Pathogenetic mechanisms of hepatitis C virus-induced B-cell lymphomagenesis.

Fabio Forghieri,Roberto Marasca,Rossana Maffei,Patrizia Barozzi,Mario Luppi,Franco Narni,Leonardo Potenza

doi:10.1155/2012/807351

Abstract

Hepatitis C virus (HCV) infection is probably the most common chronic viral infection and affects an estimated 180 million people worldwide, accounting for 3% of the global population. Although the liver is considered to be the primary target, extrahepatic manifestations are well recognized among patients with chronic HCV infection. Epidemiological studies have clearly demonstrated a correlation between chronic HCV infection and occurrence of B-cell non-Hodgkin's lymphomas (B-NHL). The clinical evidence that antiviral therapy has a significant role in the treatment at least of some HCV-associated lymphoproliferative disorders, especially indolent B-NHL, further supports the existence of an etiopathogenetic link. However, the mechanisms exploited by HCV to induce B-cell lymphoproliferation have so far not completely clarified. It is conceivable that different biological mechanisms, namely, chronic antigen stimulation, high-affinity interaction between HCV-E2 protein and its cellular receptors, direct HCV infection of B-cells, and “hit and run” transforming events, may be combined themselves and cooperate in a multifactorial model of HCV-associated lymphomagenesis.

Highlights

Hepatitis C virus (HCV) is an enveloped positive, singlestranded RNA virus, belonging to the Flaviviridae family [1]
The results showed that both E2 and HCV particles produced by cell culture (HCVcc) triggered phosphorylation of IkBα, with subsequent increased expression of NF-kB and NF-kB target genes, such as antiapoptotic Bcl-2 family proteins (Bcl-2 and Bcl-xL)
Epidemiological studies have clearly demonstrated a correlation between chronic HCV infection and occurrence of B-cell non-Hodgkin’s lymphomas (B-NHL)

Summary

Introduction

Hepatitis C virus (HCV) is an enveloped positive, singlestranded RNA virus, belonging to the Flaviviridae family [1]. HCV is a well-recognized etiologic agent of chronic hepatitis. The natural history of HCV infection is highly variable, an estimated 15% to 30% of patients in whom chronic infection develops have progression to cirrhosis over the ensuing three decades, and these latter patients warrant surveillance for complications, including hepatocellular carcinoma (HCC), which develops in 1%–3% of such patients per year [6, 7]. The liver is considered to be the primary target of HCV infection, extrahepatic manifestations, such as mixed cryoglobulinemia (MC), which is a systemic immune complex-mediated disorder characterized by B-cell proliferation that may evolve into overt B-cell non-Hodgkin’s lymphoma (B-NHL) in about 10%–20% of patients several years after diagnosis, are often recognized among patients with chronic HCV infection [10,11,12]. The possible pathogenetic mechanisms of HCV-induced B-cell lymphomagenesis are reviewed

Epidemiologic Association of HCV and B-NHL

Mechanisms of HCV-Induced Lymphoproliferation

C Direct infection of B cells by HCV

Findings

Conclusion