The Characteristic Features of Japanese Lean Patients with Nonalcoholic Steatohepatitis

Nonalcoholic steatohepatitis (NASH) is a hepatic manifestation of metabolic syndrome and develope based on insulin resistance.As NASH cases with lean body type are also recognized in addition to complication of obesity observed in about 60% of NASH patients, the characteristics has drawn attention.In addition, with significant involvement of ethnic difference, Asian people have been known its severe organ disorder compared with the degree of obesity.We have conducted a clinicopathological study to clarify characteristics of lean NASH patients. We classified 808 biopsy-proven NASH patients into three categories by body mass index (BMI); 91 lean NASH (BMI<22kg/m 2 ), 193 normal weight NASH (22<=BMI<25), 524 obese NASH (BMI>=25), comparative discussion was performed for gender, age, complication, laboratory findings, skeletal mass index (SMI) by bio-electrical impedance analysis (BIA), fat measurement by computed tomography, histological findings by steatosis, activity, fibrosis (SAF) score, allele specific analysis of rs738409 single nucleotide polymorphism on patatin-like phospholipase domain-containing protein (PNPLA)3 gene. Ratios of men were 41% in lean NASH /49% in normal weight NASH / 58% in obese NASH (p<0.05),age (median) 59/55/49y.o.(p<0.05), with more postmenopausal women observed in lean NASH.As for complication, type 2 diabetes mellitus (DM) were observed in 46/48/50%, hypertension 43/52/54%, dyslipidemia 46/47/ 50% (p<0.05),ratios of postgastrointestinal surgery cases 10/1/0.1% (p<0.05),surgical forms in lean NASH were 4 cases of intestinal resection, 3 total gastrectomy, 2 pancreatoduodenectomy.About laboratory test values, serum hemoglobin, prothrombin time (%), albumin, transaminases, total cholesterol, triglyceride were significantly low, and the aspartate aminotransferase/alanine aminotransferase ratios high in lean NASH patients.Compicated ratios of insulin resistance with homeostasis model assessment of insulin resistance >2.5 or under medication for DM were 56/57/67% (p<0.05).Visceral fat areas were 108/135/178cm 2 (p<0.05),ratios of visceral fat>100cm 2 52/82/93%(p<0.05),subcutaneous fat areas 90/161/ 275 cm 2 (p<0.05),V/S ratios 0.96/0.76/0.61(p<0.05).While SMI were 8.6/8.9/10.8kg/m 2 (p<0.05),Sarcopenia diagnosed by Asian Working Group of Sarcopenia was only one case for normal weight and obese NASH.Histologically, ratios with F3+F4 were 45/39/50%, A2+A3 58/75/86% (p<0.05), and S3 27/39/59% (p<0.05).Genetically, PNPLA3 risk allele positive ratio was 100%, 83% and 84%(p<0.05). With lean NASH frequently observed in elderly women in Japan along with lifestyle diseases, insulin resistance and visceral obesity complication recognized by at around 50% of patients, histological activity and fatty deposition was mild and PNPLA3 risk allele was frequently observed.