Predictors of Nonalcoholic Steatohepatitis and Significant Fibrosis in Non-obese Nonalcoholic Fatty Liver Disease

Donghee Kim; Won Kim; Sae Kyung Joo; Jung Ho Kim; Stephen A. Harrison; Zobair M. Younossi; Aijaz Ahmed


Liver International. 2019;39(2):332-341. 

In This Article


Nonalcoholic fatty liver disease (NAFLD) encompasses a broad spectrum of hepatic injury ranging from nonalcoholic fatty liver (NAFL) to nonalcoholic steatohepatitis (NASH), which may lead to progressive fibrosis culminating in cirrhosis with risk of hepatic decompensation.[1,2] The alarmingly high prevalence of NAFLD is particularly concerning because the subset of subjects with NASH and advanced fibrosis are at increased risk of all-cause and cardiovascular disease-related mortality compared to general population.[3–5]

Nonalcoholic fatty liver disease is commonly associated with metabolic comorbidities, including obesity, type II diabetes, dyslipidemia and metabolic syndrome. However, there are credible epidemiologic data demonstrating that not all obese subjects will invariably develop NAFLD and, contrarily, NAFLD can be found in non-obese individuals.[6] Non-obese NAFLD occurs in children and adults of all ethnicities, even when using strict ethnicity-specific criteria for defining obesity.[6] Therefore, risk factors other than obesity may play a key role in the pathogenesis of NAFLD in the non-obese population. Currently, characteristics and risk factors for non-obese NASH and fibrosis are not well documented.

Visceral adipose tissue (VAT) area is more directly related to NAFLD than is the body mass index (BMI) as a surrogate marker of general obesity.[7,8] We previously reported that increased VAT area is independently associated with NASH or significant fibrosis.[9] Several studies have reported that an increased visceral fat is associated with metabolic syndrome in metabolically obese, normal-weight (MONW) subjects.[10,11] In our previous longitudinal cohort study, the VAT area was associated with incident non-obese NAFLD in a dose-dependent manner.[12] Therefore, we hypothesized that the body fat distribution rather than general obesity may have a stronger association with increased risk of advanced disease in non-obese NAFLD rather than in obese NAFLD. Our study compared subjects with non-obese NAFLD to those with obese NAFLD with a focus on (a) clinical and histological characteristics and (b) determinants of NASH and significant fibrosis, including body fat distribution.