Abstract

The relationship between Hepatitis C Virus (HCV) infection and immunosuppression is complex and multifaceted. Although HCV-related hepatocytolysis is classically interpreted as secondary to the attack by cytotoxic T lymphocytes against infected cells, the liver disease is usually exacerbated and more rapidly evolutive in immunosuppressed patients. This generally occurs during the immunosuppression state, and not at the reconstitution of the host response after immunosuppressive therapy discontinuation. The field of immunosuppression and HCV infection is complicated both by the different outcome observed in different situations and/or by contrasting data obtained in the same conditions, with several still unanswered questions, such as the opportunity to modify treatment schedules in the setting of post-transplant follow-up. The complexity of this field is further complicated by the intrinsic tendency of HCV infection in itself to lead to disorders of the immune system. This review will briefly outline the current knowledge about the pathogenesis of both hepatic and extrahepatic HCV-related disorders and the principal available data concerning HCV infection in a condition of impairment of the immune system. Attention will be especially focused on some conditions - liver or kidney transplantation, the use of biologic drugs and cancer chemotherapy - for which more abundant and interesting data exist.

Highlights

  • The relationship between Hepatitis C Virus (HCV) infection and immunosuppression, when compared with Hepatitis B Virus (HBV) infection, seems quite peculiar

  • An explanation for the hypothesis of different effects on recurrent HCV-related liver damage after liver transplantation (LT) using CS - or cyclosporin A (CsA) - based protocols, can be found in recent studies performed in vitro using the replicon system and showing that - unlike what is known in the case of HBV CS does not act by increasing viral replication, but by dramatically increasing the ability of HCV to enter into target cells and spread the infection through the transactivation and consequent overexpression of genes codifying for HCV cellular receptors [106,107]

  • The combination of HCV infection and immunosuppression may lead to different conditions ranging from enhancement to inhibition of HCV replication/infection and from worsening to improvement of liver damage

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Summary

Introduction

The relationship between Hepatitis C Virus (HCV) infection and immunosuppression, when compared with Hepatitis B Virus (HBV) infection, seems quite peculiar. An explanation for the hypothesis of different effects on recurrent HCV-related liver damage after LT using CS - or CsA - based protocols, can be found in recent studies performed in vitro using the replicon system and showing that - unlike what is known in the case of HBV CS does not act by increasing viral replication, but by dramatically increasing the ability of HCV to enter into target cells and spread the infection through the transactivation and consequent overexpression of genes codifying for HCV cellular receptors (occludin, SR-B1) [106,107]. The average level of ALT did not increase [134] These effects of RTX therapy [40], and the rapidity of their appearance following B-cell depletion, strongly suggested a consistent role played by modifications in the cytokine network and a previously unknown key role played by B-cells in the pathogenesis of HCV-related liver damage [40]. The current data appear insufficient to draw definitive conclusions regarding the effect of HCV viral load, reactivation, and treatment on the prognosis of cancer, and especially in patients with lymphoma

Conclusions
15. Koziel MJ
Findings
24. Rehermann B
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