Long-term Outcomes and Survival in Moderate-Severe Portopulmonary Hypertension After Liver Transplant.
- 作者列表："Sadd CJ","Osman F","Li Z","Chybowski A","Decker C","Henderson B","Goss KN","Hammel LL","Runo JR
BACKGROUND:Portopulmonary hypertension is present in an estimated 5.3-8.5% of liver transplant candidates. Untreated, 5-year survival is estimated between 14-28%. Moderate-severe disease is a contraindication to liver transplant due to the high perioperative mortality, but patients optimized with pulmonary vasodilator therapy can become eligible for transplant. There is minimal data regarding posttransplant outcomes and ability to discontinue pulmonary vasodilator therapy posttransplant. METHODS:We performed a single-center retrospective analysis to evaluate long term outcomes of patients with moderate-severe POPH who were optimized with pulmonary vasodilator therapy, became eligible for liver transplant, and subsequently underwent transplant. We identified 24 patients optimized with pulmonary vasodilator therapy who underwent subsequent liver transplantation and 25 patients who were treated with pulmonary vasodilator therapy alone. RESULTS:In the transplanted cohort; 1-year survival from POPH diagnosis date: 95.8%, 3-year survival: 90.9%, and 5-year survival: 90.9%. Posttransplant; 1-year, 3-year, and 5-year survival was 86.9%. Among transplanted patients, 41.6% (10/24) were optimized with nonparenteral therapy. Following transplantation, 100% (14/14) of the surviving patients were able to discontinue parenteral therapy; median time: 7.2 months (IQR: 5.1, 8.9 months), while 61.9% (13/21) were able to discontinue pulmonary vasodilator therapy altogether; median time: 13.9 months (IQR: 5.1, 17.6 months). CONCLUSION:Patients who are optimized with pulmonary vasodilator therapy prior to liver transplant can have excellent long-term outcomes posttransplant. Oral pulmonary vasodilator therapy can be effective treatment to qualify a patient for transplant, and the majority are able to wean from pulmonary vasodilator therapy entirely posttransplant.
背景: 估计 5.3-8.5% 的肝移植候选者存在门脉性肺动脉高压。未经治疗的 5 年生存率估计在 14-28% 之间。由于围手术期死亡率高，中重度疾病是肝移植的禁忌症，但经肺血管扩张剂治疗优化的患者可以获得移植。关于移植后结果和移植后停止肺血管扩张剂治疗的能力的数据很少。 方法: 我们进行了一项单中心回顾性分析，以评估中重度 POPH 患者的长期预后，这些患者经过肺血管扩张剂治疗优化，有资格接受肝移植。随后接受了移植。我们确定了 24 例经肺血管扩张剂治疗优化后接受后续肝移植的患者和 25 例仅接受肺血管扩张剂治疗的患者。 结果: 在移植队列中; POPH 诊断日期的 1 年生存率: 95.8%，3 年生存率: 90.9%，5 年生存率: 90.9%。移植后; 1 年、 3 年和 5 年生存率为 86.9%。在移植患者中，41.6% (10/24) 采用非胃肠外治疗优化。移植后，100% (14/14) 的存活患者能够停止肠外治疗; 中位时间: 7.2 个月 (IQR: 5.1，8.9 个月)，而 61.9% (13/21) 能够完全停止肺血管扩张剂治疗; 中位时间: 13.9 个月 (IQR: 5.1，17.6 个月)。 结论: 肝移植前优化肺血管扩张剂治疗的患者可以在移植后获得良好的长期疗效。口服肺血管扩张剂治疗可以是使患者获得移植资格的有效治疗，大多数患者能够完全在移植后脱离肺血管扩张剂治疗。
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.