Hepatitis C viral infection in the immunosuppressed patient

Collier, Jane; Heathcote, Jenny

doi:10.1002/hep.510270102

Cited by 73 publications

(44 citation statements)

References 43 publications

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“…been noted that immunosuppressed nontransplantation patients may have an accelerated course of HCV, 16 particularly those with HIV, 17 and HCV progression in such individuals took less than half the time as in nonimmunocompromised patients. 18 Overall, post-OLT recurrent HCV is considered a relatively benign process.…”

Section: Discussionmentioning

confidence: 99%

Histological recurrence and progression of hepatitis C after orthotopic liver transplantation: Influence of immunosuppressive regimens

Hunt

Gordon²,

Lewis³

et al. 2001

Liver Transplantation

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H epatitis C is the most common indication for orthotopic liver transplantation (OLT) in the world today. 1 In the United States, approximately 1.8% of patients are seropositive for the hepatitis C virus (HCV) antibody. 2 Of those infected, approximately 20% progress to cirrhosis and 8,000 to 12,000 die in 1 year in the United States alone. 3 Specific reasons for this progression are not clear, and a combination of environmental, viral, and host factors have been implicated, but not proven. 4 There is almost universal recurrence of HCV infection after OLT, which can progress more rapidly than the disease in the native liver. 5-7 However, some patients show no histological recurrence or progression of disease, even after extended follow-up, despite polymerase chain reactionproven HCV viremia 8 . Reasons for the variable progression are unclear. Viral genotype 5,7,9 and viral load 6,10 may affect the severity and rate of recurrent disease. Others implicate such host factors as the state of immunosuppression. 11,12 In our program, patients who underwent OLT for HCV have had variable post-OLT courses, with some long-term survivors showing no histological evidence of a hepatitic process.Although abundant data exist on biochemical, virological, and serological markers of disease recurrence and progression, there is less information on the histological progression of disease after OLT. The goal of this study is to evaluate possible predictors of post-OLT HCV progression and recurrence.

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Section: Discussionmentioning

confidence: 99%

Histological recurrence and progression of hepatitis C after orthotopic liver transplantation: Influence of immunosuppressive regimens

Hunt

Gordon²,

Lewis³

et al. 2001

Liver Transplantation

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“…This rate is consistent with the reported rates of HCV seroconversion in other groups of immunocompromised patients. 3,15,16 This underscores the importance of the fact that, in heart transplant recipients, HCV antibody is a poor marker of de novo HCV infection and that HCV-RNA testing is the most sensitive diagnostic test.…”

Section: Discussionmentioning

confidence: 99%

“…However, the true incidence of HCV-related liver disease may be underestimated because liver biopsies were not performed systematically on all patients. 3,15,16 Many patients with virological evidence of HCV infection show no abnormalities in liver enzymes. 4,5,17 However, because the absence of liver enzyme abnormalities does not necessarily correlate with histologic activity, 15,[18][19][20] a liver biopsy would be necessary to accurately determine the presence and severity of HCVrelated liver disease.…”

Section: Discussionmentioning

confidence: 99%

Outcome of De Novo hepatitis C virus infection in heart transplant recipients

et al. 1999

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The outcome of de novo hepatitis C virus (HCV) infection in heart transplant recipients of HCV-antibody positive organs is not known. The aim of the study was to determine the short-term outcome of de novo HCV infection in recipients of HCV-positive donor organs. HCV-antibody negative recipients of HCV-antibody positive hearts were identified from January 1, 1991 to February 28, 1998. Control patients matched for year of transplantation were also identified. Twenty-eight patients (22 males, mean age of 56 ؎ 11 SD) received hearts from HCV-antibody-positive donors. The control group was similar to the patients in all clinical and demographic aspects. Twenty-three patients had detectable viremia by reverse-transcription polymerase chain reaction (RT-PCR). Of these 23 patients with de novo HCV infection, 7 (30%) developed HCV-related liver disease. Three patients (13%) had chronic hepatitis and 4 patients (17%) developed severe acute cholestatic hepatitis (ACH). Mycophenolate mofetil (MMF) use (P ‫؍‬ .04) and high viral load at onset of acute liver disease (P ‫؍‬ .02) were associated with ACH. Overall survival was similar between patients with de novo HCV infection and controls (P ‫؍‬ .20). Development of ACH (P ‫؍‬ .02) and MMF use (P ‫؍‬ .0009) were associated with decreased survival in patients with de novo HCV infection. The present study showed that survival of patients with de novo HCV infection was similar to a matched control group. HCV-related severe ACH is associated with a poor short-term outcome in patients with de novo HCV infection. MMF use may be associated with a higher incidence of HCV-related severe ACH and a poor short-term outcome. (HEPATOLOGY 1999;30:1293-1298

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“…However, sampling bias is less likely to be relevant in the OLT setting given the extreme simplification of viral populations that occurs under immunosuppression. 18 Methods based on electrophoretic mobility, such as heteroduplex mobility assay, also have been used to assess QS variation in liver transplant recipients. 19,20 These techniques may allow a good description of QS variation, but preclude phylogenetic studies because specific nucleotide changes cannot be identified.…”

Section: Discussionmentioning

confidence: 99%

Sequence variation in the hypervariable region 1 of hepatitis C virus and posttransplantation recurrent hepatitis

Silini¹

2003

Liver Transplantation

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Hepatitis C virus (HCV) shows remarkable genetic variation in both populations and individuals, in whom it circulates as quasispecies (QS). Sequence variation within an infected host has adaptive significance and reflects the modes and intensity of selection mechanisms operating on the virus. We investigated the sequence diversity of hypervariable region 1 of HCV in liver transplant recipients and correlated it with the recurrence of hepatitis. Twenty-six patients were considered during a 2-year period; all had graft reinfection, and 14 patients developed hepatitis recurrence. Cloned sequences were obtained from sera collected before or within 1 month after orthotopic liver transplantation (OLT) and at 3 and 24 months thereafter. Sequence diversity within single sera and over consecutive samples was analyzed quantitatively by matrix comparison and phylogenetic analysis. Propagation of viral QS in the graft was markedly dependent on individual factors. Viral QS in post-OLT sera were less complex and evolved slower compared with immunocompetent subjects with chronic hepatitis. Sequence variation was greater during the first 3 months post-OLT than during the remaining period. Genetic diversity within single samples was not related to hepatitis recurrence or other clinical features. Conversely, sequence diversity over consecutive samples was reduced in patients who experienced hepatitis recurrence, in particular, in those infected with genotype 1b and with an HLA-DR mismatched graft. Selection of viral sequences was markedly impaired in liver transplant recipients and tended to be greater early after OLT. H epatitis C virus (HCV) shows high genetic diversity both in populations and within infected individuals, in whom it exists as a complex mixture of related molecular species known as viral quasispecies (QS). 1 The highly heterogeneous nature of viral populations has a central role in the mechanisms of the transmission, persistence, and pathogenesis of HCV infection. 2 The QS structure of the viral genome allows an extraordinary plasticity and an ability to adapt to variable environmental conditions and escape the host's immune surveillance. Thus, in most subjects, the immune system is unable to eradicate the infection and provide durable protection from reinfection despite persistent B-and T-cell reactivity. 3 This inefficient antiviral response is paralleled by a continuous turnover of viral variants that results from adaptation of the virus to different selective forces, rather than a progressive genetic drift. 4 Small selective advantages have greater effects on genetic compositions of viruses than major differences in spontaneous mutation rates. 5 We previously showed that in chronic HCV infection of immunocompetent hosts, genetic variation in hypervariable region 1 (HVR1) of the second envelope protein (E2) was adaptive in nature and directly dependent on the intensity and amplitude of anti-HVR1 antibody response. 6,7 Because levels of immune responsiveness can positively influence the outcome of infection, m...

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Hepatitis C viral infection in the immunosuppressed patient

Cited by 73 publications

References 43 publications

Histological recurrence and progression of hepatitis C after orthotopic liver transplantation: Influence of immunosuppressive regimens

Histological recurrence and progression of hepatitis C after orthotopic liver transplantation: Influence of immunosuppressive regimens

Outcome of De Novo hepatitis C virus infection in heart transplant recipients

Sequence variation in the hypervariable region 1 of hepatitis C virus and posttransplantation recurrent hepatitis

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