Elevated Serum Cyclophilin D Level is Associated with Nonalcoholic Fatty Liver Disease and Higher Fibrosis Scores in Patients with Diabetes Mellitus

BACKGROUND: Cyclophilin D (CypD) is a mitochondrial matrix protein involved in liver steatosis and fibrosis in vitro. However, the role of CypD in the development of fatty liver and liver fibrosis in humans has not been determined. PURPOSE: To measure the serum level of CypD in patients with type 2 diabetes (T2DM) and nonalcoholic fatty liver disease (NAFLD) and to assess its relation to the presence of hepatic steatosis and fibrosis in this group of patients. PATIENTS AND METHODS: In this cross-sectional study, 30 patients with diabetes and NAFLD were compared to 30 patients with diabetes without NAFLD and 30 age- and sex-matched healthy subjects. Abdominal ultrasound was used to diagnose NAFLD. Serum CypD was measured using ELISA. Fibrosis-4 (FIB-4) index, AST to platelet ratio index (APRI), and NAFLD fibrosis score (NFS) were used as markers of liver fibrosis in patients with NAFLD. Patients with NAFLD were divided into two subgroups based on FIB-4 index: patients with liver fibrosis (FIB-4 >1.45) and patients without liver fibrosis (FIB-4 <1.45). CypD and other clinical and biochemical parameters were validated as predictors of NAFLD and liver fibrosis in diabetic patients in multivariate logistic regression analysis. RESULTS: Diabetic patients with NAFLD had higher serum CypD levels than those without NAFLD (11.65±2.96 vs 6.58±1.90 ng/mL, respectively, P <0.001). Correlation analysis revealed a significant positive correlation between CypD and FIB-4 index (P=0.001), APRI (P=0.013) and NFS (P<0.001). GGT and CypD were the only predictors of NAFLD. For the prediction of significant fibrosis, AUROC of CypD was 0.835 with a cutoff >14.05 ng/mL provides specificity of 81.8% and sensitivity of 75%. CONCLUSION: Serum CypD is related to hepatic steatosis and fibrosis in diabetic patients. Serum CypD may thus provide a novel marker and therapeutic target of NAFLD and liver fibrosis.