Clinical Question

Is weight loss an effective treatment for nonalcoholic fatty liver disease?

Evidence-Based Answer

There are insufficient high-quality studies to determine patient-oriented outcomes of weight loss for the treatment of fatty liver disease. Nonetheless, weight loss remains a reasonable goal because it may reduce liver inflammation and improve comorbidities. In two of the studies reviewed, liver enzyme levels were essentially halved in patients who lost weight with lifestyle changes. (Strength of Recommendation: C, based on consensus, disease-oriented evidence, usual practice, expert opinion, or case series.)

Practice Pointers

Nonalcoholic fatty liver disease encompasses a disease spectrum ranging from simple fatty liver to nonalcoholic steatohepatitis to end-stage cirrhosis. Experts consider steatosis in a person consuming less than 20 to 30 g of alcohol daily (i.e., 1.5 standard alcoholic beverages for women and two standard alcoholic beverages for men) to be a criterion for the diagnosis of nonalcoholic fatty liver disease.¹ More than two-thirds of adults who are obese have fatty liver, and 20 percent may have nonalcoholic steatohepatitis.² More than 90 percent of adults with morbid obesity have fatty liver, and almost one-half have nonalcoholic steatohepatitis.³ According to this Cochrane review, nonalcoholic fatty liver disease has been identified as a cause of cirrhosis, especially cryptogenic cirrhosis.

Weight loss currently has the most supporting evidence for improving liver enzyme levels, compared with other therapies.^1,4 This Cochrane review analyzed seven randomized trials (373 participants) that investigated weight loss as a treatment for fatty liver disease. One study examined children; the other studies focused on adults. The intensity of lifestyle changes in the intervention groups and counseling in the placebo groups differed among studies. All but one trial were judged to be at high risk of bias, and comparisons were hindered by different end points. Only one trial reported histologic changes. Statistically significant reductions in alanine transaminase (ALT) levels were seen in the treatment arms of two of the four lifestyle intervention trials that measured liver enzyme levels (one of which was the study involving children). In these trials, lifestyle changes were associated with reductions in ALT levels (from 84 to 42 U per L [1.40 to 0.70 μkat per L] and from 152 to 63 U per L [2.54 to 1.05 μkat per L]), as well as appreciable weight loss (a loss of 19.33 lb [8.7 kg] and a two-point reduction in body mass index, respectively).

Orlistat (Xenical) was used for weight loss in two other studies, but there was no notable reduction in liver enzyme levels or body mass index compared with patients in placebo groups who were counseled on restrictive diets. However, both the orlistat and placebo groups achieved halving of liver enzyme levels and an approximate weight loss of 17.78 lb (8 kg).

In a 2004 meta-analysis, bariatric surgery was reported to resolve 77 percent of diabetes mellitus cases, 62 percent of hypertension cases, and 70 percent of hyperlipidemia cases.⁵ Although some experts believe that bariatric surgery may also improve fatty liver disease that accompanies metabolic syndrome, no clinical trials have been performed. In addition, there have been some reports of histologic deterioration with rapid weight loss after bariatric surgery, so these patients should be monitored closely.¹

Consensus guidelines on nonalcoholic fatty liver disease have been published in the Journal of Digestive Diseases and by the American Gastroenterological Association (AGA).^4,6 The AGA recommends that the initial target weight loss be 10 percent of baseline weight at a rate of 1 to 2 lb (0.45 to 0.90 kg) per week. An algorithm for the workup of mildly elevated liver enzyme levels can be found at https://www.aafp.org/afp/2005/0315/p1105.html#afp20050315p1105-f1.