Citations

328 Background: Patients with a history of solid organ transplants have been excluded from PD-1/PD-L1 inhibitor clinical trials due to concern for graft rejection. Only 2 case reports of PD-1 inhibitor use in patients with liver transplantation (LT) have been reported thus far. Here, we report our experience with using checkpoint inhibitors in metastatic cancer patients with LT. Methods: A single center pilot evaluation was conducted to evaluate the safety and efficacy of PD-1/PD-L1 inhibitors in patients with LT. PD-L1 staining on both the tumor and allograft were assessed if there was available tissue. The primary endpoint was evaluation of the risk for allograft rejection. Secondary endpoints included RECIST v1.1 and Immune-Related Response criteria (iRC) response rates, progression free survival (PFS) and overall survival (OS). Translational objectives included the relationship of PD-L1/PD-1 staining of tumor/allograft with response and rejection. Results: Six metastatic cancer patients with a history of LT received PD-1 inhibitor therapy (hepatocellular n=5, melanoma n=1). 3 patients were on mTOR inhibitor as immunosuppressive regimen and 3 on calcineurin inhibitor. Overall, allograft rejection was observed in 1/6 patients (on mTOR inhibitor). One patient achieved a CR (melanoma), 3 patients had PD and 2 patients discontinued therapy prior to restaging assessments. A single response (by both RECIST v1.1 and iRC) and rejection were reported in patients who received mTOR inhibitors (1 of 3). Three patients were tested for PD-L1 staining in the allograft tissue and all of them were negative (0% staining) with no graft rejections observed. Four patients had tumor PD-L1 evaluated (2 patients tested positive with 1 patient obtained a CR). The median OS, PFS and duration of therapy were 1.2, 1.8 and 1.2 months respectively. Conclusions: In this pilot evaluation of PD-1/PD-L1 inhibitors in LT patients both preliminary efficacy (1 of 4) and allograft rejection (1 of 6) was exhibited. Larger, prospective trials are needed to elucidate optimal patient and immunosuppressive regimen selection in these patients.

Introduction: Dobutamine stress echocardiography (DSE) is frequently used to screen for obstructive coronary artery disease in the pre-liver transplant evaluation. Although atropine is a commonly used adjunctive medication, no study has evaluated its side effect profile in patients with end-stage liver disease (ESLD). Research Question: What is the safety of atropine in candidates undergoing pre-liver transplant evaluation when atropine is used in stress testing? Design: This multicenter, prospective study enrolled patients over a 6-month period undergoing pre-liver transplant evaluation. Each patient completed a questionnaire assessing anticholinergic-related symptoms within 24 hours of testing and 48 hours following. Comparisons were made among patients receiving any atropine dose versus those who did not and among patients receiving at least 1 mg atropine and those receiving less/none. Results: Forty patients were evaluated, and 32 (80%) had adjunctive atropine administered. No differences in clinical characteristics were noted. In comparisons among patients receiving any dose of atropine with those who did not, questionnaire results indicated a higher rate of nausea prior to testing and higher overall symptom severity following testing in patients not receiving atropine. In comparisons among patients receiving less than 1 mg atropine with those receiving at least 1 mg atropine, no difference in pre- or posttesting questionnaire responses was present. No patient in the study required reversal agents or hospitalization within 7 days of testing. Conclusions: Atropine, a hepatically metabolized medication, did not predispose patients with ESLD to an increased symptom burden, and clinical outcomes related to DSE were unaffected.

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)

Treatment with an all‐oral interferon‐free antiviral regimen using simeprevir and sofosbuvir with or without ribavirin (RBV) for 12 weeks resulted in high sustained virologic response (SVR) rates along with minimal adverse events in non–liver transplant (LT) patients with hepatitis C virus (HCV) genotype 1 infection. This is the first multicenter report on the efficacy, safety, and tolerability of this regimen in LT recipients. A total of 123 patients (76% male, 74% white, 60% genotype 1a, 30% METAVIR F3‐F4, 4% decompensation, 11% cholestatic recurrence, 7% had kidney transplant, and 82% previously failed pegylated interferon/RBV‐based regimens) received treatment and were followed for a median of 30 weeks (range 12‐53 weeks). The median time from LT to treatment was 32 months (range 2‐317 months). Tacrolimus was the primary immunosuppression in 91% of patients. Minimal immunosuppression dose adjustments were required. An SVR 12 weeks after treatment completion (SVR12) was achieved in 90% of patients (95% confidence interval 84%‐96%). In patients with genotype 1a infection, the SVR12 rate was significantly lower in those with METAVIR F3‐F4 (71%) compared to those with F0‐F2 (91%). Half of the patients achieved undetected HCV RNA at treatment week 4, and their SVR12 rate was significantly higher (96%) compared to those with detectable HCV RNA (83%). Treatment was very well tolerated with mild degrees of adverse events, except for one death possibly due to drug‐induced lung injury. In the 25 patients who received RBV, 72% developed anemia requiring intervention. Conclusion : An all‐oral interferon‐free antiviral regimen using simeprevir and sofosbuvir with or without RBV for 12 weeks was very well tolerated and resulted in excellent SVR12 rates in LT recipients with HCV genotype 1 infection. (H epatology 2015;61:1880–1886)

AbstractSarcopenia, or loss of skeletal muscle mass, is associated with increased mortality and morbidity in liver transplant (LT) candidates. Six‐minute walk distance (6MWD) and health‐related quality of life (HRQOL) as assessed by short form 36 scores (SF‐36) also impact clinical outcomes in these patients. This study explored the relationship between the sarcopenia, 6MWD, and HRQOL in LT candidates. Sarcopenia was evaluated based on skeletal muscle mass index (SMI) quantified from abdominal computed tomography. Patients were followed until death, removal from the wait list or the end of the study period. Two hundred and thirteen patients listed for LT were included. The mean SMI, 6MWD and mean gait speed were 54.3 ± 9.7, 370.5 m and 1 m/s, respectively. Sarcopenia was noted in 22.2% of LT candidates. There was no correlation between sarcopenia, 6MWD, and SF‐36 scores. The 6MWD, but not sarcopenia, was an independent predictor of mortality (hazard ratio = 2.1 [0.9–4.7]). In summary, sarcopenia did not emerge as a significant predictor of waitlist mortality and also failed to correlate with either functional capacity or HRQOL in LT candidates. In patients with ESLD awaiting LT, 6MWD appears to be a more useful prognostic indicator than the presence of sarcopenia.