Association of Weight Loss Interventions With Changes in Biomarkers of Nonalcoholic Fatty Liver Disease

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; I 2 = 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; I 2 = 97%), histologically or radiologically measured liver steatosis (standardized mean difference:-1.48; 95% CI,-2.27 to-0.70; I 2 = 94%), histologic NAFLD activity score (-0.92; 95% CI,-1.75 to-0.09; I 2 = 95%), and presence of nonalcoholic steatohepatitis (OR, 0.14; 95% CI, 0.04-0.49; I 2 = 0%). No statistically significant change in histologic liver fibrosis was found (-0.13; 95% CI,-0.54 to 0.27; I 2 = 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.

The Effect of Moderate Weight Loss on a Non-Invasive Biomarker of Liver Fibrosis: A Randomised Controlled Trial

“…However, it is not clear whether this is an effect of weight loss per se or confounded by specific effects of the pharmacotherapy on fibrosis. In a systematic review and meta-analysis, weight loss interventions in people with NAFLD and NASH led to similar weight loss as in the current study and in improvement in biopsy-proven steatosis and the NAFLD activity score [22]. Furthermore, the direction of the association between weight loss interventions and biopsy-proven liver fibrosis went in the expected direction, albeit not significant (change in fibrosis score: -0.13, 95% CI: -0.54 to 0.27), and we would have expected to see a reduction in fibrosis if the estimate were more precise.…”

“…As progression of liver fibrosis is slow, 1 year is the minimum recommended follow-up to detect fibrosis changes [21]. Fibrosis improved at 1 year in a large single-arm weight loss trial in NASH [20], although there was no evidence of changes in fibrosis in randomised trials with smaller samples [22]. Most participants in our study consumed some alcohol, but none had a diagnosis indicative of alcohol abuse.…”

Chronic high dietary sucrose induces sexually dimorphic metabolic adaptations in liver and adipose tissue

“…Together with our observation that males had a higher capacity to store lipid in their adipose tissue than females ( Figure 1A and B), these findings suggest that steatosis in the setting of high sugar intake may begin as a secondary consequence of dysregulated adipose tissue lipolysis and a reduced ability to store lipid in adipocytes, rather than a primary defect in hepatic metabolism per se. If this assertion is correct, it may help to explain why the most effective treatments for NAFLD to date have involved the reduction of adiposity, either via diet and exercise (Koutoukidis et al, 2019) or following surgical weight loss (Fakhry et al, 2019).…”

Evolution of NAFLD and Its Management

“…Over 16 randomized controlled trials (RCTs) have evaluated the impact of weight loss through lifestyle modifications on NAFLD . Overall, these studies have taken similar approaches to dietary interventions by either aiming for a caloric deficit of 300–1000 kcal/d or creating an overall calorie target for the day (1200–1800 kcal/d or 20–30 kcal/kg/d).…”

“…These interventions have been compared with either usual care, minimal lifestyle intervention, or exercise alone. A recent meta‐analysis noted that these interventions lead to a weight loss of −3.61 kg (95% CI, −5.11 to −2.12) . Although this was modest weight loss, it resulted in significant improvement in blood tests, including a reduction of ALT (−9.81 U/L; 95% CI, −13.12 to −6.50), AST (−4.84 U/L; 95% CI, −7.31 to −2.38), alkaline phosphatase (−5.53 U/L; 95% CI, −20.48 to 9.22), and gamma‐glutamyl transpeptidase (GGT) (−4.35 U/L; 95% CI, −7.67 to −1.04).…”