Better Studies Needed on Nutritional Supplementation in NAFLD

Nonalcoholic fatty liver disease (NALFD) is associated with decreased life expectancy, increased risks of liver cirrhosis, hepatocellular carcinoma (HCC), and liver transplant. Due to the lack of high-quality randomized controlled trials, it remains unclear at this time if patients with NAFLD might benefit from nutritional supplementation, according to a review published in Cochrane Database of Systematic Reviews.

The researchers performed a meta-analysis of randomized controlled trials to assess the benefits and harms of different nutritional supplements to treat NAFLD. They searched the Cochrane Central Register of Controlled Trials, MEDLINE, Embase, Science Citation Index Expanded, Conference Proceedings Citation Index‐Science, the World Health Organization International Clinical Trials Registry Platform, and trials registers until February 2021.

“Various medical treatments have been tried for treatment of NAFLD. However, no current evidence suggests that any of them work,” the authors explained. “Nutritional supplementation has the potential to decrease liver damage, but whether this occurs is currently unclear.”

The review included 202 trials with 14,200 participants, and 115 studies with 7732 participants were included in 1 or more comparisons. Only 19 trials were at low risk of bias.

The follow-up for the studies ranged from just 1 month to 28 months, and during the follow-up, clinical events related to NAFLD were sparse, likely a result of the short follow-up. As a result of the sparse data, the authors did not calculate effect estimates for mortality. The clinical outcomes that were of interest to the authors were mortality, liver cirrhosis, liver decompensation, liver transplantation, HCC, and liver‐related mortality.

“It takes follow‐up of 8 to 28 years to detect differences in mortality between people with NAFLD and the general population,” the authors explained.

The evidence around adverse events (AEs) was of very low certainty, but the authors did surmise that people taking polyunsaturated fatty acid (PUFA) may be more likely to experience an AE than patients not receiving an intervention (network meta‐analysis results: odds ratio [OR], 4.44, 95% credible intervals [CrI], 2.40-8.48; low‐certainty evidence; 4 trials, 203 participants; direct evidence: OR, 4.43, 95% CrI, 2.43-8.42).

There was not enough data for liver transplantation, liver decompensation, and HCC to perform outcome analysis.

The average age of patients ranged from 7 to 61 years in the studies, and the studies evaluated a variety of different treatments, including various vitamins and other nutritional supplements.

The authors highlighted the need for registry-based clinical trials that compare interventions such as vitamin E, prebiotics/probiotics/synbiotics, PUFAs, and no nutritional supplementation to understand the impact of these interventions on indirect outcomes.

“The evidence indicates considerable uncertainty about effects of nutritional supplementation compared to no additional intervention on all clinical outcomes for people with non‐alcohol‐related fatty liver disease,” the authors concluded. “Accordingly, high‐quality randomized comparative clinical trials with adequate follow‐up are needed.”

Reference

Komolafe O, Buzzetti E, Linden A, et al. Nutritional supplementation for nonalcohol-related fatty liver disease: a network meta-analysis. Cochrane Database Syst Rev. 2021;7:CD013157. doi:10.1002/14651858.CD013157.pub2