Medscape Medical News
Janis C. Kelly
July 11, 2014

Nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) lack definitive etiology, effective therapy, and evidence-based clinical guidelines, but World Gastroenterology Organisation (WGO) recommendations offer pragmatic guidance for clinicians. In the guidelines, published in the July issue of the Journal of Clinical Gastroenterology, the WGO review team, led by Douglas R. LaBrecque, MD, from the Department of Internal Medicine, Liver Service, University of Iowa Hospital and Clinics, Iowa City, emphasize that NAFLD and NASH cause liver disease worldwide, not just in Western countries. They are the number 1 cause of liver disease.

NAFLD is defined by excessive fat accumulation in the form of triglycerides (steatosis) in the liver, and a subgroup of patients with NAFLD develop liver cell injury and inflammation in addition to excessive fat (steatohepatitis), termed NASH. Diagnosis is complicated by the fact that histologically, NASH is virtually indistinguishable from alcoholic steatohepatitis. Basic NAFLD is not associated with increased short-term morbidity or mortality, but progression to NASH increases the risks for cirrhosis, liver failure, and hepatocellular carcinoma, according to the authors. The cause of NASH is unclear, but the disease is associated with insulin resistance, obesity, and metabolic syndrome in some patients.

The WGO guidelines provide a “resource-sensitive” cascade of recommendations that reflect the “best opinions of a group of experts from all areas of the globe,” taking local resources into account, the authors write.

They defined cascade as “a hierarchical set of diagnostic, therapeutic, and management options to deal with risk and disease, ranked by the resources available.” They note that NAFLD/HASH is a diagnosis of exclusion, often requiring liver biopsy for confirmation, staging, differential diagnosis, or determining the need for aggressive therapy.

According to the authors, NAFLD and NASH now represent “a major global public health problem, which is pandemic and affects rich and poor countries alike,” but for which there is not sufficient evidence to justify population screening. They advise looking for NASH in patients who present with risk factors such as hypertension, type 2 diabetes, sleep apnea, a positive family history, nonblack ethnicity, obesity, hyperlipidemia, and a sedentary lifestyle.

“Patients with NASH or risk factors for NASH should first be treated with diet and exercise. Vitamin E or pentoxifylline may be added in these patients. Experimental therapy should be considered only in appropriate hands and only in patients who fail to achieve a 5% to 10% weight reduction over 6 months to 1 year of successful lifestyle changes,” the authors write. Drugs targeting insulin resistance (thiazolidine-diones, metformin), antioxidants (vitamin E), antifibrotic agents, and pentoxifylline are considered to be experimental treatment for this condition because their use is not supported by adequate data from double-blind controlled trials.

The suggested weight loss goal is 5% to 10%, with a 25% decrease in calories from the normal diet. The suggested exercise goal is moderate exercise 3 to 4 times per week. Clinicians should assess the efficacy of these interventions after 6 months, with consideration for pharmacologic intervention.

The WGO also emphasized that fatty liver does not always indicate a need for aggressive therapy, and that clinicians should reserve liver biopsy for patients with risk factors for NASH and/or other liver diseases.

The authors conclude, “Ultimately, NAFLD and NASH are diagnoses of exclusion and require careful consideration of other diagnoses. Just as the clinician cannot diagnose NASH on the basis of clinical data alone, the pathologist can document the histologic lesions of steatohepatitis, but cannot reliably distinguish those of nonalcoholic origin from those of alcoholic origin.”

Clinicians should consider weight loss (bariatric) surgery early in the treatment course for patients with morbid obesity for whom other approaches fail because cirrhosis renders patients ineligible for this surgery at most institutions.

WGO Recommendations for NAFLD/NASH Diagnosis

• Suspected NAFLD involves central obesity, diabetes mellitus, dyslipidemia, metabolic syndrome, abnormal liver function tests, and/or ultrasound changes consistent with fatty liver.
• Minimal assessment should include bilirubin, alanine aminotransferase, aspartate aminotransferase, g-glutamyl transferase, albumin, fasting serum lipids, complete blood count, anti- hepatitis C virus, hepatitis B surface antigen, antinuclear antibody, fasting blood glucose, oral glucose tolerance test if fasting blood glucose level of 5.6 mmol/L or higher, height, weight, body mass index, waist circumference, blood pressure, and abdominal ultrasound.
• Optional tests include abdominal computed tomography if uninformative ultrasound or liver biopsy if diagnostic uncertainty or for patients at risk for advanced hepatic fibrosis.
• Additional tests include tests for hereditary hemochromatosis, Wilson’s disease alpha-1 antitrypsin deficiency, polycystic ovary syndrome, and autoimmune liver diseases.

The authors have disclosed no relevant financial relationships.

J Clin Gastroenterol. 2014;48:467-473. Full text