Risk Factors associated with Outcome in Korean Split-Liver transplantation Analysis of the 10-year Korean Network for Organ Sharing data base I will present my study, Outcome of Split-Liver Transplantation in Korea : Analysis of the KONOS Database Kyung Chul Yoon2 Sanghee Song1, Ok-Kyung Kim1, Ok Soo Kim1, Nam-Joon Yi2, Hyeyoung Kim2, Suk Kyun Hong2, Kyung Chul Yoon2, Hyo-Sin Kim2, Kwang-Woong Lee2 and Kyung-Suk Suh2 .1Organ Transplantation Center, Seoul National University Hospital, 2Department of Surgery, Seoul National University College of Medicine, Seoul, Korea

SLT in KOREA SLT (split liver transplantation): 5% of DDLT cases The number of Split liver transplantation cases has increased in the past years: less than 5 cases in 2005 to 20 cases in 2014. The proportion of SLT in DDLT cases is 5%. The most common type of split is adult with child. SLT (split liver transplantation): 5% of DDLT cases In SLT cases, Adult/Child splitting: 90-95%

Indication for SLT Criteria of deceased donor 1) Hemodynamic stable DBD donor 2) Age ≤ 40, Body weight ≥ 50kg 3) Inotrophics : Dopamin ≤ 15㎍/kg/min, dobutamin ≤ 15㎍/kg/min, norepinephrine ≤ 0.75㎍/kg/min, epinephrine ≤ 0.075㎍/kg/min no limit of vasopressin Criteria of Child recipient 1) Age <16 2) Body weight ≤ 30㎏ 3) ≤ Left lateral section Criteria of Adult recipient  No criteria When a deceased donor occurs, KONOS checks whether or not if the donor’s liver can be split with this criteria. Hemodynamic stable DBD donor, age less than 40, and weight greater than 50 kg, and the use of inotropics. Child recipient can be on a waiting list according to the following criteria: Age less than 16, body weight less than 30kg. However, adult recipient criteria has not yet been decided.

Outcome of SLT Lee et al . Am J tranpl. 2008 Overall survival (OS) Similar or worse than whole liver DBD LT 5yr survival rate: 72% vs 65% on SRTR data Lee et al . Am J tranpl. 2008 Complication - Similar or more common in SLT than whole liver DBD LT ( esp. biliary, hepatic a. ) Risk factors of outcome - Recipient factors - Age, UNOS Status, ABOi, dialysis, tumor.. - Donor factors – Age, weight, cold ischemic time. - Technical factor – Small volume center, Ex situ technique Outcomes in Korea have not been reported. There are some studies for OS and complication in SLT Overall survival was simiar or worse outcomes on SRTR data comparing whole LT. and complication rate also similar or worse oucomes than whole liver transplantation. Especially biliary problem and , Hepatic a. thrombosis..   These are some of the known risk factors, and it is similar with whole liver transplantation. recipient’s age and status, donor age and weight, and ischemic time. And ex situ technique. But Outcomes in Korea have not been reported as yet Lauterio A et al. World J Gastroentrol. 2009 Lee et al . Am J tranpl. 2008

Purpose 1. Overall survival of Korean SLT 2. Factors affecting patient overall survival   So we analyzed overall survival of Korean SLT and factors affection patient overall survival.

Method Retrospectively reviewed 2005-2014 for 10 years KONOS Data base of 23 centers, - 200 cases (adult n=107 / child n=93) - Exclusion criteria: status 1 d/t reLT (n=4) Seoul National University Hospital data - Adult Whole liver LT (n=322), Child LDLT(n=85) - Exclusion criteria: reLT (n=18), LT with KT (n=3) Analysis for risk factors, Overall survival 1. Adult SLT (104 in KONOS) vs Adult whole liver (303 in SNUH) 2. Child SLT (92 in KONOS) vs Child LDLT (85 in SNUH)

Graft Volume Issue in Adult SLT DRWR (Donor Weight : Recipient Weight) - KONOS to match recipient: 0.5 ≤ DRWR ≤ 2 - GV: recipient ideal LV 50~200% Whole Liver LT DRWR 1 GV = 100% recipient LV* SLT DRWR 1, GV (right/left liver) = 65% / 35% recipient LV adjusted DRWR (aDRWR) = 0.65 or 0.35 X DRWR Before comparing split and whole Liver Transplantation, we adjusted DRWR. DRWR is donor weight and recipient weight ratio and it is used by KONOS to match recipient. if there are recipient whose DRWR is 1, we assume that the recipient can get 100% recipient liver volume. But in case of Split, DRWR 1 does not mean the same graft volume, so we multiply 0.65 in right split group and or 0.35 in Left split group by DRWR. GV: graft volume; LV: liver volume

Demographics Adult : SLT vs Whole LT  Factors Split (n=104) Whole (n=303) p- value Recipient   Age (year) 53 ± 10 53 ± 11 0.974 Male Gender 59 (56.7) 188 (62%) 0.354 Weight (kg) 61.9 ± 11.8 60.11 ± 13 0.222 Diagnosis <0.001 HBV 54 (51.9%) 85 (28.1%) HCV 4 (3.8%) 11 (3.6%) Alcohol 13 (12.5%) 51(12.9%) Cholestatic 2 (1.9%) 8 (2.6%) Malignancy 5 (4.8%) 110 (36.3%) Fulminant 12 (11.5%) 15 (5%) Others 14 (13.5%) 22 (7.3%) KONOS status 0.071 1 5(4.8%) 21 (6.9%) 2A 49 (47.1%) 172 (56.8%) 2B 45 (43.3%) 96 (31.7%) 3 6 (2%) Factors  Split (n=103) Whole (n=303) p- value Donor   Age (year) 25.1 ± 8 42.9 ± 14.6 (missing 18 %) <0.001 Male 74 (71%) 153 (50.5%) (missing 18 %) 0.112 D-weight (kg) 67.7 ± 15.6 65.19 ± 14.8 (missing 42 .5%) 0.167 DRWR 1.13 ± 0.3 1.12 ± 0.3 (missing 43%) 0.848 aDRWR or DRWR 0.69 ± 0.19 1.12 ±0.3 (missing 43%) This is the demographics of the split and whole liver. The recipients’ diagnosis was somewhat different, especially HBV fulminant hepatitis was more common in the SLT group while malignancy was more common in the whole liver group. The status was not significantly different. The donor’s age was of course lower in split group

Adult OS : SLT vs Whole LT Split had worse outcomes than the whole liver group. and 5yr survival was 66% 1 yr 3 yr 5 yr HR p-value Whole liver (n=303) 87.1 80 78 Reference Split liver (n=104) 72.5 68 66 1.881(1.237 – 2.861) 0.003

Risk factors for OS in DDLT Uni p-value Multi p-value HR (95% CI) Recipient factor   - Age ≤ 56 (year) > 56 0.005  0.126  Reference 1.478 ( 0.896 – 2.438) - Weight ≤55 (kg) >55 0.015  0.076 1.721 ( 0.945 - 3.134) - Split Whole 0.011  0.306 1.368 (0.751 – 2.491) Reference  - Status 0.078 1 ( 10/ 26, 38.5%) not 1 ( 84 / 373, 18% ) 0.064 0.02 2.710 (1.168 – 6.288) Reference - aDRWR or DRWR ≤ 1.23 ( 38/ 103, 35%) >1.23 ( 30 / 175, 18% ) 0.001 2.273 (1.402 – 3.683)

Adjusted OS in Adult DDLT SLT vs Whole LT After that, Adjusted OS between split and whole liver was not different. p-value = 0.345   HR (95%CI) P value Status 1 2.710 (1.168 – 6.288) 0.02 aDRWR or DRWR< 1.23 2.273 (1.402 – 3.683) 0.001

Demographics Child: SLTvs LDLT   Child SLT (n=92) Child LDLT (n=85) p-value Recipient Age (yr) 3.29 ± 3.92 5.38±5.62 <0.001 Male Gender 35 (38%) 43 (50.6%) 0.098 R-weight (kg) 13.1 ± 10 25.0 ± 17 Diagnosis 0.001 Cholestatic 50 (54.8%) 48 (56.5%) Malignant 2 (2.2%) 5 (5.9%) Fulminant 13 (15.3%) Others 38 (41.3%) 19 (22.4%) Status 0.005 1 9 (9.8%) 12 (15.8%) 2B 57 (62%) 28 (36.8%) 3 26 (28.3%) 36 (47.4%) Ischemic Time (min) 258 ± 274 (missing 40) 71 ± 37 (missing 26) Donor 24.8 ± 7.82 35.3 ± 6.88 65 (70.7%) 35 (41.2%) D-weight (kg) 64.6 ± 13.9 61.3± 8.46 Ill move to the children cases. Recipient age, weight, is lower in SLT group and fulminant hepatitis and status 1 cases is more in LDLT group. Ischemic time is of couse longer in SLT group and donor age and gender, donor weight are different.

Child OS: SLT vs. LDLT 1yr 3yr 5yr HR (95% CI) p-value LDLT (n=92) Child overall survival was worse in SLT group. 1yr 3yr 5yr HR (95% CI) p-value LDLT (n=92) 96.2 93.7 Reference 0.044 SLT (n=85) 87.9 86 83.5 2.862 ( 1.029 – 7.958)

Risk factors for OS in Children Uni p-value Multi p -value HR (95%) Recipient   Age 0.093 Weight <20 kg >20kg 0.061 0.302  3.268 ( 0.346 – 30.908) Reference Status 0.832 status 1 not status1 0.686 Diagnosis Cholestatic (2 / 100, 2%) not cholestatic (17 / 79, 25%) <0.001 0.008 7.992 (1.737 – 36.738) Donor factor Donor age <30 >30 0.006 0.072 4.359 (0.879 – 21.616) Male Gender 0.037 0.206  2.768 (0.572 – 13.398) Graft factor Split SLT LDLT 0.053 0.111  4.088 (0.724 – 23.071) Ischemic time (min) ≤360 8/107 (7.5%) >360 4/6 (66.7%) 0.001  0.002  7.257 ( 2.031 – 25.928)

Adjusted OS in Children p-value = 0.111 After that adjusted OS was not different between split and LDLT.   HR (95%CI) p-value Not cholestatic 7.992 (1.737 – 36.738) 0.008 Ischemic time >360 7.257 (2.031 – 25.928) 0.002

Summary and Conclusion 1. Adult: SLT vs Whole liver LT 1) Adjusted split recipient OS is comparable to that of whole LT. 2) Status 1 and graft volume are risk factors in DDLT. 3) DRWR in whole liver LT and aDRWR in SLT > 1.23 could lead better survival. 2. Child: SLT vs LDLT 1) Adjusted split recipient OS is comparable to that of LDLT. 2) Cholestatic liver disease and short ischemic time (≤360min) have better OS.

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