Successful switch from inhalative iloprost to oral bosentan in portopulmonary hypertension associated with liver cirrhosis

Portopulmonary hypertension (PPHTN) is a rare complication of liver cirrhosis. Prostanoids have been shown to be effective in the treatment of PPHTN and have been used as a bridge to orthotopic liver transplantation. However, inhibition of platelet aggregation might be a limitation of prostacyclin therapy in patients with end-stage liver disease having an increased risk of bleeding from esophageal varices. The effect of oral bosentan, a dual endothelin-receptor antagonist in the reversal of PPHTN, is still unclear. We report a case of PPHTN (mean pulmonary artery pressure [mPAP] of 51 mmHg) that was successfully switched from inhalative iloprost to oral bosentan therapy. Hemodynamic and symptomatic improvements were maintained after a 12-month long-term treatment with inhalative iloprost as well as after single oral bosentan therapy. This is the first reported case of a successful switch from therapy with an inhalative prostacyclin analogue to oral bosentan in a patient suffering from PPHTN. Thus, oral bosentan therapy might be a promising new option for patients suffering from PPHTN.     

The direct and indirect effects of vancomycin-resistant enterococci colonization in liver transplant candidates and recipients

Introduction: Vancomycin-resistant enterococci (VRE) colonization and subsequent infection results in increased morbidity, mortality and use of health-care resources. The burden of VRE colonization in liver transplant candidates and recipients is significant. VRE colonization is a marker of gut dysbiosis and its impact on the microbiota-liver axis, may negatively affect graft function and result in negative outcomes pre- and post-transplantation.

Areas covered: In this article we describe the epidemiology of VRE colonization, risk factors for VRE infection, health-care costs associated with VRE, with a focus on the impact of VRE colonization on liver transplant recipients’ fecal microbiota, the therapeutic strategies for VRE decolonization and proposed pathophysiologic mechanisms of VRE colonization in liver transplant recipients.

Expert opinion: VRE colonization results in a significant loss of bacterial microbiome diversity. This may have metabolic consequences, with low production of short-chain fatty acids which may, in turn, result in immune dysregulation. As antibiotics have failed to decolonize the gut, alternative strategies such as fecal microbiota transplantation (FMT), stimulation of intestinal antimicrobial peptides and phage therapy warrants future studies.     

Presence of auto-antibodies in patients who are candidates for heart transplant

A preliminary research, in order to evaluate by immunofluorescent technique the prevalence of heart specific and non specific autoantibodies, has been performed on a population of 58 cardiac patients, allograft applying. Two other populations (cardiac patients not allograft candidates, and healthy blood donors), were also tested as controls. Significant differences in the presence of specific anti-heart antibodies were revealed among the three populations (89.7, 39.1 and 10%, respectively). No relevant correlation has appeared with the antibody titer between the two groups of cardiac patients.     

Intracoronary stem cell infusion in heart transplant candidates

The stem cell transplantation is emerging as a potential therapeutic modality for patients with heart failure. It has been demonstrated that intracoronary stem cell transplantation had beneficial effects on left ventricular perfusion and contractile functions. We hypothesized that patients with end-stage ischemic cardiomyopathy, who are candidates for heart transplantation, could also benefit from autologous intracoronary stem cell transplantation. We performed a prospective, open-labeled study in 10 patients with end-stage ischemic cardiomyopathy, who were on the waiting list for heart transplantation. Each patient received bone marrow-derived mononuclear cell infusion via balloon catheter in the target vessel, which had been revascularized by percutaneous intervention and was patent before the procedure. Clinical and laboratory evaluations, a treadmill exercise test, echocardiography, and single photon emission tomography (SPECT) were performed to the patients at baseline and 6 months after stem cell infusion. At 6-month follow-up of the eight patients who were able to complete the study, we revealed a significant increase in ejection fraction (from 30.0 +/- 6.6% to 36.2 +/- 7.3%; p = 0.001) in echocardiographic evaluation. SPECT evaluation also displayed a reduction in infarct area (50.4 +/- 16.1% to 44.1 +/- 12.5%; p = 0.003). Both myocardial oxygen consumption (p = 0.001) and metabolic equivalents (p = 0.001) were significantly increased at 6-month follow-up. These results demonstrate that intracoronary stem cell transplantation ameliorates heart failure symptoms and improves left ventricular function and perfusion. Therefore intracoronary stem cell transplantation may be used as an alternative treatment option for heart transplant candidates.     

Immunoadsorption: a novel treatment for sensitized kidney transplant candidates

Sensitized patients frequently have a positive crossmatch against kidneys available for transplant. A positive crossmatch precludes transplantation in most cases because it is usually predictive of rejection after transplant. Immunoadsorption is an extracorporeal treatment combined with immunosuppression to decrease sensitization in patients and thereby enable transplantation. This article discusses sensitization, its detection, and the benefits of immunoadsorption.     

钆贝葡胺增强MRC与3D-SPACE-T2WI-MRC显示活体肝移植供体胆管的比较

目的 比较钆贝葡胺(Gd-BOPTA)CE-MRC与3D-SPACE-T2WI-MRC对活体肝移植供体胆管解剖及变异的显示.方法 32名肝移植供体,术前接受Gd-BOPTA CE-MRC与3D-SPACE-T2WI-MRC.以术中胆管造影为标准,分析并比较两种方法诊断胆管变异情况.结果 两种方法对胆总管、肝总管、左肝管及右肝管的显示差异有统计学意义(P＜0.05),CE-MRC优于3D-SPACE-T2WI-MRC;对胆囊管,左前、后肝管,右前、后肝管及3级以上胆管的显示差异无统计学意义(P＞0.05).术中胆管造影诊断胆管变异17例,3D-SPACE-T2WI-MRC诊断14例,CE-MRC诊断15例,两者联合诊断17例.结论 3D-SPACE-T2EI-MRC与CE-MRC均可用于评估术前肝移植供体胆管解剖,CE-MRC对部分胆管的显示优于3D-SPACE-T2WI-MRC,二者联合应用效果更佳.     

肝移植受者等待供肝期间认知行为干预及效果评价

背景：随着肝移植技术的不断发展和完善,等待供肝期和肝移植后的患者也不断增多,由于其对手术的恐惧和对移植后康复的担心等原因,其身心处于应激状态,大多存在着各种精神心理障碍,影响着患者的康复。目前对于肝移植患者心理问题的研究多集中在肝移植后,而对于等待供肝期患者的心理状态没有得到足够的评估和干预。目的：探讨适合肝移植受者等待供肝期间认知行为的干预模式,评价其改善患者身心状态的效果。方法：将12例进行移植前评估的肝移植受者随机分为实验组和对照组各6例,对照组接受常规治疗和护理,实验组除接受常规治疗和护理外还接受认知行为干预。在两组患者入院时、入院1周和3周时分别采用Zung焦虑自评量表进行评定,并测量两组生命体征的变化。结果与结论：入院1周和3周时实验组Zung焦虑自评量表得分低于对照组,随干预时间的延长,Zung焦虑自评量表得分逐渐降低;入院3周时实验组收缩压低于对照组,但两组舒张压比较和组内不同时间点比较差异无显著性意义;入院1周和3周时实验组心率值低于对照组;入院3周时实验组呼吸频率低于同期对照组。结果可见认知行为干预可降低肝移植受者等待供肝期间的焦虑恐惧程度,保持生命体征平稳,具有较好的可行性和有效性。     

Verbal learning in cardiac transplant candidates: A preliminary report

Previous research has found that cardiac transplant candidates demonstrate impaired verbal learning, as measured by the Rey Auditory Verbal Learning Test (AVLT). The present study investigated verbal learning in transplant candidates to provide preliminary data on the nature of the verbal learning impairment. Two samples of cardiac transplant candidates and one sample of heart-lung transplant candidates received the California Verbal Learning Test (CVLT) as part of a precandidacy psychological evaluation. The three samples were grouped according to transplant type and ejection fraction (EF): 6 heart-lung transplant candidates (mean EF=62.50), 11 high-EF heart transplant candidates (mean EF=32.10), and 12 low-EF heart transplant candidates (mean EF=14.20). All three samples evidenced impaired learning ability, relative to age-matched norms from the CVLT manual. A repeated-measure ANOVA found main effects on group and trial (1–5) factors and a group x trial interaction. Univariate ANOVAs on the CVLT revealed significant group differences on short-delay free recall and cued recall, semantic clustering, primary recall, and middle recall. Post hoc analyses found the low-EF heart transplant sample to be impaired on the CVLT measures compared to the other two samples. The pattern of results indicates that cardiac transplant candidates evidence verbal learning deficits and that patients' EF relates to the extent of their verbal learning ability.     

Selection criteria for liver transplant donors

As the number of successful liver transplants has increased, the demand for donors has outpaced the supply. Approximately 25% of patients die awaiting an appropriate donor. Current criteria for assessing potential donors need to be closely examined. Fifty-six potential donors were evaluated by our transplant team by utilizing standard liver function tests (LFT's)-SGOT, SGPT, bilirubin. Additionally, a lidocaine metabolism test was performed by giving a 1 mg/kg IV dose of lidocaine over 1 minute and measuring the accumulation of the major metabolite monoethylglycinxylidide (MEGX) at 15 minutes by fluorescent polarization immunoassay (Abbott Diagnostics, Abbott Park, IL). Previous work has suggested that a MEGX less than 50 ng/mL is associated with initial non-function. Thirty-four donors were transplanted (group I) and all had initial function (all MEGX values were greater than 50). Twenty-two donors (39%) were judged unacceptable (group II) by our transplant team and by outside centers based upon one of the following criteria: II A) elevated LFT's--8, 11 B) donor age--5, II C) donor instability--4, II D) no available recipient--3, II E) miscellaneous--2. Standard LFT's were not statistically different in the donors used and in those not used when excluding category II A. Six of seven donors excluded in group I had acceptable MEGX values indicating they may have been transplantable. Ten of 12 patients excluded in groups II B-D had normal LFT's and nine of 12 had acceptable MEGX values indicating they may have been transplantable also. In this era of organ shortage, a reevaluation of donor selection criteria utilizing new tests like MEGX may be necessary to meet the increased need.     

Novel serum biomarker candidates for liver fibrosis in hepatitis C patients

BACKGROUND: Liver biopsy is currently the gold standard for assessing liver fibrosis, and no reliable noninvasive diagnostic approach is available. Therefore a suitable serologic biomarker of liver fibrosis is urgently needed. METHODS: We used a proteomics method based on 2-dimensional gel electrophoresis to identify potential fibrosis biomarkers. Serum samples from patients with varying degrees of hepatic scarring induced by infection with the hepatitis C virus (HCV) were analyzed and compared with serum from healthy controls. RESULTS: We observed the most prominent differences when we compared serum samples from cirrhotic patients with healthy control serum. Inter-alpha-trypsin inhibitor heavy chain H4 (ITIH4) fragments, alpha1 antichymotrypsin, apolipoprotein L1 (Apo L1), prealbumin, albumin, paraoxonase/arylesterase 1, and zinc-alpha2-glycoprotein were decreased in cirrhotic serum, whereas CD5 antigen-like protein (CD5L) and beta2 glycoprotein I (beta2GPI) were increased. In general, alpha2 macroglobulin (a2M) and immunoglobulin components increased with hepatic fibrosis, whereas haptoglobin and complement components (C3, C4, and factor H-related protein 1) decreased. Novel proteins associated with HCV-induced fibrosis included ITIH4 fragments, complement factor H-related protein 1, CD5L, Apo L1, beta2GPI, and thioester-cleaved products of a2M. CONCLUSIONS: Assessment of hepatic scarring may be performed with a combination of these novel fibrosis biomarkers, thus eliminating the need for liver biopsy. Further evaluation of these candidate markers needs to be performed in larger patient populations. Diagnosis of fibrosis during early stages will allow early treatment, thereby preventing fibrosis progression.     

Coronary artery disease is common in nonuremic, asymptomatic type 1 diabetic islet transplant candidates

OBJECTIVE: Coronary artery disease (CAD) is the most common cause of death in patients with type 1 diabetes. Asymptomatic CAD is common in uremic diabetic patients, but its prevalence in nonuremic type 1 diabetic patients is unknown. The prevalence of CAD was determined by coronary angiography and the performance of noninvasive cardiac investigation evaluated in type 1 diabetic islet transplant (ITX) candidates with preserved renal function. RESEARCH DESIGN AND METHODS: A total of 60 consecutive type 1 diabetic ITX candidates (average age 46 years [mean 24-64], 23 men, and 47% ever smokers) underwent coronary angiography, electrocardiographic stress testing (EST), and myocardial perfusion imaging (MPI) in a prospective cohort study. CAD was indicated on angiography by the presence of stenoses >50%. Models to predict CAD were examined by logistic regression. RESULTS: Most subjects (53 of 60) had no history or symptoms of CAD; 23 (43%) of these asymptomatic subjects had stenoses >50%. CAD was associated with age, duration of diabetes, hypertension, and smoking. Although specific, EST and MPI were not sensitive as predictors of CAD on angiography (specificity 0.97 and 0.93, sensitivity 0.17 and 0.04, respectively) but helped identify two of three subjects requiring revascularization. EST and MPI did not enhance logistic regression models. A clinical algorithm to identify low-risk subjects who may not require angiography was highly sensitive but was applicable only to a minority (n = 8, sensitivity 1.0, specificity 0.27, negative predictive value 1.0). CONCLUSIONS: Nonuremic type 1 diabetic patients with hypoglycemic unawareness and/or metabolic lability referred for ITX are at high risk for asymptomatic CAD despite negative noninvasive investigations. Aggressive management of cardiovascular risk factors and further investigation into optimal cardiac risk stratification in type 1 diabetes are warranted.