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Semin Liver Dis 2019; 39(01): 086-095
DOI: 10.1055/s-0038-1677517
Review Article
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

NASH in Lean Individuals

Ramy Younes
1   Department of Medical Sciences, Division of Gastroenterology, University of Torino, AOU Città della Salute e della Scienza, Torino, Italy
,
Elisabetta Bugianesi
1   Department of Medical Sciences, Division of Gastroenterology, University of Torino, AOU Città della Salute e della Scienza, Torino, Italy
› Author Affiliations
Funding The study was supported by grants for EPoS (Elucidating Pathways of Steatohepatitis, Grant Agreement No: 634413) and for LITMUS (Liver Investigation: Testing Marker Utility in Steatohepatitis, Grant Agreement No: 777377) projects, funded by the Horizon 2020 Framework Program of the European Union.
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Publication History

Publication Date:
17 January 2019 (online)

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Abstract

Nonalcoholic fatty liver disease (NAFLD) is generally associated with obesity and the related comorbidities but it can also develop in subjects with a body mass index (BMI) within the ethnic-specific cutoff of 25 kg/m2 BMI in Caucasian and 23 kg/m2 in Asian subjects, the so-called “lean” NAFLD. This sub-phenotype of NAFLD patients has been described across populations of different ethnicity, particularly in Asia, but it can be diagnosed in 10 to 20% of nonobese Americans and Caucasians. Pathophysiological mechanisms underpinning the “lean” phenotype are not completely understood, but they may include a more dysfunctional fat (visceral obesity, differences in adipocyte differentiation and altered lipid turnover), altered body composition (decreased muscle mass), a genetic background, not limited to patatin-like phospholipase domain-containing protein 3 (PNPLA3) C > G polymorphisms, epigenetic changes occurring early in life and a different pattern of gut microbiota. Lean subjects with NAFLD have milder features of the metabolic syndrome when compared with obese patients. Nonetheless they have a higher prevalence of metabolic alterations (e.g., dyslipidemia, arterial hypertension, insulin resistance, and diabetes) compared with healthy controls. Data on histological severity are controversial, but they can develop the full spectrum of liver disease associated with nonalcoholic steatohepatitis NASH. Since lean NAFLD usually present with less obesity-related comorbidities, it is commonly believed that this group would follow a relatively benign clinical course but recent data challenge this concept. Here, the authors describe the current knowledge about NAFLD in lean individuals and highlight the unanswered questions and gaps in the field.

Keywords

nonalcoholic fatty liver disease - body mass index - visceral adiposity - insulin resistance - genetic polymorphism - ethnicity