Aqel, Bashar A.

Background. Portopulmonary hypertension (POPH) is the presence of pulmonary arterial (PA) hypertension in patients with portal hypertension and is associated with significant morbidity and mortality. In a cohort of POPH patients, we describe the clinical outcomes of POPH patients who underwent liver transplantation (LT). Methods. Retrospectively collected data from a prospectively assembled cohort of all consecutive POPH adults evaluated in 3 transplant centers from 1996 to 2019. Results. From a cohort of 228 POPH patients, 50 patients underwent LT. Significant hemodynamic improvement after PA-targeted therapy was observed, with 58% receiving only monotherapy pretransplant. After LT, 21 (42%) patients were able to discontinue and remained off PA-targeted therapy. The 1-, 3-, and 5-y unadjusted survival rates after LT were 72%, 63%, and 60%, respectively. An elevated pulmonary vascular resistance (PVR) before LT was associated with worse survival rate (HR, 1.91; 95% CI, 1.07-3.74, P = 0.04). No survival difference was observed in those granted MELD exception or transplants performed before or after the year 2010. Conclusions. Significant number of POPH patients discontinued PA-targeted therapy after LT. Higher PVR before LT was associated with worse survival, as was monotherapy use. Despite effective PA-targeted therapies, POPH survival outcomes after LT in our cohort were modest and may reflect the need for more aggressive therapy.

Background: Steatotic grafts are increasingly being used for liver transplant (LT); however, the impact of graft steatosis on renal function has not been well described. Methods: A total of 511 allografts from Mayo Clinic Arizona and Minnesota were assessed. We evaluated post-LT acute kidney injury (AKI) patterns, perioperative variables and one-year outcomes for patients receiving moderately steatotic allografts (>30% macrovesicular steatosis, n = 40) and compared them to non-steatotic graft recipients. Results: Post-LT AKI occurred in 52.5% of steatotic graft recipients versus 16.7% in non-steatotic recipients (p < 0.001). Ten percent of steatotic graft recipients required new dialysis post-LT (p = 0.003). At five years, there were no differences for AKI vs. no AKI patient survival (HR 0.95, 95% CI 0.08–10.6, p = 0.95) or allograft survival (HR 1.73, 95% CI 0.23–13.23, p = 0.59) for those using steatotic grafts. Lipopeliosis on biopsy was common in those who developed AKI (61.0% vs. 31.6%, p = 0.04), particularly when the Model for End-Stage Liver Disease (MELD) was ≥20 (88.9%; p = 0.04). Lipopeliosis was a predictor of post-LT AKI (OR 6.0, 95% CI 1.1–34.6, p = 0.04). Conclusion: One-year outcomes for moderately steatotic grafts are satisfactory; however, a higher percentage of post-LT AKI and initiation of dialysis can be expected. Presence of lipopeliosis on biopsy appears to be predictive of post-LT AKI.

494 Background: Our aim was to compare survival between patients receiving neoadjuvant chemoradiation and orthotopic liver transplantation (OLT group) versus definitive chemoradiation (CRT group) for extrahepatic or hilar cholangiocarcinoma. Methods: 49 patients (20 in OLT group vs. 29 in CRT group) with unresectable hilar/extrahepatic cholangiocarcinoma were treated at Mayo Clinic Arizona between Feb. 1998–Sep. 2019. Treatment included external beam radiation therapy (median 4500cGy) and boost (median 900cGy) with either continuous 5-flurouracil (dose range 180–225 mg/m2) or capecitabine (dose range 825–1000 mg/m2 BID) prior to or without OLT. Radiation boosts were delivered with EBRT or bile duct brachytherapy. Patients were between 27.9–84.3 years (median 64.3) at diagnosis. 18 patients had previous diagnosis of PSC. Results: Between Feb. 1998–Sep. 2019, 31(63%) of 49 patients died by the end of follow-up. Of patients treated with neoadjuvant therapy and OLT, 7(35%) of 20 patients died. 24(86%) of 28 patients treated with definitive therapy died. The OLT cohort were younger (mean age 56.5 vs. 69.0 years), more likely to have PSC and UC (65% vs. 17%), and had a lower CA 19-9 (median 43 vs. 535)(P < 0.003). From the end date of radiation, median overall survival was 76.8 months vs. 15.6 months for the OLT and CRT groups, respectively. Survival rates at 3 and 5 years were 78% and 69% in the OLT group compared to 19% and 6% in the CRT group (HR 7.73; 3.04-19.65:(P < 0.0001)). Progression-free survival (89% vs. 30% at 3 years), and distant metastasis-free survival (88% vs. 66% at 3 years) favored OLT versus CRT alone (HR 5.74;1.12-29.34:(P < 0.02)). Univariate analysis demonstrated that the method of treatment (OLT vs. CRT) was the only variable associated with better clinical outcomes. Conclusions: In patients with unresectable extrahepatic/hilar cholangiocarcinoma, survival was higher in those who underwent chemoradiation and OLT. Patients who received definitive chemoradiation in the absence of OLT were expected to have worse overall, progression-free, and metastasis-free survival.

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.