Treatment of HCV infection in liver transplant recipients with ledipasvir and sofosbuvir without ribavirin.

BACKGROUND: Ledipasvir and sofosbuvir is a well-tolerated regimen with high sustained virological response (SVR) rates in pre-liver transplant patients infected with chronic hepatitis C virus (HCV), but data in liver transplant recipients outside of clinical trials is limited. AIM: To address this knowledge gap and assess SVR rates without the use of ribavirin in liver transplant recipients METHODS: This is a retrospective study examining the treatment of 75 post-liver transplant recipients with ledipasvir and sofosbuvir without ribavirin. Differences between SVR cohorts and predictors of SVR were analysed in an intention-to-treat (ITT) fashion. RESULTS: A total of 408 genotype 1, HCV patients were treated with ledipasvir/sofosbuvir from October 2014 to August 2015 at our centre. Seventy-three patients were post-liver transplant and were treated with a median of 2.9 years from transplant. Ledipasvir/sofosbuvir achieved an SVR12 of 95.9%. African Americans made up 28.8% of the cohort. Sixty-three per cent of patients were treated previously, including 13.7% of patients previously treated with direct-acting antivirals. Only 2.7% had recurrent allograft cirrhosis, and the majority (90.4%) was on calcineurin inhibitor based immunosuppressive therapy. Approximately 82% of patients had chronic kidney disease (CKD) stage 2 or 3. In univariate logistic regression, only detectable week 8 viral load was predictive of failure to achieve SVR. CONCLUSION: Our data confirm excellent SVR outcomes and favourable safety and tolerability profiles with ledipasvir/sofosbuvir without ribavirin in post-liver transplant recipients infected with HCV, despite treatment guidelines to use ribavirin.

One Size Does Not Fit All--Regional Variation in the Impact of the Share 35 Liver Allocation Policy.

Allocation policies for liver transplantation underwent significant changes in June 2013 with the introduction of Share 35. We aimed to examine the effect of Share 35 on regional variation in posttransplant outcomes. We examined two patient groups from the United Network for Organ Sharing dataset; a pre-Share 35 group composed of patients transplanted between June 17, 2012, and June 17, 2013 (n = 5523), and a post-Share group composed of patients transplanted between June 18, 2013, and June 18, 2014 (n = 5815). We used Kaplan-Meier and Cox multivariable analyses to compare survival. There were significant increases in allocation Model for End-stage Liver Disease (MELD) scores, laboratory MELD scores, and proportions of patients in the intensive care unit and on mechanical, ventilated, or organ-perfusion support at transplant post-Share 35. We also observed a significant increase in donor risk index in this group. We found no difference on a national level in survival between patients transplanted pre-Share 35 and post-Share 35 (p = 0.987). Regionally, however, posttransplantation survival was significantly worse in the post-Share 35 patients in regions 4 and 10 (p = 0.008 and p = 0.04), with no significant differences in the remaining regions. These results suggest that Share 35 has been associated with transplanting "sicker patients" with higher MELD scores, and although no difference in survival is observed on a national level, outcomes appear to be concerning in some regions.

Kidney, pancreas and liver allocation and distribution in the United States.

Kidney transplant and liver transplant are the treatments of choice for patients with end-stage renal disease and end-stage liver disease, respectively. Pancreas transplant is most commonly performed along with kidney transplant in diabetic end-stage renal disease patients. Despite a steady increase in the numbers of kidney and liver transplants performed each year in the United States, a significant shortage of kidneys and livers available for transplant remains. Organ allocation is the process the Organ Procurement and Transplantation Network (OPTN) uses to determine which candidates are offered which deceased donor organs. OPTN is charged with ensuring the effectiveness, efficiency and equity of organ sharing in the national system of organ allocation. The policy has changed incrementally over time in efforts to optimize allocation to meet these often competing goals. This review describes the history, current status and future direction of policies regarding the allocation of abdominal organs for transplant, namely the kidney, liver and pancreas, in the United States.