Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2019 Sep 1;179(9):1262-1271.
doi: 10.1001/jamainternmed.2019.2248.

Association of Weight Loss Interventions With Changes in Biomarkers of Nonalcoholic Fatty Liver Disease: A Systematic Review and Meta-analysis

Dimitrios A Koutoukidis  1   2 , Nerys M Astbury  1   2 , Kate E Tudor  1   2 , Elizabeth Morris  1 , John A Henry  1 , Michaela Noreik  1   2 , Susan A Jebb  1   2 , Paul Aveyard  1   2
Affiliations

Association of Weight Loss Interventions With Changes in Biomarkers of Nonalcoholic Fatty Liver Disease: A Systematic Review and Meta-analysis

Dimitrios A Koutoukidis et al. JAMA Intern Med. .

Erratum in

  • Errors in Figure Headings.
    [No authors listed] [No authors listed] JAMA Intern Med. 2019 Sep 1;179(9):1303-1304. doi: 10.1001/jamainternmed.2019.4091. JAMA Intern Med. 2019. PMID: 31476001 Free PMC article. No abstract available.

Abstract

Importance: Nonalcoholic fatty liver disease (NAFLD) affects about 25% of adults worldwide and is associated with obesity. Weight loss may improve biomarkers of liver disease, but its implications have not been systematically reviewed and quantified.

Objective: To estimate the association of weight loss interventions with biomarkers of liver disease in NAFLD.

Data sources: MEDLINE, Embase, PsycINFO, CINAHL, Cochrane, and Web of Science databases along with 3 trial registries were searched from inception through January 2019.

Study selection: Randomized clinical trials of people with NAFLD were included if they compared any intervention aiming to reduce weight (behavioral weight loss programs [BWLPs], pharmacotherapy, and surgical procedures) with no or lower-intensity weight loss intervention. The review followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines.

Data extraction and synthesis: Two independent reviewers screened the studies, extracted the data, and assessed the risk of bias using the Cochrane tool. Pooled mean differences or odds ratios (ORs) were obtained from random-effects meta-analyses.

Main outcomes and measures: Blood, radiologic, and histologic biomarkers of liver disease.

Results: Twenty-two studies with 2588 participants (with a mean [SD] age of 45 [14] years and with approximately 66% male) were included. Fifteen studies tested BWLPs, 6 tested pharmacotherapy, and 1 tested a surgical procedure. The median (interquartile range) intervention duration was 6 (3-8) months. Compared with no or lower-intensity weight loss interventions, more-intensive weight loss interventions were statistically significantly associated with greater weight change (-3.61 kg; 95% CI, -5.11 to -2.12; I2 = 95%). Weight loss interventions were statistically significantly associated with improvements in biomarkers, including alanine aminotransferase (-9.81 U/L; 95% CI, -13.12 to -6.50; I2 = 97%), histologically or radiologically measured liver steatosis (standardized mean difference: -1.48; 95% CI, -2.27 to -0.70; I2 = 94%), histologic NAFLD activity score (-0.92; 95% CI, -1.75 to -0.09; I2 = 95%), and presence of nonalcoholic steatohepatitis (OR, 0.14; 95% CI, 0.04-0.49; I2 = 0%). No statistically significant change in histologic liver fibrosis was found (-0.13; 95% CI, -0.54 to 0.27; I2 = 68%). Twelve studies were at high risk of bias in at least 1 domain. In a sensitivity analysis of the 3 trials at low risk of bias, the estimates and precision of most outcomes did not materially change.

Conclusions and relevance: The trials, despite some heterogeneity, consistently showed evidence of the association between weight loss interventions and improved biomarkers of liver disease in NAFLD in the short to medium term, although evidence on long-term health outcomes was limited. These findings appear to support the need to change the clinical guidelines and to recommend formal weight loss programs for people with NAFLD.

PubMed Disclaimer

Conflict of interest statement

Conflict of Interest Disclosures: Drs Astbury, Jebb, and Aveyard reported receiving grants from Cambridge Weight Plan outside of the submitted work. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Association Between Weight Loss Intervention (WLI) and Weight Loss (WL)
D indicates diet group; D+E, diet and exercise group; L, low-intensity intervention group; LF, low-fat diet group; M, moderate-intensity intervention group; and MF, moderate-fat diet group.
Figure 2.
Figure 2.. Association Between Weight Loss Intervention (WLI) and Alanine Aminotransferase (ALT)
D indicates diet group; D+E, diet and exercise group; L, low-intensity intervention group; LF, low-fat diet group; M, moderate-intensity intervention group; and MF, moderate-fat diet group.
Figure 3.
Figure 3.. Association Between Weight Loss Intervention (WLI) and Liver Steatosis
Standardized mean difference was assessed by histologic examination, magnetic resonance imaging, or ultrasonography. D indicates diet group; D+E, diet and exercise group.
Figure 4.
Figure 4.. Association Between Weight Loss Intervention (WLI) and NAS (Nonalcoholic Fatty Liver Disease Activity Score)
The NAS range is 0-8, with the highest score indicating more severe disease. LF indicates low-fat diet group; MF, moderate-fat diet group.
See this image and copyright information in PMC

References

    1. Younossi Z, Anstee QM, Marietti M, et al. . Global burden of NAFLD and NASH: trends, predictions, risk factors and prevention. Nat Rev Gastroenterol Hepatol. 2018;15(1):11-20. doi:10.1038/nrgastro.2017.109 - DOI - PubMed
    1. Polyzos SA, Kountouras J, Mantzoros CS. Obesity and nonalcoholic fatty liver disease: from pathophysiology to therapeutics. Metabolism. 2019;92:82-97. doi:10.1016/j.metabol.2018.11.014 - DOI - PubMed
    1. Leung JC, Loong TC, Wei JL, et al. . Histological severity and clinical outcomes of nonalcoholic fatty liver disease in nonobese patients. Hepatology. 2017;65(1):54-64. doi:10.1002/hep.28697 - DOI - PubMed
    1. Younossi ZM, Blissett D, Blissett R, et al. . The economic and clinical burden of nonalcoholic fatty liver disease in the United States and Europe. Hepatology. 2016;64(5):1577-1586. doi:10.1002/hep.28785 - DOI - PubMed
    1. Targher G, Byrne CD, Lonardo A, Zoppini G, Barbui C. Non-alcoholic fatty liver disease and risk of incident cardiovascular disease: a meta-analysis. J Hepatol. 2016;65(3):589-600. doi:10.1016/j.jhep.2016.05.013 - DOI - PubMed