Hla Dr Mismatch is Associated with Recurrent Autoimmune Hepatitis After Liver Transplantation: A Single Center Experience with Tacrolimus Based Immunosuppression

Multivariate regression models for mortality due to ALI in patients with history of bariatric surgery

Cummulative hazard ratio of recipient according to donor age adjusting for recipient age and etiology of liver disease in the young (<50) and old donor (≥50) (hazard ratio 1.46, p =0.0029)

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Introduction: The incidence of morbidity and mortality after living donor liver transplantation (LDLT) is published in literature but potentially life-threatening near miss events (during which a donor's life may be in danger but after which there are no long-term sequelae) are rarely reported. Reporting such complications is necessary to improve upon living donor safety. Aim: To analyze and determine the incidence of potential life threatening near miss events, in our center. Material and methods: We evaluated retrospectively collected and prospectively maintained database of Liver donor patients from 2004 to 2015. We Enrolled these patient's morbidity events according to Clavien-Dindo classification of surgical complications. Results: Overall 392 patients underwent exploration for liver donor hepatectomies from 2004 to October 2015, out of which four patients had aborted hepatectomies due to the liver appearing nodular and were excluded from study group as they were aborted before liver resection started. Overall 228 complications were observed. At least one complication was noted in 45.3% (n 176) patients, however multiple complications were observed in 8.2% (n 32) patients. Donor mortality was 0.2%. Total 17 near-miss events occurred in 16 (4.1%) patients. Three patients with pulmonary embolism (PE) (0.7%) required mechanical ventilation and anticoagulation. Massive cardiac tamponade (0.2%) requiring urgent pericardiocentesis was observed in one patient on anticoagulation following PE. Vascular complication leading to life threatening bleed were observed in three patients (0.7%). They were slipped vascular clamp from a hepatic vein, blow out from a right hepatic vein and slipped IVC clip. Delayed partial portal vein thrombosis leading to delayed liver function was observed in one patient. Left hepatic vein outflow obstruction noted in one patient requiring immediate patch repair. ARDS was observed in two patients (0.5%) on 2nd postoperative day (POD 2) requiring mechanical ventilation. Bile leak with sever sepsis occurred in three patients (0.7%) requiring multiple intervention ERCP, PCD and one required laparotomy for intraperitoneal sepsis. A marginal donor patient with peritoneovenous shunt developed sepsis leading to meningitis, cholestasis, and small for size. Urgent coronary artery stent was required in a donor on post operative day 2 following inferior wall MI. One patient had atrial fibrillation which was reversed with amiodarone. Conclusion: Most complications were of low grade severity but 4.1% patients had severe or life-threatening events. Availability of data is useful for counseling , risk stratification and taking preventive measures in a potential living liver donor. Clavien-Dindo classification of surgical complications.

279 EFFECT OF DONOR AGE ON RECIPIENT OUTCOMES AFTER ADULT LIVING DONOR LIVER TRANSPLANT Wuttiporn Manatsathit, Hrishikesh Samant, Karn Wijarnpreecha, Smitha Sagaram, Jane Suh, Marco Olivera-Martinez Background: With the improvement in surgical technique, organ transportation, and antirejection medication in the past decades, the negative effect of donor age on recipient outcomes after deceased donor liver transplant has been significantly minimized. However, the data in patients undergoing living donor liver transplant (LDLT) has shown conflicting results. Hence, we aimed to evaluate the effect of donor age on recipient outcomes after LDLT utilizing the Organ Procurement and Transplantation Network (OPTN) registry. Methods: We evaluated adult cirrhotic patients who underwent LDLT from the OPTN registry after 2003. Patients with multi-organ transplant and history of previous liver transplant were excluded. The patients were subsequently categorized into two groups according to donor age; young (<50 years) and old donor (≥50 years). Baseline characteristic of recipient and donor between two groups were compared utilizing Chi-square and Student's T test. Primary outcome was overall survival of recipient of the two groups utilizing Kaplan Meier analysis. Multivariate Cox proportional hazard model was performed adjusting for clinical relevant variables. Results: Of the 3897 patients included, 3382 patients were in the young donor group and 515 patients in the old donor group respectively. Mean age, BMI, MELD, diagnosis of HCC, and type of graft were similar between the two groups. The most common liver etiology was hepatitis C followed by biliary cirrhosis, NASH, and cryptogenic. Kaplan Meier curve demonstrated significant lower survival in the old donor compared with young donor (p=0.0006). (Figure 1) Most importantly, after adjusting for etiology of liver diseases and recipient age, donor age remains a significant factor in survival with hazard ratio of 1.46 in old donor compared with young donor. (figure 2) (p=0.0029) Conclusion: Older donor age significantly affects the survival of the recipient after LDLT.

281 HLA DR MISMATCH IS ASSOCIATED WITH RECURRENT AUTOIMMUNE HEPATITIS AFTER LIVER TRANSPLANTATION: A SINGLE CENTER EXPERIENCE WITH TACROLIMUS BASED IMMUNOSUPPRESSION Marshall E. McCabe, Natalia Rush, Craig Lammert, Marco Lacerda, Naga P. Chalasani, Romil Saxena, Jinmei Lin, Oscar W. Cummings, Burcin Ekser, Shekhar Kubal, Richard S. Mangus, Jonathan Fridell, Marwan S. Ghabril Background: Outcomes of liver transplantation (LT) for autoimmune hepatitis (AIH) in the MELD era with tacrolimus based immunosuppression are not well described. Aims: To describe the incidence and outcomes of recurrent AIH (R-AIH) after LT, and to examine the factors associated with R-AIH. Methods: We studied patients receiving their first LT for AIH during 2002-2014 at our center. All patients received anti-thymocyte globulin and rituximab induction with tacrolimus based immunosuppression initially. R-AIH was defined based on clinical, serological and histological criteria. Data were reported as median (interquartile range) or number (percentage). Clinical factors at LT, including explant histology were analyzed for predictors of R-AIH. Results: 68 patients underwent LT for AIH, median age 47 (34-59), 45 (66%) female and 55 (81%) Caucasian. 1, 5 and 7 yr patient and graft survival were 91%, 80% and 78%, and 87%, 77% and 75% respectively. After a median follow-up of 6 (3-9.8) yrs, R-AIH was diagnosed in 24 (35%) patients. The median interval to R-AIH was 251 (125-1166) days, (13 recurred by 1 yr and 21 by 5 yrs post LT). Patients with and without R-AIH were compared (Table 1). 6 patients with R-AIH progressed to≥F3 fibrosis, with 1 reLT and 4 liver related deaths. Explant pathology was available in 49 cases and graded for interface hepatitis and centrilobular collapse in a blinded fashion by 2 pathologists. Interface hepatitis correlated with degree of collapse (Pearson coefficient 0.5, p<0.001), and IgG levels at LT (Pearson coefficient 0.47, p=0.02), but neither histologic finding was associated with R-AIH or acute rejection (Table 2). On uni/multivariate Cox Regression analysis HLA DR mismatch level predicted R-AIH, [Hazard ratio (HR) 5 (95%Confidence interval (CI) 1.6-19, p=0.02)], with a statistical trend for recipient age [HR 0.96 (95%CI 0.92-1, p=0.07)] and recipient HLA DR4 status [HR 0.32 (95%CI 0.08-1.2, p= 0.09)]. Conclusions: Despite potent induction and tacrolimus based immunosuppression, AIH recurs in a third of patients, commonly within a year of LT. R-AIH is associated with HLA DR mismatch and younger recipient age, while recipient HLA DR4 status was protective. These data may guide immunosuppression in higher risk LT recipients with AIH.

Kaplan Meier demonstrating survival of recipient who underwent LDLT from young (<50) and old donor (≥50).

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AASLD Abstracts

AASLD Abstracts

POTENTIALLY LIFE-THREATENING NEAR-MISS EVENTS IN LIVING DONOR HEPATECTOMY: SINGLE CENTRE EXPERIENCE FROM SOUTHERN INDIA Anand Patel, Dinesh Balakrishnan, Ramachandran Menon, Unnikrishnan G, Sudhindran S

AASLD Abstracts

accumulation associated with postoperative SFSS in mice. MRI may be used as a new tool to predict SFSS in the early postoperative course.

Clinical, transplant and immunosuppression characteristics in patients with and without recurrent autoimmune hepatitis post liver transplantation.

Figure 1 Increased liver fat accumulation associated with SFSS can be detected noninvasively by MRI. (A) In-phase and opposed-phase MRI shows increased percentage liver fat after 86% partial hepatectomy (PH) (SFSS) compared to 70%PH controls. Percentage liver fat in mice dying due to SFSS after 86%PH was most increased (* comparing the 70%PH and 86%PH group, + comparing the 86%PH and 86%PH + Death group and # comparing the 70%PH and 86%PH + Death group. */+/#p<0.05, **/++/##p<0.01,). (B) Chemical liver fat quantification per mg liver tissue confirms increased fat content after 86%PH compared to 70%PH and sham operation. (* comparing the 70%PH and 86%PH group, + comparing the 86%PH and sham group and # comparing the 70%PH and sham group. */+/#p<0.05, **/++/##p<0.01,). (C) Red Oil O staining showing delayed clearing of microsteatosis after 86%PH compared to 70%PH and sham operation.

339 AN INNOVATIVE APP FOCUSED ON PATIENTS AND CAREGIVERS SIGNIFICANTLY DECREASES AVOIDABLE AND HE-RELATED READMISSIONS IN CIRRHOTIC PATIENTS Dinesh Ganapathy, Jatinder Lachar, Chathur Acharya, Melanie B. White, Richard K. Sterling, Kavish R. Patidar, Catherine Ignudo, Swamy Bommidi, Jasmohan S. Bajaj

Table 2. Explant grading of interface hepatitis and collapse in relation to recurrent autoimmune hepatitis and acute rejection post liver transplant.

282 EARLY MRI-BASED LIVER FAT QUANTIFICATIONPREDICTS OUTCOME AFTER EXTENDED HEPATECTOMY IN MICE Andrea Wirsching, Christian Eberhardt, Moritz C. Wurnig, Andreas Boss, Mickaël Lesurtel Background Small for Size Syndrome (SFSS) is defined as liver failure after extended hepatectomy due to insufficient regeneration of a too small liver remnant. We investigated early postoperative MRI as a new tool to predict SFSS following hepatectomy. Methods Mice (C57BL/6) underwent either extended hepatectomy (86% partial hepatectomy (PH), SFSS-model) or 70% PH as a control group for regular liver regeneration. Serial fast low angle shot MRI sequences and in-phase and opposed-phase MRI sequences on postoperative days 1-7 were used to compare liver volume- and percentage liver fat changes, respectively. Biochemical liver fat analysis and liver tissue staining with Oil Red O was performed to validate MR liver fat quantification. Liver regeneration capacity was assessed by MR liver volumetry and hepatocyte proliferation (analysis of Ki67, proliferating cell nuclear antigen, BrdU and phosphorylated histone 3). Diagnosis of SFSS was based on survival, impaired liver regeneration and liver function parameters. Receiver Operating Characteristic curve statistics were used to define a cut-off value for percentage liver fat to diagnose SFSS. Results Extended hepatectomy was associated with a decreased survival, early cholestasis and impaired proliferation compared to 70% PH (p<0.01, p<0.001 and p=0.031, respectively). In phase and opposed phase MRI sequences showed an increased liver fat accumulation 48h and 72h after extended hepatectomy compared to 70% PH controls (48h: 11.8±6% vs. 4.3±2%, p<0.001; 72h: 5.3±3% vs. 1.2±0.8%, p=0.008). Death associated with SFSS yielded an additional increase in liver fat accumulation 48h after hepatectomy compared to 86% PH survivors (16.4±6% vs. 9.2±5%, p=0.02). MRI- and biochemical liver fat quantification correlated significantly (p<0.001). At 48h after surgery, a cut-off value of 5.7% liver fat (assessed by MRI) was found to predict SFSS with a sensitivity and specificity of 100% and 90%, respectively. Conclusion MRI is able to quantify early posthepatectomy liver fat

AASLD Abstracts

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Background: Cirrhotic patients have a high rate of avoidable readmissions, which could be potentially preventable by greater communication. PatientBuddy in an innovative App developed to reduce readmissions by enhancing communication. Aim: To determine if the use of PatientBuddy can prevent avoidable readmissions in cirrhosis compared to a historical cohort Methods: PatientBuddy was adapted for cirrhosis with 3 foci; hepatic encephalopathy (HE), ascites & falls. It includes medicine adherence, orientation questions, weights & Na monitoring. Inpt cirrhotics & caregivers were trained on PatientBuddy & given iPhones that directly linked with the App loaded onto case manager devices. In addition to daily communications, the dyads were followed at day 7,14,21 &30. Pts without caregivers, discharged to hospice/facilities &active drinkers were excluded. Readmissions within 30 days were recorded. Readmission reasons were adjudicated by a hepatologist not participating as avoidable or not. These were compared to a cohort of inpatient cirrhotics enrolled with their caregivers 1 year prior whose readmissions were studied without PatientBuddy Results: PatientBuddy cohort: 57 subjects were considered; 9 did not have caregivers, 12 refused, 8 were discharged to hospice/facilities. 40 pts/caregiver dyads were included (Age 58±9, MELD 20±5, 70% prior HE, 90% ascites). Four dyads withdrew within 1 wk due to the complexity. Of the remainder 15(37.5%)were readmitted in 30 days(5 infections,3 anasarca,2 GI bleeding,2 chest pain, 1 anemia, 1 opioid overdose & 1 jaundice post-TIPS). Of these 3 (7.5%) were considered avoidable; 2 had ascites that could have receoved an outpt tap & 1 had opioid overdose on drugs given by outside MD. None were readmitted for HE. Historical cohort: 73 cirrhotic pts/caregivers were enrolled with similar disease severity as PatientBuddy (Age 57±7, MELD 18±10, 66% prior HE,88% ascites, all p>0.05).34 (46%) had a 30-day readmission (HE 17, ascites 7, infection 5, GI bleeding 3, others 2). Of these 18 (25%) were considered avoidable (12 HEs due to non-adherence, 6 ascites that could have received outpatient taps). While the total was similar, avoidable &HE-related readmissions were significantly lower in the PatientBuddy cohort (Figure). Conclusions : PatientBuddy use focused on patients and caregivers, which promotes active feedback, significantly reduces avoidable and HE-related 30-day readmissions in cirrhotic patients