Excess mortality in COVID-19-affected solid organ transplant recipients across the pandemic.

The excess mortality of coronavirus disease 2019 (COVID-19) solid organ transplant recipients (SOTRs) throughout the pandemic remains unclear. This prospective cohort study based on the Japanese nationwide registry included 1632 SOTRs diagnosed with COVID-19 between February 1, 2020, and July 31, 2022, categorized based on dominant phases of variants of concern (VOCs): Waves 1 to 3 (Beta), 4 (Alpha), 5 (Delta), 6 (Omicron BA.1/BA.2), and 7 (Omicron BA.5). Excess mortality of COVID-19-affected SOTRs was analyzed by calculating standardized mortality ratios (SMRs). Overall, 1632 COVID-19-confirmed SOTRs included 1170 kidney, 408 liver, 25 lung, 20 heart, 1 small intestine, and 8 multiorgan recipients. Although disease severity and all-cause mortality decreased as VOCs transitioned, SMRs of SOTRs were consistently higher than those of the general population throughout the pandemic, showing a U-shaped gap that peaked toward the Omicron BA.5 phase; SMR (95% CI): 6.2 (3.1-12.5), 4.0 (1.5-10.6), 3.0 (1.3-6.7), 8.8 (5.3-14.5), and 21.9 (5.5-87.6) for Waves 1 to 3 (Beta), Wave 4 (Alpha), Wave 5 (Delta), Wave 6 (Omicron BA.1/2), and Wave 7 (Omicron BA.5), respectively. In conclusion, COVID-19 SOTRs had greater SMRs than the general population across the pandemic. Vaccine boosters, immunosuppression optimization, and other protective measures, particularly for older SOTRs, are paramount.

International Multicenter Study of Ultra-Low GRWR Grafts in Adult Living Donor Liver Transplantation.

Decreasing the graft size in living donor liver transplantation (LDLT) increases the risk of early allograft dysfunction. Graft-to-recipient-weight-ratio (GRWR) of 0.8 is considered the threshold. There is evidence that smaller volume grafts may also provide equally good outcomes, the cut-off of which remains unknown. In this retrospective multi-center study, 92 adult LDLT with a final GRWR<=0.6 performed at 12 international liver transplant (LT) centers over a 3-year period were included. Perioperative data including preoperative status, portal flow hemodynamics (PFH) and portal flow modulation (PFM), development of SFSS, morbidity and mortality was collated and analyzed. Thirty-two (36.7%) patients developed SFSS and this was associated with increased 30-day, 90-day and one-year mortality. Pre-operative MELD and inpatient status were independent predictors for SFSS (p<0.05). Pre-LT renal dysfunction was an independent predictor of survival (Hazard ratio- 3.1;95% ci 1.1,8.9, p=0.035). PFH or PFM were not predictive of SFSS or survival. We report the largest ever multi-center study of LDLT outcomes using ultralow-GRWR grafts and for the first-time validate the ILTS-iLDLT-LTSI consensus definition and grading of SFSS. Pre-operative recipient condition rather than GRWR and PFH were independent predictors of SFSS. Algorithms to predict SFSS and LT outcomes should incorporate recipient factors along with GRWR.

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.

OBJECTIVE: 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. BACKGROUND: The JLTS registry has been accurate and complete in characterizing and following trends in patient characteristics and survival of all patients with LDLT. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Comparison of BNT162b2 and mRNA1273 vaccines in solid organ transplant recipients: Post-Hoc analysis of a Japanese national prospective study.

The coronavirus disease-19 (COVID-19) vaccine efficacy and immunogenicity in the immunocompetent population are well established. However, in solid organ transplant (SOT) recipients, because of their use of immunosuppressive medication, the immunogenicity of these severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines remains suboptimal. Both BNT162b2 and mRNA1273 have been used for some time, but their immunogenicity has not been directly compared in this immunocompromised patient group. We performed a post-hoc analysis of a previous prospective cohort study. The inclusion criteria were adult SOT recipients with active grafts at least 1 month after SOT. After giving consent, participants chose to receive either BNT162b2 or mRNA1273 vaccine. Anti-spike-protein-S antibody against SARS-CoV-2 was measured. Propensity scores were calculated via logistic regression to transform the probability of having received either BNT162b2 or mRNA1273 vaccine, and a model was developed. We enrolled 623 SOT recipients. In the propensity score-matched analysis, 100 recipients were selected for BNT162b2 and 100 for mRNA1273. SARS-CoV-2 anti-spike protein antibody positivity with BNT162b2 versus mRNA1273 at 3 weeks after the first dose, 1 month after the second dose, 3 months after the second dose, and 6 months after the second dose were 10% versus 19% (P = .07), 51% versus 58% (P = .30), 74% versus 88% (P = .01), and 78% versus 87% (P = .13), respectively. We conducted a propensity score-matched comparison of BNT162b2 and mRNA1273 vaccines as the primary series of COVID-19 vaccines in SOT recipients. We found significantly better immunogenicity with the mRNA1273 vaccine than with BNT162b2.

Impact of sustained viral response for hepatitis C virus on the outcomes of liver transplantation in hemophilic patients with human immunodeficiency virus/hepatitis C virus co-infection: A nationwide survey in Japan.

AIM: Human immunodeficiency virus (HIV)/hepatitis C virus (HCV) co-infection from blood products for hemophilia has been a social problem in Japan, and liver transplantation (LT) for these patients has been a challenging procedure. However, with the advent of the direct-acting antiviral agent for HCV and change in the policy for prioritization of deceased donor LT, the results of LT for patients co-infected with HCV/HIV may have improved. METHODS: This study was conducted to provide updated results of our nationwide survey of LT for patients co-infected with HCV/HIV, from January 1997 to December 2019. We collected data on 17 patients with HIV/HCV co-infection who underwent either deceased donor LT (n = 5) or living donor LT (n = 12). RESULTS: All the patients were men with hemophilia, and the median age was 41 (range, 23-61) years. The median CD4 count before LT was 258 (range, 63-751). Most patients had poor liver function before surgery with Child-Pugh grade C and a Model for End-stage Liver Disease score of 20 (range, 11-48). The right lobe was used for most grafts for living donor liver transplantation (n = 10). Overall survival was significantly better with a sustained viral response (SVR) than without an SVR, and a univariate analysis indicated that SVR after direct-acting antiviral or interferon/ribavirin showed the highest hazard ratio for patient survival after LT. A multivariate analysis was not possible because of the limited number of cases. CONCLUSION: SVR for HCV showed the highest impact on the outcome of LT for patients with hemophilia co-infected with HIV/HCV. SVR for HCV should be achieved before or after LT for patients with hemophilia co-infected with HIV/HCV for a better outcome.

Improved Mortality, Morbidity, and Long-Term Outcome After Anatomical Hepatectomy With the Glissonean Pedicle Approach in Patients With Hepatocellular Carcinoma: 30 Years' Experience at a Single Institute.

OBJECTIVE: We evaluated the morbidity and mortality after anatomical hepatectomy with the Glissonean pedicle approach, and long-term outcomes in relation to the morbidity in patients with hepatocellular carcinoma (HCC). SUMMARY BACKGROUND DATA: The mortality, morbidity, and long-term outcomes were evaluated retrospectively. METHODS: A total of 1953 patients with HCC underwent various anatomical hepatectomies with the Glissonean pedicle approach between 1985 and 2014. The mortality (30-day and 90-day) and morbidity (Clavien-Dindo class Ilia or higher) were evaluated among six 5-year eras (1985-1989, 1990-1994, 1995-1999, 2000-2004, 2005-2009, 2010-2014). RESULTS: A total of 460 patients (24%) showed morbidity, and the overall 30-day and 90-day mortality rates were 1.8% and 3.3%, respectively. The 30-day (3.9%, 3.0%, 1.8%, 1.3%, 0.3%, 0.5%: P = 0.0074) and 90-day mortality (6.0%, 4.3%, 3.8%, 2.8%, 2.2%, 1.4%: P = 0.0445) significantly improved over the eras. Blood loss >2 L (odds ratio: 11.808, P = 0.0244) was an independent risk factor for 30-day mortality, and blood loss >2 L (odds ratio: 4.046, P = 0.0271) and bile leakage (odds ratio: 2.122, P = 0.0078) were independent risk factors for 90-day mortality on multivariate analysis. Morbidity was significant independent prognostic factors for overall survival (relative risk: 2.129, P < 0.0001) and recurrence-free survival (relative risk: 1.299, P < 0.0001) in patients with HCC. CONCLUSIONS: Anatomical hepatectomy with the Glissonean pedicle approach was achieved safely in patients with HCC. For more safety and longer survival, blood loss, bile leakage, and morbidity should be reduced. Longterm outcomes after anatomical hepatectomy with the Glissonean pedicle approach in patients with HCC have been improved over 30 years with gradually less mortality and morbidity due to decreases in blood loss >2 L and bile leakage.

The role of graft to recipient weight ratio on enhanced recovery of the recipient after living donor liver transplantation - A systematic review of the literature and expert panel recommendations.

BACKGROUND: There continues to be debate about the lower limit of graft-to-recipient weight ratio (GRWR) for living donor liver transplant (LDLT). OBJECTIVES: To identify the lower limit of GRWR compatible with enhanced recovery after living donor liver transplant and to provide international expert panel recommendations. DATA SOURCES: Ovid MEDLINE, Embase, Scopus, Google Scholar, and Cochrane Central. METHODS: Systematic review following PRISMA guidelines and recommendations using the GRADE approach derived from an international expert panel. Studies assessing how GRWR affects recipient outcomes such as small for size syndrome, other complications, patient and graft survival, and length of stay were included. PROTOCOL REGISTRATION: CRD42021260794. RESULTS: Twenty articles were included in the qualitative synthesis, and all were retrospective observational studies. There was heterogeneity in the definition of study cohorts and key outcome measures such as small-for-size syndrome. Most studies lacked risk adjustment given limited single-center sample size. GRWR of ≥ .8% is associated with enhanced recovery. Recipients of grafts with GRWR < .8%, however, were found to have similar outcomes as those with ≥ .8% when appropriate consideration is made for portal flow modulation and recipient illness severity. CONCLUSIONS: GRWR ≥ .8% is often compatible with enhanced recovery, but grafts < .8% can be used in selected LDLT recipients with optimal donor-recipient selection, surgical technique, and perioperative management (Quality of Evidence; Low | Grade of Recommendation; Strong).

Impact of COVID-19 on living donor liver and kidney transplantation programs in Japan in 2020.

BACKGROUND: Although many transplant programs have been forced to suspend living donor transplants due to the emergence of coronavirus disease (COVID-19), there are relatively few real-time databases to assess center-level transplant activities. We aimed to delineate the actual impact of COVID-19 on living donor transplant programs and the resumption process in Japan. METHODS: In a nationwide survey, questionnaires were sent to 32 liver transplant programs that had performed at least more than one case of living donor liver transplantation in 2019 and 132 kidney transplant programs that had performed more than one living donor kidney transplantation in 2018. RESULTS: Thirty-one (96.9%) and 125 (94.7%) liver and kidney transplant programs responded, respectively. In the early pandemic period, 67.7% (21/31) of liver programs and 29.8% (37/125) of kidney programs were able to maintain transplant activities similar to those during the pre-pandemic period. After temporal suspension, 58.1% of kidney programs resumed their transplant activity after the number of local COVID-19 cases peaked. Establishing institutional COVID-19 screening, triage, and therapeutic management protocols was mandatory to resume transplant activity for 64.5% and 67.7% of liver and kidney programs, respectively. In the future wave of COVID-19, 67.7% of liver programs would be affected by institutional COVID-19 intensive care unit-bound patient numbers, and 55.7% of kidney programs would stop if hospital-acquired severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection spreads. CONCLUSIONS: THIS NATIONWIDE SURVEY REVEALED FOR THE FIRST TIME HOW LIVING DONOR LIVER AND KIDNEY: transplant programs changed in response to the COVID-19 pandemic in a country where living donor transplantations are predominant.

Prevalence of fatty liver disease after liver transplantation and risk factors for recipients and donors.

INTRODUCTION AND OBJECTIVES: Fatty liver disease (FLD) may develop in liver transplant recipients. We investigated the recipient and donor risk factors for FLD development after liver transplantation (LT). METHODS: A total of 108 liver transplant recipients (54 men [50.0%]; median age, 52 [20-68] years) treated from 2011-2020 was enrolled. Three recipients died at < 3 months as a result of infection or blood flow impairment, and were excluded from the long-term FLD study. On evaluation of 88 prospective living donors, fatty liver was observed in 21. The prevalence and risk factors for FLD and survival were evaluated. RESULTS: After LT, 28 of 105 recipients (26.7%) developed FLD. FLD was more common in patients with a high body mass index (BMI) and dyslipidemia (both p < 0.01), primary nonalcoholic steatohepatitis (p = 0.02), after living-donor LT (p = 0.03) and everolimus (EVL) use (p = 0.08). Factors predictive of FLD included EVL use and a high BMI (hazard ratios = 3.00 and 1.34; p = 0.05 and p < 0.01, respectively). Sixteen donors lost 6.5 kg (range: 2.0-16.0 kg) of body weight prior to LT. However, there were no cases of primary non-function, which did not affect the FLD prevalence. Development of FLD did not have a negative impact on LT outcome; the 5-year survival rate was 92.6%. CONCLUSIONS: Recipient factors were more important than donor factors for FLD onset after LT.

National survey on deceased donor organ transplantation during the COVID-19 pandemic in Japan.

PURPOSE: We investigated the status of deceased organ donation and transplantation through a questionnaire distributed to transplant centers in Japan during the COVID-19 pandemic. METHODS: The questionnaire was distributed electronically to 206 transplant centers for heart (n = 11), lung (n = 10), liver (n = 25), kidney (n = 130), pancreas (n = 18), and small intestine (n = 12) transplantation. Organ donations and organ transplantation data were extracted from the Japan Organ Transplant Network website. RESULTS: We received questionnaire responses from 177 centers (response rate, 86%). In 2020, the number of brain-dead donors (BDDs) decreased to 68 (69% of the year-on-year average) and the number of donors after cardiac death (DCDs) decreased to 9 (32% of the year-on-year average). Eighty-five (48%) transplant centers (heart, n = 0; lung, n = 0; liver, n = 4; kidney, n = 78; pancreas, n = 22; and small intestine, n = 0) suspended transplant surgeries in response to the COVID-19 pandemic. Consequently, the number of organ transplantations from deceased donors was significantly lower in 2020 than in 2019. CONCLUSION: Although the COVID-19 pandemic has had less impact in Japan than in other countries, it has affected transplantation activity significantly, suspending transplantation surgeries in 48% of the transplantation centers, including 78% of the kidney transplantation centers, and reducing the number of organ donations to 61% of the year-on-year average.

Expert Consensus Guidelines on Minimally Invasive Donor Hepatectomy for Living Donor Liver Transplantation From Innovation to Implementation: A Joint Initiative From the International Laparoscopic Liver Society (ILLS) and the Asian-Pacific Hepato-Pancreato-Biliary Association (A-PHPBA).

OBJECTIVE: The Expert Consensus Guidelines initiative on MIDH for LDLT was organized with the goal of safe implementation and development of these complex techniques with donor safety as the main priority. BACKGROUND: Following the development of minimally invasive liver surgery, techniques of MIDH were developed with the aim of reducing the short- and long-term consequences of the procedure on liver donors. These techniques, although increasingly performed, lack clinical guidelines. METHODS: A group of 12 international MIDH experts, 1 research coordinator, and 8 junior faculty was assembled. Comprehensive literature search was made and studies classified using the SIGN method. Based on literature review and experts opinions, tentative recommendations were made by experts subgroups and submitted to the whole experts group using on-line Delphi Rounds with the goal of obtaining >90% Consensus. Pre-conference meeting formulated final recommendations that were presented during the plenary conference held in Seoul on September 7, 2019 in front of a Validation Committee composed of LDLT experts not practicing MIDH and an international audience. RESULTS: Eighteen Clinical Questions were addressed resulting in 44 recommendations. All recommendations reached at least a 90% consensus among experts and were afterward endorsed by the validation committee. CONCLUSIONS: The Expert Consensus on MIDH has produced a set of clinical guidelines based on available evidence and clinical expertise. These guidelines are presented for a safe implementation and development of MIDH in LDLT Centers with the goal of optimizing donor safety, donor care, and recipient outcomes.

Longterm Outcome of Liver Transplantation for Congenital Extrahepatic Portosystemic Shunt.

Liver transplantation (LT) is often viewed as the last resort for the treatment of congenital extrahepatic portosystemic shunt (CEPS) due to advancement of imaging and interventional radiology techniques. However, some patients still require LT, and criteria for LT are yet to be determined. We conducted a national survey of patients undergoing LT for CEPS between June 1998 and August 2018 and evaluated the clinical data and outcomes with a review of previously reported patients from the English-language medical literature. A total of 26 patients underwent LT in Japan at a median age of 5.2 years old. The most common indications for LT were persistent hyperammonemia (54%) and liver mass (50%), followed by pulmonary complications (38%). Pulmonary complications in all patients, including intrapulmonary shunt and pulmonary hypertension (PH), were improved after LT. Regarding the 29 previously reported patients in the English-language literature, a liver nodule (49%), including hepatoblastoma and hepatocellular carcinoma, was the most common indication for LT, followed by pulmonary complications (34%). A total of 25 (96%) patients in our survey and 26 (90%) patients in the literature review were alive with a median follow-up period of 9.5 and 1.6 years, respectively. Although LT has a limited role in management of CEPS, our study indicated that LT was safe as an alternative treatment for select patients with malignant tumor or pulmonary complications and those with complications related to new portosystemic collateral vessels after shunt closure, such as PH or hepatopulmonary syndrome.

Donor age (≥45 years) and reduced immunosuppression are associated with the recurrent primary sclerosing cholangitis after liver transplantation - a multicenter retrospective study.

The present study investigated the possible risk factors, including relationship/HLA matching between donor and recipient, and immunosuppressive therapies on the recurrence of primary sclerosing cholangitis (PSC) after liver transplantation (LT). Subjects were 197 recipients of LT for PSC, among whom 180 surviving more than 1 year after LT were further analyzed for risk factors of recurrence. The 5- and 10-year patient- and graft survival rates were 83% and 68%, and 71% and 62%, respectively. The overall PSC recurrence rate was 25% with a 5- and 10-year graft survival rate of 34% and 18%, which was significantly lower than the survival rate of those without recurrence (P < 0.001). Univariate analysis identified the following as risk factors for recurrence: donor age (P < 0.001), cyclosporine use (P = 0.012), mono or no immunosuppressive agent (P < 0.001), postoperative biliary complication (P < 0.001), and active intestinal bowel disease after LT (P < 0.001). Among these factors, donor age ≥45 years [hazard ratio (HR), 1.65; 95% confidence interval (CI), 1.21-2.69; P = 0.003] and mono or no immunosuppressive agent 1-year after LT (HR, 2.38; 95% CI, 1.23-3.45; P = 0.011) were identified as independent risk factors in the final multivariate Cox regression model. The results were similar in sub-analysis for ABO-identical/compatible adult living donor LT cases.

Impacts of single nucleotide polymorphisms in Fc gamma receptor IIA (rs1801274) on lung transplant outcomes among Japanese lung transplant recipients.

This study aimed to analyze the influences of single nucleotide polymorphisms (SNPs) in Fc gamma receptor IIA (FCGR2A) on postoperative outcomes after lung transplantation (LTx). We enrolled 191 lung transplant recipients [80 undergoing living-donor lobar lung transplants (LDLLTs) and 111 undergoing deceased-donor lung transplants (DDLTs)] in this study. We identified SNPs in FCGR2A (131 histidine [H] or arginine [R]; rs1801274) and reviewed the infectious complication-free survival after ICU discharge. The SNPs in FCGR2A comprised H/H (n = 53), H/R (n = 24), and R/R (n = 3) in LDLLT and H/H (n = 67), H/R (n = 42), and R/R (n = 2) in DDLT. Recipients with H/H (H/H group) and those with H/R or R/R (R group) were compared in the analyses of infectious complications. In multivariate analyses, the R group of SNPs in FCGR2A was associated with pneumonia-free survival {HR: 2.52 [95% confidence interval (CI): 1.35-4.71], P = 0.004}, fungal infection-free survival [HR: 2.50 (95% CI: 1.07-5.84), P = 0.035], and cytomegalovirus infection-free survival [HR: 2.24 (95% CI: 1.07-4.69), P = 0.032] in LDLLT, but it was not associated with infectious complication-free survival in DDLT. Therefore, in LDLLT, more attention to infectious complications might need to be paid for LTx recipients with H/R or R/R than for those with H/H.

An analysis of the outcomes in living donor liver transplantation for pediatric malignant hepatic tumors using nationwide survey data in Japan.

Malignant hepatic tumors (MHTs) in children are rare and account for approximately 5% of candidates for pediatric liver transplantation (LT) in Japan. We conducted a national survey of pediatric patients undergoing living donor LT for MHTs between October 1990 and April 2018. In total, 116 children underwent LT for MHTs during this study period: 100 hepatoblastomas (HBLs), 10 hepatocellular carcinomas (HCCs), and six other MHTs. The overall patient survival rate at 5 years was 81.3% for HBL, 60.0% for HCC, and 80.0% for other MHTs (P = 0.047). In patients with HBL, there was no significant difference in the 1- and 5-year patient survival rates between patients undergoing primary LT and those who received salvage LT for tumor recurrence (89.7%, 81.6% vs. 88.0%, 76%; P = 0.526). The 5-year overall survival rate after LT for HBL significantly improved from 63.2% in 1996-2008 to 89.8% in 2009-2018 (P = 0.018). The presence of lung metastasis before LT had no significant influence on the long-term survival (P = 0.742). Five patients with HCC died, including two who fell outside the Milan criteria. In conclusion, LT for pediatric MHTs, especially HBL, is a valuable treatment option for select patients.

The efficacy of rituximab treatment for antibody-mediated rejection in liver transplantation: A retrospective Japanese nationwide study.

AIM: Antibody-mediated rejection (AMR) has been consistently elucidated in liver transplantation (LT); however, the treatment for AMR, including rituximab, has not been indicated as a strongly recommended therapeutic protocol. METHODS: This study was conducted as the Japanese multicenter retrospective study to accumulate data on the use of rituximab for AMR among patients undergoing LT between August 2001 and December 2016. Thirteen patients (five children and eight adults) were enrolled. RESULTS: The types of AMR in the pediatric cases were chronic AMR in four cases and indeterminate AMR in one case. Among the pediatric cases, rituximab treatment only showed therapeutic efficacy in two patients with chronic AMR. Among the adult patients, five patients had chronic AMR, and three had acute AMR. Although two patients with chronic AMR died due to graft failure, liver function tests revealed improvement after rituximab treatment in the other patients. Two of the three patients with acute AMR died due to graft failure; rituximab treatment showed no therapeutic efficacy in these cases. Although bacterial infections occurred within 3 months after rituximab administration in three patients, rituximab treatment could be safely administered without any direct adverse effects. CONCLUSIONS: The indication of rituximab therapy as an additional treatment for mild acute AMR and chronic AMR may be feasible; however, a prospective randomized control study is needed to evaluate the therapeutic efficacy of rituximab treatment for AMR.

Indications and waiting list priority for deceased donor liver transplantation in HIV/HCV co-infected hemophilic patients in Japan through contaminated blood product.

HIV/HCV co-infection from blood products for hemophilia has been a social problem in Japan. Liver transplantation (LT) is an important treatment option for hepatic failure and cirrhosis of the liver in co-infected patients, and appropriate indications for LT, especially organ form deceased donors, are required by society. The aim is to propose priority status for the waiting list for deceased donor (DD) LT in HIV/HCV co-infected patients in Japan based on medical and scientific considerations. Since 2009, we have been working on the subject in research projects under grants-in-aid for health and labour sciences research on AIDS measures provided by the Ministry of Health, Labour and Welfare (the Kanematsu project and Eguchi project). Our research showed that hepatic fibrosis is advanced in HIV/HCV co-infected Japanese patients, especially those with hemophilia who became infected from blood products at a faster rate than HCV mono-infected patients. In addition, those patients who developed portal hypertension had a poor prognosis at a young age. The results of our research contributed to increasing the priority score of those patients on the deceased donor liver transplantation (DDLT) waiting list in 2013 and to establishing a scoring system for DDLT corresponding to the Model for End-stage Liver disease (MELD) score in 2019. This paper introduces changes in priority and the current state of priority of the DDLT waiting list for HIV/HCV co-infected patients in Japan.

Narrowing of the remnant portal vein diameter and decreased portal vein angle are risk factors for portal vein thrombosis after perihilar cholangiocarcinoma surgery.

PURPOSE: To evaluate the incidence, risk factors, management options, and outcomes of portal vein thrombosis following major hepatectomy for perihilar cholangiocarcinoma. METHODS: A total of 177 perihilar cholangiocarcinoma patients who (1) underwent major hepatectomy and (2) underwent investigating the portal vein morphology, which was measured by rotating the reconstructed three-dimensional images after facilitating bone removal using Aquarius iNtuition workstation between 2002 and 2018, were included. Risk factors were evaluated using the Kaplan-Meier method and Cox proportional hazard models. RESULTS: Six patients developed portal vein thrombosis (3.4%) within a median time of 6.5 (range 0-22) days. Portal vein and hepatic artery resection were performed in 30% and 6% patients, respectively. A significant difference in the probability of the occurrence of portal vein thrombosis (PV) within 30 days was found among patients with portal vein resection, a postoperative portal vein angle < 100°, remnant portal vein diameter < 5.77 mm, main portal vein diameter > 13.4 mm, and blood loss (log-rank test, p = 0.003, p = 0.06, p < 0.0001, p = 0.01, and p = 0.03, respectively). Decreasing the portal vein angle and narrowing of the remnant PV diameter remained significant predictors on multivariate analysis (p = 0.027 and 0.002, respectively). Reoperation with thrombectomy was performed in four patients, and the other two patients were successfully treated with anticoagulants. All six patients subsequently recovered and were discharged between 25 and 70 days postoperatively. CONCLUSION: Narrowing of the remnant portal vein diameter and a decreased portal vein angle after major hepatectomy for perihilar cholangiocarcinoma are significant independent risk factors for postoperative portal vein thrombosis.

COVID-19: A global transplant perspective on successfully navigating a pandemic.

The COVID-19 pandemic has rapidly evolved and changed our way of life in an unprecedented manner. The emergence of COVID-19 has impacted transplantation worldwide. The impact has not been just restricted to issues pertaining to donors or recipients, but also health-care resource utilization as the intensity of cases in certain jurisdictions exceeds available capacity. Here we provide a personal viewpoint representing different jurisdictions from around the world in order to outline the impact of the current COVID-19 pandemic on organ transplantation. Based on our collective experience, we discuss mitigation strategies such as donor screening, resource planning, and a staged approach to transplant volume considerations as local resource issues demand. We also discuss issues related to transplant-related research during the pandemic, the role of transplant infectious diseases, and the influence of transplant societies for education and disseminating current information.

Outcome of patients with acute liver failure awaiting liver transplantation in Japan.

AIM: To clarify the outcome and predictive factors in patients with acute liver failure (ALF) awaiting deceased donor liver transplantation (DDLT) in Japan. METHODS: Of the DDLT candidates in Japan between 2007 and 2016, 264 adult patients with ALF were retrospectively enrolled in this study. Factors associated with DDLT and waiting-list mortality were assessed using the Cox proportional hazard model. The DDLT and transplant-free survival probabilities were evaluated using Kaplan-Meier analysis and the log-rank test. RESULTS: The waiting-list registration year after the Transplant Law revision in 2010 was a significant factor associated with DDLT. The adjusted hazard ratio indicated that DDLT probability after 2010 was four times higher than that before, and the 28-day cumulative DDLT probability was more than 35%. The median survival time of the entire cohort was 40 days. Multivariate analysis identified the following three factors associated with waiting-list mortality: age, coma grade, and international normalized ratio. The transplant-free survival probabilities were significantly stratified by the number of risks, and patients with all three risks showed extremely poor short-term prognosis (median survival time = 23 days). CONCLUSIONS: The DDLT probability of ALF patients increased after the law revision in 2010; however, patients at high risk of short-term waiting-list mortality might need emergent living donor transplantation.