Efficacy of proposed treatments on patient-oriented clinical outcomes in NAFLD

The latest issue of Hepatology reviews the treatment of nonalcoholic fatty liver disease.

Nonalcoholic fatty liver disease (NAFLD) encompasses a histological spectrum ranging from simple steatosis to nonalcoholic steatohepatitis (NASH).

NAFLD carries a higher risk of cardio-metabolic and liver-related complications, the latter being confined to NASH and demanding specific treatment.

Dr Giovanni Musso and colleagues from Italy assessed the efficacy of proposed treatments for NAFLD/NASH by reviewing reports of randomized controlled trials (RCTs) on online databases and national and international meeting abstracts through 2010.

Primary outcome measure was histological improvement, and secondary outcome was biochemical improvement.

Improvement in radiological steatosis was also evaluated.

More than 50% of patients failed to achieve target weight loss.

Hepatology

There were 2 reviewers that extracted articles using predefined quality indicators, independently and in duplicate.

Main outcomes of randomized controlled trials were pooled using random-effects or fixed-effects models.

Publication bias was assessed by funnel plots.

The research team identified 49 randomized controlled trials, of which 23 had post-treatment histology.

Most randomized controlled trials were small and did not exceed 1-year duration.

Weight loss, thiazolidinediones (especially pioglitazone), and antioxidants were most extensively evaluated.

Weight loss was safe and dose-dependently improved histological disease activity in NASH, but more than 50% of patients failed to achieve target weight loss.

The team noted that thiazolidinediones improved steatosis and inflammation but yielded significant weight gain.

Randomized controlled trials with antioxidants yielded conflicting results and were heterogeneous with respect to type and dose of drug, duration, implementation of lifestyle intervention.

Among the other agents, pentoxifylline, telmisartan and L-carnitine improved liver histology in at least 1 randomized controlled trial in NASH, and olyunsaturated fatty acid (PUFA) ameliorated biochemical and radiological markers of NAFLD.

Other approaches yielded negative results.

Dr Musso's team concludes, "Well-designed randomized controlled trials of adequate size and duration, with histological endpoints, are needed to assess long-term safety and efficacy of proposed treatments on patient-oriented clinical outcomes."