- 作者列表："Kitajima T","Nagai S","Segal A","Magee M","Blackburn S","Ellithorpe D","Yeddula S","Qadeer Y","Yoshida A","Moonka D","Brown K","Abouljoud MS
:Alcohol relapse after liver transplantation (LT) in patients with alcohol-related liver disease (ALD) is a major challenge. Although its association with pretransplant psychosocial factors was extensively studied, the impacts of posttransplant courses on alcohol relapse have not been well investigated. The aim of this study is to analyze peritransplant factors associated with posttransplant alcohol relapse in patients with ALD. This study evaluated 190 adult LT patients with ALD from 2013 to 2019. Risk factors for alcohol relapse were analyzed, focusing on posttransplant chronic complications, which were classified as Clavien-Dindo classification 3a or higher that lasted over 30 days. The posttransplant alcohol relapse rate was 13.7% (26/190) with a median onset time of 18.6 months after transplant. Multivariate Cox regression analysis revealed that posttransplant chronic complications were an independent risk factor for posttransplant alcohol relapse (hazard ratio [HR], 5.40; P = 0.001), along with psychiatric comorbidity (HR, 3.93; P = 0.001), history of alcohol relapse before LT (HR, 3.00; P = 0.008), and an abstinence period <1.5 years (HR, 12.05; P = 0.001). A risk prediction model was created using 3 pretransplant risk factors (psychiatric comorbidity, alcohol relapse before LT, and abstinence period <1.5 years). This model clearly stratified the risk of alcohol relapse into high-, moderate-, and low-risk groups (P < 0.001). Of the 26 patients who relapsed, 11 (42.3%) continued drinking, of whom 3 died of severe alcoholic hepatitis, and 13 (50.0%) achieved sobriety (outcomes for 2 patients were unknown). In conclusion, posttransplant chronic complications increased the risk of alcohol relapse. Recognition of posttransplant chronic complications in conjunction with the risk stratification model by pretransplant psychosocial factors would help with the prediction of posttransplant alcohol relapse.
: 酒精相关性肝病 (ALD) 患者肝移植 (LT) 后酒精复发是一大挑战。尽管对其与移植前心理社会因素的相关性进行了广泛研究，但移植后病程对酒精复发的影响尚未得到很好的研究。本研究的目的是分析与 ALD 患者移植后酒精复发相关的围手术期因素。本研究评估了 190 例成人 LT 患者 2013年至 2019年 ALD。分析酒精复发的危险因素，重点是移植后慢性并发症，分为 Clavien-Dindo 分类 3a 或更高，持续时间超过 30 天。移植后酒精复发率为 13.7% (26/190)，中位发病时间为移植后 18.6 个月。多变量 Cox 回归分析显示，移植后慢性并发症是移植后酒精复发的独立危险因素 (风险比 [HR]，5.40; P = 0.001)，以及伴有精神合并症 (HR，3.93; P = 0.001) 、 LT 前酒精复发史 (HR，3.00; P = 0.008) 和戒断期
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.