Primary Living Donor Liver Transplantation Research Articles

Chronological alterations in de novo malignancies after living-donor liver transplantation: A cohort study of 1781 recipients using annual comparisons of standardized incidence ratios.

De novo malignancies (DNMs) are a major adverse event after solid organ transplantation; however, their characteristics and recent trends after living-donor liver transplantation (LDLT) remain unclear. We retrospectively reviewed 1781 primary LDLT recipients (1990-2020) and annually calculated standardized incidence ratios (SIRs) of DNMs compared to the age-adjusted Japanese general population. After 21 845 person-years follow-up, 153 DNM lesions (8.6%) were identified in 131 patients (7.4%). The incidence was 0.007 person-years. DNMs included 81 post-transplant lymphoproliferative disorders (PTLDs), 14 colorectal, 12 lung, and 12 gastric cancers, and so on. Comorbid DNMs significantly worsened recipient survival than those without (p < .001). The 5- and 10-year recipient survival after DNM diagnosis were 65% and 58%, respectively. Notably, SIR1993-1995: 8.12 (95% CI: 3.71-15.4, p < .001) and SIR1996-1998: 3.11 (1.34-6.12, p = .01) were significantly high, but had decreased time-dependently to SIR2005-2007: 1.31 (0.68-2.29, p = .42) and SIR2008-2010: 1.34 (0.75-2.20, p = .33), indicating no longer significant difference in DNMs development. Currently, however, SIR2014-2016: 2.27 (1.54-3.22, p < .001) and SIR2017-2019: 2.07 (1.40-2.96, p < .001) have become significantly higher again, reflecting recent aging of recipients (>50 years) and resultant increases in non-PTLD DNMs. Furthermore, characteristically in LDLT, the fewer the donor-recipient HLA-mismatches, the less the post-transplant DNMs development. DNM development after LDLT was significantly higher than in the general population due to higher PTLD incidence (1993-1998), but once became equivalent (2005-2013), then significantly increased again (2014-2019) due to recent recipient aging and resultant increase in solid cancers.

Cognitive function of children with biliary atresia after primary living donor liver transplantation

BackgroundThe survival rate of children with biliary atresia (BA) after liver transplantation (LT) is significantly improved, and their quality of life has attracted much attention.This study aimed to investigate the cognition and its influencing factors in children with BA after primary living donor LT (BA-pLDLT) during infancy.MethodsChildren with BA were recruited 6 months after pLDLT at Children’s Hospital of Chongqing Medical University (2018–2022). Demographic and clinical data were collected from the health information system. Cognition was assessed using the Chinese version of the Griffiths Mental Development scale (GMDS-C). Multivariate linear regression were used to analyze the influencing factors of their cognitive function.ResultsIn total, 57 children with BA-pLDLT, aged 5.00(3.90–9.30) months at transplantation and 25.00(14.00-60.80) months at evaluation were included. The general developmental quotient (89.02 ± 12.07) and motor, language, eye-hand coordination, performance, and practical reasoning quotients of these children were significantly lower than the normative mean values of GMDS-C(P < 0.05). Of the 57 children, 16 (28.07%) had borderline developmental delay (DQ between 70 and 84), 3 (5.26%) had developmental delay (DQ < 70), and 11(19.29%) had language delay. Reoperation for biliary or vascular complications after pLDLT was a risk factor for decreased general development quotient and motor quotient and lower ZW at assessment was associated with decline motor quotient.ConclusionChildren with BA-pLDLT have varying degrees of developmental delays in early life. Reoperation and nutritional deficiencies had adverse effects on cognitive development.

Infection as the main complication of primary living donor liver transplantation in biliary atresia patients: Data from single-centre, Indonesian national-referral hospital

Infection as the main complication of primary living donor liver transplantation in biliary atresia patients: Data from single-centre, Indonesian national-referral hospital

The Impact of Hepatic Artery Thrombosis on the Outcome of Pediatric Living Donor Liver Transplantations

The aim of our study was to assess risk factors for hepatic artery thrombosis (HAT) and to evaluate the impact of HAT management on long-term outcomes after pediatric living donor liver transplantation (LDLT). We retrospectively analyzed 400 patients who underwent primary LDLT between 1999 and 2020. We compared preoperative data, surgical factors, complications, and patient and graft survivals in patients with HAT (HAT Group) and without HAT (non-HAT Group). A total of 27 patients (6.75%) developed HAT. Acute liver failure, a hepatic artery (HA) anastomosis diameter below 2 mm, and intraoperative HA flow dysfunction were significantly more common in the HAT Group (p < 0.05, p = 0.02026, and p = 0.0019, respectively). In the HAT Group, 21 patients (77.8%) underwent urgent surgical revision. The incidence of biliary stenosis and retransplantation was significantly higher in the HAT Group (p = 0.00002 and p < 0.0001, respectively). Patient and graft survivals were significantly worse in the HAT Group (p < 0.05). The close monitoring of HA flow with Doppler ultrasound during the critical period of 2 to 3 weeks after LDLT and the immediate attempt of surgical revascularization may attenuate the elevated risk of biliary stenosis, graft loss, and the need for retransplantation due to HAT.

312.8: What Is the Risk Factor of Graft Mortality in Patients Who Underwent Simultaneous Splenectomy During Living Donor Liver Transplantation?

Introduction: Splenectomy is performed in living donor liver transplantation (LDLT) for portal flow modulation. The aim of this study was to identify the risk factor of 6-month graft mortality in patients who underwent splenectomy in LDLT. Methods: Data from 441 adult patients who underwent simultaneous splenectomy during primary LDLT were collected retrospectively. Risk factors of 6-month graft mortality were investigated. Results: Mean recipient age was 55 years. Mean donor age was 38.7 years. Two hundred and five patients (46.5%) received left lobe graft. Mean graft weight (GW)-standard liver weight ratio was 41.5% and GW-recipient weight ratio was 0.79%. Six-month graft survival rate after LDLT in 441 patients was 93.8%, which was significantly better compared to patients without simultaneous splenectomy or splenic artery ligation (83.9%, p<0.0001). Univariate analysis revealed the following risk factors for 6-month graft mortality in patients with splenectomy: neutrophil-lymphocyte ratio > 4, acute liver failure, hospitalized before LDLT, donor > 60 years of age, MELD score > 22, pre-LDLT platelet < 40, 000/mm3, portal vein pressure when LDLT finished (PVP) > 20 mmHg. Multivariate analysis identified that donor > 60 years of age (Hazard ratio=4.50, p=0.049), pre-LDLT platelet < 40, 000/mm3 (Hazard ratio=2.58, p=0.03), and PVP > 20 mmHg (Hazard ratio=7.46, p<0.001) were the independent risk factors of 6-month graft mortality after LDLT.Conclusion: Splenectomy in LDLT improves survival rate after LDLT. Careful attention is needed for patients with platelet < 40, 000/mm3, PVP > 20 mmHg, and received graft from donor > 60 years of age.

The impact of human leukocyte antigen mismatch on recipient outcomes in living-donor liver transplantation.

Donor-recipient human leukocyte antigen (HLA) compatibility has not been considered to significantly affect liver transplantation (LT) outcomes; however, its significance in living-donor LT (LDLT), which is mostly performed between blood relatives, remains unclear. This retrospective cohort study included 1954 LDLTs at our institution (1990-2020). The primary and secondary endpoints were recipient survival and the incidence of T cell-mediated rejection (TCMR) after LDLT, respectively, according to the number of HLA mismatches at all five loci: HLA-A, HLA-B, HLA-C, HLA-DR, and HLA-DQ. Subgroup analyses were also performed in between-siblings that characteristically have widely distributed 0-10 HLA mismatches. A total of 1304 cases of primary LDLTs were finally enrolled, including 631 adults (recipient age at LT ≥18 years) and 673 children (<18 years). In adult-to-adult LDLT, the more HLA mismatches at each locus, the significantly worse the recipient survival was (p=0.03, 0.01, 0.03, 0.001, and <0.001 for HLA-A, HLA-B, HLA-C, HLA-DR, and HLA-DQ, respectively). This trend was more pronounced when multiple loci were combined (all p < 0.001 for A + B + DR, A + B + C, DR + DQ, and A + B + C + DR + DQ). Notably, a total of three or more HLA-B + DR mismatches was an independent risk factor for both TCMR (hazard ratio [HR] 2.66, 95% confidence interval [CI] 1.21-5.87; p=0.02) and recipient survival (HR 2.44, 95% CI 1.11-5.35; p=0.03) in between-siblings. By contrast, HLA mismatch did not affect pediatric LDLT outcomes at any locus or in any combinations; however, it should be noted that all donor-recipient relationships are parent-to-child that characteristically possesses one or less HLA mismatch at each locus and maximally five or less mismatches in total. In conclusion, HLA mismatch significantly affects not only TCMR development but also recipient survival in adult LDLT, but not in children.

Predicting the Recurrence of Hepatocellular Carcinoma after Primary Living Donor Liver Transplantation Using Metabolic Parameters Obtained from 18F-FDG PET/CT.

This study evaluated the prognostic value of metabolic parameters based on the standardized uptake value (SUV) normalized by total body weight (bwSUV) and by lean body mass (SUL) measured on 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) for predicting tumor recurrence after primary living donor liver transplantation (LDLT) in patients with hepatocellular carcinoma (HCC) without transplantation locoregional therapy. This retrospective study enrolled 49 patients with HCC. The maximum tumor bwSUV (T-bwSUVmax) and SUL (T-SULmax) were measured on PET. The maximum bwSUV (L-bwSUVmax), mean bwSUV (L-bwSUVmean), maximum SUL (L-SULmax), and mean SUL (L-SULmean) were measured in the liver. All metabolic parameters were evaluated using survival analyses and compared to clinicopathological factors. Tumor recurrence occurred in 16/49 patients. Kaplan–Meier analysis revealed that all metabolic parameters were significant (p < 0.05). Univariate analysis revealed that prothrombin-induced by vitamin K absence or antagonist-II; T-stage; tumor number; tumor size; microvascular invasion; the Milan criteria, University of California, San Francisco (UCSF), and up-to-seven criteria; T-bwSUVmax/L-bwSUVmean; T-SULmax; T-SULmax/L-SULmax; and T-SULmax/L-SULmean were significant predictors. Multivariate analysis revealed that the T-SULmax/L-SULmean (hazard ratio = 115.6; p = 0.001; cut-off, 1.81) and UCSF criteria (hazard ratio = 172.1; p = 0.010) were independent predictors of tumor recurrence. SUL-based metabolic parameters, especially T-SULmax/L-SULmean, were significant, independent predictors of HCC recurrence post-LDLT.

What is the Risk Factor of Graft Mortality in Patients who Underwent Simultaneous Splenectomy during Living Donor Liver Transplantation?

Introduction: Splenectomy is performed in living donor liver transplantation (LDLT) for portal flow modulation. The aim of this study was to identify the risk factor of 6-month graft mortality in patients who underwent splenectomy in LDLT. Methods: Data from 441 adult patients who underwent simultaneous splenectomy during primary LDLT were collected retrospectively. Risk factors of 6-month graft mortality were investigated. Results: Mean recipient age was 55 years. Mean donor age was 38.7 years. Two hundred and five patients (46.5%) received left lobe graft. Mean graft weight (GW)-standard liver weight ratio was 41.5% and GW-recipient weight ratio was 0.79%. Six-month graft survival rate after LDLT in 441 patients was 93.8%, which was significantly better compared to patients without simultaneous splenectomy or splenic artery ligation (83.9%, p<0.0001). Univariate analysis revealed the following risk factors for 6-month graft mortality in patients with splenectomy: neutrophil-lymphocyte ratio > 4, acute liver failure, hospitalized before LDLT, donor > 60 years of age, MELD score > 22, pre-LDLT platelet < 40, 000/mm3, portal vein pressure when LDLT finished (PVP) > 20 mmHg. Multivariate analysis identified that donor > 60 years of age (Hazard ratio=4.50, p=0.049), pre-LDLT platelet < 40, 000/mm3 (Hazard ratio=2.58, p=0.03), and PVP > 20 mmHg (Hazard ratio=7.46, p<0.001) were the independent risk factors of 6-month graft mortality after LDLT. Conclusion: Splenectomy improves graft survival rate after LDLT. Careful attention is needed for patients with platelet < 40, 000/mm3, PVP > 20 mmHg, and received graft from donor > 60 years of age.

Recent Improvement in Survival Outcomes and Reappraisal of Prognostic Factors in Pediatric Living Donor Liver Transplantation.

Living donor liver transplantation (LDLT) is a significant advancement for the treatment of children with end-stage liver disease given the shortage of deceased donors. The ultimate goal of pediatric LDLT is to achieve complete donor safety and zero recipient mortality. We conducted a retrospective, single-center assessment of the outcomes as well as the clinical factors that may influence graft and patient survival after primary LDLTs performed between 1994 and 2020. A Cox proportional hazards model was used for multivariate analyses. The trends for independent prognostic factors were analyzed according to the following treatment eras: 1, 1994 to 2002; 2, 2003 to 2011; and 3, 2012 to 2020. Primary LDLTs were performed on 287 children during the study period. Biliary atresia (BA; 52%), acute liver failure (ALF; 26%), and monogenic liver disease (11%) were the leading indications. There were 45 graft losses (16%) and 27 patient deaths (7%) in this population during the study period. During era 1 (n=81), the cumulative survival rates at 1 and 5 years after LDLT were 90.1% and 81.5% for patients and 86.4% and 77.8% for grafts, respectively. During era 2 (n=113), the corresponding rates were 92.9% and 92% for patients and 89.4% and 86.7% for grafts, respectively. During era 3 (n=93), the corresponding rates were 100% and 98.6% for patients and 98.9% and 95.4% for grafts, respectively. In the multivariate analyses, primary diagnosis ALF, bloodstream infection, posttransplant lymphoproliferative disease, and chronic rejection were found to be negative prognostic indicators for patient survival. Based on generalized care guidelines and center-oriented experiences, comprehensive advances in appropriate donor selection, refinement of surgical techniques, and meticulous medical management may eventually realize a zero-mortality rate in pediatric LDLT.

No diffuse intrahepatic biliary stricture after ABO-incompatible adult living donor liver transplantation using tailored rituximab-based desensitization protocol.

BackgroundRituximab (RTx) desensitization protocol offered good outcome in ABO-incompatible (ABOi) living donor liver transplantation (LDLT). However, diffuse intrahepatic biliary stricture (DIHBS) is still inevitable hurdle. We selectively added postoperative high dose intravenous immunoglobulin (IVIG) and/or simultaneous splenectomy if ABO isoagglutinin titer just before liver transplantation after plasma exchange (PE) was higher than 1/16. Herein, we reported the excellent outcome of ABOi LDLT without DIHBS using tailored desensitization protocol and compared it with that of ABO-compatible (ABOc) LDLT.MethodsSixty-five cases (14.8%) of ABOi LDLTs were performed among 438 primary adult LDLTs in our center between March 2012 and June 2017. We performed 1-to-2 propensity score matching (PSM) to extract 60 cases of ABOi LDLTs and 120 cases of ABOc LDLTs.ResultsThere were no significant differences in clinical characteristics between ABOi and ABOc recipients. There were no significant differences in complications and rejection. There was no DIHBS in both groups. The 1-, 3-, and 5-year overall survival rates were 98.3%, 86.7%, and 82.9% in ABOi group and 96.7%, 86.7%, and 85.4% in ABOc group, respectively (P=0.88). Most common cause of deaths of both groups was hepatocellular recurrence. The 1-, 3-, and 5-year biliary complication (anastomosis leakage or stricture) free survival rates were 81.4%, 69.5%, and 67.5% in ABOi group and 83.0%, 81.3%, and 80.0% in ABOc group, with no significant differences (P=0.11).ConclusionsRTx-based tailored (optional IVIG + splenectomy) desensitization protocol for ABOi LDLT was feasible and acceptable.

An international evaluation of trends and outcomes of living donor liver transplantation: United States, United Kingdom, and Canada

Presenter: Tommy Ivanics MD | University Health Network, Toronto General Hospital Background: Living donor liver transplantation (LDLT) offers an opportunity to decrease the liver transplant waitlist and reduce waitlist mortality. We sought to compare donor and recipient characteristics and post-transplant outcomes after LDLT in the United States (US), United Kingdom (UK), and Canada, where deceased donors provide the majority of organs available for transplantation. Methods: We studied adults (≥18-years) who underwent primary LDLT between Jan-2008 and Dec-2018 from three national liver transplantation registries: United Network for Organ Sharing (UNOS;US), National Health Service Blood and Transplantation (NHSBT;UK), and the Canadian Organ Replacement Registry (CORR;Canada). Patients undergoing re-transplantation, multi-visceral transplantation, or had waitlist drop-out were excluded. Recipient and donor characteristics were compared across countries. A non-parametric Cox-Stuart trend test for LDLT was performed in each country. Post-transplant survival was evaluated using the Kaplan-Meier method, and multivariable adjustments were performed using Cox Proportional Hazard models. Results: A total of 3,086 LDLTs were performed (US:n = 2,433; UK:n = 97; Canada:n = 556). A trend toward increased LDLT over time was present in the US (Cox-Stuart trend test: US: p = 0.08; UK:p = 0.73; Canada: p = 0.49). Overall, the proportion of LDLTs compared to other grafts has remained stable (Figure 1) with Canada maintaining the highest proportion over time (proportion of LDLT 2008: US 3.4%; UK:1.7%; Canada: 20.1%; p<0.001; 2018: US: 5.0%; UK: 0.4%; Canada: 13.8%; p<0.001). The US and Canadian recipients had the highest body mass index (median [IQR]], US 26 [23-30]; UK 24 [22-28]; Canada 26 [23-29]; overall p<0.001) and the highest donor age (years, median [IQR]: US 36 [28-45]; UK 33 [25-40]; Canada 35 [27-46]; overall p = 0.010). The laboratory Model for End-Stage Liver disease (MELD) score was highest in Canada (median [IQR]: US 15 [11-19]; UK 11 [8-18]; Canada 17 [13-21]; p<0.001). UK had a higher proportion of hepatitis C virus as disease etiology (US 2%; UK 21%; Canada 12%;p<0.001) whereas the US had a higher proportion of non-alcoholic steatohepatitis (US 17%; UK 11%; Canada 7%;p<0.001). Time on the waitlist was longest in the US (days, median [IQR]; US 151 [79-308]; UK 92 [7-202]; Canada 122 [64-230];overall p<0.001). At 1-year there was a non-statistically significant superior survival in Canada (1-year%[95%CI]]; US 93.0% [(92.0-94.1]; UK 91.4% [85.8-97.3]; Canada 95.8% [94.1-97.5];p = 0.06]. The 3-, 5-, 10-year survival rate was superior in Canada (3-year% [95%CI]; US 88.1% [86.8-89.5]; UK 90.0% [84.0-96.5]; Canada 92.1% [89.8-94.5];p = 0.04), (5-year%[95%CI]; US 83.5% [81.8-85.3]; UK 85.4% [77.1-94.5]; Canada 89.9% [87.1-92.7];p = 0.005), and (10-year%; US 71.1% [67.6-74.8]; UK 66.7% [45.0-98.8]; Canada 82.7% [78.2-87.5];p = 0.001). The median survival was not reached in any of the registries. After adjustment for characteristics of donors, recipients, annual center volume, and year of transplantation, all countries had an equivalent hazard of mortality post-LT ([HR] for mortality, US Reference, UK HR:1.26, 95%CI 0.67-2.39;p = 0.47; Canada HR:0.61,95%CI 0.30-1.26;p = 0.18). Stratification by hepatocellular carcinoma status did not alter the patterns observed in the data. Conclusion: LDLT use has remained stably low in western countries. Despite this, long-term survival is excellent. Continued efforts to increase LDLT in these countries is thus warranted due to the growing waitlist and differences in allocation that may disadvantage patients currently awaiting liver transplantation.

Salvage living donor liver transplantation for hepatocellular carcinoma recurrence after hepatectomy: Quantitative prediction using ADV score.

Salvage liver transplantation is a definite treatment for recurrent hepatocellular carcinoma (HCC) after hepatectomy. ADV score is calculated by multiplying α-fetoprotein and des-γ-carboxyprothrombin concentrations and tumor volume. Prognostic accuracy of ADV score was assessed in patients undergoing salvage living donor liver transplantation (LDLT) and their outcomes were compared with patients undergoing primary LDLT. This study was a retrospective, single-center, case-controlled study. Outcomes were compared in 125 patients undergoing salvage LDLT from 2007 to 2018 and in 500 propensity score-matched patients undergoing primary LDLT. In patients undergoing salvage LDLT, median intervals between hepatectomy and tumor recurrence, between first HCC diagnosis and salvage LDLT, and between hepatectomy and salvage LDLT were 12.0, 37.2, and 29.3months, respectively. Disease-free survival (DFS, P=.98) and overall survival (OS, P=.44) rates did not differ significantly in patients undergoing salvage and primary LDLT. Pretransplant and explant ADV scores were significantly predictive of DFS and OS in patients undergoing salvage and primary LDLT (P<.001). DFS after prior hepatectomy (P=.52) and interval between hepatectomy and LDLT (P=.82) did not affect DFS after salvage LDLT. Milan criteria and ADV score were independently prognostic of DFS and OS following salvage LDLT, and prognosis of patients within and beyond Milan criteria could be further stratified by ADV score. Risk factors and posttransplant outcomes were similar in patients undergoing salvage and primary LDLT. ADV score is surrogate biomarker for posttransplant prognosis in salvage and primary LDLT recipients. Prognostic model incorporating ADV scores can help determine whether to perform salvage LDLT.

Salvage living-donor liver transplantation and ADV score

Background: Salvage liver transplantation is a definite treatment for recurrent hepatocellular carcinoma (HCC) after hepatecto my. ADV score is calculated by multiplying α-fetoprotein and des-γ-carboxyprothrombin concentrations and tumor volume. Prog nostic accuracy of ADV score was assessed in patients undergoing salvage living-donor liver transplantation (LDLT) and their outcomes were compared with patients undergoing primary LDLT. Methods: This study was retrospective single-center case-controlled study. Outcomes were compared in 125 patients undergo ing salvage LDLT from 2007 to 2018 and in 500 propensity score-matched patients undergoing primary LDLT. Results: In patients undergoing salvage LDLT, median intervals between hepatectomy and tumor recurrence, between first HCC diagnosis and salvage LDLT, and between hepatectomy and salvage LDLT were 12.0, 37.2, and 29.3 months, respectively. Dis ease-free survival (DFS, P=0.98) and overall survival (OS, P=0.44) rates did not differ significantly in patients undergoing salvage and primary LDLT. Pre-transplant and explant ADV scores were significantly predictive of DFS and OS in patients undergoing salvage and primary LDLT (P<0.001). DFS after prior hepatectomy (P=0.52) and interval between hepatectomy and LDLT (P=0.82) did not affect DFS after salvage LDLT. Milan criteria and ADV score were independently prognostic of DFS and OS following sal vage LDLT, and prognosis of patients within and beyond Milan criteria could be further stratified by ADV score. Conclusions: The risk factors and post-transplant outcomes were similar in patients undergoing salvage and primary LDLT. ADV scores were shown to be an integrated surrogate biomarker for post-transplant prognosis in salvage and primary LDLT recipients. This prediction model using pre-transplant and explant ADV scores can therefore provide reliable information on the post-transplant prognosis, thus assisting in the decision whether to perform salvage LDLT.

Retransplantation After Living Donor Liver Transplantation: Data from the Adult to Adult Living Donor Liver Transplantation Study.

The use of living donor liver transplantation (LDLT) for primary liver transplantation (LT) may quell concerns about allocating deceased donor organs if the need for retransplantation (re-LT) arises because the primary LT did not draw from the limited organ pool. However, outcomes of re-LT after LDLT are poorly studied. The purpose of this study was to analyze the Adult to Adult Living Donor Liver Transplantation Study (A2ALL) data to report outcomes of re-LT after LDLT, with a focus on long-term survival after re-LT. A retrospective review of A2ALL data collected between 1998 and 2014 was performed. Patients were excluded if they received a deceased donor LT. Demographic data, postoperative outcomes and complications, graft and patient survival, and predictors of re-LT and patient survival were assessed. Of the 1065 patients who underwent LDLT during the study time period, 110 recipients (10.3%) required re-LT. In multivariable analyses, hepatitis C virus, longer length of stay at LDLT, hepatic artery thrombosis, biliary stricture, infection, and disease recurrence were associated with an increased risk of re-LT. Patient survival among re-LT patients was significantly inferior to those who underwent primary transplant only at 1 (86% versus 92%), 5 (64% versus 82%), and 10 years (44% versus 68%). Approximately 10% of A2ALL patients who underwent primary LDLT required re-LT. Compared with patients who underwent primary LT, survival among re-LT recipients was worse at 1, 5, and 10 years after LT, and re-LT was associated with a significantly increased risk of death in multivariable modeling (hazard ratios, 2.29; P < 0.001).

Do Recipients of Genetically Related Donors Have Better Outcomes After Living Donor Liver Transplantation?

There are few data on genetic relation of the donor and outcomes in living donor liver transplantation (LDLT) recipients. We compared outcomes of LDLT between recipients of genetically related and unrelated donors in a large single-center series. The study included 1372 adult, ABO-compatible, primary LDLT recipients, who received a graft from either a first-degree relative (parent, sibling, son, or daughter; n = 756) or unrelated donor (spouse or relative of the spouse; n= 616). The mean age of the recipients with a related donor was 50.2 ± 10.8 years compared with 47.3±9.3 years for recipients with unrelated donors (P= 0.000). Chronic rejection was significantly more common in the genetically unrelated donor group than in the genetically related donor group (28 [4.5%] versus 9 [1.1%]; P= 0.000) at a mean follow-up of 37 months (15-95 months). There were no significant differences in other outcomes between the 2 groups. The 12-month and 36-month survival between the unrelated and related groups was 87.6% versus 90%, and 86.3% versus 89.7% respectively (P = 0.115). The multivariate analysis revealed genetically unrelated donors (odds ratio [OR]: 3.88, 95% confidence interval [CI]: 1.80-8.34, P= 0.001) and history of acute cellular rejection (OR: 3.39, 95% CI: 1.68-6.81, P= 0.001) as predictors of chronic rejection. Although chronic rejection was found to be more common in genetically unrelated donors, the patient survival after LDLT was similar.

Outcomes of a tailored rituximab-based desensitization protocol without local infusion therapy for ABO-incompatible adult living donor liver transplantation

Introduction: Rituximab (RTx) desensitization protocol in ABO-incompatible (ABOi) living donor liver transplantation (LDLT) offered new paradigm shift beyond ABO blood barrier to obtain donor pool expanding. The Aim of our study is to evaluate the outcome of ABOi adult LDLT using tailored desensitization protocol and to compare with that of ABO compatible (ABOc) LT in single center experience. Method: Between March 2012 and June 2017, 65 cases (14.8%) of ABOi LDLTs were performed in our center among 438 primary adult LDLTs. In ABOi cases, reduced RTx (300mg/m2) was administered around 3 weeks before LDLT, followed by 3 times of plasmapheresis at one week before LT regardless initial and final isoagglutinin titer. If issoagglutinin titer was higher than x32 after plasmapheresis, simultaneous splenectomy with perioperative high dose intravenous immunoglobulin (5 day s/0.8g/Kg) was selectively added. The immunosuppression was maintained with triple therapy (tacrolimus, steroids and mycophenolate mofetil). We performed propensity score matching and 120 ABOc cases and 60 ABOi cases were selected. Outcomes were then retrospectively compared between two groups. Result: There were no significant differences in recipients’ characteristics including MELD score, with HCC or not, and final graft to recipient weight ratio (GRWR) between two groups. Overall survival rates at 5 years are 89.2% in ABOc cases, and 87.8% in ABOi cases without any significant differences. There were also no significant differences in complication rates such as biliary complication, infection, acute cellular rejection. There were no cases with antibody-mediated rejection in ABOi cases. In cases with HCC (89 cases of ABOc group, and 42 cases of ABOi group), recurrence-free survival at 5 years were 90.4% in ABOc, and 77.5% in ABOi. There was also no significant difference. Conclusion: Our RTx-based tailored desensitization protocol for ABOi LDLT was feasible and the outcome was considered acceptable.

Actual outcomes and technical feasibility of living donor-related liver re-transplantation

Introduction: The aim of this study was to analyze the experience of liver re-transplantation (re-LT) at a large volume living donor liver transplantation (LDLT) center and reviewed the technical feasibility of LDLT related re-LT. Methods: Adult (≥18 years) patients who underwent liver transplantation (LT) more than twice between February 1994 and December 2015 were included. The retrospective study was conducted based on the review of medical record. Results: Among 4,666 adult LTs including 3,843 LDLTs and 697 deceased donors LTs (DDLT), 126 cases (2.8%) were re-LTs. The mean age and MELD score was 53.3 ± 9.4 years and 25.7 ± 8.1, respectively. The mean interval from primary LT to re-LT was 28.8 ± 45.0 months. The overall 1-, 5- and 10-year survival rates of re-LT were 58.8%, 53.4% and 50.4%, respectively which were significantly lower than those of primary LT (p < 0.001). In multivariate analysis, re-LT timing, portal vein thrombosis, MELD score >20, bacteremia and pneumonia were independent risk factors for survival. Out of 126 re-LTs, 16 cases (12.7%) were re-LDLTs. In re-LDLTs, interposition graft for PV reconstruction was used in 2 cases. For hepatic artery anastomosis, right gastroepiploic artery was used in 2 cases and greater saphenous vein interposition was employed in 2 cases. The patient's survival rate of re-LDLT was significantly lower than that of primary LDLT (p < 0.001) and comparable to that of re-DDLT (p = 0.724). Conclusions: Re-LDLT can be the feasible option for the irreversible graft dysfunction to overcome the donor scarcity despite technical demand.

Impact of Enteral Nutrition with an Immunomodulating Diet Enriched with Hydrolyzed Whey Peptide on Infection After Liver Transplantation.

Infection is a leading cause of death after liver transplantation (LT). Therefore, prevention of infection is crucial for improving outcomes after LT. We examined the impact of early enteral nutrition with an immunomodulating diet (IMD) enriched with hydrolyzed whey peptide (HWP) formulation on infection after living donor LT (LDLT), focusing on sarcopenia. This study enrolled 279 consecutive patients who underwent primary LDLT at our institute between January 2008 and April 2015. Early enteral nutrition with the IMD enriched with HWP formulation and a conventional elemental diet were started within the first 24h after surgery for 164 (IMD-HWP) and 115 (conventional) patients. Sequential changes in nutritional parameters, and the incidences of acute cellular rejection (ACR) and bacteremia were compared between the IMD-HWP and control groups. The comparison was made between those members of each group that did or did not exhibit sarcopenia. Risk factors for post-transplant bacteremia were also assessed. Postoperative nutritional parameters and the incidence of ACR were comparable between the groups, except for the prealbumin level. The incidence of bacteremia was significantly lower in the IMD-HWP group, and among patients without sarcopenia in the IMD-HWP group compared with the conventional group (24.4 vs. 41.7%; P = 0.002 and 20.8 vs. 39.0%; P = 0.040, respectively). Independent risk factor for bacteremia comprised bleeding ≥10,000mL (P = 0.025). In contrast, enteral nutrition without HWP formulation was not significantly associated with bacteremia. However, enteral nutrition without HWP formulation (P = 0.080), MELD scores (P = 0.097), and ABO incompatibility (P = 0.088) showed a trend toward increased incidence of bacteremia, although they did not reach statistical significance in the multivariate analysis. Postoperative immunonutrition with an IMD enriched with HWP formulation was closely involved with post-transplant bacteremia.

The surgical challenges of salvage living donor liver transplantation for Hepatocellular carcinoma; The cumulative experience of 100 cases - A retrospective cohort study and a propensity score analysis

BackgroundHepatocellular carcinoma (HCC) is increasingly managed by liver resection first then salvage liver transplantation in case of recurrence within accepted criteria. Many reports compared the safety of the salvage against the primary surgery in the setting of deceased donation but the difference in case of living donation is not sufficiently defined. Salvage living donor liver transplantation (SLDLT) is believed to be a more challenging surgery than primary living donor liver transplantation (PLDLT) due to operative field adhesions, in addition to the inherent difficulties particularly short vasculobiliary stumps. In this report, we compared both pathways from a surgical perspective in a homogenous LDLT-only cohort. Materials and methodsOver 15 years, 448 LDLTs for HCC were performed in a single liver transplant institution in Taiwan, including PLDLT (n = 348) and SLDLT (n = 100). A retrospective comparative review of the surgical outcomes of both pathways using a propensity score matching model (1–1, 100 pairs) was performed with adjustment for age, Child score and MELD score. The surgical outcome and survival were compared across 2 time eras. ResultsThe operative data showed that SLDLT surgery encountered more extensive adhesions (57% vs. 0%, p < 0.001), longer operative duration (650 vs. 618 min, p=0.04), and was followed by more incidence of re-exploration (16% vs. 5%, p=0.01), than the PLDLT surgery. There was no significant difference regarding the incidence of in-hospital mortality, vascular and biliary complications, or overall survival (OS). The 1-year OS of SLDLT was inferior to PLDLT in the first 50 cases (90% vs. 98%, p=0.03), then the same OS was found in the 2nd 50 cases (96% vs. 96%, p=0.9). ConclusionsThe SLDLT surgery is a demanding lengthy procedure with extensive adhesions and possibility of frequent re-explorations. Significant case load and high centre volume are important factors for safe practice of SLDLT and better cumulative OS.

Significance of Portal Venous Velocity in Short-term Graft Function in Living Donor Liver Transplantation

BackgroundGraft regeneration and functional recovery after reperfusion of transplanted graft are very important for successful living donor liver transplantation (LDLT). The aim of this study was to evaluate the significance of postoperative portal venous velocity (PVV) in short-term recovery of graft function in LDLT. Patients and MethodsFrom February 2007 through December 2015, we performed 17 primary LDLTs, which were included in the present study. The patients ranged in age from 12 to 65 years (mean: 50 years), and 11 were female patients. Postoperatively, Doppler ultrasonography was performed daily to measure PVV (cm/s), and liver function parameters were measured daily. The change in PVV (ΔPVV) was defined as follows: ΔPVV = PVV on postoperative day (POD) 1 − PVV on POD 7. Maximal value of serum aspartate aminotransferase (ASTmax) and maximal value of serum alanine transaminase (ALTmax) at 24 hours after graft reperfusion were used as parameters of reperfusion injury. Correlation analyses were performed as follows: (1) correlation of ΔPVV and PVV on POD 1 (PVV-POD 1) with the values such as ASTmax, ALTmax, other liver function parameters on POD 7 and graft regeneration rate; (2) correlation of ASTmax and ALTmax with other liver function parameters on POD 7. ResultsΔPVV significantly correlated with the values of serum total bilirubin (P < .01), prothrombin time (P < .01), and platelet count (P < .05), and PVV-POD 1 significantly correlated with the values of serum total bilirubin (P < .05) and prothrombin time (P < .05). ConclusionΔPVV and PVV-POD 1 may be useful parameters of short-term functional recovery of the transplant liver in LDLT.