Further analysis by immunohistochemistry demonstrated elevated expression of pChk2, γH2AX (S139), phosphorylated p53 (on serine 15 and 20) in β2SP+/− mice at different timepoints in comparison to wildtype mice (Fig. 4A,B, Supporting Table 2). Moreover, peak phosphorylated p53 expression correlated with elevated p21 expression, suggesting activation of the DNA damage response and downstream target gene regulation by p53, leading to growth arrest and delayed liver regeneration. Given the elevated levels of p53 in β2SP+/− mouse livers following PHx, we further investigated whether

down-regulation of p53 influences cell cycle progression of β2SP+/− MEFs and primary hepatocytes Nutlin-3 cost in which β2SP levels were reduced by shRNA-mediated Angiogenesis inhibitor knockdown. Under serum-starved

conditions, β2SP−/− mutant (MT) MEFs showed a marked reduction of the G0/G1 population in comparison to wildtype control MEFs (Fig. 5), consistent with in vivo data obtained from β2SP+/− PHx mouse livers. There was no significant difference between wildtype MEFs transfected with p53 shRNA and untransfected wildtype MEFs. These results suggest that, whereas p53 induction is associated with reduced β2SP levels in vivo following PHx, p53 is not the exclusive mediator of aberrant cell cycle in β2SP+/− hepatocytes. It is likely that factors other than p53 also contribute to the defects in cell cycle progression observed in regenerating β2SP+/− hepatocytes. β2SP has been previously demonstrated to be a key adaptor protein in TGF-β signaling and a key tumor-suppressor protein in foregut cancers: nearly 40% of β2SP+/− mice develop hepatocellular carcinoma by 15 months of age and nearly 90% of β2SP+/−/Smad4+/− double heterozygote mutants develop gastric tumors.13, 20 Moreover, FACS analysis of β2SP−/− MEFs following serum starvation and release demonstrated reduction of the G1 population and faster entry into S phase in mutant MEFs compared with wildtype.16 These observations suggest that β2SP plays a key role in

cell cycle progression and tumorigenesis. To further investigate this role in vivo, we examined liver regeneration Loperamide following PHx. Interestingly, our results demonstrated that diminished expression of β2SP is associated with increased DNA damage, activation of the DNA damage response proteins p53 and p21, and G2/M-phase arrest following PHx. TGF-β, which is capable of inducing an antiproliferative gene response at any point in the cell cycle, is most effective at inhibiting cell cycle progression during G1 by way of inhibition of cyclins D, E, and A or by way of Cdk4 synthesis.21-24 Disruption of TGF-β signaling in liver regeneration, by way of conditional knockout of the TGF-β type II receptor (TBRII), has similarly demonstrated a nearly 2-fold increase and acceleration of S-phase entry following hepatectomy.

“
“Factor XIII congenital deficiency (FXIII CD) is a serious bleeding disorder resulting in a lifelong bleeding tendency, defective wound healing and recurrent miscarriage. The aim of this study was to review available literature on the burden and management of FXIII CD. To this end, Medline, Embase and Cochrane databases were searched. In current literature, FXIII CD is described as one of selleck the most severe forms

of a congenital coagulation disorder, primarily due to a high risk of severe bleeding events. The published literature suggests that over 50% of untreated FXIII CD patients experience severe bleeding symptoms. Intracranial haemorrhage (ICH) – a major cause of death and morbidity – is reported to occur in up to one-third of patients. Nonetheless, data on the social and financial burden in patients with FXIII CD are sparse. Identified reports on the effectiveness I-BET-762 solubility dmso and safety of recommended treatments support that patients with FXIII CD should receive prophylactic treatment as early as possible in their lives to prevent the occurrence of bleeds, including potentially life-threatening ICHs. In conclusion,

limited data on the social and economic consequences related specifically to FXIII CD have been published to date. However, it is widely acknowledged that the high risk of severe bleeds and ICH results in a high level of burden in patients with bleeding disorders. To inform future clinical decision-making and reimbursement decisions, further research is required to gain insight in how specifically FXIII CD affects quality of life and to fully understand associated economic consequences. “
“This chapter contains sections titled: Frequency of inhibitors in hemophilia B Risk Fluorometholone Acetate factors for development of factor IX inhibitors Age and number of exposure days to fix at detection of factor IX inhibitors Anaphylaxis and other allergic reactions developing in close association with factor IX inhibitor development Management of patients with hemophilia B complicated by a factor IX inhibitor References “
“This chapter contains sections titled: Introduction Structure/function

Molecular genetics Clinical presentation Diagnosis Treatment Prognosis References “
“Summary.  On-demand therapy enables stopping haemorrhages rapidly, reducing joint pain and restoring joint mobility, but does not prevent the beginning and subsequent development of haemophilic arthropathy. The main objective of this study was to identify the clinical and orthopaedic status of severe haemophilic patients with bleeding phenotype receiving on-demand treatment in Spain. We conducted an epidemiological, observational, retrospective study, recruiting 167 patients from 36 centres (92% of them with haemophilia A), median age at enrolment of 35 years. Forty per cent of the patients received a combination of on-demand and short-term prophylaxis regimen; the rest was under on-demand treatment.

22 of 37 PWH who underwent MJP between 1995 and 2012 were available for assessment. Pain (WFH score) and range of motion were compared pre and postoperatively. Current outcome was

described by VAS per joint, nocturnal and overall pain, MACTAR, Hemophilia Activity List, SF36, and EQ-5D. Mean age at surgery AZD6738 research buy was 50, 3 years (SD 8, 3); mean follow-up 12 years (1–18 years). Pain (VAS) decreased post-surgery (Median 1 – 1, 5), but moderate pain remained. Extension of knees slightly increased, but both knee flexion and ankle plantar and dorsal flexion decreased. PWH reported the ability to stand longer but also pointed at specific problems, e.g. riding a bike (MACTAR). The HAL showed limited activities (functional domains), especially in the ‘complex lower extremity’ (22, 8/100). The SF36 and EQ-5D showed a mix of physical problems of our population, while experiencing moderate pain and reasonable physical functioning. This led us to the conclusion that adequate follow-up is needed: ROM of all joints, VAS of all joints as well as nocturnal and overall pain, HAL, SF36 and EQ5D. Performance selleck chemicals llc based activities and participation need further attention. “
“While chronic degenerative arthropathy is the main morbidity of haemophilia, a very high prevalence of low bone density is also seen in men and boys with haemophilia.

This study investigates bone degradation in the knee joint of haemophilic mice resulting from haemarthrosis and the efficacy of aggressive treatment with factor VIII in the period surrounding injury to prevent bone pathology. Skeletally mature factor VIII knock-out mice were subjected to knee joint haemorrhage induced by puncture of the left knee joint capsule. Mice received either intravenous factor VIII

treatment or placebo immediately prior to injury and at hours 4, 24, 48, 72 and 96 after haemorrhage. Mice were killed 2-weeks after injury and the joint morphology and loss of bone in the proximal tibia was assessed using microCT imaging. Quantitative microCT imaging of the knee joint found acute bone loss at the proximal tibia following injury including loss of trabecular bone volumetric density and bone mineral density, as well selleck products as trabecular connectivity density, number and thickness. Unexpectedly, joint injury also resulted in calcification of the joint soft tissues including the tendons, ligaments, menisci and cartilage. Treatment with factor VIII prevented this bone and soft tissue degeneration. Knee joint haemorrhage resulted in acute changes in adjacent bone including loss of bone density and mineralization of joint soft tissues. The rapid calcification and loss of bone has implications for the initiation and progression of osteoarthritic degradation following joint bleeding. “
“Summary.

marsci.uga.edu/fidoplankter. “
“Microalgal strains for algal biofuels production in outdoor ponds will need to have high net growth rates under diverse environmental conditions. A small,

variable salinity pond in the San Elijo Lagoon estuary in southern California was chosen to serve as a model pond due to its routinely high chlorophyll content. Profiles of microalgal assemblages from water samples collected from April 2011 to January 2012 were obtained by constructing 18S rDNA environmental clone libraries. Pond assemblages were found to be dominated by green algae Picochlorum sp. and Picocystis sp. throughout the year. Pigment analysis suggested that the two species contributed most of the chlorophyll a of the pond, which ranged from 21.9 to 664.3 μg · L−1 with the Picocystis contribution check details increasing at higher salinities. However, changes of temperature, Selleckchem CH5424802 salinity or irradiance may have enabled a bloom of the diatom Chaetoceros sp. in June 2011. Isolates of these microalgae were obtained and their growth rates characterized as a function of temperature and salinity. Chaetoceros

sp. had the highest growth rate over the temperature test range while it showed the most sensitivity to high salinity. All three strains showed the presence of lipid bodies during nitrogen starvation, suggesting they have potential as future biofuels strains. “
“Inorganic carbon uptake by Alexandrium catenella

estimated from incorporation of 13C labelled bicarbonate (an estimate of carbon gain by autotrophy) was compared to increases in particulate carbon (PC) that integrate all processes leading to carbon gain by cells (autotrophy, heterotrophy, mixotrophy). During blooms of A. catenella in the field, the 13C tracer technique could account for only 47% (range 29%–59%) of the increase in PC in conventional 24 h incubations. From dilution experiments, the ratio of PC increases Calpain to bicarbonate uptake was related significantly and positively to the grazing rate, indicating that dissolved organic carbon contributes to growth as a direct function of grazing activity. In addition, as grazing rate increases, the contribution of dissolved inorganic carbon uptake to carbon-based growth decreases in a linear way (from 56% to 33% of total C acquisition) and the contribution of non autotrophic processes increases (from 54% to 67%). Thus, grazing appears to closely control the balance between autotrophic and non autotrophic processes leading to carbon acquisition by natural populations of A. catenella. “
“Resource allocation and translocation are fundamental physiological functions for autotrophs. The mobilization and use of resources drive population dynamics by regulating growth and recovery of individuals, but also influences ecosystem-level processes such as primary productivity and carbon cycling.

In this report, we compare cellular responses in the livers of rats exposed to hepatocarcinogenesis beginning at 3 weeks of age, beginning at 8 weeks of age, and in retired breeders (10-12 months of age), using a previously well-studied chemical regimen, choline-deficient, ethionine-supplemented (CDE) diet.8-10 Following the hierarchical model of Pierce et al.,11 combined with analysis of the cellular events selleck compound during chemical hepatocarcinogenesis, we

previously concluded that, in adults, liver cancers can arise from liver stem cells (oval cells), transit-amplifying cells (ducts or immature hepatocytes), or mature hepatocytes, depending on the stage of maturation arrest.12-15 Although that model fit the experimental

observations on the cellular origin of hepatocellular carcinomas (HCCs) and cholangiocarcinomas (CCAs), it did not include the step between pluripotent stem cells (teratocarcinoma) and the liver lineage cells. The missing link is a cancer known as hepatoblastoma (HB).16, 17 HB completes the cellular lineage of liver cancer that extends from pluripotent stem cells to liver-determined stem cells to ductular stem cells to mature liver cells (Fig. 1A). We reasoned that if more liver stem cells are present, or if liver stem cells have greater potential in young rats as compared to old rats, then treatment of very young rats with a potent hepatocarcinogenic regimen should induce a more intense oval cell response and result in production of less well-differentiated HCCs, possibly such as HBs, than does treatment SPTLC1 of older rats.18 We report here that cyclic CDE treatment

EPZ-6438 in vivo of rats beginning at 3 weeks of age indeed caused a much higher level proliferation of oval cells than did treatment of rats beginning at 8 weeks of age and older. However, unexpectedly, exposure of the younger rats resulted in a high incidence of cholangiofibrosis and bile duct cancers, rather than HBs, suggesting that by 3 weeks of age the reactive liver-specific stem cells of the rat that give rise to cancer are already determined beyond the hepatoblast stage to ductal cell precursors. CCA, cholangiocarcinoma; CD, choline-deficient; CDE, choline-deficient, ethionine-supplemented; HCC, hepatocellular carcinoma Male Fischer 344 rats were obtained from Taconic Farms, Germantown, NY. Rats were housed in the Wadsworth Center’s animal facility and had free access to standard laboratory chow and water when not in the cyclic CDE regimen. All animal experiments were approved by and performed under the guidelines of the Wadsworth Center’s Institutional Animal Care and Use Committee (IACUC). A choline-deficient diet was obtained from Dyets, Inc., Bethlehem, PA (catalogue #518753). D,L-Ethionine was purchased from Sigma Chemical Co., St. Louis, MO (catalogue #E5139). A cyclic feeding regimen of the CDE diet was followed. One cycle consisted of 2 weeks on the choline-deficient (CD) diet, followed by 1 week off.

In 1987, through an interagency agreement with HRSA, the CDC initiated funding for HTCs to conduct HIV risk-reduction services

to determine the HIV prevalence among individuals with haemophilia who were exposed to contaminated blood products, their sexual partners and children. To monitor HIV risk-reduction service delivery, in 1989 a national committee of HTC clinicians and HRSA staff established a registry, the Hemophilia Minimal Data Set (HDS). Registry data were aggregated at the HTC level in response to widespread fears that individual-level data would threaten the HIV-status confidentiality, and lead to discrimination. Since 1990, HDS data from all HTCS have STI571 been submitted annually to HRSA and CDC by the 12 regional grantee centres. Over the years, the HDS broadened to capture more detailed demographic, diagnostic, mortality and health services data. It evolved into an electronic system to enhance data quality, by ensuring that inclusion criteria are met and purging old records. Each HTC uses a glossary that defines the data elements and outlines their proper entry to generate accurate reports. The annual HDS report Kinase Inhibitor Library molecular weight includes patients who have any HTC visit type during the calendar year. Patients who die are considered ‘active’ for that calendar year and purged from future reports. Individuals are

considered to be ‘active’ only at their primary HTC. Duplication is a consistent but presumed small problem, typically occurring when patients need access to specialty services (e.g. complex orthopaedic surgery) that are offered only at another HTC. The HDS report more likely undercounts patients because it does

not include those with mild disorders who commonly visit the Center every 2 or 3 years. HDS variables and definitions changed between 1990 and 2010, limiting the number of data elements that could be compared. This analysis examines trends where variable definitions were consistent. From 1990 to 2010, the numbers of patients seen at oxyclozanide HTCs experienced growth and change (Fig. 1). While the general US population grew 24% [18], the HTC population grew 90% from 17 177 to 32 612. Milestones were achieved in 1994 with >20 000 HTC patients, in 2000 with >25 000 patients and in 2008 with >30 000 patients. From 1990 to 2010, the HTC haemophilia population with FVIII deficiency grew by 35% from 9 805 to 13 276; and those with FIX deficiency grew by 66% from 2 531 to 4 209. Factor IX as a percent of the haemophilia patients grew from 20% in 1990 to 24% in 2010. HTC patients with VWD grew by 148% from 5 326 in 1996 to 13 239 in 2010; they now nearly equal the HTC FVIII population. The total number of HTC patients with ‘Other’ rare factor deficiencies (e.g. factors I, II, V, VII, X, XI and XIII) grew by 43% from 1 237 in 2002 to 1 772 in 2010. These factor deficiencies have extremely low prevalence in the general population. Starting in 2002, disorder severity was collected, and appeared to remain constant.

45 and those with a FIB-4 index of more than 3.25 were significant (P = 0.010). In addition, the FIB-4 index was significantly correlated with BCAA and tyrosine (BCAA, r = −0.28, P = 0.029; tyrosine, r = 0.38, P = 0.001). Table 2 shows the correlation between HOMA-IR and clinical parameters, and Figure 3 shows the correlation between HOMA-IR and BTR and serum levels of BCAA and tyrosine. There was a significant correlation between HOMA-IR

and BMI (r = 0.40), hemoglobin (r = −0.26), platelet count (r = −0.29), total bilirubin (r = 0.38), total protein (r = −0.25), albumin (r = −0.53), PT (r = −0.36), total cholesterol (r = −0.32), fasting glucose (r = 0.35), BTR (r = −0.46) and tyrosine (r = 0.55). However, BCAA and FIB-4 index were not significantly correlated

with HOMA-IR (BCAA, r = −0.21, P = 0.082; FIB-4 index, r = 0.15, P = 0.223). Twenty-six patients had a HOMA-IR of 2.5 or more (22 Rapamycin price patients with LC and four patients with CH). A ROC analysis was performed to calculate the AUC for the clinical parameters that were significantly correlated with HOMA-IR. Six parameters had an AUC of 0.7 or more (tyrosine [AUC, 0.78], total cholesterol [AUC, 0.77], albumin [AUC, 0.77], BTR [AUC, 0.76], total bilirubin [AUC, 0.74] and PT [AUC, 0.70]) (Fig. 4). For each of these six parameters, the cut-off value was set according to the sensitivity and specificity determined by the ROC analysis (tyrosine, 113 μmol/L [sensitivity, 65.4%; specificity, 80.0%]; total cholesterol, 140 mg/dL [sensitivity, 61.5%; specificity, 86.4%]; albumin, 3.1 g/dL selleck compound [sensitivity, 30.8%; specificity, 97.8%]; BTR, 3.14 [sensitivity, 46.2%; specificity, 93.3%]; total bilirubin, 1.2 mg/dL [sensitivity, 53.8%; specificity, 82.2%]; and PT, 70% [sensitivity, 46.2%; specificity, 95.5%]). In three clinical parameters (hemoglobin, platelet count and total protein), the cut-off value was the

lower limit of the normal range (hemoglobin, 14 g/dL; platelet count, 15 × 1010/L; and total protein, 6.8 g/dL). The cut-off value for fasting glucose was the upper limit of the normal range (110 mg/dL), ADAM7 and the cut-off value for BMI was 25 kg/m2 (according to the Japan Society for the Study of Obesity, the currently recommended BMI cut-off value for obesity is ≥25 kg/m2). We assessed the clinical parameters contributing to HOMA-IR 2.5 or more using logistic regression. The univariate analysis showed that total bilirubin, albumin, PT, total cholesterol, BTR and tyrosine were independent parameters contributing to a HOMA-IR of 2.5 or more, and the multivariate analysis further identified total cholesterol (OR, 6.511; 95% CI, 1.554–27.284; P = 0.010) and tyrosine (OR, 4.839; 95% CI, 1.087–21.549; P = 0.039) (Table 3). INSULIN RESISTANCE IS a risk factor for hepatic fibrosis and HCC in patients with HCV-related chronic liver disease, as well as a sign of poor prognosis in these patients.

Stable CAL-101 nmr transfection is described in the Supporting Materials and Methods. Whole cell protein was extracted with cell lysis buffer (Sigma-Aldrich, St. Louis, MO). Cytoplasmic protein extraction and western blotting analysis were performed by following

a standard protocol, as described previously.17 The RNA interference experiment protocol is described in the Supporting Materials and Methods. HMGB1 level in serums from humans and mice was detected by enzyme-linked immunosorbent assay (ELISA) (IBL, Toronto, Ontario, Canada), according to the manufacturer’s instructions. Cultures were fixed, stained, and examined under a confocal microscope (Olympus, Tokyo, Japan), as described in the Supporting Materials and Methods. The Caspase-1 Colorimetric Assay kit (R&D Systems, Minneapolis, MN) was used according to the manufacturer’s protocol. We determined migration and invasion as previously described.18 To examine the metastatic potential of stable HMGB1 knockdown

clones, 2 × 106 Hepa1-6, in 0.3 mL of phosphate-buffered this website saline, were injected into the tail vein of C57BL/6 mice. For in vivo tracking, the Hepa1-6 cells were stably transfected with firefly luciferase. One hundred milligrams per kilogram of D-luciferin (Caliper Life Sciences, Hopkinton, MA) were injected into the peritoneal cavities of mice, and bioluminescence was detected with the IVIS 100 Imaging System (Caliper Life Sciences). Results are expressed as the mean ± standard error of the mean (SEM). Statistical Phospholipase D1 analysis was performed using

the Student’s t test or one-way analysis of variance test. All statistical analyses were performed using Sigma Stat v.3.5 (Systat Software, Inc., Chicago, IL). Graphs were generated using Sigma Plot v.10 (Systat Software). P < 0.05 was denoted as statistically significant. Overexpression of HMGB1 is associated with tumor progression.13 To study the role of HMGB1 in HCC, we first examined the amount of HMGB1 in 20 HCC tissue samples and their corresponding nontumor liver by immunoblotting analysis. The detailed clinicopathological information of 20 cases is shown in Supporting Table 1. We found that the expression of HMGB1 was higher in all HCC tissues (Fig. 1A). Compared to normal primary hepatocytes, the expression of HMGB1 was also much stronger in five HCC cell lines (Fig. 1B). We then examined the level of nuclear and cytoplasmic HMGB1 by the fractionation of nuclear and cytoplasmic proteins in HCC tissues and nontumor liver tissues. The amount of nuclear HMGB1 in HCC tissues and nontumor tissues was not significantly different (data not shown). However, cytoplasmic HMGB1 was absent or present at low levels in nontumor tissues, whereas cytoplasmic HMGB1 was found at high levels in HCC tissues (Fig. 1C). High cytoplasmic levels of HMGB1 usually occur in the context of active HMGB1 release.

Between 2003 Selleck Veliparib and 2013, 18 exercises were undertaken (Table 1), the most recent

was circulated in June 2013 (Exercise 22). The disorders and underlying genetic mutations evaluated by UK NEQAS have been chosen to reflect the routine workload in molecular genetics laboratories. Ten exercises have involved analysis of the F8 gene of which three were for the Inv22, one for Inv1 and the remainder diverse sequence variations. Four exercises involved analysis of F9, two for a promoter mutation (not associated with HB Leiden) and two for missense mutations. Finally, three exercises involved analysis of missense mutations within VWF. A formalized template for scoring reports was introduced in 2003. This template was employed to introduce a degree of objectivity to a subjective

assessment process. The template is based upon recommendations of the UK CMGS best practice guidelines on report writing [24] with a maximum score of 2 marks for each of three sections; namely clerical accuracy, genotyping and interpretation. In each category, information considered ‘essential’ or ‘recommended’ has a different weighting and this weighting is established in advance of the laboratory report assessment. A score of <1 in any one category constitutes a ‘fail’ in that exercise. Reports are scored independently by four experienced individuals and a consensus subsequently reached. Laboratories that are BGB324 purchase registered with the scheme who either fail to submit a report or do so outside the allocated turnaround time of 6 weeks (chosen to reflect UKHCDO recommendations) will also fail. A fail in any exercise generates a letter from the Director of UK NEQAS BC with the offer of assistance. Each participating laboratory is assigned a unique identification

number that allows the continuing performance of each laboratory many to be reviewed. The identification of participating laboratories remains unknown to the reviewers. All participating laboratories use the mutation nomenclature system proposed by the Human Gene Variation Society (HGVS) [25] that requires all sequence variations to be defined in relation to a specified reference sequence. The ‘A’ nucleotide of the ATG-translation initiation codon to be numbered as +1 with the protein sequence representing the primary translation product numbered from the initiator methionine and therefore, includes signal peptide sequence. For some genes and proteins, this requires renumbering and makes reference to previously described mutations challenging. Laboratories are, therefore, encouraged to include legacy nomenclature as a number of published mutations including some of those listed in online locus-specific mutation databases remain in the ‘legacy’ format.

10-40.0), only 2 as a result of non-liver-related death. The remaining 49 were alive after a median of 55 months (range, 0.7-69.0). Uni- and multivariable analysis for intervention-free

survival is detailed in Supporting Table 5. The Rotterdam score had an excellent prognostic value, and no further variable could significantly improve its prognostic ability. This validates the Rotterdam score as a useful prognostic tool in this post-therapeutic series of BCS. Supporting Fig. 2 shows survival curves for Rotterdam class I, II, and III. Because the Rotterdam score includes the INR, which could not be RG7204 order calculated in a substantial number of patients (already on oral anticoagulants), we performed a multivariable analysis without including scores or INR. Baseline ascites, bilirubin, and creatinine were independently associated with intervention or death (BCS-intervention-free survival prognostic score [BCIS score]: ascites

[yes = 1, no = 0]*1.675 + ln creatinine [umol/L]*0.613 + ln bilirubin [umol/L]*0.440). This data-driven new score showed an adequate discrimination BAY 80-6946 chemical structure (area under the curve [AUC] = 0.819), but it did not outperform the Rotterdam score (AUC, 0.821)9 (Supporting Fig. 3). The probability of intervention-free survival among different intervals of the BCIS score is shown in Supporting Table 7. Thirty-six patients (23%) died during the study. Median time to death was 10 months (range, 0.1-41.0). Main causes of death are reported in Table 2. Factors associated with mortality are shown in Supporting Table 6. The BCS-TIPS PI score was strongly associated with the risk of death, so that no other variable could improve its predictive capacity. Supporting

Table 8 shows survival among different ranges of BCS-TIPS PI scores. Because this score includes the INR, we performed a multivariable analysis excluding all scores and INR. Age, bilirubin, and creatinine were independently associated these with survival [BCSurvival score: age/10*0.370 + ln creatinine [umol/L]*0.809 + ln bilirubin [umol/L]*0.496). The discriminative capacity was comparable to that of the BCS-TIPS PI score and better than the Rotterdam score (Supporting Fig. 4). BCS is a rare, life-threatening disorder caused by obstruction of hepatic venous outflow. Until recently, most evidence regarding BCS was generated in small retrospective studies of patients diagnosed over long periods and managed using heterogeneous strategies.7, 9, 14 However, an international initiative, funded by the Fifth Framework Program of the European Commission, entitled the EN-Vie, was able to prospectively gather a large multicenter cohort of consecutive patients with BCS diagnosed and treated following homogeneous criteria.4 Previous retrospective studies evaluating prognosis in BCS showed that fatal events occur throughout the first 5 years after diagnosis.