The outcome of orthotopic liver transplantation (OLT) with controlled graft donation after cardiac death (DCD) is usually inferior to that with graft donation after brain death (DBD). This study compared outcomes from OLT with DBD versus controlled DCD donors with predefined restrictive acceptance criteria. All adult recipients in the Netherlands in 2001–2006 with full-size OLT from DCD (n = 55) and DBD (n = 471) donors were included. Kaplan–Meier, log rank and Cox regression analyses were used. One- and 3-year patient survival rates were similar for DCD (85 and 80 per cent) and DBD (86·3 and 80·8 per cent) transplants (P = 0·763), as were graft survival rates (74 and 68 per cent versus 80·4 and 74·5 per cent; P = 0·212). The 3-year cumulative percentage of surviving grafts developing non-anastomotic biliary strictures was 31 per cent after DCD and 9·7 per cent after DBD transplantation (P < 0·001). The retransplantation rate was similar overall (P = 0·081), but that for biliary stricture was higher in the DCD group (P < 0·001). Risk factors for 1-year graft loss after DBD OLT were transplant centre, recipient warm ischaemia time and donor with severe head trauma. After DCD OLT they were transplant centre, donor warm ischaemia time and cold ischaemia time. DCD graft was a risk factor for non-anastomotic biliary stricture. OLT using controlled DCD grafts and restrictive criteria can result in patient and graft survival rates similar to those of DBD OLT, despite a higher risk of biliary stricture.

Background: The potential anti-cancer effects of mammalian target of rapamycin (mTOR) inhibitors are being intensively studied. To date, however, few randomised clinical trials (RCT) have been performed to demonstrate anti-neoplastic effects in the pure oncology setting, and at present, no oncology endpoint-directed RCT has been reported in the high-malignancy risk population of immunosuppressed transplant recipients. Interestingly, since mTOR inhibitors have both immunosuppressive and anti-cancer effects, they have the potential to simultaneously protect against immunologic graft loss and tumour development. Therefore, we designed a prospective RCT to determine if the mTOR inhibitor sirolimus can improve hepatocellular carcinoma (HCC)-free patient survival in liver transplant (LT) recipients with a pre-transplant diagnosis of HCC. Methods/Design: The study is an open-labelled, randomised, RCT comparing sirolimus-containing versus mTOR-inhibitor-free immunosuppression in patients undergoing LT for HCC. Patients with a histologically confirmed HCC diagnosis are randomised into 2 groups within 4-6 weeks after LT; one arm is maintained on a centre-specific mTOR-inhibitor-free immunosuppressive protocol and the second arm is maintained on a centre-specific mTOR-inhibitor-free immunosuppressive protocol for the first 4-6 weeks, at which time sirolimus is initiated. A 2^1/2 -year recruitment phase is planned with a 5-year follow-up, testing HCC-free survival as the primary endpoint. Our hypothesis is that sirolimus use in the second arm of the study will improve HCC-free survival. The study is a non-commercial investigator-initiated trial (IIT) sponsored by the University Hospital Regensburg and is endorsed by the European Liver and Intestine Transplant Association; 13 countries within Europe, Canada and Australia are participating. Discussion: If our hypothesis is correct that mTOR inhibition can reduce HCC tumour growth while simultaneously providing immunosuppression to protect the liver allograft from rejection, patients should experience less post-transplant problems with HCC recurrence, and therefore could expect a longer and better quality of life. A positive outcome will likely change the standard of posttransplant immunosuppressive care for LT patients with HCC. Trial Register: Trial registered at http://www.clinicaltrials.gov: NCT00355862 (EudraCT Number: 2005-005362-36)

Summary: Background: After liver transplantation primary sclerosing cholangitis (PSC), the condition returns in the transplanted liver in a subset of patients (recurrent primary sclerosing cholangitis, rPSC).Aim: To define risk factors for rPSC.Methods: We searched Pubmed, Embase, Web of Science, and Cochrane library for articles published until March 2018. Studies addressing risk factors for developing rPSC were eligible for inclusion. A random effects meta‐analysis was conducted using hazard ratios (HR) as effect measure. Study quality was evaluated with the Newcastle Ottawa scale. Statistical analysis was performed using Cochrane Review Manager.Results: The electronic database search yielded 449 results. Twenty‐one retrospective cohort studies met the inclusion criteria for the review; 14 were included in the meta‐analysis. The final cohort included 2159 patients (age range 31‐49 years, 68.8% male), of whom 17.7% developed rPSC. Colectomy before liver transplantation, HR 0.65 (95% CI: 0.42‐0.99), cholangiocarcinoma before liver transplantation, HR 2.42 (95% CI: 1.20‐4.86), inflammatory bowel disease, HR 1.73 (95% CI: 1.17‐2.54), donor age, HR 1.24 (95% CI 1.0‐1.45) per ten years, MELD score, HR 1.05 (95% CI: 1.02‐1.08) per point and acute cellular rejection, HR of 1.94 (95% CI: 1.32‐2.83) were associated with the risk of rPSC.Conclusions: Multiple risk factors for rPSC were identified. Colectomy before liver transplantation reduced the risk of rPSC.

Patients with autoimmune hepatitis (AIH) almost inevitably require lifelong immunosuppressive treatment. There is genuine concern about the efficacy and tolerability of the current standard combination therapy of prednisolone and azathioprine. Mycophenolate mofetil (MMF) has emerged as an alternative option. The aim of this study was to compare MMF to azathioprine as induction therapy. In this 24-week, prospective, randomised, open-label, multicentre superiority trial, 70 patients with treatment-naive AIH received either MMF or azathioprine, both in combination with prednisolone. The primary endpoint was biochemical remission defined as normalisation of serum levels of alanine aminotransferase and immunoglobulin G after 24 weeks of treatment. Secondary endpoints included safety and tolerability. Seventy patients (mean 57.9 years (standard deviation (SD) 14.0); 72.9% female) were randomly assigned to the MMF plus prednisolone (n=39) or azathioprine plus prednisolone (n=31) group. The primary endpoint was met in 56.4% and 29.0% of patients assigned to the MMF group and the azathioprine group, respectively (difference, 27.4 percentage points; 95% confidence interval (CI), 4.0 to 46.7; p=0.022). The MMF group exhibited higher complete biochemical response rates at 6 months (72.2% vs. 32.3%; p=0.004). No serious adverse events occurred in patients who received MMF (0%) but serious adverse events were reported in four patients who received azathioprine (12.9%) (p=0.034). Two patients in the MMF group (5.1%) and eight patients in the azathioprine group (25.8%) discontinued treatment owing to adverse events or serious adverse events (p=0.018). In patients with treatment-naive AIH, MMF with prednisolone achieved a significantly higher rate of biochemical remission at 24 weeks compared to azathioprine combined with prednisolone. Azathioprine use was associated with more (serious) adverse events leading to cessation of treatment, suggesting superior tolerability of MMF. This randomised controlled trial directly compares azathioprine and mycophenolate mofetil (MMF), both in combination with prednisolone, for the induction of biochemical remission in treatment-naive patients with autoimmune hepatitis (AIH). Achieving complete remission is desirable to prevent disease progression. Patients assigned to the MMF group reached biochemical remission more often and experienced fewer adverse events. The findings in this trial may contribute to the re-evaluation of international guidelines for the standard of care in treatment-naive patients with AIH. #NCT02900443.