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肿瘤坏死因子-α拮抗剂致急性肝衰竭:4 例报告并文献复习。

Acute Liver Failure from Tumor Necrosis Factor-α Antagonists: Report of Four Cases and Literature Review.

机构信息

Division of Gastroenterology (Liver Unit), Department of Critical Care Medicine, University of Alberta, 1-40 Zeidler-Ledcor Building, Edmonton, AB, T6G-2X8, Canada.

Department of Surgery, University of Alberta, Edmonton, Canada.

出版信息

Dig Dis Sci. 2018 Jun;63(6):1654-1666. doi: 10.1007/s10620-018-5023-6. Epub 2018 Mar 21.

Abstract

BACKGROUND

Tumor necrosis factor-α antagonists (anti-TNF-α) have been associated with drug-induced liver injury. However, cases of anti-TNF-α-associated acute liver failure have only been rarely reported.

AIMS

To identify cases of anti-TNF-α-associated acute liver failure and evaluate patterns of liver injury and common characteristics to the cases.

METHODS

The United States Acute Liver Failure Study Group database was searched from 1998 to 2014. Four subjects were identified. A PubMed search for articles that reported anti-TNF-α-associated acute liver failure identified five additional cases.

RESULTS

The majority of individuals affected were female (eight of nine cases). Age of individual ranged from 20 to 53 years. The most common anti-TNF-α agent associated with acute liver failure was infliximab (n = 8). The latency between initial drug exposure and acute liver failure ranged from 3 days to over a year. Of the nine cases, six required emergency LT. Liver biopsy was obtained in seven cases with a preponderance toward cholestatic-hepatitic features; none showed clear autoimmune features.

CONCLUSIONS

Anti-TNF-α-associated acute liver failure displays somewhat different characteristics compared with anti-TNF-α-induced drug-induced liver injury. Infliximab was implicated in the majority of cases. Cholestatic-hepatitic features were frequently found on pre-transplant and explant histology.

摘要

背景

肿瘤坏死因子-α 拮抗剂(抗 TNF-α)与药物性肝损伤有关。然而,抗 TNF-α 相关性急性肝衰竭的病例却很少有报道。

目的

确定抗 TNF-α 相关性急性肝衰竭的病例,并评估肝损伤的模式和这些病例的共同特征。

方法

从 1998 年到 2014 年,检索美国急性肝衰竭研究组数据库。确定了 4 例病例。通过 PubMed 检索报告抗 TNF-α 相关性急性肝衰竭的文章,又确定了另外 5 例病例。

结果

大多数受影响的个体为女性(9 例中的 8 例)。个体年龄从 20 岁到 53 岁不等。与急性肝衰竭最相关的抗 TNF-α 药物是英夫利昔单抗(n = 8)。初次药物暴露与急性肝衰竭之间的潜伏期从 3 天到 1 年以上不等。在 9 例病例中,有 6 例需要紧急进行肝移植。7 例病例进行了肝活检,主要表现为胆汁淤积性肝炎特征;均无明确的自身免疫特征。

结论

与抗 TNF-α 诱导的药物性肝损伤相比,抗 TNF-α 相关性急性肝衰竭具有一些不同的特征。英夫利昔单抗与大多数病例有关。在移植前和肝移植组织学中经常发现胆汁淤积性肝炎特征。

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