Treatment Options for Nonalcoholic Fatty Liver Disease in Children: A Systematic Review

Abstract

Introduction: Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease, affecting almost 6 million children and adolescents. Currently, there are multiple treatment options available for these patients, however treatment guidelines do not exist. We reviewed the current literature to assess the efficacy of pharmacological and nonpharmacological treatments proposed to treat NAFLD in children. Methods: MEDLINE, PubMed, EMBASE and Cochrane library were searched for prospective, peerreviewed, treatment-based articles in pediatric patients with NAFLD, in English language. Search strategy included: “NAFLD”, “treatment”, and “children”. Results: A total of 313 articles were identified, and 72 articles met the inclusion criteria. Our final analysis included 10 out of 72 articles, with six randomized controlled trials (RCTs) and four observational studies. Most commonly compared treatments were lifestyle modification (both caloric restriction and physical exercise; 10), metformin use (4), and vitamin E supplementation (4). One study showed positive outcome with cysteamine bitartarate and 2 studies reported improved alanine aminotransferase (ALT) levels and sonographic findings with docosahexaenoic acid (DHA). Only 3 studies had follow-up liver biopsies. Across all studies, lifestyle modification showed statistically significant improvement in serum ALT levels. Both metformin and vitamin E decreased ALT levels, but when compared with lifestyle modification, none of these therapies seemed to be providing any additional benefit. Data on histological improvement is scarce. The TONIC trial (2010) and 2 separate studies from Nobili et al (2008) are the only studies reporting pre- and post-intervention liver biopsy findings. In the TONIC trial, even though both metformin and vitamin E failed to show improvement in serum ALT levels, they both improved histology, especially “ballooning”, as compared to lifestyle modification (P=0.02 and P=0.006, respectively). In 2 separate studies, Nobili et al reported significant improvement in histology with antioxidant supplementation and metformin, but these findings were not statistically different from lifestyle modification. Conclusion: At this time, lifestyle modifications, including caloric restriction and physical exercise, are the only treatment options consistently showing significant improvement in NAFLD parameters in the pediatric population. There seems to be no additional benefit of metformin or vitamin E, contrary to what some of the adult studies have reported. Like the TONIC trial, we need more well-designed RCTs of adequate size and duration, with histological endpoints, to assess the long term effect and safety of proposed treatment options.