Study of Nitric Oxide in Patients with Chronic Hepatitis C Genotype 4: Relationship to Viremia and Response to Antiviral Therapy

Abstract

Hepatitis C virus (HCV) infection is a global medical problem. The role of Nitric oxide (NO) in chronic viral hepatitis is still unknown. It may play a prominent role as an antiviral agent that reduces its replication or as a mediator that causes accumulation of oxidative DNA damage and oncogenesis. The present study was carried out to study effect of combined peginterferon and ribavirin therapy for hepatitis C on NO in both responders and in non responder patients. The study included seventy three patients with positive serological markers for HCV. They were classified according to presence or absence of HCV viremia and the response to therapy. In addition sixteen control subjects were included. NO levels were determined as the stable end product nitrate and nitrite.

Serum nitrite and nitrate concentrations in the patients with viral hepatitis were significantly higher than normal subjects and patients with serological evidence of hepatitis C infection in absence of viral load. The levels of nitrite ≥ 31 μM, nitrate ≥ 15 μM and NO₂/NO₃ ratio < 1.5 μM were associated with increased risk of resistance to therapy. The multivariate logistic regression analysis showed that NO₂/NO₃ ratio at levels < 1.5 μM was associated with HCV eradication independently. This study provides new insight into the pathogenesis of hepatitis C and highlights the effect of combined peginterferon and ribavirin on nitrite and nitrate as markers of endogenous NO system. There is a limitation level of NO that if it is increased above it may lead to non response to antiviral therapy. Therefore, it may be an important factor for chronic hepatitis C, which suggests an additional therapeutic pathway of anti-oxidants in combination with the standard regimen for further study.

Keywords:

• Chronic hepatitis C
• Nitric oxide
• Interferon
• Ribavirin