Keaveny, Andrew P.

Abstract Early allograft dysfunction (EAD) identifies allografts with marginal function soon after liver transplantation (LT) and is associated with poor LT outcomes. The impact of EAD on post-LT renal recovery, however, has not been studied. Data on 69 primary LT recipients (41 with and 28 without history of renal dysfunction) who received renal replacement therapy (RRT) for a median (range) of 9 (13-41) days before LT were retrospectively analyzed. Primary outcome was renal nonrecovery defined as RRT requirement 30 days from LT. Early allograft dysfunction developed in 21 (30%) patients, and 22 (32%) patients did not recover renal function. Early allograft dysfunction was more common in the renal nonrecovery group (50% vs 21%, P = 0.016). Multivariate logistic regression analysis demonstrated that EAD (odds ratio, 7.25; 95% confidence interval, 2.0-25.8; P = 0.002) and baseline serum creatinine (odds ratio, 3.37; 95% confidence interval, 1.4-8.1; P = 0.007) were independently associated with renal nonrecovery. History of renal dysfunction, duration of renal dysfunction, and duration of RRT were not related to renal recovery ( P > 0.2 for all). Patients who had EAD and renal nonrecovery had the worst 1-, 3-, and 5-year patient survival, whereas those without EAD and recovered renal function had the best outcomes ( P < 0.001). Post-LT EAD was independently associated with renal nonrecovery in LT recipients on RRT for a short duration before LT. Furthermore, EAD in the setting of renal nonrecovery resulted in the worst long-term survival. Measures to prevent EAD should be undertaken in LT recipients on RRT at time of LT.

Variation in average Model for End‐Stage Liver Disease (MELD) score at liver transplantation (LT) by United Network for Organ Sharing (UNOS) regions is well documented. The present study aimed to investigate MELD variation at the interregional, intraregional, and intra–donation service area (DSA) levels. Patients undergoing LT between 2015 and 2016 were obtained from the UNOS standard analysis and research file. The distribution of allocation MELD score including median, skew, and kurtosis was examined for all transplant programs. Intraregional median allocation MELD varied significantly within all 11 UNOS regions. The largest variation between programs was seen in region 5 (MELD 24.0 versus 38.5) and region 3 (MELD 20.5 versus 32.0). Regions 1, 5, and 9 had the largest proportion of programs with a highly negative skewed MELD score (50%, 57%, and 57%, respectively), whereas regions 3, 6, 10, and 11 did not have any programs with a highly negative skew. MELD score distribution was also examined in programs located in the same DSA, where no barriers exist and theoretically no significant difference in allocation should be observed. The largest DSA variation in median allocation MELD score was seen in NYRT‐OP1 LiveOnNY (MELD score variation 11), AZOB‐OP1 Donor Network of Arizona (MELD score variation 11), MAOB‐OP1 New England Organ Bank (MELD score variation 9), and TXGC‐OP1 LifeGift Organ Donation Ctr (MELD score variation 9). In conclusion, the present study demonstrates that this MELD disparity is not only present at the interregional level but can be seen within regions and even within DSAs between programs located as close as several city blocks away. Although organ availability likely accounts for a component of this disparity, the present study suggests that transplant center behavior may also play a significant role.Liver Transplantation 24 488–496 2018AASLD.

The tragedy of the national opioid epidemic has resulted in a significant increase in the number of opioid‐related deaths and accordingly an increase in the number of potential donors designated Public Health Service (PHS) increased risk. Previous studies have demonstrated reluctance to use these PHS organs, and as a result, higher discard rates for these organs have been observed. All patients listed for liver transplantation in the United States from January 2005 to December 2016 were investigated. Patients on the waiting list were divided into 2 groups: those in which a PHS liver was used for transplantation (accepted PHS group) and those in which a PHS liver was declined and transplanted into a recipient lower on the match run (declined PHS group). Intention‐to‐treat patient survival from the time of PHS offer was significantly higher in the accepted PHS compared with the declined PHS group (P < 0.001). On Cox multivariate regression, declining a PHS donor liver was associated with a hazard ratio of 2.36 (95% confidence interval, 2.23‐2.49; P < 0.001). For patients in which a PHS organ offer was declined, 11.6% died or were delisted for being too sick within the subsequent year. Donor liver allografts implanted in the accepted PHS group were of a lower donor risk index (1.28 versus 1.44) compared with the non‐PHS organs that patients in the declined PHS group ultimately received if they underwent transplantation. In conclusion, there is a significantly higher survival for patients in which a PHS liver is accepted and used compared with those patients in which a PHS organ is declined. These data will help inform decisions about whether or not to accept a PHS donor liver for both patients and transplant professionals. Liver Transplantation 24 497–504 2018 AASLD.

The use of liver grafts from donation after cardiac death (DCD) has been limited due to the increased rate of graft failure, mostly related to ischemic cholangiopathy (IC). It is our hypothesis that longterm outcomes and quality of life (QOL) similar to patients undergoing liver transplantation (LT) with donation after brain death (DBD) can be achieved. Clinical outcomes of all patients undergoing DCD LT (n = 300) between 1998 and 2015 were compared with a propensity score–matched cohort of patients undergoing DBD LT (n = 300). Patients were contacted for a follow‐up questionnaire and short‐form (SF)–12 QOL Survey administration. Median follow‐up was >5 years. Graft survival at 1‐, 3‐, and 5‐years was 83.8%, 75.5%, and 70.1% in the DCD LT group and 88.4%, 80.3%, and 73.9% in the DBD LT group ( P = 0.27). Patient survival at 1‐, 3‐, and 5‐years was 92.3%, 86.1%, and 80.3% in the DCD LT group and 92.3%, 85.1%, and 79.5% in the DBD LT group ( P = 0.81). IC developed in 11.7% and 2% of patients in the DCD LT group and DBD LT group, respectively ( P < 0.001). DCD LT recipients who developed IC had inferior graft survival compared with both the DCD non‐IC group ( P < 0.001) and the DBD LT group ( P < 0.001); no difference in graft survival was observed between the DCD non‐IC group and the DBD LT group ( P = 0.50). Physical and Mental Composite Scores on the SF‐12 QOL questionnaire were similar between the DCD LT and DBD LT groups (44.0 versus 45.4; P = 0.34 and 51.9 versus 52.2; P = 0.83), respectively. Similar longterm survival and QOL scores can be achieved between DCD LT and DBD LT. Prevention of IC in DCD LT yields excellent graft and patient survival with virtually no difference compared with DBD LT. Liver Transplantation 23 342–351 2017 AASLD .

Interferon (IFN)‐free regimens are needed to treat hepatitis C virus (HCV) infection. Combined simeprevir (SMV) and sofosbuvir (SOF) with or without ribavirin (RBV) results in high sustained virological response (SVR) rates along with minimal adverse events (AEs) in patients with hepatitis C genotype 1 (HCV GT1). The aim of this study was to report on the virological response, safety, and tolerability of SOF and SMV with or without RBV in compensated and decompensated patients with cirrhosis with HCV GT1 infection. Patients treated with standardized clinical protocol utilizing SMV+SOF with or without RBV at three transplant centers were retrospectively reviewed. A total of 119 patients (61% male, 87% white, 69% subtype 1a, 30% Child‐Pugh‐Turcott [CPT]‐B liver cirrhosis [LC], and 82% were treatment experienced) received treatment and were followed for a median of 38 weeks (range, 12‐58). Sustained virological response (SVR) at week 12 (SVR12) was achieved in 78% (92 of 118) of patients (95% confidence interval: 69‐85). Lower pretreatment Model for End Stage Liver Disease (MELD) score was a predictor of SVR12 ( P = 0.018). Baseline viral load, previous treatment status, RBV use, or GT1 subtype did not impact SVR 12. The majority of patients with SVR12 showed stability or improvement in MELD score. Treatment was very well tolerated with mild degrees of AEs. Conclusions: The regimen of SMV+SOF with or without RBV for 12 weeks was very well tolerated and resulted in high SVR12 rates (78%) in HCV GT1 patients with LC. SVR12 was inversely related to pretreatment MELD. SVR12 had favorable short‐term impact on MELD score. Long‐term impact on disease stability is yet to be determined. Longer treatment duration or the use of different regimen may still be needed in this population. (H epatology 2015;62:1004‐1012)