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Metamizole: an underrated agent causing severe idiosyncratic drug-induced liver injury.

安乃近: 一种被低估的药物,引起严重的特异质药物性肝损伤。

  • 影响因子:3.57
  • DOI:10.1111/bcp.14254
  • 作者列表:"Sebode M","Reike-Kunze M","Weidemann S","Zenouzi R","Hartl J","Peiseler M","Liwinski T","Schulz L","Weiler-Normann C","Sterneck M","Lohse AW","Schramm C
  • 发表时间:2020-02-20
Abstract

AIMS:Drug-induced liver injury (DILI) is a heterogenous entity leading to liver damage. We have analysed the frequency, biochemical and histological patterns and clinical courses of DILI cases due to metamizole at our tertiary care centre in Hamburg, Germany. METHODS:Consecutive patients with DILI who presented to our clinic were analysed retrospectively. Causes of acute hepatitis other than DILI were excluded. RESULTS:154 DILI cases were admitted to our centre from 2008 to 2017. After phenprocoumon, metamizole was the second most frequent putative agent causing DILI (23 of all 154 DILI cases, 14,9%). The biochemical pattern on admission of metamizole-induced DILI cases was hepatocellular with median levels of ALT (779U/l, 64-3532U/l) by far exceeding median ALP levels (131U/l, 42-578U/l). In 17 of the 23 cases (74%) liver biopsy was performed. Moderate to severe inflammatory histological activity and severe centrilobular necrosis (>30%) was present in 76.5% and 35.3%, respectively. Metamizole was involved in two DILI cases progressing to acute liver failure, then receiving liver transplantation and still alive at time of assessment. Our data were supported by re-exposure in four patients. Furthermore, a database search for metamizole-induced liver injury in the European Medicines Agency's (EMA) database identified about 300 reports on suspected metamizole-induced DILI in Europe. CONCLUSION:Elevation of liver enzymes or acute liver failure are not mentioned in the German drug label of metamizole as potential side effects. Our study reveals that in Germany and Europe, metamizole is a frequent and underrated agent causing DILI.

摘要

目的: 药物性肝损伤 (DILI) 是一种导致肝损伤的异质性实体。我们分析了德国汉堡三级医疗中心安乃近所致 DILI 病例的频率、生化和组织学模式及临床病程。 方法: 对就诊于本诊所的连续 DILI 患者进行回顾性分析。排除 DILI 以外的急性肝炎原因。 结果: 本中心 2008年至 2017年共收治 DILI 病例 154 例。在 phenprocoumon 之后,安乃近是引起 DILI 的第二常见假定药物 (所有 154 例 DILI 中 23 例,9%)。安乃近诱导的 DILI 病例入院时的生化模式为肝细胞,ALT 中位数水平 (779U/l,64-3532U/l) 远远超过 ALP 中位数水平 (131U/l, 42-578U/l)。23 例中 17 例 (74%) 行肝活检。中度至重度炎症组织学活性和重度小叶中心坏死 (> 30%) 分别为 76.5% 和 35.3%。2 例 DILI 进展为急性肝衰竭,随后接受肝移植,评估时仍存活。我们的数据得到了 4 例患者再暴露的支持。此外,在欧洲药品管理局 (EMA) 数据库中搜索安乃近引起的肝损伤的数据库,发现了约 300 份关于欧洲疑似安乃近引起的 DILI 的报告。 结论: 安乃近的德国药物标签中没有提到肝酶升高或急性肝衰竭是潜在的副作用。我们的研究揭示,在德国和欧洲,安乃近是引起 DILI 的常见和被低估的药剂。

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翻译标题与摘要 下载文献
影响因子:3.87
发表时间:2020-02-01
DOI:10.1111/liv.14321
作者列表:["Chen VL","Chen Y","Du X","Handelman SK","Speliotes EK"]

METHODS:BACKGROUND AND AIMS:Cirrhosis is characterized by extensive fibrosis of the liver and is a major cause of liver-related mortality. Cirrhosis is partially heritable but genetic contributions to cirrhosis have not been systemically explored. Here, we carry out association analyses with cirrhosis in two large biobanks and determine the effects of cirrhosis associated variants on multiple human disease/traits. METHODS:We carried out a genome-wide association analysis of cirrhosis as a diagnosis in UK BioBank (UKBB; 1088 cases vs. 407 873 controls) and then tested top-associating loci for replication with cirrhosis in a hospital-based cohort from the Michigan Genomics Initiative (MGI; 875 cases of cirrhosis vs. 30 346 controls). For replicating variants or variants previously associated with cirrhosis that also affected cirrhosis in UKBB or MGI, we determined single nucleotide polymorphism effects on all other diagnoses in UKBB (PheWAS), common metabolic traits/diseases and serum/plasma metabolites. RESULTS:Unbiased genome-wide association study identified variants in/near PNPLA3 and HFE, and candidate variant analysis identified variants in/near TM6SF2, MBOAT7, SERPINA1, HSD17B13, STAT4 and IFNL4 that reproducibly affected cirrhosis. Most affected liver enzyme concentrations and/or aspartate transaminase-to-platelet ratio index. PheWAS, metabolic trait and serum/plasma metabolite association analyses revealed effects of these variants on lipid, inflammatory and other processes including new effects on many human diseases and traits. CONCLUSIONS:We identified eight loci that reproducibly associate with population-based cirrhosis and define their diverse effects on human diseases and traits.

翻译标题与摘要 下载文献
影响因子:2.57
发表时间:2020-02-01
DOI:10.1111/eci.13198
作者列表:["Li H","Wieser A","Zhang J","Liss I","Markwardt D","Hornung R","Neumann-Cip AC","Mayerle J","Gerbes A","Steib CJ"]

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