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Helicobacter pylori was recognized in 1994 as a class I carcinogen by the International Agency for Research on Cancer (IARC). The prevalence of H. pylori infection varies from 20 to 50% in industrialized countries to over 80% in developing countries. The cagA strains are more virulent than others, being able to induce morphological changes, vacuolization and degeneration of in vitro cultured cells.During this study we investigated the possible correlations between the presence of H. pylori cagA (cytotoxin associated gene antigen)-IgG antibodies and the severity of clinical and endoscopical findings.Anti-cagA IgG was screened by ELISA in 104 selected patients exhibiting resistance to first line therapy for H. pylori, bleeding gastroduodenal ulcers, non cardia gastric cancer and gastric polyps.A statistically significant association between resistant cases to first line therapy for H. pylori, bleeding gastroduodenal ulcers, non cardia gastric cancer, gastric polyps and cag A Ig G antibodies (p value 0.02 calculated by T-Test) was observed. As Cag A antibodies titer persist up to four months, their level could be an useful marker in detecting previous long-term H pylori infection especially in gastric cancer patients.CagA positive H. pylori are virulent strains and the cagA IgG antibodies titer is associated with persistence of infection after treatment, upper gastroduodenal ulcers or gastric cancer. The presence of these antibodies, associated with positive biopsy for H. pylori, indicates the need of H. pylori treatment.

Helicobacter pylori is one of the most common among the numerous bacterial species of the stomach. It is classified as a class 1 carcinogen because of its causal relationship to gastric adenocarcinoma. The epidemiology of H. pylori infection is characterized by a marked difference between developing and developed countries. Treatment of H. pylori still remains a challenge due to the high rate of antibiotic resistance. The aim of this study was to investigate the susceptibility of H. pylori strains isolated from gastric biopsies to different antibiotics currently used in the H. pylori infection treatment schemes.Upper gastrointestinal GI endoscopy was performed, followed by the rapid urease test on gastric biopsies. The positive samples were cultivated on specific media under microaerophilic conditions and the antibiotic susceptibility assay was performed on the isolated strains.A positivity rate of 70% was obtained for cultures performed from the biopsy samples positive for the urease test. The resistance rates for the antibiotics used in the classic triple therapy proved to be high, i.e. 92.8% for metronidazole, 50% for amoxicillin and 32% for clarithromycin. The isolated strains proved to be sensitive to ciprofloxacin and levofloxacin.The role of gastric microbiota and its contribution to the H. pylori associated pathology need to be established. The problem of antibiotic treatment failure in case of resistant H. pylori strains can be surpassed by routine culture and antibiotic susceptibility testings.

Large epidemiological studies showed that one of the most important causes of death in patients with rheumatoid arthritis (RA) is represented by cardiovascular disease. Thus, the presence of RA is associated with an increased risk of the occurrence of stable angina, myocardial infarction, heart failure and stroke. However, studies performed during the last years failed to bring us clear evidence regarding the role of traditional cardiovascular risk factors (hyperlipidemia, diabetes mellitus, hypertension, smoking and obesity) in the pathogenesis of cardiovascular disease in these patients. Recently, the role of inflammation and its mediators not only in the atherosclerosis plaque development but also in the mechanisms of vulnerable plaque was clearly demonstrated. From this point of view, recent studies showed that inflammatory cells and mediators of inflammation are both markers of an increased cardiovascular risk and unfavorable cardiovascular outcome, and also cardiovascular risk factors that act in an active manner in the processes that promote atherosclerosis. Taking into account the fact that RA is a systemic inflammatory status, recent reports demonstrated the involvement of inflammation mediators in connection with prothrombotic factors and endothelial dysfunction in the development of cardiovascular disease in RA patients. There are only scarce data in the literature regarding the benefice of cardiovascular risk reduction therapies in this group. Further studies are required for the refinement of the cardiovascular risk stratification algorithms and for the improvement of the cardiovascular risk management in rheumatoid arthritis.

This is an overview of cytokine-induced cholestasis, justified by the insufficient knowledge of this frequent type of cholestasis. In the presence of an infectious agent a systemic and intrahepatic production of proinflammatory cytokines results (TNF-alpha, IL-1beta, IL-6 etc.), stimulated by microbial lipopolysaccharides. In patients having systemic infections, the liver has several major functions: source of the inflammatory cytokines produced as a response to infection and a target of these inflammation mediators. The inflammatory cytokines interfere with the activity of both the sinusoidal and canalicular transporting systems. One of the potential consequences of this process is the appearance of cholestasis. An infection can lead to cholestasis despite the absence of direct invasion of the liver by the infectious agent. Particularly the cholestasis produced when the infection generating agent is not located in the liver (sepsis or extrahepatic infections) has been emphasized. The clinical aspect of the diseases associated with this type of cholestasis and the effects of anti-infectious therapy on cholestasis are presented. Cytokine-induced cholestasis represents a common pathogenic path for several diseases: hepatitides that present with an intrahepatic cholestatic pattern (viral, ethanol-induced, NSAID-induced), but also many other infections, which are sometimes overlooked because of the lack of clinical signs. When a preexistent liver disease is present, the cholestasis incidence is higher. In this latter condition, ignorance of this possible mechanism of cholestasis will lead to misdiagnosis and unnecessary tests, sometimes expensive and useless.

Background & Aims TG4040 is a modified vaccinia Ankara (MVA) virus that expresses the hepatitis C virus (HCV) proteins NS3, NS4, and NS5B. We performed a phase II open-label study to determine the efficacy, safety, and immunotherapeutic properties of TG4040 in combination with pegylated interferon α-2a and ribavirin (PEG-IFNα/RBV) in patients with chronic HCV infection. Methods Treatment-naive patients with HCV genotype 1 infection were assigned randomly to 1 of the following groups: PEG-IFNα/RBV for 48 weeks (group A, n = 31), PEG-IFNα/RBV for 4 weeks followed by PEG-IFNα/RBV for 44 weeks with 6 injections of TG4040 (group B, n = 63), or TG4040 for 12 weeks (7 injections) followed by PEG-IFNα/RBV for 48 weeks with 6 injections of TG4040 (group C, n = 59). The primary end point was complete early virologic response (cEVR), defined as HCV-RNA level less than 10 IU/mL after 12 weeks of PEG-IFNα/RBV treatment. Results In group C, 64.2% of evaluable patients achieved cEVR, compared with 30.0% in group A and 45.9% in group B ( P = .0003 for group C vs A). A higher percentage of patients achieved a sustained virologic response 24 weeks after therapy ended in group C (58.2%) than in groups A (48.4%) or B (50.8%). HCV- and MVA-specific T-cell responses were observed predominantly in group C. As expected, most patients given injections of TG4040 developed anti-MVA antibodies. The combination of TG4040 and PEG-IFNα/RBV was reasonably well tolerated. However, PEG-IFNα–associated thrombocytopenia developed in 3 patients who carried the class II HLA allele DRB01*04. Conclusions A higher percentage of patients with chronic HCV infection who received immunotherapy with TG4040 followed by TG4040 and PEG-IFNα/RBV achieved a cEVR compared with patients who received only PEG-IFNα/RBV therapy. These findings show that immunotherapies that activate T cells are effective in patients with chronic HCV infection. ClinicalTrials.gov number, NCT01055821.

1403 SIGNIFICANT IMPROVEMENT OF COMPLETE EVR IN HCVAC PHASE II CLINICAL TRIAL WHEN ADDING TG4040 THERAPEUTIC VACCINE TO PEGIFNa2A AND RIBAVIRIN H. Wedemeyer, E. Janczewska, M. Wlodzimierz, C. Stanciu, F. Habersetzer, V. Carreno, A.M. Di Bisceglie, C. Tanasescu, R. Flisiak, M. Romero-Gomez, A. Fich, C. Zemmour, A. Fournillier, P. Zerr, D. Agathon, H. He, J.-Y. Bonnefoy, G. Inchauspe, J.-M. Limacher. Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany; Department of Infectious Diseases, Medical University of Silesia, Chorzow, Department of Internal Medicine, Medical University of Silesia, Katowice, Poland; Gr. T. Popa University of Medicine and Pharmacy, Institute of Gastroenterology and Hepatology, Iasi, Romania; Hepato-Digestive Unit, Strasbourg University Hospitals, Strasbourg, France; Foundation for the Study of Viral Hepatitis, Madrid, Spain; Hepatology, Saint Louis University Liver Center, Saint Louis, MO, USA; Internal Medicine Clinic, Colentina Clinical Hospital, Bucharest, Romania; Department of Infectious Diseases and Hepatology, Medical University of Bialystok, Bialystok, Poland; Unit for the Clinical Management of Digestive Diseases and Ciberehd, Valme University Hospital, Sevilla, Spain; Department of Gastroenterlogy, Soroka Medical Center, Beersheba, Israel; TRANSGENE SA, Illkirch, TRANSGENE SA, Lyon, France E-mail: wedemeyer.heiner@mh-hannover.de