Successful auxiliary two-staged partial resection liver transplantation (ASPIRE-LTx) for end-stage liver disease to avoid small-for-size situations

Background Risks for living-liver donors are lower in case of a left liver donation, however, due to lower graft volume, the risk for small-for-size situations in the recipients increases. This study aims to prevent small-for-size situations in recipients using an auxiliary two-staged partial resection liver transplantation (LTX) of living-donated left liver lobes. Case presentation Two patients received a two-stage auxiliary LTX using living-donated left liver lobes after left lateral liver resection. The native extended right liver was removed in a second operation after sufficient hypertrophy of the left liver graft had occurred. Neither donor developed postoperative complications. In both recipients, the graft volume increased by an average of 105% (329 ml to 641 ml), from a graft-to-body-weight ratio of 0.54 to 1.08 within 11 days after LTX, so that the remnant native right liver could be removed. No recipient developed small-for-size syndrome; graft function and overall condition is good in both recipients after a follow-up time of 25 months. Conclusions Auxiliary two-staged partial resection LTX using living-donor left lobes is technically feasible and can prevent small-for-size situation. This new technique can expand the potential living-donor pool and contributes to increase donor safety

Influence of hepatic fibrosis and inflammation: Correlation between histopathological changes and Gd-EOB-DTPA-enhanced MR imaging

Objective To evaluate the influence of an active inflammatory process in the liver on Gd-EOB-DTPA-enhanced MR imaging in patients with different degrees of fibrosis/cirrhosis. Material and methods Overall, a number of 91 patients (61 men and 30 women; mean age 58 years) were included in this retrospective study. The inclusion criteria for this study were Gd-EOB-DTPA-enhanced MRI of the liver and histopathological evaluation of fibrotic and inflammatory changes. T1-weighted VIBE sequences of the liver with fat suppression were evaluated to determine the relative signal change (RE) between native and hepatobiliary phase (20 min). In simple and multiple linear regression analyses, the influence of liver fibrosis/cirrhosis (Ishak score) and the histopathological degree of hepatitis (Modified Hepatic Activity Index, mHAI) on RE were evaluated. Results RE decreased significantly with increasing liver fibrosis/cirrhosis (p < 0.001) and inflammation (mHAI, p = 0.004). In particular, a correlation between RE and periportal or periseptal boundary zone hepatitis (moth feeding necrosis, mHAI A, p = 0.001) and portal inflammation (mHAI D, p < 0.001) was observed. In multiple linear regression analysis, both the degree of inflammation and the degree of fibrosis were significant predictors for RE (p < 0.01). Conclusion The results of this study suggest that the MR-based hepatic enhancement index RE is not only influenced by the degree of fibrosis, but also by the degree of inflammation

Good outcomes after repeated pediatric liver retransplantations: A justified procedure even in times of organ shortage

Background Pediatric liver transplantations generally represent advanced surgery for selected patients. In case of acute or chronic graft failure, biliary or vessel complications, a retransplantation (reLT) can be necessary. In these situations massive adhesions, critical patient condition or lack of good vessels for anastomosis often are problematic. Methods Between 2008 and 2021, 208 pediatric patients received a liver transplantation at our center. Retrospectively, all cases with at least one retransplantation were identified and stored in a database. Indication, intra- and postoperative course and overall survival (OS) were analyzed. Results Altogether 31 patients (14.9%) received a reLT. In 22 cases only one reLT was done, 8 patients received 2 reLTs and 1 patient needed a fourth graft. Median age for primary transplantation, first, second and third reLT was 14 (range: 1–192 months), 60.5 (range: 1–215 months), 58.5 (range: 14–131 months) and 67 months, respectively. Although biliary atresia (42%) and acute liver failure (23%) represented the main indications for the primary liver transplantation, acute and chronic graft failure (1st reLT: 36%, 2nd reLT: 38%), hepatic artery thrombosis (1st reLT: 29%, 2nd reLT: 25%, 3rd reLT: 100%) and biliary complications (1st reLT: 26%, 2nd reLT: 37%) were the most frequent indications for reLT. OS was 81.8% for patients with 1 reLT, 87.5% with 2 reLTs and 100% with 3 reLTs. Conclusion Pediatric liver retransplantation is possible with a good outcome even after multiple retransplantations in specialized centers. Nevertheless, careful patient and graft selection, as well as good preoperative conditioning, are essential

Early γGT and bilirubin levels as biomarkers for regeneration and outcomes in damaged bile ducts after liver transplantation

Background Early patient and allograft survival after liver transplantation (LT) depend primarily on parenchymal function, but long-term allograft success relies often on biliary-tree function. We examined parameters related to cholangiocyte damage that predict poor long-term LT outcomes after donation after brain death (DBD). Methods Sixty bile ducts (BD) were assessed by a BD damage-score and divided into groups with “major” BD-damage (n = 33) and “no relevant” damage (n = 27) during static cold storage. Patients with “major” BD damage were further investigated by measuring biliary excretion parameters in the first 14 days post-LT (followed-up for 60-months). Results Patients who received LT showing “major” BD damage had significantly worse long-term patient survival, versus grafts with “no relevant” damage (p = .03). When “major” BD damage developed, low bilirubin levels (p = .012) and high gamma-glutamyl transferase (GGT)/bilirubin ratio (p = .0003) were evident in the early post-LT phase (7–14 days) in patients who survived (> 60 months), compared to those who did not. “High risk” patients with bile duct damage and low GGT/bilirubin ratio had significantly shorter overall survival (p < .0001). Conclusions Once “major” BD damage occurs, a high GGT/bilirubin ratio in the early post-operative phase is likely indicator of liver and cholangiocyte regeneration, and thus a harbinger of good overall outcomes. “Major” BD damage without markers of regeneration identifies LT patients that could benefit from future repair therapies

EnGraft: a multicentre, open-label, randomised, two-arm, superiority study protocol to assess bioavailability and practicability of Envarsus® versus Advagraf™ in liver transplant recipients

Background Graft rejection and chronic CNI toxicity remain obstacles to organ transplant success. Current formulations of tacrolimus, such as Prograf® and Advagraf™, exhibit limitations in terms of pharmacokinetics and tolerability, related in part to suboptimal bioavailability. As dosing non-compliance can result in graft rejection, the once daily formulation of tacrolimus, Advagraf™, was developed (vs 2x/day Prograf®). Benefits of Advagraf™ are counterbalanced by delayed achievement of therapeutic trough levels and need for up to 50% higher doses to maintain Prograf®-equivalent troughs. Envarsus® is also a prolonged-release once-daily tacrolimus formulation, developed using MeltDose™ drug-delivery technology to increase drug bioavailability; improved bioavailability results in low patient drug absorption variability and less pronounced peak-to-trough fluctuations. In phase III de novo kidney transplant studies, Envarsus® proved non-inferior to twice-daily tacrolimus; however, no phase IV studies show superiority of Envarsus® vs Advagraf™ in de novo liver transplant (LTx) recipients. Methods The EnGraft compares bioavailability and tests superiority of Envarsus® (test arm) versus Advagraf™ (comparator arm) in de novo LTx recipients. A total of 268 patients from 15 German transplant centres will be randomised 1:1 within 14 days post-LTx. The primary endpoint is dose-normalised trough level (C/D ratio) measured 12 weeks after randomisation. Secondary endpoints include the number of dose adjustments, time to reach first defined trough level and incidence of graft rejections. Additionally, clinical and laboratory parameters will be assessed over a 3-year period. Discussion C/D ratio is an estimate for tacrolimus bioavailability. Improving bioavailability and increasing C/D ratio using Envarsus could reduce renal dysfunction and other tacrolimus-related toxicities; previous trials have shown that a higher C/D ratio (i.e. slower tacrolimus metabolism) is not only associated with improved renal function but also linked to reduced neurotoxic side effects. A higher C/D ratio could improve clinical outcomes for LTx recipients; EnGraft has begun, with one third of patients recruited by January 2022

CVD OF SiC IN LARGE COATING VESSELS

In large coating vessels deposition processes are very sensitive to hydrodynamics and kinetics. As one is operating in practice far away from equilibrium thermodynamic predictions are of secondary importance. This partly explains discrepancies with results obtained in laboratory reactors. Therefore optimization of the heat transfer and the gas distribution is a fundamental prerequisite for homogeneous and well-defined depositions. Furthermore temperature increase with simultaneous decrease of the total pressure during a deposition cycle improves the uniformity of the coating along the reaction chamber

In-situ-spectroscopic monitoring for SIC-CVD process control

The objectives of this contribution are the integration of a FTIR spectrometer onto a waste gas line of a SiC-CVD demonstrator unit and the correlation of the measured gas phase spectra with formation of polychlorosilane deposits. The formation of polychlorosilanes during low pressure CVD processes of SiC is the most limiting factor in scaling up of CVD units. Therefore, it is absolutely necessary to monitor and to control this waste gas process. It is shown that FTIR measurements can be applied to solve such a problem. The paper is subdivided in the following three parts. First, the optical and mechanical adaption of the FTIR equipment are shown ; second, FTIR measurements in the SiC-CVD demonstrator and interpretation of the measured spectra are presented ; and third, the opportunities for process control are discussed

Laser CVD vs. Hot Wall CVD : Coating of Fibres for Ceramic Composites

Based on a technological 5 kW cw-CO2 laser, an atmospheric pressure laser assisted CVD process has been established which performs a continuous high rate coating of carbon fibre rovings. Layers of pyrolytic carbon have been deposited from CH4 with a rate of 0.6 µm/s which enhances the tensile strength and Weibull modulus of fibres. In another variant, pyro-C layers have been deposited in a technological thermal hot-wall CVD reactor on fabrics and on preforms. The layer thickness is uniform over the cross section of the fibre bundles, but variations in flow direction have been detected. Composite materials with SiC matrix have been processed by both liquid precursor infiltration using Si-polymers and by converting a carboneous matrix being infiltrated with liquid silicon. Preforms with uncoated and coated fibres have been infiltrated. The resulting composites are characterized by high tensile strength and crack resistance due to the favourable pull-out behaviour of coated fibres