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.
Portopulmonary hypertension (PoPH) and hepatopulmonary syndrome are severe pulmonary complications associated with liver cirrhosis (LC) and portal hypertension. Three key pathways, involving ...endothelin, nitric oxide, and prostacyclin, have been identified in the development and progression of pulmonary arterial hypertension (PAH). To obtain a good effect with PAH-specific drugs in PoPH patients, it is important to diagnose PoPH at an early stage and promptly initiate therapy. The majority of therapeutic drugs are contraindicated for Child-Pugh grade C LC, and their effects decrease in the severe PAH stage. Among many LC patients, the measurement of serum brain natriuretic peptide levels might be useful for detecting PoPH. Previously, liver transplantation (LT) for PoPH was contraindicated; however, the indications for LT are changing and now take into account how well the PoPH is controlled by therapeutic drugs. In Japan, new registration criteria for deceased-donor LT have been established for PoPH patients. PoPH patients with a mean pulmonary arterial pressure <35 mmHg and pulmonary vascular resistance <400 dyn/s/cm−5 are indicated for LT, regardless of whether they are using therapeutic drugs. Combined with PAH-specific drugs, LT may lead to excellent long-term outcomes in PoPH patients. We aimed to review current therapies for PoPH, including LT.
ABO‐incompatible (ABO‐I) living donor liver transplantation (LDLT) has been performed in Japan to overcome the organ shortage. Reported herein are the results of this approach through March 2006 in ...the National Registry of the Japan Study Group for ABO‐incompatible transplantation. The questionnaires consisted of patient characteristics, operative data, and strategies for preventing antibody‐mediated rejection (AMR). Data of 291 patients (follow‐up period, 8 months‐15 years; mean, 35 months) from 28 institutions were collected. Age was younger than 1 year in 68 patients, 1 to 7 years in 60 patients, 8 to15 years in 27 patients, and 16 years or older in 136 patients. The strategy for the blood‐type barrier was heterogeneous in terms of recipient age, transplant center, and era. Local infusion and rituximab prophylaxis were applied in 2000 and 2003, respectively. The 5‐year patient survival rate was 85% in infants and 52% in adults. The major causes of death were infection and antibody‐mediated rejection (AMR). Multivariate analysis showed that age group, preoperative condition, antibody titer, and infection significantly affected survival. Age group, antibody titer, and local infusion treatment significantly affected the incidence of AMR. Patient survival rates were significantly higher and the incidence of AMR was significantly lower in adult patients after 2000 (3 year‐survival rate, 29%, 56%, and 61%; incidence of AMR, 47%, 27%, and 16%, through May 2000, from June 2000 through October 2003, and from November 2003, respectively). Conclusion: ABO‐incompatible LDLT is a standard practice in children, and local infusion and rituximab prophylaxis are promising in adults. (HEPATOLOGY 2007.)
In Japan, the yearly number of liver transplantations reached the highest level of 570 cases in 2005, and decreased thereafter to 395. One-year survival after liver transplantation increased from ...79.4% in deceased donors and 83.2% in living donors to 89.2% and 85.4%, respectively. To overview the present status of transplant hepatologists at transplant centers in Japan, a nation-wide survey was conducted in 2020 to both transplant surgeons and hepatologists at 14 facilities which performed more than 10 cases of liver transplantation in 2017. Although hepatologists performed preoperative evaluation and consultation at outpatient clinics, surgeons did not recognize the fact. As hepatologists were interested in preoperative treatment, postoperative immunosuppressant control and lifestyle-related chronic disease, the constitution of cooperation systems and training systems is mandatory to securely train transplant hepatologists.
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.
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).
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.
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%.
Recipient factors were more important than donor factors for FLD onset after LT.
Couinaud described three fundamental approaches at the hepatic hilus in liver surgery. The Glissonean pedicle approach at the hepatic hilus is one of these procedures and provides anatomical ...hepatectomy for hepatocellular carcinoma (HCC). The Glissonean pedicle approach was introduced by Couinaud and Takasaki in the early 1980s. The key of the Glissonean pedicle approach is clamping the pedicle first, secondly confirming the territory, which includes the HCC, and finally dissecting the liver parenchyma. This procedure prevents intrahepatic metastasis of HCC, which spreads along the portal vein and improves the overall survival after surgery. Another key feature is that we do not have to consider any variations of the vascular elements in the hepatoduodenal ligament under the hilar plate. This procedure allows an approach to the tertiary branches, which feed a smaller anatomical area than Couinaud's segment. We refer to this area as a cone unit of the liver. The procedure is also available in laparoscopic hepatectomy and provides new knowledge of the surgical anatomy, especially for small anatomical liver resection in the cirrhotic liver.
This study investigated the clinical characteristics of patients with gastric tube cancer following esophagectomy at our hospital, and to examine the outcomes of gastrectomy versus endoscopic ...submucosal dissection. Of 49 patients who underwent treatment for gastric tube cancer that developed 1 year or more after esophagectomy, 30 patients underwent subsequent gastrectomy (Group A), and 19 patients underwent endoscopic mucosal resection (EMR) or endoscopic submucosal dissection (ESD) (Group B). The characteristics and outcomes of these two groups were compared. The interval between esophagectomy and diagnosis of gastric tube cancer ranged from 1 to 30 years. The most common location was the lesser curvature of the lower gastric tube. When the cancer was detected early, EMR or ESD was performed, and the cancer did not recur. In advanced tumors, gastrectomy was performed but the gastric tube was difficult to approach and lymph node dissection was difficult; two patients died as a result of the gastrectomy. In Group A, recurrence occurred most often as axillary lymph node, bone, or liver metastases; in Group B, no recurrence or metastases were observed. In addition to recurrence and metastasis, gastric tube cancer is often observed after esophagectomy. The present findings highlight the importance of early detection of gastric tube cancer after esophagectomy and that the EMR and ESD procedures are safe and have significantly fewer complications compared with gastrectomy. Follow-up examinations should be scheduled with consideration given to the most frequent sites of gastric tube cancer occurrence and the time elapsed since esophagectomy.
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.
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