Mechanisms of increased insulin resistance in non-cirrhotic patients with chronic hepatitis C virus infection

Background and Aim: Evidence showing a higher prevalence of diabetes mellitus (DM) in patients with chronic hepatitis C virus (HCV) infection has been accumulating. However, the reason why chronic HCV infection promotes DM remains unknown. In the present study, the authors focused on non-cirrhotic and non-diabetic patients with chronic HCV infection and evaluated the factors responsible for increases in insulin resistance.

Methods: Fifty-six patients diagnosed with HCV-related chronic liver disease were included. Biochemical information including body mass index (BMI), aspartate aminotransferase (AST), alanine aminotransferase, cholinesterase, triglyceride, total cholesterol, hemoglobin, platelet count, glycosylated hemoglobin, immunoreactive insulin (IRI), and serum levels of tumor necrosis factor (TNF)-α and HCV-RNA were determined using venous blood samples obtained from each patient after overnight fasting. Homeostasis model assessment of insulin resistance (HOMA-IR), a simple and convenient measure of insulin resistance, was also calculated. The relationship between the stage of liver fibrosis and HOMA-IR, and the clinical factors responsible for the increase in HOMA-IR in non-diabetic patients was investigated.

Results: Homeostasis  model  assessment  of  insulin  resistance  and  IRI  levels  increased  parallel  with the progression of fibrosis. Among the non-diabetic patients with mild to moderate liver fibrosis, BMI,  serum  levels  of  AST  and  TNF-α were  related  with  HOMA-IR  (BMI:  r = 0.395,  P = 0.041; AST: r = 0.465, P = 0.014; TNF-α: r = 0.396, P = 0.040). In contrast, HOMA-IR related to TNF-α (r = 0.526, P = 0.013) in non-diabetic patients with advanced liver fibrosis.

Conclusion: Collectively, hepatic fibrosis and inflammation appear to play key roles in the increase in insulin resistance in patients with chronic HCV infection.