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Preoperative albumin-bilirubin score and liver resection percentage determine postoperative liver regeneration after partial hepatectomy

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World Journal of Gastroenterology 2024年第14期30卷 2006-2017页

作者： kazuhiro takahashi Masahiko Gosho Yoshihiro Miyazaki Hiromitsu Nakahashi Osamu Shimomura Kinji Furuya Manami Doi Yohei Owada Koichi Ogawa Yusuke Ohara Yoshimasa Akashi Tsuyoshi Enomoto Shinji Hashimoto Tatsuya Oda Department of Gastrointestinal and Hepatobiliary-Pancreatic Surgery University of TsukubaTsukuba 3058-575IbarakiJapan Department of Biostatistics University of TsukubaTsukuba 3058-575IbarakiJapan

BACKGROUND The success of liver resection relies on the ability of the remnant liver to *** of the knowledge regarding the pathophysiological basis of liver regeneration comes from rodent studies,and data on humans are ***,there is limited knowledge about the preoperative factors that influence postoperative *** To quantify postoperative remnant liver volume by the latest volumetric software and investigate perioperative factors that affect posthepatectomy liver *** A total of 268 patients who received partial hepatectomy were *** were grouped into right hepatectomy/trisegmentectomy(RH/Tri),left hepa-tectomy(LH),segmentectomy(Seg),and subsegmentectomy/nonanatomical hepatectomy(Sub/Non)*** regeneration index(RI)and late rege-neration rate were defined as(postoperative liver volume)/[total functional liver volume(TFLV)]×100 and(RI at 6-months-RI at 3-months)/RI at 6-months,*** lower 25th percentile of RI and the higher 25th percentile of late regeneration rate in each group were defined as“low regeneration”and“delayed regeneration”.“Restoration to the original size”was defined as regeneration of the liver volume by more than 90%of the TFLV at 12 months *** The numbers of patients in the RH/Tri,LH,Seg,and Sub/Non groups were 41,53,99 and 75,*** RI plateaued at 3 months in the LH,Seg,and Sub/Non groups,whereas the RI increased until 12 months in the RH/Tri *** to our multivariate analysis,the preoperative albumin-bilirubin(ALBI)score was an independent factor for low regeneration at 3 months[odds ratio(OR)95%CI=2.80(1.17-6.69),P=0.02;per 1.0 up]and 12 months[OR=2.27(1.01-5.09),P=0.04;per 1.0 up].Multivariate analysis revealed that only liver resection percentage[OR=1.03(1.00-1.05),P=0.04]was associated with delayed ***,multivariate analysis demonstrated that the preoperative ALBI score[OR=2.63(1.00-1.05),P=0.02;per 1.

关键词： Liver regeneration Albumin-bilirubin score Liver resection percentage Partial hepatectomy Human Regeneration index

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Dualistic role of platelets in living donor liver transplantation: Are they harmful?

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World Journal of Gastroenterology 2022年第9期28卷 897-908页

作者： Chen Liang kazuhiro takahashi Kinji Furuya Nobuhiro Ohkohchi Tatsuya Oda Gastrointestinal and Hepatobiliary-Pancreatic Surgery University of TsukubaTsukuba 3058575IbarakiJapan

Platelets are anucleate fragments mainly involved in hemostasis and thrombosis,and there is emerging evidence that platelets have other nonhemostatic potentials in inflammation,angiogenesis,regeneration and ischemia/reperfusion injury(I/R injury),which are involved in the physiological and pathological processes during living donor liver transplantation(LDLT).LDLT is sometimes associated with impaired regeneration and severe I/R injury,leading to postoperative complications and decreased patient *** studies have suggested that perioperative thrombocytopenia is associated with poor graft regeneration and postoperative morbidity in the short and long term after *** it is not fully understood whether thrombocytopenia is the cause or result,increasing platelet counts are frequently suggested to improve posttransplant outcomes in clinical *** on rodent experiments,previous studies have identified that platelets stimulate liver regeneration after partial ***,the role of platelets in LDLT is controversial,as platelets are supposed to aggravate I/R injury in the ***,a rat model of partial liver transplantation(LT)was used to demonstrate that thrombopoietin-induced thrombocytosis prior to surgery accelerated graft regeneration and improved the survival rate after *** was clarified that platelet-derived liver regeneration outweighed the associated risk of I/R injury after partial *** strategies to increase perioperative platelet counts,such as thrombopoietin,thrombopoietin receptor agonist and platelet transfusion,may improve graft regeneration and survival after LDLT.

关键词： Platelet Liver transplantation Regeneration Ischemia/reperfusion injury Kupffer cell Oxidative stress

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Thrombocytopenia after liver transplantation:should we care?

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World Journal of Gastroenterology 2018年第13期24卷 1386-1397页

作者： kazuhiro takahashi Shunji Nagai Mohamed Safwan Chen Liang Nobuhiro Ohkohchi Department of Surgery Division of Gastroenterological and Hepatobiliary Surgery and Organ Transplantation University of TsukubaTsukubaIbaraki 3058575Japan Transplant and Hepatobiliary Surgery Henry Ford HospitalDetroitMl 48202United States

Transient thrombocytopenia is a common phenomenon after liver transplantation. After liver transplantation(LT), platelet count decreases and reaches a nadir on postoperative days 3-5, with an average reduction in platelet counts of 60%; platelet count recovers to preoperative levels approximately two weeks after LT. The putative mechanisms include haemodilution, decreased platelet production, increased sequestration, medications, infections, thrombosis, or combination of these processes. However, the precise mechanisms remain unclear. The role of platelets in liver transplantation has been highlighted in recent years, and particular attention has been given to their effects beyond hemostasis and thrombosis. Previous studies have demonstrated that perioperative thrombocytopenia causes poor graft regeneration, increases the incidence of postoperative morbidity, and deteriorates the graft and decreases patient survival in both the short and long term after liver transplantation. Platelet therapies to increase perioperative platelet counts, such as thrombopoietin, thrombopoietin receptor agonist, platelet transfusion, splenectomy, and intravenous immunoglobulin treatment might have a potential for improving graft survival, however clinical trials are lacking. Further studies are warranted to detect direct evidence on whether thrombocytopenia is the cause or result of poor-graft function and postoperative complications, and to determine who needs platelet therapies in order to prevent postoperative complications and thus improve post-transplant outcomes.

关键词： Thrombocytopenia Liver regeneration Platelet therapy Platelet Thrombopoietin receptor agonist Intravenous immunoglobulin treatment Liver transplantation

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Recurrent renal cell carcinoma leading to a misdiagnosis of polycystic liver disease: A case report

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World Journal of Gastroenterology 2019年第18期25卷 2264-2270页

作者： Chen Liang kazuhiro takahashi Masanao Kurata Shingo Sakashita Tatsuya Oda Nobuhiro Ohkohchi Department of Surgery University of Tsukuba Department of Diagnostic Pathology University of Tsukuba

BACKGROUND Polycystic liver disease(PCLD) with a large cystic volume deteriorates the quality of life of patients through substantial effects on the adjacent organs,recurrent cyst infections, cyst rupture, and hemorrhage. Surgical or radiological intervention is usually needed to alleviate these symptoms. We report a rare case of the cystic metastasis of renal cell carcinoma(RCC), which was misdiagnosed as PCLD, as a result of the clinical and radiological similarity between these *** SUMMARY A 74-year-old female who had undergone nephrectomy for papillary-type RCC(PRCC) was suffering from abdominal pain and the recurrent intracystic hemorrhage of multiple cysts in the liver. Imaging studies and aspiration cytology of the cysts showed no evidence of malignancy. With a diagnosis of autosomal dominant polycystic liver disease, the patient received hepatectomy for the purpose of mass reduction and infectious cyst removal. Surgery was performed without complications, and the patient was discharged on postoperative day 14. Postoperatively, the pathology revealed a diagnosis of recurrent PRCC with cystic *** This case demonstrates the importance of excluding the cystic metastasis of a cancer when liver cysts are observed.

关键词： Polycystic liver disease Polycystic kidney disease Cystic metastasis Renal cell carcinoma Case report

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Extrahepatic metastasis of hepatocellular carcinoma to the paravertebral muscle:A case report

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World Journal of Hepatology 2017年第22期9卷 973-978页

作者： kazuhiro takahashi Krishna G Putchakayala Mohamed Safwan Dean Y Kim Transplant and Hepatobiliary Surgery Henry Ford HospitalDetroitMI 48202United States

Identification of extrahepatic metastases(EHM) of hepatocellular carcinoma(HCC) has been paradoxically increasing due to an increase in the survival of HCC patients. However, metastasis of HCC to the skeletal muscle tissue is extremely rare. We describe a unique case of HCC metastasizing to the paravertebral muscle. A 55-year-old man with a history of hepatitis B cirrhosis underwent partial liver resection with complete removal of HCC. Three months later, a computed tomography(CT) scan showed intrahepatic recurrence. The tumors were treated with yttrium-90 microspheres, transcatheter arterial chemoembolization, and sorafenib. Six months later, a CT scan showed an enhancing lesion of the left paravertebral muscle that on biopsy were consistent with metastatic HCC. The tumor was treated with stereotactic hypo-fractionated imageguided radiation therapy(SHFRT). A follow-up scan 3 mo post-radiotherapy revealed a stable appearance of the paravertebral muscle metastasis. Because of the progression in the intrahepatic tumors, the patient was treated with capecitabine, which was changed to dasatinib 6 mo later. The patient passed away three years after the primary surgical resection. Management of EHM poses an extreme challenge. This is the first case of HCC with EHM to the paravertebral muscle in which stability of disease was achieved using SHFRT. This case highlights the importance of early detection of hepatitis B viral infection and initiation of anti-viral therapy to decrease recurrence of HCC and prevent EHM.

关键词： Hepatocellular carcinoma Skeletal muscle Paravertebral muscle Extrahepatic metastasis Stereotactic hypo-fractionated image guided radiation therapy Hepatitis B virus

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Pegylated interferon α-2b plus ribavirin for older patients with chronic hepatitis C

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World Journal of Gastroenterology 2010年第35期16卷 4400-4409页

作者： Mosaburo Kainuma Norihiro Furusyo Eiji Kajiwara kazuhiro takahashi Hideyuki Nomura Yuichi Tanabe Takeaki Satoh Toshihiro Maruyama Makoto Nakamuta kazuhiro Kotoh Koichi Azuma Junya Shimono Shinji Shimoda Jun Hayashi Department of General Internal Medicine Kyushu University Hospital Department of Internal Medicine Nippon Steel Yawata Memorial Hospital Department of Medicine Hamanomachi Hospital The Center for Liver Disease Shin-Kokura Hospital Department of Medicine Fukuoka City HospitalYoshiduka-honmachi Center for Liver Disease National Hospital Organization Kokura Medical Center Department of Medicine Kitakyushu Municipal Medical Center Department of Gastroenterology Kyushu Medical CenterNational Hospital Organization Department of Medicine and Bioregulatory Science Graduate School of Medical ScienceKyushu University Department of Medicine and Clinical Science Graduate School of Medical SciencesKyushu University Saiseikai Yahata General Hospital Harunomachi Department of Medicine and Biosystemic Science Graduate School of Medical ScienceKyushu University

AIM:To analyze the efficacy and safety of a combination therapy of pegylated interferon(PEG-IFN) α-2b plus ribavirin(RBV) in older Japanese patients(65 years or older) infected with hepatitis C virus(HCV).METHODS:This multicenter study included 938 patients with HCV genotype 1 who received 1.5 μg/kg per week PEG-IFN α-2b plus RBV 600-1000 mg/d for 48 wk and 313 HCV genotype 2 patients who received this treatment for 24 ***:At 24 wk after the end of combination therapy,the overall sustained virological response(SVR) for genotypes 1 and 2 were 40.7% and 79.6%,*** SVR rate decreased signif icantly with age in each genotype,and was markedly reduced in genotype 1(P<0.001).Moreover,the SVR was significantly higher in patients with genotype 1 who were less than 65 years(47.3% of 685) than in those 65 years or older(22.9% of 253)(P<0.001) and was higher in patients with genotype 2 who were less than 65 years(82.9% of 252) than in those 65 years or older(65.6% of 61)(P=0.004).When patients received a dosage at least 80% or more of the target dosage of PEG-IFN α-2b and 60% or more of the target dosage of RBV,the SVR rate significantly increased to 66.5% in patients less than 65 years and to 45.2% in those 65 years or older(P<0.001).Adverse effects resulted in treatment discontinuation more often in patients with genotype 1(14.4%) than in patients with genotype 2(7.3%),especially by patients 65 years or older(24.1%).CONCLUSION:PEG-IFN α-2b plus RBV treatment was effective in chronic hepatitis C patients 65 years or older who completed treatment with at least the minimum acceptable treatment dosage.

关键词： Hepatitis C virus Gerontology Pegylated interferon Ribavirin

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Long-term lamivudine treatment for chronic,hepatitis B in Japanese patients:A project of Kyushu University Liver Disease Study

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World Journal of Gastroenterology 2006年第4期12卷 561-567页

作者： Norihiro Furusyo Hiroaki Takeoka kazuhiro Toyoda Masayuki Murata Yuichi Tanabe Eiji Kajiwara Junya Shimono Akihide Masumoto Toshihiro Maruyama Hideyuki Nomura Makoto Nakamuta kazuhiro takahashi Shinji Shimoda Koichi Azuma Hironori Sakai Jun Hayashi Department of General Medicine Kyushu University Hospital Department of Environmental Medicine and Infectious Diseases Graduate School of Medical Sciences. Kyushu University Fukuoka Japan Department of Medicine Fukuoka City HospitalFukuoka Japan Department of Internal Medicine Nippon SteelYawata Memorial Hospital Kitakyushu Japan Department of Medicine Yahata SaiseikaiHospital Kitakyushu Japan Department of Clinical Research NationalHospital Organization Kokura Hospital Kitakyushu Japan Department of Medicine KitakyushuMunicipal Medical Center Kitakyushu Japan Department of Internal Medicine ShinKokura Hospital Kitakyushu Japan Department of Medicine and Bioregulatory Science Graduate School of Medical Sciences Kyushu University Fukuoka Japan Department of Medicine HamanomachiHospital Fukuoka Japan Department of Medicine and Biosystemic Science Graduate School of Medical Sciences Kyushu University Fukuoka Japan Department of Medicine and Clinical Science Graduate School of Medical Sciences Kyushu University Fukuoka Japan Department of Gastroenterology National Hospital Organization Kyushu Medical Center Fukuoka Japan

AIM： To determine the efficacy of long-term lamivudine treatment of a large number of Japanese patients with chronic hepatitis B. METHODS： In this retrospective, multi-center trial, 318 Japanese patients with chronic hepatitis B received 100 mg of lamivudine daily for up to 36 （median 21） mo. Virological response was a decline to a serum HBV DNA level less than 3.7 log copies/mL. Virological breakthrough was defined as the reappearance of a serum HBV DNA level to more than 10-fold the minimum during treatment. RESULTS： Lamivudine produced virological response in 86.8% of the 318 patients at 6 mo, in 80.2% of 252 patients at 12 mo, in 69.2% of 133 patients at 24 mo, and in 53.6% of 28 patients at 36 mo. Forward stepwise logistic regression analysis showed an HBV DNA level less than 6.8 log copies/mL （P〈 0.0001）, HBeAg negativity （P〈 0.0001）, a platelet count of 100×10^9/L or more （P= 0.0162） at baseline, and a decline of the HBV DNA level of more than 3.2 log copies/mL as compared with the baseline level at 3 mo after the start of treatment （P= 0.0003） to be significantly associated with virological response. Among patients with a virological response, virological breakthrough was seen in 5.3% of 19 patients who responded virologically at 1 mo, in 20.7% of 203 patients at 3 mo, in 27.5% of 51 patients at 6 mo, in 33.3% of 12 patients at 9 mo, and in 100% of 3 patients at ≥15 mo. A virological breakthrough was found significantly more often in patients with delayed virological response. CONCLUSION： Lamivudine treatment could suppress serum HBV DNA in most of the tested Japanese patients. Long-term efficacy might be seen in patients without HBeAg at baseline, in the absence of cirrhosis, and in patients with a decline in HBV DNA level soon after the start of treatment.

关键词： Hepatitis B virus Lamivudine HBeAg Cirrhosis

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Relationship between body surface area and ALT normalization after long-term lamivudine treatment

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World Journal of Gastroenterology 2005年第44期11卷 6948-6953页

作者： Makoto Nakamuta Shusuke Morizono Yuichi Tanabe Eiji Kajiwara Junya Shimono Akihide Masumoto Toshihiro Maruyama Norihiro Furusyo Hideyuki Nomura Hironori Sakai kazuhiro takahashi Koichi Azuma Shinji Shimoda kazuhiro Kotoh Munechika Enjoji Jun Hayashi Kyushu University liver Disease Study Group Department of Medicine and Bioregulatory Science Department of Medicine Department of Internal Medicine Department of Clinical Research Department of Environmental Medicine and Infectious Diseases Department of Gastroenterology Department of Medicine and Clinical Science Department of Medicine and Biosystemic Science

AIM： To further evaluate the relationship between BSA and the effects of lamivudine in a greater number of cases and over a longer period of observation than in our previous evaluation. METHODS： We evaluated 249 patients with chronic hepatitis B. The effects of treatment for one year （n = 249）, two years （n = 147）, and three years （n = 72） were evaluated from the levels of serum ALT and HBVoDNA, as biological and virological effects （undetectable levels by PCR）, respectively. Moreover, several variables that could influence the response to treatment, including ALT, albumin, bilirubin, platelet counts, BSA, HBVoDNA, and HBeAg were analyzed. RESULTS： For 1-year treatment, multivariate analysis revealed that BSA （P = 0.0002） was the only factor for the biological effect, and that ALT （P = 0.0017）, HBV- DNA （P = 0.0004）, and HBeAg （P = 0.0021） were independent factors for the virological effect. For 2-year treatment, multivariate analysis again showed that BSA （P = 0.0147） was the only factor for the biological effect, and that ALT （P = 0.0192） and HBeAg （P = 0.0428） were independent factors for the virological effect. For 3-year treatment, multivariate analysis, however, could not reveal BSA （P = 0.0730） as a factor for the normalization of ALT levels. CONCLUSION： BSA is a significant predictor for the normalizing the effect of lamivudine therapy on ALT for an initial 2-year period, suggesting that lamivudine dosage should be based on the individual BSA.

关键词： Lamivudine Hepatitis B virus Body surface area Dose Long-term treatment

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Human platelets inhibit liver fibrosis in severe combined immunodeficiency mice

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World Journal of Gastroenterology 2013年第32期19卷 5250-5260页

作者： kazuhiro takahashi Soichiro Murata Kiyoshi Fukunaga Nobuhiro Ohkohchi Department of Surgery University of Tsukuba

AIM:To investigate the role of human platelets in liver ***:Severe combined immunodeficiency(SCID)mice were administered CCl4and either phosphate-buffered saline(PBS group)or human platelet transfusions(hPLT group).Concentrations of hepatocyte growth factor(HGF),matrix metallopeptidases(MMP)-9,and transforming growth factor-β(TGF-β)in the liver tissue were compared between the PBS and the hPLT groups by enzyme-linked immunosorbent assay(ELISA)and Western *** effects of a human platelet transfusion on liver fibrosis included the fibrotic area,hydroxyproline content,and-smooth muscle actin(α-SMA)expression,which were evaluated by picrosirius red staining,ELISA,and immunohistochemical staining using an anti-mouse-SMA antibody,*** of mesenchymal-epithelial transition factor(Met)and SMAD3,downstream signals of HGF and TGF-β,were compared between the two groups by Western blotting and were quantified using *** apoptosis was evaluated by terminal deoxynucleotidyl transferase dUTP nick end ***,the accumulation of human platelets in the liver 2 h after platelet transfusion was compared between normal and fibrotic livers by immunohistochemical staining using an anti-human CD41 ***:The fibrotic area and hydroxyproline content in the liver were both significantly lower in the hPLT group when compared to the PBS group(fibrotic area,1.7%±0.6%vs 2.5%±0.6%,P=0.03;hydroxyproline content,121±26 ng/g liver vs 156±47 ng/g liver,P=0.04).There was less α-smooth muscle actin staining in the hPLT group than in the PBS group(0.5%±0.1%vs 0.8%±0.3%,P=0.02).Hepatic expression levels of mouse HGF and MMP-9were significantly higher in the hPLT group than in the PBS group(HGF,109±13 ng/g liver vs 88±22 ng/g liver,P=0.03;MMP-9,113%±7%/GAPDH vs 92%±11%/GAPDH,P=0.04).In contrast,the concentration of mouse TGF-β in the liver tissue was significantly lower in the hPLT group than in the PBS group(22±5ng/g

关键词： Human platelet Liver fibrosis Hepatocyte apoptosis Hepatocyte growth factor Transforming growth factor-β Matrix metallopeptidases

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Conversion hepatectomy for hepatocellular carcinoma with main portal vein tumour thrombus after lenvatinib treatment: A case report

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World Journal of Hepatology 2021年第3期13卷 384-392页

作者： kazuhiro takahashi Jaejeong Kim Amane takahashi Shinji Hashimoto Manami Doi Kinji Furuya Ryosuke Hashimoto Yohei Owada Koichi Ogawa Yusuke Ohara Yoshimasa Akashi Katsuji Hisakura Tsuyoshi Enomoto Osamu Shimomura Masayuki Noguchi Tatsuya Oda Department of Gastrointestinal and Hepatobiliary Pancreatic Surgery University of TsukubaTsukuba 3058575IbarakiJapan Department of Gastroenterological Surgery Saitama Cancer CenterSaitama 3620806SaitamaJapan Department of Diagnostic Pathology University of TsukubaTsukuba 3058575IbarakiJapan

BACKGROUND Hepatocellular carcinoma(HCC)accompanied by portal vein tumour thrombus(PVTT)presents an aggressive disease course,worsening liver function reserve,and a high recurrence *** practice guidelines recommend systemic therapy as the first-line option for HCC with portal ***,to achieve longer survival in these patients,the treatment strategy should be concluded with removal of the tumour by locoregional *** experienced a case of initially unresectable HCC with main PVTT converted to radical hepatectomy after lenvatinib *** SUMMARY A 59-year-old male with chronic hepatitis C infection visited our clinic as a regular post-surgery ***-enhanced abdominal computed tomography revealed a liver mass diffusely located at the lateral segment with a massive PVTT extending from the umbilical portion to the main and contralateral third-order portal *** the diagnosis of unresectable HCC with Vp4(main trunk/contralateral branch)PVTT,lenvatinib was started at 12 mg/*** computed tomography taken 3 mo after starting lenvatinib showed regression of the PVTT,which had retreated to the contralateral first-order portal *** tolerated the full dose without major adverse *** cessation of lenvatinib for 7 d,radical left lobectomy and PVTT thrombectomy were *** patient’s postoperative course was ***,the primary lesion showed fibrotic changes,with moderately to poorly differentiated tumour cells surrounded by granulation tissues in some *** majority of the PVTT showed *** was alive without recurrence for 8 *** This is the first case of HCC with Vp4 PVTT in which radical conversion hepatectomy was succeeded after lenvatinib treatment.

关键词： Hepatocellular carcinoma Lenvatinib Portal vein tumour thrombus Conversion hepatectomy Case report

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