Published online Dec 9, 2014. doi: 10.5497/wjp.v3.i4.209
Revised: October 15, 2014
Accepted: October 23, 2014
Published online: December 9, 2014
Processing time: 204 Days and 15.4 Hours
AIM: To the look at the current strength of evidence and the potential application of anti-oxidants in this setting.
METHODS: Two electronic databases (PubMed and Web of Knowledge) were searched to January 2013 to find studies addressing serum bilirubin levels in non-alcoholic fatty liver disease (NAFLD). The search used key word combinations in relation to NAFLD and serum bilirubin specific to human adults only. After screening selected studies were reviewed in depth by two independent reviewers. Data synthesis with further meta-analysis was planned but not possible due to the heterogeneity of the outcome measures in these studies.
RESULTS: Out of 416 studies screened only seven studies were considered suitable for inclusion. All seven studies consistently reported an inverse association of bilirubin with NAFLD despite the heterogeneous sample of studies. Only two studies were prospective. No negative studies were found.
CONCLUSION: Most studies suggest a correlation between high bilirubin levels of any type are inversely correlated with NAFLD. But to date most of these studies have been poorly designed to allow meaningful conclusions, except one cohort study. There is a need for a large prospective cohort study in multiple populations to test this hypothesis fully before mechanistic associations can be established and therapeutic options of the apparent anti-oxidant effect of bilirubin be explored in NAFLD. Furthermore these studies should include analysis of UGT1A1 gene to expound upon underlying cause of unconjugated hyperbilirubinaemia.
Core tip: This systematic review summarises and highlights the deficiencies in the current studies on the association of serum bilirubin with non-alcoholic fatty liver disease (NAFLD). It explores the potential underpinning of the mechanistic association of NAFLD with bilirubin. Potential novel therapeutic avenues of bilirubin are explored in NAFLD, a common condition with oxidative damage as a core pathogenetic factor. Although this area of study is still in its infancy, this review is a timely summary of current key studies in this subject area and provides an up to date thought perspective with focus on future direction and potential therapeutic application.