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Efficacy of MK615 for the treatment of patients with liver disorders

World Journal of Gastroenterology 2012年第31期18卷 4118-4126页

作者： Atsushi Hokari Tomohisa Ishikawa Hisao Tajiri Takahide Matsuda Osamu Ishii Nobuyuki Matsumoto chiaki okuse Hideaki Takahashi Takeshi Kurihara Ko-ichi Kawahara Ikuro Maruyama Mikio Zeniya Department of Internal Medicine Division of General Internal MedicineSt.Marianna University School of MedicineKawasaki 2168511Japan Department of Internal Medicine Division of Gastroenterology and HepatologySt.Marianna University School of MedicineKawasaki 2168511Japan Keio University Graduate School of Media and GovernanceFujisawa 2520882Japan Department of Biomedical Engineering Osaka Institute of TechnologyOsaka 5358585Japan Department of Systems Biology in Thromboregulation Kagoshima University Graduate School of Medical and Dental SciencesKagoshima 8908580Japan Department of Internal Medicine Division of Gastroenterology and HepatologyThe Jikei University School of MedicineTokyo 1058471Japan

AIM:To investigate the hepatoprotective effect of MK615,a Japanese apricot extract,in an animal model,and its clinical therapeutic ***:Wistar rats were administered physiological saline(4 mL/kg) or MK615 solution(4 mL/kg) for 7 *** the sixth d,acute hepatic injury was induced by administering a single intraperitoneal injection(ip) of D-galactosamine hydrochloride(D-GalN)(600 mg/kg).Plasma levels of alanine aminotransferase(ALT) and aspartate aminotransferase(AST) were determined,and liver tissues were used for histopathological ***-eight patients with liver disorders [hepatitis C(n = 40),non-alcoholic fatty liver disease(n = 15),and autoimmune liver disease(n = 3)] were orally administered commercially available Misatol ME-containing MK615(13 g/d) daily for 12 *** and urine were sampled immediately before and 6 wk,12 wk,and 16 wk after the start of intake to measure various biochemical *** percentage change in ALT and AST levels after 12 wk from the pre-intake baseline served as a primary ***:D-GalN effectively induced acute hepatic injury in the *** 48 h after the ip injection of D-GalN,the plasma levels of ALT(475.6 ± 191.5 IU/L vs 225.3 ± 194.2 IU/L,P < 0.05) and AST(1253.9 ± 223.4 IU/L vs 621.9 ± 478.2 IU/L,P < 0.05) in the MK615 group were significantly lower than the control *** single cell necrosis,loss of hepatocytes,and extensive inflammatory cell infiltration were observed in hepatic tissue samples collected from the control ***,these findings were less pronounced in the group receiving *** the end of the clinical study,serum ALT and AST levels were significantly decreased compared with pre-intake baseline levels from 103.5 ± 58.8 IU/L to 71.8 ± 39.3 IU/L(P < 0.05) and from 93.5 ± 55.6 IU/L to 65.5 ± 34.8 IU/L(P < 0.05),respectively.A reduction of ≥ 30% from the pre-study baseline ALT level was observed in 26(45%) of the 58 patients,while 25(43%) patients exhibited similar A

关键词：肝脏疾病治疗效果患者疗效观察 Wistar大鼠急性肝损伤食盐水 ALT

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Pancreatic involvement in chronic viral hepatitis

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World Journal of Gastroenterology 2005年第23期11卷 3508-3513页

作者： Yoshiki Katakura Hiroshi Yotsuyanagi Kiyoe Hashizume chiaki okuse Noriaki okuse Kohji Nishikawa Michihiro Suzuki Shiro Iino Fumio Itoh Division of Gastroenterology and Hepatology

AIM: To elucidate the frequency and characteristics of pancreatic disorders in the course of chronic viral hepatitis. METHODS: We prospectively assessed the serum pancreatic enzyme levels and imaging findings in patients with chronic viral hepatitis and healthy control subjects. RESULTS: Serum amylase (t-Amy), salivary amylase (s-Amy), pancreatic amylase (p-Amy) and serum lipase levels were higher in hepatitis patients in comparison to control subjects. However, in asymptomatic viral carriers, only the serum t-Amy levels were higher than those of the controls. The levels of each enzyme rose with the progression of liver disease in patients with hepatitis B or C; whereas the levels of each enzyme within the same clinical stage of the disease did not differ between patients diagnosed with either hepatitis B or hepatitis C virus. Imaging findings demonstrated chronic pancreatitis in only 1 out of 202 patients (0.5%).CONCLUSION: Our data suggest that serum levels of pancreatic enzymes increase with the progression of liver disease in patients diagnosed with viral hepatitis. Pancreatic disease, asymptomatic in most cases, may represent an extrahepatic manifestation of chronic viral hepatitis.

关键词：慢性病毒肝炎胰腺损伤病理机制临床表现

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Need for pancreatic stenting after sphincterotomy in patients with difficult cannulation

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World Journal of Gastroenterology 2014年第26期20卷 8617-8623页

作者： Kazunari Nakahara chiaki okuse Keigo Suetani Yosuke Michikawa Shinjiro Kobayashi Takehito Otsubo Fumio Itoh Department of Gastroenterology and Hepatology St. Marianna University School of Medicine Department of Gastroenterological and General Surgery St. Marianna University School of Medicine

AIM:To investigate the need for pancreatic stenting after endoscopic sphincterotomy(EST)in patients with difficult biliary ***:Between April 2008 and August 2013,2136 patients underwent endoscopic retrograde cholangiopancreatography(ERCP)-related *** them,55 patients with difficult biliary cannulation who underwent EST after bile duct cannulation using the pancreatic duct guidewire placement method(P-GW)were divided into two groups:a stent group(n=24;pancreatic stent placed)and a no-stent group(n=31;no pancreatic stenting).We retrospectively compared the two groups to examine the need for pancreatic stenting to prevent post-ERCP pancreatitis(PEP)in patients undergoing EST after biliary cannulation by ***:No differences in patient characteristics or endoscopic procedures were observed between the two *** incidence of PEP was 4.2%(1/24)and29.0%(9/31)in the Stent and no-stent groups,respectively,with the no-stent group having a significantly higher incidence(P=0.031).The PEP severity was mild for all the patients in the stent *** contrast,8 had mild PEP and 1 had moderate PEP in the no-stent *** mean serum amylase levels(means±SD)3 h after ERCP(183.1±136.7 vs 463.6±510.4 IU/L,P=0.006)and on the day after ERCP(209.5±208.7vs 684.4±759.3 IU/L,P=0.002)were significantly higher in the no-stent group.A multivariate analysis identified the absence of pancreatic stenting(P=0.045;odds ratio,9.7;95%CI:1.1-90)as a significant risk factor for ***:In patients with difficult cannulation in whom the bile duct is cannulated using P-GW,a pancreatic stent should be placed even if EST has been performed.

关键词： Pancreatic stenting Pancreatic guidewire placement

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Risk factors for retinopathy associated with interferonα-2b and ribavirin combination therapy in patients with chronic hepatitis C

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World Journal of Gastroenterology 2006年第23期12卷 3756-3759页

作者： chiaki okuse Hiroshi Yotsuyanagi Yoshihiko Nagase Yuhtaro Kobayashi Kiyomi Yasuda Kazuhiko Koike Shiro Iino Michihiro Suzuki Fumio Itoh Division of Gastroenterology and Hepatology Department of Internal Medicine St. Marianna University School of MedicineKawasakiKanagawa 216-8511Japan Department of Infectious Diseases Internal MedicineFaculty of MedicineUniversity of Tokyo7-3-1HongoBunkyoTokyo 113-8655Japan Division of Gastroenterology and Hepatology Department of Internal MedicineSt.Marianna University School of MedicineKawasakiKanagawa 216-8511Japan Center for Liver Diseases Kiyokawa HospitalMinamiasagayaSuginamiTokyo166-0004Japan Department of Infectious Diseases Internal MedicineFaculty of MedicineUniversity of Tokyo7-3-1KongoBunkyoTokyo 113-8655Japan Division of Gastroenterology and Hepatology Department of Internal MedicineSt.Marianna University School of MedicineKawasakiKanagawa216-8511Japan

AIM: To elucidate the frequency and risk factors for retinopathy in patients with chronic hepatitis C who are treated by interferon-ribavirin combination therapy. METHODS: We prospectively analyzed 73 patients with histologically confirmed chronic hepatitis C, who underwent combination therapy for 24 wk. Optic fundi were examined before, and 2, 4, 12 and 24 wk after the start of combination therapy. RESULTS: Fourteen patients (19%) developed retinopathy, which was initially diagnosed by the appearance of a cotton wool spot in 12 patients. Retinal hemorrhage was observed in 5 patients. No patient complained of visual disturbance. Retinopathy disappeared in 9 patients (64%) despite the continuation of combination therapy. However, retinopathy persisted in 5 patients with retinal hemorrhage. A comparison of the clinical background between the groups with and without retinopathy showed no significant differences in age, gender, viral genotype, RNA level, white blood cell count, platelet count, prothrombin time, complications by diabetes mellitus or hypertension, or pretreatment arteriosclerotic changes in the optic fundi. However, multiple logistic regression analysis revealed that complication by hypertension was observed with a high frequency in the group with retinopathy (P = 0.004, OR=245.918, 95% CI=5.6-10786.2). CONCLUSION: Retinopathy associated with combination therapy of interferon a-2b and ribavirin tends to develop in patients with hypertension.

关键词：视网膜病干扰素α-2b 病毒唑丙型病毒肝炎

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Fatal liver failure caused by reactivation of lamivudine-resistant hepatitis B virus:A case report

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World Journal of Gastroenterology 2007年第6期13卷 964-969页

作者： Yuka Suzuki Hiroshi Yotsuyanagi chiaki okuse Yoshihiko Nagase Hideaki Takahashi Kyoji Moriya Michihiro Suzuki Kazuhiko Koike Shiro Iino Fumio Itoh Division of Gastroenterology and Hepatology Department of Internal Medicine St. Marianna University School of Medicine 2-16-1 Sugao Miyamae-ku Kawasaki 216-8511 Japan Division of Infectious Diseases Department of Internal Medicine University of Tokyo 7-3-1 Hongo Bunkyo-ku Tokyo 113-0033 Japan Center for Liver Diseases Seizankai Kiyokawa Hospital 2-31-12 Asagayaminami Suginami Tokyo 166-0004 Japan

We present a case of fetal liver failure caused by the activation of lamivudine-resistant hepatitis B virus (HBV) nine months after lamivudine treatment. A 57-year old man visited our hospital for the treatment of decompensated chronic hepatitis B. Lamivudine was started in December 2001. Subsequently, serum HBV was negative for HBV DNA with seroconversion from HBeAg to anti-HBe and improvement of liver function. However, HBV DNA and HBeAg were again detected in September 2002. He was complicated by breakthrough hepatitis and admitted to our hospital in November for severely impaired liver function. Vidarabine treatment was started and serum HBV DNA and alanine aminotransferase (ALT) decreased transiently. However, after the start of α-interferon treatment, HBV DNA level increased and liver function deteriorated. He died 1 mo after admission. An analysis of amino acid sequences in the polymerase region revealed that rtM204I/V with rtL80I/V occurred at the time of viral breakthrough. After the start of antiviral treatment, rtL180M was detected in addition to rtM204I/V and rtL80I/V, and became predominant in the terminal stage of the disease. HBV clone with a high replication capacity may be produced by antiviral treatment leading to the worsening of liver function. Antiviral therapy for patients with breakthrough hepatitis in advanced liver disease should be carefully performed.

关键词：乙型肝炎病毒拉米夫定耐药病毒再活化肝衰竭病例报告

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Correlation between hepatic blood flow and liver function in alcoholic liver cirrhosis

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World Journal of Gastroenterology 2014年第45期20卷 17065-17074页

作者： Hideaki Takahashi Ryuta Shigefuku Yoshihito Yoshida Hiroki Ikeda Kotaro Matsunaga Nobuyuki Matsumoto chiaki okuse Shigeru Sase Fumio Itoh Michihiro Suzuki Division of Gastroenterology and Hepatology Department of Internal Medicine St.Marianna University School of Medicine Division of Gastroenterology Department of Internal Medicine Sapporo Shirakabadai Hospital Department of Molecular Biology Sapporo Medical University School of Medicine Anzai Medical Co. Ltd.

AIM:To elucidate the correlation between hepatic blood flow and liver function in alcoholic liver cirrhosis(AL-LC).METHODS:The subjects included 35 patients with ALLC(34 men,1 woman;mean age,58.9±10.7 years;median age,61 years;range:37-76 years).All patientswere enrolled in this study after obtaining written informed *** function was measured with tests measuring albumin(Alb),prothrombin time(PT),brain natriuretic peptide(BNP),branched amino acid and tyrosine ratio(BTR),branched chain amino acid(BCAA),tyrosine,ammonia(NH3),cholinesterase(Ch E),immunoreactive insulin(IRI),total bile acid(TBA),and the retention rate of indocyanine green 15 min after administration(ICG R15).Hepatic blood flow,hepatic arterial tissue blood flow(HATBF),portal venous tissue blood flow(PVTBF),and total hepatic tissue blood flow(THTBF)were simultaneously calculated using xenon computed ***:PVTBF,HATBF and THTBF were 30.2±10.4,20.0±10.7,and 50.3±14.9 m L/100 m L/min,***,PT,BNP,BTR,BCAA,tyrosine,NH3,Ch E,IRI,TBA,and ICG R15 were 3.50±0.50 g/d L,72.0%±11.5%,63.2±56.7 pg/m L,4.06±1.24,437.5±89.4μmol/L,117.7±32.8μmol/L,59.4±22.7μg/d L,161.0±70.8 IU/L,12.8±5.0μg/d L,68.0±51.8μmol/L,and 28.6%±13.5%,*** showed a significant negative correlation with ICG R15(r=-0.468,P<0.01).No significant correlation was seen between ICG 15R,HATBF and *** was a significant correlation between PVTBF and Alb(r=0.2499,P<0.05),and NH3 tended to have an inverse correlation with PVTBF(r=-0.2428,P=0.0894).There were also many significant correlations between ICG R15 and liver function parameters,including Alb,NH3,PT,BNP,TBA,BCAA,and tyrosine(r=-0.2156,P<0.05;r=0.4318,P<0.01;r=0.4140,P<0.01;r=0.3610,P<0.05;r=0.5085,P<0.001;r=0.4496,P<0.01;and r=0.4740,P<0.05,respectively).CONCLUSION:Our investigation showed that there is a close correlation between liver function and hepatic blood flow.

关键词： Alcoholic liver cirrhosis Hepatic tissue blood flo

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Thrombomodulin in the management of acute cholangitisinduced disseminated intravascular coagulation

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World Journal of Gastroenterology 2015年第2期21卷 533-540页

作者： Keigo Suetani chiaki okuse Kazunari Nakahara Yosuke Michikawa Yohei Noguchi Midori Suzuki Ryo Morita Nozomi Sato Masaki Kato Fumio Itoh Department of Gastroenterology and Hepatology St.Marianna UniversitySchool of MedicineKawasaki 216-8511Japan

AIM: To evaluate the need for thrombomodulin(r TM) therapy for disseminated intravascular coagulation(DIC) in patients with acute cholangitis(AC)-induced DIC. METHODS: Sixty-six patients who were diagnosedwith AC-induced DIC and who were treated at our hospital were enrolled in this study. The diagnoses of AC and DIC were made based on the 2013 Tokyo Guidelines and the DIC diagnostic criteria as defined by the Japanese Association for Acute Medicine, respectively. Thirty consecutive patients who were treated with r TM between April 2010 and September 2013(r TM group) were compared to 36 patients who were treated without r TM(before the introduction of r TM therapy at our hospital) between January 2005 and January 2010(control group). The two groups were compared in terms of patient characteristics at the time of DIC diagnosis(including age, sex, primary disease, severity of cholangitis, DIC score, biliary drainage, and anti-DIC drugs), the DIC resolution rate, DIC score, the systemic inflammatory response syndrome(SIRS) score, hematological values, and outcomes. Using logistic regression analysis based on multivariate analyses, we also examined factors that contributed to persistent DIC. RESULTS: There were no differences between the r TM group and the control group in terms of the patients' backgrounds other than administration. DIC resolution rates on day 9 were higher in the r TM group than in the control group(83.3% vs 52.8%, P < 0.01). The mean DIC scores on day 7 were lower in the r TM group than in the control group(2.1 ± 2.1 vs 3.5 ± 2.3, P = 0.02). The mean SIRS scores on day 3 were significantly lower in the r TM group than in the control group(1.1 ± 1.1 vs 1.8 ± 1.1, P = 0.03). Mortality on day 28 was 13.3% in the r TM group and 27.8% in the control group; these rates were not significantly different(P = 0.26). Multivariate analysis identified only the absence of biliary drainage as significantly associated with persistent DIC(P < 0.01, OR = 12, 95%CI: 2.

关键词： Disseminated intravascular coagulation Acute chola

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Obstructive jaundice caused by secondary pancreatic tumor from malignant solitary fibrous tumor of pleura:A case report

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World Journal of Gastroenterology 2006年第30期12卷 4922-4926页

作者： Norie Yamada chiaki okuse Masahito Nomoto Mayu Orita Yoshiki Katakura Toshiya Ishii Takuo Shinmyo Hiroaki Osada Ichiro Maeda Hiroshi Yotsuyanagi Michihiro Suzuki Fumio Itoh Division of Gastroenterology and Hepatology Department of Internal Medicine St. Marianna University School of Medicine 2-16-1 Sugao Miyamae-ku Kawasaki 216-8511 Japan Department of Chest Surgery St. Marianna University School of Medicine 2-16-1 Sugao Miyamae-ku Kawasaki 216-8511 Japan Department of Diagnostic Pathology St. Marianna University School of Medicine 2-16-1 Sugao Miyamae-ku Kawasaki 216-8511 Japan Division of Infectious Diseases Department of Internal Medicine University of Tokyo 7-3-1 Hongo Bunkyo-ku Tokyo 113-0033 Japan

对胸膜的恶意的独居的含纤维的肿瘤的手术后的双边的多重肺转移的全身的化疗上的一个 77 岁的人受不了瘙痒和黄疸。血检查显示出肝胆管酶的提高的层次。腹的计算断层摄影术在胰腺的头与外部改进显示出一个肿瘤，与 intra 肝、额外肝的... 详细信息

对胸膜的恶意的独居的含纤维的肿瘤的手术后的双边的多重肺转移的全身的化疗上的一个 77 岁的人受不了瘙痒和黄疸。血检查显示出肝胆管酶的提高的层次。腹的计算断层摄影术在胰腺的头与外部改进显示出一个肿瘤，与 intra 肝、额外肝的胆汁管的膨胀伴随了。他作为把妨碍的黄疸被一个胰腺的头肿瘤引起了被诊断。胰腺的头肿瘤大概作为胸膜的恶意的独居的含纤维的肿瘤的转移被诊断，因为腹的 CT 上的胰腺的头肿瘤上的调查结果类似于胸膜的恶意的独居的含纤维的肿瘤的主要的肺损害上的那些。胰腺的肿瘤在胆总管的劣等的部分在金属性的斯滕特氏印模膏的培植以后很快成长了。病人死于肺的癌性淋巴管炎。尸体揭示了从胰腺的头传播了到肝的核的一个肿瘤。用显微镜，和骨胶原免职展出原子 atypicality 或分割的塑造锭子的房间被观察。Immunohistochemically 胰腺的头肿瘤房间为 alpha 光滑的肌肉肌动朊(alpha-SMA ) 或 CD117 染色是否定的，但是为 vimentin， CD34 和 CD99 积极。这些调查结果与胸膜的恶意的独居的含纤维的肿瘤上的那些一致。我们报导一个第二等的胰腺的肿瘤从胸膜的恶意的独居的含纤维的肿瘤引起的妨碍的黄疸的第一个案例。

关键词：阻塞性黄疸胰腺肿瘤胸膜癌病例报告

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Enteral metallic stenting by balloon enteroscopy for obstruction of surgically reconstructed intestine

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World Journal of Gastroenterology 2015年第24期21卷 7589-7593页

作者： Kazunari Nakahara chiaki okuse Nobuyuki Matsumoto Keigo Suetani Ryo Morita Yosuke Michikawa Shun-ichiro Ozawa Kosuke Hosoya Shinjiro Kobayashi Takehito Otsubo Fumio Itoh Department of Gastroenterology and Hepatology St. Marianna University School of Medicine Department of Gastroenterogical and General Surgery St. Marianna University School of Medicine

We present three cases of self-expandable metallic stent(SEMS) placement using a balloon enteroscope(BE) and its overtube(OT) for malignant obstruction of surgically reconstructed intestine. A BE is effective for the insertion of an endoscope into the deep bowel. However, SEMS placement is impossible through the working channel, because the working channel of BE is too small and too long for the stent device. Therefore, we used a technique in which the BE is inserted as far as the stenotic area; thereafter, the BE is removed, leaving only the OT, and then the stent is placed by inserting the stent device through the OT. In the present three cases, a modification of this technique resulted in the successful placement of the SEMS for obstruction of surgically reconstructed intestine, and the procedures were performed without serious complications. We consider that the present procedure is extremely effective as a palliative treatment for distal bowel stenosis, such as in the surgically reconstructed intestine.

关键词： Enteral stent Gastrointestinal obstruction Balloon enteroscopy Overtube Self-expandable metallicstent

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Acute hepatitis B of genotype H resulting in persistent infection

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World Journal of Gastroenterology 2014年第11期20卷 3044-3049页

作者： Norie Yamada Ryuta Shigefuku Ryuichi Sugiyama Minoru Kobayashi Hiroki Ikeda Hideaki Takahashi chiaki okuse Michihiro Suzuki Fumio Itoh Hiroshi Yotsuyanagi Kiyomi Yasuda Kyoji Moriya Kazuhiko Koike Takaji Wakita Takanobu Kato Department of Virology Ⅱ National Institute of Infectious DiseasesShinjyuku-KuTokyo 162-8640Japan Department of Internal Medicine Center for Liver DiseasesKiyokawa HospitalSuginamiTokyo 166-0004Japan Division of Gastroenterology and Hepatology Department of Internal MedicineSt. Marianna University School of MedicineKanagawa 216-8511Japan Department of Infectious Diseases Graduate School of MedicineThe University of TokyoTokyo 113-8655Japan Department of Infection Control and Prevention Graduate School of MedicineThe University of TokyoTokyo 113-8655Japan Department of Gastroenterology Graduate School of MedicineThe University of TokyoTokyo 113-8655Japan

A 47-year-old man presented with general fatigue and dark *** laboratory data showed increased levels of hepatic *** patient was positive for hepatitis B virus(HBV)markers and negative for antihuman immunodeficiency *** HBV-DNA titer was set to 7.7 log copies/*** patient was diagnosed with acute hepatitis *** HBV infection route was *** serum levels of hepatic transaminases decreased to normal ranges without any treatment,but the HBVDNA status was maintained for at least 26 mo,indicating the presence of persistent *** isolated HBV from the acute-phase serum and determined the genome sequence.A phylogenetic analysis revealed that the isolated HBV was genotype *** this patient,the elevated peak level of HBV-DNA and the risk alleles at human genome single nucleotide polymorphisms s3077and rs9277535 in the human leukocyte antigen-DP locus were considered to be risk factors for chronic *** case suggests that there is a risk of persistent infection by HBV genotype H following acute hepatitis;further cases of HBV genotype H infection must be identified and ***,the complete determination of the HBV genotype may be essential during routine clinical care of acute hepatitis B outpatients.

关键词： Acute hepatitis Chronic hepatitis Genotyping Hepat

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