Search

The risk of keratinocyte cancer is determined by intrinsic and extrinsic factors, which also influence skin aging. Few studies have linked skin aging and UV exposure with the incidence of non-melanoma skin cancer (NMSC). We evaluated signs of actinic skin damage and aging, individual UV burden, and melanocortin-1 receptor ( MC1R ) variants. A total of 194 organ transplant recipients (OTR) who suffered from NMSC were compared to 194 tumor-free controls matched for gender, age, type of transplanted organ, post-transplantation (TX) period, and immunosuppressive therapy. Compared with the cases, the controls scored higher in all skin aging scores and there were no differences in UV burden except for intentional whole-body UV exposure for specific UV scenarios and periods of life in favor of cases. The number of NMSCs correlated with all types of skin aging scores, the extent of intentional sun exposure, older age, longer post-TX period, shorter interval from TX to first NMSC, and specific MC1R risk groups. Multivariable models revealed a 7.5-fold risk of developing NMSC in individuals with actinic keratosis; 4.1- or 3.6-fold in those with green or blue eyes, respectively; and a 1.9-fold increased risk in the MC1R medium- + high-risk group. In the absence of skin aging contributing to NMSC development, certain MC1R risk types may identify OTR at risk for high tumor burden.

Objective: Early diagnosis or rule-out of acute coronary syndrome (ACS) is a key competence of emergency medicine. Changes in the NSTE-ACS guidelines of the European Society of Cardiology (ESC) in 2015 and 2020 both warranted a henceforth more conservative approach regarding high-sensitivity troponin t (hsTnt) testing. We aimed to assess the impact of more conservative guidelines on the frequency of early rule-out and prolonged observation with repeated hsTnt testing at a high-volume tertiary care emergency department., Patients and Methods: We conducted a pre- and post-changeover analysis 3 months before and 3 months after transition from less (hsTnt cut-off 30 ng/L, 3-hour rule-out) to more conservative (hsTnt cut-off 14 ng/L, 1-hour rule-out) guidelines in 2015, comparing proportions of patients requiring repeated testing., Results: We included 5442 cases of symptoms suspicious of acute cardiac origin (3451 before, 1991 after, 2370 (44%) female, age 55 (SD 19) years). The proportion of patients fulfilling early-rule out criteria decreased from 68% (2348 patients) before to 60% (1195 patients) with the 2015 guidelines (P < .01). Those requiring repeated testing significantly (P < .01) increased from 22% (743 patients) to 25% (494 patients). Positive results in repeated testing significantly (P = .02) decreased from 43% (320 patients) to 37% (181 patients). Invasive diagnostics were performed in 91 patients (2.6%) before and in 75 patients (3.8%) after (P = .02) the guideline revision., Conclusion: The implementation of the more conservative 2015 ESC guidelines led to a minor rise in prolonged observations because of an increase in negative repeated testing and to an increase in invasive procedures., (© 2021 The Authors. International Journal of Clinical Practice published by John Wiley & Sons Ltd.)

Background: The Milan criteria are recommended to select hepatocellular carcinoma (HCC) patients for liver transplantation (LT). The utility of other selection criteria, such as the alpha-fetoprotein-adjusted-to-HCC-size (AFP-UTS) criteria, is still unclear., Objective: We investigated, in HCC patients who underwent LT, the survival and the recurrence after LT according to AFP-UTS and Milan criteria, the impact of early recurrence and the correlation between radiological and pathological staging., Methods: Adult HCC patients undergoing deceased donor LT at the Medical University of Vienna between 1997 and 2014 were retrospectively analysed., Results: Among 166 patients included, the number of patients who fulfilled Milan or AFP-UTS criteria was the same (139 [84%] each), although not all of them were the same individuals; 127 patients (77%) fulfilled both Milan and AFP-UTS criteria. Median overall survival of patients within AFP-UTS was 126.9 versus 34.2 months outside AFP-UTS (5-year survival rate 71% vs. 43%; p = 0.104). The 5-year recurrence rate was significantly lower in patients fulfilling the AFP-UTS criteria (18%) than in those exceeding AFP-UTS (64%; p < 0.001). Of the 139 patients within Milan criteria on imaging, 24 (17%) had microvascular invasion and 47 (34%) were outside Milan according to explant histology. Early recurrence correlated with AFP-UTS and was associated with dismal survival (median overall survival 17.2 vs. 122.1 months, p = 0.002)., Conclusions: The overall survival of patients within AFP-UTS criteria was favourable with a 5-year survival rate above 70%. Early recurrence is associated with worse survival after LT. The AFP-UTS criteria may be more suitable to exclude patients at high risk of (early) recurrence than Milan criteria., (© 2020 The Authors. United European Gastroenterology Journal published by Wiley Periodicals LLC. on behalf of United European Gastroenterology.)

The quantification of donor-derived cell-free DNA (ddcfDNA) in recipient's plasma is a novel, but technically challenging noninvasive method to assist the diagnosis of acute rejection (AR). A quantitative real-time PCR (qPCR) approach targeting insertion/deletion polymorphisms (INDEL) was adapted to measure ddcfNA in plasma samples from 29 kidney transplant recipients obtained at time of clinically indicated biopsies (eight patients with a histologically verified AR, nine with borderline rejection and 12 without evidence of rejection). Measured ddcfDNA levels of smaller INDEL amplicon targets differed significantly (P = 0.016, Kruskal-Wallis H test) between recipients with biopsy-proven AR (median 5.24%; range 1.00-9.03), patients without (1.50%; 0.41-6.50) and patients with borderline AR (1.91%; 0.58-5.38). Similarly, pairwise testing by Mann-Whitney U-tests revealed significant differences between recipients with AR and without AR (P = 0.012) as well as patients with AR and borderline histology (P = 0.015). Receiver operating characteristic (ROC) analysis revealed an area under the ROC curve for discriminating AR and non-AR biopsies of 0.84 (95% CI: 0.66-1.00). The determined cutoff value of 2.7% ddcfDNA showed a sensitivity of 0.88 (95% CI: 0.63-1.00) and specificity of 0.81 (95% CI: 0.64-0.98). INDEL qPCR represents a novel method to quantify ddcfDNA on standard qPCR instruments within 6-8 h with high sensitivity and specificity to detect AR., (© 2019 The Authors. Transplant International published by John Wiley & Sons Ltd on behalf of Steunstichting ESOT.)

Background: Serum C-reactive protein (CRP) is a prognostic factor for overall survival (OS) and recurrence of hepatocellular carcinoma (HCC) in patients treated with resection or non-surgical treatment. Here, we investigated the association of elevated CRP (≥1 vs. <1 mg/dL) with (i) recurrence of HCC and (ii) OS after liver transplantation (LT)., Methods: Adult HCC patients undergoing orthotopic deceased donor LT at the Medical University of Vienna between 1997 and 2014 were retrospectively analysed., Results: Among 216 patients included, 132 (61.1%) were transplanted within the Milan criteria and forty-two patients (19.4%) had microvascular invasion on explant histology. Seventy patients (32.4%) showed elevated CRP (≥ 1 mg/dL). On multivariate analysis, a CRP ≥ 1 mg/dL was an independent risk factor for HCC recurrence with a 5-year recurrence rate of 27.4% vs. 16.4% (HR 2.33; 95% CI 1.13-4.83; p = 0.022). OS was similar in patients with normal vs. elevated CRP levels., Conclusions: Elevated serum CRP is associated with HCC recurrence after LT and may be a marker for more aggressive tumor biology. Future studies should evaluate whether patients with elevated pre-transplant CRP levels benefit from closer monitoring for HCC recurrence., Competing Interests: We have read the journal's policy and the authors of this manuscript have the following competing interests: T.M. declares no competing interests. S.R.-R. declares no competing interests. G.G. declares no competing interests. W.S. received speaker and consulting fees and research grants from Bayer Schering Pharma; he also served as consultant for Eisai, Lilly, and BMS. T.R. has received grant support from Abbvie, Boehringer-Ingelheim, Gilead, MSD, Philips Healthcare, Gore; speaking honoraria from Gilead, Gore, Intercept, Roche, MSD; consulting/advisory board fee from Abbvie, Boehringer-Ingelheim, Gilead, MSD; and travel support from Boehringer-Ingelheim, Gilead and Roche. M.T. served as speaker for BMS, Falk, Gilead, and MSD; advisory boards for Albireo, Falk, Genfit, Gilead, Intercept, MSD, Novartis, Phenex, and Regulus. He further received travel grants from Abbvie, Falk, Gilead, and Intercept, and unrestricted research grants from Albireo, Cymabay, Falk, Gilead, Intercept, MSD, and Takeda. He is also co-inventor of a patent on the medical use of norUDCA. T.S. declares no competing interests. G.B. has received grant support from Sandoz, Chiesi, MSD, Shire; speaking honoraria from Neovii, Chiesi, Astellas; consulting/advisory board fee from Astellas, Neovii, Chiesi, Sanofi; and travel support from Astellas, Chiesi, Neovii, Biotest. M.P. served as consultant for Bayer, BMS, Eisai, and Ipsen, and received travel support from Bayer and speaking fees from Bayer and BMS. He is also an investigator for Bayer, BMS and Lilly. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Background: Drug-induced immunosuppression in kidney transplant recipients is crucial to prevent allograft rejection, but increases risk for infectious disease. Immunologic monitoring to tailor immunosuppressive drugs might prevent alloreactivity and adverse effects simultaneously. The apathogenic torque teno virus (TTV) reflects the immunocompetence of its host and might act as a potential candidate for a holistic monitoring., Methods: We screened all 1010 consecutive patients from the prospective Vienna Kidney Transplant Cohort Study for availability of allograft biopsies and adequately stored sera for TTV quantification by polymerase chain reaction., Results: Patients with acute biopsy-proven alloreactivity according to the Banff classification (n = 33) showed lower levels of TTV in the peripheral blood compared to patients without rejection (n = 80) at a median of 43 days before the biopsy. The risk for alloreactivity decreased by 10% per log level of TTV copies/mL (risk ratio, .90 [95% confidence interval, .84-.97]; P = .005). TTV levels >1 × 106 copies/mL exclude rejection with a sensitivity of 94%. Multivariable generalized linear modeling suggests an independent association between TTV level and alloreactivity., Conclusions: TTV is a prospective biomarker for risk stratification of acute biopsy-proven alloreactivity in kidney transplant recipients and might be a potential tool to tailor immunosuppressive drug therapy., (© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America.)

Background: Renal impairment (RI) is a negative prognostic factor in Multiple Myeloma (MM) and affected patients are often excluded from autologous stem cell transplantation (ASCT). However, it remains unclear whether historically inferior outcome data still hold true., Methods: From a total of 475 eligible MM patients who had undergone ASCT between 1998 and 2016, 374 were included in this multi-centric retrospective cohort study. Renal function was determined both at the time of MM diagnosis and ASCT by estimated glomerular filtration rate (eGFR according to the MDRD formula, RI defined as eGFR < 60 ml/min/1.73m 2 ). Patients were categorized into 3 groups: A) no RI diagnosis and ASCT, B) RI at diagnosis with normalization before ASCT and C) RI both at the time of diagnosis and ASCT. Log-rank testing was used for overall and progression-free survival (OS, PFS) analysis., Conclusion: While severe RI at MM diagnosis confers a risk of shorter OS, MM progression after ASCT is not affected by any stage of renal failure. It can be concluded that ASCT can be safely carried out in MM patients with mild to moderate RI and should be pro-actively considered in those with severe RI., Results: When comparing all groups, no difference in OS and PFS was found (p = 0.319 and p = 0.904). After further stratification according to the degree of RI at the time of diagnosis, an OS disadvantage was detected for patients with an eGFR < 45 ml/min/m 2 . PFS was not affected by any RI stage.

Background: Liver transplantation (LT) in elderly recipients is controversially discussed in the literature with only little data on long-term outcome available. We aimed to evaluate the safety and efficiency of LT in elderly recipients (>65 years)., Methods: Between 1989-2016, 139 patients >65 years-old were listed for liver transplantation, and 76 (55%) were transplanted. Patient outcome and characteristics were evaluated separately for the time period before (1989-2004) and after (2005-2016) MELD-implementation. Post-transplant outcome was compared between the elderly cohort and LT-recipients aged 18-65 years (n = 1395)., Results: Overall survival of patients >65 years was better in the MELD-era compared to the earlier period (1- and 5-year-survival: 73%, 60% vs. 69%, 37%, respectively; p = 0.055). The main differences between the two groups included higher recipient age (p = 0.001) and BMI (p = 0.001), higher donor age (p < 0.001), less need of intraoperative red blood cells (p = 0.008) and a lower number of postoperative rejections (p = 0.03) after 2004. Comparing the overall survival of patients transplanted in the MELD-era aged 18-65 years vs. >65 years displayed comparable 1- and 5 year-survival rates (81%, 68% vs. 73% and 60%, respectively, p = 0.558)., Conclusion: In the modern era, outcome of patients receiving LT with >65 years is comparable to <65 year-old patients. After careful evaluation, patients >65 years old should be considered for LT., (Copyright © 2018 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Background: This study investigated the impact of Model of end-stage liver disease (MELD)-score introduction (MELDi) on waitlist mortality and post-liver transplant (LT) survival in primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC)., Methods: LT candidates with PSC or PBC listed between January 1983 and March 2016 were included and followed until December 2016. After MELDi in 2004, PBC patients were listed according to labMELD, PSC patients according to the highest MELD during active cholangitis (chMELD)., Results: In total, 100 PBC and 76 PSC patients were included. Waitlist mortality in PBC was significantly higher than in PSC (16% vs. 5.3%, p = 0.031), whereas PSC patients were significantly more often withdrawn from the waitlist due to improved condition (3.0% vs. 13.2%, p = 0.017). Competing risks analysis identified MELDi (HR = 4.12) and PBC (HR = 2.95) as significant predictors of waitlist mortality. Yet, overall 10 y-patient survival increased after MELDi by 18.8% leading to a 1 y-, 5 y-, and 10 y-patient survival of 98.2%, 70.6% and 70.6% in PBC, and 83.3%, 83.3%, and 80.6% in PSC, respectively., Conclusions: PSC patients showed significantly lower waitlist mortality irrespective of MELDi, whereas in PBC waitlist mortality further increased after MELDi. Utility of MELD and chMELD did not impair post LT outcome., (Copyright © 2018 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)

Background: Drug-induced immunosuppression following kidney transplantation is crucial to prevent allograft rejection, but increases risk for infectious disease. Tailoring of drug dosing to prevent both rejection and infection is greatly desirable. The apathogenic and ubiquitous torque teno virus (TTV) reflects immunocompetence of the host and might be a potential candidate for immunologic monitoring., Methods: To assess TTV as an infection biomarker, virus load was prospectively quantified in peripheral blood of 169 consecutive renal allograft recipients at the Medical University Vienna., Results: Patients with infection showed higher TTV levels compared to patients without infection (4.2 × 108 copies/mL [interquartile range, IQR, 2.7 × 107-1.9 × 109] vs 2.9 × 107 [IQR 1.0 × 106-7.2 × 108]; P = .006). Differences in TTV load became evident almost 3 months before infection (median 77 days, IQR 19-98). Each log level of TTV copies/mL increased the odds ratio for infection by 23% (95% confidence interval 1.04-1.45; P = .014). TTV >3.1 × 109 copies/mL corresponded to 90% sensitivity to predict infections. Logistic regression demonstrated independent association between TTV levels and infection., Conclusions: TTV quantification predicts infection after kidney transplantation and might be a potential tool to tailor immunosuppressive drug therapy.

Background & Aims: Excellent efficacy and safety profile of second-generation DAA combinations improved treatment of chronic hepatitis C (HCV) as well as in HCV recurrence after orthotopic liver transplantation (OLT). The need of ribavirin addition is under debate as anaemia and decreased renal function are prevalent in transplant cohorts. The aim of this study was thus to assess safety and long-term efficacy of RBV-free DAA combinations in HCV-recurrent patients after OLT., Patients & Methods: A total of 62 OLT recipients (male: 50%/81%; age: 60.7 ± 8.5 years [mean ± SD]; GT - 1: 48, GT - 3: 9, GT - 4: 5; cirrhosis: 34%/55% [7%/21% decompensated], fibrosing cholestatic hepatitis: 1%/2%) received RBV-free treatment with second-generation DAA combinations: sofosbuvir (SOF)/daclatasvir (DCV): 42%/68%, SOF/simeprevir (SMV): 10%/16%, SOF/ledipasvir (LDV): 6%/10% and PrOD: 4%/7%., Results: Data of at least 96 weeks of FUP after treatment cessation (mean: 120; up to 167 weeks) were analysed. All patients showed on-treatment response. By intention-to-treat (ITT) analysis, SVR12 was 97% (60/62, GT-1a: 11/11 [100%]; 1b: 33/34 [97%]; 1g: 1/1 [100%]; subtype not specified: 2/2 [100%]; GT3a: 9/9 [100%]; GT4: 4/5 [80%]) compared to SVR96 of 89% (55/62). No late relapses occurred. In total, 16 severe adverse events occurred, including two newly diagnosed carcinoma (lung cancer, hepatocellular carcinoma). Six patients died; one at treatment week 24 (HCV-RNA undetectable) and five during treatment-free FUP and after achieving SVR (SVR4: N = 1, SVR12: N = 3, after SVR96: N = 1 respectively). Reasons for death were: multi-organ failure (N = 4), impaired graft function (N = 1) and unknown (N = 1)., Conclusion: RBV-free DAA combinations for the treatment of HCV recurrence after OLT are highly efficacious and well tolerated. Our long-term data show that viral eradication is durable but not necessarily translated into beneficial long-term clinical outcome., (© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Transjugular intrahepatic portosystemic shunt (TIPS) implantation is used for treatment of several complications in patients with liver cirrhosis. Recent studies have identified a survival benefit for patients on the waiting list after TIPS implantation, but the optimal time point for TIPS implantation prior to orthotopic liver transplantation (OLT) has not been established., Study: This study retrospectively assessed patients undergoing TIPS implantation before or after listing for OLT at the Medical University of Vienna. n  = 98 patients with TIPS on the waiting list between January 1993 and December 2013 were identified ( n  = 73 (74.5%) pre-listing TIPS, n  = 25 (25.5%) post-listing TIPS). A matched control group at the time of OLT without TIPS ( n  = 60) was included., Results: More patients with post-listing TIPS (28.0%, 7/25) showed clinical improvement and went off-list than patients with pre-listing TIPS (8.2%, 6/73, p  = .0119). A similar proportion of patients with pre-listing TIPS (19.2%, 14/73) and post-listing TIPS (20.0%, 5/25) died on the OLT waiting list. Transplant surgery time was similar in patients with and without TIPS: 348(±13) vs. 337(±10) minutes ( p  = .5139). Estimated 1-year post-transplant survival was similar across all groups (pre-listing TIPS: 76.2%, post-listing TIPS: 86.0%, no TIPS: 91.2%, log-rank p  = .1506)., Conclusion: TIPS should be considered in all liver transplant candidates, since it can obviate the need for OLT and optimize bridging to OLT.

Background: Kidney transplantation represents the treatment of choice for end-stage renal disease (ESRD). However, nephrectomy bears certain short- as well as long-term risks for the healthy, voluntary donor. As obesity is increasing and is a known risk factor for surgical complications, we wanted to assess the impact of BMI on perioperative complication rates and renal function., Materials and Methods: We retrospectively assessed patients undergoing living donor kidney nephrectomy at our institution. We identified 289 donors that underwent unilateral nephrectomy between January 2006 and December 2015. Donors were categorized according to their BMI (BMI <25 kg/m 2 , BMI ≥25/<30 kg/m 2 , BMI ≥30 kg/m 2 ). Where indicated, analysis of variance (ANOVA) was used to compare groups, a stepwise linear regression model was used to assess impact of BMI on the change of eGFR., Results: 126 donors (43.6%) had a BMI <25 while 120 (41.5%) had a BMI ≥25/<30 and 43 (14.9%) were obese with a BMI ≥30. BMI had no statistically significant influence on the percentage of laparoscopic approach (86.5% vs. 83.3% vs. 88.4%, p = 0.6564), on conversion rates (0% vs. 2.0% vs. 2.6%, p = 0.2879) or postoperative complication rates defined as Clavien Dindo ≥ II (8.7% vs. 13.3% vs. 14.0%, respectively; p = 0.4474). Notably, there were no Grade III or higher complications in any group. There was no difference in pre-operative kidney function, postoperative surgical site infection or systemic infection. BMI and male sex had a statistically significant influence on short-term decline of eGFR., Conclusion: Obese donors do not suffer from an increased risk of intraoperative or perioperative complication rates. However, male sex and high BMI are associated with a more pronounced short-term decline in renal function. The impact of BMI on long-term consequences for kidney donors needs to be defined in larger prospective cohorts., (Copyright © 2017 IJS Publishing Group Ltd. Published by Elsevier Ltd. All rights reserved.)

Background & Aims: Current guidelines discourage renal replacement therapy (RRT) in critically ill cirrhotics in the lack of liver transplant (LT) options. This study aimed to identify patients who benefit from RRT in the short and long-term., Methods: Critically ill cirrhotics were included over a time period of 6 years and followed for at least 1 year. CLIF-C ACLF, CLIF-SOFA, SOFA and MELD scores on admission, 24 h prior to RRT, 24 and 48 hours after start of RRT were analysed for their predictive value of ICU-mortality. Additionally, long-term renal recovery and successful bridging to LT was assessed., Results: In total, 40% (78/193) of patients required RRT. ICU-, 28 days-, 90 days-, and 1 year-mortality was 71%, 83%, 91%, and 92%, respectively, and was significantly higher than in patients without need for RRT (4%, 30%, 43%, and 50%), P<.001. CLIF-C ACLF and CLIF - SOFA scores within 24 hours prior to RRT showed good discriminant power to predict ICU-mortality. CLIF-C ACLF calculated 48 hours after commencing RRT was the most suitable predictor of ICU-mortality in RRT-patients irrespective of LT options (AUC: 0.866). In patients with ≥5 organ failure assessed by CLIF-SOFA at any time point showed 100% ICU-mortality. 13% of patients with RRT showed renal recovery; 14% of patients could be bridged to LT., Conclusions: Mortality in critically ill cirrhotics with need for RRT is substantially high independent of LT options. Only a small proportion showed renal recovery after ICU discharge. CLIF-C ACLF and CLIF-SOFA score may assist in identifying patients who would not benefit from RRT., (© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Hypothyroidism is referred to be a rare but possible cause of hyponatremia. However, there is only poor evidence supporting this association. Since hyponatremia and hypothyroidism are both common conditions themselves, co-occurrence does not have to be causal., Methods: To address a potential relationship, a retrospective analysis of data from the Division of Endocrinology of the Medical University of Vienna from April 2004 to February 2016 was performed. A total of 8053 hypothyroid patients (48 ± 18 years of age; 71% female) with thyrotropin >4.0 μIU/mL and available blood tests for free thyroxine and sodium (Na + ) within maximal ± seven days were included and screened for hyponatremia. Patients' records were searched for concomitant disease and medication when Na + concentration was <135 mmol/L., Results: Hyponatremia was present in 448/8053 (5.56%) patients. Analysis of medical history revealed potential alternative causes of hyponatremia in 442/448 (98.88%) patients (i.e., side effects of medication, concomitant underlying disease, or other endocrine disorders). This distribution did not differ between patients suffering from clinical or subclinical hypothyroidism. No case of clinically relevant hyponatremia (Na + < 130 mmol/L), present in 111/448 (24.78%) patients could be attributed only to hypothyroidism. There was a very weak but statistically significant trend toward a positive association between thyroid function and serum Na + levels (Na + /thyrotropin: R = 0.022, p = 0.046; Na + /free thyroxine: R = -0.047, p < 0.001)., Conclusion: The results suggest that hypothyroid patients with moderate to severe hyponatremia often have other potential explanations for their low serum Na + concentrations in routine care.

Background: Nonalcoholic fatty liver disease (NAFLD) can be considered the hepatic manifestation of the metabolic syndrome with nonalcoholic steatohepatitis (NASH) as its progressive form. With increasing prevalence of the metabolic syndrome, NASH cirrhosis is becoming a leading cause for liver transplantation. Some cases of orthotopic liver transplantation (OLT) due to cryptogenic cirrhosis (CC) might show typical features of NASH cirrhosis. Therefore, our aim was to assess recurrence of liver fibrosis in patients transplanted for NASH versus CC after OLT., Patients and Methods: Patients transplanted for CC or NASH between 1 January 2004 and 30 September 2015 were included. The histological NAFLD activity score and the NAFLD fibrosis score (NFS) were assessed., Results: In total, 15 and 12 patients underwent OLT because of NASH and CC, respectively. The case load for OLT because of NASH was constantly increasing (n=2 in 2004-2007 vs. n=9 in 2012-2015) whereas decreasing for CC (n=6 in 2004-2007 vs. n=2 in 2012-2015). Patient characteristics at OLT were similar, except for an older age and a higher BMI in NASH patients (59.1±2.2 vs. 51.8±2.9 years, P=0.05; 27.7±1.2 vs. 24.3±0.8 kg/m, P=0.035). Although post-OLT plasma lipid levels and incidence of de-novo hypertension, diabetes, and hyperlipidemia were similar between groups, the post-transplant NFS re-increased in the NASH group (but not in the CC: -0.1317 vs. -1.3645 at 12 months post-OLT, P=0.0400). Post-transplant survival was similar in NASH and CC patients., Conclusion: According to the NFS, some NASH patients show recurrence of fibrosis as early as 6-12 months after OLT.

Background: Circulating donor-specific antibodies (DSA) detected on bead arrays may not inevitably indicate ongoing antibody-mediated rejection (AMR). Here, we investigated whether detection of complement-fixation, in parallel to IgG mean fluorescence intensity (MFI), allows for improved prediction of AMR., Methods: Our study included 86 DSA+ kidney transplant recipients subjected to protocol biopsy, who were identified upon cross-sectional antibody screening of 741 recipients with stable graft function at 6 months or longer after transplantation. IgG MFI was analyzed after elimination of prozone effect, and complement-fixation was determined using C1q, C4d, or C3d assays., Results: Among DSA+ study patients, 44 recipients (51%) had AMR, 24 of them showing C4d-positive rejection. Although DSA number or HLA class specificity were not different, patients with AMR or C4d + AMR showed significantly higher IgG, C1q, and C3d DSA MFI than nonrejecting or C4d-negative patients, respectively. Overall, the predictive value of DSA characteristics was moderate, whereby the highest accuracy was computed for peak IgG MFI (AMR, 0.73; C4d + AMR, 0.71). Combined analysis of antibody characteristics in multivariate models did not improve AMR prediction., Conclusions: We estimate a 50% prevalence of silent AMR in DSA+ long-term recipients and conclude that assessment of IgG MFI may add predictive accuracy, without an independent diagnostic advantage of detecting complement-fixation.

Background: Antibody-mediated rejection (AMR) represents one of the cardinal causes of late allograft loss after kidney transplantation, and there is great need for noninvasive tools improving early diagnosis of this rejection type. One promising strategy might be the quantification of peripheral blood DNA levels of the highly prevalent and apathogenic Torque Teno virus (TTV), which might mirror the overall level of immunosuppression and thus help determine the risk of alloimmune response., Methods: To assess the association between TTV load in the peripheral blood and AMR, 715 kidney transplant recipients (median, 6.3 years posttransplantation) were subjected to a systematical cross-sectional AMR screening and, in parallel, TTV quantification., Results: Eighty-six of these recipients had donor-specific antibodies and underwent protocol biopsy, AMR-positive patients (n = 46) showed only 25% of the TTV levels measured in patients without AMR (P = 0.003). In a generalized linear model, higher TTV levels were associated with a decreased risk for AMR after adjustment for potential confounders (risk ratio 0.94 per TTV log level; 95% confidence interval 0.90-0.99; P = 0.02)., Conclusions: Future studies will have to clarify whether longitudinal assessment of TTV load might predict AMR risk and help guide the type and intensity of immunosuppression to prevent antibody-mediated graft injury., Competing Interests: The authors declare no conflicts of interest.

Background: In the Eurotransplant Kidney Allocation System (ETKAS), transplant candidates can be considered for high-urgency (HU) status in case of life-threatening inability to undergo renal replacement therapy. Data on the outcomes of HU transplantation are sparse and the benefit is controversial., Methods: We systematically analysed data from 898 ET HU kidney transplant recipients from 61 transplant centres between 1996 and 2010 and investigated the 5-year patient and graft outcomes and differences between relevant subgroups., Results: Kidney recipients with an HU status were younger (median 43 versus 55 years) and spent less time on the waiting list compared with non-HU recipients (34 versus 54 months). They received grafts with significantly more mismatches (mean 3.79 versus 2.42; P < 0.001) and the percentage of retransplantations was remarkably higher (37.5 versus 16.7%). Patient survival (P = 0.0053) and death with a functioning graft (DwFG; P < 0.0001) after HU transplantation were significantly worse than in non-HU recipients, whereas graft outcome was comparable (P = 0.094). Analysis according to the different HU indications revealed that recipients listed HU because of an imminent lack of access for dialysis had a significantly worse patient survival (P = 0.0053) and DwFG (P = 0.0462) compared with recipients with psychological problems and suicidality because of dialysis. In addition, retransplantation had a negative impact on patient and graft outcome., Conclusions: Facing organ shortages, increasing wait times and considerable mortality on dialysis, we question the current policy of HU allocation and propose more restrictive criteria with regard to individuals with vascular complications or repeated retransplantations in order to support patients on the non-HU waiting list with a much better long-term prognosis., (© The Author 2016. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.)

Background: Apheresis-based desensitization allows for successful transplantation across major immunological barriers. For donor-specific antibody (DSA)- and/or crossmatch-positive transplantation, however, it has been shown that even intense immunomodulation may not completely prevent antibody-mediated rejection (ABMR)., Methods: In this study, we evaluated transplant outcomes in 101 DSA+ deceased donor kidney transplant recipients (transplantation between 2009 and 2013; median follow-up: 24 months) who were subjected to immunoadsorption (IA)-based desensitization. Treatment included a single pre-transplant IA session, followed by anti-lymphocyte antibody and serial post-transplant IA. In 27 cases, a positive complement-dependent cytotoxicity crossmatch (CDCXM) was rendered negative immediately before transplantation. Seventy-four of the DSA+ recipients had a negative CDCXM already before IA., Results: Three-year death-censored graft survival in DSA+ patients was significantly worse than in 513 DSA- recipients transplanted during the same period (79 versus 88%, P = 0.008). Thirty-three DSA+ recipients (33%) had ABMR. While a positive baseline CDCXM showed only a trend towards higher ABMR rates (41 versus 30% in CDCXM- recipients, P = 0.2), DSA mean fluorescence intensity (MFI) in single bead assays significantly associated with rejection, showing 20 versus 71% ABMR rates at <5000 versus >15 000 peak DSA MFI. The predictive value of MFI was moderate, with the highest accuracy at a median of 13 300 MFI (after cross-validation: 0.72). Other baseline variables, including CDC assay results, human leukocyte antigen mismatch, prior transplantation or type of induction treatment, did not add independent predictive information., Conclusions: IA-based desensitization failed to prevent ABMR in a considerable number of DSA+ recipients. Assessing DSA MFI may help stratify risk of rejection, supporting its use as a guide to organ allocation and individualized treatment., (© The Author 2016. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.)

Alcoholic liver disease (ALD) is the second most common indication for liver transplantation (LT). The utility of fixed intervals of abstinence prior to listing is still a matter of discussion. Furthermore, post-LT long-term observation is challenging, and biomarkers as carbohydrate-deficient transferrin (CDT) may help to identify alcohol relapse. We retrospectively analyzed data from patients receiving LT for ALD from 1996 to 2012. A defined period of alcohol abstinence prior to listing was not a precondition, and abstinence was evaluated using structured psychological interviews. A total of 382 patients received LT for ALD as main (n = 290) or secondary (n = 92) indication; median follow-up was 73 months (0-213). One- and five-year patient survival and graft survival rates were 82% and 69%, and 80% and 67%, respectively. A total of 62 patients (16%) experienced alcohol relapse. Alcohol relapse did not have a statistically significant effect on patient survival (P = 0.10). Post-transplant CDT measurements showed a sensitivity and specificity of 84% and 85%, respectively. In conclusion, this large single-center analysis showed good post-transplant long-term results in patients with ALD when applying structured psychological interviews before listing. Relapse rates were lower than those reported in the literature despite using a strict definition of alcohol relapse. Furthermore, post-LT CDT measurement proved to be a useful supplementary tool for detecting alcohol relapse., (© 2016 Steunstichting ESOT.)

Belatacept was recently evaluated in liver transplantation (LT) in a phase II multicenter trial, which was terminated prematurely. Patients were more than two yr post-LT at the time. As high rates of spontaneous tolerance after LT have been reported and as belatacept has marked immunomodulatory effects, we decided to maintain the belatacept patients enrolled at our center (n = 4) on MMF monotherapy. All belatacept patients on MMF monotherapy developed graft dysfunction consistent with acute rejection after a mean period of 10.3 (7-14) wk. Patients were therefore switched to triple therapy with CNI, MMF, and corticosteroids. Graft dysfunction resolved within 1-3 wk after switch. At the time of belatacept discontinuation, mean eGFR was 105.1 mL/min/1.73 m² (92.1-118.9) in belatacept patients compared to 58 mL/min/1.73 m² (36.1-98.2) in controls (p = 0.022). One yr after the switch to CNI therapy, eGFR had declined by 27.4 mL (19.2-39.3; p = 0.008). Thus, LT patients treated with belatacept show superior kidney function that declines upon institution of CNIs. MMF monotherapy following withdrawal of belatacept is associated with a high incidence of graft dysfunction. Belatacept has no obvious immunomodulatory effects in LT recipients that would be sufficient to allow drug withdrawal with a high rate of success., (© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

No effective interventions to reduce risk for new-onset diabetes after transplantation (NODAT), a condition associated with postoperative hyperglycemia and reduced patient and graft survival, have been established. In this 1-year, proof-of-concept clinical trial, we randomly assigned 50 renal transplant recipients to immediate-postoperative isophane insulin for evening blood glucose ≥140 mg/dl (treatment group) or short-acting insulin and/or oral antidiabetic agents for blood glucose ≥180-250 mg/dl (standard-of-care control group). We included only patients without a history of diabetes who received tacrolimus. By the third postoperative evening, all patients in the treatment group had blood glucose ≥140 mg/dl and were subsequently treated with basal insulin; during the first 3 weeks after transplantation, the mean ± SD daily insulin dosage was 17±11 IU/d. Among controls, 23 (92%) of 25 had blood glucose ≥200 mg/dl and 18 (72%) of 25 received standard-of-care antihyperglycemic treatment. Asymptomatic hypoglycemia occurred five times in the treatment group and once in the control group. Throughout follow-up, the treatment group had 73% lower odds of NODAT (odds ratio, 0.27) than the control group, and hemoglobin A1c was on average 0.38% lower in the treatment group than the control group. Twelve months after transplantation, all patients in the treatment group were insulin-independent, whereas 7 (28%) of 25 controls required antidiabetic agents. The groups did not differ for insulin sensitivity, but the treatment group showed better β-cell function throughout the 1-year follow-up. In conclusion, this study suggests regimens that include basal insulin significantly reduce the odds for NODAT after renal transplantation, presumably via insulin-mediated protection of β cells.

During the 2009/10 pandemic of influenza A (H1N1), the American Society of Transplantation and other health organizations recommended that immunocompromised patients should be vaccinated as the key preventive measure. Since there are no data available for the immunogenicity of the unadjuvanted pandemic influenza vaccine in immunocompromised patients - as opposed to the adjuvanted preparation - the objective of this study was to evaluate the immunogenicity of an adjuvant-free H1N1 vaccine in recipients of solid organ transplants. Patients were recruited at the Vienna General Hospital, Austria. The vaccination schedule consisted of 2 doses of a whole-virion, vero cell derived, inactivated, non-adjuvanted influenza A/California/07/2009 (H1N1) vaccine given with an interval of 3 weeks. A hemagglutination inhibition (HI) assay on blood samples obtained prior to the first and after each vaccination was used for serologic analysis. The primary immunologic endpoint was the seroconversion rate, defined as the proportion of subjects with an individual 4-fold increase in HI titer of at least 1:40. In addition, virus-specific IgG antibodies to the pandemic H1N1 strain were measured using a commercially available ELISA. Twenty-five organ transplant patients (16 males, 9 females) aged 25-79 years were vaccinated and provided blood samples for serologic analysis. The time elapsed since transplantation was 10 months to 25 years (mean: 9 years; 95% CI 6-13 years). The vaccine was well tolerated and no local adverse events were noticed. After two vaccinations 37% of the patients demonstrated seroconversion in the HI assay as defined above and 70% had virus-specific IgG antibodies. Among the HI vaccine responders were 6 of 14 heart transplant recipients and 1 of 4 liver transplant recipients. The number and type of immunosuppressive agents did not significantly differ in their effect on the immune response. Our results show that the novel vero cell derived and adjuvant-free pandemic A/California/07/2009 (H1N1) influenza vaccine induced limited but measurable immune responses in adult recipients of solid organ transplants., (Copyright © 2011 Elsevier Ltd. All rights reserved.)