Weight loss is known to improve markers of fatty liver disease but authors of a recent meta-analysis took their investigation deeper. Scan through the research to the findings.
In the absence of pharmacotherapies for nonalcoholic fatty liver disease (NAFLD), weight loss is the primary intervention recommended and is known to be successful, with greater weight reduction associated with greater improvements in a range of disease markers.
Against this background, authors of a meta-analysis published recently in Metabolism Clinical and Experimental looked further to identify the relationship between magnitude of weight loss and improvements in NAFLD. We break down the study for easy-reading in the slides that follow.
NAFLD + Obesity = Worse Outcomes. Estimates suggest ~50% of persons with NAFLD also have obesity—a risk factor for disease progression. Currently no pharmacologic treatments available for NAFLD management. Current guidelines: recommend weight loss, other lifestyle interventions as management cornerstones. BUT: Evidence is of moderate quality.
Looking Deeper. Combined evidence of previous meta-analyses of weight loss in NAFLD point to greater improvement in liver disease biomarkers with greater weight loss. Study question: is there evidence also of a clear dose-response relationship?
Search: 9 Databases, Trial Registries (through October 2020). Inclusion criteria: single-arm, nonrandomized comparative, or randomized trials of weight loss interventions in people with NAFLD that reported an association between changes in weight and in blood, radiologic, or histologic biomarkers of liver disease. Interventions: behavioral weight loss programs (BWLPs), pharmacotherapy, bariatric surgery.
43 Studies Analyzed for NAFLD-Weight Loss Association. 2809 participants: high/middle-income countries; hypertension, diabetes prevalent. NAFLD dx made by biopsy, MRI, CT, ultrasound, liver function tests. Mean age 46.8 yrs, women 44%, mean BMI 32.8 kg/m2 Median follow-up: 6 mos; longer for bariatric surgery.
Steatosis, LFTs Show Dose-Response Change. Initial weight loss of ~5kg associated with minimal clinically meaningful improvement in steatosis of 5%, on average. Additional 5% reduction in steatosis seen with each additional 6 kg of weight loss. Initial loss of 4 kg and 2 kg saw clinically meaningful improvements in ALT (12 U/L) and AST (7 U/L), respectively.
Liver Disease Biomarker Change (per 1kg weight loss). ALT (U/L) 0.83 unit reduction. AST (U/L) 0.56 unit reduction. Steatosis 0.77 percentage point reduction
Dose-Response Evidence Limited for Fibrosis, NAFLD Activity. Evidence of dose-response relationship observed with: Liver inflammation, ballooning, resolution of NAFLD or NASH. BUT: limited evidence only of relationship with fibrosis or NAFLD activity score.
Clinical Conversation Starter. Author suggestion: Use results in conversations with patients to help support recommendations for weight loss. •Offer patients structured support, eg, as would be found in community or other type of weight loss programs. Referral for support more likely to be successful vs “simply advising weight loss.”
Study Strengths & Weaknesses. Study strengths: initial search limited to interventions intended for weight loss; inclusion of studies that included bariatric surgery. Given the absence of an ideal biomarker for NAFLD/NASH, the concordance of a dose response relationship between weight loss and various liver biomarkers minimized risk of false positive findings. Limitations include: assumption of linear relationship between changes in weight loss and biomarkers of liver disease; high level of heterogeneity among studies.
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