The core promoter dictates the expression of the HBV e antigen, core

protein, and DNA polymerase. The X promoter controls the transcription of the X RNA. After its synthesis, the core protein packages the core RNA, which is larger than the genome size and is also known as the pregenomic RNA (pgRNA), to form the core particle. The pgRNA then serves as the template to direct the synthesis of the partially double-stranded viral DNA genome, using the viral DNA polymerase that is also packaged. The core RNA plays a pivotal role in the HBV life cycle and its increased expression has been shown to enhance viral replication.3, 4 The identification of host factors that interact with the HBV DNA genome has made significant contributions to our understanding of mechanisms that regulate HBV gene

expression. Indeed, both liver-enriched and ubiquitous transcription factors, such as hepatocyte Tanespimycin ic50 nuclear factor 1 (HNF1), HNF3, HNF4, CCAAT enhancer-binding protein (C/EBP), chicken ovalbumin upstream promoter transcription factor (COUP-TF), nuclear transcription factor Y (NF-Y), and specificity protein 1 (Sp1), have been shown to regulate the expression NU7441 supplier of the S and C genes.5-13 The liver specificity of the preS1 promoter, the major surface promoter, and the core promoter is attributed to the need of liver-enriched transcription factors for their activities.10, 14-18 In this study, we used a yeast one-hybrid screen to identify additional transcription factors that could activate the major surface promoter. Using cDNA libraries prepared from the human hepatoma cell line, Huh7, and mouse liver, we identified several MCE members of the Krüppel-like factor (KLF) family as potential activators of the surface promoter (T. Tan and T.S.B. Yen, unpublished

data). KLF family members are characterized by their three carboxy-terminal C2H2 zinc fingers and share a high degree of homology with Sp1-like proteins. At least 21 Sp1/KLF proteins have been identified in the human genome. They have highly conserved DNA-binding domains, but show significant variations in the transactivation domain in their amino terminus.19, 20 Krüppel-like factor 15 (KLF15) has been shown to regulate the expression of a number of genes involved in many aspects of physiological homeostasis, including glucose uptake and adipogenesis.21-25 Moreover, KLF15 is highly expressed in the human liver.25 These observations led us to hypothesize that KLF15 might be a potential activator for HBV gene expression. Indeed, our results indicate that KLF15 can activate the expression of the HBV S and C genes both in vitro and in vivo. Our results thus uncovered previously unrecognized functions of KLF15 in HBV gene expression.

Skulls from the University of Canterbury (UC) collection (n = 9) were used without additional preparation.

Cranial volume of clean, dry skulls (n = 21) was determined in triplicate using spherical plastic beads with a mean diameter of 5.6 ± 0.03 mm. The density of packed beads was first determined from the mass of beads that could be packed into the spherical (i.e., cranium-like) portion of volumetric flasks (100, 250, 500, http://www.selleckchem.com/products/MLN-2238.html and 1,000 mL capacity); the volume of the spherical portion was measured by weighing distilled water at 20°C and dividing the resulting mass by the density of water at this temperature (0.998203 g/cm3). The relationship of bead bulk volume (y, cm3) to bead mass (x, g) was (1) Skulls sectioned for brain mass (Fig. 1) were reassembled using masking tape, and in all skulls foramina were plugged with foam ear plugs and/or masking tape to prevent loss of beads. Prepared skulls were

weighed empty to determine the tare mass before filling the cranial buy 3-Methyladenine cavity with beads through the foramen magnum. Care was taken to shake skulls during filling to ensure close packing of beads (Donev et al. 2004) and reduce interference by the bony tentorium (tentorium cerebelli osseum) present in Weddell seals. The net mass of the beads was determined as the difference between the mass of empty (tare) and filled skulls (tare + beads), and cranial capacity was calculated from net bead mass according to the relationship between bead mass and bead volume derived previously in vitro (Eq. (1) above).

The relationship between measured brM (x, g) and measured CC (y, cm3) was used to estimate brM from CC for adult (n = 9; UC collection) and neonatal (n = 3) skulls for which brM could not be directly determined (Fig. 2, Table 1). Unless otherwise indicated, results are expressed as mean ± SEM. BL, body length; BM, body mass; brM, brain mass; CC, cranial capacity (intracranial volume); CMR, cerebral metabolic rate; DGB, daily glucose demand of the brain; f. dom., forma domestica; MF, multiplication factor; RCMR, relative cerebral metabolic rate; MCE公司 UC, University of Canterbury, New Zealand. The relationship of measured brain mass (brM: x, g) and cranial capacity measured using plastic beads (CC: y, cm3) for pups and adults is shown in Fig. 2. Mean CC and brM of the two adult females measured directly (181, 5028; Table 1) were 574.7 cm3 and 563.4 g, respectively. Mean CC of skulls from the UC collection (n = 9) was 624.4 ± 16 cm3 (range 539–709 cm3), corresponding to a mean estimated brM of 626.9 ± 21 g. There was no significant difference in CC between the two sets of adult seals (t-test, P = 0.21). One stillborn pup (7547; Table 1) appeared to be premature on the basis of low body mass and small size, and was therefore omitted from analysis of brain size (but not from the comparison of brM and CC shown in Fig. 2, n = 7). Only skulls were available for pups 7639 and 7949, and brM for pup 7524 was not determined due to a taring error.

Skulls from the University of Canterbury (UC) collection (n = 9) were used without additional preparation.

Cranial volume of clean, dry skulls (n = 21) was determined in triplicate using spherical plastic beads with a mean diameter of 5.6 ± 0.03 mm. The density of packed beads was first determined from the mass of beads that could be packed into the spherical (i.e., cranium-like) portion of volumetric flasks (100, 250, 500, Selleckchem NVP-BGJ398 and 1,000 mL capacity); the volume of the spherical portion was measured by weighing distilled water at 20°C and dividing the resulting mass by the density of water at this temperature (0.998203 g/cm3). The relationship of bead bulk volume (y, cm3) to bead mass (x, g) was (1) Skulls sectioned for brain mass (Fig. 1) were reassembled using masking tape, and in all skulls foramina were plugged with foam ear plugs and/or masking tape to prevent loss of beads. Prepared skulls were

weighed empty to determine the tare mass before filling the cranial Rapamycin clinical trial cavity with beads through the foramen magnum. Care was taken to shake skulls during filling to ensure close packing of beads (Donev et al. 2004) and reduce interference by the bony tentorium (tentorium cerebelli osseum) present in Weddell seals. The net mass of the beads was determined as the difference between the mass of empty (tare) and filled skulls (tare + beads), and cranial capacity was calculated from net bead mass according to the relationship between bead mass and bead volume derived previously in vitro (Eq. (1) above).

The relationship between measured brM (x, g) and measured CC (y, cm3) was used to estimate brM from CC for adult (n = 9; UC collection) and neonatal (n = 3) skulls for which brM could not be directly determined (Fig. 2, Table 1). Unless otherwise indicated, results are expressed as mean ± SEM. BL, body length; BM, body mass; brM, brain mass; CC, cranial capacity (intracranial volume); CMR, cerebral metabolic rate; DGB, daily glucose demand of the brain; f. dom., forma domestica; MF, multiplication factor; RCMR, relative cerebral metabolic rate; MCE公司 UC, University of Canterbury, New Zealand. The relationship of measured brain mass (brM: x, g) and cranial capacity measured using plastic beads (CC: y, cm3) for pups and adults is shown in Fig. 2. Mean CC and brM of the two adult females measured directly (181, 5028; Table 1) were 574.7 cm3 and 563.4 g, respectively. Mean CC of skulls from the UC collection (n = 9) was 624.4 ± 16 cm3 (range 539–709 cm3), corresponding to a mean estimated brM of 626.9 ± 21 g. There was no significant difference in CC between the two sets of adult seals (t-test, P = 0.21). One stillborn pup (7547; Table 1) appeared to be premature on the basis of low body mass and small size, and was therefore omitted from analysis of brain size (but not from the comparison of brM and CC shown in Fig. 2, n = 7). Only skulls were available for pups 7639 and 7949, and brM for pup 7524 was not determined due to a taring error.

3% and 14.4%, respectively. Cirrhosis was found in 14.2% of all patients, with a higher frequency in the LdT group (28.4%) than the other two groups (12.2% in the ETV group and 14.6% in the LVD group). The proportions of patients who completed 1, 2, and 3 years of treatment are summarized in Table 2. Overall, 96.6% of patients did not modify the initial NA treatment. The ETV group had the highest rate of treatment maintenance

throughout the 3 years of treatment (≥ 98.2%), whereas the rate dropped from 90.5% and 97.0% at year 1 to 77.8% and 87.2% at year 3 in the LVD and LdT group, respectively. Figure 2 5-Fluoracil in vitro shows that the time to treatment modification was significantly different among the three groups (P < 0.001). A total of 16.1% of our patients had treatment modification: 9.0% in the ETV group, 38.8% in the LdT group, and 54.2% in the LVD group during the 3 years of treatment (Table 3). The most common type of treatment modification in the ETV group was “discontinuation of the initial NA” (59.5%), while “switch to another NA” was the most common in the LVD (50.0%) and LdT (42.3%) groups. None of the seven patients in the ETV group switched to another NA because of a clinical reason. The reasons for www.selleckchem.com/products/r428.html treatment modification were mainly clinical (83.0%

overall), with the major reasons being “fulfilling stopping criteria” in the ETV group (40.5%) and “virological breakthrough (including drug resistance)” in the LVD (46.2%) and LdT (61.5%) groups. The overall rate of adherence (mean ± SD) remained stable

throughout the entire treatment period (year 1: 96.8% ± 15.4%, year 2: 96.8% ± 11.5%, and year 3: 97.5% ± 10.3%) (Table 4). Further statistical analysis was performed to compare the patients with adherence rate > 90% with those ≤ 90%. For the first 2 years of treatment, the ETV group has statistically significant higher proportion of patients with > 90% adherence 上海皓元 rate among the 3 treatment groups. The proportion of patients with adherence rate > 90% at year 3 was 90.8% in the ETV group, 83.9% in the LdT group, and 83.9% in the LVD group; however, there is no statistical significant difference among the treatment groups. A total of five patients had at least one serious adverse event during the treatment period, four in the ETV group, and one in the LVD group. However, none of these were related to the NA used. In this multicenter observational study, we found that among ETV, LVD, and LdT, ETV had the lowest likelihood of initial NA treatment modification in treatment- naïve CHB patients in Taiwan during the 3-year treatment period. Our patients with ETV treatment also demonstrated the best adherence compared with those with LVD or LdT treatment. In this study, most patients completed the 3-year treatment without any modification of the initial NA, suggesting a satisfactory control of HBV replication during the treatment period. At year 1 of treatment, the rates of treatment modification were similar among the three groups.

Conclusion: We have isolated an epithelial cell population from primary mouse gallbladder with stem cell characteristics and found it to be unique, compared to IHBD cells. (HEPATOLOGY 2011) Understanding the resident stem cell populations of the biliary system has great importance for basic biology and biliary diseases. The biliary tree is divided into the intra- and extrahepatic biliary systems. The latter consists of the gallbladder, cystic duct, and the common bile duct.1 The biliary system CHIR-99021 concentration is a conduit for bile to be transported from the liver to the intestine. The gallbladder, in

turn, stores the bile and regulates its content and concentration, playing an important role in the digestive process.2, 3 Though there has been a lot of recent interest in the liver stem cell field,4 there is still a paucity of data regarding gallbladder stem cells. The biliary system, hepatocytes, and ventral pancreas develop from the ventral foregut endoderm.5, 6 Histological evidence suggesting that both intra- and extrahepatic systems originate from the hepatic diverticulum has led to the hypothesis that they see more descend from the same progenitor cell. However, the cell-intrinsic factors that result in their specification have heretofore been unclear. Recently, it has been shown that the progenitor cells that give rise to each system separate out during development.7 Using

a Pdx1-Cre mouse, Spence et al.7 demonstrated that hepatocytes and intrahepatic bile duct (IHBD) cells derive from Pdx1- cells, whereas the extrahepatic bile duct (EHBD) cells and ventral pancreas derive from Pdx1+ cells. Sox17 controls the specification medchemexpress of the EHBD and pancreatic cells.

Sox17 loss-of-function embryos exhibit gallbladder agenesis and the presence of ectopic pancreatic tissue in the extrahepatic bile duct. Conversely, Sox17 gain of function results in ectopic ductal tissue in the developing pancreas. In both cases, the intrahepatic system is not affected. It appears that the IHBD and EHBD cells descend from separate progenitor cells governed by separate transcriptional cascades. It is, therefore, possible that adult IHBD and EHBD cells could be distinct, as well. The aims of this study were to isolate and characterize stem cells from the adult mouse gallbladder and compare their phenotypic and expression profiles with IHBD cells. In addition to basic biology, an understanding of gallbladder stem cells would be vital to the study of gallbladder carcinoma, a rare, but poorly understood, malignancy8 and congenital diseases involving biliary dysmorphogenesis, such as biliary atresia.9 It would also elucidate the ontogeny of cells in the biliary system. Stem cells are defined as undifferentiated cells that can self-renew at the single-cell level and form lineage-committed progeny.

Third, evidence suggests that antigen-naïve B cells exert anti-inflammatory properties,48 which may inhibit APC maturation and proinflammatory differentiation49; in this regard, it has been demonstrated

that dendritic cells from B cell–deficient mice produce higher levels of IL-12 and promote proinflammatory T cell differentiation.8 Thus, our findings suggest that B cell depletion therapy may be contraindicated in PBC. Indeed, we know that B cell depletion in dnTGF-βRII mice exacerbates inflammation of bile ducts.24 Although a biochemical benefit of anti-CD20 therapy in PBC patients refractory to ursodeoxycholic acid has been reported,50 we suggest that additional data regarding the role of B cells PLX3397 ic50 in human mucosal autoimmune diseases such as PBC are needed. Finally, our findings underscore the fact that unanticipated problematic issues can arise from the use of biologics in humans and thus the importance

of trials in murine models and rigorous post marketing surveillance of such agents in humans. “
“To investigate the impact of hospital-acquired Clostridium difficile infection (CDI) on hospital costs and patient length of stay. Data from the 2007–2008 New York State Department of Health’s Statewide Planning and Research Cooperative System (SPARCS) database was analyzed using regression analysis and descriptive statistics. After analysis of 4 853 800 patient discharges, the incidence rate of hospital-acquired CDI was 0.8 cases per 1000 discharges. The estimated marginal cost associated with each hospital

infection was approximately $29 000. The estimated Selleckchem Olaparib annual cost of CDI in New York State was approximately $55 million with nearly 23 000 additional hospital days. The development of hospital-acquired CDI is associated with a significant increase in hospital costs and patient length of stay. Extrapolation of 上海皓元 these estimates to all US hospitals suggests this condition represents a major burden to the US healthcare system. Our findings may help hospitals understand the impact of these infections, as well as potential implications if deemed preventable by Centers for Medicare & Medicaid Services and/or private payers. Additionally, this information may benefit hospitals or health care systems transitioning to alternative payment models, such as episode-based payments or accountable care. Healthcare providers and hospitals would benefit from better understanding the impact and frequency of these infections in order to best target preventive strategies. “
“Aim:  Nuclear factor-κB (NF-κB) is a critical signaling mediator in inflammation, apoptosis resistance and oncogenesis. It has been reported that NF-κB is activated in several cancers, including hepatocellular carcinoma (HCC). Studies of genetic disruptions in mice also suggest that NF-κB plays critical roles in hepatocarcinogenesis. The aim of the present study is to characterize NF-κB activation and correlate it with the degree of malignancy in HCC.

Thus, they serve as an alternative for prognosis prediction. Furthermore, most patients died of non–tumor-related events, likely related to

increased viral replication and progression of liver disease. In this view, serum HBV-DNA might offer a better prediction value, because liver tissue sampling bias could be avoided. Of note, more patients in this study had genotype B than genotype C, which appears to contradict what previous studies have demonstrated: that genotype C, not genotype B, X-396 chemical structure is associated with HCC. However, among younger patients, genotype B has also been found to be associated with HCC.30 In this study, most of the patients included were under 60 years of age, because patients receiving surgical resections were more likely LY2157299 molecular weight to be younger. Furthermore, the present data as well as a previous study indicate that genotype C–related HCC is associated with a poorer prognosis and is likely to be more invasive11; this makes it less likely to be associated with resectable HCC, because resectable HCC tends to be less aggressive and is therefore diagnosed at earlier stages. As such,

it was not surprising that more of genotype B but not genotype C was found in the patients of this study, seeing as they had resectable HCCs. In this study, consistent with previous studies, the HBV-DNA level was closely associated with postoperative prognosis, albeit intrahepatic and not serum viral load was measured in this study. Additionally, univariate analysis indicated that genotype C was associated with a poorer prognosis. However, this factor did not appear to be significant in multivariate analysis. It was likely that the contribution of genotype C to the prognosis of HCC was masked by the presence of the BCP mutation, because genotype C was closely associated with the BCP mutation in HBV infection.31 The reason why the BCP mutation was independently linked to hepatocarcinogenesis is not well understood.

This could not be explained by better replication efficiency, because the mutation did not appear to be associated with changes in HBV-DNA levels, and one study revealed that HBV with BCP mutations actually had lower promoter activities.32 A possible explanation MCE is that the reduced promoter activities in BCP mutants help with evasion of host immunity during development of liver cancer. Alternatively, the concurrent amino acid substitutions in the X protein might enhance its oncogenicity. However, the latter possibility has not been supported by experimental evidence to date. Recent studies have shown that pre-S deletion mutants are highly implicated in hepatocarcinogenesis.28, 29, 33 Other studies, however, have demonstrated that pre-S deletions occur often in the stage of chronic active hepatitis, with almost the same frequency as that seen in HCC.

Thus, they serve as an alternative for prognosis prediction. Furthermore, most patients died of non–tumor-related events, likely related to

increased viral replication and progression of liver disease. In this view, serum HBV-DNA might offer a better prediction value, because liver tissue sampling bias could be avoided. Of note, more patients in this study had genotype B than genotype C, which appears to contradict what previous studies have demonstrated: that genotype C, not genotype B, PF-02341066 mouse is associated with HCC. However, among younger patients, genotype B has also been found to be associated with HCC.30 In this study, most of the patients included were under 60 years of age, because patients receiving surgical resections were more likely Alectinib purchase to be younger. Furthermore, the present data as well as a previous study indicate that genotype C–related HCC is associated with a poorer prognosis and is likely to be more invasive11; this makes it less likely to be associated with resectable HCC, because resectable HCC tends to be less aggressive and is therefore diagnosed at earlier stages. As such,

it was not surprising that more of genotype B but not genotype C was found in the patients of this study, seeing as they had resectable HCCs. In this study, consistent with previous studies, the HBV-DNA level was closely associated with postoperative prognosis, albeit intrahepatic and not serum viral load was measured in this study. Additionally, univariate analysis indicated that genotype C was associated with a poorer prognosis. However, this factor did not appear to be significant in multivariate analysis. It was likely that the contribution of genotype C to the prognosis of HCC was masked by the presence of the BCP mutation, because genotype C was closely associated with the BCP mutation in HBV infection.31 The reason why the BCP mutation was independently linked to hepatocarcinogenesis is not well understood.

This could not be explained by better replication efficiency, because the mutation did not appear to be associated with changes in HBV-DNA levels, and one study revealed that HBV with BCP mutations actually had lower promoter activities.32 A possible explanation MCE is that the reduced promoter activities in BCP mutants help with evasion of host immunity during development of liver cancer. Alternatively, the concurrent amino acid substitutions in the X protein might enhance its oncogenicity. However, the latter possibility has not been supported by experimental evidence to date. Recent studies have shown that pre-S deletion mutants are highly implicated in hepatocarcinogenesis.28, 29, 33 Other studies, however, have demonstrated that pre-S deletions occur often in the stage of chronic active hepatitis, with almost the same frequency as that seen in HCC.

FIB 4 values inversely correlated with TGF-beta1 (Rho correlation coefficient −0.38; p=0.0155). as well as with liver stiffness values (Rho

correlation coefficient −0.31; p=0.0498. CD14 (soluble and surface) levels were significantly different between HIV+ vs the healthy controls, HIV+HCV+ vs the healthy controls, HCV+ vs HIV+ HCV+ (p< 0.0001, Kruskal-Wallis test). IL17 was significantly different between HCV+ vs the others 3 groups. Bacterial DNA BAY 57-1293 purchase was significantly different in HIV+ vs the others 3 groups Conclusions: Foxp3+ levels are higher in patients with HIV, but they do not influence liver fibrosis staging. TGF-b1 levels inversely correlate with fibrosis suggesting a protective effect. Our data show that the group of HIV- HCV+ has increased levels of bacterial DNA, CD14 (soluble and surface) and IL17 expression of a major translocation as compared with the others groups. The existent correlation between the translocation index and FIB4 suggest that fibrosis stage http://www.selleckchem.com/products/PD-0325901.html may depend on immunoactivation caused by bacterial translocation Disclosures: The followinq

people have nothinq to disclose: Paolo Sacchi, Raffaele Bruno, Serena M. Cima, Marta Corbella, Giuditta Comolli, Antonella Chiesa, Fausto Baldanti, Catherine Klersy, Stefano Novati, Mara Mariconti, Claudio Baldi Background/Aims: Biological and epidemiological data suggest that vitamin D levels may influence cancer development. Several single nucleotide polymorphisms have been described in the vitamin D receptor (VDR) gene in association with cancer risk. We aimed to investigate the association of VDR polymorphisms with hepatocellular carcinoma MCE (HCC) development in chronic hepatitis C patients. Methods: In a cross-sectional, hospital-based setting, 340 patients (201 chronic hepatitis, 47 cirrhosis and 92 HCC) and 100 healthy controls receiving VDR genotyping (bat-haplotype: Bsml rs1544410 C, Apal rs7975232 A and Taql rs731236 A) and interleukin (IL)−28B genotyping

were enrolled. Results: Patients with HCC had a higher frequency of Apal CC genotype (P=0.018) and bAt[CCA]-hapiotype (P=0.019) as compared to control subjects. There were no differences in Bsml, Taql and IL28B polymorphisms between two groups. In patients with chronic hepatitis C, HCC subjects had a higher frequency of Apal CC genotype and bAt[CCA]-haplotype than those with chronic hepatitis (P=0.001 and 0.002, respectively) and cirrhosis (P=0.019 and 0.026, respectively). After adjusting age and sex, logistic regression analysis showed that Apal CC genotype (odds ratio: 3.02, 95% confident interval: 1.65-5.51) was independently associated with HCC development. Conclusion: VDR Apal polymorphism may play a role in the development of HCC among chronic hepatitis C patients. Further explorations of this finding and its implications are required.

Again the evidence is quite limited, but low-dose aspirin should not be withheld. There may be other considerations in this population. For example, there is some evidence that administration of a selective serotonin reuptake inhibitor post MI, when combined with low-dose aspirin or dual antiplatelet therapy, increases the risk of bleeding [18]. In contrast, administration of omeprazole with antiplatelet therapy reduces the risk of gastrointestinal bleeding [19]. Based upon the uncertainties in the haemophilic

population relative to the drugs they are receiving for their underlying coagulation defect and for vascular protection, platelet function testing would seem to be a step forward in the goal of developing personalized treatment strategies [20]. The prevailing Protein Tyrosine Kinase inhibitor view that patients with haemophilia are at low risk of ischaemic heart Lorlatinib manufacturer disease has led to a level of complacency regarding other CV risk factors, and as this population ages we need to pay more attention to treating disorders such as dyslipidaemias, where suitable safe therapies are available such as the statins. There are a small number of publications investigating outcomes in patients undergoing cardiac catheterization or cardiac surgery [coronary artery bypass grafting (CABG), cardiac valve replacement and percutaneous transluminal coronary angioplasty (PTCA)]

[21–23]. Replacement of deficient factor was the cornerstone of treatment in the studies and other therapeutic options included tranexamic acid, desmopressin and aprotinin. In this small group of patients with haemophilia (36 cases) cardiac surgery was performed safely with minimal morbidity and the results were similar to those achieved in patients

without haemophilia. Cardiac surgery is therefore clearly possible in patients with haemophilia, providing meticulous attention is paid to haemostatic treatment regimens. Some unanswered questions remain. For example, is it better to perform CABG immediately rather than MCE公司 PTCA which requires the administration of antiplatelet agents? With regards to valve replacement, bioprosthetic (tissue) valves are preferred to mechanical valves as they avoid the need for long-term anticoagulation [24]. The American Heart Association recommends that patients undergoing mitral valve replacement receive anticoagulation for 3 months. Patients having aortic valve replacement may not need anticoagulation unless they have certain risk factors such as: a history of thromboembolism/hypercoagulable condition; arrhythmia; low left ventricular ejection fraction (<30%); or an enlarged left atrium. All patients should be on low-dose aspirin. In patients with haemophilia during anticoagulation, factor trough levels should be ≥5%. Atrial fibrillation (AF) is becoming an increasing problem as the haemophilic population ages. A recent workshop recommended for a haemophiliac patient with AF [24]: 1  No anticoagulation if the AF was <48 h.