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

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 C. MEtHODS： 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 low-dose ribavirin （10 mg（kg·d）） additionally. 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 3 showed 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 achieved. CONCLUSION： In chronic HCV-infected patients with genotype 2 or 3, a SVr can be expe

关键词： Chronic hepatitis C virus infection Genotype 2 and 3 Alpha interferon Daily dose interferon therapy

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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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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) *** liver transplantation(Ltx),steroids are commonly used for immunosuppression and acute rejection is usually treated by high steroid *** can worsen the outcome of recurrent HCV ***, we evaluated the outcome of HCV infected liver recipients receiving initial steroid-free immunosuppression. MEtHODS:thirty patients undergoing Ltx received initial steroid-free *** for Ltx included 7 patients with HCV related *** immunosuppression consisted of tacrolimus 2×0.05mg/kg.d po and mycophenolate mofetil(MMf)2×15mg/kg.d *** tacrolimus dosage was adjusted to trough levels in the target range of 10-15μg/L during the first 3 mo and 5-10μg/L *** of acute rejection were verified histologically. rESULtS:Patient and graft survival of 30 patients receiving initial steroid-free immunosuppression was 86% and 83% at 1 and 2 *** rejection occurred in 8/30 patients, including 1 HCV infected *** HCV-infected patients had HCV genotype Ⅱ(lb).HCV seropositivity occurred within the first 4 mo after *** virus load was not remarkably increased during the first year after ***,grafts had no severe recurrent hepatitis. CONCLUSION:from our experience,initial steroid-free immunosuppression does not increase the risk of acute rejection in HCV infected liver ***,none of the HCV infected patients developed serious chronic liver *** suggests that it may be beneficial to avoid steroids in this particular group of patients after Ltx.

关键词： Liver transplantation Adult Drug therapy, Combination female Hepatitis C Humans Immunosuppressive Agents Liver Cirrhosis Male Middle Aged Mycophenolic Acid derivatives Postoperative Care tacrolimus

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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： Living donor liver transplantation Donors biliary tree Endoscopic retrograde cholangiography Magnetic resonance cholangiography

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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 serum and PBMC preparations from 15 patients with chronic HCV infection before, during and after an IfN-alpha therapy using a nested rt/PCr technique. In a second approach, PBMC from healthy donors were incubated in HCV positive plasma. rESULtS: In the IfN-alpha responding patients,HCV-rNA disappeared first from total rNA preparations of PBMC and then from serum. In contrast, in relapsing patients, HCV-rNA reappeared first in serum and then in PBMC. A quantitative analysis of the HCV-rNA concentration in serum was performed before and after transition from detectable to non detectable HCV-rNA in PBMC-rNA and vice versa. When HCV-rNA was detectable in PBMC preparations, 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 PBMC from healthy donors with several dilutions of HCV positive plasma for two hours showed a concentration dependent PCr positivity for HCV-rNA in reisolated PBMC. CONCLUSION: 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 PBMC preparations of chronically infected patients.

关键词： Adult Aged Antiviral Agents female Hepacivirus Hepatitis C, Chronic Humans Interferon-alpha Leukocytes, Mononuclear Male Middle Aged rNA, Viral research Support, Non-U.S. Gov't reverse transcriptase Polymerase Chain reaction Viral Load Virus replication

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Controlled and reversible induction of differentiation and activation of adult human hepatocytes by a biphasic culture technique

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World Journal of Gastroenterology 2005年第14期11卷 2080-2087页

作者： Marcus K.H. Auth Kim A. Boost Kerstin Leckel Wolf-Dietrich Beecken tobias Engl Dietger Jonas Elsie Oppermann Philip Hilgard Bernd H. Markus Wolf-Otto Bechstein roman A. Blaheta universit(a|¨)ts-Kinderklinik Essen abteilung für Allgemeine P(a|¨)diatrie Germany Zentrum der An(a|¨)sthesiologie und Wiederbelebung Johann Wolfgang Goethe-universit(a|¨)t Frankfurt am MainGermany Klinik für Allgemein-und Gef(a|¨)βchirurgie Germany Klinik für Urologie und Kinderurologie Zentrum der Chirurgie Johann Wolfgang Goethe-Universit(a|¨)tFrankfurt am MainGermany Klinik für Allgemein- und Gef(a|¨)βchirurgie Germany universit(a|¨)tsklinikum Essen abteilung für gastroenterologie und Hepatologie Germany Klinik für Allgemein- und Viszeralchirurgie St(a|¨)dt. Klinikum Kemperhof KoblenzGermany

AIM:Clinical application of human hepatocytes (HC) is hampered by the progressive loss of growth and differentiation in vitro. the object of the study was to evaluate the effect of a biphasic culture technique on expression and activation of growth factor receptors and differentiation of human adult HC. MEtHODS: Isolated HC were sequentially cultured in a hormone enriched differentiation medium (DM) containing nicotinamide, insulin, transferrin, selenium, and dexame-thasone or activation medium (AM) containing hepatocyte growth factor (HGf), epidermal growth factor (EGf), and granulocyte-macrophage colony-stimulating factor (GMCSf). Expression, distribution and activation of the HC receptors (MEt and EGfr) and the pattern of characteristic cytokeratin (CK) filaments were measured by fluorometry, confocal microscopy and Western blotting. rESULtS: In the biphasic culture system, HC underwent repeated cycles of activation (characterized by expression and activation of growth factor receptors) and re-differentiation (illustrated by distribution of typical filaments CK-18 but low or absent expression of CK-19). In AM increased expression of MEt and EGfr was associated with receptor translocation into the cytoplasm and induction of atypical CK-19. In DM low expression of MEt and EGfr was localized on the cell membrane and CK-19 was reduced. receptor phosphorylation required embedding of HC in collagen type I gel. CONCLUSION: Control and reversible modulation of growth factor receptor activation of mature human HC can be accomplished in vitro, when defined signals from the extracellular matrix and sequential growth stimuli are provided. the biphasic technique helps overcome dedifferentiation, which occurs during continuous stimulation by means of growth factors.

关键词： Human hepatocytes Differentiation Hepatocyte growth factor Epidermal growth factor HGf receptor EGf receptor Cytokeratin Collagen gel

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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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Managementofearlyasymptomaticgastrointestinalstromaltumorsofthe stomach

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World Journal of Gastrointestinal Endoscopy 2014年第7期6卷 266-271页

作者： Scherübl H faiss S Knoefel Wt Wardelmann E Hans Scherübl Klinik für Innere Medizin II Gastroenterologie GI Onkologie und Infektiologie Vivantes Klinikum Am Urban 10967 Berlin GermanySiegbert Faiss III. Med. Abteilung Asklepios Klinik Barmbek 22291 Hamburg GermanyWolfram-Trudo Knoefel Klinik für Allgemein- Viszeral- und Kinderchirurgie Universit?tsklinikum 40225 Düsseldorf GermanyEva Wardelmann Gerhard-Domagk-Institut für Pathologie Universit?tsklinikum Münster 48149 Münster Germany

Gastrointestinal stromal tumors(GISt) are the most common mesenchymal tumors of the digestive tract. Approximately two thirds of clinically manifest tumors occur in the stomach, nearly one third in the small bowel, and the rest in the colorectal region with a few cas-es in the esophagus. GISt originate within the smooth muscle layer in the wall of the tubular gastrointestinal tract and grow mostly toward the serosa, far less often toward the mucosa. In the latter case, ulceration may develop and can cause gastrointestinal bleeding as the cardinal symptom. However, most GISt of the stomach are asymptomatic. they are increasingly detected incidentally as small intramural or submucosal tumors during endoscopy and particularly during endoscopic ultra-sound. Epidemiological and molecular genetic findings suggest that early asymptomatic GISt of the stomach(f-limiting tumorigenesis. thus, early(tomatic gastric GISt(synonym: micro-GISt) are found in 20%-30% of the elderly. the mostlyelderly people with early gastric GISt have an excellent GISt-specific prognosis. Patients with early GISt of the stomach can therefore be managed by endoscopic sur-veillance.

关键词： Mirco-gastrointestinal stromal tumors Gas-trointestinal stromal tumor Gastric Neoplasia Cancer Endoscopy Endoscopic ultrasound

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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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慢性病毒性肝炎的干扰素治疗

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德国医学 1994年第4期11卷 233-234页

作者： C.Niederau t.Heintges 唐振亚 Medizinische Klinik und Poliklinik Abteilung für Gastroenterologie der Heinrieh-Heine-Universitt DüsseldorfGermany 同济医科大学附属同济医院

20%～30%慢性乙型和丙型肝炎患者发展为肝硬化,其发生肝癌的危险性比一般人群增加一百多倍。慢性乙型肝炎的预后取决于血清学检测结果和肝炎的活动度。HBeAg 阳性慢性活动性肝炎患者的预后较 HBeAg 阴性慢性迁延性肝炎患者的预后要差。... 详细信息

20%～30%慢性乙型和丙型肝炎患者发展为肝硬化,其发生肝癌的危险性比一般人群增加一百多倍。慢性乙型肝炎的预后取决于血清学检测结果和肝炎的活动度。HBeAg 阳性慢性活动性肝炎患者的预后较 HBeAg 阴性慢性迁延性肝炎患者的预后要差。因此。

关键词：病毒性肝炎干扰素丙型肝炎乙型肝炎治疗

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