ABO incompatible living donor liver transplantation has the potential to expand the donor pool for patients with end stage liver diseases on the expense of challenges to overcome immunological ...barriers across blood type. There is a profound impact of age on incidence and severity of antibody mediated rejection (AMR). Even children older than 1 year have chances of AMR; children aged 8 years or older have risks of hepatic necrosis similar to adult liver recipients. The mechanism of AMR is based on circulatory disturbances secondary to inflammation and injury of the vascular endothelium caused by an antibody-antigen-complement reaction. The strategy to overcome ABO blood type barrier is based on both pre-transplant desensitization and adequate treatment of this phenomenon. Nowadays, rituximab is the standard means of desensitization but unfortunately an insufficient aid to treat AMR. Because of low incidence (less than 5% in the rituximab era), in practice of AMR only some case reports about the treatment of clinical AMR are available in the literature. Initial experiences revealed that the proteasome inhibitor, bortezomib might be a promising treatment based on its capacity to deplete plasma cell agents. Although ABO blood type barrier has been counteracted in 95% of patients by applying “rituximab-desensitization”, many issues, such as prediction of high-risk patients of infection and AMR and secure treatment strategies for evoked AMR, remain to be resolved.
Liver transplantation in Japan Soyama, Akihiko; Eguchi, Susumu; Egawa, Hiroto
Liver transplantation,
October 2016, Letnik:
22, Številka:
10
Journal Article
Recenzirano
As of December 31, 2014, 7937 liver transplants (7673 living donor transplants and 264 deceased donor liver transplantations DDLTs; 261 from heart‐beating donors and 3 from non–heart‐beating donors) ...have been performed in 67 institutions in Japan. The revised Organ Transplant Law in Japan came into effect in July 2010, which allows organ procurement from brain‐dead individuals, including children, with family consent if the patient had not previously refused organ donation. However, the number of deceased donor organ donations has not increased as anticipated. The rate of deceased organ donations per million population (pmp) has remained at less than 1. To maximize the viability of the limited numbers of donated organs, a system has been adopted that includes the partnership of well‐trained transplant consultant doctors and local doctors. For compensating for the decreased opportunity of on‐site training, an educational system regarding quality organ procurement for transplant surgeons has also been established. Furthermore, experts in the field of liver transplantation are currently discussing adoption of the Model for End‐Stage Liver Disease score for allocation, promoting split‐liver transplantation, arranging in‐house coordinators, and improving the frequency of proposing the option to donate organs to the families. To overcome the shortage of donors during efforts to promote organ donation, living donor liver transplantation (LDLT) has been developed in Japan. Continuous efforts to increase DDLT in addition to the successful experience of LDLT will increase the benefits of liver transplantation for more patients. Liver Transplantation 22 1401–1407 2016 AASLD.
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: 1 year, 89.1%; 3 years, 85.2%; 5 years, 82.9%; 10 years, 75.4%; 15 years, 70.7%) was similar to that from living‐donor (8794 transplants: 1 year, 85.0%; 3 years, 80.9%; 5 years, 78.5%; 10 years, 73.2%; 15 years, 68.5%; 20 years, 65.7%; 25 years, 64.6%). Graft survival was very much the same as patient survival (heart‐beating donor: 1 year, 88.4%; 3 years, 84.5%; 5 years, 82.2%; 10 years, 74.7%; 15 years, 70.1%; living donor: 1 year, 84.3%; 3 years, 79.9%; 5 years, 77.3%; 10 years, 71.4%; 15 years, 66.3%; 20 years, 63.3%; 25 years, 61.9%). Survival data are reported according to age and sex of recipient, indication, age and sex of donor, ABO compatibility, and other factors.
Background
Rituximab has greatly improved the outcomes of ABO‐incompatible living donor liver transplantation (ABO‐I LDLT). To clarify the optimal regimen for rituximab in adult ABO‐I LDLT, a ...multicenter study was conducted in Japan.
Methods
Clinical data of 33 adult patients undergoing ABO‐I LDLT at 15 centers in 2013 were retrospectively corrected.
Results
The targeted blood type was A1 in 18, B in 14, and AB in one patient. Rituximab was administered at 7 to 48 days before LT, at a dose of 375 mg/m2 in 12 patients, 500 mg in 15 patients, 300 mg in five patients, and 100 mg in one patient. Adverse effects of rituximab were tolerable. Overall 1‐year patient survival was 81%; antibody‐mediated rejection (AMR) occurred in three patients (9%), two of whom died. Rituximab dose was significantly lower in patients with AMR (P < 0.001, 137 ± 61 vs. 307 ± 66 mg/m2). Among rituximab dose (n = 28), local infusion (n = 11), splenectomy (n = 23), prophylactic intravenous immunoglobulins (n = 12), preoperative tacrolimus (n = 9), preoperative antimetabolites (n = 21), and plasmapheresis (n = 23), only rituximab dose was a significantly favorable factor for AMR (P < 0.001).
Conclusion
The use of rituximab at sufficient doses is recommended in adult ABO‐I LDLT.
HighlightIn this multicenter study, Egawa and colleagues evaluated the association between rituximab dosage and successful desensitization to prevent antibody‐mediated rejection in ABO‐incompatible liver transplantation. They found that single administration of 500 mg or 375 mg/m2 was effective and that single administration of 300 mg or less could be insufficient.
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.
The aim of this study was to assess inter-hospital laboratory variability (coefficient of variation; CV) of immunoassay methods for tacrolimus and the comparability of control samples and results ...obtained by immunoassay measurements. One hundred seven hospital laboratories routinely performing therapeutic drug monitoring (TDM) of tacrolimus participated in the study. Thirteen spiked samples with known tacrolimus concentrations in the range of 0–26.0 ng/mL were prepared. Each spiked sample was analyzed according to the manufacturer’s instructions using an affinity column-mediated immunoassay (ACMIA) on a Dimension® analyzer, the enzyme multiplied immunoassay technique (EMIT) on a Viva-E® analyzer, a chemiluminescent enzyme immunoassay (CLIA) on the Architect® system, and the electro-chemiluminescence immunoassay (ECLIA) on a cobas® analyzer. The 20% coefficient of variation values for the CLIA, ACMIA, EMIT, and ECLIA assays in the hospital laboratories were 1.82, 5.36, 4.59, and 0.89 ng/mL, respectively. CLIA and ECLIA had positive biases at concentrations of tacrolimus above 12 ng/mL relative to the spiked concentration, whereas the assay bias for ACMIA tended to be more negative at concentrations of tacrolimus above 6 ng/mL. EMIT had positive biases over the wide concentration range of 0.0–26.0 ng/mL (mean of mean errors 1.224). CLIA and ECLIA provided adequate precision at the target tacrolimus concentration of 3.0 ng/mL, whereas ACMIA and EMIT were unable to respond to target concentrations between 3.0 and 5.0 ng/mL for renal transplant recipients. Appropriate assessment of tacrolimus concentration by an assay having higher sensitivity, precision, and accuracy is necessary to ensure long-term survival of transplant recipients receiving tacrolimus.
Hepatic hemangiomas are benign liver tumors, and most of them progress asymptomatically. We report a case of hepatic hemangioma considered the cause of fever. A 53-year-old woman had a fever of 40°C ...for about 3 months without infection. Hepatic hemangiomas with internal bleeding of 10 cm in size on liver S8/7 and S3/2 were observed. These were resected laparoscopically for diagnostic treatment. She was afebrile after the operation. The pathological diagnosis was hematoma inside cavernous hemangioma. It should be noted that a bleeding hepatic hemangioma may cause fever of unknown origin and be indicated for resection.
Portopulmonary hypertension (PoPH) is a rare and serious complication of liver cirrhosis and portal hypertension that can interfere with liver transplantation (LT). We evaluated the prevalence of ...PoPH and the clinical features of right ventricular systolic pressure (RVSP), which is equivalent to pulmonary artery systolic pressure, in LT candidates.
This was a single-center retrospective study. A total of 157 Japanese patients with decompensated liver cirrhosis or portal hypertension (76 men, median age = 52 years range: 18-68 years) were enrolled. The relationships between RVSP and clinical parameters, and the prevalence of PoPH in LT candidates, were evaluated.
The cardiological parameters were as follows: brain natriuretic peptide (BNP), 39.1 (4.0-780.5) pg/mL; RVSP, 31.2 (16.0-122.4) mmHg; ejection fraction, 58% (28-72%); and mean peak tricuspid regurgitation velocity, 2.3 (1.5-5.3) m/s. The RVSP was significantly higher in females (p = 0.02) and primary biliary cholangitis (PBC) patients (p = 0.01), and was weakly correlated with the BNP level (r = 0.40, p = 0.01). For RVSPs of < 36 and ≥ 36 mmHg, the 5-year survival rates were 36.1% versus 34.1%, and 85.4% versus 85.3%, in non-LT and LT cases, respectively (p = 0.47 and 0.69, respectively). Among six patients with an RVSP ≥ 50 mmHg, three (1.9%) were diagnosed with PoPH and treated with vasodilators.
PoPH was observed in 3 cases (1.9%) in 157 LT candidates. In patients with suspected mild pulmonary hypertension (RVSP, 36 - 50 mmHg), LT was successfully performed.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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 5.9 years and body weight of 18.6 kg. 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 <18 years) 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
This study analyzes the factors that might influence the outcomes of patients with biliary atresia who undergo living donor liver transplantation and demonstrates that donor body mass index, blood type incompatibility, graft type, recipient age, center experience, transplant era, and adolescent age are significant predictors of overall graft survival.
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