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Hepatobiliary & Pancreatic Diseases International 2005年第4期4卷 550-553页

作者： Dao-Zhen Xu, Yao Xie and Zheng-Qin Li Beijing Ditan Hospital, Beijing 100011, china Beijing Ditan Hospital Beijing 100011 China. xudzh@***

BAcKGROUND: The resolution of hepatitis c, evidenced by normalization of liver function and disappearance of hepatitis c virus RNA from serum as determined by conventional laboratory assays, reflects virus eradication. But in interferon treated patients the HcV RNA in serum sometimes could not show the virus in cells. Such factors as virus genotype, HcV RNA contents in serum, HcV specific cellular immunities after treatment were reported to predict the response to interferon therapy. In most patients, HcV RNA could detect the virus in peripheral blood mononucle-ar cell. The aim of this study was to investigate the predictive value of HcV RNA in PBMc of patients with chronic hepatitis c after interferon treatment. METHODS: Sixteen patients with chronic hepatitis c were treated with interferon for 24 weeks, and they all get complete responses at 12 weeks of treatment. At the end of treatment, the HcV RNA in PBMc and serum were detected by RT-PcR, and after stopping treatment, HcV RNA in serum was monitored continually. RESULTS: In 9 patients who were HcV RNA positive in their PBMc at the end of treatment, 8 showed serum HcV RNA positive after 24 weeks and another 1 after 1 year. In 7 patients with negative HcV RNA in their PBMc, only 2 patients relapsed in serum HcV RNA after 1-year follow-up, and others remained viral response after 3.5 years. cONcLUSION: HcV RNA in PBMc at the end of IFN treatment is a predictor of durable response to antiviral therapy in patients with chronic hepatitis c.

关键词： chronic hepatitis c HcV RNA interferon peripheral blood mononuclear cell

Long-term outcome of chronic hepatitis c patients with sustained virological response to peginterferon plus ribavirin

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World Journal of Gastroenterology 2011年第4期17卷 493-498页

作者： María Trapero-Marugán Jorge Mendoza María chaparro Leticia González-Moreno José Andrés Moreno-Monteagudo María Jesús Borque Ricardo Moreno-Otero Gastroenterology-Hepatology Department University Hospital La Princesa and Princesa Research Institute Autonomous University of Madrid and CIBERehd (Centro de Investigación Biomédica en Red en Enfermedades Hepáticas y Digestivas)

AIM: To assess the clinical, biochemical and virological long-term outcome in chronic hepatitis c (cHc) patients with a sustained virological response (SVR) after peginterferon (PEG-IFN) plus ribavirin combination therapy. METHODS: One hundred and fifty three patients with a SVR after treatment with PEG-IFN plus ribavirin were included in a 5-year follow-up study in a single Spanish center, based on standard clinical practice. clinical anamnesis, biochemical analysis, hepatitis c virus RNA and alpha-fetoprotein measurement, ultrasonography and transient elastography were performed annually. RESULTS: The mean follow-up period of the 153 patients was 76 ± 13 mo after they obtained a SVR. Five patients (3.26%) presented with cirrhosis before treatment and 116 (75.8%) had genotype 1. No patient showed evidence of hepatic decompensation. One patient (0.65%) developed a hepatocellular carcinoma at month 30 after achieving SVR. There were no virological relapses during this follow-up period. Persistently elevated alanine aminotransferase was found in only one patient (0.65%). At the end of the 5-year follow-up, the mean value of transient elastography was 7 ± 4.3 kPa (F1). There were no deaths and no other tumors. cONcLUSION: The long-term outcome of 153 cHc patients with SVR to PEG-IFN plus ribavirin was good. No evidence of a virological relapse was seen. One patient (0.65%) developed a hepatocellular carcinoma.

关键词： chronic hepatitis c Peginterferon Ribavirin Sustained virological response Long-term effects

Effect of Breathwalk on body composition,metabolic and mood state in chronic hepatitis c patients with insulin resistance syndrome

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World Journal of Gastroenterology 2007年第46期13卷 6213-6218页

作者： M Vázquez-Vandyck S Roman JL Vázquez L Huacuja G Khalsa R Troyo-Sanromán A Panduro Molecular Biology in Medicine Civil Hospital of GuadalajaraFray Antonio AlcaldeGuadalaiara JaliscoMéxico Health Sciences University CenterUniversity of GuadalajaraGuadalajara JaliscoMéxico Epidemiology Department Regional General Hospital No.110Mexican Institute of Social Security and Public Health DepartmentUniversity of GuadalajaraGuadalajara JaliscoMéxico chronic Degenerative Diseases Institute Health Sciences University CenterUniversity of GuadalajaraGuadalajara JaliscoMéxico Kundalini Research Institute Beth Israel Deaconess Medical CenterHarvard Medical SchoolBostonMA 02215United States Research Unit Health Sciences University CenterUniversity of GuadalajaraGuadalajara JaliscoMéxico

AIM： To identify the anthropometric, metabolic and mood state in hepatitis c virus （HcV）-infected patients from the west of Mexico and to evaluate the effect of 13reathwalk （13W）, a combination of walking, synchronized breathing and focussed attention, on those patients. METHODS： In an experimental study, 17 patients with serological and molecular diagnosis of HcV, not receiving pharmacological treatment, were studied. One hour sessions of 13W were practiced 3 times at week for six months. Body composition was assessed by electric impedance. Biochemical profiles and insulin resistance （IR） risk was assessed by conventional methods. Mood state was evaluated with specific and open questions at the beginning and at the end of the program. RESULTS： Seventy percent of patients were overweight or obese, and 77% of the patients presented with IR at the beginning of the study. Improvements were observed at the 3^rd mo, and statistically significant differences were recorded at the 6^th mo using the fitness score （76 vs 83, P 〈 0.01）, in alanine aminotransferase （ALT）（106±93 U/L vs 59 ± 32 U/L, P 〈 0.01）, total bilirubin （0.09 ± 1 mg/dL vs 0.62 ± 0.2 mg/dL, P 〈 0.01）, ALT/ AST ratio （1.04 vs 0.70, P 〈 0.01）, triglycerides （165 ± 86 mg/dL vs 124 ± 49 mg/dL, P 〈 0.01） and the IR risk （4.0 vs 2.7）. Most patients （88%） indicated to feel better at the end of BW （P 〈 0.01）.cONcLUSION： Breathwalk has an important effect on body composition, lipid profile and liver enzymes. It is also easy, inexpensive and has a beneficial effect on metabolic and mood state in HcV patients.

关键词： Breathwalk chronic hepatitis c Insulinresistance Obesity Quality of life

Interferon β-1a alone or in combination with ribavirin: A randomized trial to compare efficacy and safety in chronic hepatitis c

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World Journal of Gastroenterology 2005年第29期11卷 4484-4489页

作者： Rinaldo Pellicano Antonio craxì Piero Luigi Almasio Mario Valenza Giovanna Venezia Alfredo Alberti Silvia Boccato Luigi Demelia Orazio Sorbello Antonino Picciotto Francesco Torre Gaetano Ideo carlo cattaneo Mara Berrutti Mario Rizzetto U.O.A.D.U. Gastro-Hepatology S. Giovanni Battista (Molinette) Hospital Turin Italy Venezia Department of Gastroenterology and Hepatology University of Palermo Italy Department of Internal Medicine University of Padua Italy Institute of clinical Medicine University of cagliari Italy Department of Internal Medicine University of Genoa Italy Department of Hepatology San Giuseppe Hospital Milan Italy U.O.A.D.U. Gastro-Hepatoiogy S. Giovanni Battista (Molinette) Hospital Turin Italy

AIM： To compare the efficacy and safety of recombinant human IFN β-la alone or in combination with ribavirin in treatment-naive subjects with chronic hepatitis c. METHODS： Open, randomized trial was performed in 6 Italian tertiary centers： 102 of the 108 patients screened were randomized to receive 6 MIU of recombinant human IFN β-la subcutaneously daily for 24 wk, alone （Group 1, n = 51） or in combination with ribavirin 1 000 to 1 200 mg/d （Group 2, n = 51）. RESULTS： The end-of-treatment virologic response rate was 29.4% in Group 1 and 41.2% in Group 2 （nonsignificant）. Twenty-four weeks after stopping therapy, sustained virologic response rate was 21.6% in Group 1 and 27.4% in Group 2 （non-significant）. All subjects in Group 1 completed treatment, while two subjects in Group 2 stopped therapy due to treatment-related adverse events. cONcLUSION： Recombinant human IFN β-la, alone or in combination with ribavirin, has an excellent safety profile and, may represent an alternative for chronic hepatitis c patients who are unable to tolerate pegylated α-interferon.

关键词： chronic hepatitis c IFN β-1a Ribavirin

correlation of serum leptin levels with anthropometric and metabolic parameters and biochemical liver function in chinese patients with chronic hepatitis c virus infection

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World Journal of Gastroenterology 2005年第22期11卷 3357-3362页

作者： Zheng-WenLiu NiZhang Qun-YingHan Jun-TaoZeng Yong-Liechu Jian-MingQiu Ya-WenWang Lie-TingMa xiao-Qinwang DepartmentofInfectiousDiseases FirstHospitalXi'anJiaotongUniversityXi'an710061ShaanxiProvinceChina centralMedicalLaboratory FirstHospitalXi'anJiaotongUniversityXi'an710061ShaanxiProvinceChina DepartmentofInfectiousDiseases FirstHospitalXi'anJiaotongUniversityXi'an710061ShaanxiProvinceChina

AIM: To determine serum leptin levels and investigate their correlations with anthropometric and metabolic parameters and biochemical liver function in patients with chronic hepatitis c virus (HcV) infection and their potential clinical ***: Forty-two chronic HcV-infected patients without anti-viral treatment were enrolled in this study, 30 patients had chronic hepatitis c, 10 had cirrhosis, and 2 had hepatocellular carcinoma (Hcc). Thirty age- and sex-matched healthy individuals served as controls. Serum leptin levels were determined by ELISA. The biochemical liver function and serum lipids were determined at the same time. The height and body weight of patients and controls were measured, and body mass index (BMI) and body fat were calculated simultaneously. The correlations of serum leptin levels with anthropometric and metabolic parameters and biochemical liver function were assessed ***: The mean of serum leptin levels in patients with chronic hepatitis c, HcV-associated cirrhosis, HcVassociated Hcc and control groups was (6.13±3.94),(5.25±4.21), (4.17±0.28), and (3.59±3.44) ng/mL, respectively. The serum leptin level in patients with chronic hepatitis c was significantly higher than that in controls. The serum leptin levels between cirrhotic patients and controls and between male and female cirrhotic patients had no significant difference. Serum leptin levels were positively-correlated with body fat, BMI, and apolipoprotein B (Apo B) in patients with chronic HcV infection. The serum alanine aminotransferase (ALT) levels were closelycorrelated with BMI in patients with chronic hepatitis c. cONcLUSION: HcV infection interferes with fat and lipid metabolism in patients with chronic HcV infection and leptin may play a role in hepatosteatosis.

关键词： chronic hepatitis c Leptin Anthropometric parameter Lipid metabolism

Randomized controlled trial of consensus interferon with or without zinc for chronic hepatitis c patients with genotype 2

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World Journal of Gastroenterology 2006年第6期12卷 945-950页

作者： HideyukiSuzuki KenSato HitoshiTakagi DaisukeKanda NaondoSohara SatoruKakizaki HiroakiNakajima ToshiyukiOtsuka TakeakiNagamine MasatomoMori Department of Medicine and Molecular Science Gunma University Graduate School of Medicine 3-39-15 ShowaMaebashiGunma 371-8511Japan

AIM： The beneficial effect of zinc supplementation on the efficacy of interferon as a treatment for chronic hepatitis c had been demonstrated in hepatitis virus genotype lb of high viral load. This study focused on patients with genotype 2, which is more sensitive to interferon than genotype lb, and used consensus interferon （cIFN） with or without zinc. METHODS： We randomized 83 patients with chronic hepatitis c to cIFN at 18 MIU six times/wk for 4 wk, followed by cIFN at 18 MIU six times/wk for another 20 wk, in combination with polaprezinc 300 mg （regimen A, n = 41） or as monotherapy （regimen B, n = 42）. Thirtyone patients in regimen A and 33 patients in regimen B completed the clinical trial; the remaining patients withdrew because of side effects or a transfer to another hospital. RESULTS： Sustained biochemical response, defined as a normal aminotransferase level at the end of the 6-too post-treatment observation, was 68% and 69%, and sustained virological response, defined as undetectable HcV-RNA at the end of the 6-too post-treatment observation, was 54% and 67% for regimens A and B, respectively. cONcLUSION： cIFN treatment combined with zinc did not enhance the effect of cIFN as shown by biochemical, virological criteria. No side effects related to polaprezinc were noted.

关键词： Randomized controlled trial consensus interferon Zinc chronic hepatitis c Genotype 2

Pegylated interferon plus ribavirin for genotype Ib chronic hepatitis c in Japan

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World Journal of Gastroenterology 2008年第47期14卷 7225-7230页

作者： Takayuki Kogure Yoshiyuki Ueno Koji Fukushima Futoshi Nagasaki Yasuteru Kondo Jun Inoue Yasunori Matsuda Eiji Kakazu Takeshi Yamamoto Hiroyoshi Onodera Yutaka Miyazaki Hiromasa Okamoto Takehiro Akahane Tomoo Kobayashi Yutaka Mano Takao Iwasaki Motoyasu Ishii Tooru Shimosegawa Division of Gastroenterology Tohoku University HospitalSendai 980-8574Japan Department of Gastroenterology Tohoku Rosai HospitalSendai 980-8574Japan Department of Gastroenterology Miyagi Cancer CenterNatori 981-1293Japan Department of Internal Medicine Tohoku Kosai HospitalSendai 980-0803Japan Department of Internal Medicine Shirakawa Kosei General HospitalShirakawa 961-0005Japan Department of Gastroenterology Ishinomaki Municipal HospitalIshinomaki 986-0835Japan Department of Gastroenterology Osaki Citizen HospitalFurukawa 989-6183Japan Department of Gastroenterology Sendai Medical CenterSendai 983-8520Japan Department of Internal Medicine Miyagi Social Insurance HospitalSendai 981-1103Japan

AIM:To evaluate the efficacy of pegylated interferon α-2b(peg-IFNα-2b) plus ribavirin(RBV) therapy in Japanese patients with chronic hepatitis c(cHc) genotype Ib and a high viral ***:One hundred and twenty cHc patients(58.3% male) who received peg-IFNα-2b plus RBV therapy for 48 wk were *** virological response(SVR) and clinical parameters were ***:One hundred(83.3%) of 120 patients completed 48 wk of treatment.53 patients(44.3%) achieved *** virological response(EVR) and end of treatment response(ETR) rates were 50% and 73.3%,*** clinical parameters(SVR vs non-SVR) associated with SVR,ALT(108.4 IU/L vs 74.5 IU/L,P = 0.063),EVR(76.4% vs 16.4%,P ce to peg-IFN(≥ 80% of planned dose) at week 12(48.1% vs 13.6%,P = 0.00036),adherence to peg-IFN at week 48(54.7% vs 16.2%,P ce to RBV at week 48(56.1% vs 32.1%,P = 0.0102) were determined using univariate analysis,and EVR and adherence to peg-IFN at week 48 were determined using multivariate *** the older patient group(> 56 years),SVR in females was significantly lower than that in males(17% vs 50%,P = 0.0262).EVR and adherence to Peg-IFN were demonstrated to be the main factors associated with ***:Peg-IFNα-2b plus RBV combination therapy demonstrated good tolerability in Japanese patients with cHc and resulted in a SVR rate of 44.3%.Treatment of elderly female patients is still challenging and maintenance of adherence to peg-IFNα-2b is important in improving the SVR rate.

关键词： chronic hepatitis c Pegylated interferon Ribavirin

“Liverscore”is predictive of both liver fi brosis and activity in chronic hepatitis c

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World Journal of Gastroenterology 2011年第41期17卷 4607-4613页

作者： Shoukat Ali Arain Qamar Jamal Amir Omair Department of Pathology Ziauddin University4/BShara-e-GhalibBlock 6 Clifton college of Medicine Alfaisal University Department of Medical Education King Saud bin Abdulaziz University for Health Sciences

AIM:To formulate a noninvasive index predictive of se-verity of liver f ibrosis and activity in chronic hepatitis ***:This cross sectional study was conducted on polymerase chain reaction positive,treatment nave *** was staged on a f ive point scale from F0-F4 and activity was graded on a four point scale from A0-A3,according to the METAVIR *** were divided into two overall severity groups,minimal disease(cant disease(≥ F2 or ≥ A2).Eleven markers were measured in ***-tistically,the primary outcome variable was identif ica-tion of minimal and signif icant overall *** were formulated using β regression values of different combinations of nine statistically significant *** performance of these indices was assessed through receiver-operating characteristic curve ***:A total of 98 patients were included and of these 46 had an overall clinically significant *** f inal six marker index,Liverscore for hepatitis c,consisted of age,alanine transaminase,gamma-gluta-myl transpeptidase,apolipoprotein A-1,alpha-2 macro-globulin and hyaluronic *** area under the curve was found to be *** a 0-1 scale,negative predic-tive value at a cutoff level of ≤ 0.40 was 83%,while positive predictive value at ≥ 0.80 remained 89%.Al-together,61% of the patients had these discriminative ***:This index is discriminative of minimal and significant overall liver disease in a majority of chronic hepatitis c patients and can help in clinical de-cision making.

关键词： chronic hepatitis c Staging and grading Liver fibrosis and activity, Noninvasive assessment Liverscore

Interferon augments the anti-fibrotic activity of an angiotensin-converting enzyme inhibitor in patients with refractory chronic hepatitis c

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World Journal of Gastroenterology 2006年第42期12卷 6786-6791页

作者： Hitoshi Yoshiji Ryuichi Noguchi Hideyuki Kojima Yasuhide Ikenaka Mitsuteru Kitade Kosuke Kaji Masahito Uemura Junichi Yamao Masao Fujimoto Masaharu Yamazaki Masahisa Toyohara Akira Mitoro Hiroshi Fukui Third Department of Internal Medicine Nara Medical University Nara Japan

AIM： To evaluate the effect of combination treatment with the interferon （IFN） and angiotensin-converting enzyme inhibitor （AcE-Ⅰ） on several fibrotic indices in patients with refractory chronic hepatitis c （cHc）. METHODS： Perindopril （an AcE-Ⅰ; 4 mg/d） and/or natural IFN （3 MU/L; 3 times a week） were administered for 12 mo to refractory cHc patients, and several indices of serum fibrosis markers were analyzed. RESULTS： AcE-Ⅰ decreased the serum fibrosis markers, whereas single treatment with IFN did not exert these inhibitory effects. However, IFN significantly augmented the effects of AcE-Ⅰ, and the combination treatment exerted the most potent inhibitory effects. The serum levels of alanine transaminase and HcV-RNA were not significantly different between the groups, whereas the plasma level of transforming growth factor-β was significantly attenuated almost in parallel with suppression of the serum fibrosis markers. cONcLUSION： The combination therapy of an AcE-Ⅰand IFN may have a diverse effect on disease progression in patients with cHc refractory to IFN therapy through its anti-fibrotic effect.

关键词： Interferon Angiotensin-converting enzyme inhibitor Liver fibrosis chronic hepatitis c Transforming growth factor-β

Expression of bcl-2 protein in chronic hepatitis c:Effect of interferon alpha 2b with ribavirin therapy

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World Journal of Gastroenterology 2005年第19期11卷 2949-2952页

作者： Panasiuk Anatol Prokopowicz Danuta Dzieciol Janusz Panasiuk Bozena Department of Infectious Diseases Medical University of Bialystok Zurawia Str.1415-540 BialystokPoland Department of Human Anatomy Medical University of Bialystok Zurawia Str.1415-540 BialystokPoland

AIM: Mechanisms responsible for persistence of HcV infection and liver damage in chronic hepatitis c are not clear. Apoptosis is an important form of host immune response against viral infections. Anti-apoptotic protein bcl-2 expression on liver tissue as well as the influence of interferon alpha 2b (IFNa2b) and ribavirin (RBV) were analyzed in patients with chronic hepatitis c. METHODS: In 30 patients with chronic hepatitis c (responders - R and non-responders - NR) treated with IFNα2b+RBV, protein bcl-2 was determined in hepatocytes and in liver associated lymphocytes before and after the treatment. RESULTS: The treatment diminished bcl-2 protein accumulation in liver cells in_patients with hepatitis c (Pcted bcl-2 protein in R in 87±15% and 83±20% of hepatocytes and in 28±18% and 26±10% of liver-associated lymphocytes, respectively. In NR, the values before treatment decreased from 94±32% to 88±21% of hepatocytes and 39±29% to 28±12% of lymphocytes with bcl-2 expression. There was no statistical correlation between bcl-2 expression on liver tissue with inflammatory activity, fibrosis and biochemical parameters before and after the treatment. cONcLUSION: IFNα2b+RBV treatment, by bcl-2 protein expression decrease, enables apoptosis of hepatocytes and associated liver lymphocytes, which in turn eliminate hepatitis c viruses.

关键词： Bcl-2 chronic hepatitis c Interferon alpha Ribavirin hepatitis c virus