COMMENTARY

Eschewing the Fat: What's on the Horizon for Treating NASH?

William F. Balistreri, MD

Disclosures

March 10, 2015

In This Article

The Next Epidemic of Liver Disease

Hepatitis C virus may be on the run, but nonalcoholic steatohepatitis (NASH) has emerged as the leading cause of chronic liver disease, an increasing indication for liver transplantation, and a precursor of primary liver cancer.[1,2,3,4]

The rising prevalence of fatty liver disease has paralleled the expanding obesity population, as obesity rates have doubled in adults and tripled in children in the past 10 years.[1,2] Obesity also contributes to diabetes and hypercholesterolemia, which exacerbate morbidity in patients with NASH. In fact, mortality in patients with NASH is often related to cardiovascular disease and not to end-stage liver disease.

What Can Be Done?

The recommendation for the prevention and treatment of obesity and its hepatic complications is weight loss prompted by lifestyle changes—diet and physical activity, control of hyperglycemia, and treatment of hyperlipidemia with statins.[5] A 7%-10% reduction in body weight can induce histologic improvement in NASH.[6] Weight loss through calorie restriction and exercise can also have a favorable impact on abdominal obesity, insulin resistance, cardiovascular disease, and extrahepatic malignancy, all of which are associated with fatty liver disease.

Patel and colleagues[7] measured changes in liver fat and volume associated with weight loss in adults with biopsy-proven NASH. Patients who had at least a 5% reduction in body mass index (BMI) had significant reductions in liver fat, as estimated by MRI proton density fat fraction (PDFF) and liver volume.

In another study[8] of the effect of lifestyle changes in patients with NASH, those who lost 10% or more total body weight exhibited significantly higher rates of fibrosis regression (63% vs 9%).

However, weight loss is a major clinical challenge for patients and clinicians—it is difficult to achieve and maintain. No pharmacologic therapy has demonstrated consistent effectiveness, although there is significant interest in developing effective pharmacologic strategies for the treatment of NASH, either to prevent or reverse the progression of hepatic fibrosis.

A "magic diet pill" is highly elusive; of the many agents that have been the subject of clinical studies, few have shown sustained benefit. New approaches continually emerge, though; for example, at the end of December 2014, the US Food and Drug Administration approved liraglutide injection (Saxenda®), a glucagon-like peptide-1 receptor agonist, for obese patients with weight-related comorbid conditions. This drug, used in combination with a healthy lifestyle, may provide an additional option for chronic weight management and resolution of NASH. However, we await "real-world" experience with respect to the safety and long-term efficacy of this drug, in view of the unimpressive history of its predecessors.[9]

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