IMPORTANCE Ischemic cold storage (ICS) of livers for transplant is associated with serious posttransplant complications and underuse of liver allografts.OBJECTIVE To determine whether portable normothermic machine perfusion preservation of livers obtained from deceased donors using the Organ Care System (OCS) Liver ameliorates early allograft dysfunction (EAD) and ischemic biliary complications (IBCs). DESIGN, SETTING, AND PARTICIPANTSThis multicenter randomized clinical trial (International Randomized Trial to Evaluate the Effectiveness of the Portable Organ Care System Liver for Preserving and Assessing Donor Livers for Transplantation) was conducted between November 2016 and October 2019 at 20 US liver transplant programs. The trial compared outcomes for 300 recipients of livers preserved using either OCS (n = 153) or ICS (n = 147). Participants were actively listed for liver transplant on the United Network of Organ Sharing national waiting list. INTERVENTIONS Transplants were performed for recipients randomly assigned to receive donor livers preserved by either conventional ICS or the OCS Liver initiated at the donor hospital. MAIN OUTCOMES AND MEASURESThe primary effectiveness end point was incidence of EAD. Secondary end points included OCS Liver ex vivo assessment capability of donor allografts, extent of reperfusion syndrome, incidence of IBC at 6 and 12 months, and overall recipient survival after transplant. The primary safety end point was the number of liver graft-related severe adverse events within 30 days after transplant. RESULTSOf 293 patients in the per-protocol population, the primary analysis population for effectiveness, 151 were in the OCS Liver group (mean [SD] age, 57.1 [10.3] years; 102 [67%] men), and 142 were in the ICS group (mean SD age, 58.6 [10.0] years; 100 [68%] men). The primary effectiveness end point was met by a significant decrease in EAD (27 of 150 [18%] vs 44 of 141 [31%]; P = .01). The OCS Liver preserved livers had significant reduction in histopathologic evidence of ischemia-reperfusion injury after reperfusion (eg, less moderate to severe lobular inflammation: 9 of 150 [6%] for OCS Liver vs 18 of 141 [13%] for ICS; P = .004). The OCS Liver resulted in significantly higher use of livers from donors after cardiac death (28 of 55 [51%] for the OCS Liver vs 13 of 51 [26%] for ICS; P = .007). The OCS Liver was also associated with significant reduction in incidence of IBC 6 months (1.3% vs 8.5%; P = .02) and 12 months (2.6% vs 9.9%; P = .02) after transplant.CONCLUSIONS AND RELEVANCE This multicenter randomized clinical trial provides the first indication, to our knowledge, that normothermic machine perfusion preservation of deceased donor livers reduces both posttransplant EAD and IBC. Use of the OCS Liver also resulted in increased use of livers from donors after cardiac death. Together these findings indicate that OCS Liver preservation is associated with superior posttransplant outcomes and increased donor liver use.

Recurrent NAFLD is common post-LT occurring in nearly 88% of all patients, whereas nearly a quarter of patients were noted to have advanced fibrosis.

Coronary artery disease (CAD) is an important contributor to morbidity and mortality in patients undergoing liver transplantation (LT). However, the current literature is limited by sampling bias and nondefinitive assessment of CAD. The current study examines the prevalence of CAD via per protocol coronary angiography and its relationship to etiology of liver disease in patients undergoing liver transplantation evaluation (LTE). Data on 228 patients were prospectively collected who had coronary angiography as part of LTE between 2011 and 2014. Coronary angiography was done in all patients age ≥50 years or with CAD risk factors. CAD was defined as any coronary artery stenosis, whereas stenosis ≥ 70% in distribution of 1 or 3 major coronary arteries was considered as single- or triple-vessel disease. CAD was detected in 36.8% of patients, with the highest prevalence among nonalcoholic steatohepatitis (NASH) patients with cirrhosis (52.8%). Prevalence of single-vessel disease was higher among patients with NASH compared with hepatitis C virus (HCV) and alcoholic cirrhosis (15.1% versus 4.6% versus 6.6%; P = 0.02). Similarly, patients with NASH were more likely to have triple-vessel disease when compared with HCV and alcoholic cirrhosis (9.4% versus 0.9% versus 0%; P = 0.001). While adjusting for traditional risk factors for CAD, only NASH as etiology of liver disease remained significantly associated with CAD. Complications from diagnostic coronary angiography or percutaneous coronary intervention were low (2.6%). In conclusion, patients undergoing LTE have a high prevalence of CAD, which varies widely depending on etiology of liver cirrhosis. The procedural complications from coronary angiography are low. Liver Transplantation 24 333-342 2018 AASLD.

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.

Cardiovascular disease (CVD) is a major contributor to longterm mortality after liver transplantation (LT) necessitating aggressive modification of CVD risk. However, it is unclear how coronary artery disease (CAD) and the development of dyslipidemia following LT impacts clinical outcomes and how management of these factors may impact survival. Patients undergoing LT at Virginia Commonwealth University from January 2007 to January 2017 were included (n = 495). CAD and risk factors in all potential liver transplantation recipients (LTRs) over the age of 50 years were evaluated via coronary angiography. The impact of pre‐LT CAD after transplantation was evaluated via a survival analysis. Additionally, factors associated with new‐onset dyslipidemia, statin use, and mortality were assessed using multiple logistic regression or Cox proportional hazards models. The mean age of the cohort was 55.3 ± 9.3 years at the time of LT, and median follow‐up was 4.5 years. CAD was noted in 129 (26.1%) patients during the pre‐LT evaluation. The presence or severity of pre‐LT CAD did not impact post‐LT survival. Dyslipidemia was present in 96 patients at LT, and 157 patients developed new‐onset dyslipidemia after LT. Statins were underused as only 45.7% of patients with known CAD were on therapy. In patients with new‐onset dyslipidemia, statin therapy was initiated in 111 (71.1%), and median time to initiation of statin therapy was 2.5 years. Statin use conferred survival benefit (hazard ratio, 0.25; 95% confidence interval, 0.12‐0.49) and was well tolerated with only 12% of patients developing an adverse event requiring the cessation of therapy. In conclusion, pre‐LT CAD did not impact survival after LT, potentially suggesting a role of accelerated atherosclerosis that may not be captured on pre‐LT testing. Although statin therapy confers survival benefit, it is underused in LTRs.