William F. Balistreri, MD


December 27, 2013

In This Article

Insight Into the Mechanism, Diagnosis, and Treatment of NAFLD

An altered fecal microbiome has been implicated in the pathogenesis of nonalcoholic fatty liver disease (NAFLD). Puri and colleagues[15] set out to more clearly characterize the microbiome and metabolome of patients with NAFLD.

They performed 16S ribosomal RNA multitag pyrosequencing for fecal microbiome and mass spectrometry for small-molecule metabolomic profiling from plasma and feces. They found that NAFLD was associated with significant changes in fecal and systemic metabolites of microbial origin or contribution, despite no significant differences in microbial biodiversity. Puri and colleagues postulate pathophysiologic implications to explain their findings, including microbial influences on altering membrane permeability and aromatic amino acid metabolism, as well as induction of cellular stress.

These findings offer the potential for novel therapeutic approaches as well as biomarker discovery to noninvasively distinguish NAFLD from nonalcoholic steatohepatitis (NASH).

The goal of several recent studies has been to develop valid diagnostic and prognostic tools for use in patients with fatty liver disease. Cross-sectional studies have shown an association between steatohepatitis and serum levels of keratin 18 fragments (CK18). Jain and colleagues[16] assessed serial changes in serum CK18 levels in relationship to changes in liver histology. The changes in serum CK18 levels strongly predicted changes in all histologic components of NAFLD over 96 weeks of observation. They suggest that serum CK18 is a potentially useful biomarker for predicting histologic improvement in children and adolescents with NAFLD.

Other than lifestyle changes, a paucity of options for the treatment of patients with NAFLD have been validated. Polyunsaturated fatty acids (PUFA) are known to reduce insulin resistance, triglyceride levels, lipogenesis, oxidant stress, and inflammation, all key features of NASH.

Sanyal and colleagues[17] reported the results of a phase 2b prospective, double-blind, randomized, placebo-controlled trial of ethyl eicosapentaenoic acid (EPA-E), a highly purified synthetic PUFA, in patients with NASH. Although EPA-E was found to be safe and produced a modest improvement in serum triglyceride levels, this agent did not improve the histologic features or biomarkers of inflammation or fibrosis among patients with NASH.


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