The diagnosis and management of non-alcoholic fatty liver disease: practice guideline by the American Association for the Study of Liver Diseases, American College of Gastroenterology, and the American Gastroenterological Association.
[Link to free full text Guideline Summary at National Clearinghouse]
Chalasani N, Younossi Z, Lavine JE, Diehl AM, Brunt EM, Cusi K, Charlton M, Sanyal AJ. The diagnosis and management of non-alcoholic fatty liver disease: practice guideline by the American Association for the Study of Liver Diseases, American College of Gastroenterology, and the American Gastroenterological Association. Hepatology 2012 Jun;55(6):2005-23. [Free full-text Hepatology article PDF | PubMed® abstract]
The definition of nonalcoholic fatty liver disease (NAFLD) requires that (a) there is evidence of hepatic steatosis, either by imaging or by histology and (b) there are no causes for secondary hepatic fat accumulation such as significant alcohol consumption, use of steatogenic medication or hereditary disorders (see Table 2 in the original guideline document). In the majority of patients, NAFLD is associated with metabolic risk factors such as obesity, diabetes mellitus, and dyslipidemia. NAFL is defined as the presence of hepatic steatosis with no evidence of hepatocellular injury in the form of ballooning of the hepatocytes. NASH is defined as the presence of hepatic steatosis and inflammation with hepatocyte injury (ballooning) with or without fibrosis.
Alcohol Consumption & Definition of NAFLD
- Ongoing or recent alcohol consumption >21 drinks on average per week in men and >14 drinks on average per week in women is a reasonable definition for significant alcohol consumption when evaluating patients with suspected NAFLD in clinical practice. (Strength – 2, Quality – C)
Screening in Primary Care, Diabetes, and Obesity Clinics
- Screening for NAFLD in adults attending primary care clinics or high-risk groups attending diabetes or obesity clinics is not advised at this time due to uncertainties surrounding diagnostic tests and treatment options, along with lack of knowledge related to the long-term benefits and cost-effectiveness of screening. (Strength – 1, Evidence – B)
- When evaluating a patient with suspected NAFLD, it is essential to exclude competing etiologies for steatosis and co-existing common chronic liver disease. (Strength – 1, Evidence – A)
- Persistently high serum ferritin and increased iron saturation, especially in the context of homozygote or heterozygote C282Y hemochromatosis (HFE) mutations may warrant a liver biopsy. (Strength – 1, Evidence – B)
- High serum titers of autoantibodies in association with other features suggestive of autoimmune liver disease (very high aminotransferases, high globulin) should prompt a more complete work-up for autoimmune liver disease. (Strength – 1, Evidence – B)
When to Obtain a Liver Biopsy in Patients with NAFLD?
- Liver biopsy should be considered in patients with NAFLD who are at increased risk to have steatohepatitis and advanced fibrosis. (Strength – 1, Evidence – B)
- The presence of metabolic syndrome and the NAFLD Fibrosis Score may be used for identifying patients who are at risk for steatohepatitis and advanced fibrosis. (Strength – 1, Evidence – B)
- Liver biopsy should be considered in patients with suspected NAFLD in whom competing etiologies for hepatic steatosis and co-existing chronic liver diseases cannot be excluded without a liver biopsy. (Strength – 1, Evidence – B)
Management of Patients with NAFLD
- Weight loss generally reduces hepatic steatosis, achieved either by hypocaloric diet alone or in conjunction with increased physical activity. (Strength – 1, Evidence – A)
- Loss of at least 3-5% of body weight appears necessary to improve steatosis, but a greater weight loss (up to 10%) may be needed to improve necroinflammation. (Strength – 1, Evidence – B)
- Exercise alone in adults with NAFLD may reduce hepatic steatosis but its ability to improve other aspects of liver histology remains unknown. (Strength – 1, Evidence – B)
Insulin Sensitizing Agents
- Metformin has no significant effect on liver histology and is not recommended as a specific treatment for liver disease in adults with NASH.
- Pioglitazone can be used to treat steatohepatitis in patients with biopsy-proven NASH. However, it should be noted that majority of the patients who participated in clinical trials that investigated pioglitazone for NASH were non-diabetic and that long term safety and efficacy of pioglitazone in patients with NASH is not established. (Strength – 1, Evidence – B)
- Vitamin E (alpha-tocopherol) administered at daily dose of 800 IU/day improves liver histology in non-diabetic adults with biopsy-proven NASH and therefore it should be considered as a first-line pharmacotherapy for this patient population.(Strength - 1, Quality – B)
- Until further data supporting its effectiveness become available, vitamin E is not recommended to treat NASH in diabetic patients, NAFLD without liver biopsy, NASH cirrhosis, or cryptogenic cirrhosis (Strength - 1, Quality – C)
- UDCA is not recommended for the treatment of NAFLD or NASH. (Strength – 1, Quality – B)
- It is premature to recommend omega-3 fatty acids for the specific treatment of NAFLD or NASH but they may be considered as the first line agents to treat hypertriglyceridemia in patients with NAFLD. (Strength – 1, Quality – B)
Alcohol Use in Patients with NAFLD and NASH
- Patients with NAFLD should not consume heavy amounts of alcohol. (Strength – 1, Quality – B)
- No recommendation can be made with regards to non-heavy consumption of alcohol by individuals with NAFLD.(Strength – 1, Quality – B)
Statin Use in Patients with NAFLD and NASH
- Given the lack of evidence to show that patients with NAFLD and NASH are at increased risk for serious drug-induced liver injury from statins, statins can be used to treat dyslipidemia in patients with NAFLD and NASH. (Strength – 1, Quality – B)
- Until randomized controlled trials with histological endpoints prove their efficacy, statins should not be used to specifically treat NASH. (Strength – 1, Quality – B)
NAFLD in Patients with Other Chronic Liver Diseases
- When steatosis and steatohepatitis are evident in patients with other types of chronic liver disease, it is important to assess for metabolic risk factors and alternate etiologies for hepatic steatosis. (Strength – 1, Quality – B)
- In patients with other types of chronic liver diseases who have co-existing NAFLD and NASH, there are no data to support the use of vitamin E or pioglitazone to improve the liver disease. (Strength – 1, Quality – B)
Miscellaneous Recommendations Pertinent to Clinical Practice
- Patients with NASH cirrhosis should be screened for gastroesophageal varices according to the AASLD/American College of Gastroenterology (ACG) practice guidelines. (Strength – 1, Quality – B)
- Patients with NASH cirrhosis should be considered for hepatocellular carcinoma (HCC) screening according to the AASLD/ACG practice guidelines. (Strength – 1, Quality – B)
- Current evidence does not support routinely repeating a liver biopsy in patients with NAFL or NASH. (Strength – 2, Quality – C)
The grading system for the class of recommendations [are available online].
[Free full-text Hepatology article PDF | PubMed® abstract]
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