In Brief Background We investigated whether sirolimus-based immunosuppression improves outcomes in liver transplantation (LTx) candidates with hepatocellular carcinoma (HCC). Methods In a prospective-randomized open-label international trial, 525 LTx recipients with HCC initially receiving mammalian target of rapamycin inhibitor–free immunosuppression were randomized 4 to 6 weeks after transplantation into a group on mammalian target of rapamycin inhibitor–free immunosuppression (group A: 264 patients) or a group incorporating sirolimus (group B: 261). The primary endpoint was recurrence-free survival (RFS); intention-to-treat (ITT) analysis was conducted after 8 years. Overall survival (OS) was a secondary endpoint. Results Recurrence-free survival was 64.5% in group A and 70.2% in group B at study end, this difference was not significant (P = 0.28; hazard ratio [HR], 0.84; 95% confidence interval [95% CI], 0.62; 1.15). In a planned analysis of RFS rates at yearly intervals, group B showed better outcomes 3 years after transplantation (HR, 0.7; 95% CI, 0.48-1.00). Similarly, OS (P = 0.21; HR, 0.81; 95% CI, 0.58-1.13) was not statistically better in group B at study end, but yearly analyses showed improvement out to 5 years (HR, 0.7; 95% CI, 0.49-1.00). Interestingly, subgroup (Milan Criteria-based) analyses revealed that low-risk, rather than high-risk, patients benefited most from sirolimus; furthermore, younger recipients (age ≤60) also benefited, as well sirolimus monotherapy patients. Serious adverse event numbers were alike in groups A (860) and B (874). Conclusions Sirolimus in LTx recipients with HCC does not improve long-term RFS beyond 5 years. However, a RFS and OS benefit is evident in the first 3 to 5 years, especially in low-risk patients. This trial provides the first high-level evidence base for selecting immunosuppression in LTx recipients with HCC. In a large prospective randomized open-label international trial, liver transplant recipients for HCC were randomized to receive non-mTOR-inhibitor-based-treatment or mTOR-inhibitor-based-treatment. Results indicate overall sirolimus does not improve long-term recurrence-free survival beyond 5 years while a benefit was seen in low-risk patients.

BACKGROUND:We investigated whether sirolimus-based immunosuppression improves outcomes in liver transplantation (LTx) candidates with hepatocellular carcinoma (HCC). METHODS:In a prospective-randomized open-label international trial, 525 LTx recipients with HCC initially receiving mammalian target of rapamycin inhibitor-free immunosuppression were randomized 4 to 6 weeks after transplantation into a group on mammalian target of rapamycin inhibitor-free immunosuppression (group A: 264 patients) or a group incorporating sirolimus (group B: 261). The primary endpoint was recurrence-free survival (RFS); intention-to-treat (ITT) analysis was conducted after 8 years. Overall survival (OS) was a secondary endpoint. RESULTS:Recurrence-free survival was 64.5% in group A and 70.2% in group B at study end, this difference was not significant (P = 0.28; hazard ratio [HR], 0.84; 95% confidence interval [95% CI], 0.62; 1.15). In a planned analysis of RFS rates at yearly intervals, group B showed better outcomes 3 years after transplantation (HR, 0.7; 95% CI, 0.48-1.00). Similarly, OS (P = 0.21; HR, 0.81; 95% CI, 0.58-1.13) was not statistically better in group B at study end, but yearly analyses showed improvement out to 5 years (HR, 0.7; 95% CI, 0.49-1.00). Interestingly, subgroup (Milan Criteria-based) analyses revealed that low-risk, rather than high-risk, patients benefited most from sirolimus; furthermore, younger recipients (age ≤60) also benefited, as well sirolimus monotherapy patients. Serious adverse event numbers were alike in groups A (860) and B (874). CONCLUSIONS:Sirolimus in LTx recipients with HCC does not improve long-term RFS beyond 5 years. However, a RFS and OS benefit is evident in the first 3 to 5 years, especially in low-risk patients. This trial provides the first high-level evidence base for selecting immunosuppression in LTx recipients with HCC.

Background. Selective interleukin-2 receptor (IL2R) blockade is one option to decrease acute rejection rates in kidney transplant recipients. However, there are little data on the impact of basiliximab in a triple immunosuppressive regimen (tacrolimus, mycophenolate mofetil, and low-dose steroids). Thus, this analysis aims at investigating the impact of basiliximab induction on rejection rates and immediate graft function following kidney transplantation.Methods. Basiliximab was introduced in our center according to our center's policy in the beginning of 2011. Patients who received basiliximab (n = 83) were compared with patients without induction therapy (n = 65) transplanted before the introduction of IL2R antibody induction.Results. The use of basiliximab as induction therapy decreased the incidence of biopsyproven acute rejection (BPAR) within the 1st year after transplantation (21.5% vs 14.5%; P = .283). Overall rejection episodes (including BPAR and borderline rejection) were significantly reduced in patients with basiliximab compared with patients without (41.5% vs 24.1%; P = .033). However, graft function (incidence of delayed graft function, primary nonfunction, slow graft function, and serum creatinine decline) and overall outcome (patient and graft survivals) were similar in both groups.Conclusions. We found a favorable impact of basiliximab induction therapy on early acute rejection rate. The impact on long-term outcome must be addressed in further randomized controlled trials.

While belatacept has shown favorable short- and midterm results in kidney transplant recipients, only projections exist regarding its potential impact on long-term outcome. Therefore, we performed a retrospective case-match analysis of the 14 belatacept patients originally enrolled in the phase II multicenter trial at our center. Fifty six cyclosporine (CyA)-treated patients were matched according to age at transplantation, first/retransplant, and donor type. Ten years after kidney transplantation, kidney function remained superior in belatacept-treated patients compared with the CyA control group. Moreover, none of the belatacept-treated patients had donor-specific antibodies ≥10 years post-transplantation compared with 38.5% of tested CyA-treated subject (0/10 vs. 5/13; P = 0.045). Notably, however, patient and graft survival was virtually identical in both groups (71.4% vs. 71.3%; P = 0.976). In the present single-center study population, patients treated with belatacept demonstrated a patient and graft survival at 10 years post-transplant which was comparable to that of similarly selected CNI-treated patients. Larger studies with sufficient statistical power are necessary to definitively determine long-term graft survival with belatacept.

Belatacept was recently evaluated in liver transplantation (LT) in a phase II multicenter trial, which was terminated prematurely. Patients were more than twoyr 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 1-3wk after switch. At the time of belatacept discontinuation, mean eGFR was 105.1mL/min/1.73m(2) (92.1-118.9) in belatacept patients compared to 58mL/min/1.73m(2) (36.1-98.2) in controls (p=0.022). Oneyr after the switch to CNI therapy, eGFR had declined by 27.4mL (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.

In November 2004, the Austrian Society of Gastroenterology and Hepatology (ÖGGH) held for the first time a consensus meeting on the definitions and treatment of portal hypertension and its complications in the Billroth-Haus in Vienna, Austria (Billroth I-Meeting). This meeting was preceded by a meeting of international experts on portal hypertension with some of the proponents of the Baveno consensus conferences (http://www.oeggh.at/videos.asp). The consensus itself is based on the Baveno III consensus with regard to portal hypertensive bleeding and the suggestions of the International Ascites Club regarding the treatment of ascites. Those statements were modified by new knowledge derived from the recent literature and also by the current practice of medicine as agreed upon by the participants of the consensus meeting. In October 2011, the ÖGGH organized the second consensus meeting on portal hypertension and its complications in Vienna (Billroth II-Meeting). The Billroth II-Guidelines on the definitions and treatment of portal hypertension and its complications take into account the developments of the last 7 years, including the Baveno-V update and several key publications.

Transarterial chemoembolization (TACE) of hepatocellular carcinoma (HCC) is one of the most frequently applied standard treatments for this disease. The role for TACE is fairly well defined within the most widely used treatment algorithm for HCC, die Barcelona Clinic Liver Cancer (BCLC) staging system and treatment algorithm. But no general treatment algorithm will go into the technical details of any procedure and several patients will not fit ideally into the patient groups predefined in BCLC or any other treatment algorithm. Furthermore, indications and contraindications sometimes are viewed differently by the various medical specialties involved in taking care of such patients. We present here the joint expert position statement of the Austrian Societies of Gastroenterology and Hepatology (ÖGGH), Interventional Radiology (ÖGIR), Hematology and Oncology (ÖGHO), and Surgical Oncology (ASSO) on the technical aspects, indications, and contraindication for the use of TACE in the management of HCC.

The predictive value of MELD score for post-transplant survival has been under constant debate since its implementation in 2001. Aim of this study was to assess the impact of alterations in MELD score throughout waiting time (WT) on post-transplant survival. A single-centre retrospective analysis of 1125 consecutive patients listed for liver transplantation between 1997 and 2009 was performed. The impact of MELD score and dynamic changes in MELD score (DeltaMELD), as well as age, sex, year of listing and WT were evaluated on waiting list mortality and post-transplant survival. In this cohort, 539 (60%) patients were transplanted, 223 (25%) died on list and 142 (15%) were removed from the waiting list during WT. One-, three- and five-year survival after liver transplantation were 83%, 78% and 76% respectively. DeltaMELD as a continuous variable proved to be the only significant risk factor for overall survival after liver transplantation (hazard ratio (HR): 1.06, 95% confidence interval (CI) 1.021.1, P = 0.013). The highest risk of post-transplant death could be defined for patients with a DeltaMELD > 10 (HR: 4.87, 95% CI 2.0911.35, P < 0.0001). In addition, DeltaMELD as well as MELD at listing showed a significant impact on waiting list mortality. DeltaMELD may provide an easy evaluation tool to identify patients on the liver transplant waiting list with a high mortality risk after transplantation in the current setting. Temporarily withholding and re-evaluating these patients might improve overall outcome after liver transplantation.

OBJECTIVES:The aim of this study was to evaluate gadoxate-enhanced magnetic resonance imaging (MRI) in liver transplant recipients with regard to graft function and mortality at 1 year from imaging.MATERIAL AND METHODS:This was a retrospective, proof-of-concept study of gadoxate-enhanced 3-T MRI in 51 patients with orthotopic liver transplantation. Relative liver enhancement was calculated as the ratio between the signal intensities in unenhanced and gadoxate-enhanced T1-weighted gradient echo sequences with fat saturation. Impaired excretion was defined as the absence of gadoxate visualization in the common bile duct 20 minutes after intravenous injection.RESULTS:Of the 51 liver transplant recipients, 31 patients showed a normal hepatobiliary excretion of gadoxate after 20 minutes (group A), whereas 20 patients showed an impaired excretion (group B). Group B had significantly higher serum levels of bilirubin (P < 0.001), aspartate-aminotransferase (P = 0.003), and alkaline phosphatase (P = 0.007), and a higher median Model for End-Stage Liver Disease score (P < 0.001). Within one-year of MRI, 55% of group B died (n = 7) or had to undergo retransplantation (n = 4), whereas all patients in group A survived without retransplantation (P < 0.001). The relative liver enhancement 20 minutes after gadoxate injection was directly related to serum levels of cholinesterase (P < 0.001) and inversely related to the serum levels of bilirubin (P = 0.0098), aspartate-aminotransferase (P = 0.007), and the Model for End-Stage Liver Disease score (P < 0.001). The relative liver enhancement 20 minutes after contrast injection was directly related to the probability of 1-year retransplantation-free survival in proportional hazard regression analysis (P = 0.005).CONCLUSION:Gadoxate-enhanced MRI may be a helpful noninvasive prognostic biomarker for chronic rejection and increased risk for 1-year mortality or retransplantation.

In this case report we have described a patient suffering from sclerosing cholangitis, diabetes mellitus type I, and consequent end-stage renal disease who was successfully treated with simultaneous pancreas and kidney transplantation 9 years after orthotopic liver transplantation.

The impact of vesicoureteral reflux (VUR) on renal allograft outcomes is debatable, with small cohort studies reporting controversial results. The objective of this retrospective study was to evaluate long-term clinical effects of early VUR in a large cohort of kidney transplant patients. Posttransplantation voiding cystourethrography was used to evaluate 646 consecutive kidney transplant recipients before discharge. The study endpoints included VUR grade, death-censored graft or patient survival, renal function, proteinuria and occurrence of urinary tract infections (UTIs). Of the 646 recipients, 263 (40.7%) were diagnosed with VUR. VUR grade II was most common (19.8%), followed by grades III (10.2%), I (7.9%) and IV (2.8%). VUR was less common in transplantations performed by experienced compared to inexperienced surgeons (36% vs. 48%; p = 0.004). VUR did not affect death-censored graft or patient survival and was not associated with proteinuria or occurrence of UTIs. Patients with VUR had a lower eGFR at 1 year after transplantation than did patients without VUR (60 vs. 52 mL/min/1.73 m2; p = 0.02), although this difference was not observed at 3 and 5 years after transplantation. We conclude that early VUR, a common finding among renal transplant patients, may not have a meaningful impact on long-term transplant outcomes.