Dose-response Relationship Between Weight Loss and Improvements in NAFLD

Sarfaroj Khan 


December 29, 2020


  • This meta-analysis suggests a dose-response relationship between weight loss and improvements in biomarkers of liver disease in people with non-alcoholic fatty liver disease (NAFLD) or non-alcoholic steatohepatitis (NASH).

  • Clinically significant improvements in liver disease are achieved even with modest weight loss, but greater weight loss is associated with greater improvements.

Why this matters

  • Findings suggest that embedding support for weight loss as part of the clinical care pathway for the treatment of NAFLD could reduce the burden of disease.

Study design

  • 43 studies including 2809 participants met eligibility criteria after a search across MEDLINE, Embase, and other electronic databases.

  • Funding: National Institute for Health Research Oxford Biomedical Research Centre.

Key results

  • Every 1 kg of weight loss was associated with a:

    • 0.83-unit (95% CI, 0.53-1.14; I2, 92%; P<.0001) reduction in alanine aminotransferase (U/L);

    • 0.56-unit (95% CI, 0.32-0.79; I2, 68%; P<.0001) reduction in aspartate transaminase (U/L); and

    • 0.77 percentage point (95% CI, 0.51-1.03; I2, 72%; P<.0001) reduction in steatosis assessed by histology or radiology.

  • Weight loss correlated with other radiological or histological markers, including liver inflammation (β=0.02; 95% CI, 0.01-0.04; P=.0005), ballooning (β=0.03; 95% CI, 0.02-0.03; P<.0001); and resolution of NAFLD or NASH (OR, 1.23; 95% CI, 1.03-1.47; I2, 93%; P=.022).

  • The evidence on improvements in histological liver fibrosis was inconsistent and imprecise (β=0.02; 95% CI, 0.00-0.04; P=.037).

  • No evidence was found that weight loss was associated with histological reduction in the NAFLD activity score (β=0.11; 95% CI, −0.01 to 0.22; I2, 89%; P=.077).


  • Heterogeneity among included studies.


Koutoukidis DA, Koshiaris C, Henry JA, Noreik M, Morris E, Manoharan I, Tudor K, Bodenham E, Dunnigan A, Jebb SA, Aveyard P. The effect of the magnitude of weight loss on non-alcoholic fatty liver disease: A systematic review and meta-analysis. Metabolism. 2020 Nov 29 [Epub ahead of print];115:154455. doi: 10.1016/j.metabol.2020.154455. PMID: 33259835 View abstract

This clinical summary originally appeared on Univadis, part of the Medscape Professional Network.


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