Association of multispecific CD4+ response to hepatitis C and severity of recurrence after liver transplantation

Rosen, Hugo R.; Hinrichs, David J.; Gretch, David R.; Koziel, Margaret James; Chou, Sunwen; Houghton, Michael; Rabkin, John M.; Corless, Christopher L.; Bouwer, H. G. A.

doi:10.1016/s0016-5085(99)70352-5

Cited by 146 publications

(56 citation statements)

References 25 publications

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“…Patients with rapidly progressive cholestatic hepatitis seem to have very high levels of HCV RNA, more than 10-fold greater than the average patient with recurrent HCV, fewer quasispecies, and reduced lymphocyte recognition of HCV antigens. [9][10][11][42][43][44][45][46][47] These observations support a scenario in which the immune response to HCV is reduced, and in which the virus can proliferate rapidly without mutations. It is therefore important to note that most cases of rapidly progressive cholestatic hepatitis C seem to develop after treatment of presumed acute rejection with either monoclonal antibodies or high-dose bolus corticosteroids.…”

Section: Rapidly Progressive Cholestatic Hepatitis Csupporting

confidence: 60%

Controversies in the management of hepatitis C virus infection after liver transplantation

Shiffman¹,

Vargas²,

Everson³

2003

Liver Transplantation

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Recurrence of hepatitis C virus infection after liver transplantation is universal. A significant percentage of these patients develop progressive graft injury and cirrhosis. Those factors that modulate disease progression in liver transplant recipients with recurrent hepatitis C virus infection remain controversial and are poorly understood. Treatment of recurrent hepatitis C virus after liver transplantation with either interferon or interferon and ribavirin has yielded only limited success. Regardless of this, treatment is instituted. Peginterferon is more effective than standard interferon for treatment of chronic hepatitis C virus infection in the nontransplantation setting when used either alone or with ribavirin. The effectiveness of peginterferon, both with and without ribavirin in the posttransplantation setting, is currently being explored. In this review those factors thought to affect disease progression in patients with recurrent hepatitis C virus will be discussed, strategies that have been used to treat recurrent hepatitis C virus will be reviewed, and the impact that peginterferon may have on hepatitis C virus infection in the pretransplantation and posttransplantation setting will be explored. C irrhosis secondary to chronic infection with the hepatitis C virus (HCV) is the leading indication for liver transplantation. 1,2 Although transplantation is an effective treatment for end-stage liver disease secondary to chronic HCV infection, virus recurs in essentially all patients. 1-3 Progressive graft injury leading to cirrhosis occurs in about 25% to 33% of patients within just 5 years. [4][5][6][7][8] In addition, a limited group of patients (about 1% to 5% of recipients) develop rapidly progressive cholestatic hepatitis and liver failure within just 1 to 2 years. [8][9][10][11] Numerous studies have attempted to identify those factors that affect disease progression in these patients. Unfortunately, nearly all studies in this area have been retrospective in nature, conducted in patient populations of limited size, at single centers, utilized an array of immune suppressive medications in an uncontrolled manner, and have failed to consistently utilize protocol liver biopsy to investigate histologic progression. In addition, allograft rejection has not been either universally defined or treated and assays to measure serum HCV RNA have varied between centers and changed over time. As a result, data from many studies seem to contradict each other and the interpretation of these findings has varied widely. It is therefore not surprising how little progress has been made in our understanding of recurrent HCV over the past decade and that no universally accepted algorithm for managing these patients has emerged.Interferon (IFN) alfa with or without ribavirin (RBV) is the treatment of choice for patients with chronic HCV infection. 12,13 These medications have also been used to treat recurrent HCV after liver transplantation, but the interpretation of these data has been plagued by a similar set of limit...

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Section: Rapidly Progressive Cholestatic Hepatitis Csupporting

confidence: 60%

Controversies in the management of hepatitis C virus infection after liver transplantation

Shiffman¹,

Vargas²,

Everson³

2003

Liver Transplantation

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“…19 Moreover, specific HCV immune responses have been examined in this syndrome. 21 In this particular study, Rosen et al 21 compared the CD4 response in severe versus mild HCV recurrence; however, the majority of patients described with severe disease had cholestatic syndrome (H.…”

Section: Immunopathogenesis Of Hcv-related Cholestatic Hcv Recurrencementioning

confidence: 99%

Impact of immunosuppression on immunopathogenesis of liver damage in hepatitis C virus-infected recipients following liver transplantation

McCaughan

Zekry

2003

Liver Transplantation

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“…Similarly, studies assessing the presence of HCV-specific T-cell responses in liver transplant recipients have shown that these were indeed detectable despite immunosuppression [16][17][18][19][20]. However, none of the studies in HIV/HCV co-infected patients and in liver transplant recipients have simultaneously investigated the presence of HCV-specific CD4 1 and CD8 1 T-cell responses throughout the complete HCV genome.…”

Section: Introductionmentioning

confidence: 99%

Polyfunctional HCV‐specific T‐cell responses are associated with effective control of HCV replication

Comte²,

et al. 2008

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HCV infection has a severe course of disease in HIV/HCV co-infection and in liver transplant recipients. However, the mechanisms involved remain unclear. Here, we evaluated functional profiles of HCV-specific T-cell responses in 86 HCV mono-infected patients, 48 HIV/HCV co-infected patients and 42 liver transplant recipients. IFN-c and IL-2 production and ability of CD4 and CD8 T cells to proliferate were assessed after stimulation with HCVderived peptides. We observed that HCV-specific T-cell responses were polyfunctional in HCV mono-infected patients, with presence of proliferating single IL-2-, dual IL-2/IFN-c and single IFN-c-producing CD4 1 and dual IL-2/IFN-c and single IFN-c-producing CD8 1 cells. In contrast, HCV-specific T-cell responses had an effector profile in HIV/HCV coinfected individuals and liver transplant recipients with absence of single IL-2-producing HCV-specific CD4 1 and dual IL-2/IFN-c-producing CD8 1 T cells. In addition, HCV-specific proliferation of CD4 1 and CD8 1 T cells was severely impaired in HIV/HCV co-infected patients and liver transplant recipients. Importantly, ''only effector'' T-cell responses were associated with significantly higher HCV viral load and more severe liver fibrosis scores.Ã These two authors contributed equally to this work. Therefore, the present results suggest that immune-based mechanisms may contribute to explain the accelerated course of HCV infection in conditions of HIV-1 co-infection and liver transplantation.

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Association of multispecific CD4+ response to hepatitis C and severity of recurrence after liver transplantation

Cited by 146 publications

References 25 publications

Controversies in the management of hepatitis C virus infection after liver transplantation

Controversies in the management of hepatitis C virus infection after liver transplantation

Impact of immunosuppression on immunopathogenesis of liver damage in hepatitis C virus-infected recipients following liver transplantation

Polyfunctional HCV‐specific T‐cell responses are associated with effective control of HCV replication

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