Detrimental impact of immunosuppressive burden on clinical course in patients with Cytomegalovirus infection after liver transplantation.

INTRODUCTION: Cytomegalovirus (CMV)-infection and reactivation remain a relevant complication after liver transplantation (LT). The recipient and donor serum CMV-IgG-status has been established for risk stratification when choosing various pharmaceutical regimens for CMV-prophylaxis in the last two decades. However, factors influencing course of CMV-infection in LT remain largely unknown. In this study, the impact of immunosuppressive regimen was examined in a large cohort of patients. METHODS: All patients that underwent primary LT between 2006 and 2018 at the Charité-Universitaetsmedizin, Berlin, were included. Clinical course as well as histological and laboratory findings of patients were analyzed our prospectively maintained database. Univariate and multivariate regression analysis for impact of variables on CMV-occurrence was conducted, and survival was examined using Kaplan-Meier analysis. RESULTS: Overall, 867 patients were included in the final analysis. CMV-infection was diagnosed in 325 (37.5%) patients after transplantation. Significantly improved overall survival was observed in these patients (Log rank = 0.03). As shown by correlation and regression tree classification and regression tree analysis, the recipient/donor CMV-IgG-status with either positivity had the largest influence on CMV-occurrence. Analysis of immunosuppressive burden did not reveal statistical impact on CMV-infection, but statistically significant inverse correlation of cumulative tacrolimus trough levels and survival was found (Log rank < .001). Multivariate analysis confirmed these findings (p = .02). DISCUSSION: CMV-infection remains of clinical importance after LT. Undergone CMV-infection of either recipient or donor requires prophylactic treatment. Additionally, we found a highly significant, dosage-dependent impact of immunosuppression (IS) on long-term outcomes for these patients, underlying the importance of minimization of IS in liver transplant recipients.

Successful Desensitization with Imlifidase and Daratumumab in a Highly Immunized, Crossmatch Positive, Blood Group-Incompatible Living-Donor Re-Transplant Recipient with Systemic Lupus Erythematosus and Antiphospholipid Syndrome.

Introduction: The transplantation of highly sensitized patients remains a major obstacle. Immunized patients wait longer for a transplant if not prioritized, and if transplanted, their transplant outcome is worse. Case Presentation: We report a successful AB0- and HLA-incompatible living donor kidney transplantation in a 35-year-old female patient with systemic lupus erythematosus (SLE) and antiphospholipid syndrome. The patient had a positive T- and B-cell complement-dependent cytotoxicity (CDC) crossmatch and previous graft loss due to renal vein thrombosis. We treated the patient with intravenous immunoglobulins, rituximab, horse anti-thymocyte globulin, daratumumab, and imlifidase, besides standard immunosuppression. All IgG antibodies were sensitive to imlifidase treatment. Besides donor-specific HLA antibodies, anti-dsDNA antibodies and antiphospholipid antibodies were cleaved. The patient initially had delayed graft function. Two kidney biopsies (day 7 and day 14) revealed acute tubular necrosis without signs of HLA antibody-mediated rejection. On posttransplant day 30, hemodialysis was stopped, and creatinine levels declined over the next weeks to a baseline creatinine of about 1.7 mg/dL after 12 months. Conclusion: In this case, a novel multimodal treatment strategy including daratumumab and imlifidase enabled successful kidney transplantation for a highly immunized patient with antiphospholipid antibodies.

Robotic versus laparoscopic versus open major hepatectomy - an analysis of costs and postoperative outcomes in a single-center setting.

PURPOSE: In the era of minimal-invasive surgery, the introduction of robotic liver surgery (RS) was accompanied by concerns about the increased financial expenses of the robotic technique in comparison to the established laparoscopic (LS) and conventional open surgery (OS). Therefore, we aimed to evaluate the cost-effectiveness of RS, LS and OS for major hepatectomies in this study. METHODS: We analyzed financial and clinical data on patients who underwent major liver resection for benign and malign lesions from 2017 to 2019 at our department. Patients were grouped according to the technical approach in RS, LS, and OS. For better comparability, only cases stratified to the Diagnosis Related Groups (DRG) H01A and H01B were included in this study. Financial expenses were compared between RS, LS, and OS. A binary logistic regression model was used to identify parameters associated with increased costs. RESULTS: RS, LS and OS accounted for median daily costs of 1,725 €, 1,633 € and 1,205 €, respectively (p < 0.0001). Median daily (p = 0.420) and total costs (16,648 € vs. 14,578 €, p = 0.076) were comparable between RS and LS. Increased financial expenses for RS were mainly caused by intraoperative costs (7,592 €, p < 0.0001). Length of procedure (hazard ratio [HR] = 5.4, 95% confidence interval [CI] = 1.7-16.9, p = 0.004), length of stay (HR [95% CI] = 8.8 [1.9-41.6], p = 0.006) and development of major complications (HR [95% CI] = 2.9 [1.7-5.1], p < 0.0001) were independently associated with higher costs. CONCLUSIONS: From an economic perspective, RS may be considered a valid alternative to LS for major liver resections.

Hepatic artery reconstruction using an operating microscope in pediatric liver transplantation-Is it worth the effort?

INTRODUCTION: In pediatric liver transplantation (pLT), hepatic artery thrombosis (HAT) is associated with inferior transplant outcome. Hepatic artery reconstruction (HAR) using an operating microscope (OM) is considered to reduce the incidence of HAT. METHODS: HAR using an OM was compared to a historic cohort using surgical loupes (SL) in pLT performed between 2009 and 2020. Primary endpoint was the occurrence of HAT. Secondary endpoints were 1-year patient and graft survival determined by Kaplan-Meier analysis and complications. Multivariate analysis was used to identify independent risk factors for HAT and adverse events. RESULTS: A total of 79 pLTs were performed [30 (38.0%) living donations; 49 (62.0%) postmortem donations] divided into 23 (29.1%) segment 2/3, 32 (40.5%) left lobe, 4 (5.1%) extended right lobe, and 20 (25.3%) full-size grafts. One-year patient and graft survival were both 95.2% in the OM group versus 86.2% and 77.8% in the SL group (p = .276 and p = .077). HAT rate was 0% in the OM group versus 24.1% in the SL group (p = .013). One-year patient and graft survival were 64.3% and 35.7% in patient with HAT, compared to 93.9% and 92.8% in patients with no HAT (both p < .001). Multivariate analysis revealed HAR with SL (p = .022) and deceased donor liver transplantation (DDLT) (p = .014) as independent risk factors for HAT. The occurrence of HAT was independently associated with the need for retransplantation (p < .001) and biliary leakage (p = .045). CONCLUSION: In pLT, the use of an OM is significantly associated to reduce HAT rate, biliary complications, and graft loss and outweighs the disadvantages of delayed arterial perfusion and prolonged warm ischemia time (WIT).

Hypothermic oxygenated machine perfusion for extended criteria donor allografts: Preliminary experience with extended organ preservation times in the setting of organ reallocation.

BACKGROUND: In times of critical organ shortage, poor organ pool utilization and increased use of extended-criteria donor (ECD) allografts remain a major problem. Hypothermic oxygenated machine perfusion (HOPE) has emerged as a promising and feasible strategy in ECD liver transplantation (LT). However, potential safety limits regarding the duration of perfusion are yet to be explored. Besides marginal allograft quality (steatosis), prolonged cold ischemia time remains the most important factor for a high number of liver allografts being declined for transplantation. PATIENTS AND METHODS: Two ECD-allografts were each allocated to two recipients, who proved to be unsuitable to receive the assigned allograft upon arrival at the transplant center. The organs were reallocated by Eurotransplant and accepted by our center for two different backup patients. During that time, HOPE was commenced and continued until the recipient hepatectomy was completed. Postoperative allograft function was assessed by serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), bilirubin, and International Normalized Ratio. Incidence of early allograft dysfunction (EAD), postoperative complications, and length of hospital stay were analyzed. RESULTS: HOPE was applied for 4 h 35 min and 4 h 20 min, resulting in a total cold preservation time of 17 h 29 min and 15 h 20 min, respectively. Both recipients displayed decreasing serum transaminases and bilirubin levels postoperatively. No EAD or major postoperative complications occurred in either patient. Serum ALT and AST levels were within the normal range at discharge. CONCLUSIONS: Extended HOPE enables the safe extension of preservation time for up to 18 h in human LT. End-ischemic HOPE may significantly improve organ pool utilization, while simultaneously facilitating operating room logistics and preventing organ injury.

Feasibility of robotic-assisted pancreatic resection in patients with previous minor abdominal surgeries: a single-center experience of the first three years.

BACKGROUND: Robotic-assisted pancreatic surgery is limited to specialized high-volume centers and selected patient cohorts. Especially for patients with a history of previous abdominal surgeries, the standard procedure remains open surgery due to the fear of complications caused by abdominal adhesions. METHODS: Clinical data of all consecutive patients undergoing robotic-assisted pancreatic surgery using the daVinci Xi system (Intuitive Surgical) at our center (Department of Surgery, Universitätsmedizin Berlin, Germany) were collected prospectively and further analyzed from October 2017 to October 2020. Prior abdominal surgeries were specified according to the surgical approach and localization. In univariate and multivariate analysis, baseline and perioperative parameters of patients with a history of prior abdominal surgeries (PS) were compared to those of patients with no history of prior abdominal surgeries (NPS). RESULTS: Out of 131 patients undergoing robotic-assisted pancreatic surgery, 62 (47%) had a history of abdominal surgery. Previous procedures included most often appendectomy (32%) followed by gynecological surgery (29%) and cholecystectomy (27%). 24% of PS had received multiple surgeries prior to the robotic-assisted pancreatic resections. Baseline characteristics and comorbidities were comparable between the groups. We did not detect differences in the duration of surgery (262 min), conversion rates (10%), and postoperative complications between NPS and PS. Postoperative pancreatic fistula (POPF), postpancreatectomy hemorrhage (PPH), and in-house mortality showed no significant differences between the two groups. Multivariate analysis revealed male sex and high BMI as a potential predictive factor for severe postoperative complications. Other characteristics like the type of pancreatic resection, ASA, and underlying malignancy showed no difference in the multivariable analysis. CONCLUSIONS: We propose robotic-assisted pancreatic surgery to be safe and feasible for patients with a history of minor prior abdominal surgery. Hence, each patient should individually be evaluated for a minimally invasive approach regardless of a history of previous operations.

Transplantation programs facing lack of empirical evidence on SARS-CoV-2 vaccination: A society recommendation consensus update.

BACKGROUND: Since phase III trials for the most prominent vaccines excluded immunocompromised or immunosuppressed patients, data on safety and efficacy of SARS-CoV-2 vaccines for recipients of solid organ transplantations are scarce. AIMS: Our study offers a synthesis of expert opinions aligned with available data addressing key questions of the clinical management of SARS-CoV-2 vaccinations for transplant patients. METHOD: An online research was performed retrieving available recommendations by national and international transplantation organizations and state institutions on SARS-CoV2 vaccination management for transplant recipients. RESULTS: Eleven key statements were identified from recommendations by 18 national and international societies, and consensus for the individual statements was evaluated by means of the Society Recommendation Consensus score. The highest consensus level (SRC A) was found for prioritized access to vaccination for transplant patients despite anticipation of a weakened immune response. All currently authorized vaccines can be considered safe for transplant patients (SRC A). The handling of immunosuppressive medication, the timely management of vaccines, and other aspects were aligned with available expert opinions. CONCLUSION: Expert consensus can be determined for crucial aspects of the implementation of SARS-CoV-2 vaccination programs. We hereby offer a tool for immediate decision-making until empirical data becomes available.

Orthotopic Liver Transplantation for Budd-Chiari Syndrome: Observations from a 30-Year Liver Transplant Program.

Background and objectives Budd-Chiari syndrome (BCS) refers to a complete thrombotic obstruction of the venous hepatic outflow tract due to various etiologies and constitutes a rare indication for ortothopic liver transplantation (LT). Few studies investigated long-term outcomes after LT for BCS. The aim of this study was to examine potential risk factors for late mortality and to evaluate long-term outcomes after LT for BCS. Materials and methods: 46 patients received an LT for BCS between 1989 and 2019 at the transplant center of the Charité-Universitätsmedizin Berlin. We analyzed potential effects of disease etiology, vascular events, rejection, and immunosuppression on long-term survival after transplantation using Kaplan-Meier curves and Cox logistic regression. Results: Of the 46 patients, 70% were female and 30% were male. Median age at the time of transplantation was 36 years. A total of 41 vascular events, including 26 thrombotic and 17 hemorrhagic incidents, occurred. The 1 year, the 5 year, the 10 year, and the 20 year survival rates were 87%, 83%, 76%, and 60%, respectively. By comparison, survival rates of the liver transplant cohort across all other indications at our center were slightly inferior with 85%, 75%, 65%, and 46%, respectively. In the study population, patients with myeloproliferative disorders showed worse outcomes compared to patients with other causes of BCS. Conclusion: Liver transplantation for BCS showed excellent results, even superior to those for other indications. Vascular events (i.e., thrombotic or hemorrhagic complications) did not have any prognostic value for overall mortality. Patients with myeloproliferative disorders seem to have a disadvantage in survival.

Liver Transplantation Is Highly Effective in Children with Irresectable Hepatoblastoma.

Background and Objectives: In children, hepatoblastoma preferentially is managed by liver resection (LR). However, in irresectable cases, liver transplantation (LT) is required. The aim of our study was to compare short- and long-term results after LR and LT for the curative treatment of hepatoblastoma. Materials and Methods: Retrospective analysis of all patients treated surgically for hepatoblastoma from January 2000 until December 2019 was performed. Demographic and clinical data were collected before and after surgery. The primary endpoints were disease free survival and patient survival. Results: In total, 38 patients were included into our analysis (n = 28 for LR, n = 10 for LT) with a median follow-up of 5 years. 36 patients received chemotherapy prior to surgery. Total hospital stay and intensive care unit (ICU) stay were significantly longer within the LT vs. the LR group (ICU 23 vs. 4 days, hospital stay 34 vs. 16 days, respectively; p < 0.001). Surgical complications (≤Clavien-Dindo 3a) were equally distributed in both groups (60% vs. 57%; p = 1.00). Severe complications (≥Clavien-Dindo 3a) were more frequent after LT (50% vs. 21.4%; p = 0.11). Recurrence rates were 10.7% for LR and 0% for LT at 5 years after resection or transplantation (p = 0.94). Overall, 5-year survival was 90% for LT and 96% for LR (p = 0.44). Conclusions: In irresectable cases, liver transplantation reveals excellent outcomes in children with hepatoblastoma with an acceptable number of perioperative complications.

Clinical and Histological Long-Term Follow-Up of De Novo HBV-Infection after Liver Transplantation.

Background and Objectives: Development of hepatitis-B is considered a serious complication after liver transplantation. HBV de novo infection is a rather rare phenomenon, however it deserves attention in the era of donor organ shortage. The aim of the present analysis was to examine its course in liver transplant patients. Materials and Methods: Prevalence of de novo HBV-infections was extracted from our local transplant data base. Analysis focused on the moment of HBV-detection and on the long-term follow-up in terms of biochemical and histological changes over 30 years. Results: 46 patients were identified with the diagnosis of de novo hepatitis B. Median time from liver transplantation to diagnosis was 397 days (7-5505). 39 patients received antiviral therapy. No fibrosis progression could be detected, whereas the grade of inflammation significantly lessened from the moment of HBV detection to the end of histological follow-up over a median of 4344 days (range 123-9490). Patients with a poor virological control demonstrated a significantly poorer overall survival. Conclusions: De novo hepatitis B in liver transplant patients is a condition that can be controlled very well without significant fibrosis progression or graft loss if recognized on time within a regular transplant follow-up schedule.

Successful implementation of preventive measures leads to low relevance of SARS-CoV-2 in liver transplant patients: Observations from a German outpatient department.

BACKGROUND: Immunosuppressed liver transplant (LT) patients are considered to be at high risk for any kind of infection. What the outbreak of the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) means for the transplant cohort is a question that, as of now, cannot easily be answered. Data on prevalence, relevance of the novel virus, and clinical course of the infection in stable LT patients are limited. METHODS: Nasopharyngeal swabs were performed in our outpatient department during the shutdown between March and April 2020 in Germany. RESULTS: The prevalence of SARS-CoV-2 was 3%. Three out of a cohort of 101 LT patients were asymptomatic for respiratory diseases. Respiratory complaints were common and not associated with SARS-CoV-2 infection. The overall monthly mortality rate was 0.22% and did not show alterations during the shutdown in Germany. CONCLUSIONS: If preventive measures are applied, LT patients do not seem to be at a higher risk for SARS-CoV-2 infection. Telemedicine in the outpatient setting may help to maintain distance and to reduce direct patient contact. However, standard of care must be guaranteed for patients with relevant comorbidities in spite of pandemics, because complications may arise from preexisting conditions.

Outcome after pediatric liver transplantation for staged abdominal wall closure with use of biological mesh-Study with long-term follow-up.

Abdominal wall closure after pediatric liver transplantation (pLT) in infants may be hampered by graft-to-recipient size discrepancy. Herein, we describe the use of a porcine dermal collagen acellular graft (PDCG) as a biological mesh (BM) for abdominal wall closure in pLT recipients. Patients <2 years of age, who underwent pLT from 2011 to 2014, were analyzed, divided into definite abdominal wall closure with and without implantation of a BM. Primary end-point was the occurrence of postoperative abdominal wall infection. Secondary end-points included 1- and 5-year patient and graft survival and the development of abdominal wall hernia. In five out of 21 pLT recipients (23.8%), direct abdominal wall closure was achieved, whereas 16 recipients (76.2%) received a BM. BM removal was necessary in one patient (6.3%) due to abdominal wall infection, whereas no abdominal wall infection occurred in the no-BM group. No significant differences between the two groups were observed for 1- and 5-year patient and graft survival. Two late abdominal wall hernias were observed in the BM group vs none in the no-BM group. Definite abdominal wall closure with a BM after pLT is feasible and safe when direct closure cannot be achieved with comparable postoperative patient and graft survival rates.

Postoperative acute necrotizing pancreatitis of the pancreatic remnant (POANP): a new definition of severe pancreatitis following pancreaticoduodenectomy.

BACKGROUND: Recent studies have suggested acute pancreatitis as a separate pancreatic-specific complication following pancreaticoduodenectomy. However, data on necrotizing pancreatitis of the pancreatic remnant is limited. This study aimed to evaluate parameters of patients undergoing completion pancreatectomy (CP) after initial pancreaticoduodenectomy (PD) and compare those with or without necrosis of the pancreatic remanent. METHODS: Patients who underwent CP following PD between January 2005 and December 2017 were identified from a prospectively collected database. Perioperative parameters were recorded, and patients were divided into those with or without histological evidence of necrosis of the pancreatic remnant. RESULTS: Postoperative acute necrotizing pancreatitis (POANP) was histologically detected in 33 (41%) of 79 patients after CP. Serum CRP levels on POD 2 and the day of revision were significantly higher in the POANP group (p < 0.001 for each). POANP was reflected by higher APACHE II and SOFA scores after PD (P < 0.001 for each). Although patients with POANP had an earlier revision, length of ICU and total hospital stay was prolonged (p < 0.001 for each). POANP was associated with more major complications (Clavien-Dindo ≥ 3) and more often necessitated reoperations within 30 days (p < 0.001 for each). CONCLUSION: Patients requiring CP following PD for POANP have an increased risk of major complications, and longer hospital stay. CRP levels, APACHE II and SOFA score, seem to correlate with the severity and might predict POANP. Universally accepted definitions with a clinically validated grading system of severity for POAP and POANP are needed to facilitate appropriate treatment strategies and enable comparison of future studies.

Liver transplantation for Hepatitis-B-associated liver disease - Three decades of experience.

BACKGROUND: Hepatitis B (HBV)-associated end-stage liver disease used to be a relevant indication for liver transplantation (LT). After transplantation, HBV-reinfection remains a serious issue. Different strategies to prevent HBV-reinfection range from the single application of immunoglobulins (HBIG), to the use of modern nucleoside/nucleotide analogues (NUC) in combination with HBIG, followed by HBIG-discontinuation. The aim of this analysis was to compare different strategies and to sum up the results of 30 years at a high-volume transplant center and deliver additional information on the histopathological level. METHODS: Data of 372 liver transplantations performed for the HBV-induced liver disease in 352 patients were extracted from a prospectively organized database. HBV-reinfection was determined in the entire cohort, according to the mode of HBV-prophylaxis. Differences in survival rates were analyzed in patients with successful prophylaxis, untreated and controlled HBV-reinfection. Histopathological results were obtained from protocol biopsies in 151 patients. RESULTS: HBV-reinfection was significantly associated with the type of prophylaxis, presence of HBs-Antigen at the moment of LT, transplant year and influencing the overall survival before 2005. After the introduction of modern NUCs, HBV-reinfection stopped to impact HBV-associated transplant loss and survival. Controlled HBV-infection prevents from HBV-associated transplant hepatitis and fibrosis development. The role of HBIG declines in favor of NUCs. CONCLUSIONS: Uncontrolled HBV-reinfection does not occur any more. Even in the presence of Hbs-antigen, transplant fibrosis does not develop. The most reliable mode to prevent HBV-recurrence remains the combination of NUCs with a high genetic barrier and HBIG. However, HBIG can safely be discontinued after LT.

Evaluation of histological dynamics, kidney function and diabetes in liver transplant patients after antiviral treatment with direct-acting antivirals: Therapy of HCV-recurrence.

BACKGROUND: Direct-acting antivirals allow efficient and safe treatment of hepatitis C (HCV) before and after liver transplantation (LT). However, the impact of sofosbuvir on the graft, diabetes, and on kidney function is not answered yet. Primary endpoint of this analysis was the evaluation of kidney function after antiviral treatment (AVT). Secondary endpoints were the assessment of extrahepatic manifestation of HCV-infection by diabetes mellitus and the histopathological changes in terms of inflammation, content of fat, and fibrosis stage. METHODS: From 2014 to 4/2015, 100 patients with HCV-recurrence after LT were successfully treated with AVT. Ninety-eight received a sofosbuvir-based regimen. Indication was based on genotype, transplant fibrosis stage, and urgency. Biopsies were evaluated before and after treatment. Renal function and diabetes were assessed before, during, and after AVT. RESULTS: All patients achieved sustained virological response. A significant improvement of inflammation (P = 0.001) and fibrosis stage (P = 0.031) were observed. Significantly less insulin was required in 32 patients with diabetes (P < 0.001) to keep Hb1Ac unchanged after AVT. Kidney function was stable during, 12 weeks after and 48 weeks after antiviral therapy. Stages of renal insufficiency were comparable before and after AVT. CONCLUSION: Successful sofosbuvir-based AVT leads to a variety of positive development in transplant patients including a significant improvement of inflammation, fat content and fibrosis, a significant decrease in daily insulin dose and no significant impairment of kidney function.

Treatment of hepatitis C virus recurrence after transplantation with sofosbuvir/ledipasvir: The role of ribavirin.

BACKGROUND: Hepatitis C virus (HCV) recurrence after liver transplantation (LT) used to be a serious problem in the era of interferon-based treatment. Since the introduction of modern directly acting antivirals, treatment has become easier and shorter. According to published data, in the natural course of hepatitis C infection the duration of antiviral treatment with sofosbuvir (SOF) and ledipasvir (LDV) may be shortened to 12 instead of 24 weeks, using ribavirin (RBV) in addition. Furthermore, the question of whether or not RBV is really necessary, in a 12-week SOF/LDV treatment in the post-transplant setting, is still unanswered. PATIENTS AND METHODS: At our institution, 100 liver transplant patients with HCV recurrence underwent interferon-free SOF-based treatment. A total of 51 patients received SOF/LDV with or without RBV. Twenty-nine HCV genotype 1 or 4 patients with histologically proven stage 0-2 fibrosis were treated with SOF/LDV for 12 weeks; another 22 patients with advanced fibrosis (stage 3-4) either received SOF/LDV plus weight-adjusted RBV or prolonged treatment for 24 weeks. RESULTS: End of treatment response and sustained virological response (SVR) were achieved in 100% of the 51 patients, irrespective of the treatment group. Patients with prolonged treatment duration or with RBV developed significantly more adverse events (AEs) compared to the SOF/LDV group: 19 (86.4%) vs 8 (27.6%), P<.001. One of the predominant and most relevant AEs was the development of anemia in 43.1% of 10 patients receiving RBV, which was a significant result (P<.001). RBV co-medication had to be reduced in 11 (55%) patients and then stopped in 8 (40%) patients because of AEs. No significant difference was observed among the groups regarding kidney function. CONCLUSION: The SOF/LDV combination is a reliable therapy of recurrent HCV infection after LT. It is easy to administer and to achieve SVR in immunocompromised patients without interactions with immunosuppressive medications. Considering the high rate of AEs, frequent discontinuation of RBV treatment, and the 100% SVR, the use of RBV as co-medication in a 12-week SOF/LDV regimen does not seem to be justified after LT.

Different cava reconstruction techniques in liver transplantation: piggyback versus cava resection.

BACKGROUND: Originally, cava reconstruction (CR) in liver transplantation meant complete resection and reinsertion of the donor cava. Alternatively, preservation of the recipients inferior vena cava (IVC) with side-to-side anastomosis (known as "piggyback") can be performed. Here, partial clamping maintains blood flow of the IVC, which may improve cardiovascular stability, reduce blood loss and stabilize kidney function. The aim of this study was to compare both techniques with particular focus on kidney function. METHODS: A series of 414 patients who had had adult liver transplantations (2006-2009) were included. Among them, 176 (42.5%) patients had piggyback and 238 had classical CR operation, 112 (27.1%) of the patients underwent CR accompanied with veno-venous bypass (CR-B) and 126 (30.4%) without a bypass. The choice of either technique was based on the surgeons' individual preference. Kidney function [serum creatinine, calculated glomerular filtration rate (GFR), RIFLE stages] was assessed over 14 days. RESULTS: Lab-MELD scores were significantly higher in CR-B (22.5+/-11.0) than in CR (17.3+/-9.0) and piggyback (18.8+/-10.0) (P=0.008). Unexpectedly, the incidences of arterial stenoses (P=0.045) and biliary leaks (P=0.042) were significantly increased in piggyback. Preoperative serum creatinine levels were the highest in CR-B [1.45+/-1.17 vs 1.25+/-0.85 (piggyback) and 1.13+/-0.60 mg/dL (CR); P=0.033]. Although a worsening of postoperative kidney function was observed among all groups, this was most pronounced in CR-B [creatinine day 14: 1.67+/-1.40 vs 1.35+/-0.96 (piggyback) and 1.45+/-1.03 mg/dL (CR); P=0.102]. Accordingly, the proportion of patients displaying RIFLE stages ≥2 was the highest in CR/CR-B (26%/19%) when compared to piggyback (18%). CONCLUSIONS: Piggyback revealed a shorter warm ischemic time, a reduced blood loss, and a decreased risk of acute kidney failure. Thus, piggyback is a useful technique, which should be applied in standard procedures. When piggyback is unfeasible, cava replacement, which displayed a lower incidence of vascular and biliary complications in our study, remains as a safe alternative.

Validation of risk scores for allograft failure after liver transplantation in Germany: a retrospective cohort analysis.

A growing number of clinical risk scores have been proposed to predict allograft failure after liver transplantation. However, validation of currently available scores in the Eurotransplant region is still lacking. We aimed to analyze all clinically relevant donor and recipient risk scores on a large German liver transplantation data set and performed a retrospective cohort analysis of liver transplantations performed at the Charité-Universitätsmedizin Berlin from January 2007 until December 2021 with organs from donation after brain death. We analyzed 9 previously published scores in 906 liver transplantations [Eurotransplant donor risk index (ET-DRI/DRI), donor age and model for end-stage liver disease (D-MELD), balance of risk (BAR), early allograft dysfunction (EAD), model for early allograft function (MEAF), liver graft assessment following transplantation (L-GrAFT7), early allograft failure simplified estimation (EASE), and a score by Rhu and colleagues). The EASE score had the best predictive value for 3-month, 6-month, and 12-month graft survival with a c-statistic of 0.8, 0.77, and 0.78, respectively. In subgroup analyses, the EASE score was suited best for male recipients with a high-MELD (>25) and an EAD organ. Scores only based on pretransplant data performed worse compared to scores including postoperative data (eg, ET-DRI vs. EAD, p<0.001 at 3-month graft survival). Out of these, the BAR score performed best with a c-statistic of 0.6. This a comprehensive comparison of the clinical utility of risk scores after liver transplantation. The EASE score sufficiently predicted 12-month graft and patient survival. Despite a relatively complex calculation, the EASE score provides significant prognostic value for patients and health care professionals in the Eurotransplant region.

Correction: Felsenstein M. et al. Perineural Invasion in Pancreatic Ductal Adenocarcinoma (PDAC): A Saboteur of Curative Intended Therapies? J. Clin. Med. 2022, 11, 2367.

In the original publication [...].

Reducing the Pill Burden: Immunosuppressant Adherence and Safety after Conversion from a Twice-Daily (IR-Tac) to a Novel Once-Daily (LCP-Tac) Tacrolimus Formulation in 161 Liver Transplant Patients.

Non-adherence to immunosuppressant therapy reduces long-term graft and patient survival after solid organ transplantation. The objective of this 24-month prospective study was to determine adherence, efficacy and safety after conversion of stable liver transplant (LT) recipients from a standard twice-daily immediate release Tacrolimus (IR-Tac) to a novel once-daily life cycle pharma Tacrolimus (LCP-Tac) formulation. We converted a total of 161 LT patients at baseline, collecting Tacrolimus trough levels, laboratories, physical examination data and the BAASIS© questionnaire for self-reported adherence to immunosuppression at regular intervals. With 134 participants completing the study period (17% dropouts), the overall adherence to the BAASIS© increased by 57% until month 24 compared to baseline (51% vs. 80%). Patients who required only a morning dose of their concomitant medications reported the largest improvement in adherence after conversion. The intra-patient variability (IPV) of consecutive Tacrolimus trough levels after conversion did not change significantly compared to pre-conversion levels. Despite reducing the daily dose by 30% at baseline as recommended by the manufacturer, Tac-trough levels remained stable, reflected by an increase in the concentration-dose (C/D) ratio. No episodes of graft rejection or loss occurred. Our data suggest that the use of LCP-Tac in liver transplant patients is safe and can increase adherence to immunosuppression compared to conventional IR-Tac.