Ribavirin treatment of acute and chronic hepatitis E: a single-centre experience.

BACKGROUND: The role of ribavirin for treatment of severe acute or chronic hepatitis E virus (HEV) infection is not well defined. AIMS: To investigate the applicability and efficacy of ribavirin therapy in acute and chronic HEV infections within a large single-centre cohort. MATERIALS & METHODS: Clinical courses of forty-four German HEV-infected individuals were analysed. RESULTS: In a prospective case series, we observed spontaneous recovery from acute symptomatic HEV-infection in 10/11 immunocompetent individuals. Ribavirin therapy was initiated in one patient with severe acute HEV-genotype-1e infection who rapidly improved liver function and cleared HEV. Of 15 organ transplant recipients with prolonged HEV viraemia, reduction in immunosuppression led to HEV-clearance in three patients, while ribavirin therapy was initiated in 11 subjects. A rapid response with undetectable HEV-RNA occurred in nine subjects. One patient died after experiencing a virological breakthrough associated with ribavirin dose reduction because of severe anaemia. DISCUSSION: Ribavirin is a safe treatment option for HEV infections. However, the optimal dose of ribavirin for the treatment of chronic hepatitis E remains to be determined as treatment failure may occur.

Hemodynamic markers of pulmonary vasculopathy for prediction of early right heart failure and mortality after heart transplantation.

BACKGROUND: Elevated pulmonary vascular resistance (PVR) is broadly accepted as an imminent risk factor for mortality after heart transplantation (HTx). However, no current HTx recipient risk score includes PVR or other hemodynamic parameters. This study examined the utility of various hemodynamic parameters for risk stratification in a contemporary HTx population. METHODS: Patients from seven German HTx centers undergoing HTx between 2011 and 2015 were included retrospectively. Established risk factors and complete hemodynamic datasets before HTx were analyzed. Outcome measures were overall all-cause mortality, 12-month mortality, and right heart failure (RHF) after HTx. RESULTS: The final analysis included 333 patients (28% female) with a median age of 54 (IQR 46-60) years. The median mean pulmonary artery pressure was 30 (IQR 23-38) mm Hg, transpulmonary gradient 8 (IQR 5-10) mm Hg, and PVR 2.1 (IQR 1.5-2.9) Wood units. Overall mortality was 35.7%, 12-month mortality was 23.7%, and the incidence of early RHF was 22.8%, which was significantly associated with overall mortality (log-rank HR 4.11, 95% CI 2.47-6.84; log-rank p < .0001). Pulmonary arterial elastance (Ea) was associated with overall mortality (HR 1.74, 95% CI 1.25-2.30; p < .001) independent of other non-hemodynamic risk factors. Ea values below a calculated cutoff represented a significantly reduced mortality risk (HR 0.38, 95% CI 0.19-0.76; p < .0001). PVR with the established cutoff of 3.0 WU was not significant. Ea was also significantly associated with 12-month mortality and RHF. CONCLUSIONS: Ea showed a strong impact on post-transplant mortality and RHF and should become part of the routine hemodynamic evaluation in HTx candidates.

Angiographic assessment of cardiac allograft vasculopathy: results of a Consensus Conference of the Task Force for Thoracic Organ Transplantation of the German Cardiac Society.

Angiograms of cardiac transplant (HTx) recipients were to be evaluated in a ring experiment and a joint consensus on criteria of angiographic evaluation of coronary arteries of HTx patients was to be reached. Twenty-four coronary angiograms from 11 hospitals were circulated. One hundred eighty-eight blinded evaluations were returned. A joint evaluation by six experienced cardiologists was used as reference standard and a consensus evaluation form was developed. Significant lesions (stenosis 75%, 50% in the left main coronary artery) were diagnosed in 10/23 abnormal coronary angiograms (41.7%). Interventional revascularization was recommended in 8/10 (80%). In 21 coronary angiograms distal pruning was found and in 11/21 (52.4%) cases with distal pruning occlusion of at least one peripheral vessel was detected. The best kappa value (0.7) was found for the presence of at least one clinically significant stenosis. Agreement on the site and grade of local stenosis was much less. Some agreement on remodeling was found in assessing diffuse narrowing in the LCA (kappa=0.371, P<0.001). The kappa value for peripheral obliteration was 0.331 (P=0.001). Angiographic evaluation of cardiac allograft vasculopathy, particularly of diffuse and peripheral disease and remodeling, needs standardization. This should be performed in a downward compatible improvement process.

Gastrointestinal Endoscopy Is Safe in Patients Before and After Lung or Heart Transplantation.

BACKGROUND: Gastrointestinal complications are common in patients after lung and heart transplantation. Endoscopy is a standard method for the assessment of gastrointestinal morbidities. The aim of this study was to analyze the number and type of complications during endoscopic procedures in patients before and after lung or heart transplantation. METHODS: A retrospective single centre analysis of endoscopic procedures in patients before and after lung and heart transplantation from May 1999 to September 2012 was performed compared to a control group. RESULTS: Four hundred fifty-nine endoscopic procedures were performed in 175 patients after transplantation (84 lung and 91 heart) and 213 procedures in 160 transplant candidates on the waiting list for lung (n = 126) or heart (n = 34) transplantation. In 26% (n = 56/214) of the endoscopic examinations, an intervention was necessary in the lung transplant group compared to 32% (n = 79/245) in the heart transplant group and 27% (n = 43/160) and 21% (n = 11/53) in the lung and heart transplant candidates, respectively. In the control group, endoscopic interventions were performed in 24% (n = 195/805) of the examinations. Overall, 14 (1%) complications resulted from 1,477 endoscopic examinations. Only four (0.9%) of 459 endoscopic examinations were followed by complications in the transplant recipients, whereas in the control group, 10 complications (1.2%) of 805 endoscopies were documented. No endoscopic complication occurred in the lung and heart transplant candidates. CONCLUSION: Diagnostic and therapeutic endoscopies can be safely performed after lung and heart transplantation and in patients on the waiting list for these organs.

Steroid withdrawal and reduction of cyclosporine A under mycophenolate mofetil after heart transplantation.

Survival and quality of life after heart transplantation are limited by a significant incidence of cardiovascular complications. Side effects of immunosuppressives contribute unfavorably. Aim of this study was to determine (1) whether withdrawal of corticosteroids and dose reduction of cyclosporine A can be performed safely under immunosuppressive therapy with mycophenolate mofetil and (2) if this is beneficial for renal function and cardiovascular risk reduction. Long term heart transplant recipients on steroids and cyclosporine A were examined in a monocentric, prospective, single-arm cohort study. Steroids were withdrawn, mycophenolate mofetil introduced and cyclosporine A dose reduced (target level 50-90 ng/ml). Follow up was 24 months. 23 patients were analyzed: Renal parameters (creatinine, urea, uric acid) improved significantly (p<0.01), as did cardiovascular parameters (heart rate [p<0.05], systolic and diastolic blood pressure [p<0.01]), HbA1c (p<0.05) and triglycerides (p<0.05). In contrast, the self-percepted state of health (SF36™) decreased. Drop outs occurred mostly due to steroid withdrawal syndrome [n=7]. The incidence of adverse events reflected the usual course after heart transplantation. We conclude that CS free immunosuppression comprising reduced cyclosporine levels and addition of MMF in long term heart transplant recipients is safe and improves the cardiovascular risk profile, carbohydrate metabolism and renal function.

Simulation of the fluid dynamics in artificial aortic roots: comparison of two different types of prostheses.

As a consequence of the growing number of elderly people, the incidence of degenerative aortic diseases continues to increase. Often, artificial aortic roots are needed to replace the native tissue. Some physical characteristics of the artificial aortic root, however, are quite different from native aorta and need to be optimized. The supposed benefit of a prosthesis with artificial sinuses of Valsalva could first be checked by numerical calculations. Two simplified base geometries were used for simulating the flow and pressure distributions, especially in the coronary arteries. One model approximates the ascending aorta as a tube, and the other uses a design with toroidal dilation of the aortic root to approximate the native geometry of the sinuses of Valsalva. The flow and pressure distributions in both models were compared in the ascending aorta as well as in the right and the left coronary arteries. Both the pressure and the velocity distribution in the coronary artery region were not significantly higher in the model with the sinus design compared to the tube model. The sinus design only slightly increased the mean pressures and the velocities in both the ascending aorta and in the coronary arteries. Higher pressure in the coronary arteries should improve the blood circulation and decrease the risk of a surgery-related coronary incident. The sinus design did not show the hoped-for benefits, and therefore it is only a minor factor in optimizing future aortic root prostheses.