Prevalence and Severity of Nonalcoholic Fatty Liver Disease in Non-Obese Patients: A Population Study Using Proton-Magnetic Resonance Spectroscopy

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OBJECTIVES:Some studies suggest that non-obese patients with nonalcoholic fatty liver disease (NAFLD) may have more severe disease. We aim to study the epidemiology and severity of non-obese NAFLD.METHODS:A total of 911 community subjects were randomly recruited from the census database of the Hong Kong Government. Intrahepatic triglycerides (IHTG) and liver fibrosis were assessed by proton-magnetic resonance spectroscopy and transient elastography, respectively. The Asian body mass index cutoff of 25 kg/m2 was used to define non-obese NAFLD.RESULTS:The prevalence of NAFLD was 19.3% in non-obese subjects and 60.5% in obese subjects (P<0.001). Compared with obese NAFLD patients, non-obese NAFLD patients had similar IHTG content (median 9.8% vs. 9.9%;P=0.100) but lower cytokeratin-18 fragments (149 vs. 182 IU/l;P=0.019) and liver stiffness (4.6 vs. 5.6 kPa;P<0.001). The G allele at the patatin-like phospholipase domain-containing protein 3 gene (PNPLA3rs738409) was more common in non-obese than obese NAFLD patients (78.4% vs. 59.8%;P=0.001). Obesity, high hemoglobin A1c, insulin resistance, hyperferritinemia, and thePNPLA3G allele were independent factors associated with NAFLD in non-obese subjects. Even among non-obese subjects with normoglycemia, those with NAFLD were more insulin resistant (mean homeostasis model assessment of insulin resistance: 2.0±1.0 vs. 1.1±1.1;P<0.001).CONCLUSIONS:One-fifth of the general non-obese Chinese population has NAFLD. Non-obese patients with NAFLD do not have a higher risk of steatohepatitis or advanced fibrosis. Patients with risk factors of advanced fibrosis such as metabolic syndrome andPNPLA3G allele carriage should be assessed for severe NAFLD.

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