Abstract

Chronic hepatitis C is a leading cause of liver disease. Infection triggers an immediate immune response in the host that is mediated by humoral/cellular mechanisms. T cells respond to infection via secretion of cytokines, which inhibit or stimulate one another, leading to cytokine imbalance and ultimately affecting treatment. Studies using interferon (IFN) and ribavirin (RBV) showed that TCD8+ cells and cytokine levels are associated with sustainable virological response (SVR). However, studies that investigated the effects of triple therapy (TT) are limited. The study included hepatitis C virus (HCV)+ RNA, naives, genotype 1, ≥18 years, and advanced fibrosis (F≥3) patients. Samples were collected at baseline and after 12 weeks (W12) of TT. Six cytokines were analyzed by flow cytometry. Of 31 patients, four were excluded (two deaths, one interrupted TT, and one F2 patient). Of the 27 remaining patients, 21 (78%) were cirrhotic. SVR was achieved in 63% of the patients. The patients had a mean age of 55.11 ± 10.03 years. Analyses at baseline showed that the chemokine CCL5/Regulated on Activation, Normal T Cell Expressed and Secreted (RANTES) (p=0.04) and interleukin (IL)-6 (p=0.02), which was associated with SVR. RANTES (p=0.04) and IL-8 (p=0.01) levels were associated with SVR at W12. Similar to patterns observed during double therapy, IL-6, IL-8, and RANTES levels were associated with SVR in TT, indicating the potential role of interferon in immune response to hepatitis C virus.

Highlights

  • Chronic hepatitis C is a leading cause of liver disease

  • Plasma cytokine and chemokine levels [IL-6, IL-8, monocyte chemotactic protein-1 (MCP-1), RANTES, monokine induced by IFN gamma (MIG), and IFN gamma-induced protein 10 (IP-10)] were quantified at two time points of treatment

  • Cytokine and chemokine levels were analyzed by flow cytometry following the CBA method using the kits CBA Human Chemokine (MCP-1, RANTES, IL-8, monokine induced by gamma IFN (MIG), and IP-10) and Human IL-6 Flex Set

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Summary

INTRODUCTION

A total of 184 million people, corresponding to 3% of the world population, are estimated to be infected with the hepatitis C virus[1]. Infection with hepatitis C virus is considered to be one of the major causes of liver disease and leads to the development of cirrhosis and hepatocellular carcinoma[2]. T helper (Th)[1] response in the baseline period, and the increase in Th2 cytokines during treatment may define treatment success or failure[11,14,23,24]. These studies were performed on patients treated with dual therapy (IFN alpha or PegIFN and RBV). The present study aimed to evaluate whether the RVS is influenced by the IR by analyzing chemokine levels in patients undergoing TT treatment

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