Lean non-alcoholic fatty liver disease (Lean-NAFLD): a major cause of cryptogenic liver disease.

ABSTRACT

AIMS: Non-alcoholic fatty liver disease (NAFLD) is strongly associated to obesity and type 2 diabetes, but may occur in the absence of these factors. Based on a large series of liver biopsies, we have evaluated the clinical, biochemical, metabolic and pathological characteristics of a new entity, which we refer to as "lean-NAFLD". METHODS: Among 1,777 patients, who underwent liver biopsy for chronic liver disease, Lean-NAFLD, defined as patients with NAFLD without obesity (BMI < 30 kg/m2) and without diabetes was found in 50 of them (2.8%), being the most frequent cause (38%) of cryptogenic liver disease. Thirty-one patients from the Lean-NAFLD group were compared to 48 Obese-NAFLD patients diagnosed during the same period and 8 healthy control patients. Insulin resistance was determined using the homeostasis model assessment method. RESULTS: In the Lean-NAFLD group as compared to the obese-NAFLD group, patients were younger median 40 vs. 49 years, p = 0.047, with male predominance 71 vs. 46%, p = 0.037. Fasting glucose and HbA1c were lower, as was insulin sensitivity 1.7 vs. 3.0, p = 0.049. Blood pressure was significantly lower (p = 0.001) while triglycerides and HDL-cholesterol were similar. Although there was less inflammation (p = 0.038) and fibrosis (p = 0.029), non-alcoholic steatohepatitis and fibrosis were present in 61% and 55% of the Lean-NAFLD group, respectively. Compared to healthy controls, Lean-NAFLD were less insulin sensitive, with a insulin sensitivity index of 59 vs. 110 (p = 0.015), and more hypertriglyceridemic (p = 0.003). CONCLUSIONS: Lean-NAFLD is a new unrecognized clinicopathological entity, a frequent cause of cryptogenic liver disease.