Serum adipokine levels predictive of liver injury in non-alcoholic fatty liver disease

Aims: The aim of this study was to determine whether serum levels of adipokines, including the ratio of serum adiponectin to leptin (A/L) levels could predict the severity of liver injury in patients with non-alcoholic fatty liver disease (NAFLD). Patients and methods: Fifty-seven patients with biopsy-proven non-alcoholic steatohepatitis (NASH) (mean age 51 +/- 12, sex ratio 1), 17 with simple steatosis (mean age 47 +/- 12, sex ratio 1.4) and 10 controls without steatosis (mean age 51 +/- 11, sex ratio 4) were investigated. In all subjects, serum concentrations of triglycerides, ultrasensitive C reactive protein, leptin, adiponectin, soluble tumour necrosis factor receptor 1, interleukin (IL)-6 and Homeostasis Model Assessment Method (HOMA) were measured. Hepatic expression of adiponectin and its two receptors was assessed by quantitative reverse transcriptase polymerase chain reaction. Results: Body mass index (BMI) and HOMA were correlated positively with leptin levels (r = 0.44 and 0.28 respectively) and negatively with the A/L ratio (r = 0.51 and 0.41 respectively). Independent parameters associated with NASH vs steatosis were HOMA > 3 [odds ratio (OR) = 6.9] and A/L ratio < 1.4 10(3) (OR = 5.2). The combination of HOMA with A/L ratio showed an area under the receiver operating characteristic curve of 0.82 for distinguishing between NASH and steatosis. Extensive portal fibrosis was present in 17 (23%) patients with NAFLD. Three independent parameters were associated with fibrosis: age (OR = 1.1), BMI (OR = 1.3) and high IL-6 levels (OR = 1.6). The hepatic expression of adiponectin receptor 2 was significantly higher in patients with NASH compared with controls and was related with necroinflammatory injury. Conclusions: This study shows that in patients with NAFLD, the combination of HOMA with A/L ratio may be a useful noninvasive approach to appreciate the severity of liver damage.