Japanese Liver Transplantation Society Research Articles

Improved survival of pediatric deceased donor liver transplantation recipients after introduction of the pediatric prioritization system: Analysis of data from a Japanese national survey.

In Japan, there has never been a national analysis of pediatric deceased donor liver transplantation (pDDLT) based on donor and recipient factors. We constructed a Japanese nationwide database and assessed outcomes of pDDLT focusing on the pediatric prioritization system introduced in 2018. We collected data on pDDLTs (<18 years) performed between 1999 and 2021 from the Japan Organ Transplant Network and Japanese Liver Transplantation Society, identified risk factors for graft survival and compared the characteristics and graft survival in pDDLTs conducted before and after the introduction of the pediatric prioritization system. Overall, 112 cases of pDDLT were included, with a 1-year graft survival rate of 86.6%. Four poor prognostic factors were identified: recipient intensive care unit stay, model for end-stage liver disease/pediatric end-stage liver disease score, donor cause of death, and donor total bilirubin. After the introduction of the system, allografts from pediatric donors were more reliably allocated to pediatric recipients and the annual number of pDDLTs increased. The 1-year graft survival rate improved significantly as did pDDLT conditions indicated by the risk factors. Under the revised allocation system, opportunities for pDDLT increased, resulting in favorable recipient and donor conditions and improved survival.

An Analysis of 10,000 Cases of Living Donor Liver Transplantation in Japan: Special Reference to the Graft-Versus-Recipient Weight Ratio and Donor Age.

To analyze 10,000 cases of living donor liver transplantation (LDLT) recipient data to elucidate outcomes with special reference to the graft-versus-recipient weight ratio (GRWR), based on the Japanese Liver Transplantation Society (JLTS) registry. The JLTS registry has been accurate and complete in characterizing and following trends in patient characteristics and survival of all patients with LDLT. Between November 1989 and August 2021, 10,000 patients underwent LDLT in Japan. The procedures performed during the study period included pediatric liver transplantation (age <18 years, n = 3572) and adult liver transplantation (age ≥18 years, n=6428). Factors related to patient survival (PS) and graft survival (GS) were also analyzed. The GRWR was <0.7, 0.7 to <0.8, 0.8 to <3, 3 to <5, and ≥5 in 0.2%, 2.0%, 61.8%, 31.8%, and 2.6% of pediatric patients and <0.6, 0.6 to <0.7, 0.7 to <0.8, and ≥0.8 in 8.0%, 12.7%, 17.7%, and 61.5% of adult patients, respectively. Among pediatric recipients, the PS rate up to 5 years was significantly better in cases with a GRWR ≤5 than in those with a GRWR >5. When the GRWR and donor age were combined, among adult recipients 50 to 60 years old, the early PS and GS up to 5 years were significantly better in cases with a GRWR ≥0.7, than in those with a GRWR <0.7. (P = 0.02). In adults, a multivariate analysis showed that GRWR <0.6, transplant era (<2011), donor age (>60 years), recipient age (>60 years), model for end-stage liver disease score (≥20), and center volume (<10) were significant prognostic factors for long-term PS. Although a satisfactory long-term PS and GS, especially in the recent era (2011-2021), was achieved in the JLTS series, a GRWR ≥5 in pediatric cases and relatively old donors with a GRWR <0.7 in adult cases should be managed with caution.

Achieving clinically optimal balance between accuracy and simplicity of a formula for manual use: Development of a simple formula for estimating liver graft weight with donor anthropometrics.

In developing a formula for manual use in clinical settings, simplicity is as important as accuracy. Whole-liver (WL) mass is often estimated using demographic and anthropometric information to calculate the standard liver volume or recommended graft volume in liver transplantation. Multiple formulas for estimating WL mass have been reported, including those with multiple independent variables. However, it is unknown whether multivariable models lead to clinically meaningful improvements in accuracy over univariable models. Our goal was to quantitatively define clinically meaningful improvements in accuracy, which justifies an additional independent variable, and to identify an estimation formula for WL graft weight that best balances accuracy and simplicity given the criterion. From the Japanese Liver Transplantation Society registry, which contains data on all liver transplant cases in Japan, 129 WL donor-graft pairs were extracted. Among the candidate models, those with the smallest cross-validation (CV) root-mean-square error (RMSE) were selected, penalizing model complexity by requiring more complex models to yield a ≥5% decrease in CV RMSE. The winning model by voting with random subsets was fitted to the entire dataset to obtain the final formula. External validity was assessed using CV. A simple univariable linear regression formula using body weight (BW) was obtained as follows: WL graft weight [g] = 14.8 × BW [kg] + 439.2. The CV RMSE (g) and coefficient of determination (R2) were 195.2 and 0.548, respectively. In summary, in the development of a simple formula for manually estimating WL weight using demographic and anthropometric variables, a clinically acceptable trade-off between accuracy and simplicity was quantitatively defined, and the best model was selected using this criterion. A univariable linear model using BW achieved a clinically optimal balance between simplicity and accuracy, while one using body surface area performed similarly.

No impact of donor sex on the recurrence of hepatocellular carcinoma after liver transplantation.

We aimed to verify a recent theory that female donors reduced the risk of hepatocellular carcinoma (HCC) recurrence after liver transplantation (LT). A total of 1118 recipients registered in the Japanese Liver Transplantation Society database were evaluated for HCC, of whom 446 received a graft from female donors (F-D group) and 672 from male donors (M-D group). Between the groups, donor age, recipient age and sex, positivity of hepatitis viruses, and graft type were different, whereas tumor-related factors were all comparable. The 5-year overall recurrence rates were 14% and 16% in the F-D and M-D groups, respectively (P=0.59). The 5-year graft recurrence rate was also comparable between the groups (4% and 6%, respectively, P=0.17). Neither univariate nor multivariate analysis identified donor sex as a significant risk factor for recurrence. Propensity score matching showed similar 5-year overall recurrence rates (15% in the F-D group and 14% in the M-D group, P=0.63) and graft recurrence rates (5% and 5%, respectively, P=0.94) between the groups. Donor sex did not affect post-LT recurrence of HCC in the Japanese cohort and should not be considered in the process of donor selection or organ allocation.

Liver Transplantation in Japan—Registry by the Japanese Liver Transplantation Society—

Liver Transplantation in Japan—Registry by the Japanese Liver Transplantation Society—

Report of the 39th Annual Meeting of the Japanese Liver Transplantation Society

Report of the 39th Annual Meeting of the Japanese Liver Transplantation Society

Outcomes of Pediatric Liver Transplantation in Japan: A Report from the Registry of the Japanese Liver Transplantation Society.

The Japanese Liver Transplantation Society (JLTS), a cooperative research consortium, was established in 1980 to characterize and follow trends in patient characteristics and graft survival among all liver transplant patients in Japan. This study analyzed factors that may affect the current outcomes of pediatric patients who undergo liver transplantation (LT) by evaluating one of the largest pediatric LT cohorts in the world. Between November 1989 and December 2018, 3347 pediatric patients underwent LT in Japan. The survival outcomes of each donor and recipient variant were evaluated. The procedures performed during the study period included living donor LT (LDLT; n = 3271), deceased donor LT (DDLT; n = 69), and domino LT (n = 7). There were 1510 male (45.1%) and 1837 female (54.9%) recipients with a median age of 1.7 y (range: 9 d to 17.9 y). The graft survival rates at 1, 10, 20, and 30 y were 88.9%, 82.2%, 77.1%, and 75.4%, respectively. Donor age, donor BMI, blood type incompatibility, recipient age, etiology of liver disease, transplant type, center experience, and transplant era were found to be significant predictors of overall graft survival. LDLT is a major treatment modality for the end-stage liver disease in children; DDLT and domino LT were applied as alternative treatments for LDLT in patients with specific pediatric liver diseases that are considered to have a poor prognosis following LDLT. Satisfactory long-term pediatric patient survival outcomes were achieved in the JLTS series, and we should continue to promote the deceased donor organ transplantation program in Japan.

Liver Transplantation in Japan—Registry by the Japanese Liver Transplantation Society—

Liver Transplantation in Japan—Registry by the Japanese Liver Transplantation Society—

Liver Transplantation in Japan. —Registry by the Japanese Liver Transplantation Society—

Liver Transplantation in Japan. —Registry by the Japanese Liver Transplantation Society—

Liver transplantation in Japan: Registry by the Japanese Liver Transplantation Society.

As of 31 December 2017, a total of 9242 liver transplants have been carried out in 67 institutions in Japan. There were 447 deceased donor transplants (444 from heart-beating donors and 3 from non-heart-beating donors) and 8795 living-donor transplants. The annual total of liver transplants in 2017 was 416 (69 deceased donor transplants and 347 living-donor transplants). The most frequent indication was cholestatic disease, followed by neoplastic disease and hepatocellular disease. In terms of hepatocellular disease in 2017, cirrhosis due to hepatitis C and B decreased (13 and 8, respectively), whereas alcoholic cirrhosis markedly increased (32). Patient survival following transplantation from heart-beating donor (444 transplants: 1year, 89.1%; 3years, 85.2%; 5years, 82.9%; 10years, 75.4%; 15years, 70.7%) was similar to that from living-donor (8794 transplants: 1year, 85.0%; 3years, 80.9%; 5years, 78.5%; 10years, 73.2%; 15years, 68.5%; 20years, 65.7%; 25years, 64.6%). Graft survival was very much the same as patient survival (heart-beating donor: 1year, 88.4%; 3years, 84.5%; 5years, 82.2%; 10years, 74.7%; 15years, 70.1%; livingdonor: 1year, 84.3%; 3years, 79.9%; 5years, 77.3%; 10years, 71.4%; 15years, 66.3%; 20years, 63.3%; 25years, 61.9%). Survival data are reported according to age and sex of recipient, indication, age and sex of donor, ABO compatibility, and other factors.

Liver Transplantation in Japan —Registry by the Japanese Liver Transplantation Society—

Liver Transplantation in Japan —Registry by the Japanese Liver Transplantation Society—

Liver Transplantation in Japan —Registry by the Japanese Liver Transplantation Society—

Liver Transplantation in Japan —Registry by the Japanese Liver Transplantation Society—

Liver transplantation for biliary atresia: a systematic review.

Biliary atresia (BA) is an idiopathic neonatal cholangiopathy characterized by progressive inflammatory obliteration of the intrahepatic or extrahepatic bile ducts. Although the Kasai operation has dramatically improved the outcomes in children with BA, most patients with BA eventually require liver transplantation (LT) even after undergoing a successful Kasai procedure. The Japanese LT Society (JLTS) was established in 1980 to characterize and follow trends in patient characteristics and the graft survival among all liver transplant patients in Japan. The 1-, 5-, 10-, 15- and 20-year survival rates for the patients and grafts undergoing living donor LT were 91.6, 91.5, 87.1, 85.4 and 84.2 and 90.5, 90.4, 84.6, 82.0 and 79.9%, respectively. LDLT was able to be performed even in patients weighing less than 5kg with early liver failure following a Kasai operation using a reduced left lateral segments. As LT has been revealed to increase the donor pool and decrease the waiting list mortality with an excellent long-term graft survival, early referral to a transplant center should be considered when at least one complication of cirrhosis occurs during its natural history, especially in adolescents.

Living donor liver transplantation for biliary atresia: An analysis of 2085 cases in the registry of the Japanese Liver Transplantation Society.

Biliary atresia (BA) is the most common indication for liver transplantation (LT) in pediatric population. This study analyzed the comprehensive factors that might influence the outcomes of patients with BA who undergo living donor LT by evaluating the largest cohort with the longest follow-up in the world. Between November 1989 and December 2015, 2,085 BA patients underwent LDLT in Japan. There were 763 male and 1,322 female recipients with a mean age of 5.9years and body weight of 18.6kg. The 1-, 5-, 10-, 15-, and 20-year graft survival rates for the BA patients undergoing LDLT were 90.5%, 90.4%, 84.6%, 82.0%, and 79.9%, respectively. The donor body mass index, ABO incompatibility, graft type, recipient age, center experience, and transplant era were found to be significant predictors of the overall graft survival. Adolescent age (12 to <18years) was associated with a significantly worse long-term graft survival rate than younger or older ages. We conclude that LDLT for BA is a safe and effective treatment modality that does not compromise living donors. The optimum timing for LT is crucial for a successful outcome, and early referral to transplantation center can improve the short-term outcomes of LT for BA. Further investigation of the major cause of death in liver transplanted recipients with BA in the long-term is essential, especially among adolescents.

Liver transplantation in Japan. -Registry by the Japanese Liver Transplantation Society-

Liver transplantation in Japan. -Registry by the Japanese Liver Transplantation Society-

肝臓移植に関わる肝臓内科医の役割：肝移植実施施設および関連施設へのアンケート調査結果報告

わが国において肝臓内科医が肝移植医療にどの程度関わっているかを明らかにするため，2015年11月，肝移植研究会の施設会員を対象にアンケート調査を実施した．69人（58施設）から回答を得，うち移植実施施設は39施設（67％）で，各施設の平均年間移植実施件数は10±13例であった．移植を担当する肝臓内科医が在任していたのは移植実施施設中22施設（56%）で，内科医数は2（1～8）人であった．移植実施施設では，移植待機中の外来および入院診療，移植後6カ月以降の外来を内科外科両方が関わると答えた施設がそれぞれ71％，69％，74%と過半数であったが，移植6カ月以内の外来および入院診療への内科医の関わりは43%，25％と低かった．肝臓内科医は既に殆どの移植医療施設で活躍していることが明らかになった．今後，より積極的な肝臓内科医の関与によって，移植医療のさらなる発展を期待したい．

Liver transplantation in Japan: Registry by the Japanese Liver Transplantation Society.

As of December 31, 2013, a total of 7474 liver transplants have been carried out at 66 institutions in Japan. This total included 7255 living-donor transplants and 219 deceased-donor transplants (216 from heart-beating donors and 3 from non-heart-beating donors). The annual total of liver transplants in 2013 decreased to 408, from 422 in 2012. The number of liver transplants from living donors decreased to 369, from 381, whereas the number of liver transplants from heart-beating deceased donors did not change significantly. The most frequent indication was cholestatic disease, followed by neoplastic disease. In terms of graft liver in living-donor cases, right-lobe graft was the most popular (36%). Patient survival following transplantations from heart-beating donors (1year, 85.9%; 3years, 82.6%; 5years, 81.3%; 10years, 73.8%) was similar to those from living donors (1year, 83.8%; 3years, 79.6%; 5years, 77.1%; 10years, 71.9%; 15years, 67.8%; 20years, 66.1%). Graft survival was very much the same as patient survival. As for ABO-incompatible transplantation, transplant period affected the outcome significantly, probably due to local infusion therapy and rituximab prophylaxis, which were introduced in many transplant centers after 2000 and 2004, respectively.

Liver Transplantation in Japan -Registry by the Japanese Liver Transplantation Society-

Liver Transplantation in Japan -Registry by the Japanese Liver Transplantation Society-

Therapeutic Outcomes and Factors Affecting the Prognosis in Primary Biliary Cirrhosis

Introduction: The prognosis of primary biliary cirrhosis (PBC) is affected by its complication such as portal hypertension (PH) or hepatocellular carcinoma (HCC). In this study, efficacy of Ursodeoxycholic acid(UDCA) with or without Bezafibrate(BF) as well as factors associated with the prognosis of PBC was evaluated. Methods: Thirty-six patients (male/female 5/31, age at diagnosis 58.3±9.3, median observation period 114.5 months) diagnosed as PBC histologically or clinically during the period between 1994 and 2014 were enrolled. Liver-biopsy was conducted in 25 patients, consisting of 10/9/5/1 in Scheuer staging 1/2/3/4, respectively. Among these 36 patients, 23 received only UDCA, 12 received both UDCA and BF, and 1 received only BF. The trend of serum parameters (AST, ALT, ALP, gamma-GTP, T.Bil, PLT) after treatment as well as the relation between change in serum parameters (same as above) and incidence of complications (HCC, PH etc.) was assessed. Results: In all patients, each parameter such as AST, ALT, ALP and gamma-GTP (before treatment/3 months after treatment) was 76.3±93.7/36.9±20.8 IU/l, 80.4±89.7/32.2±19.9 IU/l, 706.1±365.5/443.8±196.1 IU/l, 271.9±215.2/89.0±67.9 IU/l, respectively, indicating significant amelioration (p150,000; group B: PLT < 150,000), the mortality rate after 6 months based on the predictive formula of prognosis by Japanese Liver Transplantation Society was higher in group B (P < 0.05). Furthermore, more complications were observed in group B (A/B: 11%(3/27)/44%(4/9)). Thus, the low number of PLT at diagnosis could be associated with higher incidence of complications. Conclusion: In patients with PBC, either UDCA monotherapy or combination therapy using UDCA and BF could be useful in ameliorating serum parameters. The state of symptoms as well as the number of PLT at diagnosis could be associated with the prognosis of PBC.

Liver Transplantation in Japan -Registry by the Japanese Liver Transplantation Society-

Liver Transplantation in Japan -Registry by the Japanese Liver Transplantation Society-