October 10, 2012

First Guideline on NAFLD Published

Gastroenterology & Endoscopy News


by Christina Frangou

Three leading American gastroenterology societies have published a new guideline on the diagnosis and management of non-alcoholic fatty liver disease (NAFLD). Prompted by the fact that physicians are seeing a growing number of patients with the disease, this is the first time that any of these professional societies have developed practice guidelines for NAFLD.

In the report, an expert panel representing the American Gastroenterological Association (AGA), the American Association for the Study of Liver Diseases (AASLD) and the American College of Gastroenterology (ACG) made 45 recommendations for clinicians who treat patients with this increasingly common disease.

The panel addressed many of the major questions in the field, including when patients should be screened and when they should undergo liver biopsy, and outlined the evidence supporting diagnostic techniques and interventions, as well as diagnosis and treatment of children with NAFLD.

The guidelines were published simultaneously in the June issues of the journals Gastroenterology, Hepatology and The American Journal of Gastroenterology.

Senior author Naga Chalasani, MD, professor of medicine and director of the Division of Gastroenterology and Hepatology at Indiana University, in Indianapolis, urged gastroenterologists and hepatologists to read the guideline and “apply it as they deem appropriate for their practice.”

Recommendations of the Report

The panel opposed routine screening for NAFLD in adults, even those at diabetes or obesity clinics, because of uncertainties surrounding diagnostic tests and treatment options, and a lack of knowledge about long-term benefits and cost-effectiveness. They also recommended against routine screening of family members of patients with known NAFLD.

The panel also stressed the importance of ruling out excessive daily alcohol consumption before making a NALFD diagnosis. However, they used a liberal definition of “significant alcohol consumption”—at more than 21 drinks, on average, per week for men and more than 14 drinks per week for women. This recommendation was made on a relatively low level of evidence (2C).

For patients with unsuspected hepatic steatosis detected on imaging, the panel made several recommendations backed by the highest level of evidence (1A). They called for patients with symptoms or signs of liver disease or abnormal liver biochemistries to be evaluated as though they have suspected NALFD. Patients with normal liver biochemistries and no symptoms should be assessed for metabolic risk factors and other causes for hepatic steatosis. The panel did not recommend liver biopsies for asymptomatic patients with normal liver biochemistries.

They confirmed liver biopsy as the gold standard for characterizing liver histology in patients with NAFLD. However, they said liver biopsy should be reserved for those who would benefit the most from the information gleaned by biopsy. Patients with metabolic syndrome or those with suspected NAFLD who are at increased risk for steatohepatitis and advanced fibrosis may be good candidates for liver biopsy, according to the panel.

When evaluating a patient with suspected NAFLD, the guidelines recommend that clinicians exclude all competing etiologies for steatosis and coexisting chronic liver disease. A liver biopsy should be considered, when necessary, to rule out competing etiologies.

Additionally, persistently high serum ferritin and increased iron saturation, especially in the context of homozygote or heterozygote C282Y HFE mutations, may warrant a liver biopsy.

It was premature to recommend serum/plasma CK18 as a biomarker for identifying steatohepatitis, the panel said and noted that patients with high serum titers of autoantibodies, and other features suggesting autoimmune liver disease, should undergo a more complete workup for this.

Several recommendations for treatment were presented that stressed weight loss and lifestyle interventions as key to the management of steatosis. Treatments aimed at improving liver disease should be limited to patients with nonalcoholic steatohepatitis (NASH), as NAFLD patients without steatohepatitis have an “excellent prognosis from a liver standpoint,” the panel said.

With regard to specific interventions, they found the following:

  • Weight loss generally reduces hepatic steatosis, and a weight loss of up to 10% may be needed to improve necroinflammation.
  • Metformin has no significant effect on liver histology and is not recommended as a specific treatment for liver disease in patients with NASH.
  • Pioglitazone can be used to treat steatohepatitis in patients with biopsy-proven NASH, but its long-term safety and efficacy in patients with NASH is not established.
  • Vitamin E administered at a daily dose of 800 IU per day should be considered a first-line pharmacotherapy in nondiabetic adults with biopsy-proven NASH; however, without more data supporting its effectiveness, vitamin E is not recommended to treat NASH in diabetic patients, NAFLD without liver biopsy, NASH cirrhosis or cryptogenic cirrhosis.
  • Ursodeoxycholic acid is not recommended for the treatment of NAFLD or NASH. Omega-3 fatty acids may be considered first-line therapy for hypertriglyceridemia in patients with NAFLD but it is premature to recommend Omega-3 for the specific treatment of NAFLD or NASH.
  • Statins can be used to treat dyslipidemia in patients with NALFD and NASH but should not be used to treat NASH specifically until randomized controlled trials (RCTs) are conducted.

The panel briefly addressed bariatric surgery, saying most patients who undergo weight loss surgery have associated fatty liver disease. They noted that foregut bariatric surgery is not contraindicated in otherwise eligible obese individuals with NALFD or NASH but without established cirrhosis. It is premature to consider foregut bariatric surgery as an established option to treat NASH, they said.

The small number of RCTs limits recommendations for treatment options in children, the panel noted. The treatment recommendations for children were similar to adults: Intensive lifestyle modification should be the first-line treatment, metformin offers no benefit and vitamin E offers histologic benefits but confirmatory studies are needed.

The guidelines offer a good summary of the published evidence for NAFLD but, unfortunately, the evidence is limited, said Eric Kallwitz, MD, assistant professor of medicine at Loyola University Medical College, Maywood, Ill.

“I think this guideline gives us clearer recommendations on what patients we should be aggressive in evaluating. Until now, there has been limited guidance on the necessity of procedures such as biopsy, given the high prevalence of NAFLD.”

He added that he would like to see more information on screening patients’ dietary intake and evidence supporting specific prescription for dietary modifications and exercise requirements.

Authors of the guidelines reported financial relationships involving Abbott Laboratories, Advanced Life Sciences, Amylin, Astellas Pharma, Biolex Therapeutics, Bristol-Myers Squibb, Celgene, Cumberland Pharmaceuticals, Daiichi Sankyo, Eli Lily, Genentech, Geneva Foundation, Gilead, GlaxoSmithKline, Ikaria, Immuron, Intercept, Johnson & Johnson, Karo Bio, Merck & Co., Mochida, Norgine, Pfizer, Quark Pharmaceuticals, Raptor Pharmaceuticals, Roche, Rottapharm, Salix Pharmaceuticals, Sanofi-Aventis, Schering-Plough, Synageva BioPharma, Takeda, Teva Pharmaceuticals, Tibotec and Vertex Pharmaceuticals.


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