Direct oral anticoagulants and warfarin in patients with cirrhosis: a comparison of outcomes
- 作者列表："Davis, Kyle A.","Joseph, Joel","Nisly, Sarah A.
Anticoagulation management in patients with cirrhosis presents several challenges as a result of alterations in hemostasis. Historically vitamin k antagonists and low molecular weight heparins have been the agents of choice in this patient population. Direct oral anticoagulants (DOACs) may provide an alternative to traditional anticoagulant therapy. To evaluate the rate of major bleeding among patients receiving DOACs or warfarin with cirrhosis. A retrospective, observational, cohort study of adult patients admitted between January 2012 and July 2018 with diagnosis of cirrhosis receiving anticoagulation with DOAC or warfarin therapy was performed. Patients were stratified based on the receipt of a DOAC or warfarin. The primary endpoint was incidence of major bleeding at 90 days. Secondary endpoints included stroke or embolic event at 90 days as well as rehospitalization and mortality at 1 year. One hundred sixty-seven patients were included for analysis; of which 110 received warfarin and 57 received a DOAC. The most commonly used DOAC was apixaban (52.6%) followed by rivaroxaban (45.6%) and dabigratran (1.8%). The incidence of major bleeding was similar between warfarin and DOAC groups (9.1% vs. 5.2% p = 0.381). No difference in the rate of stroke or recurrent embolic event at 90 days was identified between the two groups (0% vs. 1.58% p = 0.341; 1.8% vs. 1.8% p = 0.731). In conclusion DOACs appear to be a safe alternative to warfarin in patients with mild to moderate cirrhosis. Further studies are warranted to confirm these findings.
肝硬化患者的抗凝管理由于止血的改变提出了几个挑战。历史上，维生素k 拮抗剂和低分子量肝素一直是该患者人群的首选药物。直接口服抗凝药 (DOACs) 可能提供传统抗凝治疗的替代方案。评估接受 DOACs 或华法林治疗的肝硬化患者的大出血发生率。对 2012年1月至 2018年7月收治的诊断为肝硬化接受 DOAC 或华法林抗凝治疗的成人患者进行了一项回顾性、观察性、队列研究。根据 DOAC 或华法林的接收情况对患者进行分层。主要终点是 90 天大出血的发生率。次要终点包括 90 天的卒中或栓塞事件以及 1 年时的再住院和死亡率。110 例患者被纳入分析; 其中例接受华法林治疗，57 例接受 DOAC 治疗。最常用的 DOAC 是阿哌沙班 (52.6%)，其次是利伐沙班 (45.6%) 和达比格拉坦 (1.8%)。华法林组和 DOAC 组的大出血发生率相似 (9.1% vs.5.2%，p = 0.381)。两组间 90 天卒中或栓塞事件复发率无差异 (0% vs.1.58% p = 0.341; 1.8% vs.1.8% p = 0.731)。总之，DOACs 似乎是轻中度肝硬化患者华法林的安全替代品。需要进一步的研究来证实这些发现。
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.