A recent study has shown high levels of serum CXCL-8, CXCL-9 and CXCL-10 are associated with hepatic flare. However, the pathogene-sis of HBV reactivation in HBeAg negative chronic hepatitis B infection is not clear. In this study, we evaluated levels of serum cytokines and chemokines including IFN-α, Selleck Enzalutamide IL-1b, TNF-a, IL-6, IL-8, IL-10, CCL-2, CCL-3, CXCL-9, and CXCL-10 in HBeAg negative chronic hepatitis B patients with a range of ALT values. METHODS: Eighty five serum samples of chronic hepatitis B HBeAg negative patients with different levels of abnormal

ALT (1 sample/patient, all ALT>70 IU/L) were studied. In these patients/samples, 39 were during HBV reactivation while the rest 46 were not. Serum cytokines/chemokines were analyzed using Affymetrix 10-plex human cytokine kit and Bio-Plex MAGPIX system. Cytokine/chemokine concentrations were calculated using Bio-Plex Manager 6.1. HBV DNA levels were quantified using serum extracted DNA as template and real time PCR with a VQC standard panel. Statistical analyses were carried out using SPSS v17. Data were presented as mean ± SE. RESULTS: Correlation analysis of all variables

showed a positive correlation between CXCL9 and ALT levels (Pearson’s r=0.37, p<0.001), and between CXCL9 and HBV DNA levels (Pearson's r=0.33, p<0.001). Whereas, other cytokines/ chemokines were not correlate with ALT and HBV DNA levels in HBeAg negative patients. In addition, the ALT and HBV DNA levels in samples of during HBV reactivation this website were significantly higher than those without reactivation (478.5 ± 97.4 vs. 161.6 ± 25.9 IU/L, p=0.003; and 6.2 ± 0.19 vs. 5.0 ± 0.21 Log10 IU/mL, p<0.001 respectively) selleckchem as were the CXCL9 levels (249.3 ± 39.9 vs. 116.2 ± 24.4 pg/mL, p=0.005). There was no significant difference in levels of other cytokines/chemokines between samples during and non-during HBV reactivation. CONCLUSION: CXCL9 is correlated with ALT and HBV DNA levels in HBeAg negative patients. HBeAg negative patients have higher serum CXCL9 levels during HBV reactivation. CXCL9 seems to be not just important in hepatic

flares but also in milder forms of abnormal ALT elevation. CXCL9 may play an important role in HBV reactivation in HBeAg negative chronic hepatitis B infection. Disclosures: Seng Gee Lim – Advisory Committees or Review Panels: Bristol-Myers Squibb, Achillon Pharmaceuticals, Pfizer Pharmaceuticals, Janssen Pharmaceuticals, Novartis Pharmaceuticals, Merck Sharp and Dohme Pharmaceuticals, Vertex Pharmaceuticals, Boehringer-Ingelheim, Gilead Pharmaceuticals, Roche Pharmaceuticals, Tobira Pharmaceuticals; Speaking and Teaching: GlaxoSmithKline, Bristol-Myers Squibb, Merck Sharp and Dohme Pharmaceuticals, Boehring-er-Ingelheim, Gilead Pharmaceuticals, Novartis Pharmaceuticals The following people have nothing to disclose: Yan Cheng, Veonice Bijin Au, John E.

Our meta-analysis has provided the most comprehensive quantitative evidence beta-catenin inhibitor for the practice by far. Furthermore, this significant association might also exist between PBC and stomach and pancreatic cancer risks, at least in male patients (which, however, needs to be further confirmed by a larger number of studies). In contrast, there is no significant association between PBC and breast cancer risk, which suggested that PBC patients do not need to be submitted to stricter surveillance programs for breast cancer than the general population. Also,

there is no significant association between PBC and other cancer risks; however, this assessment needs to be further confirmed by a larger number of studies. Additional Supporting Information may be found in the online version of this article. “
“Ironically, as we are phasing out interferon (IFN)-based combinations to treat chronic hepatitis C, IFN signaling in hepatocytes is getting more attention. In this issue of Hepatology, two groups present their results comparing response to different types of IFNs. They exposed Huh7 cells and primary human hepatocytes to IFNs and performed gene expression profiling with a microarray. Both groups found that type I and III IFNs induced the same set of IFN-stimulated

genes, but that the strength of this response differed. Type I IFNs induce a strong response, which is transient with IFN-α and sustained with IFN-β. Type III IFN-λs induce a much weaker, but sustained, response. Bolen et al. correlate gene expression pattern with different phosphorylation of the transcription SCH772984 concentration see more factor, signal transducer and activator of transcription

1. Jilg et al. investigated the transcriptomic response in Huh7 cells infected with hepatitis C virus (HCV). They found that the presence of HCV blunted the transient response to IFN-α, which became similar to the response to IFN-λ. Because polymorphisms in IFN-λ3 (interleukin-28B) are associated with clinical outcomes, further details on its signaling are relevant. (Hepatology 2014;1250-1261. Hepatology 2014;59:1262-1272) Nucleotide analogs are capable of changing the natural history of chronic hepatitis B. If hard endpoints are the occurrence of clinical complications of cirrhosis and death, rendering hepatitis B virus (HBV) viremia negative is a prerequisite for beneficial effects. Therefore, a lack of decline of the HBV viremia has been proposed as a measure of a lack of efficacy of nucleotide analogs and primary nonresponse, based on the HBV viremia kinetic, a reason to stop their administration. Yang et al. investigate how the American Association for the Study of Liver Diseases and European Association for the Study of the Liver stopping rules perform for entecavir. They examined 1,254 treatment-naïve patients who were treated with entecavir.

For miR-224, Wang et al.15 had already demonstrated that through targeting to the cellular target of apoptosis inhibitor-5 (API-5) gene, its elevation could stimulate the carcinogenic process. However, the

target gene(s) ABT-263 and the underlying regulatory mechanism for the elevation of miR-216a in hepatocarcinogenesis had not yet been addressed, and this is the main topic under investigation in the current study. Increasing evidence for sex steroids affecting the carcinogenic process through regulating specific miRNAs has been documented in breast cancers and prostate cancers.16-19 Our previous studies have identified an intriguing positive regulatory loop between the HBx viral protein and the androgen pathway in male HBV patients.13, 20, 21 It thus raises the possibility that miRNAs could be the candidates affected by the androgen pathway in early hepatocarcinogenesis of HBV-related male HCC. In that case, we expect the candidate miRNAs to show a gender-difference expression pattern in liver tissues at the precancerous stage. Of note, our current study pointed out that miR-216a was preferentially elevated in the precancerous

liver tissues of male HBV-related HCC patients, even in ≈70% of dysplastic nodules, suggesting it as a candidate miRNA regulated by the androgen pathway. This pattern was also noted in HCV-related HCC, although less significantly than that in HBV-related HCC, which is consistent with the fact that the

HCV core viral proteins can also activate the androgen pathway in hepatocytes.22 Daporinad mouse Aided by our successful identification of the TSS for pri-miR-216a, the effect of AR and HBx on the transcription of pri-miR-216a was investigated. The results indicated that through direct binding to the ARE site within the promoter region of pri-miR-216a (−349 to −335 bp upstream of TSS), the ligand-stimulated AR can increase its transcription and lead to the elevation of miR-216a. It is noteworthy that the elevation of miR-216a in the nontumorous liver tissues of male HCC patients showed a higher risk for mortality (hazard ratio [HR] = 4.62, 95% confidence interval [CI] = 0.74-29.05), suggesting that the levels of miR-216a are associated with the patients’ prognosis. Furthermore, we identified TSLC1 as a putative target gene of miR-216a. TSLC1 is selleck chemical a transmembrane glycoprotein, whose major tumor suppressor function is mediated through its extracellular immunoglobulin-like C2 type domains to regulate the cell adhesion activity, which in turn suppresses the tumor invasion and metastasis.23 Some other tumor suppressor functions of TSLC1 were reported to be mediated by its cytoplasmic domain, modulating the cell cycle progression, cell proliferation, and inducing apoptosis.24, 25 The decreased expression of the TSLC1 protein has been identified in a variety of tumors, including lung, prostate, pancreatic, colorectal, and gastric cancers.

13,20 Moreover, F sequences sampled from sporadic cases among the non-Amerindian population appear as nested clades within the “Amerindian” genotype F radiation.3 Genotype H, which has been isolated from Amerindians in North and Central America, displays a close phylogenetic relationship with genotype F.21,22 This suggests an ancient introduction of the F/H ancestral strains to the Americas, certainly occurring before the recent European colonization. HBV sequences sampled from several isolated indigenous populations, such as the Canadian Arctic, Indonesian tribes, Papua Indonesia, and Pacific islands, form distinct subgenotypes (B6 for Canadian Arctic, C3 for Pacific,

C3 and C5-C10 for Indonesia). This pattern suggests that HBV genotypes and subgenotypes were shaped by different waves of human NVP-BKM120 purchase migration across the continents.12,23–26 This hypothesis is further supported by the observed gradient of nucleotide and amino acid diversity from west to east, as well as the clustering of HBV sequences from three Polynesian islands, which is in accordance with archeological and linguistic evidence for the initial west-to-east settlement of Polynesia.19 Crucially, analyses of the Y chromosome and the mitochondrial DNA (mtDNA) markers revealed a dual genetic origin of Polynesians (Remote Oceania) from Near Oceania (Melanesia) and Asia

(see Supporting Information).19 The detection of two autochthonous subgenotypes (C3 and D4) in Remote Oceania is consistent with MLN8237 cell line the dual genetic origin of this population.19 Phylogenetic analyses of the HBV sequences isolated from Haiti revealed that a proportion of them formed a monophyletic clade within subgenotype A5 from Africa. The latter finding

suggests that the particular strains spread as the result of a founder effect that occurred during the period of the slave transport from Africa to Haiti between the 16th and 19th centuries. The fact that the nested “Haitian” A5 clade originated 200-500 years in the past suggests that the subgenotypes within selleck A have been circulating in Africa for several centuries, well before the start of slave migration from Africa to the Caribbean. To test the co-divergence of HBV with humans, we examined whether the tMRCA of HBV lineages from particular regions correlated with previous estimates of divergence times of isolated human populations. Briefly, we employed a stepwise calibration of the HBV molecular clock. We initially tested whether the oldest calibration points (i.e., the migration into the Americas and Oceania) were reciprocally concordant. We then added a series of younger calibration points (see Materials and Methods and Supporting Information), allowing us to cover a larger part of the HBV history.

29 Therefore, APO866 chemical structure the effect of telaprevir on these drugs may also vary based on CYP3A5 genotype. Although cyclosporine is a CYP3A and P-gp inhibitor,18 the effects of a single cyclosporine dose on systemic telaprevir exposure were considered negligible, because the cyclosporine dose (10 mg) was low and administered 2 hours after telaprevir administration. This study was not designed to test the effect of cyclosporine and tacrolimus on telaprevir exposure. However, telaprevir steady-state exposure in Parts A and B were similar to previous Phase I studies,22 so it is unlikely that coadministration of cyclosporine

or tacrolimus had a relevant effect on telaprevir exposure. Food decreases cyclosporine and tacrolimus exposure (Cmax by 33% and 65%; AUC by 13% and 28%, respectively),18, 19 whereas telaprevir exposure increases with food. Telaprevir was administered 30 minutes after the start

of a meal and cyclosporine or tacrolimus were administered 2 hours after telaprevir during coadministration. Volunteers refrained from further food or drink during the period see more between administration of telaprevir and cyclosporine or tacrolimus. This approach was used to minimize food effect on cyclosporine and tacrolimus exposure, while providing appropriate telaprevir dosing conditions. The extent to which simultaneous telaprevir administration with cyclosporine or tacrolimus in the fed state would impact these results is unknown. Another important consideration about concomitant tacrolimus or cyclosporine use with telaprevir in organ transplant patients is that after telaprevir treatment is completed or stopped, its inhibitory effect on CYP3A/P-gp would wear off and doses of immunosuppressant would need readjustments. Estimates of the recovery time of CYP3A activity vary widely30 and precise timing for CYP3A activity to resume to the levels before the start of telaprevir is unknown. Therefore, careful

blood concentration monitoring of immunosuppressants will be needed for approximately 2 weeks after telaprevir is stopped. Besides cyclosporine and tacrolimus, other immunosuppressants that are likely to have a significant interaction with telaprevir include those known 上海皓元 to have increased exposures when coadministered with strong CYP3A inhibitors, such as sirolimus and everolimus. Exposure of corticosteroids known to be metabolized by way of CYP3A may also increase in the presence of strong CYP3A inhibitors. However, studies with these drugs in combination with telaprevir have not been conducted. Finally, telaprevir has not been studied in pre-, post-, or peritransplant patients. The degree of the interaction with calcineurin inhibitors reported here suggests potential implications for patient safety.

Hepatic VLDLR overexpression plays an important role in the pathogenesis of ALD. (Hepatology 2014;59:1381-1392)

“
“In the 1930s, serious concerns about the health risks of cigarette smoking (CS) began to surface. During subsequent Obeticholic Acid decades, scientific reports linking CS and specific ailments rapidly accumulated,1, 2 but it was not until 1964 that the Surgeon General’s Advisory Committee on Smoking and Health finally acknowledged that CS was linked to specific diseases and to increased mortality. Today, the evidence is robust: the adverse effects of CS on several cancer outcomes and on cardiovascular and respiratory disease are established.3, 4 Although in the United States the prevalence of CS has been decreasing,5 the overall worldwide prevalence is steadily rising. Independently of prevalence rates, the absolute number of smokers everywhere keeps increasing because of population growth. The case against CS in patients with chronic liver disease (CLD) has been highlighted recently as data reporting hepatic injury due to smoking have emerged.6, 7 A role for CS in CLD was first suggested by two studies in the mid 1990s.8, 9 By now, CS has been clearly identified as a risk factor for hepatocellular carcinoma in CLD,10, 11 but its effect on histological

AG-014699 mouse activity or fibrosis progression in CLD still needs further characterization. Published studies have been limited predominantly by cross-sectional and retrospective study designs and a

lack of supportive experimental data. Nonetheless, the evidence from clinical studies consistently indicates that CS may accelerate liver disease progression in patients with chronic hepatitis C and B and in those with primary biliary cirrhosis (Table 1).8, 12-17 CS also appears to exacerbate liver injury in alcoholic liver disease.8, 9 With respect to nonalcoholic fatty liver disease (NAFLD), data supporting a potential role of CS have just recently started to surface. ALT, alanine aminotransferase; CLD, chronic liver disease; CS, cigarette smoking; HBV, hepatitis B virus; HCV, hepatitis C virus; IR, insulin resistance; NAFLD, nonalcoholic fatty liver disease; NASH, nonalcoholic steatohepatitis. Delineating the effect of CS in NAFLD is essential 上海皓元医药股份有限公司 because of the vast number of subjects that may benefit from risk factor modification. Over 30 million adults in the United States have NAFLD,18 and approximately 8 million may have nonalcoholic steatohepatitis (NASH) and hence a significant risk of developing cirrhosis, its complications, and liver-related mortality.19, 20 Unfortunately, no beneficial therapy can be recommended yet for patients with NASH. Therefore, the identification of modifiable risk factors that may affect disease progression, by itself important, is even more critical.

Basal biliary cholesterol secretion in Abcg5−/− mice was 72% lower than in Abcg5+/+ mice. T3 treatment increased cholesterol secretion 3.1-fold in Abcg5+/+ mice, whereas this response was severely blunted in Abcg5−/− mice. In contrast, biliary cholesterol Pritelivir clinical trial secretion in T3-treated Lxra+/+

and Lxra−/− mice was increased 3.5- and 2.6-fold, respectively, and did not differ significantly. Conclusions: TH-induced secretion of cholesterol into bile is largely dependent on an intact ABCG5/G8 transporter complex, whereas LXRa is not critical for this effect. (HEPATOLOGY 2012;56:1828–1837) “
“Acute hepatitis C virus (HCV) infection is underdiagnosed because most patients are asymptomatic. The majority of new infections occur among people who inject drugs (PWID), many of whom have a history of incarceration. In a previous pilot study, we identified symptomatic HCV cases, mainly among Caucasian inmates. We designed a cross-sectional study to evaluate whether risk factor–based screening of newly incarcerated inmates would enhance identification of asymptomatic acute HCV infection and elucidate any demographic shifts in HCV acquisition. From October 2006 to March 2008, 6,342 inmates underwent C646 health assessments and 3,470 inmates (55%) were screened. The racial distribution was as follows: African American, 24.0%; Caucasian, 49.5%; Hispanic, 22.2%. One hundred seventy-one inmates (4.9%) were classified as

high-risk. After further evaluation, 35 (20.5%) inmates were diagnosed with acute HCV with a mean age of 29 years; 62.9% were female and 91% were Caucasian. No African Americans were diagnosed with acute HCV. Our case-finding rate was 1.9 patients/month nearly a three-fold increase compared

with our historical control period with a higher proportion of asymptomatic cases. We estimate medchemexpress a prevalence of ∼1.0% (95% confidence interval, 0.7%-1.4%) of acute HCV infections among newly incarcerated inmates. Conclusion: Within the correctional system, systematic screening based on risk factors successfully identifies acute HCV infection among PWID, including asymptomatic patients. Our data also reflect changing nationwide patterns of injection drug use that vary by age, ethnicity, and race, leading to a marked reduction of acute HCV infections among African Americans compared with non-Hispanic whites. The nationwide implementation of this simple low-cost strategy in prison-based settings could identify more than 7,000 acute HCV infections among PWID, provide insight into changing epidemiologic trends, and facilitate appropriate therapeutic and preventive interventions. (HEPATOLOGY 2013) Most people who inject drugs (PWID) acquire hepatitis C virus (HCV) infection within the first years of unsafe injection practices.1, 2 National surveillance data demonstrate that PWID account for 46% of symptomatic acute HCV infections in the United States.

1) and reported by more than 10% of cases. Dental procedures, blood transfusions, and healthcare encounters that do not identify a specific healthcare procedure (e.g., overnight hospital stay or emergency room visit) were not included in multivariate models. A second multivariate model was constructed using interview data that were changed after medical chart review. A third model containing only acute hepatitis B cases and their matched controls was also constructed. Data were analyzed using SAS version 9.1 (SAS Institute Inc., Cary, NC). Population-attributable risks were calculated for exposures that were independently associated

with acute hepatitis B or C infection in the multivariate models.17 A total of 71 cases of acute hepatitis B and acute hepatitis www.selleckchem.com/screening/selective-library.html C among noninstitutionalized individuals 55 years or older were identified from 2006 to 2008 by the three participating health departments. Two additional cases were deemed

ineligible because they occurred in institutionalized persons: one in a correctional facility and the other in a long-term care facility. Fifty-eight (82%) of the seventy-one eligible cases were acute hepatitis B, and 13 (18%) were acute hepatitis C. Fifty-nine (83%) cases were identified in New York and 12 (17%) in Oregon (Table 1). Of the 71 cases identified, 48 (68%) were enrolled in the study. Of the 23 cases not enrolled, 13 (57%) declined to participate in the study, 7 (30%) were lost to follow-up (i.e., after being interviewed to complete the standard surveillance case report form), this website and 3 (13%) were unable to consent (e.g., because of a language barrier). Enrolled and

nonenrolled cases were not significantly different with regard to age category, study site, sex, race or ethnicity, and acute hepatitis diagnosis (Table 1). It was not possible to calculate the overall participation rate among controls because telephone medchemexpress screening of potential controls was terminated in many instances before it could be determined whether any household members met the age requirements for case matching. However, participation was 60% among potential controls who were successfully contacted and indicated that they met the age criteria. All of the 48 enrolled case patients reported symptoms of acute hepatitis with discrete onset of symptoms, consistent with requirements of the surveillance case definitions. From onset of symptoms to study enrollment and interview, the median interval was 10 weeks. Jaundice was reported by 67% of case patients. Symptoms of acute hepatitis were listed as a primary indication for viral hepatitis diagnostic testing by 79% of the case patients. Insurance status among cases and controls was similar, with 2% of cases and 3% of controls reporting that they were uninsured; similar percentages of cases (56%) and controls (55%) reported Medicaid or Medicare coverage.

Methods:  This retrospective study enrolled 38 chronic hepatitis B patients treated with IFN-α plus a nucleos(t)ide analog who achieved HBsAg seroconversion during the period from June 2001 to May 2009. Clinical and laboratory data of the patients were collected before and after treatment every 3 months. All patients with HBsAg seroconversion in this study were followed up for at least 12 months post-treatment. Results:  A total of 38 out of 142 patients achieved HBsAg seroconversion after treatment with IFN-α and a nucleos(t)tide analog for a prolonged period of time (medium 31 months). The median time to hepatitis B e antigen seroconversion and INCB024360 to HBsAg seroconversion was 19.5 months

(range 3–60 months) and 25.5 months (range 9–63 months), respectively. Thirty-six patients (95%) sustained HBsAg seroconversion during the post-treatment follow up. Three different HBsAg response patterns were observed with classical model accounting for 57.9% (22/38 cases), simultaneous transition

mode accounting for 23.7% (9/38 cases), and HBsAg prior transition model accounting for 18.4% (7/38 cases). Conclusions:  Extended treatment with IFN-α in combination with a nucleos(t)ide analog in patients with hepatitis-B-e-antigen-positive appears to be a promising approach for achieving a high rate of HBsAg clearance—the closest outcome to cure. “
“Drug-induced liver injury (DILI) is Z-VAD-FMK solubility dmso largely a diagnosis of exclusion and is therefore challenging. The US Drug-Induced Liver Injury Network (DILIN) prospective

study used two methods to assess DILI causality: a structured expert opinion process and the Roussel-Uclaf Causality Assessment Method (RUCAM). Causality assessment focused on detailed clinical and laboratory data from patients with suspected DILI. The adjudication process used standardized numerical and descriptive definitions and scored cases as definite, highly likely, probable, possible, or unlikely. Results of the structured expert opinion procedure were compared with those derived by the RUCAM approach. Among 250 patients with suspected DILI, the expert opinion adjudication 上海皓元医药股份有限公司 process scored 78 patients (31%) as definite, 102 (41%) as highly likely, 37 (15%) as probable, 25 (10%) as possible, and 8 (3%) as unlikely. Among 187 enrollees who had received a single implicated drug, initial complete agreement was reached for 50 (27%) with the expert opinion process and for 34 (19%) with a five-category RUCAM scale (P = 0.08), and the two methods demonstrated a modest correlation with each other (Spearman’s r = 0.42, P = 0.0001). Importantly, the RUCAM approach substantially shifted the causality likelihood toward lower probabilities in comparison with the DILIN expert opinion process. Conclusion: The structured DILIN expert opinion process produced higher agreement rates and likelihood scores than RUCAM in assessing causality, but there was still considerable interobserver variability in both.

Whole blood samples distributed internationally yield sufficient quantity and quality of DNA for analysis even when transport delays of several days occur. The majority of laboratories in each exercise achieve full marks,

and failing is unusual. Reasons for failing an exercise include clerical inaccuracies [e.g. a failure to include unique identifiers for each individual(s)]; genotyping errors (e.g. incorrectly numbering the mutation or predicted effect on the protein; failing to identify a mutation that was present; identifying a second mutation that was not present) and finally interpretation errors. Many of the errors that have led to a fail were based upon incorrect interpretation, e.g. failure to answer the clinical question; incorrectly assigning carrier status (or not) to an ‘at-risk’ female; failing to establish CHIR-99021 mw the significance of a novel mutation and failing to consider the possibility of mosaicism. The aim of EQA schemes is to highlight problems and deficiencies in laboratory procedures. This EQA

scheme has led to a more uniform inclusion of information into reports selleck chemical and a standardized use of mutation nomenclature. There are currently 27 laboratories registered for this scheme: 24 in the EU of which 12 are in the UK and three in non-EU countries. The scheme has received very positive feedback from participants and is seen as a fundamental part of good laboratory practice. This article has demonstrates (i) the continuing development of molecular genetic analysis of haemophilia directed towards identifying the causative mutation in virtually all patients; and (ii) that for mutations identified, participation in an medchemexpress EQA scheme promotes reporting and interpretation of the effect of these mutations to a recognized international standard. This work was supported by a DFG grant (Deutsche Forschungsgemeinschaft: EL499/2-1), a Baxter bioscience grant (number: H12-000820)

and the Bayer Haemophilia Awards Program. Dr Carlos de Brasi has not received any commercial support during the past 2 years. Dr El-Maarri has received support to attend meetings from Bayer and Baxter. Dr Pezeshkpoor has received support to attend meetings from Biotest and Baxter. Professor Oldenburg received reimbursement for attending symposia/congresses and/or honoraria for speaking or consulting, and/or funds for research from Baxter, Bayer, Biogen Idec, Biotest, CSL Behring, Grifols, Inspiration, Novo Nordisk, Octapharma, Swedish Orphan Biovitrum, and Pfizer. Professor Goodeve has received honoraria for presentations given from Novo Nordisk and Octapharma and receives support for the ISTH VWF mutation database from CSL Behring. Dr Perry has received educational grants and support to attend meetings from Baxter Healthcare and Novo Nordisk. He has also received consultancy fees from Biogenidec and Amgen.