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Vitamin d in addition to peg-interferon-alpha/ribavirin in chronic hepatitis C virus infection: ANRS-HC25-VITAVIC study

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World Journal of Gastroenterology 2015年第18期21卷 5647-5653页

作者： Benjamin Terrier Nathanael Lapidus Stanislas Pol Lawrence serfaty Vlad Ratziu Tarik Asselah Vincent Thibault Jean-Claude Souberbielle Fabrice Carrat Patrice Cacoub Inflammation-ImmunopathologyBiotherapy department (dHU i2B) Sorbonne Universités department of Internal Medicine Groupe Hospitalier Cochin AP-HP Université Paris Descartes INSERM UMR_S 1136 Institut Pierre Louis d’Epidémiologie et de Santé Publique Sorbonne Universités UPMC Univ Paris 06 UMR_S 1136 Institut Pierre Louis d’ Epidémiologie et de Santé Publique Public Health department Saint-Antoine Hospital department of Hepatology Groupe Hospitalier Cochin AP-HP Université Paris Descartes department of Hepatology H?pital SaintAntoine AP-HP Université Pierre et Marie Curie department of Hepatology Groupe Hospitalier Pitié-Salpetrière AP-HP Université Pierre et Marie Curie department of Hepatology H?pital Beaujon department of Virology Groupe Hospitalier Pitié-Salpetrière AP-HP Université Pierre et Marie Curie Explorations Fonctionnelles H?pital Necker-Enfants Malades AP-HP Université Paris Descartes INSERM UMR_S 959 F-75013 Paris France CNRS UMR 7211 F-75005 Paris France department of Internal Medicine and Clinical Immunology H?pital Pitié-Salpétrière AP-HP 47-83 boulevard de l’H?pital

AIM: To investigate if correction of hypovitaminosis d before initiation of Peg-interferon-alpha/ribavirin(Peg IFN/RBV) therapy could improve the efficacy of Peg IFN/RBV in previously null-responder patients with chronic genotype 1 or 4 hepatitis C virus(HCV) infection.METHOdS:Genotype 1 or 4 HCV-infected patients with null response to previous Peg IFN/RBV treatment and with hypovitaminosis d(d cholecalciferol 100000 IU per week for 4 wk[from week-4(W-4)to W0],followed by 100000 IUper month in combination with Peg IFN/RBV for 12 mo(from W0 to W48).The primary outcome was the rate of early virological response defined by an HCV RNAded,19(59%)and 13(41%)patients were HCV genotype1 and 4,respectively.The median baseline vitamin d level was 15 ng/m L(range:7-28).In modified intention-to-treat analysis,29 patients who received at least one dose of Peg IFN/RBV were included in the analysis.All patients except one normalized their vitamin d serum levels.The rate of early virologic response was 0/29(0%).The rate of HCV RNAddition of vitamin d to Peg IFN/RBV does not improve the rate of early virologic response in previously null-responders with chronic genotype 1or 4 HCV infection.

关键词： Vitamin d Hepatitis C virus Chronic hepatitis Pegylated interferon Ribavirin

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生活方式干预对脂肪储存库动员的影响

中华高血压杂志 2017年第12期25卷 1199-1199页

作者： Gepner Y Shelef I Schwarzfuchs d Zelicha H Tene L Yas-kolka Meir A Tsaban G Cohen N Bril N Rein M serfaty d Kenigsbuch S Komy O Wolak A Chassidim Y Golan R Avni-Hassid H Bilitzky A Sarusi B Goshen E Shemesh E Henkin Y Stumvoll M Blüher M Thiery J Ceglarek U Ru-dich A Stampfer MJ Shai I 黄洁叶鹏

该研究的目的是评估不同的生活方式干预能否对身体的脂质储存部位产生不同的影响。方法：研究者在278名腹型肥胖（209名，占75％）或脂质代谢紊乱的成年人中进行了一项为期18个月的随机对照研究，提供午餐并对用餐情况进行监督。

关键词：生活方式干预储存脂质代谢紊乱脂肪随机对照研究腹型肥胖成年人

原发性胆汁性肝硬化:自身免疫性肝炎重叠综合征的长期预后和疗效

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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 54-55页

作者： Chazouillères O. Wendum d. serfaty L. 赵菊辉(译) 尹勇(校) O. Chazouillères Service d' Hépatologie Hoepital Saint Antoine 184 rue du Faubourg Saint Antoine 75571 Paris Cedex 12 France 不详

Background/Aims: Whether primary biliary cirrhosis (PBC) autoimmune hepatitis (AIH) overlap syndrome requires immunosuppressive therapy in addition to ursodeoxycholic acid (UdCA) is a controversial issue. Methods: Seventeen patients with simultaneous form of strictly defined overlap were followed for 7.5 years. First-line treatment was UdCA alone (UdCA) in 11 and combination of immunosuppressors and UdCA (UdCA+ IS) in 6. Results: Characteristics at presentation were not significantly different between the 2 groups. In the UdCA+ IS group (f-up 7.3 years), biochemical response in terms of AIH features (ALTd IgGd in 4/6 and fibrosis did not progress. In the UdCA group, biochemical response was observed in three patients together with stable or decreased fibrosis (f-up 4.5 years) whereas the eight others were non-responders with increased fibrosis in four (f-up 1.6 years). Seven of these eight patients subsequently received combined therapy for 3 years. Biochemical response was obtained in 6/7 and no further increase of fibrosis was demonstrated. Overall, fibrosis progression in non-cirrhotic patients occurred more frequently under UdCA monotherapy (4/8) than under combined therapy (0/6) (P=0.04). Conclusions: Combination of UdCA and immunosuppressors appears to be the best therapeutic option for strictly defined PBC-AIH overlap syndrome.

关键词：原发性胆汁性肝硬化自身免疫性肝炎重叠综合征长期预后 UdCA治疗肝纤维化程度生化指标改变免疫抑制剂疗效一线治疗

脂肪变性对轻度丙型肝炎患者纤维化进程的影响

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世界核心医学期刊文摘（胃肠病学分册） 2005年第5期1卷 39-40页

作者： Fartoux L. Chazouilléres O. Wendum d. L. serfaty 杨雪娟 Service d’Hépatologie Hpital Saint-Antoine 184 Rue Du Faubourg Saint-Antoine 75571 Paris Cedex 12 France

In patients with mild hepatitis C, the usefulness of antiviral therapy is subject of debate, as a low risk for progression of fibrosis is assumed. Several studies have shown that steatosis is a strong and independent predictor of the severity as well as the progression of fibrosis in chronic hepatitis C. Therefore, this study assessed the impact of steatosis on the progression of fibrosis between paired liver biopsies in untreated patients with mild hepatitis on index biopsy. One hundred thirty-five untreated patients (mean age, 38 years; M/Fsex ratio, 1.43) with one known risk factor of infection (68 transfusions, 67 injecting drug use) had 2 liver biopsies after a median interval of 61 months (18-158). All had METAVIR score of A1F1 or lower at first liver biopsy. Unequivocal progression of fibrosis was considered if patients had a fibrosis score of 3 or 4 at the second liver biopsy. The probability of progression of fibrosis was estimated by using the Kaplan-Meier method. during followup, progression of fibrosis occurred in 21 patients (16%) after a median delay of 65 months. Cumulative probabilities of the progression of fibrosis at 4 and 6 years were 5.2%and 19.8%, respectively. In multivariate analysis, steatosis was the only independent factor predictive of progression of fibrosis (RR, 4.8; CI, 1.3-18.3). Probability of progression of fibrosis was significantly related to the percentage of hepatocytes with steatosis. In conclusion, steatosis is a major determinant of the progression of fibrosis in mild hepatitis C, regardless of the genotype. Our results argue for antiviral treatment in the subgroup of patients with mild hepatitis and steatosis.

关键词：丙型肝炎患者纤维化进程脂肪变性肝纤维化慢性丙型肝炎抗病毒疗法肝活检轻度肝炎纤维化进展肝组织活检

胰岛素抵抗是慢性丙型肝炎患者肝脂肪变性和肝纤维化进展的一个诱发因素

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世界核心医学期刊文摘（胃肠病学分册） 2005年第10期1卷 34-35页

作者： Fartoux L. Poujol-Robert A. Guéchot J. L. serfaty 程欣 Service d'Hépatologie Hopital Saint-Antoine 184 rue du Faubourg Saint-Antoine 75571 Paris Cedex 12 France Dr.

Background: Insulin resistance is a frequent feature of chronic hepatitis C. Whether insulin resistance could be the cause or consequence of steatosis and fibrosis is unknown. The ability of HCV genotype 3 to promote steatosis by itself provides an unique opportunity to answer this question. Aims: The aim of the present study was to assess the relationships between insulin resistance, steatosis, and fibrosis according to genotype in 141 non-diabetic patients with biopsy proven noncirrhotic chronic hepatitis C. Methods: All patients had fasting serum glycaemia and insulinaemia measurements. Insulin resistance was evaluated using the homeostasis model assessment (HOMA IR) method. Liver steatosis was determined according to hepatitis C virus genotype (1 or 3). Logistic regression and multivariate regression analysis were used to identify variables independently associated with insulin resistance, fatty liver, and fibrosis. Results: Although steatosis and fibrosis were more severe in genotype 3 patients, median HOMA IR was significantly higher in patients with genotype 1 related steatosis than in those with genotype 3 related steatosis (2.1 v 1; p = 0.001). Independent risk factors for steatosis were insulin resistance in genotype 1 patients (p = 0.001) and viral load in genotype 3 patients (p = 0.003). Among genotype 1 patients, independent parameters associated with insulin resistance were age (p = 0.04) and steatosis (p = 0.004). Steatosis was associated with more severe fibrosis whatever the genotype (p = 0.002). Among genotype 1 patients, although there was a significant relationship between circulating insulin level and fibrosis stage (p = 0.006), only steatosis and inflammatory score were independently associated with fibrosis. Conclusion: This study shows that insulin resistance is the cause rather than the consequence of steatosis and fibrosis in genotype 1 patients and that increased circulating insulin is a risk factor for fibrosis through insulin resistance induced steatosis.

关键词：慢性丙型肝炎肝脂肪变性胰岛素抵抗肝纤维化血清胰岛素空腹血糖硬化性多变量回归病毒载量独立参数

过去二十年间肝硬化患者静脉曲张出血的生存率提高

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世界核心医学期刊文摘（胃肠病学分册） 2005年第2期1卷 40-40页

作者： Carbonell N. Pauwels A. serfaty L. 樊菁 Hpital Saint-Antoine Service d'Hepatogastronterologie 184 Rue du Faubourg Sainte-Antoine Paris Cedex 12 75571 France

Over the past two decades, new treatment modalities have been introduced for t he management of variceal bleeding. The aim of this retrospective study in a sin gle center was to assess whether these treatments have improved the prognosis fo r cirrhotic patients with variceal bleeding. We reviewed the clinical records of all patients with cirrhosis admitted to our Liver Intensive Care Unit due to va riceal bleeding during the years 1980, 1985, 1990, 1995, and 2000. Whereas ballo on tamponade was still the first-line treatment in 1980, patients treated in 20 00 received a vasoactive agent, an endoscopic treatment, and an antibiotic proph ylaxis in, respectively, 90%, 100%, and 94%of cases. The in-hospital mortali ty rate steadily decreased over the study period: 42.6%, 29.9%, 25%, 16.2%, and 14.5%in 1980, 1985, 1990, 1995, and 2000, respectively (P decreased from 9%in 1980 to 0%in 2000 in Child-Turcotte-Pugh class A patien ts, from 46%to 0%in class B patients, and from 70%to 32%in class C patients. This improved survival was associated with a decrease of rebleeding (from 47%i n 1980 to 13%in 2000) and bacterial infection rates (from 38%to 14%).On multi variable analysis, endoscopic therapy and antibiotic prophylaxis were independen t predictors of survival. In conclusion, in-hospital mortality of patients with cirrhosis and variceal bleeding decreased three fold over the past two decades, in concurrence with an early and combined use of pharmacological and endoscopic therapies and short-term antibiotic prophylaxis.

关键词：静脉曲张出血三腔管再出血发生率内窥镜治疗重症监护临床记录细菌感染早期联合单中心多因素分析

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奥美拉唑致低胃酸对营养素吸收影响的研究

营养学报 2000年第1期22卷 63-67页

作者：郑家驹汤光文 AlastairJ.Turnbull Catherineserfaty-Lacrosniere 江苏省苏州市消化系疾病与营养研究中心苏州市第三人民医院苏州2150081 美国Tufts大学人类营养抗衰老研究中心

目的　以奥美拉唑 ( OM)致低胃酸的人体和动物模型进行有关矿物质和微量元素(钙、磷、镁与锌 )吸收 ,以及血浆β-胡萝卜素水平的研究。方法　分别以 1 .全胃肠道灌洗法 ;2 .血清β-胡萝卜素升高反应 ;3.小肠细菌培养 ;4.65Zn标记试餐法... 详细信息

目的　以奥美拉唑 ( OM)致低胃酸的人体和动物模型进行有关矿物质和微量元素(钙、磷、镁与锌 )吸收 ,以及血浆β-胡萝卜素水平的研究。方法　分别以 1 .全胃肠道灌洗法 ;2 .血清β-胡萝卜素升高反应 ;3.小肠细菌培养 ;4.65Zn标记试餐法进行四项实验。结果　 1 .健康成人口服OM( 4 0 mg,q d× 9d)并不影响食物中上述矿物质的吸收 ;2 .口服 OM( 4 0 mg,bid× 9d) ,人体血清中总 β-胡萝卜素水平升高反应低于对照组 ;3.这一剂量所致低胃酸时 ,小肠细菌呈过度生长 ,但细菌并未与 β-胡萝卜素结合而干扰其肠道吸收 ;4.OM诱发低胃酸并不影响大鼠肠道锌吸收。结论　膳食中的

关键词：奥美拉唑胃酸营养素吸收低胃酸模型

On a Ginzburg-Landau Type Energy with discontinuous Constraint for High Values of Applied Field

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Chinese Annals of Mathematics,Series B 2011年第1期32卷 15-26页

作者： Hassen AYdI Université de Monastir Institut Supérieur d'Informatique de MahdiaKm 4Réjiche5121 MahdiaTunisie

In the presence of applied magnetic fields H such that |lnε|《H《1/ε2,the author evaluates the minimal Ginzburg-Landau energy with discontinuous constraint.Its expression is analogous to the work of Sandier and Serf... 详细信息

关键词：应用间断能源 u型 Landau 磁场类似