- 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
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.
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。
METHODS:BACKGROUND:Opioids are often prescribed for pain in cirrhosis and may increase the risk of hepatic encephalopathy (HE). AIMS:To assess the association between opioids and HE in patients with well-compensated cirrhosis. METHODS:We used the IQVIA PharMetrics (Durham, NC) database to identify patients aged 18-64 years with cirrhosis. We excluded patients with any decompensation event from 1 year before cirrhosis diagnosis to 6 months after cirrhosis diagnosis. Over the 6 months after cirrhosis diagnosis, we determined the duration of continuous opioid use and classified use into short term (1-89 days) and chronic (90-180 days). We assessed whether patients developed HE over the subsequent year (ie 6-18 months after cirrhosis diagnosis). We used a landmark analysis and performed multivariable Cox proportional hazards regression to assess associations between opioid use and HE, adjusting for relevant confounders. RESULTS:The cohort included 6451 patients with compensated cirrhosis, of whom 23.3% and 4.7% had short-term and chronic opioid prescriptions respectively. Over the subsequent year, HE occurred in 6.3% patients with chronic opioid prescriptions, 5.0% with short-term opioid prescriptions and 3.3% with no opioid prescriptions. In the multivariable model, an increased risk of HE was observed with short-term (adjusted hazard ratio, HR 1.44, 95% CI 1.07-1.94) and chronic opioid prescriptions (adjusted HR 1.83, 95% CI 1.07-3.12) compared to no opioid prescriptions. CONCLUSION:In this national cohort of privately insured patients with cirrhosis, opioid prescriptions were associated with the risk of incident HE. Opioid use should be minimised in those with cirrhosis and, when required, limited to short duration.
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.
METHODS:BACKGROUND:Spontaneous bacterial peritonitis (SBP) is a serious complication in patients with liver cirrhosis. In recent years, it has been postulated that the rate of multidrug-resistant organisms (MDROs) is increasing, especially in nosocomial SBP patients. Aim of the present work was to investigate this hypothesis and its possible clinical consequences. MATERIALS AND METHODS:One hundred and three culture-positive patients between 2007 and 2014 were compared with 81 patients between 2015 and 2017, to study the change of microbiological profiles and their clinical consequences. The cirrhosis patients with bacterascites requiring treatment were included as well. RESULTS:The most prevalent Gram-negative bacteria isolated from ascites were Enterobacterales (31.6%) and in Gram-positive pathogens Staphylococci (22.8%). There was a significant increase in MDROs (22.3% ICU 40.7%, P = .048), accompanied by an increased incidence of sepsis (from 21.4% to 37.0%, P = .021), hepatorenal syndrome (from 40.8% to 58.0%, P = .007) and the need of catecholamine therapy (from 21.4% to 38.8%, P = .036). Nosocomial origin correlated with higher MDRO proportion, more complications and lower antimicrobial susceptibility rates in 12 commonly used antibiotics. MDROs were confirmed as an isolated predictor for inpatient mortality and complications in multivariable logistic regression. CONCLUSIONS:The feeling in clinical practice that MDROs have increased in the last 11 years could be confirmed in our study in Munich, Germany. Nosocomial SBP correlated with significantly higher MDRO rates (nearly 50%) and complication rates. In our opinion, an antibiotic combination with comprehensive effect should be taken into account in nosocomial SBP patients in this region.