis, hepatic decompensation, or hepatocellular carcinoma. Identifying people at high risk of experiencing these complications is important in order to prevent disease progression. This review synthesises the evidence on metabolic risk factors and their potential to predict liver disease outcomes in the general population at risk of NAFLD or with diagnosed NAFLD. Methods and findings: We conducted a systematic review and meta-analysis of population-based cohort studies. Databases (including MEDLINE, EMBASE, the Cochrane Library, and ClinicalTrials.gov) were searched up to 9 January 2020. Studies were included that reported severe liver disease outcomes (defined as liver cirrhosis, complications of cirrhosis, or liver-related death) or advanced fibrosis/non-alcoholic steatohepatitis (NASH) in adult individuals with metabolic risk factors, compared with individuals with no metabolic risk factors. Cohorts selected on the basis of a clinically indicated liver biopsy were excluded to better reflect general population risk. Risk of bias was assessed using the QUIPS tool. The results of similar studies were pooled, and overall estimates of hazard ratio (HR) were obtained using random-effects meta-analyses. Of 7,300 unique citations, 22 studies met the inclusion criteria and were of sufficient quality, with 18 studies contributing data suitable for pooling in 2 random-effects meta-analyses. Type 2 diabetes mellitus (T2DM) was associated with an increased risk of incident severe liver disease events (adjusted HR 2.25, 95% CI 1.83–2.76, p 30 kg/m2) as a prognostic factor, providing data on 19.3 million individuals followed up for a median of 13.8 years (IQR 9.0 to 19.8) experiencing 49,541 liver events. Obesity was associated with a modest increase in risk of incident severe liver disease outcomes (adjusted HR 1.20, 95% CI 1.12–1.28, p

Suggested Citation

  • Helen Jarvis & Dawn Craig & Robert Barker & Gemma Spiers & Daniel Stow & Quentin M Anstee & Barbara Hanratty, 2020. "Metabolic risk factors and incident advanced liver disease in non-alcoholic fatty liver disease (NAFLD): A systematic review and meta-analysis of population-based observational studies," PLOS Medicine, Public Library of Science, vol. 17(4), pages 1-20, April.
    • Handle: RePEc:plo:pmed00:1003100
    DOI: 10.1371/journal.pmed.1003100
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    Cited by:

    1. Byung-Kwan Jeong & Won-Il Choi & Wonsuk Choi & Jieun Moon & Won Hee Lee & Chan Choi & In Young Choi & Sang-Hyun Lee & Jung Kuk Kim & Young Seok Ju & Pilhan Kim & Young-Ah Moon & Jun Yong Park & Hail K, 2024. "A male mouse model for metabolic dysfunction-associated steatotic liver disease and hepatocellular carcinoma," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    2. Lawrence Mabasa & Anri Kotze & Samukelisiwe Shabalala & Clare Kimani & Kwazi Gabuza & Rabia Johnson & Nonhlakanipho F. Sangweni & Vinesh Maharaj & Christo J. F. Muller, 2022. "Sclerocarya birrea (Marula) Extract Inhibits Hepatic Steatosis in db/db Mice," IJERPH, MDPI, vol. 19(7), pages 1-15, March.

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