Immunopathogenesis of hepatitis C virus in the immunosuppressed host

Abstract

The prevalence of chronic hepatitis C virus (HCV) infection among various groups of immunosuppressed patients is high. These groups include patients co-infected with human immunodeficiency virus (HIV), recipients of organ transplants, and those with hypogammaglobulinemia. The liver disease in the immunosuppressed host is typically severe with an unusually rapid progression to cirrhosis. This is somewhat paradoxical, as the classical model for HCV-induced liver disease assumes that cell-mediated immune responses induce liver injury. It is likely that a combination of viral-related factors and host-related factors plays a role in this accelerated natural history of HCV. Data are accumulating in immunocompromised hosts that address the immunopathogenesis of liver injury, although there are still fundamental gaps in our understanding of this process. In this review, we will focus on our current understanding of the mechanisms of liver injury and how it relates to the accelerated liver disease progression in immunocompromised hosts.

Hepatitis C virus dynamics and pathology: the role of CTL and antibody responses

“…The overall message of the model is that evolution of escape from antibodies paves the way for disease progression and liver pathology by shifting the balance of immunity in favour of lytic responses. This is supported by data from immunosuppressed patients who show faster disease progression (McCaughan & Zekry, 2000;Einav & Koziel, 2002). Such patients are characterized by a deficiency of antibodies.…”

The magnitude and breadth of hepatitis C virus–specific CD8+ T cells depend on absolute CD4+ T-cell count in individuals coinfected with HIV-1

“…[6][7][8][9][10][11] Some have proposed that the phenomenon of accelerated fibrosis in individuals coinfected with HCV and HIV-1 may be related to loss or dysregulation of these immuneresponses. 12,13 In murine models of persistent viral infection, CD4 ϩ T cells are vital for maintenance of cytotoxic T lymphocyte (CTL) effector functions such as cytokine secretion and secondary expansion upon encounter with antigen, and the development of virus-specific memory responses is impaired in the absence of CD4 ϩ T cells at the time of exposure. 14,15 Moreover, recent depletion experiments in chimpanzees highlight the importance of both CD4 ϩ and CD8 ϩ T cells in control of HCV viremia and illustrate the vital role of CD4 ϩ cells in supporting HCV-specific CTLs.…”

Management of Chronic Hepatitis in Special Hosts and Special Situations: A Consensus Report of the Study Group for Viral Hepatitis of the Turkish Society of Clinical Microbiology and Infectious Diseases

“…HCV'ye bağlı hepatositoliz, infekte hücrelere karşı sitotoksik T lenfositlerin saldırısına bağlı olmakla birlikte, immünosüprese hastalardaki karaciğer hasarı genellikle daha şiddetli ve hızlıdır (181). Son dönem kronik böbrek hastalığı gelişme süresi, HCV infeksiyonu olan immünokompetan hastalarda ortalama 30 yıl iken, kemik iliği transplantasyonu olan hastalarda 10.1 yıl, hipogammaglobülinemisi olan hastalarda 8.8 yıldır (182).…”