The clinical and histological characteristics of patients with biopsy-proven non-alcoholic fatty liver disease in the absence of insulin resistance

BACKGROUND AND AIM: Non-alcoholic fatty liver disease (NAFLD) is closely associated with insulin resistance (IR). While a minority of patients with NAFLD does not have evidence of IR, no detailed characterization of this specific phenotype is currently available. This study was undertaken to investigate the clinical and histological characteristics of this patient group. MATERIALS AND METHODS: We retrospectively reviewed the clinical records of 263 patients with biopsy-proven NAFLD. IR was defined by a Homeostatic Model Assessment of IR (HOMA-IR) score >2.73. The histological diagnosis of non-alcoholic steatohepatitis (NASH) was performed using 1) the steatosis, activity and fibrosis score and 2) the NASH Clinical Research Network (NASH CRN) criteria. Significant fibrosis was defined by the presence of a histological fibrosis score higher than F≥2. Patients with and without evidence of IR were compared concerning clinical, laboratory, and histological characteristics. RESULTS: Of the 263 patients with biopsy-proven NAFLD, 53 (20.2%) patients had no evidence of IR. Patients without IR were younger [IR (-): 42 (22–65) years versus IR (+): 49 (22−71) years, p=0.001] and had a higher prevalence of men [IR (-): 39 (73.6%) versus IR (+): 113 (53.8%), p=0.009]. Moreover, they were characterized by a lower body mass index [IR (-): 30.06±3.61 kg/m(2) versus IR (+): 33.19±5.06 kg/m(2), p=0.000] and lower frequencies of metabolic risk factors–including the metabolic syndrome, diabetes, hypertension, hyperlipidemia, and lower waist/hip circumference. Liver histology was generally less severe in patients without IR; specifically, they showed a lower prevalence of NASH [IR (-): 38 (71.7%) versus IR (+): 190 (90.5%), p=0.000] and significant fibrosis [IR (-): 9 (17.0%) versus IR (+): 106 (50.5%), p=0.000] than did patients with IR. Multivariate analysis identified obesity [odds ratio (OR): 9.321, 95% confidence interval (CI): 1.031−84.261, p<0.05] and an international normalized ratio >1.1 (OR: 10.116, 95% CI: 1.325−77.225, p<0.05) as independent predictors of significant fibrosis in patients with NAFLD and no IR. CONCLUSION: Patients with NAFLD and no IR has less severe liver histology than patients with IR. However, obesity appears to be independently associated with significant fibrosis in this patient group.