Evidence of oxidative stress as a cofactor in the development of insulin resistance in patients with chronic hepatitis C

Aim: The mechanisms by which metabolic disorders develop in patients with chronic hepatitis C are unknown. Our study aimed to test whether oxidative stress contributes to these mechanisms. Methods: The index of homeostasis model assessment-insulin resistance (HOMA-IR) and serum and hepatic levels of thioredoxin (Trx), which are markers of oxidative stress, were evaluated in 203 biopsy-proven chronic hepatitis C patients with hepatitis C virus (HCV) genotype 1 or 2 infection. HOMA-IR and Trx levels were compared with baseline values after phlebotomy in 23 patients. Results: HOMA-IR and serum Trx levels were significantly correlated with disease stage (HOMA-IR, P < 0.00001; Trx, P < 0.0001) and independently predicted fibrosis scores (HOMA-IR, P < 0.05; Trx, P < 0.005). Steatosis (%) was significantly correlated with HOMA-IR (P < 0.00005) and Trx (P < 0.001) stage (P < 0.00001). Serum Trx levels were significantly correlated with HOMA-IR (P < 0.05), even after adjustment for body mass index (P < 0.05). Furthermore, the mRNA levels of hepatic Trx were significantly correlated with HOMA-IR (P < 0.05) and independently-predicted HOMA-IR (P < 0.05). The alanine aminotransferase (P < 0.00001), Trx (P < 0.05), and HOMA-IR (P < 0.05) serum levels decreased significantly after phlebotomy; these effects were similar even in non-responders to interferon. Conclusion: Oxidative stress contributed to the development of IR irrespective of obesity in patients with HCV genotype 1 or 2 infection. This study could contribute to our understanding of how metabolic disorders develop and how they should be treated in chronic hepatitis C patients.