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Epidemiology and Management of Drug-induced Liver Injury: Importance of the Updated RUCAM

Journal of Clinical and Translational Hepatology 2023年第5期11卷 1239-1245页

作者： takashi Kobayashi Michihiro Iwaki Asako Nogami Masato Yoneda Department of Gastroenterology and Hepatology Yokohama City University Graduate School of MedicineYokohamaJapan

Drug-induced liver injury(DILI)is a major cause of acute liver injury,liver failure,and liver transplantation worldwide.In recent years,immune checkpoint inhibitors have become widely used.This has led to an increase in DILI,for which pathophysiology and management methods differ significantly from the past.As the number of cases of acute liver injury and liver transplantation due to DILI is expected to increase,information about a DILI is becoming more valuable.DILI is classified into two types according to its etiology:intrinsic DILI,in which the drug or its metabolites cause liver damage that is dose-dependent and predictable;and idiosyncratic DILI,in which liver damage is also dose-independent but unpredictable.In addition,depending on the course of the disease,chronic DILI or drug-induced autoimmune hepatitis may be present.The number of DILI cases caused by antimicrobial agents is decreasing,whereas that caused by drugs for malignant tumors and health foods is increasing.The Roussel Uclaf Causality Assessment Method is widely used to assess causality in DILI.Liver injury is a type of immune-related adverse event.The pattern of hepatic injury in immune-related adverse events is mostly hepatocellular,but mixed type and bile stasis have also been reported.Sclerosing cholangitis caused by immune checkpoint inhibitors has also been reported as a unique type of injury.Treatment mainly comprises withdrawal of immune checkpoint inhibitors and steroid administration;however,mycophenolate mofetil may be considered if the disease is refractory to steroids.

关键词： Drug-induced liver injury Immune-related adverse events Immune checkpoint inhibitor Updated RUCAM

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Small-for-size syndrome in living donor liver transplantation

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Hepatobiliary & Pancreatic Diseases International 2012年第6期11卷 570-576页

作者： Shintaro yagi Shinji Uemoto Department of Hepatobiliary Pancreas and Transplant Surgery Kyoto University Graduate School of Medicine 54 Kawara-cho Shogoin Sakyo-ku Kyoto 606-8507 Japan

When the graft volume is too small to satisfy the recipient’s metabolic demand, the recipient may thus experience small-for-size syndrome (SFSS). Because the occurrence of SFSS is determined by not only the liver graft volume but also a combination of multiple negative factors, the definitions of small-for-size graft (SFSG) and SFSS are different in each institute and at each time. In the clinical setting, surgical inflow modulation and maximizing the graft outflow are keys to overcoming SFSS. Accordingly, relatively smaller-sized grafts can be used with surgical modification and pharmacological manipulation targeting portal circulation and liver graft quality. Therefore, the focus of the SFSG issue is now shifting from how to obtain a larger graft from the living donor to how to manage the use of a smaller graft to save the recipient, considering donor safety to be a priority.

关键词： living donor liver transplantation small-for-size syndrome

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DEVELOPMENT OF A MATERIALS RISK INFORMATION PLATFORM FOR A SAFE SOCIETY

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Acta Metallurgica Sinica(English Letters) 2004年第4期17卷 375-380页

作者： K.yagi National Institute for Materials Science Tsukuba Ibaraki 305-0047 Japan Materials Risk Information Platform is being developed under the cooperation of companies and academic societies with NIMS as project core. To combine safety and economy which are sometimes contrary to each other it is important to find an optimal solution using a new concept: risk based engineering. A 5-year project the Materials Risk Information Platform was started in 2001 in NIMS on the boilers of thermal power plants and the objectives of this project research areas and its present state were outlined.

A Materials Risk Information Platform is being developed under the cooperation of companies and academic societies with NIMS as project core. To combine safety and economy, which are sometimes contrary to each other, it is important to find an optimal solution using a new concept: risk based engineering. A 5-year project, the Materials Risk Information Platform, was started in 2001 in NIMS on the boilers of thermal power plants and the objectives of this project, research areas and its present state were outlined.

关键词： risk accident structural material aged plant life prediction,equipment diagnostic system

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Cholangiocarcinoma after flow diversion surgery for congenital biliary dilatation: A case report and review of literature

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World Journal of Hepatology 2019年第11期11卷 743-751页

作者： Ryo Ataka takashi Ito Toshihiko Masui Satoru Seo Takamichi Ishii Satoshi Ogiso Shintaro yagi Kojiro Taura Shinji Uemoto Department of Hepato-Biliary-Pancreatic Surgery and Transplantation Graduate School of Medicine Kyoto University

BACKGROUND Pancreaticobiliary maljunction(PBM)can be classified into two categories,PBM with congenital biliary dilatation(CBD)or PBM without biliary dilatation,and the management of PBM is often controversial.The treatment for PBM with CBD is prophylactic flow diversion surgery,and some authors have reported that the incidence of cancer after extrahepatic bile duct excision is less than 1%.A very rare case of intrahepatic cholangiocarcinoma 6 years after flow diversion surgery for PBM with CBD is reported.CASE SUMMARY A 30-year-old man was diagnosed as having PBM with CBD,Todani classification type IVA,because of abnormal liver enzyme profiles.He underwent flow diversion surgery and cholecystectomy,and the specimen showed adenocarcinoma foci,pT1,pStage IA.Five and a half years passed without any recurrence of bile duct cancer.However,6 years after his operation,computed tomography showed a gradually growing nodule in the bile duct.Fluorodeoxyglucose positron emission tomography showed high uptake,and magnetic resonance imaging showed restricted diffusion signals.On double balloon enteroscopy,the nodule at the posterior bile duct-jejunum anastomosis was directly visualized,and its biopsy specimen showed adenocarcinoma.The patient underwent right lobectomy and biliary reconstruction.The pathological diagnosis was intraductal papillary neoplasm with high-grade intraepithelial neoplasia,pTis,pN0,pStage 0.The patient’s postoperative course was uneventful,and he has had no recurrence up to the present time.CONCLUSION This case suggests the necessity of careful observation after flow diversion surgery,especially when PBM with CBD is detected in adulthood.

关键词： Congenital biliary dilatation Pancreaticobiliary maljunction Cholangiocarcinoma Recurrence Metachronous neoplasm Case report

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Enhanced electrical property of graphite/Al_(2)O_(3) composite fabricated by reductive sintering of gel-casted body using cross-linked epoxy polymer

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Journal of Advanced Ceramics 2022年第4期11卷 523-531页

作者： Yoshiaki FUNAHASHI Yunzi XIN Kunihiko KATO Huu Hien NGUYEN takashi SHIRAI Department of Life Science and Applied Chemistry Graduate School of EngineeringNagoya Institute of TechnologyGokiso-choShowa-kuNagoyaAichi 466-8555Japan Advanced Ceramics Research Center Nagoya Institute of TechnologyGokiso-choShowa-kuNagoyaAichi 466-8555Japan

In the present study,graphite/alumina composites are fabricated via reductive sintering of gel-casted green bodies with structurally controlled cross-linked epoxy polymers for the first time.The cross-linking degrees of polymers are tuned by the amount ratio of epoxy monomer/polyvinyl alcohol cross-linker utilized in gel-casting process.Superior electrical properties with respect to 5-fold enhanced electrical conductivity and 2-fold higher carrier mobility are successfully achieved in graphite/alumina composite fabricated from cross-linked epoxy polymer,whose phenomenon is attributed to the excellent conductive path in ceramic matrix established by highly uniform network with improved graphitization degree.

关键词： ceramic composite gel-casting reductive sintering cross-linking electrical property graphitization

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Partial dehydration of brucite and its implications for water distribution in the subducting oceanic slab

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Geoscience Frontiers 2022年第2期13卷 275-283页

作者： Xinzhuan Guo takashi Yoshino Sibo Chen Xiang Wu Junfeng Zhang Key Laboratory for High-Temperature and High-Pressure Study of the Earth's Interior Institute of GeochemistryChinese Academy of SciencesGuiyang 550081China Institute for Planetary Materials Okayama UniversityMisasaTottori 682-0193Japan Department of Geosciences Stony Brook UniversityStony BrookNY 11794-2100USA State Key Laboratory of Geological Processes and Mineral Resources School of Earth SciencesChina University of GeosciencesWuhan 430074China

Hydrous minerals within the subducting oceanic slab are important hosts for water.Clarification of the stability field of hydrous minerals helps to understand transport and distribution of water from the surface to the Earth’s interior.We investigated the stability of brucite,a prototype of hydrous minerals,by means of electrical conductivity measurements in both open and closed systems at 3 GPa and temperatures up to 1300 K.Dramatic increase of conductivity in association with characteristic impedance spectra suggests that partial dehydration of single-crystal brucite in the open system with a low water fugacity occurs at 950 K,which is about 300 K lower than those previously defined by phase equilibrium experiments in the closed system.By contrast,brucite completely dehydrates at 1300 K in the closed system,consistent with previous studies.Partial dehydration may generate a highly defective structure but does not lead to the breakdown of brucite to periclase and water immediately.Water activity plays a key role in the stability of hydrous minerals.Low water activity(a H_(2)O)caused by the high wetting behavior of the subducted oceanic slab at the transition zone depth may cause the partial dehydration of the dense hydrous magnesium silicates(DHMSs),which significantly reduces the temperature stability of DHMS(this mechanism has been confirmed by previous study on super hydrous phase B).As a result,the transition zone may serve as a‘dead zone’for DHMSs,and most water will be stored in wadsleyite and ringwoodite in the transition zone.

关键词： Partial dehydration Electrical conductivity Brucite Oceanic slab Water distribution Hydrous minerals

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Greenhouse gas reduction of co-benefit-type wastewater treatment system for fish-processing industry: A real-scale case study in Indonesia

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Water Science and Engineering 2023年第3期16卷 271-279页

作者： Yoshiteru Hamatani Takahiro Watari Masashi Hatamoto takashi Yamaguchi Tjandra Setiadi Toshihiko Konda Nihon Suido Consultants Co. LtdTokyo 163-1122Japan Department of Civil and Environmental Engineering Nagaoka University of TechnologyNiigata 940-2188Japan Department of Chemical Engineering Hanoi University of Science and TechnologyHanoi 11615Vietnam Department of Science of Technology Innovation Nagaoka University of TechnologyNiigata 940-2188Japan Department of Chemical Engineering Institut Teknologi BandungJl.Ganesa 10Bandung 40132Indonesia

This study examined the application of co-benefit-type wastewater treatment technology in the fish-processing industry. Given that there was a dearth of information on fish-processing industrial wastewater in Indonesia, site surveys were conducted. For the entire fish-processing industry throughout the country, the dissemination rate of wastewater treatment facilities was less than 50%. Using a co-benefit approach, a real-scale swim-bed technology (SBT) and a system combining an anaerobic baffled reactor (ABR) with SBT (ABR–SBT) were installed in a fishmeal processing factory in Bali, Indonesia, and the wastewater system process performance was evaluated. In a business-as-usual scenario, the estimated chemical oxygen demand load and greenhouse gas (GHG) emissions from wastewater from the Indonesian fish-processing industry were 33 000 tons per year and 220 000 tons of equivalent CO_(2) per year, respectively. On the other hand, the GHG emissions in the co-benefit scenarios of the SBT system and ABR–SBT system were 98 149 and 26 720 tons per year, respectively. Therefore, introducing co-benefit-type wastewater treatment to Indonesia’s fish-processing industry would significantly reduce pollution loads and GHG emissions.

关键词： Indonesian fish-processing industry Co-benefit wastewater treatment Greenhouse gas emission mitigation Anaerobic baffled reactor Swim-bed technology

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LC-MS/MS method for the quantitation of serum tocilizumab in rheumatoid arthritis patients using rapid tryptic digestion without IgG purification

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Journal of Pharmaceutical Analysis 2022年第6期12卷 852-859页

作者： takashi Mochizuki Kaito Shibata Takafumi Naito Kumiko Shimoyama Noriyoshi Ogawa Masato Maekawa Junichi Kawakami Department of Hospital Pharmacy Hamamatsu University School of MedicineHamamatsu431-3192Japan Department of Pharmacy Shinshu University HospitalMatsumotoNagano390-8621Japan Third Division Department of Internal MedicineHamamatsu University School of MedicineHamamatsu431-3192Japan Department of Laboratory Medicine Hamamatsu University School of MedicineHamamatsu431-3192Japan

The quantitation of serum tocilizumab using liquid chromatography tandem-mass spectrometry(LC-MS/MS)method has not been widely applied in clinical settings because of its time-consuming and costly sample pretreatments.The present study aimed to develop a validated LC-MS/MS method for detecting serum tocilizumab by utilizing immobilized trypsin without an immunoglobulin G purification step and evaluate its applicability in the treatment of rheumatoid arthritis(RA)patients administered intravenously or subcutaneously with tocilizumab.The tocilizumab-derived signature peptide was deciphered using a nano-LC system coupled to a hybrid quadrupole-orbitrap mass spectrometer.The serum tocilizumab was rapidly digested by immobilized trypsin for 30 min.The chromatographic peak of the signature peptide and that of the internal standard were separated from the serum digests for a total run time of 15 min.The calibration curve of serum tocilizumab concentration was linear with a range of 2-200 μg/mL.The intra-and inter-day accuracy and relative standard deviation(RSD)were 90.7%-109.4%and<10%,respectively.The serum tocilizumab concentrations in the RA patients receiving intravenous and subcutaneous injections were 5.8-28.9 and 2.4-63.5 μg/mL,respectively.The serum tocilizumab concentrations using the current method positively correlated with those using the enzyme-linked immunosorbent assay,although a systematic error was observed between these methods.In conclusion,a validated LC-MS/MS method with minimal sample pretreatments for monitoring serum tocilizumab concentrations in RA patients was developed.

关键词： Tocilizumab LC-MS/MS Immobilized trypsin IgG purification Proteomics Rheumatoid arthritis

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Antifibrotic effect of aloe vera in viral infection-induced hepatic periportal fibrosis

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World Journal of Gastroenterology 2012年第17期18卷 2026-2034页

作者： Sahar K Hegazy Mohamed El-Bedewy Akira yagi Department of Clinical Pharmacy Faculty of PharmacyTanta UniversityTanta 8130Egypt Department of Internal Medicine Faculty of MedicineTanta UniversityTanta 8130Egypt Placenta/Aloe Research Institute Japan Bio-Products Co.Ltd.1488-4Aikawa-machiKurume-shiFukuoka Bio Factory 204Fukuoka 839-0861Japan

AIM:To investigate the anti-oxidative and anti-fibrotic effects of aloe vera in patients with liver fibrosis.METHODS:Aloe vera high molecular weight fractions(AHM) were processed by patented hyper-dry system in combination of freeze-dry technique with microwave and far infrared-ray radiation.Fifteen healthy volunteers as the control group and 40 patients were included.The patients were randomly subdivided into two equal groups:the conventional group was treated with placebo(starch),and AHM group was treated with 0.15 gm/d AHM,both for 12 consecutive weeks.The patients were investigated before and after treatment.Serum activity of aspartate aminotransferase(AST),alanine aminotransferase(ALT),alkaline phosphatase(ALP),hyaluronic acid(HA),transforming growth factor-β(TGF-β) and matrixmetalloproteinase-2(MMP-2) were determined.The reduced glutathione(GSH) and malondialdehyde(MDA) levels in liver were assayed and the expression of hepatic α-smooth muscle actin(α-SMA) was identified by immunohistochemistry.RESULTS:At the start of the study,the hematoxylin and eosin staining revealed fibro-proliferated bile ductules,thick fibrous septa and dense inflammatory cellular infiltration in the patients before treatment.The use of AHM for 12 wk significantly ameliorated the fibrosis,inhibited the inflammation,and resulted in minimal infiltration and minimal fibrosis compared to the conventional group.The enzyme activities of the liver(ALT,AST and ALP) were attenuated after treatment in both groups,and the decrease in the AHM group was more significant as compared with the conventional group.Similar to the AST,the MDA levels were significantly higher before treatment,and were attenuated after treatment in both groups.In contrast,the hepatic glutathione content in the patients were decreased significantly in the AHM group compared to the controls.The serum levels of the fibrosis markers(HA,TGF-β and MMP-2) were also reduced significantly after treatment.The expression of α-SMA was modified in patients before and after treatment a

关键词：肝纤维化肝门静脉病毒感染芦荟基质金属蛋白酶-2 转化生长因子细胞治疗还原型谷胱甘肽

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Assessment of cardiac output in liver transplantation recipients

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Hepatobiliary & Pancreatic Diseases International 2008年第4期7卷 362-366页

作者： Tomohide Hori Chiduru Yamamoto Shintaro yagi Taku Iida Kentaro Taniguchi takashi Hasegawa Koichiro Yamakado Yukinobu Hori Kan Takeda Kazuo Maruyama Shinji Uemoto Department of Hepato-Pancreato-Biliary Surgery and Transplantation Kyoto University Hospital54 Shogoinkawara- choSakyo-kuKyoto606-8507Japan Department of Hepatobiliary Pancreatic Surgery Mie University Hospital2-174 EdobashiTsu CityMie Prefecture514-8507 Japan Department of Anesthesiology and Critical Care Medicine Mie University Graduate School of Medicine2-174 EdobashiTsu CityMie Prefecture514-8507Japan Department of Radiology Mie University Graduate School of Medicine2-174 EdobashiTsu CityMie Prefecture514-8507Japan Nagoya Economic University Graduate School of Law 61-1 UchikuboInuyama City Aichi Prefecture 484-8504Japan

BACKGROUND:Liver cirrhosis causes peculiar systemic hemodynamics,and accurate evaluation of systemic hemodynamic state is important for cirrhotic recipients who underwent living donor liver transplantation(LDLT). We investigated the clinical advantages of a novel non- invasive method for measuring systemic hemodynamic parameters using indocyanine green(ICG). METHODS:Twenty-eight LDLT recipients were evaluated. Simultaneous measurements of cardiac output(CO)using Swan-Ganz catheters and pulse dye densitometry(PDD) were performed every 12 hours after LDLT.A total of 155 sets of simultaneous CO measurements were obtained. RESULTS:The CO values obtained by PDD correlated well with those obtained by the invasive catheter technique.In addition,none of the recipients developed any side-effects, and we verified the safety of repeated ICG injections.ICG is safe,even for repeated use over time in the same recipient. Moreover,PDD can measure the blood volume(BV).CONCLUSIONS:Since the cirrhotic systemic hemody- namics characterized by high CO and large BV remains, even after LDLT,the ability to measure CO and BV in a non-invasive,simple and real-time manner using PDD has advantages for cirrhotic LDLT recipients.

关键词： liver transplantation indocyanine green pulse dye densitometry blood volume cardiac output liver cirrhosis

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