Tayyab S. Diwan

Breakthroughs in hepatitis C virus (HCV) treatment and rising rates of intravenous drug use have led to an increase in the number of organ donors who are HCV antibody-positive but serum nucleic acid test (NAT)-negative. The risk of HCV transmission from the liver grafts of these donors to recipients is unknown. To estimate the incidence of HCV transmission, we prospectively followed 26 consecutive HCV antibody-negative (n = 25) or NAT-negative (n = 1) transplant recipients who received a liver graft from donors who were HCV antibody-positive but serum NAT-negative between March 2016 and March 2017. HCV transmission was considered to have occurred if recipients exhibited a positive HCV PCR test by 3 months following transplantation. Drug overdose was listed as the cause of death in 15 (60%) of the donors. One recipient died 18 days after transplantation from primary graft nonfunction and was excluded. Of the remaining 25 recipients, HCV transmission occurred in 4 (16%), at a median follow-up of 11 months, all from donors who died of drug overdose. Three of these patients were treated with direct-acting antiviral therapy, with two achieving a sustained virologic response and one an end-of-treatment response. One patient with HCV transmission died after a complicated postoperative course and did not receive antiviral therapy. CONCLUSION: In this prospective cohort of non-HCV liver recipients receiving grafts from HCV antibody-positive/NAT-negative donors, the incidence of HCV transmission was 16%, with the highest risk conferred by donors who died of drug overdose; given the availability of safe and highly effective antiviral therapies, use of such organs could be considered to expand the donor pool. (Hepatology 2018;67:1673-1682).

The use of donation after circulatory death (DCD) liver allografts has been constrained by limitations in the duration of donor warm ischemia time (DWIT), donor agonal time (DAT), and cold ischemia time (CIT). The purpose of this study is to assess the impact of longer DWIT, DAT, and CIT on graft survival and other outcomes in DCD liver transplants. The Scientific Registry of Transplant Recipients was queried for adult liver transplants from DCD donors between 2009 and 2015. Donor, recipient, and center variables were included in the analysis. During the study period, 2107 patients underwent liver transplant with DCD allografts. In most patients, DWIT and DAT were <30 minutes. DWIT was <30 minutes in 1804 donors, between 30 and 40 minutes in 248, and >40 minutes in 37. There was no difference in graft survival, duration of posttransplant hospital length of stay, and readmission rate between DCD liver transplants from donors with DWIT <30 minutes and DWIT between 30 and 40 minutes. Similar outcomes were noted for DAT. In the multivariate analysis, DAT and DWIT were not associated with graft loss. The predictors associated with graft loss were donor age, donor sharing, CIT, recipient admission to the intensive care unit, recipient ventilator dependence, Model for End-Stage Liver Disease score, and low-volume transplant centers. Any CIT cutoff >4 hours was associated with increased risk for graft loss. Longer CIT was also associated with a longer posttransplant hospital stay, higher rate of primary nonfunction, and hyperbilirubinemia. In conclusion, slightly longer DAT and DWIT (up to 40 minutes) were not associated with graft loss, longer posttransplant hospitalization, or hospital readmissions, whereas longer CIT was associated with worse outcomes after DCD liver transplants.

Nonalcoholic steatohepatitis (NASH) is projected to become the leading indication for liver transplantation (LT) in the next decade in the United States. Strategies to treat the underlying etiology of NASH, which is almost always obesity, are being pursued. One such strategy is the utilization of bariatric surgery (BS) in the peritransplant period. The use of BS prior to LT could prevent the progression of NASH and abrogate the need for LT. BS at the time of LT or postoperatively has the potential to not only improve obesity-associated conditions such as diabetes, but also the potential to influence the incidence of NASH in the post-LT setting. However, there continues to be no consensus on the use and timing of BS in this patient population. This review aims to discuss the current literature and possible future action.

BACKGROUND: Donor specific alloantibody producing plasma cells (DSA-PCs) appear resistant to conventional immunosuppressive agents. This study aimed to determine the impact of pretransplant monotherapy with the proteasome inhibitor bortezomib on DSA-PCs in sensitized renal allograft candidates and to assess if DSA-PC depletion would enhance the efficacy of DSA removal using plasma exchange (PE). METHODS: Only patients with DSA levels considered too high to successfully undergo transplantation with PE alone were included in this study: i.e. those with a baseline B flow cytometric crossmatch (BFXM) >450 against a potential living donor.Four sensitized patients received 4 doses (1.3 mg/m/dose) of bortezomib and 4 received 16 doses. The number of DSA-PCs was determined pre and post-treatment using an ELISPOT assay. Five of these patients underwent post-treatment PE and their response was compared to 8 highly-sensitized patients (BFXM >450) who underwent PE alone. RESULTS: When considering all 8 patients as one group, bortezomib treatment decreased DSA-PCs in the marrow (mean±SD=16.7±14.5 DSA-PCs/ml pre-treatment vs. 6.2±3.6 DSA-PCs/ml after treatment, P=0.048). In the time frame of the study, bortezomib alone did not decrease serum DSA levels. However, five bortezomib treated patients underwent PE and showed a greater decease in DSA compared to the historical control group of 8 sensitized patients who underwent PE alone (mean decrease in BFXM channel shift=272.6±92.1 with bortezomib vs 95.4±72.2 in PE alone P=0.008). CONCLUSIONS: Bortezomib depletes DSA-PCs and appears to potentiate DSA removal by PE in sensitized renal transplant recipients.