In line with previous data of the same authors, 15 the I148M PNPLA3 variant was associated with fatty liver, but not with insulin resistance Ixazomib concentration and dyslipidemia, whereas the GCKR rs1260326 SNP was associated with hepatic fat accumulation, large very low-density lipoproteins, and triglyceride levels. Furthermore, there was a joint effect of PNPLA3 and GCKR SNPs explaining 15%-32% of hepatic fat content variability according to ethnicity. On the contrary, APOC3

genotype did not influence hepatic fat content, insulin resistance, or dyslipidemia, as already indicated by recent studies in adults, 16, 17 thereby definitively discarding this variant as a major risk factor for steatosis and NASH. Therefore, the likely additive effect of PNPLA3 and GCKR variants explained almost one-third of hepatic fat content variance in obese children, although due to the limited number of subjects analyzed for each ethnicity, data

should be replicated and the model of interaction re-evaluated in confirmatory cohorts. The rs1260326 GCKR encodes for the P446L protein variant, influencing the ability of GCKR to inhibit glucokinase in response to fructose-6-phosphate, thereby resulting in a constant increase in hepatic glucokinase activity and glucose uptake by the liver. 18 Unrestricted hepatic glycolysis associated with the minor 446L allele leads on one hand to lower glucose

and insulin levels, but on the Roscovitine clinical trial other hand to increased levels of malonyl-CoA, which in turn may favor hepatic fat accumulation by serving as a substrate for lipogenesis and by blocking fatty acid oxidation through the inhibition of carnitine-palmytoil transferase-1. Figure 1 shows a possible simplified working model that may explain the major roles of the P446L GCKR variant in fatty liver. Based on these findings, it would be very important to evaluate whether the effect of the P446L GCKR variant on liver fat is dependent on high dietary carbohydrates and sugar consumption, as it was reported for the I148M variant of PNPLA3. 18 Finally, as also acknowledged by the authors, whether the P446L GCKR variant also influences the histological severity of NASH has yet to be determined, especially Thymidine kinase since this variant is associated with increased liver fat but with reduced insulin resistance, which is a key driver of disease progression in NAFLD. 19 In conclusion, the I148M PNPLA3 and P446L GCKR variants jointly explain a sizeable proportion of hepatic fat content in obese children and adolescents. Further studies are warranted to evaluate the interaction with acquired and other genetic risk factors for fatty liver 20 and the effect of GCKR genotype on the progression of the disease. “
“Hepatocellular carcinoma (HCC) is an aggressive malignancy with a very complex molecular process.

There are no differences in the HBeAg positive and HBeAg negative

HDV disease. Key Word(s): 1. hepatitis D; 2. hepatitis B; 3. children; 4. presentation; Presenting Author: YOGESHPURSHOTTAM HARWANI Additional Authors: PADMAVATHI CHOUDESHWARI, AJITKUMAR SHRIVASTAVA Corresponding Author: YOGESHPURSHOTTAM HARWANI Affiliations: NIMS Objective: Little is known about hepatitis B surface antigen(HBsAg) during the natural course of chronic hepatitis B infection (CHB). The aim of the study was to determine and to correlate with HBV DNA. Methods: Twenty three HBV patients were included. They were classified as immune tolerant phase(IT;n = 7). They were further classified as HBe-positive IT (n = 2)and HbeAg negetive precore mutant(PCM)IT (n = 5). Immune HM781-36B solubility dmso clearance (IC n = 4) and low replicative phase (lr n = 12). The classification was based on ALT HBV DNA and Hbe status. Results: Median HBsAg titres were different between each phase of CHB (P < 0.05).

IT (e positive): 4.87log 10 IU/ml, IT PCM 4.17 log 10 IU/ml, IC 4.49 log 10 and lr 3.64 log 10 IU/ml in the above groups respectively. The ratio of HBsAg log 10 to HBV DNA log 10 was highest in IC 3.71 followed by lr 1.95. It was 0.67 and 0.78 in IT eAg positive and IT PCM. Conclusion: HBsAg levels were significantly different in different stages of disease. A good correlation between HBV DNA and HBsAg titres was seen in IT PCM (0.92) and moderate in IC (0.64). However, study with large sample size wll be helpful in deriving conclusions. Key Word(s): 1. HBsAg titres; 2. pre core

mutant; 3. immune toletant; Presenting Author: OUDOU NJOYA Additional Authors: CHARIFA Dabrafenib manufacturer FOUWOU NJOYA, MARIE JOSÉ ESSI, ELIE NKWABONG, ELIE CLAUDE NDJITOYAP NDAM Corresponding Author: OUDOU NJOYA Affiliations: University Hospital Center Objective: Cameroon constitutes a high prevalence zone for viral hepatitis B (VHB). Mother-to-child transmission is considered as the main mode of transmission of hepatitis B virus (HBV) in Africa. This mode of transmission is particular in sub Saharan countries as it implies factor related to the virus, to the knowledge attitude and practices of pregnant women Dynein and health personnel. The aim of this study was to identify risk factors of the mother-to-child transmission of VHB. Methods: A cross sectional study was carried out in three heath districts in the City of Yaoundé in Cameroon. We recruited all the pregnant women and heath personnel working in the obstetrics departments who accepted to participate and met the criteria of selection into the study. Pregnant women (PW) were tested freely for virus B markers, namely HBs Ag; HBe Ag; HBc anti body. Secondary, they were tested for they knowledge, attitudes and practices (KAP) vis-à-vis of VHB, excluding pregnant heath personnel (HP). Pregnant women tested positive for Hbs Ag or Hbc anti body were referred for follow up.

HBV is classified into genotypes and subgenotypes that are associated with ethnicity and geography. The genetic diversity of HBV in its various aspects has been the subject of extensive investigations during the last few decades. Since molecular epidemiology research tools have become widely available, the number of new publications in this field has grown exponentially. This review summarises the recent publications

on the geographical distribution of genetic variants of HBV, and proposes updated criteria for the identification Nutlin3a of new genotypes and subgenotypes of the virus. “
“Tenofovir disoproxil fumarate (DF) is highly effective for the suppression of hepatitis B virus (HBV) in chronically infected adults. This study evaluated the safety and efficacy of tenofovir DF in adolescents with chronic hepatitis B (CHB). In this double-blind, placebo-controlled trial, adolescents 12 to <18 years of age with CHB were randomized to tenofovir DF 300 mg (n = 52) or placebo (n = 54) once daily for 72 weeks. The primary endpoint was virologic response (HBV DNA <400 copies/mL)

at week 72. One hundred six patients were enrolled; 101 patients completed 72 weeks of treatment. At baseline, 91% of patients were hepatitis B e antigen–positive and 85% had prior exposure to HBV therapy. A virologic response was observed in 89% (46/52) of patients who received tenofovir DF and 0% (0/54) of patients who received placebo (P < 0.001). Treatment response was not affected by prior HBV treatment. Furthermore, no resistance MK-8669 cell line to tenofovir DF developed through week 72. Among patients with an alanine aminotransferase (ALT) level greater than the upper limit

of normal at baseline, normalization of ALT occurred in 74% of patients receiving tenofovir DF and 31% of patients receiving placebo (P < 0.001). The rate of grade 3/4 adverse events was higher among patients treated with placebo (24%) than patients treated with tenofovir DF (10%). No patients met the safety endpoint of a 6% decrease in spine bone mineral density at week 72. Conclusion: Tenofovir DF therapy in HBV-infected adolescents was well tolerated and highly effective at suppressing HBV DNA and normalizing ALT values Sinomenine in both treatment-naïve adolescents and those with prior exposure to HBV therapy. (HEPATOLOGY 2012;56:2018–2026) Despite the success of recent vaccination efforts, chronic hepatitis B (CHB) remains a serious global health care problem and is a major cause of serious liver disease.1 It is estimated that approximately 350 million people live with CHB infection and approximately 600,000 die each year due to the acute or chronic consequences of hepatitis B.1 Mathematical modeling suggests that over 80% of these deaths are from infections contracted during childhood.2 This is most likely because approximately 90% of those infected as infants and 30%-50% of those infected from 1 to 4 years of age develop chronic infection.

The prevalence of MS was 27.5% in group A vs 46.2% in group B (p < 0.05). The later was also found to be significantly different compared with group C (12.8% - p<0.001). The waist circumference and body mass index were higher in group B than in group A (105 vs 93 cm, p<0.001 and 29.4 vs 25.1 kg/m2, p<0.001) and higher than group C (105 vs 90 cm, p<0.001 and 29.4 vs 26.0 kg/m2, p<0.004). Overweight was observed in 79.5% of patients in group B versus 45% in group A (p<0.002) and 59% in group C EGFR tumor (p<0.05). The average visceral fat area measured by CT-scan was higher in group B than in group A (18223 mm2 vs 12690 mm2, p < 0.003). Among all criteria of MS, waist circumference was the

most powerful factor associated with PVT between group B and A (OR: 6.68 [1.86-24.3] – p<0.001), and between group B and C (OR: 17.3 [3.90-76.7] – p<0.001). Conclusion: Central obesity is associated with PVT

and could become one of the first MAPK inhibitor risk factors of digestive thromboses. 1. Ahluwalia N, Drouet L, Ruidavets J-B, Perret B, Amar J, Boccalon H, et al. Metabolic syndrome is associated with markers of subclinical atherosclerosis in a French population-based sample. Atherosclerosis 2006;186:345–53. Disclosures: Jean-Marie Peron – Board Membership: BAYER; Consulting: BMS, GILEAD, BOSTON SCIENTIFIC Jean-Pierre Vinel – Grant/Research Support: Roche, Gore, LFB The following people have nothing to disclose: Julie Laurent, Camille Christol, 5-FU ic50 Jean Bernard Ruidavets, Jean Ferrieres, Marie Angele Robic, Christophe Bureau Purpose. Non-alcoholic fatty liver disease (NAFLD) is the most common cause of elevated liver enzymes and chronic liver disease in developed countries. Previous studies have shown that NAFLD is closely associated with features of the metabolic syndrome. In the present study we determined future risk of diabetes and liver-related morbidity in NAFLD patients. Moreover we assessed if clinical

and histopathological parameters at baseline predict future morbidity. Methods. In a cohort study, 129 patients referred between 1988 and 1993 because of chronically elevated aminotransferases and diagnosed with biopsy-proven NAFLD were consecutively enrolled and pro-spectively followed. Subjects still alive were re-evaluated at two consultant meetings. Clinical and biochemical data were recorded and compared with the corresponding parameters and histopathological data at baseline. Hepatic fatty infiltration was quantified with stereological point counting in biopsies collected at baseline. Fibrosis stage was assessed semi-quantitatively. Results. Eighty-eight (85 %) of 104 patients still alive were reevaluated at first follow-up. Fifty-five (70 %) of 79 patients still alive were re-evaluated at second follow-up. Mean follow-up time for first and second re-evaluation was 13.7 ± 1.3 years and 22.5 ± 2.4 years, respectively. At first follow-up 51 subjects (58 %) had diabetes. The corresponding figure at second follow-up was 59 (67 %).

These data suggest an increased antinociceptive activity in patients with migraine, which could represent a compensatory functional reorganization aimed at

modulating pain perception to the intensity of HCs. Additional enhanced activation with painful heat application was identified in the medial temporal lobe in patients specifically in the anterior TP.109 In patients, TP showed significantly increased functional Birinapant research buy connectivity in several brain regions relative to controls, suggesting that TP hyperexcitability may contribute to functional abnormalities in migraine. In healthy subjects, DTI identified white matter connectivity between TP and pulvinar, a migraine-related nucleus. The observed functional MRI activation in TP with painful heat became exacerbated during migraine, suggesting that repeated migraines

may sensitize TP. Advanced neuroimaging methods have led to a new understanding of how migraine alters brain structure, function, and neurochemistry. Structural imaging showed iron deposition, revealed grey and white matter abnormalities, and provided insights into the relationship between migraine and stroke. The clinical consequences of structural changes remain incompletely understood and in-depth investigations are warranted. Functional imaging studies demonstrated RXDX-106 that changes in vascular function do not represent the primary cause for migraine attacks and raised the question of a central migraine “generator.” In addition, they helped clarify the role of CSD and central sensitization, elucidated the intimate mechanisms underlying activation of neuronal pain pathways in vulnerable patients, and detected potential sites of action for drug therapy. Migraine, a common condition known since antiquity and long presumed to be of vascular origin, now appears in a new light, as a CNS-centered disorder

with persistent effects on the nervous system despite its episodic character. Growing evidence indicates that dysfunction of subcortical structures (ie, diencephalic and brainstem nuclei) represents an important pathogenetic mechanism in migraine. Through their relationship with trigeminovascular system activation and their connections with other brain regions, these structures can contribute to the cascade Mirabegron of phenomena resulting in migraine-associated hypersensitivity manifestations. Imaging studies prove unequivocally that structural and functional alterations exist in the migrainous brain between ictal states. Some of the structural changes may be secondary to migraine, as they are associated with higher frequency of attacks or longer disease duration. More longitudinal studies, however, are needed to ascertain whether these changes predispose to migraine or represent the effect of migraine attacks. If, in fact, the risk of structural alterations increases with greater headache frequency and duration, more aggressive treatment efforts could be warranted in migraine sufferers.

Increased ketone bodies also stabilize CYP2E1 protein, resulting in a marked increase of APAP bioactivation to generate the hepatotoxic metabolite, which causes liver injury (Fig. 8). We found that message levels of a number of cytokines were similar in liver tissues and

liver mononuclear cells (in which NKT cells are enriched) isolated from APAP-treated WT and CD1d−/− mice (data not shown). These results suggest that APAP treatment does not trigger NKT cells to produce protective cytokines. Our data do not support an active protective role for NKT cells, but rather that the lack of NKT cells renders mice more susceptible to AILI. This is the first study to examine the specific role of NKT cells in AILI. The findings provide further insights into the underlying mechanisms of drug-induced liver injury, as well as other liver conditions in which CYP2E1-mediated ROS generation plays an important pathological role.41 Aside from genetic conditions, such Sotrastaurin ic50 as abetalipoproteinemia, lipid antigens, bacterial, and viral pathogens have been demonstrated to activate NKT cells, which leads to decreased cell number.42 Under such situations, NKT cell deficiency may

result in increased susceptibility to metabolic stress, as selleck compound well as hepatotoxin-induced liver injury. The authors thank Drs. Chris Franklin and Don Backos for their assistance with glutathione cysteine ligase western blotting analysis. The authors thank Casey Trambly for conducting the proteasome and CYP2E1 activity assays and Dr. James Galligan for assistance in CYP2E1 IHC. Special thanks to Dr. Sean Colgan for the generous use of HPLC instrumentation and Brittelle Bowers and Adrianne Burgess for their technical assistance with HPLC setup. Additional Supporting Information may be found in the online version of this article.

“
“There is little information on the early kinetics of hepatitis delta those virus (HDV) and hepatitis B surface antigen (HBsAg) during interferon-α therapy. Here a mathematical model was developed and fitted to frequent HDV and HBsAg kinetic data from 10 patients during the first 28 weeks of pegylated-interferon-α2a (peg-IFN) therapy. Three patients achieved a complete virological response (CVR), defined as undetectable HDV 6 months after treatment stopped with loss of HBsAg and anti-HBsAg seroconversion. After initiation of therapy, a median delay of 9 days (interquartile range [IQR]: 5-15) was observed with no significant changes in HDV level. Thereafter, HDV declined in a biphasic manner, where a rapid first phase lasting for 25 days (IQR: 23-58) was followed by a slower or plateau second phase. The model predicts that the main effect of peg-IFN is to reduce HDV production/release with a median effectiveness of 96% (IQR: 93-99.8). Median serum HDV half-life (t1/2) was estimated as 2.9 days (IQR: 1.5-5.3) corresponding to a pretreatment production and clearance of about 1010 (IQR: 109.7-1010.7) virions/day.

The study aims to develop a CLE composite scoring system of CD healing according to enterocyte regeneration compared against a similar histopathological method of assessment. Methods: Subjects underwent eCLE (Pentax, Japan) for the evaluation of treated or untreated CD. A composite CLE Regeneration Score (CRS) was developed based on enterocyte and goblet cell features (Table 1). The summative score of 5 duodenal sites each scored between 0 and 3 represented CD severity (CRS range: 0–15). An equivalent H&E histological severity

score (HiS) of CD was developed as gold standard with blinded assessment by a GI histopathologist.

Chi-square and Mann-Whitney U scores were used for categorical and continuous variables. Spearman’s correlation was used for correlation of CLE with histology as primary endpoint. Kappa (k) interobserver agreement was performed. Efficacy of the grading systems was defined by receiver operator characteristics (ROC) >0.9. Results: 17 patients (12 females, median age 41 years old, age range 14–38) yielded 800 CLE optical biopsies paired with 80 forceps biopsies for analysis. Sex and age were not different between treated and untreated CD patients (P > 0.05). Treated patients had their CLE after a mean of 362 days (range: 147–427) of GFD. Using a cut off of ‘1’ showed the ROC area under the curve of 0.94 (95% CI: 0.83–1.00) for CLE and 0.94 (95% CI: 0.82–1.00) for histopathology. CLE detected all abnormal histology in all patients (P < 0.002). CYTH4 The median CRS for untreated and treated patients were 2.5 (IQR 2-3) and 0 (IQR 0-1) FDA approved Drug Library manufacturer respectively. CS correlated with duration of the GFD (r = 0.917,

P = 0.001). Sensitivity, specificity, PPV and NPV for CLE using this cut off in detecting enterocyte regeneration were: 85%, 100%, 79% and 100% respectively. The k values of 2 CLE endoscopists for the agreement of mild, moderate, and severe CLE features were 0.67, 0.75, and 0.84 respectively. CRS grading correlated excellently and significantly with HiS histological severity grading (r = 0.832, P < 0.001). Conclusion: Confocal laser endomicroscopy accurately detects in vivo enterocyte and goblet cellular regeneration representative of coeliac disease treatment response equivalent to histopathology. CLE may provide instantaneous reporting of GFD efficacy and avoid the cost, delay and risks of forceps biopsies. Table 1: Classification Criteria for CLE and Histology. CS: CLE-Score; HiS: Histology Score.

Dendritic cell (DC) as the most important

antigen presentation cell plays pivotal role in immune activation. Our previous study shows that intestinal lamina Ku-0059436 order propria DC (LPDCs) from PI-IBS mouse model induces CD4+T lymphocyte differentiated to Th17 and activates it. This study tested the hypothesis that LPDCs may contribute to intestinal mucosal immune activation and visceral hypersensitivity in the development of PI-IBS mouse model. Methods: Visceral hypersensitivity was induced by Trichinella spiralis infection in mice. LPDCs were isolated and purified by intestine digestion and magnetic label-based technique. Normal mice following adoptive transfer of 106 LPDCs from PI-IBS mouse by tail vein injection was sacrificed 120 hours later. HE staining of the small intestine was performed. Visceral sensitivity is assessed

by abdominal withdrawal reflex (AWR). Expression of INF-γ, IL-4 and IL-17 in ileum and proximal colon were determined by western blotting. Results: 1) Compared with control, there is neither significant hyperemia and edema nor lymphocytic infiltration in the small and large bowel after adoptive transfer of LPDCs; 2) At 40, 60 mmHg, the AWR scores of adoptive transfer group were higher than that RGFP966 in the control group (p < 0.05); 3) In the ileum, IL-17 after adoptive transfer (1.32 ± 0.22) was higher than that of control (0.95 ± 0.35, p < 0.05) while IL-4 was lower. In the comparison of control group, there were obvious changes

in proximal colon. No difference was observed in INF-γ between control and adoptive transfer group. Conclusion: Adoptive transfer of LPDCs from PI-IBS mouse model result in visceral hypersensitivity and increase proinflammatory cytokines. LPDCs play an important role in intestinal mucosal immune activation and visceral hyper sensitivity. Key Word(s): 1. PI-IBS; 2. LPDCs; 3. Adoptive transfer; 4. Visceral sensitivity; Presenting Author: XUHONG YU Corresponding Author: XUHONG YU Affiliations: The First Affiliated Hospital of Harbin Medical University Objective: To evaluate the clinical and endoscopic click here characteristics of abdominal type allergic purpura in adult patients as the evidences in early diagnosis. Methods: The clinical and endoscopic characteristics of 20 patients with abdominal type allergic purpura were analyzed retrospectively. Results: There is 20% who have remote cause; All the patients complained of the leader symptoms were paroxysmal abdominal colic, the occult blood test was positive in all patients. Purpura was found in 2–10 days after the presentation of abdominal pain. Endoscopy found hyperaemia, edema, bleeding spots, erosion and ulcer in gastroenterologic mucosa. Duodenal, ileum and caecum had more severe mucous lesions. The clinic misdiagnosis rates were 90%.

Factor VIII antibody generation

check details in these animals was markedly enhanced by the administration of FVIII by the subcutaneous route and when FVIII was co-administered with lipopolysaccharide. Finally, evidence has been gathered to show that presentation of eight different FVIII-derived peptide regions in this humanized model system results in CD4+ T-cell reactivity. Of note, most of these eight peptide regions contain promiscuous epitopes that can bind several different HLA-DR proteins. In the second humanized haemophilic mouse model, a human FVIII cDNA transgene, regulated by the liver-specific albumin promoter, has been microinjected into fertilized oocytes, and founder mice were crossed with exon 17 knockout haemophilia A mice [25]. Despite the fact that FVIII mRNA can be found in several tissues in these mice (including liver, brain and gonads), they do not express FVIII in their plasma. Nevertheless, when challenged repeatedly with intravenous human FVIII they do not develop I BET 762 anti-human FVIII antibodies. Only when exposed to FVIII whose immunogenicity has been purposely enhanced is tolerance broken. The third humanized mouse model that has been generated again involves the insertion of a human FVIII transgene. However, in this instance, a mutant cDNA encoding an Arg593Cys missense change has been utilized [26]. This variant is found as a recurring

mutation in humans with mild haemophilia A that are more prone to inhibitor development. Here again there is an absence this website of circulating FVIII and yet the mice are consistently tolerant to human FVIII unless it is delivered in a manner recognized to be associated with enhanced immunogenicity (e.g. delivered subcutaneously

with an adjuvant). To date, the mouse models described above have been utilized for a variety of purposes. They have been studied for clues to FVIII immunogenicity [27, 28], for the natural history and details of FVIII immunity [29] and for the evaluation of many different approaches to primary and secondary tolerance induction [30-34]. With the recent arrival of the various humanized haemophilia mouse models we can expect to see additional studies in which outcomes more pertinent to the human context will be forthcoming. It is well known that the inhibitor risk in previously untreated patients (PUPs) is determined by multiple interactions between genetic and environmental factors. Among the latter, treatment-related determinants including intensity of replacement treatment (FVIII dose and frequency of administration), treatment regimen (i.e. prophylaxis vs. on-demand) and FVIII product type have been reported to influence variably the inhibitor formation [13, 14, 35-38]. A systematic review first highlighted that inhibitor incidence was lower in patients treated with one plasma-derived FVIII (pd-FVIII) brand vs.

Moreover, a prophylactic effect on bleeding frequency is reported in patients who

achieved partial success, which is paramount in preventing the development of haemophilic arthropathy at an older age [19]. Our study is of clinical importance because it shows that most of the patients with pre-ITI inhibitor titres below 40 BU mL−1 can successfully be treated with low dose ITI. As a result of its lower clotting factor use and lower frequency of infusions, this ITI regimen has several advantages. We estimate the cost to be considerably lower, compared with high dose ITI regimens [4]. Furthermore, the burden for patients and parents is lower, because of the lower frequency of FVIII infusions. Implantation of a PAC system can often be avoided, thus saving clotting factor consumption. In addition, complications such as PAC infections, which are associated with a longer time to achieve complete success, may be avoided. JNK inhibitor concentration Disadvantages of the low dose ITI regimen may be the longer time needed to achieve success [7], and the

delay of effective prophylaxis with FVIII. this website For some patients, this may be a reason to switch to a high dose regimen. Although studies on prophylaxis with bypassing agents in inhibitor patients have reported beneficial effects, it is not an established therapy yet, and prophylaxis with bypassing agents may be less effective than with FVIII [20]. Low dose immune tolerance induction therapy is successful in severe haemophilia A patients with a pre-ITI titre below 40 BU mL−1. A shorter time to success selleck compound is predicted by a maximum ITI titre below 40 BU mL−1.

In patients with a titre below 5 BU mL−1, this effect is even more pronounced (P = 0.033). We suggest that patients with severe haemophilia A and a pre-ITI inhibitor titre below 5 BU mL−1 should be treated with low dose immune tolerance induction therapy. Patients with a pre-ITI titre below 40 BU mL−1 may strongly benefit from low dose ITI regimen. However, patients with a pre-ITI inhibitor titre above 40 BU mL−1, with an anamnestic response during ITI exceeding 40 BU mL−1, or without response to the low dose regimen, should rather be treated with a high dose immune tolerance induction therapy. The authors would like to thank D.E. Fransen van de Putte for critical evaluation of the manuscript. The authors stated that they had no interests which might be perceived as posing a conflict or bias. “
“This chapter contains sections titled: Introduction Cryoprecipitate Principles of manufacture Product purity Methods of viral inactivation and elimination Potency and labeling issues Selection of products Plasma-derived concentrates for rare bleeding disorders References “
“Health-related quality of life (HRQoL) assessment is recognized as an important outcome in the evaluation of different therapeutic regimens for persons with haemophilia.