Rinella – Advisory Committees or Review Panels: Gilead The following people have nothing to disclose: Brian P. Lee, David W. Victor, R. Mark Ghobrial, Zhiping Li Background: The impact of body mass index (BMI) on outcomes post liver transplant (LTx) is a challenge and results inconclusive. BMI is still used by some centers as an absolute contraindication

to LTx and can influenced resource allocation decisions. Obesity has been associated with increased post LTx complications, when controlled for cardiovascular disease and diabetes. The negative impact of BMI and previous abdominal surgery on postoperative complications has not been demonstrated. Hypothesis: We hypothesize that BMI and prior abdominal surgery contribute to higher rates of any grade of complications post LTx. Methods: Single-center, retrospective review of 616 consecutive LTx MDV3100 molecular weight patients undergoing LTx between Feb 2002 and Dec 2013. Complications were classified using Clavien-Dindo (2); only grades (Gr) II to V were examined. BMI Antiinfection Compound Library order was dichotomized at 35 kg/m2, the cutoff for severely obese (WHO). Only abdominal surgeries were included (Surgery +) and compared to none (Surgery -). Categories were: BMI < 35, and Surgery (-) n= 450; BMI < 35 and

Surgery (+), n=96; BMI > 35 and Surgery (-), n=46; and BMI > 35 and Surgery (+), n=14. Statistical analysis involved a multinomial logistic regression model. All statistical tests were 2-tailed at a 5% significance level. selleckchem Results: Compared to patients with BMI <35, those with BMI >35 had significantly higher complications in Gr II (OR 2.8, p-value<.0001), Gr III (OR 1.7, p-value=0.0015), and Gr IV or V (OR 2.7, p-value<.0001), when controlled for prior abdominal surgery. Surgery + patients were more likely

to have Gr II (OR 2, p-value<0.0001), Gr III (OR 1.5, p-value=0.0015), or Gr IV or V complications (OR 2.6, p-value<0.0001), when controlling for BMI. Prior surgery was a significant predictor of mortality (Gr V) (OR 2.5 p-value=0.0248) but BMI was not (p-value 0.163). Conclusion: Both BMI and prior abdominal surgery are independent predictors of post LTx morbidity but only prior abdominal surgery was a significant predictor of mortality. Higher rates of Gr II to V complications were demonstrated with BMI > 35, and prior abdominal surgery. Thus, both BMI and prior abdominal surgery should be considered as indexes of disease severity and risk prior to LTx. Given increasing prevalence of obesity and patients with prior abdominal surgery, a larger multicenter data will be better able to evaluate their impact. Meanwhile, their use in selecting transplant candidates should be used with caution. Reference: (1) Clavien, P. A., et al. Definition and classification of negative outcomes in solid organ transplantation. Application in liver transplantation. Ann Surg 1994; 220(2): 109-120. Disclosures: Angel Alsina – Advisory Committees or Review Panels: Bayer; Speaking and Teaching: Bayer, Novartis Edson S.

This policy thus could theoretically increase the waiting time for both patients with acute GPCR Compound Library purchase fulminant hepatitis having a 1A status and for patients

with chronic liver disease. Second, these authors found that the MELD score predicted wait list mortality for patients with acetaminophen toxicity in contrast to other studies where the MELD score did not correlate with wait list mortality for status 1 patients registered with acetaminophen toxicity. The authors do not reconcile the differences in these two studies. Third, this analysis dated back to 2001, before the advent of the MELD allocation policy, which began in February 2002. The study also does not take into account the policy revisions that redefine status 1 to 1A and 1B categories in 2005, which occurred during the www.selleckchem.com/Wnt.html study period. Furthermore, the authors did not assess center effect, which has been shown to have a substantial effect on both pre- and posttransplantation survival, particularly in patients with high MELD scores.4 Finally, and most importantly, broader sharing for status 1A patients relative to patients prioritized by MELD may have a more profound effect on reduction of wait list mortality than any change to prior rules for prioritization for organ allocation. In contrast to the author’s conclusion, one might interpret these results to support a change to distribution

policies so that deceased donor livers are offered to patients with the highest MELD score on a regional basis similar to the status 1 patients at the present time rather than changing the allocation sequence that would put patients with a MELD score greater than 40 ahead of status 1 patients. In fact, such a distribution policy change has been developed and put to public comment recently by the OPTN.5 In conclusion, any analysis of the liver transplant waiting selleckchem list

encompassing a significantly long study period is confounded by changes in policy during the period of analysis. In addition, advances in the management of acute liver failure have occurred that may impact survival. The situation is further complicated when both allocation and distribution rules have changed over time and are not taken into account. Nonetheless, it seems intuitive that offering higher priority through an allocation policy change or broader access through a distribution policy change will improve results for a selected group of the most ill-waiting candidates. Because differences in center expertise are likely to be more profound for the sickest patients, it is important that center effect be accounted for in any such analysis. Finally, what is not addressed here is what will happen to other candidates with chronic liver disease on the list if either approach is taken. Further data are required to assess the potential impact of an allocation policy change that is advocated here.

In contrast, metformin was associated with a decreased risk for liver cancer.

Consistent with previous in vitro studies on TZDs which showed antiproliferation and prodifferentiation effects, our data have provided an association between the clinical use of TZDs and a reduced risk for several cancer incidences, in particular liver cancer. The association became stronger when the duration of TZD use was longer and the dosage was higher. Rosiglitazone, but not pioglitazone, was associated with a significantly reduced risk for colorectal cancer. buy Decitabine No association between both TZDs and lung and bladder cancer was observed. Previous reports on the association between TZD use and cancer incidence have been inconsistent. The report from the data obtained from the Veterans Integrated Services Network 16 (VISN 16) cohort of 87,678 individuals showed a 33% reduction in lung cancer risk among TZD users compared with nonusers (relative risk: 0.65, 95% CI: 0.51-0.87). However, as rosiglitazone and pioglitazone were combined, the risk reduction

for colorectal Selleckchem INK 128 cancer did not reach statistical significance. 18 In contrast, the present study results did not show a decreased risk for lung cancer. Although numerous in vitro studies support the protective effect of TZDs in lung cancer, the specific tissue or type of cancer and its stage might contribute to the efficacy or failure of TZDs as antineoplastic agents. 19, 20, 24-29 Because the risk factors, genetic expressions, and pharmaceutical responses of lung cancer of the Taiwanese differ significantly from those in the Western countries, there might also be a differential response to TZDs. 30 On the contrary, our analysis showed a protective effect of rosiglitazone on colorectal cancers, which was not evident in the VISN 16 cohort. In animal studies, PPAR-γ agonists inhibited tumor growth

and colon carcinogenesis through induction of apoptosis and suppression of the cell cycle. 31-34 The current study, to the best of our knowledge, provides the first evidence that rosiglitazone but not pioglitazone might reduce check details the risk of colorectal cancer. It is initially surprising that both pioglitazone and rosiglitazone are associated with a reduced risk for liver cancer. Hepatocellular carcinoma, one of the most incident, prevalent, and lethal malignancies in Taiwan, is regarded as a late-stage sequel of chronic infection of hepatitis B and C. 35, 36 With only a few exceptions, the development of hepatocellular carcinoma almost exclusively follows the sequence of chronic hepatic inflammation, cirrhosis of the liver, repair and regeneration of hepatic cells, and then carcinogenesis. 37 This might explain the finding that risk reduction was more evident in the patients with chronic liver disease. Despite the concern that physicians may preferentially prescribe TZDs to patients with better liver function (i.e.

Matthews MBChB (UK) PhD*, Gregory J. Dore MD PhD*, * Viral Hepatitis Clinical Research Program, National Centre in HIV Epidemiology and Clinical Research, University of New South Wales, Sydney, Australia. “
“Convincing evidence that antiviral therapy contributes to reduce short-term mortality of patients with hepatitis B virus (HBV)-associated acute-on-chronic liver failure (ACLF) is still unavailable.1,

2 I read with great interest the article by Garg et al.,3 who demonstrated that tenofovir can reduce the mortality of patients with severe spontaneous reactivation Tanespimycin ic50 of chronic hepatitis B presenting as ACLF. Their optimistic results give us some evidence about antiviral therapy in HBV-associated ACLF. However, a recent prospective

cohort study by Wong et al.4 demonstrated that entecavir treatment, learn more as compared to lamivudine treatment, is associated with increased short-term mortality of patients with severe acute exacerbation of chronic hepatitis B. Both tenofovir and entecavir are now the most effective antiviral agents for chronic hepatitis B. But why did they have converse effects upon the short-term mortality of HBV-associated ACLF? Here, we would like to offer some possible reasons for this interesting question. First, Garg et al. identified patients with HBV-associated ACLF by a high HBV DNA level (>105 copies/mL).3 The criterion on which their previous study is based may be useful, but it is still immature with only 14 patients enrolled in the tenofovir treatment group. There are obviously distinct prognoses between acute hepatitis B–related liver failure and HBV-associated ACLF. Therefore, enrollment of any patients with acute HBV-related liver failure may interfere with the results. Besides,

genotype D was the predominant HBV genotype in the Indian study subjects (85.2%), but genotype B or C is the main HBV genotype in China. Also, it is still unknown whether HBV genotype may affect the results of antiviral treatment in ACLF. In addition, Wong et al. speculated that the problem of lactic acidosis or an exaggerated immune response due to rapid virological suppression may lead to and exacerbate liver injury among patients with severe acute exacerbation click here of chronic hepatitis B.4 However, the latter explanation is contradictory to the opinion of Garg et al., who proposed that rapid reduction in HBV DNA levels independently predicted a good short-term survival rate. Thus, larger prospective and multicentric studies are encouraged to further evaluate the affect of tenofovir and entecavir on short-term mortality of patients with HBV-associated ACLF. Tao Liu M.D.* †, Chunmei Zhang M.D.*, Yingjie Wang M.D.†, * Department of Internal Medicine III, The Northern Region of No. 401 Hospital, Qingdao, Shandong, China, † Department of Infectious Diseases, Southwest Hospital, Third Military Medical University, Chongqing, China.

Key Word(s): 1. Entire circumferential superficial esophageal squamous cell carcinoma; 2. ESD Presenting

Author: LINGXIA TONG Additional Authors: QI NA, ZHANG JIAN Corresponding Author: LINGXIA TONG Affiliations: Jilin Tumor Hospital, Jilin Tumor Hospital Objective: To study the value of color doppler ultrasonography in the diagnosis of gastrointestinal stromal tumor (GIST). Methods: Retrospective analysis the color Doppler manifestations of 21 patients with GIST comfirmed by pathology and immunohistochemistry. Results: There were 11 cases originated from stomach, 8 cases from small intestine, 2 cases from colorectal and 1 case from mesenteric. 11 cases were malignant which were >5 cm in diameter with unclear boundary, round or lobulated shape and uneven heterogeneous echo, some of them accompanied by necrosis. The majority was above grade II on a scale of Alder grade by Selleck Obeticholic Acid color Doppler flow imaging (CDFI); 10 cases were benign which were <5 cm in diameter with clear boundary, oval shape and heterogeneous echo, The majority was below grade II on a scale of Alder grade by color www.selleckchem.com/products/dinaciclib-sch727965.html Doppler flow imaging (CDFI). Conclusion: Ultrasound has certain value in the diagnosis

of GIST Key Word(s): 1. Gastrointestinal stromal tumor; 2. ultrasound; 3. color Doppler ultrasound Presenting Author: JAMSHID VAFAEIMANESH Additional Authors: MOHAMMAD BAGHERZADEH, MOHAMMADREZA SEYYEDMAJIDI Corresponding Author: JAMSHID VAFAEIMANESH Affiliations: Clinical Research Development Center, Golestan Research Center of Gastroenterology and H Objective: Laparoscopic cholecystectomy (LC) and common bile duct exploration (LCBDE) has become the standard surgical procedure for cholecystolithiasis and choledocholithiasis. During the operation, cystic duct and vessels are usually see more controlled by hem-o-lok

clips. Methods: We report a case with complaint of severe abdominal pain for the previous 20 days. Results: Her medical history was unremarkable except for laparoscopic cholecystectomy 8 months ago. In upper gastrointestinal endoscopy, two hem-o-lok clips at anterior wall of the first part of duodenum were detected. Conclusion: Therefore, the clip can migrate during postoperative period and Hem-o-lok is not a so safe ligation method during laparoscopic cholecystectomy. Key Word(s): 1. Laparoscopic cholecystectomy; 2. Hem-O-Lok clip; 3. migration Presenting Author: SHU JENG WOO Additional Authors: ERIC WEE, P. MATHEW SACHIN, UTHAMANAND CHINNAPPA, CHERNG HANN YIP Corresponding Author: SHU JENG AARON WOO Affiliations: Khoo Teck Puat Hospital, Khoo Teck Puat Hospital, Khoo Teck Puat Hospital, Khoo Teck Puat Hospital Objective: Endoscopic clips are available in various designs. There are no studies comparing the efficacy of these designs. The primary aim of this study is to compare the deployment success of a long, re-opening endoscopic clip, Type A (Resolution clip, Boston Scientific Corp.

Key Word(s): 1. Entire circumferential superficial esophageal squamous cell carcinoma; 2. ESD Presenting

Author: LINGXIA TONG Additional Authors: QI NA, ZHANG JIAN Corresponding Author: LINGXIA TONG Affiliations: Jilin Tumor Hospital, Jilin Tumor Hospital Objective: To study the value of color doppler ultrasonography in the diagnosis of gastrointestinal stromal tumor (GIST). Methods: Retrospective analysis the color Doppler manifestations of 21 patients with GIST comfirmed by pathology and immunohistochemistry. Results: There were 11 cases originated from stomach, 8 cases from small intestine, 2 cases from colorectal and 1 case from mesenteric. 11 cases were malignant which were >5 cm in diameter with unclear boundary, round or lobulated shape and uneven heterogeneous echo, some of them accompanied by necrosis. The majority was above grade II on a scale of Alder grade by http://www.selleckchem.com/products/Deforolimus.html color Doppler flow imaging (CDFI); 10 cases were benign which were <5 cm in diameter with clear boundary, oval shape and heterogeneous echo, The majority was below grade II on a scale of Alder grade by color selleck products Doppler flow imaging (CDFI). Conclusion: Ultrasound has certain value in the diagnosis

of GIST Key Word(s): 1. Gastrointestinal stromal tumor; 2. ultrasound; 3. color Doppler ultrasound Presenting Author: JAMSHID VAFAEIMANESH Additional Authors: MOHAMMAD BAGHERZADEH, MOHAMMADREZA SEYYEDMAJIDI Corresponding Author: JAMSHID VAFAEIMANESH Affiliations: Clinical Research Development Center, Golestan Research Center of Gastroenterology and H Objective: Laparoscopic cholecystectomy (LC) and common bile duct exploration (LCBDE) has become the standard surgical procedure for cholecystolithiasis and choledocholithiasis. During the operation, cystic duct and vessels are usually selleck screening library controlled by hem-o-lok

clips. Methods: We report a case with complaint of severe abdominal pain for the previous 20 days. Results: Her medical history was unremarkable except for laparoscopic cholecystectomy 8 months ago. In upper gastrointestinal endoscopy, two hem-o-lok clips at anterior wall of the first part of duodenum were detected. Conclusion: Therefore, the clip can migrate during postoperative period and Hem-o-lok is not a so safe ligation method during laparoscopic cholecystectomy. Key Word(s): 1. Laparoscopic cholecystectomy; 2. Hem-O-Lok clip; 3. migration Presenting Author: SHU JENG WOO Additional Authors: ERIC WEE, P. MATHEW SACHIN, UTHAMANAND CHINNAPPA, CHERNG HANN YIP Corresponding Author: SHU JENG AARON WOO Affiliations: Khoo Teck Puat Hospital, Khoo Teck Puat Hospital, Khoo Teck Puat Hospital, Khoo Teck Puat Hospital Objective: Endoscopic clips are available in various designs. There are no studies comparing the efficacy of these designs. The primary aim of this study is to compare the deployment success of a long, re-opening endoscopic clip, Type A (Resolution clip, Boston Scientific Corp.

17 Future studies in our laboratory are under way to target hsp90 in liver diseases regulated by proinflammatory responses, such as ALD, NAFLD, and liver fibrosis. The authors thank Karen Kodys for labeling oligonucleotides for EMSA analysis. Additional Supporting Information may be

found in the online version of this article. “
“Aim:  Current medical transplantation methods focus on solutions for major problems such as the shortage of donors. To overcome these issues, expanding organ preservation time has become a major concern. A new refrigerating chamber has been recently developed, which can cool the inside of a material to the required temperature by frequently sensing the temperature of both inside and surface of the materials. selleck kinase inhibitor The purpose of this study is to evaluate the usefulness of a

Temsirolimus new refrigerating system in hepatic preservation. Methods:  The liver grafts were harvested from rats and divided into two groups. Group A consisted of grafts preserved in chilled University of Wisconsin solution (UW) solution (on ice) for 24, 72 and 168 h. Group B consisted of grafts preserved in the UW solution in a new refrigerator at 4°C. Results:  In group B, aspartate aminotransferase released into effluent after cold storage for 72 h showed a marked decrease compared to group A (P < 0.05). The levels of ammonia and lactate decreased significantly in group B (P < 0.05). In group B, the levels of adenosine triphosphate were significantly preserved after cold storage for 24 h and 72 h compared to group A (P < 0.05). Immunohistochemistry showed positive cells for heme oxygenase-1 were significantly increased in group B after cold storage. Conclusion:  This new refrigerator can improve preservation injury of hepatic grafts and may provide an innovative technique for liver transplantation. "
“Background and Aim:  Inflammatory bowel disease (IBD) is a multi-factorial disease with an unknown etiology characterized by oxidative stress, leukocyte infiltration and a rise in inflammatory cytokines. This study was

conducted to investigate lithium in 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced chronic model of experimental IBD, and the contribution of potassium channels as a possible underlying mechanism. Methods:  Experimental IBD was induced in rats find more by a single colonic administration of 10 mg of TNBS. Lithium, Glibenclamide (a potassium channel blocker), Lithium + Glibenclamide, Cromakalim or Lithium + Glibenclamide + Cromakalim were given twice daily for 7 successive days. At the end of the experiment, macroscopic and histopathologic scores, colonic malondialdehyde (MDA), tumor necrosis factor-α (TNF-α) level, and myeloperoxidase (MPO) activity as well as plasma lithium level were assessed. Results:  Both macroscopic and histological features of colonic injury were markedly ameliorated by lithium. Likewise, the elevated amounts of MPO and MDA were diminished as well as those of TNF-α (P < 0.05).

The Malmö protocol combines high-dose FVIII and immunosuppressive therapies and has shown success in 10/16 (62.5%) of patients. The Van Creveld protocol, which uses low-dose FVIII (25–50 IU kg−1 every second day) in patients with an inhibitor titre <10 Bethesda units (BU)

at the start of therapy, has demonstrated success in 21/24 (87.5%) patients. In routine clinical practice, treatment often involves variations of these three main ITI protocols. To date, there is no clear understanding of how ITI works although several hypothetical mechanisms have been proposed. These include the development of anti-idiotypic antibodies [5, 6], depletion of memory www.selleckchem.com/products/atezolizumab.html B cells [7], or generation of FVIII-specific regulatory T cells [8, 9]. Based on ITI protocols currently in use, it is known that the FVIII/IX complex

is the only essential component. At present, there are no biomarkers that can be utilized to assist in understanding the mechanistic process of ITI. Thus, current knowledge stems mainly AZD1152-HQPA from clinical observations and analyses of retrospective data. Data generated during the 1990s from a global perspective indicated that ITI is significantly influenced by the maximum historical titre (higher titres are associated with poorer outcomes), the pretitre at the start of ITI, the time between diagnosis and treatment (the shorter the better), treatment age (the younger the better) and FVIII dose [10]. The protocol for the subsequent

prospective International ITI study (in good-risk patients) considered these historical observations, and recruited children (aged selleck <8 years at the time of randomization; peak historical titre ≥5 and ≤200 BU mL−1; starting titre ≤10 BU mL−1 before randomization) as soon as possible after inhibitor detection [11]. Since the mid-1970s, 91 patients with inhibitors have been treated at the Bonn Centre according to the Bonn protocol which uses plasma-derived (pd) FVIII/von Willebrand factor (VWF) for ITI in patients at any age. Of these, 68 and 23 patients were classified as high and low responders respectively. All patients were treated by the same physician using a standardized protocol. The overall success rate of ITI was 78%, with a failure rate of 15% and with some treatments either ongoing (3%) or withdrawn (4%). Considering only high responders with available data, the success rate was 71% (42/59 patients). Interestingly, patient age at the start of therapy or time from diagnosis to the start of ITI did not influence the success rate in high responders, reflecting the fact that many patients were adults. By multivariate analysis, maximum inhibitor titre was the only independent variable that significantly affected the high-responder success rate.

ARNT has been linked to cholesterol homeostasis through its regulation of the ATP-binding cassette transporter A1, a major reverse cholesterol transporter.23 Agonist treatment leads to the formation of AhR-ARNT heterodimer formation, and the ablation of ARNT expression can assess whether this heterodimer plays a role in gene repression studied here. Unlike the AhR, partial absence of ARNT in Hep3B cells had no effect on the mRNA levels of cholesterol-synthesis Cisplatin genes, suggesting that the AhR mediates gene repression in the absence of heterodimer formation (Supporting Fig.

6). This result is consistent with the ability of the DRE-binding mutant, AhR, to repress the genes described here. Based on our findings, Wnt antagonist one might speculate that the decrease in the expression of all cholesterol-synthesis genes examined in mice and humans would result in a lowered cholesterol synthesis

and subsequent secretion. For this purpose, we treated primary human hepatocytes with BNF and used the gas chromatography/mass spectrometry (GC-MS) technique to quantify cholesterol in the media. As expected, treated cells showed a significant repression in the levels of secreted cholesterol, indicating an overall regulation of the pathway by the AhR (Fig. 7). In the current study, we established a transgenic mouse model that demonstrated the ability of the AhR to modulate the expression of a number of genes that encode for enzymes involved in the cholesterol-synthetic

pathway independent of DRE-binding, leading to a repression in cholesterol-secretion rate. There has been extensive interest in assessing the effect of TCDD exposure on serum lipid levels and, more recently, on the expression of lipid metabolism genes in rodents using microarrays,9, 10 but little progress has been made with regard to the AhR modulation of those genes in vivo in the absence of an exogenous ligand. Evolutionary conservation of the receptor coupled with the ahr-null mice phenotype suggests a role for the receptor beyond mediating xenobiotic metabolism. Differential constitutive expression of cholesterol-biosynthesis genes between CreAlbAhrflox/flox mice and AhR-silenced human cell lines and their AhR-expressing counterparts, selleck screening library as well as between Ahd and Ahb allele congenic mice, suggests a function for the AhR in cholesterol homeostasis. Although whether there is an endogeneous ligand(s) that mediates this effect is not known. Considering that cholesterol and oxysterols are involved in the feedback regulation of cholesterol homeostasis, it will be important to test whether there are sterols that can act as AhR ligands. Indeed, 7-ketocholesterol is a key oxysterol present in serum that has been shown to be an AhR antagonist.24 Clearly, there is a need to examine the ability of other endogenous metabolites to act as AhR ligands and regulate cholesterol biosynthesis.

The binding was only partially possible to inhibit with the addition of each molecule, however, and was therefore considered primarily unspecific. Thirteen patients with a current negative Bethesda titre had a previous C59 wnt supplier history of inhibitors, but no exposure to ITI-therapy (see Fig. 1). Six (46.2%) of these subjects had experienced high-responding

inhibitors with a mean peak titre of 15.6 BU mL−1 (range: 5.0–37.5 BU mL−1, median: 11.5 BU mL−1), whereas the others were low-responders. In two of the plasma samples of the latter subjects, an antibody response was detected in the ELISA assay, whereas this was not the case for the others. The median age did not differ significantly (P = 0.29) in patients without (median: 13.5 years, mean: 15.7 years, range: 1–68 years) and with (median: 14.0 years, mean: 23.2 years, range: 0–74 years) Bethesda-negative see more ELISA-positive antibodies. However, within the subgroup without a history of inhibitory antibodies (n = 122), there was a significant difference in median age of patients with NNA (median: 30.0 years, mean: 28.0 years, range: 1–65 years) compared with patients without NNA (median: 14.0 years, mean: 17.0 years, range: 0–74 years) (P = 0.021). This was not the case in the subgroup with a history of inhibitors (n = 79) (P = 0.43). No significant difference in NNA prevalence was

found, in either the total cohort (n = 201) or any of the two subgroups (with and without history of inhibitors, see Fig. 1), when comparing patients carrying a high-risk mutation, defined as inversions, nonsense mutations or large deletions, with those selleck compound with a low-risk mutation. Likewise, there was no correlation between race

and NNA development in any cohort analysed (data not shown). As noted above, 53 (67.9%) families had been previously characterized as discordant with respect to an inhibitory antibody response, 8 (10.3%) families concordant with a positive inhibitor titre found in all siblings and 17 families (21.8%) concordant without a history of inhibitors. However, when considering the total FVIII antibody response, the number of discordant families was reduced to 47 (60.3%) and the number of families with an antibody response in all siblings increased to 20 (25.6%), as 10 of the discordant and two of the concordant negative (i.e. no previous antibody response) families showed a FVIII antibody response in all subjects. For example, in one family with three siblings carrying a small deletion mutation, only one had a history of inhibitory FVIII antibodies, but with inclusion of results from the ELISA assays, all three brothers showed an antigenic response towards FVIII (data not shown). In four of the 17 families without a previous inhibitor, at least one sibling had a positive antibody response. In our cohort of 201 patients with severe haemophilia A, the prevalence of NNA (i.e.