No serum or radiological findings are specific of WD. Sometimes endoscopy show erosive bulbitis or duodenitis. Immunohistochemistry allows the detection of Tropheryma whipplei in different bodily samples. Differential diagnosis includes rheumatic disease, coeliac disease, sarcoidosis, lymphoma, Addison’s disease and neurologic disorders. Disease identification is essential to avoid immunosuppressive therapy which has been observed to be associated with a rapid clinical deterioration in WD. Our case confirms that WD should be considered as differential diagnosis in patients with gastrointestinal symptoms and arthropathy, especially in middle-aged

men. In contrast with CT suggesting lymphoproliferative CDK inhibitor disease, US showed images consistent with

fat deposits, a feature typically described in Whipple’s disease. Findings of low density, highly fatty lymph nodes with a marked hyperechoic pattern in the mesentery and retroperitoneum may be associated with WD. An appropriate therapy can obtain clinical remission. However, it is well known that clinical relapse after treatment discontinuation may occur in 2-33% of cases after an average time of 5 years. Presently, optimal duration of the antibacterial mTOR inhibitor treatment and follow up strategies are not yet well established. Further studies are needed to clarify these unresolved issues. “
“E. M. Brunt illustrated in her article focusing on nonalcoholic fatty liver disease (NAFLD) the difficulty in giving names to complex entities which are not, or cannot be, fully characterized, particularly when it comes to the combination of pathological/clinical and prognostic

criteria.1 Here, we discuss another issue illustrating the confusion of terms. This concern is minor in terms of public health, but a source of diagnostic problem for liver specialists SB-3CT and important for patients who develop benign hepatocellular nodules. Focal nodular hyperplasia (FNH) is believed to be a nonspecific response to locally increased blood flow. In 1989, Wanless et al. described an entity they called telangiectatic focal nodular hyperplasia (TFNH) occurring in the multiple FNH syndrome as well as in a minority of patients with solitary FNH.2 They mentioned without detail that at the microscopic level, lesions were similar to those observed in hereditary hemorrhagic telangiectasia (HHT). Ten years later, Nguyen et al. described lesions classified as FNH of telangiectatic form.3 At the microscopic scale, the hepatic plates were separated by sinusoidal dilatation, sometimes alternating with areas of marked ectasia. In 2004, Paradis et al. showed that the molecular profile of the TFNH at the DNA, gene, and protein expression level was more similar to that of hepatocellular adenomas (HCAs) than that of typical FNH. Telangiectasia was defined at the microscopic level as areas of sinusoidal dilatation, congestion, and peliosis.

No serum or radiological findings are specific of WD. Sometimes endoscopy show erosive bulbitis or duodenitis. Immunohistochemistry allows the detection of Tropheryma whipplei in different bodily samples. Differential diagnosis includes rheumatic disease, coeliac disease, sarcoidosis, lymphoma, Addison’s disease and neurologic disorders. Disease identification is essential to avoid immunosuppressive therapy which has been observed to be associated with a rapid clinical deterioration in WD. Our case confirms that WD should be considered as differential diagnosis in patients with gastrointestinal symptoms and arthropathy, especially in middle-aged

men. In contrast with CT suggesting lymphoproliferative Adriamycin nmr disease, US showed images consistent with

fat deposits, a feature typically described in Whipple’s disease. Findings of low density, highly fatty lymph nodes with a marked hyperechoic pattern in the mesentery and retroperitoneum may be associated with WD. An appropriate therapy can obtain clinical remission. However, it is well known that clinical relapse after treatment discontinuation may occur in 2-33% of cases after an average time of 5 years. Presently, optimal duration of the antibacterial CDK inhibitor treatment and follow up strategies are not yet well established. Further studies are needed to clarify these unresolved issues. “
“E. M. Brunt illustrated in her article focusing on nonalcoholic fatty liver disease (NAFLD) the difficulty in giving names to complex entities which are not, or cannot be, fully characterized, particularly when it comes to the combination of pathological/clinical and prognostic

criteria.1 Here, we discuss another issue illustrating the confusion of terms. This concern is minor in terms of public health, but a source of diagnostic problem for liver specialists Cytidine deaminase and important for patients who develop benign hepatocellular nodules. Focal nodular hyperplasia (FNH) is believed to be a nonspecific response to locally increased blood flow. In 1989, Wanless et al. described an entity they called telangiectatic focal nodular hyperplasia (TFNH) occurring in the multiple FNH syndrome as well as in a minority of patients with solitary FNH.2 They mentioned without detail that at the microscopic level, lesions were similar to those observed in hereditary hemorrhagic telangiectasia (HHT). Ten years later, Nguyen et al. described lesions classified as FNH of telangiectatic form.3 At the microscopic scale, the hepatic plates were separated by sinusoidal dilatation, sometimes alternating with areas of marked ectasia. In 2004, Paradis et al. showed that the molecular profile of the TFNH at the DNA, gene, and protein expression level was more similar to that of hepatocellular adenomas (HCAs) than that of typical FNH. Telangiectasia was defined at the microscopic level as areas of sinusoidal dilatation, congestion, and peliosis.

12 Another important finding of our study is the discovery of JNK inhibitors originated from licorice as the regulators of miR-122 for PTP1B repression; decreased levels of PTP1B allowed cells to maintain the phosphorylation of IRβ and IRS1 at tyrosine residues with the inhibition of IRS1/2 serine

phosphorylation. IsoLQ or LQ treatment caused 50%-60% inhibition of JNK1 in a cell model exposed to TNF-α (15 minutes), being consistent with our previous report.12 More important, IsoLQ treatment at 10 and 30 mg/kg inhibited HFD-induced JNK1 activation by 50% and 100%, respectively,12 which matches the repression of PTP1B shown in the Inhibitor Library mouse present study. IR sensitization was further supported by not only the inhibition of glucose production in hepatocytes, but the increase in glucose uptake by myotubes or adipocytes. The improved glucose homeostasis was strengthened by the glucose-lowering effect shown in an animal model. Our results that IsoLQ treatment decreased body weight and liver weight gains and the plasma triacylglycerol contents in HFD-fed mice also support their beneficial effects on metabolic syndrome.12 SIRT1 levels are decreased in insulin-resistant CX-4945 cells or tissues. The effect of SIRT1 on insulin resistance is also affected by the repression

of PTP1B transcription at the chromatin level.40 The agents used in the present study had the capability to activate SIRT1, which may be associated with the regulation of glucose metabolism. However, PTP1B inhibition by IsoLQ seems to be independent of SIRT1, as supported in part by our finding that IsoLQ treatment inhibited PTP1B expression even after SIRT1 inhibition using sirtinol and nicotinamide

(data not shown). Nrf2 contributes to the inhibition of LXRα-dependent lipogenesis,41 whereas AMPK activation of SIRT1 inhibits gluconeogenesis and increases energy expenditure.42 Although the enhanced energy metabolism by IsoLQ may PRKACG involve Nrf2 and/or AMPK, PTP1B repression by IsoLQ seems to be irrelevant to the molecules. This possibility is supported by the finding that the agent decreased PTP1B levels in hepatocytes deficient in Nrf2 or those treated with compound C (an AMPK inhibitor) (data not shown). In conclusion, the present study identified miR-122 dysregulation as a cause of hepatic insulin resistance, which may depend on the posttranscriptional induction of PTP1B, as mediated by JNK1-dependent inactive phosphorylation of HNF4α. Our finding that PTP1B induction can be overcome by the pharmacological inhibitors of JNK provides key information in understanding liver pathobiology and designing a therapeutic strategy for hepatic insulin resistance. The authors thank Dr. Young Woo Kim (Daegu Haany University) for the kind additional supply of IsoLQ. Additional Supporting Information may be found in the online version of this article.

Coordinators who did not initially respond were contacted up to three additional times. Areas were asked to report data from the most recently available 12-month continuous period prior to August 2008. Across all areas, this resulted

in data collected from refugees who entered the United States between 2006 and 2008. We pooled information Enzalutamide from across jurisdictions about refugees from the same country of origin. Using these data, we estimated the prevalence of HBsAg among refugees from each country of origin by dividing the number of HBsAg-positive refugees by the total number tested. We also pooled data and estimated prevalence by continent. Several jurisdictions provided numerical count data regarding the total number of refugees screened combined with proportional data about the countries of origin and the HBsAg prevalence observed among refugees from each country of origin. For these jurisdictions, we estimated the number of refugees tested and the number of HBsAg-positive refugees from each country by multiplying the total number of refugees screened by the proportion screened from each country, then multiplied that number by the proportion screened from that country Dasatinib of origin who were HBsAg-positive. We present our results for countries

from which we estimate that 30 or more refugees were tested. We calculated 95% confidence intervals (CIs) for each prevalence rate using the Wilson procedure with a correction for continuity.6 Of the 47 jurisdictions we attempted to contact, 31 responded with at least some information and 16 states did not respond, for a 66% response rate. Of the 31 areas that responded, 28 reported that they systematically screened at least some groups of refugees for hepatitis B, whereas three areas reported that hepatitis B testing was not part of the refugee health screening process. Of these 28, 20 were able to provide a count of the total number of refugees Low-density-lipoprotein receptor kinase screened, and 13 were able to provide an estimate of the overall prevalence among all refugees

screened; of these 13, nine areas were able to provide data by country of origin. The 20 areas that provided data on the number of refugees screened screened a total of 42,303 refugees in the preceding 12 months, which is approximately 55% of the total number of refugees arriving in the United States in 2008. The nine areas that provided data by country of origin screened 31,980 refugees, or approximately 42% of refugees arriving in the United States in 2008. Screened refugees with country of origin data originated from 44 countries and 11 continental subregions across four continents. Of the 31,980 refugees with complete country of origin data, 891 (2.8%; 95% CI 2.6%–3.0%) tested positive for HBsAg. This rate varied by continent, continental region, and country of origin (Table 1).

019; IOD: 513.99 ± 79.80 vs 709.63 ± 43.25, p = 0.000). The increased TRPV1 protein expression was tightly correlated with the decreased CB1 protein expression in DRG (r = -0.606, p = 0.037), but TRPV1 was not yet correlated with CB2 protein expression (r = -0.351, p = 0.263). Conclusion: The increased TRPV1 protein expression was strongly correlated with decreased Dabrafenib chemical structure CB1 protein expression of RE rats, which indicated that the acid plays a critical

role in regulation of the receptor molecules. Key Word(s): 1. reflux diease; 2. TRPV1; 3. CB1; 4. CB2; Presenting Author: 谷 Additional Authors: 傅 春彬, 孔 Corresponding Author: 谷 Affiliations: Objective: To explore the clinical effect of the proton pump inhibitors (PPI) with mosapride treatment of gastroesophageal reflux disease (GERD). Methods: A randomized and open study in a multi-center was adopted. Clinical observation questionnaire surver was performed on 130 patients to

investigate relevant symptoms of gastroesophageal reflux disease (GERD). They were divided randomly into observed group (domperidone and rabeprazole) and control group (rabeprazole). In a follow-up of 4 weeks, scores were compared between the two groups after the treatment of 2 week and 4 week. Results: Compared with the baseline, the scores of both two groups had declined after PD-0332991 chemical structure 2 week and remarkably declined after 4 week with a significant difference. The observed group showed remarkably improvent of heartburn after 2 weeks and regurgitation after 4 weeks with a significant difference. The observed group showed a higter effective rate on the symptoms of heartburn and regurgitation than the control group after 2 week. Conclusion: The proton pump inhibitors (PPI) with mosapride can rapidly relieve the symptoms of gastroesophageal reflux disease (GERD). Key Word(s): 1. esophagealreflux; 2. mosapride; 3. Drug therapy; 4. combination; Presenting Author:

朱 Additional Authors: 傅 春彬, 刘 Corresponding Author: 朱 Affiliations: Objective: To explore the research progress of primary gastric mucosa-associated lymphoid tissue lymphoma. Methods: To oxyclozanide summarize the etiology, pathogenesis, diagnostic methods and basis, treatment and regimen of gastric MALT lymphoma. Results: Helicobacter pylori (HP) infection is the important cause of gastric MALT lymphoma, the chromosomal abnormality and the expression of NF-κB molecular pathway is also the important pathogenic factor in gastric MALT lymphoma. The chromosomal abnormalities include t (11; 18) (q21; q21), t (1; 14) (p22; q32), t (14; 18) (q32; q21) and so on. Endoscopy and immunohistochemical examination are helpful in diagnosis of this disease. Treatments include the HP eradication therapy, radiotherapy, surgery, chemotherapy and molecular targeted therapy. Conclusion: HP infection and chromosomal abnormalities are the major causes of gastric MALT lymphoma.

019; IOD: 513.99 ± 79.80 vs 709.63 ± 43.25, p = 0.000). The increased TRPV1 protein expression was tightly correlated with the decreased CB1 protein expression in DRG (r = -0.606, p = 0.037), but TRPV1 was not yet correlated with CB2 protein expression (r = -0.351, p = 0.263). Conclusion: The increased TRPV1 protein expression was strongly correlated with decreased ABT-737 purchase CB1 protein expression of RE rats, which indicated that the acid plays a critical

role in regulation of the receptor molecules. Key Word(s): 1. reflux diease; 2. TRPV1; 3. CB1; 4. CB2; Presenting Author: 谷 Additional Authors: 傅 春彬, 孔 Corresponding Author: 谷 Affiliations: Objective: To explore the clinical effect of the proton pump inhibitors (PPI) with mosapride treatment of gastroesophageal reflux disease (GERD). Methods: A randomized and open study in a multi-center was adopted. Clinical observation questionnaire surver was performed on 130 patients to

investigate relevant symptoms of gastroesophageal reflux disease (GERD). They were divided randomly into observed group (domperidone and rabeprazole) and control group (rabeprazole). In a follow-up of 4 weeks, scores were compared between the two groups after the treatment of 2 week and 4 week. Results: Compared with the baseline, the scores of both two groups had declined after CX-5461 nmr 2 week and remarkably declined after 4 week with a significant difference. The observed group showed remarkably improvent of heartburn after 2 weeks and regurgitation after 4 weeks with a significant difference. The observed group showed a higter effective rate on the symptoms of heartburn and regurgitation than the control group after 2 week. Conclusion: The proton pump inhibitors (PPI) with mosapride can rapidly relieve the symptoms of gastroesophageal reflux disease (GERD). Key Word(s): 1. esophagealreflux; 2. mosapride; 3. Drug therapy; 4. combination; Presenting Author:

朱 Additional Authors: 傅 春彬, 刘 Corresponding Author: 朱 Affiliations: Objective: To explore the research progress of primary gastric mucosa-associated lymphoid tissue lymphoma. Methods: To Phospholipase D1 summarize the etiology, pathogenesis, diagnostic methods and basis, treatment and regimen of gastric MALT lymphoma. Results: Helicobacter pylori (HP) infection is the important cause of gastric MALT lymphoma, the chromosomal abnormality and the expression of NF-κB molecular pathway is also the important pathogenic factor in gastric MALT lymphoma. The chromosomal abnormalities include t (11; 18) (q21; q21), t (1; 14) (p22; q32), t (14; 18) (q32; q21) and so on. Endoscopy and immunohistochemical examination are helpful in diagnosis of this disease. Treatments include the HP eradication therapy, radiotherapy, surgery, chemotherapy and molecular targeted therapy. Conclusion: HP infection and chromosomal abnormalities are the major causes of gastric MALT lymphoma.

Several studies tested neutralizing antibodies against mature VEGF proteins, blockade of VEGF receptors by VEGF receptor antibodies, soluble VEGF receptor mutants or fusion-proteins, and intra-cellular interference with VEGF mRNA or kinase signaling pathways in the target cell. Inhibiting the process of angiogenesis by knocking out the activity of VEGF has a significant impact Ivacaftor cell line on tumor growth and patient survival. However, it does not seem to be enough for a complete cure. So it is still necessary to explore as many regulatory steps as possible in the complex sequence of tumor-induced angiogenesis. Besides the VEGF, FGF and its family of receptors (FGFR) are potent

inducers of angiogenesis in HCC.4,5 Elevated serum FGF levels are an important prognostic factor in HCC,6 and the aberrant activation of FGFR has been shown to drive hepatocarcinogenesis.7 FGF might also modulate the resistance to VEGF/VEGFR inhibition. For example, FGF2 has been shown to synergistically augment the VEGF-mediated HCC development and angiogenesis8 and might play a central role in the “escape mechanisms” implicated in VEGF/VEGFR targeting. Clinical and translational studies suggest that FGF blockade might circumvent resistance to

the VEGFR modulating agents.9 In a study of patients undergoing surgery for HCC, the high serum levels of FGF2 was shown to be a predictor for invasiveness and recurrence.10 Although the VEGF inhibitors can reduce the growth of the primary tumors, there are data HIF-1 activation showing that they might also Axenfeld syndrome promote the invasiveness and metastasis of the tumor.11 Accordingly, novel anti-angiogenic therapies targeting FGF to synergize with VEGF-mediated anti-angiogenesis might provide a mechanism to overcome resistance to VEGF-targeted agents in HCC. So we should use the knowledge to inhibit the process of angiogenesis at a more sensitive point of angiogenesis, or at several

points simultaneously. To achieve this goal, the newly developed in vitro models of tumor growth and of blood vessel formation could be helpful. Actually, several agents that target the VEGF pathway have been tested in patients with advanced HCC, such as the oral multikinase inhibitors, sorafenib and sunitinib, whose antitumor effects are partly as a result of the inhibition of VEGF receptors. Although the SHARP trial showed only a 2.8-month improvement in median overall survival rate (P = 0.0006), along with very limited increased time to disease progression and disease control rate, and a 2.3% response rate, sorafenib became the first targeted agent approved to use in advanced HCC by the USA Food and Drug Administration.12 The monoclonal antibody against VEGF, bevacizumab, either used alone or in combination with erlotinib, has shown improved survival in advanced HCC patients. In this issue of the Journal, Jie et al.

A comparison of 29 commercial serological kits (17 ELISAs and 12 ICTs) was carried out in France.

Depending on the type of analysis performed, 2 to 4 of the ELISAs presented an excellent performance. In contrast, only one of the 12 ICTs had an accuracy >90% [32]. A line assay using 6 recombinant proteins corresponding to virulence factors (CagA, VacA, GroEL, gGT, HcpC, and UreA) was developed in Germany. It was validated on a group of 600 patients (42% H. pylori positive by histology) and showed 97.6% sensitivity and 96.2% specificity, that is, an improvement on currently available serological tests [33]. The same group in collaboration with researchers in Iran was able to identify a H. pylori protein, FliD, essential in the Pexidartinib molecular weight assembly of the flagella. The recombinant FliD protein was tested on a group of 618 patients (51.4% H. pylori positive) with 97.4% sensitivity and 99% specificity using a line assay, and 97 and 96% by ELISA, respectively [34]. Other attempts to select antigenic proteins of potential diagnostic value were made (CafI, ureG, ureB), but have not been evaluated yet [35]. Interestingly, using

Helicoblot 2.1 (Genelabs Diagnostics, Singapore), it was possible to identify a low molecular weight protein (35KDa) associated with a low risk of GC (OR = 0.4, 95% CI:0.1–0.9) and the VacA protein associated with a high risk of GC (OR = 2.7, 95 CI:1–7.1) among patients with GC (102) and dyspepsia (122) in Iran [36]. A review on ICTs was also produced last year [37]. Pepsinogen Selumetinib chemical structure I and II and their ratio as predictors of atrophy were evaluated this year in Iran [38], Turkey [39], and Italy [40], but they were found to be insensitive predictors of these Vildagliptin lesions. A toll-like receptor 4 was found helpful to differentiate between dysplasia and other precancerous lesions [39]. Both miR-106b and miR-21 were found as markers of increased risk for GC after H. pylori eradication [41]. The progress in imaging techniques allows now to have a more accurate approach of

the features associated to H. pylori infection. There are continuous attempts to improve the existing diagnostic methods or to evaluate their use in real life. Competing interest: The authors have no competing interests. “
“Background:  A remarkable variety of restriction-modification (R-M) systems is found in Helicobacter pylori. Since they encompass a large portion of the strain-specific H. pylori genes and therefore contribute to genetic variability, they are suggested to have an impact on disease outcome. Type I R-M systems comprise three different subunits and are the most complex of the three types of R-M systems. Aims:  We investigated the genetic diversity and distribution of type I R-M systems in clinical isolates of H. pylori. Material and methods:  Sixty-one H. pylori isolates from a Swedish hospital based case-control study and 6 H.

Additional endpoints included rates of rapid virologic response (RVR; HCV RNA <25 IU/mL

at week 4), end-of-treatment response (EOTR; HCV RNA <25 IU/mL at week 12), and SVR at 4 and 24 weeks after end of treatment (SVR4 and SVR24). Safety and tolerability were assessed throughout the study. Results: 44 TN patients received ombitasvir and ABT-450/r, and 42 TN and 49 TE patients received ombitasvir NVP-AUY922 and ABT-450/r with RBV. The majority of patients were white (89%) and male (65%). Most patients (93%) had F0-F2 stage fibrosis. All TN and TE patients who received ombitasvir and ABT-450/r with RBV achieved SVR12 (Figure). Three TN patients who received ombitasvir and ABT-450/r (without RBV) had virologic failure; 1 had rebound at selleck chemicals llc treatment week 8, and 2 patients had post-treatment relapse before posttreatment week 12. Common treatment-emergent adverse events (AEs; >15% in any group) were headache (27-33%), asthenia (24-33%), fatigue (7-18%), and nausea (9-17%). Most were mild in severity. One patient experienced a serious

AE (contusion due to traffic accident) and 1 patient had a grade 3 liver function test elevation (AST >5× ULN). The AST elevation was asymptomatic and resolved during continued dosing. No patients in any group interrupted or discontinued the study due to AEs. Conclusion: Interferon-free regimens of ombitasvir and ABT-450/r with/ without RBV achieved high rates of RVR, EOTR, and SVR, and were generally well tolerated in TN and TE patients with HCV GT4 infection. Disclosure/Acknowledgements: Thalidomide The authors and AbbVie

scientists designed the study, and analyzed and interpreted the data. All authors contributed to the development of the content; all authors and AbbVie reviewed and approved the presentation; the authors maintained control over the final content. Medical writing support was provided by Mariana Ovnic, PhD, of Complete Publication Solutions, LLC, Horsham, PA. AbbVie funded the research and medical writing support. Disclosures: Stanislas Pol – Board Membership: Sanofi, Bristol-Myers-Squibb, Boehringer Ingel-heim, Tibotec Janssen Cilag, Gilead, Glaxo Smith Kline, Roche, MSD, Novartis; Grant/Research Support: Glaxo Smith Kline, Gilead, Roche, MSD; Speaking and Teaching: Sanofi, Bristol-Myers-Squibb, Boehringer Ingelheim, Tibotec Janssen Cilag, Gilead, Glaxo Smith Kline, Roche, MSD, Novartis K.

Additional endpoints included rates of rapid virologic response (RVR; HCV RNA <25 IU/mL

at week 4), end-of-treatment response (EOTR; HCV RNA <25 IU/mL at week 12), and SVR at 4 and 24 weeks after end of treatment (SVR4 and SVR24). Safety and tolerability were assessed throughout the study. Results: 44 TN patients received ombitasvir and ABT-450/r, and 42 TN and 49 TE patients received ombitasvir Small molecule library and ABT-450/r with RBV. The majority of patients were white (89%) and male (65%). Most patients (93%) had F0-F2 stage fibrosis. All TN and TE patients who received ombitasvir and ABT-450/r with RBV achieved SVR12 (Figure). Three TN patients who received ombitasvir and ABT-450/r (without RBV) had virologic failure; 1 had rebound at Decitabine research buy treatment week 8, and 2 patients had post-treatment relapse before posttreatment week 12. Common treatment-emergent adverse events (AEs; >15% in any group) were headache (27-33%), asthenia (24-33%), fatigue (7-18%), and nausea (9-17%). Most were mild in severity. One patient experienced a serious

AE (contusion due to traffic accident) and 1 patient had a grade 3 liver function test elevation (AST >5× ULN). The AST elevation was asymptomatic and resolved during continued dosing. No patients in any group interrupted or discontinued the study due to AEs. Conclusion: Interferon-free regimens of ombitasvir and ABT-450/r with/ without RBV achieved high rates of RVR, EOTR, and SVR, and were generally well tolerated in TN and TE patients with HCV GT4 infection. Disclosure/Acknowledgements: Oxalosuccinic acid The authors and AbbVie

scientists designed the study, and analyzed and interpreted the data. All authors contributed to the development of the content; all authors and AbbVie reviewed and approved the presentation; the authors maintained control over the final content. Medical writing support was provided by Mariana Ovnic, PhD, of Complete Publication Solutions, LLC, Horsham, PA. AbbVie funded the research and medical writing support. Disclosures: Stanislas Pol – Board Membership: Sanofi, Bristol-Myers-Squibb, Boehringer Ingel-heim, Tibotec Janssen Cilag, Gilead, Glaxo Smith Kline, Roche, MSD, Novartis; Grant/Research Support: Glaxo Smith Kline, Gilead, Roche, MSD; Speaking and Teaching: Sanofi, Bristol-Myers-Squibb, Boehringer Ingelheim, Tibotec Janssen Cilag, Gilead, Glaxo Smith Kline, Roche, MSD, Novartis K.