COMMENTARY

Lean Patients, Yet Still at Risk for Fatty Liver Disease

William F. Balistreri, MD

Disclosures

September 20, 2016

In This Article

Fatty Liver Disease, Without Obesity

Nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) are considered to be consequences of obesity.[1] However, it has recently been recognized that some adults may develop fatty liver disease in the absence of profound obesity.[2,3,4,5,6,7]

Dufour[8] made a recent plea to replace the term "NASH" with nomenclature based on the clinical picture or the pathophysiology of the disease. Although there is no uniformly acceptable pathophysiologic or etiology-based classification, the terms "lean NAFLD" and "lean NASH" are used to describe fatty liver in patients who are not overweight or obese, as defined by the standard anthropometric parameter of body mass index (BMI). I propose the terms "nonobese fatty liver disease (NOFLD)" and "nonobese steatohepatitis (NOSH)" for these unique patients.

It is important to recognize patients with lean fatty liver disease. Some studies suggest that this phenotype is associated with a worse metabolic and liver profile than the more widely recognized obesity-related fatty liver disease.[5,9,10,11]

How Common Is NOFLD?

Several recent studies have attempted to determine the prevalence among various populations.

Presumed NAFLD, based on elevated alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, was reported in up to 10% of lean US patients enrolled in the Third National Health and Nutrition Examination Survey (NHANES III).[4] The overall prevalence of ultrasound-defined NAFLD in > 3200 Japanese individuals was 25%; the prevalence of fatty liver was 69% in obese persons and 15% in nonobese persons.[12]

Kwon and colleagues[2] reported that during routine comprehensive health evaluations of 29,994 Korean adults, abdominal ultrasound suggested the presence of NAFLD in 13% of nonobese persons and 50% of obese persons.[2] Wei and coworkers[5] reported that the estimated prevalence of NAFLD in a Hong Kong cohort was 19% in nonobese persons (BMI < 25 kg/m2) and 61% in obese persons.

Kumar and colleagues[3] reported that 13% of 205 Indian patients with NAFLD were lean, 69% were obese, and 18% were overweight. Margariti and coworkers[6] evaluated the characteristics of 162 Greek patients with NAFLD, of whom 12% had normal BMI.

Most of these reported case series diagnosed steatosis/steatohepatitis on the basis of such criteria as ultrasonographic findings or AST/ALT levels; the presumption was not validated by liver biopsy. However, one study did assess liver histology from a subset representing a general Asian population (liver donors and accidental deaths).[5] The investigators found steatosis in 15% of nonobese persons, compared with 65% in obese and 85% in morbid obese persons, which confirmed published estimates.[5] Current studies are attempting to provide accurate estimates of the global prevalence of lean NAFLD and NASH using liver histology.

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