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Opioid prescriptions are associated with hepatic encephalopathy in a national cohort of patients with compensated cirrhosis.
在国家代偿性肝硬化患者队列中,阿片类药物处方与肝性脑病相关。
- 影响因子:4.08
- DOI:10.1111/apt.15639
- 作者列表:"Moon AM","Jiang Y","Rogal SS","Tapper EB","Lieber SR","Barritt AS 4th
- 发表时间:2020-01-21
Abstract
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.
摘要
背景: 阿片类药物通常用于治疗肝硬化疼痛,并可能增加肝性脑病 (HE) 的风险。 目的: 评估阿片类药物与代偿性肝硬化患者 HE 之间的相关性。 方法: 我们使用 IQVIA PharMetrics (Durham,NC) 数据库来确定 18-64 岁肝硬化患者。我们排除了从肝硬化诊断前 1 年到肝硬化诊断后 6 个月出现任何失代偿事件的患者。在肝硬化诊断后的 6 个月内,我们确定了持续使用阿片类药物的持续时间,并将使用分为短期 (1-89 天) 和慢性 (90-180 天)。我们评估了患者在随后一年内 (即肝硬化诊断后 6-18 个月) 是否发生 HE。我们使用了里程碑式分析,并进行了多变量 Cox 比例风险回归,以评估阿片类药物使用与 HE 之间的相关性,调整了相关混杂因素。 结果: 该队列包括 6451 例代偿性肝硬化患者,其中 23.3% 和 4.7% 分别有短期和慢性阿片类药物处方。在随后的一年中,他发生在 6.3% 例慢性阿片类药物处方的患者中,5.0% 例短期阿片类药物处方,3.3% 例没有阿片类药物处方。在多变量模型中,观察到短期 (校正风险比,HR 1.44,95% CI 1.07-1.94) 和慢性阿片类药物处方 (校正 HR 1.83, 95% CI 1.07-3.12) 与无阿片类药物处方相比。 结论: 在这个私人保险肝硬化患者的全国队列中,阿片类药物处方与事件 HE 的风险相关。肝硬化患者应尽量减少阿片类药物的使用,并且在需要时,限制在短期内。
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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.