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The impact of pediatric liver transplantation on intellectual development has yet to be determined. We investigated the intellectual outcomes of school-aged patients after living donor liver transplantation for biliary atresia in infancy. The Wechsler Intelligence Scale for Children—fourth edition test was administered to 20 patients who survived $$\ge $$ 5 years after living donor liver transplantation. Borderline full scale intelligence quotient was defined as ≤ 85. Pre-, peri-, and postoperative data were compared between patients with > 85 and ≤ 85 to identify predictive factors of borderline performance. The one-sample t test demonstrated that the mean full scale intelligence quotient of patients after transplantation for biliary atresia was significantly lower than that of the general population (91.8 vs. 100.0, p = 0.026) and 7 (35%) were classified as intellectual borderline functioning. Multivariable logistic regression models were unable to identify any factors predictive of full scale intelligence quotients of ≤ 85. This is the first study to indicate that the mean full scale intelligence quotient among school-aged patients who underwent living donor liver transplantation for biliary atresia in infancy is significantly lower than that of the general population.

Minimally invasive surgery (MIS) is appropriate for the treatment of some neuroblastomas (NBs); however, the indications and technical issues are unclear. This study aimed to clarify the current status of MIS for mediastinal NB in Japan. Preliminary questionnaires requesting the numbers of neuroblastoma cases in which MIS was performed from 2004 to 2016 were sent to 159 Japanese institutes of pediatric surgery. Secondary questionnaires were sent to institutions with MIS cases to collect detailed data. One hundred thirty-four (84.2%) institutions returned the preliminary questionnaire and 83 institutions (52.2%) reported a total of 1496 operative cases. MIS was performed for 175 (11.6%) cases. Among the 175 cases, completed forms of 140 patients were returned and 40 (male, n = 28; female, n = 12) cases had mediastinal NB. Fourteen patients received thoracoscopic biopsy, none were converted to thoracotomy. Twenty-eight patients received MIS for radical resection, none were converted to thoracotomy. Perioperative complications (Horner’s syndrome) were recognized after radical resection in one (2.5%) case. MIS was performed in a limited number of mediastinal NB cases. A thoracoscopic approach would be feasible for mediastinal NB.

Patients with liver cirrhosis are at increased risk of various visceral hernia because of persistent ascites and tissue fragility. Here we report successful treatment in a patient with pararectal hernia due to liver cirrhosis by a less invasive approach via para-anal region. The patient was a 73-year-old woman with a history of chronic hepatitis B that had been untreated for at least 20 years. At the age of 68 years, she was referred to our hospital for treatment of persistent ascites and thrombocytopenia due to advanced liver cirrhosis. Neither diuretics nor cell-free and concentrated ascites reinfusion therapy could decrease the ascites. She needed repeated paracentesis. She was referred to the surgical department due to the painful swelling of the left buttock which was diagnosed as the pararectal hernia. The welling was huge enough with the erosion of the covering skin. Surgery was planned in view of concern about the possible rupture of the hernia. Due to the massive ascites with the advanced liver cirrhosis, we were reluctant to do the laparotomic approach, and simple closure of the hernial orifice via direct approach from the cutaneous side was planned and performed. The patient was fortunately discharged seven days after the operation without any complications. One year later, there has been no recurrence of the hernia. Even in cases with massive ascites, direct simple closure of the hernia by percutaneous approach may be one of the options for the treatment of the pararectal hernia in case of urgent situation.

Some neuroblastoma (NB) cases are suitable for minimally invasive surgery (MIS), but indication and technical issue are unclear. We assessed the current status of MIS for abdominal NB after mass screening period in Japan. Preliminary questionnaires requesting the numbers of NB cases that underwent MIS from 2004 to 2016 were sent to 159 Japanese institutes of pediatric surgery. The secondary questionnaires were then sent to the institutions that reported MIS cases of NB in order to collect detailed data. One hundred and thirty-four (84.2%) institutions responded to the preliminary questionnaires, and 83 (52.2%) reported managing operative cases. The total number of operative cases was 1496. MIS was performed for 175 (11.6%) cases, of which the completed forms of 140 patients were returned, including 100 abdominal NB cases. The male/female ratio was 51/49. Forty-seven cases underwent a laparoscopic biopsy, and 2 (4.3%) cases were converted to laparotomy due to bleeding. Sixty-five cases underwent MIS for radical resection, and 7 (10.8%) were converted to laparotomy. The reasons for open conversion were bleeding and severe adhesion. Regarding open conversion, there were no significant relationships between conversion and neo-adjuvant chemotherapy, biopsies, stage, size, or MYCN amplification. We found no relationship between resectability and vascular encasement in this study. There was relationship between the resected tumor size and the patients’ height, which was expressed using the following formula: $$y = 0.0316x + 1.4812$$ (x, patients height, y, tumor size; p = 0.004219, SE: 1.55566). Postoperative complications after radical resection were recognized in 7 (10.8%) cases. MIS was performed in limited cases of abdominal NB. A laparoscopic biopsy with careful attention to bleeding is feasible. The resected tumor size was shown to correlate with the patients’ height. Tumor size within 6 cm of maximum diameter can be resected safely.

Background Carpal tunnel syndrome is the most common compression syndrome of the peripheral nerve. Transthyretin amyloidosis and dialysis-related β2-microglobulin amyloidosis are known causes of carpal tunnel syndrome. Case Report A Japanese woman showed carpal tunnel syndrome 16 years after a domino liver transplantation (DLT) from the donor with hereditary transthyretin amyloidosis. DLT indication was congenital extrahepatic portosystemic shunt, and the patient had been put on maintenance hemodialysis because of chronic kidney disease 6 years before DLT. Moreover, the amyloid precursor protein of the patient was histologically confirmed not to be β2-microglobulin, but transthyretin. Conclusions The existence of amyloid was speculated when the patient who underwent DLT from hereditary transthyretin amyloidosis showed carpal tunnel syndrome. Additionally, elucidating the amyloid precursor protein when the patient has another cause of amyloidosis is necessary.

Hungry bone syndrome is a rare but potentially lethal complication that is characterized by rapid, severe, long-lasting hypocalcemia and hypophosphatemia secondary to increased bone metabolism. We present a case of hungry bone syndrome after living donor liver transplant for biliary atresia. Following a failed Kasai procedure for biliary atresia, a 5-month-old boy underwent living donor liver transplant with reduced left lateral lobe from his father. Despite the oral administration of alfacalcidol, the patient exhibited severe craniotabes before the surgery. He developed severe hypocalcemia and hypophosphatemia im-mediately after liver transplant and required supplementation of calcium and phosphorus for 1 month thereafter. After serum levels of calcium and phosphate had normalized, there was a rapid increase in the serum bone-type alkaline phosphatase level, and the craniotabes subsided remarkably. To our knowledge, this is the world's first reported case of hungry bone syndrome after liver transplant for cholestatic cirrhosis. It underscores the importance of strict nutritional and electrolyte management in the perioperative period. A prompt diagnosis and correction of hungry bone syndrome are imperative to prevent the associated significant morbidity and mortality.

Portal vein complications (PVCs) after adult living donor liver transplantation (LDLT) are potentially lethal. We categorized PVCs by the time of onset (early versus late

Pancreatic neuroendocrine tumors are a rare type of tumor with malignant potential, characterized by slowgrowth, frequent hepatic metastatic lesions that usually stay contained within the liver. In patients with unresectable liver metastatic pancreatic neuroendocrine tumors, liver transplant is the only treatment available. Insulinomas are the most common pancreatic neuroendocrine tumors, and 5% to 10% of insulinomas are malignant. We herein report a case of a living-donor liver transplant with distal pancreatectomy for a patient with hepatic metastatic pancreatic insulinoma with a 13-year postoperative survival.

The purpose of this study was to prepare clinical practice guidelines for biliary atresia according to the Medical Information Network Distribution Service (MINDS) Handbook for Clinical Practice Guideline Development 2014. The guideline drafting group determined 25 clinical questions (CQs) essential for daily clinical practice. These CQs were grouped into the following four major categories: diagnosis, treatment, complications, and prognosis. A systematic literature search was performed by the systematic review team, and medical evidence was extracted from articles published until July 2014 on PubMed and the Japan Medical Abstracts Society. To reach a consensus, majority voting (>70%) of the panel of the guideline drafting group was adopted according to the Delphi technique. Recommendations for 21 CQs were appropriately provided. However, for four CQs (CQ2, stool color; CQ9, steroid administration; and CQ24 and CQ25, liver transplantation), recommendations could not be determined due to a scarcity of evidence. The first clinical practice guidelines for biliary atresia were successfully created using procedures recommended by the MINDS. It is expected that these guidelines will be used worldwide, and that the standardization of biliary atresia treatment will improve treatment outcomes.

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.

Background Langerhans cell histiocytosis (LCH) is an abnormal accumulation of Langerhans cells in various organs that sometimes induces organ dysfunction. LCH can affect the liver, resulting in sclerosing cholangitis and biliary cirrhosis. However, liver and bile duct involvement is usually observed in the disseminated form of LCH. We herein report a rare case of LCH localized only in the extrahepatic bile duct that resulted in severe liver cirrhosis. Case presentation A 3-year-old boy with elevated liver enzymes, obstructive jaundice, and dilation of the common bile duct was referred to our institution. Contrast-enhanced computed tomography showed atrophy of the right hepatic lobe, relative hypertrophy of the left hepatic lobe, choledocholiths, and biliary debris extensively with biliary duct dilation. Magnetic resonance cholangiopancreatography revealed dilation of the intrahepatic and extrahepatic bile ducts and multiple choleliths in the gallbladder and common bile duct. Laparoscopic cholecystectomy, intraoperative cholangiography, liver biopsy, and gastrointestinal fiberscopy were performed. A liver specimen showed severe biliary cirrhosis due to sclerosing cholangitis. The patient then underwent living-donor liver transplantation because of severe liver cirrhosis 3 months after the first surgery. The common bile duct was not suitable for duct-to-duct anastomosis and was resected because of severe inflammation. Histologic sections of the common bile duct showed histiocytic cell proliferation. Immunohistochemistry revealed histiocytoses that were positive for Langerin, S-100 protein, and CD1a. However, no histiocytic cell proliferation was noted in the liver tissue. The definitive diagnosis was LCH localized to the extrahepatic bile duct. LCH in the extrahepatic bile duct seemed to cause sclerosing cholangitis. The patient was discharged uneventfully 2 months after living-donor liver transplantation. Conclusions LCH localized to the extrahepatic bile duct is extremely rare; however, LCH can still affect the extrahepatic bile ducts on occasion. LCH should be considered as a differential diagnosis if pediatric patients show the presence of sclerosing cholangitis.

Background Transomental hernias are a rare type of internal hernia. We report two cases of successful cases of laparoscopic repair. One required laparotomy due to concern for intestinal viability. Case presentation The first patient was a 67-year-old man who presented with abdominal pain and vomiting. He had no history of laparotomy or abdominal injury. Computed tomography suggested small bowel obstruction and possible intestinal strangulation. Emergent laparoscopy found approximately 200 cm of small bowel was strangulated around the greater omentum. The strangulation was released laparoscopically, but because of the color of the strangulated bowel, laparotomy was performed to evaluate viability. The involved portion of intestine was not resected. The patient experienced transient postoperative paralytic ileus and was discharged on postoperative day 14. The second patient was a 56-year-old man who presented with abdominal pain. Abdominal computed tomography revealed dilatation of the small intestine and a closed loop suggesting ileus due to intestinal strangulation. An emergency laparoscopy found a transomental hernia, and the strangulation was released laparoscopically. Recovery was uneventful, and the patient was discharged on postoperative day 6. Conclusion Transomental hernia can be successfully treated laparoscopically. In cases where bowel viability is a concern, laparotomy should not be hesitated.

Following liver transplantation (LT), allograft liver failure can be developed by various causes and requires re-LT. Hence, this study aimed to clarify the characteristics and prognostic factors of patients with allograft liver failure awaiting deceased donor LT (DDLT) in Japan.Of the 2686 DDLT candidates in Japan between 2007 and 2016, 192 adult patients listed for re-LT were retrospectively enrolled in this study. Factors associated with waitlist mortality were assessed using the Cox proportional hazards model. The transplant-free survival probabilities were evaluated using the Kaplan-Meier analysis and log-rank test.The median period from the previous LT to listing for re-LT was 1548 days (range, 4-8449 days). Primary sclerosing cholangitis (PSC), which was a primary indication, showed a higher listing probability for re-LT as compared with other primary etiologies. Recurrent liver disease was a leading cause of allograft failure and was more frequently observed in the primary indication of hepatitis C virus (HCV) infection and PSC in contrast with other etiologies. Multivariate analysis identified the following independent risk factors associated with waitlist mortality: age, Child-Turcotte-Pugh (CTP) score, mode for end-stage liver disease (MELD) score, alanine aminotransferase (ALT), and causes of allograft failure.Recurrent HCV and PSC were major causes of allograft liver failure in Japan. In addition to CTP and MELD scores, either serum ALT levels or causes of allograft failure should be considered as graft liver allocation measures.

Urea cycle disorders (UCDs) are inherited metabolic diseases causing hyperammonemia by defects in urea cycle enzymes or transporters. Liver transplantation (LT) currently is the only curative treatment option until novel therapies become available. We performed a nationwide questionnaire-based study between January 2000 and March 2018 to investigate the effect of LT in patients with UCDs in Japan. A total of 231 patients with UCDs were enrolled in this study. Of them, a total of 78 patients with UCDs (30 male and 16 female ornithine transcarbamylase deficiency (OTCD), 21 carbamoyl phosphate synthetase 1 deficiency (CPSD), 10 argininosuccinate synthetase deficiency (ASSD) and 1 arginase 1 deficiency (ARGD)) had undergone LT. Concerning the maximum blood ammonia levels at the onset time in the transplanted male OTCD (N = 28), female OTCD (N = 15), CPSD (N = 21) and ASSD (N = 10), those were median 634 (IQR: 277-1172), 268 (211-352), 806 (535-1382), and 628 (425-957) μmol/L, respectively. The maximum blood ammonia levels in female OTCD were thus significantly lower than in the other UCDs (all P < .01). LT was effective for long-term survival, prevented recurrent hyperammonemia attack, and lowered baseline blood ammonia levels in patients with UCDs. LT had limited effect for ameliorating neurodevelopmental outcome in patients with severe disease because hyperammonemia at the onset time already had a significant impact on the brain. Patients with ASSD may be more likely to survive without cognitive impairment by receiving early LT despite severe neonatal hyperammonemia ≥ 360 μmol/L. In patients with neonatal onset OTCD or CPSD, there may be additional factors with adverse effects on the brain that are not improved by LT.

Background Liver transplantation (LT) is considered the standard treatment for end-stage liver disease, but ideal donors remain in limited supply, resulting in an unavoidable increase in the need to use grafts from marginal donors. The attenuation of ischemia-reperfusion injury (IRI) in such marginal donors is therefore crucial for reducing the possibility of the primary non-function of grafts and graft loss. Some reports have found that molecular-hydrogen showed antioxidant and anti-inflammatory effects in preventing IRI in some non-hepatic transplant models. Therefore, we investigated whether or not molecular-hydrogen could attenuate IRI in LT model rats. Methods We used a hydrogen-rich water bath to dissolve hydrogen into solution and graft tissues and performed isogenic and orthotopic LT in Lewis rats with University of Wisconsin (UW) solution. Blood and tissue samples were collected 6 h after the reperfusion. Hepatic enzymes in serum were measured. Pathological findings including the expressions of cytokines and heme oxygenase (HO)-1 in liver tissues were evaluated. Results The concentration of hydrogen inside the graft tissues increased depending on the storage time, plateauing after 1 h. Serum liver enzyme levels were significantly lower and the histology score of liver damage markedly attenuated in the group given grafts preserved in hydrogen-rich UW solution than in the control group. The hydrogen-rich UW solution group also showed less oxidative damage and hepatocyte apoptosis than the control group, and the expression of proinflammatory cytokines tended to be lower while the protein levels of HO-1 were significantly increased (n = 3–12 per group, P

Although the training of liver transplant procedure is highly important to young transplant surgeons, it is too hard to secure the learning opportunity, especially in the countries like Japan whose organ transplants from deceased-donors are relatively rare. In such a situation, the surgical training in large animals such as pigs seems to be helpful in improving their skills. Consequently, under the assist by the Ministry of Education, Culture, Sports, Science and Technology (MEXT) in Japan, we established a simulation work of whole liver transplantation using laboratory pigs in the context of interinstitutional frame called the Six National University Consortium in Liver Transplant Professionals Training (SNUC-LT) Program. For this purpose, in this procedure, to guarantee stable circulatory dynamics during the anhepatic phase of pigs, we created a porto-caval-jugular shunt which is followed by addressing liver dysfunction, portal hypertension and intestinal congestion. Here, we describe the precise practical procedure. We believe that our procedure enables young transplant surgeons to gain surgical skills efficiently and effectively in addition to making a model animal in an experimental field.

Human T-cell leukemia virus type 1 (HTLV-1) spreads through cell contact. Therefore, this virus persists and propagates within the host by two routes: clonal proliferation of infected cells and de novo infection. The proliferation is influenced by the host immune responses and expression of viral genes. However, the detailed mechanisms that control clonal expansion of infected cells remain to be elucidated. In this study, we show that newly infected clones were strongly suppressed, and then stable clones were selected, in a patient who was infected by live liver transplantation from a seropositive donor. Conversely, most HTLV-1+ clones persisted in patients who received hematopoietic stem cell transplantation from seropositive donors. To clarify the role of cell-mediated immunity in this clonal selection, we suppressed CD8+ or CD16+ cells in simian T-cell leukemia virus type 1 (STLV-1)-infected Japanese macaques. Decreasing CD8+ T cells had marginal effects on proviral load (PVL). However, the clonality of infected cells changed after depletion of CD8+ T cells. Consistent with this, PVL at 24 hours in vitro culture increased, suggesting that infected cells with higher proliferative ability increased. Analyses of provirus in a patient who received Tax-peptide pulsed dendritic cells indicate that enhanced anti-Tax immunity did not result in a decreased PVL although it inhibited recurrence of ATL. We postulate that in vivo selection, due to the immune response, cytopathic effects of HTLV-1 and intrinsic attributes of infected cells, results in the emergence of clones of HTLV-1-infected T cells that proliferate with minimized HTLV-1 antigen expression., Author summary HTLV-1 spreads in vivo through two routes: de novo infection and clonal proliferation of infected cells. Reverse transcriptase inhibitors and integrase inhibitors do not influence the PVL in HTLV-1-infected individuals, indicating that clonal proliferation is dominant to maintain and increase PVL in vivo in the chronic phase. It is assumed that the host immune responses are critical factors for clonal proliferation. We found that HTLV-1-infected clones dramatically changed during de novo infection whereas the clones in the chronic phase survived long-term after transplantation, indicating that HTLV-1-infected clones are selected for survival in vivo. Surprisingly, depletion of CD8+ cells had a small impact on PVL in a STLV-1 infected Japanese macaque, but modified the clonality of infected cells. The cells after depletion of CD8+ cells showed a higher proliferative activity during short-term in vitro culture. This study reveals that intrinsic attributes of selected clones contribute to clonal proliferation of infected cells.

The Japanese Biliary Atresia Society (JBAS) prepared for clinical practice guidelines for biliary atresia (BA) according to the Medical Information Network Distribution Service (MINDS) Handbook 2014. Twenty-five clinical questions (CQs) essential for daily clinical practice for BA were grouped into diagnosis, treatment, complications, and prognosis. Systematic literature search performed by the review members and medical evidence was extracted from articles published until July 2014 on PubMed and the Japan medical abstracts society. To reach the guideline consensus, a majority (>70%) adoption was made by the guidelines drafting members according to Delphi procedures. Recommendations for 21 CQs were appropriately provided. However, for 4 CQs (stool color cord, postoperative steroid administration, timing for liver transplantation, and primary liver transplantation), recommendations could not be determined due to a scarcity of evidence. This guideline is the first clinical practice guideline for biliary atresia created by such procedures.

Long-term survival of biliary atresia (BA) patients significantly depends on the outcome of liver transplantation (LT), which is needed at least 50% of the patients. Liver transplantations for BA are commonly undergone within 2 years of age but also done later in various generations for different kinds of indications. Most patient loss after LT occurs within 6 months, and long-term mortality is not common. Twenty-year graft survival after LT for BA is now around 75%, and some the graft loss can be saved by re-transplantation. Because there is no fear of recurrence of BA after LT, in the long-term follow-up after LT, specific problems for BA are limited. As other organ transplantation, lifetime immunosuppression is necessary, although some selected patients can be weaned off from any drugs with meticulous follow-up. In addition to basic drugs like calcineurin inhibitors and steroids, mycophenolate mofetil (MMF) and mammalian target of Rapamycin (mTOR) inhibitors are available as immunosuppressants for rejections, especially for antibody-mediated ones. In surgical complications after LT for BA, portal vein thrombosis or occlusion has a big impact on the graft and patient survival in the long term. Pediatric recipients can achieve a favorable growth unless growth failure is too advanced at the time of LT due to the preceding protein-calorie malnutrition. Physicians and surgeons who follow the recipients should have a wide perspective not to focus on the liver itself. Formation of the team with assists from specialists of various fields under the leadership of the responsible main doctor is also very important. With the increase of long survivors after LT for BA, quality of life should have been more cared for in every phase of their life.

Background Lenvatinib is a novel tyrosine kinase inhibitor that exhibits an antitumor effect on hepatocellular carcinoma (HCC). An established strategy that involves surgery and usage of lenvatinib for advanced HCC remains elusive. Case presentation A 58-year-old male patient with advanced HCC and untreated hepatitis B was referred to our hospital. The tumor at the right lobe was 10 cm in diameter with right portal vein thrombus. Because of the possible lung metastasis and concern about the remaining hepatic function after extended right hepatectomy, lenvatinib was initiated before surgery. After the confirmation of a sharp decrease of tumor markers during the 3-week lenvatinib therapy, only a right portal vein transection was done leaving the enlargement of the left lobe for improved post-hepatectomy liver function while lenvatinib therapy was continued. The laparotomy revealed that the tumor was invading the right diaphragm. After 7 weeks of lenvatinib administration after right portal vein transection, an extended right hepatectomy with resection of the tumor-invaded diaphragm was successfully done. The lung nodules that were suspected as metastases had disappeared. The patient has been doing well without any sign of recurrence for 1 year. Conclusion The strategy involving the induction of lenvatinib to conversion hepatectomy including the portal vein transection was effective for advanced HCC.

Background Trousseau syndrome is a poor prognosis. We report a case of Trousseau syndrome treated by radical resection after endovascular treatment. Case A 59‐year‐old woman presented to our department reporting spontaneous dizziness and pain of the upper abdomen. Magnetic resolution imaging (MRI) showed shower embolization of Brain. Contrast‐enhanced computer tomography (CT) showed renal infarction and splenic infarction, and a tumor was observed in the retrohepatic area. On day 9, sudden right side joint prejudice, neglect of left half space, and left hemiplegia were observed. MRI revealed obstruction of the right middle cerebral artery (MCA) perfusion zone. On the same day, endovascular treatment was performed and reperfusion was obtained. We decided on a radical surgery policy because there were a primary lesion and a high risk of new embolism, and no metastasis was seen. Discussion Trousseau syndrome generally has a poor prognosis, but active treatment should be considered as an option when we can expect the recovery of function., Image diagnosis of the case. (a) Contrast‐enhanced CT showed evidence of bilateral renal infarction. (b) Contrast‐enhanced CT showed splenic infarction (pointed by arrow head). (c) Contrast‐enhanced CT showed a tumor in the retrohepatic area(pointed by arrows heads).

Adenosine triphosphatase phospholipid transporting 8B1 (ATP8B1) deficiency, an ultrarare autosomal recessive liver disease, includes severe and mild clinical forms, referred to as progressive familial intrahepatic cholestasis type 1 (PFIC1) and benign recurrent intrahepatic cholestasis type 1 (BRIC1), respectively. There is currently no practical method for determining PFIC1 or BRIC1 at an early disease course phase. Herein, we assessed the feasibility of developing a diagnostic method for PFIC1 and BRIC1. A nationwide Japanese survey conducted since 2015 identified 25 patients with cholestasis with ATP8B1 mutations, 15 of whom agreed to participate in the study. Patients were divided for analysis into PFIC1 (n = 10) or BRIC1 (n = 5) based on their disease course. An in vitro mutagenesis assay to evaluate pathogenicity of ATP8B1 mutations suggested that residual ATP8B1 function in the patients could be used to identify clinical course. To assess their ATP8B1 function more simply, human peripheral blood monocyte-derived macrophages (HMDMs) were prepared from each patient and elicited into a subset of alternatively activated macrophages (M2c) by interleukin-10 (IL-10). This was based on our previous finding that ATP8B1 contributes to polarization of HMDMs into M2c. Flow cytometric analysis showed that expression of M2c-related surface markers cluster of differentiation (CD)14 and CD163 were 2.3-fold and 2.1-fold lower (95% confidence interval, 2.0-2.5 for CD14 and 1.7-2.4 for CD163), respectively, in patients with IL-10-treated HMDMs from PFIC1 compared with BRIC1. Conclusion: CD14 and CD163 expression levels in IL-10-treated HMDMs may facilitate diagnosis of PFIC1 or BRIC1 in patients with ATP8B1 deficiency.

Background ABO-incompatible (ABOi) living donor liver transplantation (LDLT) has been performed to compensate for donor shortage. To date, few studies have reported detailed B-cell desensitization protocols and long-term outcomes of ABOi pediatric LDLT. Methods Twenty-nine pediatric ABOi LDLT recipients were retrospectively analyzed. We compared the clinical outcomes between ABOi (n = 29) and non-ABOi (n = 131) pediatric LDLT recipients. Furthermore, we evaluated the safety and efficacy of our rituximab-based regimen for ABOi pediatric LDLT (2 ≤ age < 18; n = 10). Results There were no significant differences in the incidence of infection, vascular complications, biliary complications, and acute cellular rejection between ABOi and non-ABOi groups. The cumulative graft survival rate at 1, 3, and 5 years for non-ABOi group were 92.1%, 87.0%, and 86.1%, and those for ABOi group were 82.8%, 82.8%, and 78.2%, respectively. Rituximab-based desensitization protocol could be performed safely, and reduced CD19+ lymphocyte counts effectively. Although rituximab-treated ABOi group showed comparable clinical outcomes and graft survival rate, 2 patients developed antibody-mediated rejection. Conclusions ABOi LDLT is a feasible option for pediatric end-stage liver disease patients. However, it should be noted that current desensitization protocol does not completely prevent the onset of antibody-mediated rejection in several cases., The authors of this single-center retrospective study demonstrate that ABO incompatible (ABOi) LDLT is a feasible option for pediatric end-stage liver disease patients by comparing the clinical outcomes between ABOi and non-ABOi pediatric LDLT recipients as well as assessing the safety and efficacy of a rituximab-based desensitization protocol. Supplemental digital content is available in the text.

Rituximab is a cornerstone in the regimens of desensitization for ABO-incompatible living-donor liver transplantation (ABO-i LDLT) that makes this modality an acceptable option for liver transplantation. Plasmapheresis (PP) to reduce anti-ABO antibody titer and local infusion (LI) therapy were practiced as the strategies for desensitization before the application of rituximab and were reported as additional treatments. The aim of this study was to clarify the feasibility of monotherapy by rituximab without any additional desensitization treatments in ABO-i LT.Forty patients receiving ABO-i LDLT with rituximab were enrolled in this retrospective study. The patients were divided into 2 groups: the rituximab with pretransplant PP and posttransplant LI (RPL) group (n = 20) and the rituximab monotherapy (RM) without any additional treatment group (n = 20). The groups were then compared in terms of the rates of patient survival, antibody-mediated rejection (AMR), and infection.The 1-, 3-, and 5-year patient survival rates were 85%, 85%, and 85% in the RPL group and 89%, 80%, and 80% in the RM group, respectively. There was no significant difference in patient survival between the 2 groups. There were no episodes of AMR in either group. The RM group had a lower rate of fungal and viral infections than the RPL group.Pretransplant rituximab without additional treatments yielded satisfactory outcomes comparable to that with additional treatments, such as PP and LI.