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Direct-acting antiviral (DAA) therapy has transformed the management of human immunodeficiency virus (HIV) and hepatitis C (HCV) coinfected patients with advanced liver disease. STOP-Coinfection was a multicenter prospective and retrospective, open-label study using sofosbuvir-based DAA therapy to treat HIV/HCV-coinfected participants pre- or post-liver transplant (LT). Sixty-eight participants with end-stage liver disease (Child-Turcotte-Pugh score ≥7 and Model for End-Stage Liver Disease score 6-29) were enrolled, 26 had hepatocellular carcinoma. Forty-two participants were treated pre-LT and 26 post-LT. All participants completed therapy without need for dose reduction or transfusion; eight required two or more courses of therapy. Ninety-three percent achieved a sustained virologic response and DAA therapy was well tolerated. Despite HCV cure, 12 end-stage liver disease participants required subsequent LT, 7 for decompensated liver disease. Thirteen participants died, 10 with decompensated liver disease pre-LT and three post-LT. Overall, transplant free survival was 42.8% at 4 years and post-LT survival was 87.9% at 5 years. We conclude that sofosbuvir-based DAA therapy is safe and highly effective in HCV-HIV patients with decompensated liver disease and post-LT, with post-LT survival rates comparable to other indications. This removes one of the last barriers to liver transplantation in this challenging cohort of recipients., (© 2020 The American Society of Transplantation and the American Society of Transplant Surgeons.)

With the advent of direct-acting antiviral agents, there has been a rapid rise in hepatitis C virus-infected (HCV+) heart transplantation. We aimed to understand local and regional differences in utilization and allocation of HCV+ hearts. Using United Network for Organ Sharing (UNOS) de-identified data from January 1, 2016 to September 30, 2019 we compared trends in the utilization rates (hearts transplanted/donors recovered) of HCV-uninfected (HCV-) to those of HCV+ nonviremic (HCV-NV) and viremic (HCV-V) hearts nationally and by UNOS region. We also evaluated allocation rates (hearts successfully allocated/donors recovered) by organ procurement organization (OPO). We found that (1) in 2019, national utilization rates for HCV-NV and HCV-V hearts were the same as HCV- hearts (27.6% for HCV-NV, 30.9 for HCV-V, and 31.7% for HCV-, P = .277); (2) utilization rates of HCV-NV hearts were low in regions 3 and 4 and of HCV-V hearts in regions 3, 4, and 8 even in the contemporary period since 2018; and (3) there was marked variability in allocation of HCV+ hearts at the OPO level even within the same UNOS region. We conclude that despite national strides in the utilization of HCV+ hearts for transplantation, more aggressive allocation of HCV+ hearts at the OPO level may still significantly affect the organ shortage., (© 2020 The American Society of Transplantation and the American Society of Transplant Surgeons.)

We conducted an adaptive design single-center pilot trial between October 2017 and November 2018 to determine the safety and efficacy of ultra-short-term perioperative pangenotypic direct acting antiviral (DAA) prophylaxis for deceased hepatitis C virus (HCV)-nucleic acid test (NAT) positive donors to HCV negative kidney recipients (D+/R-). In Group 1, 10 patients received one dose of SOF/VEL (sofusbuvir/velpatasvir) pretransplant and one dose on posttransplant Day 1. In Group 2A (N = 15) and the posttrial validation (Group 2B; N = 25) phase, patients received two additional SOF/VEL doses (total 4) on Days 2 and 3 posttransplant. Development of posttransplant HCV transmission triggered 12-week DAA therapy. For available donor samples (N = 27), median donor viral load was 1.37E + 06 IU/mL (genotype [GT]1a: 70%; GT2: 7%; GT3: 23%). Overall viral transmission rate was 12% (6/50; Group 1:30% [3/10]; Group 2A:13% [2/15]; Group 2B:4% [1/25]). For the 6 viremic patients, 5 (83%) achieved sustained virologic response (3 with first-line DAA therapy; and two after retreatment with second-line DAA). At a median follow-up of 8 months posttransplant, overall patient and allograft survivals were 98%, respectively. The 4-day strategy reduced viral transmission to 7.5% (3/40; 95% confidence interval [CI]: 1.8%-20.5%) and could result in avoidance of prolonged posttransplant DAA therapy for most D+/R - transplants., (© 2019 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Patients with end-stage renal disease (ESRD) who are coinfected with hepatitis C virus (HCV) and human immunodeficiency virus (HIV) have access to effective treatment options for HCV infection. However, they also have access to HCV-infected kidneys, which historically afford shorter times to transplantation. Given the high waitlist mortality and rapid progression of liver fibrosis among coinfected kidney-only transplant candidates, identification of the optimal treatment strategy is paramount. Two strategies, treatment pre- and posttransplant, were compared using Monte Carlo microsimulation of 1 000 000 candidates. The microsimulation was stratified by liver fibrosis stage at waitlist addition and wait-time over a lifetime time horizon. Treatment posttransplant was consistently cost-saving as compared to treatment pretransplant due to the high cost of dialysis. Among patients with low fibrosis disease (F0-F1), treatment posttransplant also yielded higher life months (LM) and quality-adjusted life months (QALM), except among F1 candidates with wait times ≥ 18 months. For candidates with advanced liver disease (F2-F4), treatment pretransplant afforded more LM and QALM unless wait time was <18 months. Moreover, treatment pretransplant was cost-effective for F2 candidates with wait times >71 months and F3 candidates with wait times >18 months. Thus, optimal timing of HCV treatment differs based on liver disease severity and wait time, favoring pretransplant treatment when cirrhosis development prior to transplant seems likely., (© 2018 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Currently many but not all centers transplant hepatitis C virus (HCV) viremic positive (+) donor kidneys into HCV+ recipients. Directed donation of HCV+ organs reduces the wait time to transplantation for HCV+ patients. Direct-acting antiviral (DAA) therapy can cure HCV in virtually all who are infected. Some have suggested that treatment of HCV+ waitlisted patients be deferred with the hope that earlier transplantation will provide better outcomes than early DAA therapy. However, there are not enough organs to guarantee prompt transplantation for the current waitlist of infected candidates. A Markov medical decision analysis model was created to compare the overall outcomes of delayed DAA therapy (Option 1) to immediate DAA therapy (Option 2) in waitlisted HCV+ patients. Option 1 patients were modeled to be transplanted 1 year earlier, with a higher cumulative transplant incidence (54% at 5 years post-listing vs 45% for Option 2). Despite this, Option 2 provided 0.43 (95% confidence interval [CI] 0.38-0.49) more life years than Option 1. However, Option 1 was preferred for regions with much greater access to HCV+ organs or in patients with very low HCV+-associated mortality. The best option from an individual patient's perspective will differ by region and candidate., (© 2018 The American Society of Transplantation and the American Society of Transplant Surgeons.)