Immunological dysfunction during or after antiviral therapy for recurrent hepatitis C reduces graft survival.
Immunological dysfunction during or after antiviral therapy for recurrent hepatitis C reduces graft survival.
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DOI：
10.1007/s12072-013-9436-1
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发表时间：
2013-10
影响因子：
6.6
通讯作者：
Lok, Anna S.
中科院分区：
文献类型：
--
作者：
Sharma, Pratima;Hosmer, Amy;Appelman, Henry;McKenna, Barbara;Jafri, Mohammad S.;Sullivan, Patricia;Fontana, Robert J.;Lok, Anna S.
与非移植患者相比，聚乙二醇干扰素和利巴韦林（PEGIFN/RBV）治疗肝移植（LT）后复发的丙型肝炎与较低的持续病毒学应答（SVR）率以及更频繁的副作用相关。我们的目的是确定复发性丙型肝炎患者在PEG-IFN/RBV治疗期间或之后发生免疫功能障碍（ID）的LT受者的发病率和临床特征，并评估其对患者和移植物存活的影响。从1/00至12/08，用PEG-IFN/RBV治疗了74例具有丙型肝炎组织学复发的死亡供体LT受体。ID定义为活检证实的排斥反应或中度浆细胞肝炎。患者随访至死亡、re-LT或2011年9月30日。12例患者（16%）有ID，8例（10.7%）有胆汁淤积而无ID，而54例在PEG-IFN/RBV治疗期间或停止后无ID/胆汁淤积。活检证实的急性细胞排斥反应之前（风险比= 4.87，p = 0.009）和类型的免疫抑制在开始的时候的PEG-IFN/RBV是唯一的独立预测ID。患者谁是他克莫司在开始的时候PEG-IFN/RBV有一个显着较低的风险ID相比，那些谁是环孢霉素（HR 0.254，p = 0.023）。与无ID/胆汁淤积的患者相比，ID患者的SVR率（25 vs. 54%，p = 0. 18）和移植物衰竭率（33 vs. 4%，p = 0. 004）有降低的趋势。在PEG-IFN/RBV治疗复发性丙型肝炎期间或之后，ID是常见的，并且经常与移植物存活率降低相关，趋向于低SVR率。在PEG-IFN/RBV治疗期间或之后，对活检患者，特别是接受基于环孢素的免疫抑制的患者进行低阈值的肝脏生物化学仔细监测，可能会改善这些患者的结局。
Pegylated interferon and ribavirin (PEGIFN/RBV) therapy for recurrent hepatitis C after liver transplantation (LT) is associated with a lower sustained virological response (SVR) rate as well as more frequent side effects compared to non-transplant patients. We aimed to determine the incidence and clinical characteristics of LT recipients with recurrent hepatitis C who developed immunological dysfunction (ID) during or after PEG-IFN/RBV therapy and to assess its impact on patient and graft survival. Seventy-four deceased donor LT recipients with histological recurrence of hepatitis C were treated with PEG-IFN/RBV from 1/00 to 12/08. ID was defined as biopsy-proven rejection or moderate plasma cell hepatitis. Patients were followed up until death, re-LT or 30 September 2011. Twelve patients (16 %) had ID, 8 (10.7 %) had cholestasis without ID, while 54 had no ID/cholestasis during or after discontinuation of PEG-IFN/RBV therapy. Biopsy-proven acute cellular rejection prior to (hazard ratio = 4.87, p = 0.009) and type of immunosuppression at the time of initiation of PEG-IFN/RBV were the only independent predictors of ID. Patients who were on tacrolimus at the time of initiation of PEG-IFN/RBV had a significantly lower risk of ID compared to those who were on cyclosporine (HR 0.254, p = 0.023). Patients with ID had a trend toward a lower SVR rate (25 vs. 54 %, p = 0.18) and a significantly higher rate of graft failure (33 vs. 4 %, p = 0.004) compared to patients with no ID/cholestasis. ID is common during or after PEG-IFN/RBV therapy for recurrent hepatitis C and frequently associated with decreased graft survival, trending toward low rates of SVR. Careful monitoring of liver biochemistries during or after PEG-IFN/RBV therapy with a low threshold to biopsy patients and particularly those receiving cyclosporine-based immunosuppression may improve outcomes in these patients.
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