Ascher, John P. Roberts “
“Studies using

surrogate AZD2014 research buy estimates show high prevalence of insulin resistance in hepatitis C infection. This study prospectively evaluated the correlation between surrogate and directly measured estimates of insulin resistance and the impact of obesity and ethnicity on this relationship. Eighty-six nondiabetic, noncirrhotic patients with hepatitis C virus (age = 48 ± 7 years, 74% male, 44% white, 22% African American, 26% Latino, 70% genotype 1) were categorized into normal-weight (body mass index [BMI] < 25, n = 30), overweight (BMI = 25-29.9, n = 38), and obese (BMI ≥ 30, n = 18). Insulin-mediated glucose uptake was measured by steady-state plasma glucose (SSPG) concentration during a 240-minute insulin suppression test. Surrogate estimates included: fasting glucose and insulin, glucose/insulin, homeostasis model assessment (HOMA-IR), quantitative insulin sensitivity check index (QUICKI), insulin (I-AUC) and glucose (G-AUC) area under the curve during oral glucose tolerance test, and the Belfiore and Stumvoll indexes. All surrogate estimates correlated with SSPG, but the magnitude of correlation varied (r = 0.30-0.64). The correlation http://www.selleckchem.com/products/BIBW2992.html coefficients were highest in the obese. I-AUC had the highest correlation

among all ethnic and weight groups (r = 0.57-0.77). HOMA-IR accounted for only 15% of variability in SSPG in the normal weight group. The common HOMA-IR cutoff of ≤3 to define insulin resistance had high misclassification rates especially in the overweight group independent of ethnicity. HOMA-IR > 4 had the lowest misclassification rate (75% sensitivity, 88% specificity). Repeat HOMA-IR measurements had higher within-person variation in the obese (standard deviation = 0.77 higher than normal-weight, 95% confidence interval = 0.25-1.30,

P = 0.005). Conclusion: Because of limitations of surrogate estimates, caution should be used in interpreting data evaluating insulin resistance especially in nonobese, nondiabetic patients with HCV. HEPATOLOGY 2010 Epidemiologic studies support an association between chronic hepatitis C virus (HCV) infection and type 2 diabetes mellitus.1-3 The mechanism by which HCV may induce diabetes is thought to be related to insulin resistance and potential defects in insulin signaling pathways.4, 5 selleck inhibitor Studies to date have shown a higher prevalence of insulin resistance in HCV infection compared to hepatitis B virus infection and other causes of liver disease.6 Insulin resistance and diabetes in the setting of HCV infection is of great importance due to its association with increased rates of fibrosis and faster progression of liver disease7, 8 as well as potentially lower response to antiviral HCV therapy.9-11 To date, all human studies except for one that evaluated insulin resistance in the setting of HCV have used surrogate estimates of insulin resistance rather than direct measurements of insulin-mediated glucose uptake (IMGU).

Animals were allowed food and water ad buy AZD5363 libitum. All animals received humane care according to the criteria outlined in the Guide for the Care and Use of Laboratory Animals prepared by the National Academy of Sciences. Hepatocytes were isolated by adaptation of the calcium two-step collagenase perfusion technique as described.15, 17 Hepatocytes were plated on collagen-coated six-well plates

(BD Biosciences, San Jose, CA) at 250,000 cells/well. After the initial 2-hour attachment period, plating media was changed to either HGM complete with growth factors (+GF) HGF (supplemented at 40 ng/mL) and EGF (supplemented at 20 ng/mL) or without growth factors (−GF) and every 48 hours thereafter. Cells were harvested Osimertinib nmr on day 0 (2-hour plated), 2, 4, 6, 8, and 10 for RNA and protein. Total RNA was extracted from plated cells using the RNABee

reagent (Invitrogen, Carlsbad, CA) according to the manufacturer’s protocol. The isolated RNA was treated with Turbo DNA-free (Ambion, Austin, TX) according to the manufacturer’s instructions. RNA was quantified by spectrophotometry at 260 nm and purity was assessed by optical density 260/280 ratio. The RNA was stored at −80°C. The experiment was repeated in three rats and their messenger RNA (mRNA) was pooled for further processing in primary hepatocytes as well as 70% partial hepatectomy (PHx) experiments. Four micrograms RNA per sample was reverse-transcribed using random hexamer to complementary DNA (cDNA) by using SuperScriptIII reverse transcriptase (Invitrogen, La Jolla, CA) according to the manufacturer’s protocol. A no reverse transcriptase (RT) control was also

included. The gene-specific primers used for rat were as follows. REST, cMyc, Klf4, Nanog (SuperArray Bioscience, Cat. no. PPR45101A, PPR45580A, PPR43919A, and PPR59663A, respectively). Oct4 forward: 5′-GGC GTT CTC TTT GCA AAG GTG TTC-3′; Oct4 reverse: 5′-CTC GAA CCA CAT CCT TCT CT-3′. Expression levels of REST, Oct4, cMyc, and Klf4 were determined by qRT-PCR using SYBR green and levels were normalized relative to expression of selleck screening library cyclophilin in each sample. Fold change in gene expression was calculated by using the 2(−ΔΔCt) method.18 Reverse-transcribed samples were amplified in parallel on an ABI prism 7000 SDS instrument (Applied Biosystems, Foster City, CA). qRT-PCR for each sample was performed in triplicate in a 20-μL reaction with 50 ng of cDNA, 5 picomoles of each primer, and 1× SYBR green PCR mix (Applied Biosystems). The standard conditions for real-time PCR were as follows: 2 minutes at 50°C, 10 minutes at 95°C followed by 40 cycles of 15 seconds denaturation at 95°C, and elongation at 60°C for 45 seconds. A dissociation curve analysis was performed at the end of every run. A no RT and a no template control were also included in every run.

001); clearance significantly decreased with increased VWF:Ag (P = 0.002). Annualized bleeding rate in patients treated with 3× per week rFVIII-FS significantly correlated with VWF:Ag and age (P = 0.038 and 0.021 respectively). PK parameters as well as the clinical outcome significantly correlated with endogenous VWF:Ag. The improved clinical outcome in subjects with high

VWF:Ag levels may be explained by VWF:Ag influence on FVIII PK. “
“Increase of factor VIII activity (FVIII) after physical exercise has been reported in healthy subjects and small-scale studies in patients with coagulopathies. The aim was to study whether moderate and mild haemophilia A patients are able to increase their endogenous FVIII activity levels by physical activity. We studied changes in FVIII activity levels after high-intensity exercise in 15 haemophilia A patients, 20–39 years, eight with moderate, STA-9090 seven with mild haemophilia. Patients cycled until volitional INCB018424 datasheet exhaustion, blood samples were drawn before and 10 min after the exercise test. FVIII activity increased 2.5 times (range 1.8–7.0 times), for both severities. Absolute increases were markedly different: median 7 IU dL−1 (range 3–9 IU dL−1) in patients with moderate, compared to 15 IU dL−1 (range 6–62 IU dL−1) in mild haemophilia patients. VWF and VWFpp increased independently

of severity; median 50% (range 8–123%) and median 165% (range 48–350%), respectively, reflecting acute release of VWF. These observations may be used to promote high-intensity activities

before participating in sports for moderate and mild haemophilia A patients, to reduce bleeding risk. Further studies are warranted to fully appreciate the clinical significance of exercise on different levels of intensity in patients with mild and moderate haemophilia A. “
“Summary.  Recombinant factor VIIa is indicated check details for treatment of bleeding episodes in patients with haemophilia A or B with inhibitors; in FVII deficiency and in Glanzmann’s thrombasthenia. The aim of the study reported here was to compare the pharmacokinetic profiles between two formulations of rFVIIa that are produced in two different cell lines and media: Chinese hamster ovary cells cultured in a serum-free medium (CHO-rFVIIa) and baby hamster kidney cells cultured in a non-human serum-based medium (BHK-rFVIIa). Two clinical trials were performed; one in healthy subjects and the other in patients with congenital haemophilia A or B, with or without inhibitors. Subjects were recruited into a two-way crossover trial and were randomized to receive a dose of CHO-rFVIIa and BHK-rFVIIa. Healthy subjects received one dose of 90 μg CHO-rFVIIa kg−1 bodyweight (bw) in the newly developed room-temperature stable rFVIIa formulation and one dose of 90 μg BHK-rFVIIa kg−1 bw, in the original rFVIIa formulation. Patients with haemophilia received one dose of 270 μg CHO-rFVIIa kg−1 and one dose of 270 μg BHK-rFVIIa kg−1, both in the room-temperature stable formulation.

Their multivariable analysis also showed that HCV genotype 1b is an independent predictor for the development of esophageal varices.1 The interpretation of the results, however, raises a concern. It is well known that the clinical outcome of antiviral therapy is significantly influenced by viral genotype.2, 3 That is to say, patients with different HCV genotypes may have different responses to the antiviral therapy. This is confirmed by the observation that patients infected with genotype 1b have lower rate of sustained I-BET-762 mouse virologic response.1 Therefore, HCV genotype 1b may be more likely to be an independent

predictor for the development of esophageal varices, and achievement of sustained virologic response may be merely a cofactor associated with the host response to antiviral therapy. Further study is needed to clarify this concern. Li-ping Ye M.D.*, Xin-li Mao M.D.*, * Department of Gastroenterology Taizhou Hospital of Zhejiang Province Linhai, China. “
“We read with interest the recent article by Ngu et al.1 that reports a population-based study examining mortality and the risk of hepatobiliary and nonhepatobiliary malignancy in patients with autoimmune liver disease. During the 7-year study period a total of 130 autoimmune hepatitis (AIH), 70 primary biliary cirrhosis (PBC), and 81 primary

sclerosing cholangitis patients were identified. Of those patients with AIH, three developed hepatocellular carcinoma (HCC), while 28 selleck products developed an extrahepatic malignancy. Although it is commented that cirrhosis was present in all AIH patients with HCC, no information on the severity of liver disease or fibrosis is given for the study cohort as a whole. We wish to draw the authors’ attention to a study conducted by our institution, where 243 patients with AIH were identified and prospectively followed up between 1971

to 2007.2 In this cohort, 15 patients with AIH developed HCC, which equated to an annual incidence of 1.1%. The data demonstrated that cirrhosis was the sine qua non for the development of HCC in AIH, an association that is further supported by the data from Ngu et al. Furthermore, in their study, Ngu et al. report that the see more risk of HCC is 15-fold greater in AIH patients in comparison to that in a matched general population. However, as a result of the absence of information on liver disease severity it is not possible to determine the proportion of the cohort that were “at risk” of developing HCC. Indeed, the authors comment that the increased incidence of nonhepatic malignancy in the AIH study population may be the result of lead-time bias resulting from incidental diagnoses during HCC surveillance investigations without elaborating on the proportion undergoing surveillance. Similarly, the influence of liver disease severity on HCC risk may also be reflected in the risk of malignancy observed in patients with PBC. No cases of HCC were reported within their cohort during the study period.

4 These observations seem to have great clinical importance because severe liver fibrosis per se represents a negative predictor of successful antiviral therapy with currently registered regimens. Thus, initiating antiviral therapy with pegylated interferon and ribavirin (RBV) before learn more severe fibrosis has developed seems to be clinically necessary. Recently, another main predictor of the treatment response to pegylated interferon and RBV has been identified by means of genome-wide association studies in patients with different ethnic backgrounds. These investigations unequivocally identified variants near the interleukin-28B (IL28B) gene

encoding a λ-interferon (interferon 3) as main predictors of treatment outcome across different ethnic groups.5, 6 It is even more interesting that the risk allele frequencies strongly correlated with the overall treatment RO4929097 response in these ethnic groups, and this suggests that the IL28B variants are the main reasons for the observed differences in the overall outcome of antiviral therapy for HCV infection. In the meantime, these initial observations have been replicated, and the relevance of these gene variants has been expanded by the finding that spontaneous viral clearance of HCV is also associated with the same IL28B variant.7 Fellay and colleagues8 have now taken the next step to personalized

medicine for HCV infection. The group performed a genome-wide association study in 1286 patients treated in the IDEAL (Incremental Decrease in Events through Aggressive Lipid Lowering) study with the aim of identifying gene variants that modulate RBV-induced hemolytic selleck chemicals llc anemia. This side effect of pegylated interferon/RBV therapy occurs in a considerable number of treated patients

and is one of the main reasons for dose modifications or even termination of RBV during the course of therapy. Therefore, Fellay et al. investigated a very important clinical question. Of the more than 500,000 single nucleotide polymorphisms (SNPs) genotyped in the study, several showed an association with the appearance of hemolytic anemia (defined as hemoglobin levels < 10 g/dL or a decline > 3 g/dL from the baseline at treatment week 4), but an SNP on the short arm of chromosome 20 (rs6051702) was most robustly associated with this phenotype with genome-wide significance (P = 1.1 × 10−45). Fine mapping of the chromosomal locus then identified two SNPs in the inosine triphosphatase (ITPA) gene encoding inosine triphosphatase pyrophosphatase (ITPase) as SNPs possibly responsible for the association that cosegregate with rs6051702 (Fig. 1). These SNPs had been identified previously and code for a missense mutation in exon 2 (rs1127354, 94C-A, P32T) or alter a slice site (rs7270101).

Designed human TaqMan assays (Applied Biosystems, Foster City, CA) PD-1/PD-L1 phosphorylation were used to quantify gene expression of osteocalcin (BGLAP), osteoprotegerin (TNFRSF11B), RANKL (TNFSF11), and Cbfa1 (RUNX2). Quantitative PCRs were carried out using ABI-Prism 7900 HT Fast Real-Time PCR System and a

TaqMan 5′-nuclease probe method (Applied Biosystems). Results were expressed as relative expression of each gene (versus β-actin gene expression), using arbitrary units according to the comparative CT (threshold cycle) method.20 All real-time PCR reactions for each sample were performed in triplicate. The primers used are listed in Table 1. Data are expressed as mean ± standard deviation (SD). All analyses were performed with the SPSS version 14.00 statistical package (SPSS Inc., TSA HDAC solubility dmso Chicago, IL). Significant differences between any two groups were determined by Student t test or Mann-Whitney U test. When multiple groups were compared, analysis of variance was used, followed by a Tukey’s multiple contrast test, where applicable. A P value ≤0.05 was considered significant. Nonpassage human primary osteoblasts, after synchronization, displayed the characteristic pattern of gene expression and protein production of osteoblastic differentiation markers such as osteocalcin gene expression and alkaline phosphatase activity (data not shown). Increasing concentrations

of unconjugated bilirubin in the culture media resulted in a progressive decrease in cell viability, which was observed particularly at concentrations higher than 100 μM at 48 hours and higher than 50 μM at 72 hours (Table 2). The cell viability decrease was 36% and 56%, at 50 and 100 μM, respectively, compared with nontreated cells. Moreover, the presence of bilirubin (10 μM) resulted in significantly better cell viability learn more compared with no bilirubin in the experiments performed at 48 hours and in the plates without FBS. These effects on cell survival were partially prevented by the presence of 10% FBS, because the detrimental effect of bilirubin at 50 and 100 μM was completely abolished

in the experiments with FBS. Actually, in these latter experiments, the decreased cell viability was only observed with bilirubin at 1000 μM (Table 2). Serum samples from patients and healthy subjects were added at 2%, 10%, and 20% concentrations in culture medium. Cell viability significantly decreased in samples with increasing concentrations of sera from jaundiced patients at 72 hours (Table 3), with viability decreasing by 19%, 18%, and 33% at 2%, 10%, and 20% concentrations, respectively. No significant effect was observed at the other time points, although there was a trend in the experiments performed at 48 hours. Moreover, no effect on cell viability was observed in the experiments performed with samples from patients who had normal bilirubin levels.

Conversely, a mean time to endoscopy ≤ 15 hours was significantly associated with improved survival among 312 patients in an independent population.10 However, the door-to-scope time was not a highly sensitive learn more (72%) or specific (59%) indicator of mortality because the Model for End-Stage Liver Disease score on admission, the failure to control bleeding during initial esophagogastroduodenoscopy,

and the presence of hematemesis were more influential in determining mortality. Additional studies are required to ensure that rapid endoscopy is being performed for all patients with evidence of severe AVH. The relationship between the quality and the case volume has been studied extensively with the general notion that more experience could reduce population mortality and improve the efficiency of care. In contrast to other acute conditions, a significant relationship has not been identified between the volume and the outcomes after AVH.11, 12 Issues of inadequate risk adjustment and the absence of key predictors within claims data have likely contributed to the negative findings. From the standpoint of endoscopy, there appears to be broad consensus on the use of variceal band Small molecule library ligation versus sclerotherapy in the treatment of AVH.8 However, the use of antibiotic

prophylaxis and systemic vasoconstrictors is more variable for AVH.2-6 Surprisingly, this degree of variation in the process of care has not been

associated with increased mortality from AVH. The case mix and the severity of disease likely play significant roles, and their influence on outcomes also deserves further study. “
“A 59-year-old Japanese male presented to our hospital for further examination of gastric cancer diagnosed by medical check-up. The patient had a history of hypertension, which was medically treated 3 years ago by administration of a vasodilator, but there was no past history of check details trauma or abdominal symptoms. An electrocardiogram, chest radiograph, and abdominal plain film were also normal. On computed tomography (CT) imaging as further examination for gastric cancer, there were no indications of distant metastasis or local advance. Contrast-enhanced CT imaging revealed an enlarged and irregular diameter of the superior mesenteric artery (SMA) with a mural thrombus, but without signs of bowel ischemia or ascites (Figure 1). On the CT coronal image, the thrombus in the false lumen originated 5.3 cm from the SMA origin and extended for approximately 3.7 cm (Figure 2). Although a portion of the true lumen was compressed by the thrombosed false lumen, distal blood flow was preserved. The patient underwent laparoscopy-assisted distal gastrectomy with regional lymph node dissection, resulting in the diagnosis of signet ring cell carcinoma invading the gastric submucosal layer without lymph node metastasis.

37% VS 3.46%, P<0.001), but also higher than the original atlanta classification of patients with SAP(17.37% VS 9.36%, P<0.001). Conclusion: This large clinical JQ1 concentration studies showed that the severity classification of acute pancreatits according to the revised Atlanta classification is more accurate and more useful for clinical management of AP. Key Word(s): 1. acute pancreatitis; 2. severity; 3. outcome; 4. database; Table 2 Severity classification and outcome in acute pancreatits according to the 1992 atlanta classification criteria 1992 Atlanta classification n (%) APACHEII Length of stay (days)

hospital fees SMB) risk of death MAP 366 432±2.74 6.44±3.543 12317.51 ±11276.03 0(0%) SAP 566 7.44±4.28 13.00±12.62 45081.58 ±135753.14 53(936%) Total 932 6.21±4.05 10.42±10.58 32215.00 ±107192.22 53(5.69%) Table 3 Severity classification and outcome in acute pancreatits according to the revised atlanta classification revised atlanta classification n (%) APACHEII Length of stay (days) hospital fees (RMB) risk of death MAP 279(29 94%) 4.10±2.69 5.8 ±3.0 9971.1 ±8044.9 0 MSAP 433(46.46%) 6.18±3.74 9.9 ±7.4 25207.4 ±341802 15(3.46%) SAP 220(23.61%)

8.95±4.44 17.4 ±16.8 74216.7 ±209666.4 38(17.27%) Total 932(100%) learn more 6.21±4.05 10.4 ±3.18 ±1071922 53(5.69%) Presenting Author: XIAOYIN ZHANG Additional Authors: XIN WANG, ZHIGUO LIU, YANGLIN PAN, XUEGANG GUO, KAICHUN WU, DAIMING FAN Corresponding Author: XIAOYIN ZHANG, XUEGANG GUO Affiliations: Xijing Hospital of Digestive Diseases & State Key Laboratory of Cancer Biology, Fourth Military Medical University

Objective: Finding the etiology of recurrent acute pancreatitis selleck compound (RAP) is critical for chosing treatment stratgy. This retrospective study aimed to analyze the roles of EUS/EUS-FNA in looking for the causes of RAP with cystic lesions. Methods: With Olympus Eum2000-25R or EU-ME1 endoscopy ultrasonagraghy system, we checked 17 patients, who had more than 2 times episodes of acute pancreatitis and were diagnosed as “pesudocyst” by CT or/and MRI in Xijing institute of digestive diseases from May, 2008 to April ,2012. Among them, 13 patients underwent EUS-FNA and cystic fluid anaysis including amylase, lipase, CEA , CA-199 and cytology. Results: Nine patients were diagnosed as pseudocysts according to the EUS image, fluid analysis and negative result of cytology. Four patients were diagnosed as IPMN by EUS image, among which 3 patients underwent surgery and confirmed by pathology. The other patient was followed up closely after EUS-FNA histology demonstrated a normal epithelial and fluid analysis showed a typical IPMN with very low CEA level. Three patients were diagnosed as MCN by EUS image combined with fluid analysis, among which two patients with EUS-FNA histology demonstrating high grade atypia cells secreting mucin, all were confirmed as MCC by surgery pathology.

1 on hepatitis B virus (HBV)-DNA level and basal core promoter A1762T/G1764A mutation in liver tissue independently predicting postoperative survival in hepatocellular carcinoma (HCC). According to the article, the amount

of HBV-DNA in liver tissue and the presence of the basal core promoter mutation were two independent predictors for postoperative survival in HCC. The authors also found that a short-stretch pre-S deletion located between codons 107 and 141 was associated with a poorer postoperative prognosis. This study can be hailed as an original contribution in terms of predicting postoperative survival in HCC; however, we have some concerns about it. First, as is well known, evidence suggests that HBV genetic mutations contribute to the risk of HCC. Recent studies have shown that HBV genotype- or subgenotype-specific mutations, including C1653T in the EnhII region, T1753V, and the double mutant SAR245409 purchase A1762T/G1764A in the BCP region, are independent risk factors for HCC.2 Another study has indicated that pre-S deletions, I68T in surface gene, T1762/A1764, and A1899 are independent risk factors for HCC.3 A recent meta-analysis revealed that the HBV pre-S mutations C1653T, T1753V, and A1762T/G1764A

are associated with an increased risk of HCC. These mutations alone and in combination may be predictive of hepatocarcinogenesis.4 We wonder whether the other gene mutations correlated with HCC in HBV other than the basal core promoter A1762T/G1764A mutation (e.g., this website C1653T, T1753V, ITF2357 A1899) can independently predict postoperative survival in HCC. Second, it has not been determined whether hepatitis B e antigen (HBeAg) is associated with postresection survival in HCC. According to Sun et al.,5 HBeAg was associated with a higher risk of early recurrence and poorer survival in patients after curative resection of small HCC. However, Chen et al.3 indicated that HBeAg positivity is not a negative factor for resection in HCC patients and has no significant influence on postresection survival. Therefore, we wonder whether HBeAg was associated with postresection survival in HCC in the study

by Yeh et al. Given that the serum samples used in the study had been stored in the serum bank, we think that the detection of HBeAg in both groups is convenient and has great significance. Finally, a study by Tomimaru et al.6 showed that histological assessment of the degree of fibrosis in noncancerous tissue is a unique prognostic factor for primary HCC without hepatitis B or C viral infection. If this is the case, then is histological assessment of the degree of fibrosis in noncancerous tissue one of the prognostic factors for HBV-related HCC as well? “
“Khandelwal and colleagues have elegantly demonstrated through the detection of acetaminophen–cysteine adducts that a significant proportion of indeterminate acute liver failure (ALF) is due to acetaminophen (N-acetyl-p-aminophenol; APAP) toxicity.

All patients have severe haemophilia A with high-responding inhibitors and 70% of the population has negative prognostic factors for a successful outcome. Of the 108 patients for whom data are available, at least one-third received FVIII concentrates at a dose of <95 U kg−1 day−1 and 29% did not receive FVIII concentrate on a daily basis [either Ipilimumab chemical structure three times weekly (n = 12) or every other day (n = 19)]. Thirty-nine per cent of patients received a different

FVIII concentrate than was in use at the time of inhibitor diagnosis. Twenty-seven per cent received a pdFVIII product, whilst the remaining 73% of patients received a rFVIII product at significantly higher amounts than in those treated with pdFVIII products. As was reported in 2009, the overall success rate was good and a multivariate analysis indicated that significant predictors of success included an inhibitor titre of <5 BU at the start of ITI therapy, F8

genotype (non-null mutations), and a peak inhibitor titre of <100 BU while receiving ITI therapy [36]. Since then, the data have been re-analysed based on a number of pharmacoeconomic parameters. For analysis purposes, the patient population was split by age: <14 (n = 73) and ≥14 (n = 35) years of age. Selisistat solubility dmso Significant differences emerged in terms of how younger vs. older patients are treated with regard to FVIII dose (P = 0.002), daily regimen (P = 0.003), check details use of rFVIII products (P < 0.0001) and whether or not the same concentrate is used as at the time of inhibitor diagnosis (P < 0.0001). Nevertheless,

treatment success was similar in both age groups (Table 5) with the only significant differences being the time to inhibitor negative status (6 vs. 9 months in younger vs. older patients; P = 0.04) and the time to treatment success (8 vs. 12 months respectively; P = 0.04). In terms of median consumption of FVIII concentrate required to achieve a successful outcome, the groups were virtually identical (24 690 vs. 24 840 U kg−1 for younger vs. older patients) as were the costs of a successful outcome (18 979 vs. 17 009 € kg−1). Based on previous prices for FVIII concentrates in Italy, the cost of achieving a successful outcome with ITI therapy irrespective of age equates to € 2000 kg−1 or € 150 000 overall. Expressed in current prices, the overall cost of successful ITI therapy in patients with severe haemophilia A and high-responding inhibitors who have negative prognostic features for a successful outcome is € 200 000. In conclusion, although the evidence for higher costs associated with the treatment of haemophilia in patients with inhibitors vs.