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酒精性肝病肝移植后免疫抑制方案与新发恶性肿瘤风险

Immunosuppressive regimen and risk for de novo malignancies after liver transplantation for alcoholic liver disease.

机构信息

Fédération des spécialités digestives, hôpital Edouard-Herriot, hospices civils de Lyon, 69437 Lyon cedex 03, France; Université Claude-Bernard Lyon 1, 69437 Lyon cedex 03, France.

Université Claude-Bernard Lyon 1, 69437 Lyon cedex 03, France; Service de biostatistique-bioinformatique, centre hospitalier Lyon-Sud, hospices civils de Lyon, 69437 Lyon cedex 03, France.

出版信息

Clin Res Hepatol Gastroenterol. 2018 Oct;42(5):427-435. doi: 10.1016/j.clinre.2018.04.011. Epub 2018 May 31.

Abstract

BACKGROUND AND AIMS

Long-term prognosis after liver transplantation for alcoholic liver disease is impaired because of the occurrence of de novo malignancies and recurrent disease on liver graft. The aim of the present retrospective study was to evaluate the risk of de novo malignancy and to identify the predictive factors in a large cohort of liver-transplanted patients with a long follow-up in the setting of alcoholic liver disease.

METHODS

All patients who underwent a first liver transplantation for alcoholic liver disease in our centre, from December 1985 to October 2010, and who survived more than 6 months were included. Survival, incidence of de novo malignancies and several clinical and biological parameters were studied.

RESULTS

The study population consisted in 368 patients (284 males, median age 52.6 years). The cumulative incidence of a first solid organ de novo malignancy after LT was 8.7% at 5 years, 22.3% at 10 years, 31.5% at 15 years, and 33.1% at 20 years. Tobacco use (both past and current) was associated with a significant increased risk of de novo solid organ malignancy (HR 3.35 and 4.62, respectively), whereas immunosuppressive regimen including mTOR inhibitors (mTORi) was associated with a decreased risk (post-transplant time under mTORi-including immunosuppressive regimen was significantly longer in patients who did not present de novo malignancy (10.6% vs. 2.3%, P=1.4×10)).

CONCLUSIONS

Our study provides additional evidence that de novo malignancies in alcoholic liver disease liver transplant patients is a major long-term complication, and that conversion from to an mTORi-including immunosuppressive regimen could reduce this risk.

摘要

背景与目的

由于肝移植后新发恶性肿瘤和肝移植物复发性疾病的发生,酒精性肝病患者的长期预后受损。本回顾性研究的目的是评估新发恶性肿瘤的风险,并在酒精性肝病患者的大队列中确定具有长期随访的患者的预测因素。

方法

纳入 1985 年 12 月至 2010 年 10 月期间在我院接受首次肝移植治疗酒精性肝病且存活时间超过 6 个月的所有患者。研究了生存、新发恶性肿瘤的发生率以及若干临床和生物学参数。

结果

该研究人群由 368 例患者(284 例男性,中位年龄 52.6 岁)组成。LT 后首次实体器官新发恶性肿瘤的累积发生率为 5 年时为 8.7%,10 年时为 22.3%,15 年时为 31.5%,20 年时为 33.1%。吸烟(包括既往和现在)与新发实体器官恶性肿瘤的风险显著增加相关(HR 分别为 3.35 和 4.62),而包括 mTOR 抑制剂(mTORi)的免疫抑制方案与风险降低相关(接受 mTORi 包括免疫抑制方案的移植后时间在未发生新发恶性肿瘤的患者中显著更长(10.6%比 2.3%,P=1.4×10))。

结论

我们的研究提供了额外的证据,表明酒精性肝病肝移植患者的新发恶性肿瘤是一个主要的长期并发症,并且从包含 mTORi 的免疫抑制方案转换可能会降低这种风险。

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