Randomised clinical trial: The beneficial effects of VSL#3 in obese children with non-alcoholic steatohepatitis

Abstract

Background: Gut microbiota modifiers may have beneficial effects of non-alcoholic fatty liver disease (NAFLD) but randomised controlled trials (RCT) are lacking in children.

Aim: To perform a double-blind RCT of VSL#3 vs. placebo in obese children with biopsy-proven NAFLD.

Methods: Of 48 randomised children, 44 (22 VSL#3 and 22 placebo) completed the study. The main outcome was the change in fatty liver severity at 4 months as detected by ultrasonography. Secondary outcomes were the changes in triglycerides, insulin resistance as detected by the homoeostasis model assessment (HOMA), alanine transaminase (ALT), body mass index (BMI), glucagon-like peptide 1 (GLP-1) and activated GLP-1 (aGLP-1). Ordinal and linear models with cluster confidence intervals were used to evaluate the efficacy of VSL#3 vs. placebo at 4 months.

Results: At baseline, moderate and severe NAFLD were present in 64% and 36% of PLA children and in 55% and 45% of VSL#3 children. The probability that children supplemented with VSL#3 had none, light, moderate or severe FL at the end of the study was 21%, 70%, 9% and 0% respectively with corresponding values of 0%, 7%, 76% and 17% for the placebo group (P < 0.001). No between-group differences were detected in triglycerides, HOMA and ALT while BMI decreased and GLP-1 and aGLP1 increased in the VSL#3 group (P < 0.001 for all comparisons).

Conclusions: A 4-month supplement of VSL#3 significantly improves NAFLD in children. The VSL#3-dependent GLP-1 increase could be responsible for these beneficial effects. Trial identifier: NCT01650025 (www.clinicaltrial.gov).

Conflict of interest statement

Declaration of personal interests: None.

Declaration of funding interests: This study was funded by the Italian Ministry of Health (Fondi di Ricerca Corrente and 5*1000) to Prof. Valerio Nobili. Prof. Anania is supported by US Public Health Service Grant DK062092 and Departments of Veterans’ Affairs Grant BX001746.

© 2014 John Wiley & Sons Ltd.

Figures

Figure 1

Changes in the severity of fatty liver in the placebo and VSL#3 groups during the study. Values are mean probabilities and standard errors estimated from an ordinal logistic regression model for repeated measures (cluster confidence intervals). For this reason, probabilities at each time point sum to 100. Abbreviations: FL = fatty liver; 0= no fatty liver; 1 = light fatty liver; 2 = moderate fatty liver; 3 = severe fatty liver.

Figure 2

Individual changes of GLP-1 and aGLP-1 in the placebo and VSL#3 groups during the study.