Model for End-stage Liver Disease-Lactate and Prediction of Inpatient Mortality in Patients with Chronic Liver Disease.
- 作者列表："Sarmast N","Ogola GO","Kouznetsova M","Leise M","Bahirwani R","Maiwall R","Tapper E","Trotter J","Bajaj J","Thacker LR","Tandon P","Wong F","Reddy R","O'Leary JG","Masica A","Modrykamien AM","Kamath PS","Asrani SK
BACKGROUND & AIMS:As compared to other chronic diseases, patients with chronic liver disease (CLD) have significantly higher inpatient mortality; accurate models to predict inpatient mortality are lacking. Serum lactate (LA) may be elevated in patients with CLD due to both tissue hypoperfusion as well as decreased lactate clearance. We hypothesized that a parsimonious model consisting of Model for End-stage Liver Disease (MELD) and LA at admission may predict inpatient mortality in patients with CLD. APPROACH & RESULTS:We examined all CLD patients in two large and diverse healthcare systems in Texas (North Texas, NTX and Central Texas, CTX) between 2010-2015. We developed (n=3,588) and validated (n=1,804) a model containing MELD and LA measured at time of hospitalization. We further validated the model in a second cohort of 14 tertiary care hepatology centers that prospectively enrolled non-elective hospitalized patients with cirrhosis (n=726). MELD-LA was an excellent predictor of inpatient mortality in development (c-statistic =0.81, 95% CI 0.79-0.82) and both validation cohorts (CTX cohort, c=0.85, 95% CI 0.78-0.87; multicenter cohort c=0.82, 95% CI 0.74-0.88). MELD-LA performed especially well in patients with specific cirrhosis diagnoses (c=0.84, 95% CI 0.81-0.86) or sepsis (c=0.80, 95% CI 0.78-0.82). For MELD score 25, inpatient mortality was 11.2% (LA=1 mmol/L), 19.4% (LA=3 mmol/L), 34.3% (LA=5 mmol/L) and >50% (LA >8 mmol/L). A linear increase (p<0.01) was seen in MELD-LA and increasing number of organ failures. Overall, use of MELD-LA improved the risk prediction in 23.5% of the patients as compared to MELD model alone. CONCLUSION:MELD-LA is an early and objective predictor of inpatient mortality and may serve as a novel model for risk assessment and guide therapeutic options.
背景与目的: 与其他慢性疾病相比，慢性肝病 (CLD) 患者的住院死亡率显著升高; 缺乏准确的模型来预测住院死亡率。CLD 患者血清乳酸 (LA) 可能由于组织灌注不足以及乳酸清除率降低而升高。我们假设由终末期肝病模型 (MELD) 和入院时 LA 组成的简约模型可以预测 CLD 患者的住院死亡率。 方法和结果: 我们在 2010-2015 之间检查了德克萨斯州两个大型和多样化医疗系统 (北德克萨斯，NTX 和德克萨斯州中部，CTX) 中的所有 CLD 患者。我们开发 (n = 3,588) 并验证 (n = 1,804) 包含住院时测量的 MELD 和 LA 的模型。我们进一步在 14 个三级保健肝病中心的第二个队列中验证了该模型，这些中心前瞻性地招募了非择期住院肝硬化患者 (n = 726)。MELD-LA 是发展中的住院患者死亡率 (c-statistics = 0.81，95% CI 0.79-0.82) 和两个验证队列 (CTX 队列，c = 0.85, 95% CI 0.78-0.87; 多中心队列 c = 0.82，95% CI 0.74-0.88)。MELD-LA 在特定肝硬化诊断 (c = 0.84，95% CI 0.81-0.86) 或脓毒症 (c = 0.80，95% CI 0.78-0.82) 患者中的表现尤其良好。MELD 评分 25 分，住院死亡率为 11.2% (LA = 1 mmol/L)，19.4% (LA = 3 mmol/L)，34.3% (LA = 5 mmol/L) 和> 50% (LA> 8 mmol/L)。线性增加 (p
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.