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

Abstract

Preamble These recommendations are based on the following: (i) a formal review and analysis of the recently published world literature on the topic (Medline search up to June 2011); (ii) the American College of Physicians' Manual for Assessing Health Practices and Designing Practice Guidelines; (1) (iii) guideline policies of the three societies approving this document; and (iv) the experience of the authors and independent reviewers with regards to non-alcoholic fatty liver disease (NAFLD). Intended for use by physicians and allied health professionals, these recommendations suggest preferred approaches to the diagnostic, therapeutic, and preventive aspects of care. They are intended to be flexible and adjustable for individual patients. Specific recommendations are evidence based wherever possible, and when such evidence is not available or inconsistent, recommendations are made based on the consensus opinion of the authors. To best characterize the evidence cited in support of the recommendations, the AASLD Practice Guidelines Committee has adopted the classification used by the GRADE (Grading of Recommendation Assessment, Development, and Evaluation) workgroup with minor modifications (Table 1) (2). The strength of recommendations in the GRADE system is classified as strong (1) or weak (2). The quality of evidence supporting strong or weak recommendations is designated by one of three levels: high (A), moderate (B), or low quality (C) (2). This is a practice guideline for clinicians rather than a review article and interested readers can refer to several comprehensive reviews published recently (3,4,5,6,7,8).Table 1: Grading of recommendations, assessment, development, and evaluation (GRADE)Definitions The definition of NAFLD requires that (i) there is evidence of hepatic steatosis, either by imaging or by histology and (ii) there are no causes for secondary hepatic fat accumulation such as significant alcohol consumption, use of steatogenic medication, or hereditary disorders (Table 2). In the majority of patients, NAFLD is associated with metabolic risk factors such as obesity, diabetes mellitus, and dyslipidemia. NAFLD is histologically further categorized into non-alcoholic fatty liver (NAFL) and non-alcoholic steatohepatitis (NASH) (Table 3). 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.Table 2: Common causes of secondary hepatic steatosisTable 3: Nonalcoholic fatty liver disease and related definitionsIncidence and prevalence in the general population The incidence of NAFLD has been investigated in a limited number of studies. Two Japanese studies (9,10) reported an incidence rate of 31 and 86 cases of suspected NAFLD per 1,000 person-years, respectively, whereas another study from England showed a much lower incidence rate of 29 cases per 100,000 person-years (11). More studies are needed to better understand the incidence of NAFLD across different age, ethnic, and geographic groups. The reported prevalence of NAFLD varies widely depending on the population studied and the definition used. The prevalence of histologically defined NAFLD was 20 and 51% in two different studies comprised of potential living liver donors (12,13). The reported prevalence of NAFLD when defined by liver ultrasound (US) ranged between 17 and 46% depending on the population studied (4). In a study consisting of nearly 400 middle-aged individuals, the prevalence of NAFLD defined by ultrasonography was 46% and the prevalence of histologically confirmed NASH was 12.2% (14). In the Dallas Heart Study, when assessed by magnetic resonance (MR) spectroscopy, the prevalence of NAFLD in the general population was 31% (15). The prevalence of suspected NAFLD when estimated using aminotransferases alone without imaging or histology ranged between 7 and 11%, but aminotransferases can be normal in individuals with NAFLD (4). In summary, estimates of the worldwide prevalence of NAFLD ranges from 6.3 to 33%, with a median of 20% in the general population, based on a variety of assessment methods (4). On the other hand, the estimated prevalence of NASH is lower, ranging from 3 to 5% (4). The prevalence of NASH cirrhosis in the general population is not known. Prevalence of NAFLD in high-risk groups (Table 4) Obesity is a common and well-documented risk factor for NAFLD. Both excessive body mass index (BMI) and visceral obesity are recognized risk factors for NAFLD. In patients with severe obesity undergoing bariatric surgery, the prevalence of NAFLD can exceed 90% and up to 5% of patients may have unsuspected cirrhosis (4,16,17,18,19,20). There is a very high prevalence of NAFLD in individuals with type 2 diabetes mellitus (T2DM) (4). An ultrasonographic study of patients with T2DM showed a 69% prevalence of NAFLD (