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Combination of "low-dose" ribavirin and interferon alfa-2a therapy followed by interferon alfa-2a monotherapy in chronic HCV-infected nonresponders and relapsers after interferon alfa-2a monotherapy

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World Journal of Gastroenterology 2001年第2期7卷 222-227页

作者： Perdita Wietzke-Braun Volker Meier Felix Braun Giuliano Ramadori abteilung für gastroenterologie und Endokrinologie Georg-August-UniversitatGottingenGermany

AIM To report on the efficacy, safety and tolerability of interferon alfa-2a combined with a "low dose" of ribavirin for relapsers and non responders to alpha interferon *** Thirty-four chronic hepatitis C virus-infected non-responders to interferon alfa2a monotherapy (a course of at least 3 months treatment) and 13 relapsers to interferon alfa 2a monotherapy (a dose of 3 to 6 million units three times per week for at least 20 weeks but not more than 18 months) were treated with the same dose of interferon alfa-2a used before (3 to 6 million units three times per week) and ribavirin (10 mg/ kg daily) for 6 months. In complete responders, interferon alfa-2a was administered for further 6 months at the same dose used before as *** Seven (20.6%) of 34 non-responders stopped the combined therapy due to adverse events, including two patients with histological and clinical Child A cirrhosis. In 17/27 (63%)non-responders, the combined therapy was stopped after three months because of non-response. Ten of the 27 non-responders completed the 1;2-month treatment course. At a mean follow up of 28 months (16- 37 months)after the treatment, 4/10 (15%) previous non-responders still remained complete responders,All 13 previous relapsers completed the 12-month treatment course. At a mean follow up of 22months (9 - 36 months) after treatment, 6/13(46%) the previous relapsers were stillsustained complete *** Our treatment schedule of the combined therapy for 6 months of interferon alfa2a with a low dose of ribavirin (10 mg/kg/day)followed by 6 months of interferon alfa-2amonotherapy is able to induce a sustainedcomplete response rate in 15% of non-responders and 46% of relapsers with chronic hepatitis C virus-related liver diseases comparable to those obtained with the standarddoses of ribavirin 1000 - 1200 mg/*** prospective controlled trials using lower total amounts of ribavirin in combination with interferon should be p

关键词： hepatitis C, chronic/drug therapy interferon alpha-2a/therapeutic use interferon alpha-2a/administration & dosage ribavirin/administration & dosage ribavirin/therapeutic use

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Treatment of genotype 2 and 3 chronic hepatitis C virus-infected patients

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World Journal of Gastroenterology 2005年第39期11卷 6188-6192页

作者： Perdita Wietzke-Braun Volker Meier Katrin Neubauer-Saile Sabine Mihm Giuliano Ramadori abteilung für gastroenterologie und Endokrinologie Georg-August-Universitt Gttingen Germany

AIM: Before pegylated interferon alpha (IFN) was introduced for the therapy of chronic hepatitis C virus(HCV)-induced hepatitis, conventional thrice weekly IFN therapy was supplemented by ribavirin. Also, at that time,higher and more frequent doses of IFN were expected to be more effective than the standard regimen of 3 MU thrice weekly. As ribavirin significantly increases side effects and negatively influences the quality of life particularly in young patients, we started a prospective non-randomized study with a daily IFN-2a monotherapy as an initial treatment for chronic hepatitis ***: Forty-six consecutive chronic HCV-infected patients received 3 MU IFN-2a per day as an initial treatment. Patients with genotype 2 or 3 (n = 12) were treated for 24 wk, and patients with genotypes other than 2 or 3 (n = 34) for 48 wk. Treatment outcome was followed up for 48 wk after the end of treatment (EOT).Virological response was defined as the absence of detectable serum HCV-RNA. Patients without virological response at 12 wk after the start of treatment received RESULTS: During treatment, three genotype 3 patients were excluded from the study due to incompliance. The remaining patients (n = 9) infected with genotype 2 or 3showed an initial virological response rate of 100%. Six patients (66.7%) were still found to be virus-free at the end of follow-up period. In these patients, initial virological response was evident already after 2 wk of treatment. In contrast, initial virological response occurred first after 4 wk of treatment in the three patients who relapsed(33.3%). In comparison, patients infected with genotypes other than 2 or 3 (n = 34) showed an initial virological response rate of only 23.5% (n = 8), and even in combination with ribavirin a sustained virological response(SVR) rate of only 11.8% (n = 4) could be ***: In chronic HCV-infected patients with genotype 2 or 3, a SVR can be expected after 24 wk of daily dose IFN-2a treatment without

关键词：基因型 2型肝炎 3型肝炎慢性丙型肝炎病毒感染

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HCV-RNA positivity in peripheral blood mononuclear cells of patients with chronic HCV-infection: does it really mean viral replication?

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World Journal of Gastroenterology 2001年第2期7卷 228-234页

作者： Volker Meier Sabine Mihm Perdita Wietzke-Braun Guliano Ramadori Georg-August-Universitat gottingen Zentrum innere medizinAbteilung Für Gastroenterologie Und EndokrinologieRobert-Koch-Straβe 4037075 GottingenGermany

AIM To analyze the association of HCV-RNA with peripheral blood mononuclear cells (PBMC)and to answer the question whether HCV-RNA positivity in PBMC is due to viral replication,METHODS HCV-RNA was monitored in serumand PBMC preparations from 15 patients with chronic HCV infection before, during and after an IFN-α therapy using a nested RT/ PCRtechnique. In a second approach, PBMC from healthy donors were incubated in HCV positive *** In the IFN-α responding patients,HCV-RNA disappeared first from total RNApreparations of PBMC and then from serum. In contrast, in relapsing patients, HCV-RNAreappeared first in serum and then in PBMC. A quantitative analysis of the HCV-RNAconcentration in serum was performed before and after transition from detectable to nondetectable HCV-RNA in PBMC-RNA and vice versa. When HCV-RNA was detectable in PBMCpreparations, the HCV concentration in serum was significantly higher than the serum HCV-RNA concentration when HCV-RNA in PBMC was not detectable. Furthermore, at no time during the observation period was HCV specific RNA observed in PBMC, if HCV-RNA in serum was under the detection limit. Incubation of PBMCfrom healthy donors with several dilutions of HCV positive plasma for two hours showed a concentration-dependent PCR-positivity for HCV-RNA in reisolated *** The detectability of HCV-RNA in total RNA from PBMC seems to depend on the HCV concentration in serum. Contamination or passive adsorption by circulating virus could be the reason for detection of HCV-RNA in PBMCpreparations of chronically infected patients.

关键词： hepatitis C-like viruses hepatitis C, chronic RNA, viral/blood virus replication monocytes interferon alpha/therapeutic use polymerase chain reaction

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Initial steroid-free immunosuppression after liver transplantation in recipients with hepatitis c virus related cirrhosis

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World Journal of Gastroenterology 2004年第15期10卷 2213-2217页

作者： Perdita Wietzke-Braun Felix Braun Burckhart Sattler Giuliano Ramadori Burckhardt Ringe abteilung for gastroenterologie und Endokrinologie Georg-August-Universitt37075 GttingenGermany Georg-August-Universitt 37075 GttingenGermany Zentrum Pathologie Georg-August-Universitt37075 GttingenGermany

AIM: Steroids can increase hepatitis C virus (HCV) replication. After liver transplantation (LTx), steroids are commonly used for immunosuppression and acute rejection is usually treated by high steroid dosages. Steroids can worsen the outcome of recurrent HCV infection. Therefore,we evaluated the outcome of HCV infected liver recipients receiving initial steroid-free ***: Thirty patients undergoing LTx received initial steroid-free immunosuppression. Indication for LTx included 7 patients with HCV related drrhosis. Initial immunosuppression consisted of tacrolimus 2x0.05 mg/kg.d po and mycophenolate mofetil (MMF) 2x15 mg/kg.d po. The tacrolimus dosage wasa djusted to trough levels in the target range of 10-15 μg/Ldudng the first 3 mo and 5-10 μg/L thereafter. Manifestations of acute rejection were verified ***: Patient and graft survival of 30 patients receiving initial steroid-free immunosuppression was 86% and 83% at 1 and 2 years. Acute rejection occurred in 8/30 patients,including 1 HCV infected recipient. All HCV-infected patients had HCV genotype II (lb). HCV seropositivity occurred within the first 4 mo after LTx. The virus load was not remarkably increased during the first year after LTx. Histologically, grafts had no severe recurrent ***: From our experience, initial steroid-free immunosuppression does not increase the risk of acute rejection in HCV infected liver recipients. Furthermore, none of the HCV infected patients developed serious chronic liver diseases. It suggests that it may be beneficial to avoid steroids in this particular group of patients after LTx.

关键词：初始的游离类固醇免疫反应肝移植丙型肝炎病毒肝硬化肝脏疾病

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Fontolizumab,人源化抗干扰素γ抗体治疗中重度克罗恩病的临床研究:一项关于剂量升级、安慰剂对照、双盲、药物单剂量应用和多剂量应用的安全性与耐受性的研究

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世界核心医学期刊文摘（胃肠病学分册） 2006年第12期2卷 42-43页

作者： Reinisch W. Hommes D.W. Van Assche G. 王铮 Universitaetsklinik Innere Medizin IV Abteilung Gastroenterologie and HepatologieWaehringer Guertel 18-20A-1090 ViennaAustria Prof.

Introduction:This study was designed to evaluate the safety of fontolizumab,a humanised anti-interferon γ antibody,in patients with moderate to severe Crohn’s disease(CD) .Patients and methods:Forty five patients with a CD activity index(CDAI) of 250-450 were randomised in a double blind,placebo controlled,dose escalating fashion to receive single doses of fontolizumab(0.1,1.0,and 4.0 mg/kg) or *** day 29,patients with clinical response were re-randomised to receive three additional doses of one half their initial fontolizumab dose or placebo at four weekly *** objectives were safety and *** outcomes included assessments of immunogenicity,clinical activity,and potential pharmacodynamic ***:Treatment was generally well *** were slightly more reports of chills,flu-like syndrome,asthenia,nausea,and vomiting in the 1.0 mg and 4.0 mg/kg fontolizumab *** serious adverse events rated as worsening of CD occurred under *** to fontolizumab were confirmed in one *** differences in clinical activity parameters were noted between any of the active treatment groups and placebo,with the placebo group having a particularly favourable outcome(60% response and 40% remission) .By day 29,a more enhanced decrease in median Crohn’s disease endoscopic index of severity(p = 0.02) and serum C reactive protein(p< 0.001) was observed in the 4.0 mg/kg(n = 14) fontolizumab cohort compared with placebo(n = 10) .Pharmacodynamic effects were observed by ***:Fontolizumab was well tolerated with minimal immunogenicity at doses of up to 4.0 mg/kg in patients with CD.A biological activity of fontolizumab is suggested.

关键词：克罗恩病 Fontolizumab 剂量应用干扰素γ 人源化安慰剂对照药效动力学免疫源性免

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Adult-to-adult right lobe living donor liver transplantation:Comparison of endoscopic retrograde cholangiography with standard T2-weighted magnetic resonance cholangiography for evaluation of donor biliary anatomy

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World Journal of Gastroenterology 2006年第36期12卷 5820-5825页

作者： Perdita Wietzke-Braun Felix Braun Dieter Müller Thomas Lorf Burckhardt Ringe Giuliano Ramadori abteilung für gastroenterologie und Endokrinologie Georg-August-Universitt Gttingen Germany Klinik für Allgemeine Chirurgie und Thorax-chirurgie Universitt Schleswig-Holstein Campus Kiel Germany abteilung für Diagnostische Radiologie Georg-August-Universitt Gttingen Germany Klinik für Allgemeine Chirurgie Georg-August-Universitt Gttingen Germany Center for Liver Pancreas and Biliary Disease Drexel University College of Medicine Philadelphia United States

AIM: To compare the value of endoscopic retrograde cholangiography (ERC) and standard T2-weighted magnetic resonance cholangiography (MRC) in the evaluation process as adult-to-adult right lobe living donor liver transplantation (LDLTx) demands a successful outcome, and exact knowledge of the biliary tree is implicated to avoid biliary complications, ***: After starting the LDLTx program, 18 liver transplant candidates were selected for LDLTx by a stepwise evaluation process. ERC and standard T2-weighted MRC were performed to evaluate the biliary system of the donor liver. The anatomical findings of ERC and MRC mapping were compared using the Ohkubo classification. RESULTS: ERC allowed mapping of the whole biliary system in 15/15 (100%) cases, including 14/15 (93.3%) with biliary variants while routine MRC was only accurate in 2/13 (15.4%) cases. MRC was limited in depicting the biliary system proximal of the hepatic bifurcation. Postoperative biliary complications occurred in 2 donors and 8 recipients. Biliary complications were associated with Ohkubo type C, E or G in 6/8 recipients, and 2/3 recipients with biliary leak received a graft with multiple (≥2) bile ducts. CONCLUSION: Pretransplant ERC is safe and superior over standard MRC for detection of biliary variations that occur with a high frequency. However, precise knowledge of biliary variants did not reduce the incidence of postoperative biliary complications.

关键词：肝移植排斥反应内窥镜胆管造影磁共振成像

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Synthesis　of　Glycoproteins　by　Mucosa　of　Gastric　Antrum　in　Chronic　GastritisB

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Journal of Huazhong University of Science and Technology(Medical Sciences) 1994年第2期14卷 76-76页

作者： TIAN De-an(Department of Gastroenterolegy, Tongji Hospital, Tongji Medical University, WuhanPeter MalfertheinerDepartment of Gastroenterolegy and Metabolism, Internal Medicine H ,Ulm University, Germany) abteilung für gastroenterologie Tongji Klinik Tongji medizinische Universität.

The tissue culture and autoradiography techniques were used to study the effect of infiltration by inflammatory cells and of HP infection on the synthesis of glycoproteins by the gastric antrum. The results showed that in active phase of gastritis, the synthesis of glycoprotein was increased but no correlation between HP infection and synthesis of glycoprotein was noted. The machanism of increased synthesis in chronic gastritis was discussed. It is suggested that the inflammatory cells and media released by them may play important role.

关键词： gastritis glycoproteinshelicobacter pylori

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阻止慢性肝病的进展

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德国医学 1994年第1期11卷 44-46页

作者： K.H.W.Bker M.P.Manns 郭冰 abteilung gastroenterologie und Hepatologie der Medizinischen Hochschule Hannover D-30625 HannoverGermany 同济医科大学附属同济医院

慢性肝病时,'疾病的进展'意味着各个器官的损害通过共同的发展过程,演变为纤维化和肝硬化:如图1所示。细胞坏死是反应链的开始,最终导致肝硬化和肝功能丧失。此过程涉及到肝细胞持续的再生反应,枯否细胞、窦旁贮脂(Ito)细胞以及游走的... 详细信息

慢性肝病时,'疾病的进展'意味着各个器官的损害通过共同的发展过程,演变为纤维化和肝硬化:如图1所示。细胞坏死是反应链的开始,最终导致肝硬化和肝功能丧失。此过程涉及到肝细胞持续的再生反应,枯否细胞、窦旁贮脂(Ito)细胞以及游走的单核细胞也参与其中。肝细胞或者在直接受损后崩解,或者成为淋巴细胞的免疫攻击目标。受损的肝细胞表面 HLA

关键词：肝疾病细胞保护剂抑制纤维化

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肝病患者肿瘤标记物CA19-9与CA125协同升高对重度肝纤维化具有高度特异性

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世界核心医学期刊文摘（胃肠病学分册） 2006年第9期2卷 11-12页

作者： Schniger-Hekele M. Müller C. 王顺涛 Universittsklinik für Innere Medizin IV Klinische Abteilung Gastroenterologie und HepatologieWhringer Gürtel 18-20A-1090 WienAustria Dr.

Increased tumor markers in patients with liver cirrhosis are often considered to be *** use of this unspecific elevation to discriminate minimal fibrosis from severe fibrosis has never been *** aimed to answer the question,Do tumor markers predict severe liver fibrosis? The study group consisted of 125 patients with alcoholic liver disease,hepatitis B,or hepatitis C with available liver *** markers CA 19-9,CA 15-3,and CA 125 were determined using routine laboratory methods and correlated with the extent of liver *** stages 1 and 2 were classified as minimal fibrosis;stages 3 and 4,as severe *** markers CA 19-9,CA 125,and CA 15-3 increased with stage of *** separating patients with mild fibrosis(F1+F2)from patients with severe fibrosis(F3+F4),CA 19-9 had a sensitivity of 70.5%and a specificity of 88.6,CA 125 had 38.1%and 89.7%,and CA 15-3 had 19.0%and 93.0%,*** regression of a combined score of CA19-9 and CA 125 values revealed that an increase of 1 point of the CA 19-9/CA125 score resulted in a 1.6 times increase in likelihood of the presence of severe *** CA 19-9/CA 125 score achieved a similar specificity(97.1%vs.100%)but a higher sensitivity(42.9%vs.33.3%)than the widely used cirrhosis discriminant score of Bonacini.A specificity(98.5%)similar to that of the CA 19-9/CA 125 score was reached by the easier determination of the combined elevation of CA 19-9 and CA 125,which had the best positive predictive value,92.9%.The excellent predictive ability of the combined elevation of CA 19-9 and CA 125 for severe liver fibrosis(F3+F4)was confirmed in an independent group of patients with liver *** combined elevation of CA 19-9 and CA 125 is useful for identifying patients with advanced fibrosis or cirrhosis with high *** without a combined elevation of CA 19-9 and CA 125 still require histological examination to identify severe fibrosis or cirrhosis.

关键词：肿瘤标记物CA19-9 CA125水平肝纤维化程度非特异性重度升高肝病患者 logistic回归分析

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6-硫鸟嘌呤治疗溃疡性或不确定性结肠炎:一项前瞻性、公开标识试验

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世界核心医学期刊文摘（胃肠病学分册） 2006年第5期2卷 56-57页

作者： Teml A. Schwab M. Harrer M. W. Reinisch 赵天智 Universittsklinik für Innere Medizin IV Abteilung für Gastroenterologie und Hepatologie Whringer Gürtel 18-20 AT-1090 Vienna Austria Dr.

Objective. 6-thioguanine (6-TG) has emerged as a pro-mising therapeutic alternative in patients with Crohn’ s disease intolerant or resistant to azathioprine (AZA) and/or 6-mercaptopurine (6-MP). The aim of the present study was to evaluate the safety and efficacy of 6-TG in patients with ulcerative colitis (UC) or indeterminate colitis (IC) intolerant or resistant to AZA/6-MP. Material and methods. Twenty patients with an acute flare, steroid-dependent or steroid-refractory disease attending our outpatient department were included in the study. Measurement of 6-TG nucleotide levels was done to check compliance. Complete, partial and non-response were defined by means of the clinical activity index and the daily steroid demand. Secondary outcome parameters included changes in cumulative steroid doses, C-reactive protein (CRP) levels, and an endoscopic score. Results. Out of 20 patients 4 were excluded owing to incompliance; 2/16 compliant patients (13% ) had to be prematurely withdrawn because of adverse events, which ceased upon drug discontinuation. By per-protocol analysis, 5/14 patients (36% )were complete, 6/14 (43% ) partial and 3/14 (21% ) non-responders. In addition to the reduction of the cumulative steroid dose over 3 months, CRP decreased in the study population and the endoscopic score decreased in treatment responders. Conclusions. Treatment with 6-TG was effective in patients with UC or IC previously intolerant or resistant to AZA/6-MP. Future work is needed to define a subpopulation of patients at low risk for its potential hepatotoxicity, which we assume will benefit from 6-TG.

关键词：溃疡性结肠炎 6-硫鸟嘌呤不确定治疗门诊患者试验标识 6-巯基嘌呤皮质激素 6-TG

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