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肝移植受者潜伏性结核分枝杆菌感染的异烟肼预防:对移植肝脏有害吗?

Isoniazid prophylaxis in liver transplant recipient with latent tuberculosis: Is it harmful for transplanted liver?

机构信息

Department of Internal Medicine, School of Medicine, Shahid Faghihi Hospital, Shiraz University of Medical Sciences, Shiraz, Iran.

Abu Ali Sina Organ Transplant Center, Shiraz University of Medical Sciences, Shiraz, Iran.

出版信息

Transpl Infect Dis. 2022 Aug;24(4):e13849. doi: 10.1111/tid.13849. Epub 2022 Jun 1.

Abstract

BACKGROUND

Liver transplantation (LT) is considered the only treatment for patients with end-stage liver disease and, despite its incredible impacts on the patients' health status, places them in an immunocompromised state in which opportunistic infection would find a way to present. Latent tuberculosis infection (LTBI) is the most common form of TB and can be diagnosed through tuberculin skin test (TST) or Interferon-Gamma Release Assays (IGRA). LT recipients are at significant risk of TB activation. There is no strict guideline to approaching these cases though, in most centers, Isoniazid (INH) would be prescribed prophylactically. INH is a hepatotoxic medication and can have adverse effects on the transplanted liver. There is no consensus on this issue; therefore, we aimed to survey the potential hepatotoxic effects of INH among LT recipients in Shiraz, Iran.

METHODS

A retrospective cohort study was conducted among LT candidates and recipients at Abu Ali Sina Organ Transplantation Center between 1993 and 2019. All the cases underwent TST and chest X-ray to detect LTBI. All the LTBI were treated with INH from 6-9 months and followed by the level of liver enzymes for quick detection of hepatotoxicity. A control group was selected among LT recipients and matched for age, gender, MELD score, and donor age.

RESULTS

Among 4895 medical records reviewed, 55 (1.12%) cases had LTBI. Neither INH-related hepatotoxicity, nor signs and symptoms that were suspicious to TB reactivation were reported. Overall, three deaths were reported, two because of myocardial infarction and one due to pneumonia. Ten patients (18.2%) experienced acute rejection as confirmed with pathology and responded to methylprednisolone. Aspartate aminotransferase (AST) was diminished from pre-LT time to the first time after transplantation; after that, it showed a steady pattern. Meanwhile, Alanine transaminase (ALT) was constant before and one stage later and decreased after that. Statistical analyses only showed significant changes in the total bilirubin titer between the case and control groups.

CONCLUSION

This survey showed prophylactic management of LTBI with INH in LT candidates and recipients was associated with no hepatotoxicity or related death. It seems that INH prophylaxis is safe in LT settings and can efficiently prevent TB activation; however, careful monitoring for adverse effects and liver enzymes elevation is highly recommended.

摘要

背景

肝移植(LT)被认为是治疗终末期肝病患者的唯一方法,尽管它对患者的健康状况产生了巨大影响,但使患者处于免疫功能低下的状态,使机会性感染有机会出现。潜伏性结核感染(LTBI)是最常见的结核形式,可以通过结核菌素皮肤试验(TST)或干扰素-γ释放试验(IGRA)进行诊断。LT 受者发生 TB 激活的风险显著增加。尽管大多数中心都会预防性开具异烟肼(INH),但目前尚无针对这些病例的严格指南。INH 是一种肝毒性药物,会对移植肝脏产生不良反应。在这个问题上没有共识;因此,我们旨在调查伊朗设拉子 LT 受者中 INH 的潜在肝毒性作用。

方法

对 1993 年至 2019 年阿布阿里·西纳器官移植中心的 LT 候选人和受者进行了回顾性队列研究。所有病例均接受 TST 和胸部 X 射线检查以检测 LTBI。所有 LTBI 均接受 6-9 个月的 INH 治疗,并检测肝酶水平以快速检测肝毒性。在 LT 受者中选择了一个对照组,并按年龄、性别、MELD 评分和供体年龄进行匹配。

结果

在审查的 4895 份病历中,有 55 例(1.12%)患有 LTBI。均未报告 INH 相关肝毒性或提示 TB 再激活的症状和体征。总体而言,报告了 3 例死亡,其中 2 例死于心肌梗死,1 例死于肺炎。10 例(18.2%)患者经病理学证实发生急性排斥反应,并对甲基强的松龙有反应。天冬氨酸转氨酶(AST)在 LT 前和移植后第一次检查时降低;之后,它呈现出稳定的模式。同时,丙氨酸转氨酶(ALT)在之前和一个阶段后保持不变,之后降低。统计分析仅显示病例组和对照组之间总胆红素滴度有显著变化。

结论

本调查显示,LT 候选者和受者中 LTBI 的预防性 INH 管理与肝毒性或相关死亡无关。INH 预防似乎在 LT 环境中是安全的,可以有效预防 TB 激活;然而,强烈建议密切监测不良反应和肝酶升高。

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