研究者業績
基本情報
経歴
6-
2020年4月 - 現在
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2019年5月 - 2020年3月
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2017年4月 - 2019年4月
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2015年4月 - 2017年3月
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2013年4月 - 2015年3月
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2011年4月 - 2013年3月
学歴
1-
2005年4月 - 2011年3月
主要な論文
73-
BMC infectious diseases 25(1) 97-97 2025年1月21日BACKGROUND: Cytomegalovirus (CMV) is a major infectious complication in solid-organ transplant recipients, particularly in the context of pediatric liver transplantation. CMV serostatus is a well-established risk factor for postoperative CMV infection, with CMV seronegative recipients who receive organs from seropositive donors (D+/R-) being at the highest risk. Our previous research indicated a higher incidence of CMV infection in recipients with inherited metabolic diseases (IMDs) compared with those with biliary atresia (BA). This study aimed to determine whether IMDs constitute an independent risk factor for postoperative CMV infection. METHODS: We retrospectively analyzed data from 45 IMD and 230 BA recipients. We collected information on the occurrence and timing of episodes of CMV infections, methylprednisolone (mPSL) pulse therapy, patient characteristics, and peri- and postoperative data. RESULTS: Multivariable analysis identified mPSL pulse therapy (Odds Ratio (OR): 4.43), CMV serostatus (D+/R-) (OR: 6.03), and underlying IMDs (OR: 3.28) as independent risk factors for CMV infection. Further stratified analysis, which considered the timing of CMV infection diagnosis relative to mPSL pulse therapy, confirmed that CMV serostatus with (D+/R-) (OR: 5.61) and underlying IMDs (OR: 2.83) remained independent predictors of CMV infection, even when excluding the influence of mPSL pulse therapy. CONCLUSIONS: This study demonstrates that IMDs are a potent independent risk factor for CMV infection following pediatric liver transplantation. CLINICAL TRIAL NUMBER: Not applicable.
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Biomedicines 13(1) 2024年12月31日Background: Even though many metabolic liver diseases can now be diagnosed using blood tests and diagnostic imaging, early diagnosis remains difficult. Understanding mechanisms contributing to the progression from Metabolic Dysfunction-Associated Steatohepatitis (MASH) and Alcoholic Hepatitis (AH) to cirrhosis is critical to reduce the burden of end-stage liver disease. Monitoring individual bile acids has been proposed as a way to distinguish various liver disorders. Methods: This study explored bile acid profiles in patients with MASH and AH. Plasma samples from patients with MASH, AH, and a control group were analyzed using liquid chromatography-tandem mass spectrometry (LC-MS/MS) to quantify bile acid concentrations. Targeted metabolomic analysis was performed to compare bile acid levels between the hepatitis and control groups. Results: Concentrations of ursodeoxycholic acid (UDCA), chenodeoxycholic acid (CDCA), taurocholic acid (TCA), tauroursodeoxycholic acid (TUDCA), taurochenodeoxycholic acid (TCDCA), glycoursodeoxycholic acid (GUDCA), glycochenodeoxycholic acid (GCDCA), and glycocholic acid (GCA) were significantly elevated in the hepatitis group. Correlation analysis revealed strong positive relationships between the total and direct bilirubin levels and TUDCA and GCDCA. Aspartate aminotransferase (AST) showed strong positive correlations with TCDCA and GCDCA. Child-Pugh score, Fibrosis-4 index, and non-alcoholic fatty liver disease fibrosis score were positively correlated with GCA, whereas the aspartate aminotransferase-to-platelet ratio correlated with TCA, TCDCA, and GCA. The model for end-stage liver disease (MELD) score showed a strong positive correlation with GCDCA. Implications: GCDCA may serve as a predictive biomarker for liver damage, potentially enabling early diagnosis and targeted intervention in patients with MASH and AH.
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American Journal of Transplantation 2024年3月
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American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons 21(9) 3184-3189 2021年4月1日Maternal T cells from perinatal transplacental passage have been identified in up to 40% of patients with severe combined immunodeficiency (SCID). Although engrafted maternal T cells sometimes injure newborn tissue, liver failure due to maternal T cells has not been reported. We rescued a boy with X-linked SCID who developed liver failure due to engrafted maternal T cell invasion following living donor liver transplantation (LDLT) following unrelated umbilical cord blood transplantation (UCBT). After developing respiratory failure 3 weeks postpartum, he was diagnosed with X-linked SCID. Pathological findings showed maternal T cells engrafted in his liver and hepatic fibrosis gradually progressed. He underwent UCBT at 6 months, but hepatic function did not recover and liver failure progressed. Therefore, he underwent LDLT using an S2 monosegment graft at age 1.3 years. The patient had a leak at the Roux-en-Y anastomosis, which was repaired. Despite occasional episodes of pneumonia and otitis media, he is generally doing well 6 years after LDLT with continued immunosuppression agents. In conclusion, the combination of hematopoietic stem cell transplantation (HSCT) and liver transplantation may be efficacious, and HSCT should precede liver transplantation for children with X-linked SCID and liver failure.
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Experimental and clinical transplantation : official journal of the Middle East Society for Organ Transplantation 18(5) 612-617 2020年10月 査読有り筆頭著者OBJECTIVES: Predicting the risk of posthepatectomy liver failure is important when performing extended hepatectomy. However, there is no established method to evaluate liver function and improve preoperative liver function in pediatric patients. MATERIALS AND METHODS: We show the clinical features of pediatric patients who underwent living donor liver transplant for posthepatectomy liver failure in hepatoblastoma. The subjects were 4 patients with hepatoblastoma who were classified as Pretreatment Extent of Disease III, 2 of whom had distal metastasis (chest wall and lung). RESULTS: Hepatic right trisegmentectomy was performed in 3 patients and extended left hepatectomy in 1 patient. The median alpha-fetoprotein level at the diagnosis of hepatoblastoma was 986300 ng/mL (range, 22500-2726350 ng/mL), and the median alpha-fetoprotein level before hepatectomy was 8489 ng/mL (range, 23-22500 ng/mL). The remnant liver volume after hepatectomy was 33.3% (range, 20% to 34.9%). Four patients had cholangitis after hepatectomy and progressed to posthepatectomy liver failure. The peak serum total bilirubin after hepatectomy was 11.4 mg/dL (range, 8.7-14.6 mg/dL). Living donor liver transplant was performed for these 4 patients with posthepatectomy liver failure, and they did not have a recurrence. CONCLUSIONS: When the predictive remnant liver volume by computed tomography-volumetry before extended hepatectomy for patients with hepatoblastoma is less than 40%, the possibility of posthepatectomy liver failure should be recognized.
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Surgical case reports 6(1) 159-159 2020年7月3日 査読有り筆頭著者BACKGROUND: There have been no reports on the effectiveness of the administration of antithrombin III (AT III) for post-transplant portal vein thrombosis (PVT). We herein report a case of post-transplant PVT that was resolved by AT III treatment after living donor liver transplantation (LDLT). CASE PRESENTATION: The patient was a 57-year-old man who had been diagnosed with decompensate liver cirrhosis by hepatitis C virus infection. He presented with repeated hepatic coma and refractory ascites. Computed tomography (CT) revealed PVT of Yerdel classification grade II before LDLT. He underwent ABO-identical LDLT using a right lobe graft. A liver function test revealed elevated liver enzyme levels on post-operative day (POD) 14. The CT examination on POD 15 revealed PVT in the left side of the main portal vein at the side of left gastric vein ligation. AT III treatment from POD 15 to POD 24 was performed. Magnetic resonance imaging revealed that the PVT had decreased 10% on POD 27. Furthermore, AT III treatment from POD 28 to POD 32 was performed. The CT examination demonstrated the disappearance of PVT on POD 69 and thereafter, he had no recurrence of PVT on 10 post-operative month (POM). CONCLUSIONS: The present case suggests that the administration of AT III is safe and suitable for the treatment of post-transplant PVT.
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Transplantation 103(9) 1863-1870 2019年9月BACKGROUND: We present retrospective analysis of our 15-year experience with pediatric living donor liver transplantation, focusing on the risk factors, treatments, and long-term prognosis for posttransplant biliary complications (BCs). METHODS: Between May 2001 and December 2017, 290 living donor liver transplantations were performed. The median age was 1.4 years old. The median observation period was 8.4 years. Biliary strictures were classified as anastomotic stricture (AS) or non-AS (NAS). RESULTS: Overall incidence of biliary complications was 18.6%, including AS in 46 cases, NAS in 6, and other classifications in 2. The mean period to diagnosis of the AS was 641 ± 810 postoperative days. The multivariate analysis showed that hepaticojejunostomy without external stent was an independent risk factor for AS (P = 0.011). The first treatments for AS were percutaneous transhepatic biliary drainage (PTBD) in 25 cases, double-balloon enteroscopy (DBE) in 19, and surgical reanastomosis in 2. The success and recurrence rates of PTBD treatments were 90.9% and 22.7%, respectively. The success and recurrence rates of endoscopic interventions under DBE were 93.6% and 75.3%, respectively. The 15-year graft survival rates in patients with and without AS were 95.7% and 89.1%, respectively (P = 0.255), but 2 patients with cholangitis due to multiple NAS underwent retransplantation. CONCLUSIONS: Posttransplant AS can be prevented by hepaticojejunostomy using external stent, and the long-term prognosis is good with early treatments using DBE or PTBD. However, the prognosis of multiple NAS is poor.
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Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society 25(7) 1066-1073 2019年7月Early relaparotomy of adult recipients after living donor liver transplantation (LDLT) is significantly associated with poor prognosis. However, there are few reports focusing on pediatric recipients after LDLT. The aim of this study is to clarify the causes and outcomes of early relaparotomy after pediatric LDLT. A total of 265 pediatric recipients (272 LDLTs) transplanted from May 2001 to October 2015 were retrospectively analyzed. Early relaparotomy was defined as surgical intervention performed within 3 months after LDLT. Early relaparotomy was performed 49 times for 33 recipients (12.5%). The recipient and graft survival rates in the early relaparotomy group were significantly lower than those in the nonearly relaparotomy group, respectively (75.0% and 63.6% versus 96.6% and 95.8%; both P < 0.001). Left lateral segment grafts were used significantly more frequently in the nonrelaparotomy group (P = 0.01). According to the multivariate analysis, the preoperative Pediatric End-Stage Liver Disease (PELD)/Model for End-Stage Liver Disease (MELD) score of the early relaparotomy group was significantly higher than that of the nonearly relaparotomy group (13.7 versus 6.3; P = 0.04). According to the receiver operating characteristic curve, the preoperative PELD/MELD score cutoff point was 17.2. Early relaparotomy due to infectious causes led to significantly poorer graft survival than that due to noninfectious causes (P = 0.04). In conclusion, the recipient and graft survival rates of the early relaparotomy group were significantly lower than those of the nonearly relaparotomy group. A high preoperative PELD/MELD score was a risk factor for early relaparotomy. In particular, early relaparotomy due to infection showed a poor prognosis.
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Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society 25(3) 510-514 2019年3月
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Journal of gastroenterology and hepatology 34(2) 418-424 2019年2月BACKGROUND AND AIM: Serum Mac-2 binding protein glycosylation isomer (M2BPGi) is a novel fibrosis marker for various chronic liver diseases. We investigated the ability of M2BPGi to predict liver fibrosis in liver transplant (LT) recipients. METHODS: A total of 116 liver biopsies were performed in 113 LT recipients. The serum level of M2BPGi was also measured on the same day. The median age at LT and liver biopsy was 1.1 and 11.8 years, respectively. Serum M2BPGi levels and liver fibrosis status using METAVIR fibrosis score were compared. Immunohistological evaluation by anti-α-smooth-muscle actin (αSMA) was performed, and the relationship between αSMA positive rate and serum M2BPGi levels was investigated. RESULTS: The median M2BPGi level was 0.78 (range, 0.22-9.50), and 65, 29, 16, 5, and 1 patient(s) had METAVIR fibrosis scores of F0, F1, F2, F3, and F4, respectively. In patients with F0 fibrosis, median M2BPGi level was 0.69 and was significantly lower than in patients with F1 (median 0.99, P < 0.01), F2 (median 1.00, P = 0.01), and F3 fibrosis (median 1.53, P < 0.01). Area-under-the-curve analysis of the ability of M2BPGi level to predict liver fibrosis grade were > F1: 0.716, > F2: 0.720, and > F3: 0.900. Three patients with acute cellular rejection showed high levels of M2BPGi, which decreased after the treatment. A positive correlation existed between M2BPGi levels and αSMA positive rate (r2 = 0.715, P < 0.01). CONCLUSION: Mac-2 binding protein glycosylation isomer is a novel liver fibrosis marker in LT recipients and is also increased in patients with acute liver injuries, especially acute cellular rejection, even when fibrosis is absent.
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Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society 24(3) 436-439 2018年3月
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Transplant Proc 60-65 2018年1月 査読有り筆頭著者
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Journal of gastroenterology 52(2) 245-252 2017年2月BACKGROUND AND AIM: Mac-2 Binding Protein Glycosylation Isomer (M2BPGi) is a novel fibrosis marker. We examined the ability of M2BPGi to predict liver fibrosis in patients with biliary atresia. METHODS: Sixty-four patients who underwent living donor liver transplantation (LDLT) were included [median age, 1.1 years (range 0.4-16.0), male 16 patients (25.0 %)]. We examined M2BPGi levels in serum obtained the day before LDLT, and we compared the value of the preoperative M2BPGi levels with the histological evaluation of fibrosis using the METAVIR fibrosis score. Subsequently, we assessed the ability of M2BPGi levels to predict fibrosis. RESULTS: The median M2BPGi level in patients with BA was 6.02 (range, 0.36-20.0), and 0, 1, 1, 11, and 51 patients had METAVIR fibrosis scores of F0, F1, F2, F3, and F4, respectively. In patients with F4 fibrosis, the median M2BPGi level was 6.88 (quartile; 5.235, 12.10), significantly higher than that in patients with F3 fibrosis who had a median level of 2.42 (quartile; 1.93, 2.895, p < 0.01). Area under the curve analysis for the ability of M2BPGi level to predict grade fibrosis was 0.917, with a specificity and sensitivity of 0.923 and 0.941, respectively. In comparison with other fibrosis markers such as hyaluronic acid, procollagen-III-peptide, type IV collagen 7 s, and aspartate aminotransferase platelet ratio index, M2BPGi showed the strongest ability to predict grade F4 fibrosis. CONCLUSION: M2BPGi is a novel fibrosis marker for evaluating the status of the liver in patients with BA, especially when predicting grade F4 fibrosis.
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World journal of gastroenterology 22(44) 9865-9870 2016年11月28日This is the first report of living donor liver transplantation (LDLT) for congenital hepatic fibrosis (CHF) using a mother's graft with von Meyenburg complex. A 6-year-old girl with CHF, who suffered from recurrent gastrointestinal bleeding, was referred to our hospital for liver transplantation. Her 38-year-old mother was investigated as a living donor and multiple biliary hamartoma were seen on her computed tomography and magnetic resonance imaging scan. The mother's liver function tests were normal and she did not have any organ abnormality, including polycystic kidney disease. LDLT using the left lateral segment (LLS) graft from the donor was performed. The donor LLS graft weighed 250 g; the graft recipient weight ratio was 1.19%. The operation and post-operative course of the donor were uneventful and she was discharged on post-operative day (POD) 8. The graft liver function was good, and the recipient was discharged on POD 31. LDLT using a graft with von Meyenburg complex is safe and useful. Long-term follow-up is needed with respect to graft liver function and screening malignant tumors.
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World journal of gastroenterology 22(34) 7851-6 2016年9月14日Utilizing the opened round ligament as venous grafts during liver transplantation is useful but controversial, and there are no pathological analyses of this procedure. Herein, we describe the first reported case of a pathological analysis of an opened round ligament used as a venous patch graft in a living donor liver transplantation (LDLT). A 13-year-old female patient with biliary atresia underwent LDLT using a posterior segment graft from her mother. The graft had two hepatic veins (HVs), which included the right HV (RHV; 15 mm) and the inferior RHV (IRHV; 20 mm). The graft RHV and IRHV were formed into a single orifice using the donor's opened round ligament (60 mm × 20 mm) as a patch graft during bench surgery; it was then anastomosed end-to-side with the recipient inferior vena cava. The recipient had no post-transplant complications involving the HVs, but she died of septic shock with persistent cholangitis and jaundice 86 d after LDLT. The HV anastomotic site had no stenosis or thrombus on autopsy. On pathology, there was adequate patency and continuity between the recipient's HV and the donor's opened round ligament. In addition, the stains for CD31 and CD34 on the inner membrane of the opened round ligament were positive. Hepatic venous reconstruction using the opened round ligament as a venous patch graft is effective in LDLT, as observed on pathology.
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Transplant Proc 1105-1109 2016年5月 査読有り筆頭著者
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Hepato-gastroenterology 61(133) 1368-1373 2014年7月 査読有り
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HEPATO-GASTROENTEROLOGY 61(133) 1368-1373 2014年7月 査読有り
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World journal of gastroenterology 20(21) 6638-50 2014年6月7日AIM: To assessed the clinical significance of protocol liver biopsy (PLB) in pediatric liver transplantation (LT). METHODS: Between July 2008 and August 2012, 89 and 55 PLBs were performed in pediatric patients at two and five years after LT, respectively. We assessed the histopathological findings using the Metavir scoring system, including activity (A) and fibrosis (F), and we identified factors associated with scores of ≥ A1 and ≥ F1. Our results clarified the timing and effectiveness of PLB. RESULTS: The incidences of scores of ≥ A1 and ≥ F1 were 24.7% and 24.7%, respectively, at two years after LT and 42.3% and 34.5%, respectively, at five years. Independent risk factors in a multivariate analysis of a score of ≥ A1 at two years included ≥ 2 h of cold ischemic time, no acute cellular rejection and an alanine amino transaminase (ALT) level of ≥ 20 IU/L (P = 0.028, P = 0.033 and P = 0.012, respectively); however, no risk factors were identified for a score of ≥ F1. Furthermore, no independent risk factors associated with scores of ≥ A1 and ≥ F1 at five years were identified using multivariate analysis. A ROC curve analysis of ALT at two years for a score of ≥ A1 demonstrated the recommended cutoff value for diagnosing ≥ A1 histology to be 20 IU/L. The incidence of scores of ≥ A2 or ≥ F2 at two years after LT was 3.4% (three cases), and all patients had an absolute score of ≥ A2. In contrast to that observed for PLBs at five years after LT, the incidence of scores of ≥ A2 or ≥ F2 was 20.0% (11 cases), and all patients had an absolute score of ≥ F2. In all cases, the dose of immunosuppressants was increased after the PLB, and all ten patients who underwent a follow-up liver biopsy improved to scores of ≤ A1 or F1. CONCLUSION: PLB at two years after LT is an unnecessary examination, because the serum ALT level reflects portal inflammation. In addition, immunosuppressive therapy should be modulated to maintain the ALT concentration at a level less than 20 IU/L. PLB at five years is an excellent examination for the detection of early reversible graft fibrosis because no serum markers reflect this finding.
MISC
8書籍等出版物
2講演・口頭発表等
43共同研究・競争的資金等の研究課題
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臨床薬理研究振興財団 研究奨励金 2023年4月
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日本学術振興会 科学研究費助成事業 2021年7月 - 2023年3月