Postransplant hepatitis C virus quasispecies and cholestatic hepatitis

McCaughan, G.W.; Doughty, Alison L.

doi:10.1016/s0270-9139(00)80045-2

Cited by 2 publications

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“…14,16 Third, there was the demonstration of absent CD4 immune response in this subset of patients. 20 Fourth, stable quasispecies characterized the course of these patients compared with patients with recurrent chronic hepatitis C, 16,19 suggesting an escape from immune pressure.…”

Section: Discussionmentioning

confidence: 99%

“…It is characterized by a very high posttransplantation viral load, 14,15 and we have described an association with stable quasispecies, 16,17 although this latter observation is controversial. 18,19 No data are available on the intrahepatic cytokine profile, particularly in this group of patients. However, Rosen et al 20 observed a lack of a specific HCV CD4 T-cell response in patients with severe graft dysfunction, many of whom had cholestatic hepatitis.…”

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confidence: 99%

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Intrahepatic cytokine profiles associated with posttransplantation hepatitis C virus[ndash ]related liver injury

Zekry

2002

Liver Transplantation

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Recurrent chronic hepatitis, cholestatic hepatitis, and acute rejection in conjunction with hepatitis C virus (HCV) recurrence are well-recognized clinical sequelae of reinfection of the hepatic allograft with HCV. The aim of this study is to characterize intrahepatic cytokine responses associated with reinfection of the allograft with HCV in these settings. Intrahepatic messenger RNA expression of T helper cell subtype 1 (TH1) cytokines interleukin-2 (IL-2), interferon-␥, and tumor necrosis factor-␣ and TH2 cytokines IL-4 and IL-10 was measured by real-time polymerase chain reaction system using TaqMan probes in 53 liver specimens from six groups of patients. These were: (1) recurrent chronic hepatitis C (CH-I; n ‫؍‬ 15), (2) cholestatic hepatitis (n ‫؍‬ 6), (3) acute rejection associated with HCV recurrence (AR-HCV; n ‫؍‬ 12), (4) acute rejection in non-HCV-infected allografts (AR non-HCV; n ‫؍‬ 5), (5) patients with chronic hepatitis C who did not undergo transplantation (CH-C; n ‫؍‬ 10), and (6) nondiseased liver tissue (n ‫؍‬ 6). Intrahepatic viral loads were measured using an Amplicor monitor assay (Roche Diagnostic Systems, Branchburg, NJ). The CH-I and CH-C groups had similar TH1 intrahepatic cytokine profiles. Compared with the CH-I group, the cholestatic group expressed increased levels of the TH2 cytokines IL-10 (P ‫؍‬ .024) and IL-4 (P ‫؍‬ .0024). The AR-HCV group also expressed more TH2 cytokines IL-10 (P ‫؍‬ .014) and IL-4 (P ‫؍‬ .034) compared with the CH-I group. Both the AR-HCV and AR non-HCV groups showed similar intrahepatic cytokine profiles. Intrahepatic viral loads were highest in the cholestatic group compared with the AR-HCV, CH-I, and CH-C groups (P ‫؍‬ .0007). In conclusion, a novel observation is that the cholestatic group showed upregulation of the TH2 cytokines IL-10 and IL-4, in addition to high viral loads. In this setting, the E nd-stage liver disease associated with hepatitis C virus (HCV) infection is now the leading indication for liver transplantation in adults. However, after transplantation, HCV invariably reinfects the liver allograft. 1-3 Reinfection of the graft is characterized by different patterns of allograft injury, including recurrent chronic hepatitis C, cholestatic hepatitis C, and acute rejection associated with HCV recurrence. Studies examining the immunopathogenesis of these varying forms of HCV-related liver allograft injury remain limited.In the nonimmunosuppressed setting, several studies have shown that liver injury occurs in the context of an immune response. [4][5][6] Moreover, studies have shown that the intrahepatic cytokine milieu tends toward a T helper cell subtype 1 (TH1) profile. [7][8][9][10] In addition, intrahepatic interferon-␥ (IFN-␥) and interleukin-2 (IL-2) messenger RNA (mRNA) levels correlated with hepatic fibrosis and portal tract inflammation. 7 However, data regarding intrahepatic cytokine profiles in different forms of HCV-related allograft injury remain scarce. In the posttransplantation setting, immunosuppression may modify the patho...

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Intrahepatic cytokine profiles associated with posttransplantation hepatitis C virus[ndash ]related liver injury

Zekry

2002

Liver Transplantation

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“…There have been two studies that have also examined HCV quasispecies in cholestatic HCV [49,50]. Although, the titles of these two papers suggest different results, both show that during the cholestatic phase, quasispecies tend to be stable and not fluctuating as in hepatitic disease [51].…”

Section: Cholestatic Hcv Infectionmentioning

confidence: 99%