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 see more 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 learn more 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 selleckchem 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.

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 learn more 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 Silmitasertib 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 check details 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.

23 The purpose of this multicenter headache clinic survey study was to evaluate in men and women with migraine the frequency of different types of abuse, to assess their associations with migraine characteristics, and with comorbid PARP inhibitor mental and physical health conditions. In this first paper we examine childhood maltreatment prevalence and severity, interrelatedness of abuse types, as well as the rates of revictimization in adulthood. We report on the relationship of abuse with demographic variables, and confounding conditions, including body mass index (BMI), substance abuse, depression, and anxiety. Patient Selection.— This multicenter study was conducted by the members of the Women’s Issues Section

research consortium of the American Headache Society. A detailed explanation of patient recruitment, data collection, and some of

the measures of this study were reported previously.24 The recruitment of the cross-sectional survey of headache clinic patients occurred between February 2006 and June 2008 at 11 outpatient headache centers, after each center separately obtained approval from the Institutional Review Boards (IRB). Participants were examined by a headache specialist, who determined the patient’s eligibility and obtained informed consent per the IRB protocol. Participation click here in the study was offered to consecutive patients, men or women, using the following inclusion criteria: primary headache disorder as defined by the International Classification of Headache Disorders (ICHD)-2 criteria,20 18 years and older, willingness to complete a self-administered electronic questionnaire on a Personal Digital Assistant (PDA), eg, the Palm® handheld device. Exclusion criteria included the following: not physically well enough to complete an electronic questionnaire on a PDA, and not literate in English. The physician or the study personnel provided the subjects with

verbal instructions and selleck chemical a brief demonstration of the technology to complete the survey. Data Collection.— The electronic questionnaire used in this study was designed with Pendragon® Forms 5.0 computer software (Pendragon Software Corporation, Libertyville, IL, USA). The questionnaire collected information on sociodemographic variables (age, gender, race, household income, highest educational level attained, BMI, caffeine use, smoking status, substance abuse), current depression and anxiety, childhood abuse and neglect, and abuse in adulthood. Questions on substance abuse inquired about the abuse of prescription medications, alcohol, and illegal drugs. Participants were asked if they currently abused these substances or if abuse occurred in the past. Table 1 provides the demographic details of the study population. Surveys were collected from 11 centers, which recruited participants during periods ranging from 6 weeks to 12 months. Analysis in this study includes all persons with migraine with aura, and migraine without aura, whether episodic or chronic.

23 The purpose of this multicenter headache clinic survey study was to evaluate in men and women with migraine the frequency of different types of abuse, to assess their associations with migraine characteristics, and with comorbid Palbociclib supplier mental and physical health conditions. In this first paper we examine childhood maltreatment prevalence and severity, interrelatedness of abuse types, as well as the rates of revictimization in adulthood. We report on the relationship of abuse with demographic variables, and confounding conditions, including body mass index (BMI), substance abuse, depression, and anxiety. Patient Selection.— This multicenter study was conducted by the members of the Women’s Issues Section

research consortium of the American Headache Society. A detailed explanation of patient recruitment, data collection, and some of

the measures of this study were reported previously.24 The recruitment of the cross-sectional survey of headache clinic patients occurred between February 2006 and June 2008 at 11 outpatient headache centers, after each center separately obtained approval from the Institutional Review Boards (IRB). Participants were examined by a headache specialist, who determined the patient’s eligibility and obtained informed consent per the IRB protocol. Participation CT99021 in the study was offered to consecutive patients, men or women, using the following inclusion criteria: primary headache disorder as defined by the International Classification of Headache Disorders (ICHD)-2 criteria,20 18 years and older, willingness to complete a self-administered electronic questionnaire on a Personal Digital Assistant (PDA), eg, the Palm® handheld device. Exclusion criteria included the following: not physically well enough to complete an electronic questionnaire on a PDA, and not literate in English. The physician or the study personnel provided the subjects with

verbal instructions and selleck compound a brief demonstration of the technology to complete the survey. Data Collection.— The electronic questionnaire used in this study was designed with Pendragon® Forms 5.0 computer software (Pendragon Software Corporation, Libertyville, IL, USA). The questionnaire collected information on sociodemographic variables (age, gender, race, household income, highest educational level attained, BMI, caffeine use, smoking status, substance abuse), current depression and anxiety, childhood abuse and neglect, and abuse in adulthood. Questions on substance abuse inquired about the abuse of prescription medications, alcohol, and illegal drugs. Participants were asked if they currently abused these substances or if abuse occurred in the past. Table 1 provides the demographic details of the study population. Surveys were collected from 11 centers, which recruited participants during periods ranging from 6 weeks to 12 months. Analysis in this study includes all persons with migraine with aura, and migraine without aura, whether episodic or chronic.

The estimated birth dates were used to estimate population density and recruitment. These were then compared with other data sources. We found out that density estimates, based on numerical methods [modified nodal analysis (MNA)], underestimated population density during the period of low trappability and that recruitment occurred up to 100 days earlier than was observed FK228 datasheet by capture-mark-recapture

(CMR) analysis and MNA. This study suggests that cohort analysis can be conducted on short-lived small mammals during periods when estimates based on CMR or numerical analysis fail because of low sample sizes. Furthermore, it is possible to use body weight of live-trapped individuals to estimate age. This is important in terms of ethics and conservation as such methods can be conducted without harming or killing the animals. We believe that live-trapping data obtained during a peak period in population density can be a useful aid when describing population parameters of previous months when low trappability prevents direct measurements. “
“Foraging data for terrestrial carnivorans are most often obtained by the analysis of faecal samples – an established technique. However, advances in satellite tracking technology are allowing researchers to locate kill sites by investigating global positioning

system (GPS) clusters in both space and time. Here we compare leopard selleck chemicals Panthera pardus dietary estimates (composition and biomass) of small, medium and large prey using three techniques: faecal analysis, GPS cluster analysis and GPS cluster analysis supplemented with faecal samples located at cluster sites. We demonstrate that estimates of leopard prey composition and biomass intake from each technique

produce comparatively similar results. Nevertheless, the detection of feeding events did increase by 20–23% when supplementing GPS-located kills with faecal samples. selleck kinase inhibitor The investigation of GPS clusters offers an equivalent method of leopard dietary estimation to that of faecal analysis. When carried out intensively, the GPS cluster method is capable of detecting leopard predation on prey species within small, medium and large weight categories. Although requiring additional resources, supplementing GPS-located kills with GPS-located faecal samples results in the most detailed dietary estimates by detecting kills missed during GPS cluster investigations. Practical and efficient ways to estimate prey composition and biomass intake are important for leopard Panthera pardus conservation and management. For example, kill rates, leopard-prey dynamics and foraging requirements are necessary for carrying capacity estimates, and the establishment of protected zones and habitat corridors (Hayward, Obrien & Kerley, 2007; Owen-Smith, 2008; Knopff et al., 2010). For many terrestrial carnivores, foraging data are most often obtained by the analysis of faecal samples (Klare, Kamler & Macdonald, 2011).

The estimated birth dates were used to estimate population density and recruitment. These were then compared with other data sources. We found out that density estimates, based on numerical methods [modified nodal analysis (MNA)], underestimated population density during the period of low trappability and that recruitment occurred up to 100 days earlier than was observed Cilomilast datasheet by capture-mark-recapture

(CMR) analysis and MNA. This study suggests that cohort analysis can be conducted on short-lived small mammals during periods when estimates based on CMR or numerical analysis fail because of low sample sizes. Furthermore, it is possible to use body weight of live-trapped individuals to estimate age. This is important in terms of ethics and conservation as such methods can be conducted without harming or killing the animals. We believe that live-trapping data obtained during a peak period in population density can be a useful aid when describing population parameters of previous months when low trappability prevents direct measurements. “
“Foraging data for terrestrial carnivorans are most often obtained by the analysis of faecal samples – an established technique. However, advances in satellite tracking technology are allowing researchers to locate kill sites by investigating global positioning

system (GPS) clusters in both space and time. Here we compare leopard BMS-907351 nmr Panthera pardus dietary estimates (composition and biomass) of small, medium and large prey using three techniques: faecal analysis, GPS cluster analysis and GPS cluster analysis supplemented with faecal samples located at cluster sites. We demonstrate that estimates of leopard prey composition and biomass intake from each technique

produce comparatively similar results. Nevertheless, the detection of feeding events did increase by 20–23% when supplementing GPS-located kills with faecal samples. learn more The investigation of GPS clusters offers an equivalent method of leopard dietary estimation to that of faecal analysis. When carried out intensively, the GPS cluster method is capable of detecting leopard predation on prey species within small, medium and large weight categories. Although requiring additional resources, supplementing GPS-located kills with GPS-located faecal samples results in the most detailed dietary estimates by detecting kills missed during GPS cluster investigations. Practical and efficient ways to estimate prey composition and biomass intake are important for leopard Panthera pardus conservation and management. For example, kill rates, leopard-prey dynamics and foraging requirements are necessary for carrying capacity estimates, and the establishment of protected zones and habitat corridors (Hayward, Obrien & Kerley, 2007; Owen-Smith, 2008; Knopff et al., 2010). For many terrestrial carnivores, foraging data are most often obtained by the analysis of faecal samples (Klare, Kamler & Macdonald, 2011).

We performed an audit of all EUS examinations performed at a tertiary referral centre, to determine the number of gastro-oesophageal examinations performed and to evaluate the impact this would have on the duration of EUS training required to achieve accreditation. Methods: We identified reports from all EUS examination performed over a period of three and half years (July 2009 to January 2013) at the Princess Alexandra Hospital in Brisbane. The following data were collected from each report: date of procedure, indication of procedure and procedural staff. The proportion of EUS examinations with a gastro-oesophageal indication

and Buparlisib supplier the proportion of EUS examinations where the advanced endoscopy fellow was present were determined. The total number of procedures required in 12 months to reach accreditation was then calculated using the following assumptions: (1) at least 50 supervised procedures are required before independent EUS can be performed, and (2) only one advanced endoscopy Selleck Selinexor fellow will

be attached to the unit at a time. Results: A total of 953 EUS examinations were performed over three and a half years (272 procedures per year). Of those, 206 (22%) of those examinations were performed for a gastro-oesophageal indication (59 procedures per year). An advanced endoscopy fellow was listed as a proceduralist on 79% of all reports over this period. Based on the above assumptions and a 22% rate of gastro-oesophageal

EUS, the number of EUS examinations required to achieve accreditation within 12 months would be 625 per year. A 2.3 fold increase in the volume of EUS activity would be required to reach this level and allow advanced endoscopy fellows to achieve accreditation within 12 months at our centre. Conclusion: After completing 12 months of advanced endoscopy training at our centre, fellows would not selleck chemical have reached sufficient numbers to achieve accreditation through the CCRTGE. Even under ideal conditions, it would not be possible to complete an advanced endoscopy fellowship in 12 months. The CCRTGE should consider reducing the number of gastro-oesophageal EUS procedures required to achieve accreditation. Otherwise advanced endoscopy fellows should be expected to complete two years of training to achieve accreditation in EUS. YW TANG,1 RS GILL,2 R BASKARAN,2 RW LEONG1,2 1Gastroenterology and Liver Services, Concord General Repatriation Hospital, Sydney, Australia. 2Gastroenterology Department, Bankstown-Lidcombe Hospital, Sydney, Australia Background: Serous cystadenoma (SCA) of the pancreas is the most common benign primary pancreatic neoplasm. However, the natural history and growth pattern of pancreatic SCAs are not well understood.

Disclosures: Pere Gines – Advisory Committees or Review Panels: Ferring; Grant/Research Support: Sequana Medical, Grifols Rajiv Jalan – Consulting: Ocera Therapeutics, Conatus Juan Cordoba – Advisory Committees or Review Panels: Ocera Francois Durand – Advisory Committees or Review Panels: Astellas, Novartis; Speaking and Teaching: Gilead Faouzi Saliba Epigenetics inhibitor – Advisory Committees or Review Panels: Novartis, Roche, Genzyme; Grant/Research Support: Astellas; Speaking and Teaching: Schering Plough, Gambro, MSD Julia Wendon – Consulting: Pulsion, Excalenz Stefan Zeuzem – Consulting: Abbvie, Achillion Pharmaceuticals, Boehringer Ingelheim GmbH, Bristol-Myers Squibb Co., Gilead, Novartis Pharmaceuticals,

Merck & Co., Idenix, Janssen, Roche Pharma AG, Vertex Pharmaceuticals, Presidio, Santaris, Inc Mauro Bernardi – Consulting: CLS Behring GhmB; Speaking and Teaching: CLS Behring GhmB, PPTA Europe Vicente Arroyo – Speaking and Teaching: GRIFOLS The following people have nothing to disclose: Paolo Angeli, Salvatore Piano, Elisabet Garcίa, Filippo Morando, Ezequiel Rodriguez, Xavier Ariza, Elisabetta Gola, Elsa Solá, Monica Guevara, Richard Moreau, Marco Pavesi, Thierry Gustot, Marco Domenicali, Alexander L. Gerbes, Carlo Alessandria, Wim Laleman, Jonel Trebicka Background:

Symptomatic liver disease in hereditary hemorrhagic telangiectasia (HHT) is rare but may be fatal without liver transplantation. Aims: To identify risk factors predictive of clinically significant liver disease. Methods: In this prospective cohort study, we included consecutive patients referred to our HHT center from 2001 learn more with definite HHT. Patients underwent systematic protocol screening, including contrast-enhanced CT. From a multivariable logistic regression model, we

developed a simple clinical scoring index that may predict presence of clinically selleck compound significant liver disease [symptomatic liver disease (cardiac failure, portal hypertension or biliary disease) or at-risk liver involvement with abnormal liver examination (liver bruit, thrill, palpable hepatomegaly) or biochemistry or elevated cardiac index]. Results: Three hundred seventeen patients with definite HHT were included; 171 patients (54.5%; age 50.7±14.7 y, 101 females) had hepatic involvement on imaging. Twenty nine patients had symptomatic liver disease (22 with high-output heart failure, 6 with portal hypertension and 3 with symptomatic biliary disease) and 45 patients had at-risk liver disease. Ninety seven patients (56.7%) had hepatic involve-ment without symptomatic or at-risk liver disease. Using multivariable logistic regression analysis, four clinical variables (age, gender, hemoglobin and alkaline phosphatase) were modeled to develop a simple clinical scoring index (c-statistic to distinguish clinically significant liver involvement and no or incidental liver lesions=0.83). Table shows the probability of clinically significant liver disease based on risk score.

4-fold (Fig. 5A), whereas duodenal BMP6 mRNA expression was largely unaffected (Fig. 5B). The expression of ferroportin was markedly up-regulated in the duodenum of mice lacking hepatic Hjv (Fig. 5C). We conclude that hepatic Hjv is essential for preventing iron overload by way of appropriate signaling to hepcidin. Hfe2f/f:MCK-Cre mice bearing muscle-specific disruption of Hjv presented with

physiological serum iron indices (Table 2) and did not develop iron overload in the liver, pancreas, or, notably, in the heart (Fig. 4A; Supporting Fig. S1). Splenic macrophages contained stainable nonheme iron (Fig. S1), by analogy to Hfe2f/f controls. The expression of hepcidin mRNA (Fig. 4B), hepatic BMP6 mRNA (Fig. 5A), and duodenal BMP6 mRNA (Fig. 5B) did not significantly differ between Hfe2f/f:MCK-Cre and Hfe2f/f mice, whereas expression of duodenal ferroportin was Selleckchem Lenvatinib undetectable

(Fig. 5C). Thus, the absence of muscle Hjv did not affect iron metabolism in the whole body and, apparently, also in the heart, a tissue that normally expresses Hjv. We compared DAPT nmr the hepatic iron content and hepcidin mRNA expression levels among age- and sex-matched Hfe2f/f, Hfe2f/f:Alb-Cre, Hfe2f/f:MCK-Cre, and ubiquitous Hjv-/-7 mice; all lines shared a mixed 129S6/C57 genetic background, albeit with variable genomic ratios. The degree of hepatic iron overload (Fig. 4A), the deregulation of hepcidin expression (Fig. 4B), and the increase of hepatic BMP6 mRNA (Fig. 5B) were quantitatively similar among ubiquitous Hjv−/− and liver-specific Hjv−/− (Hfe2f/f:Alb-Cre) animals. Likewise, control floxed (Hfe2f/f) and muscle-specific Hjv−/− (Hfe2f/f:MCK-Cre) mice were phenotypically indistinguishable. Taken together, these results indicate that the absence of hepatic Hjv suffices to cause full-scale iron overload, whereas the lack of muscle Hjv does

not affect iron balance. Genetic studies in humans5 and mice6, 7 uncovered an important role of Hjv in the control of systemic iron homeostasis. Corroborating evidence was this website provided from biochemical data showing that Hjv activates the iron-dependent pathway for signaling to hepcidin by acting as a BMP coreceptor,8 whereas a circulating sHjv isoform is widely considered to antagonize this response.19, 20, 22, 31 We report here that the targeted disruption of Hjv in liver hepatocytes recapitulates the hemochromatotic phenotype of mice lacking Hjv ubiquitously.6, 7 Thus, the liver-specific ablation of Hjv leads to high transferrin saturation, hyperferremia, hyperferritinemia, hepatic iron overload, macrophage iron deficiency, and inappropriately low hepcidin expression, which are hallmarks of hereditary hemochromatosis. In addition, it is associated with increased hepatic BMP6 mRNA expression, as in ubiquitous Hjv−/− mice.

4-fold (Fig. 5A), whereas duodenal BMP6 mRNA expression was largely unaffected (Fig. 5B). The expression of ferroportin was markedly up-regulated in the duodenum of mice lacking hepatic Hjv (Fig. 5C). We conclude that hepatic Hjv is essential for preventing iron overload by way of appropriate signaling to hepcidin. Hfe2f/f:MCK-Cre mice bearing muscle-specific disruption of Hjv presented with

physiological serum iron indices (Table 2) and did not develop iron overload in the liver, pancreas, or, notably, in the heart (Fig. 4A; Supporting Fig. S1). Splenic macrophages contained stainable nonheme iron (Fig. S1), by analogy to Hfe2f/f controls. The expression of hepcidin mRNA (Fig. 4B), hepatic BMP6 mRNA (Fig. 5A), and duodenal BMP6 mRNA (Fig. 5B) did not significantly differ between Hfe2f/f:MCK-Cre and Hfe2f/f mice, whereas expression of duodenal ferroportin was Rapamycin undetectable

(Fig. 5C). Thus, the absence of muscle Hjv did not affect iron metabolism in the whole body and, apparently, also in the heart, a tissue that normally expresses Hjv. We compared Selleck Peptide 17 the hepatic iron content and hepcidin mRNA expression levels among age- and sex-matched Hfe2f/f, Hfe2f/f:Alb-Cre, Hfe2f/f:MCK-Cre, and ubiquitous Hjv-/-7 mice; all lines shared a mixed 129S6/C57 genetic background, albeit with variable genomic ratios. The degree of hepatic iron overload (Fig. 4A), the deregulation of hepcidin expression (Fig. 4B), and the increase of hepatic BMP6 mRNA (Fig. 5B) were quantitatively similar among ubiquitous Hjv−/− and liver-specific Hjv−/− (Hfe2f/f:Alb-Cre) animals. Likewise, control floxed (Hfe2f/f) and muscle-specific Hjv−/− (Hfe2f/f:MCK-Cre) mice were phenotypically indistinguishable. Taken together, these results indicate that the absence of hepatic Hjv suffices to cause full-scale iron overload, whereas the lack of muscle Hjv does

not affect iron balance. Genetic studies in humans5 and mice6, 7 uncovered an important role of Hjv in the control of systemic iron homeostasis. Corroborating evidence was selleck chemical provided from biochemical data showing that Hjv activates the iron-dependent pathway for signaling to hepcidin by acting as a BMP coreceptor,8 whereas a circulating sHjv isoform is widely considered to antagonize this response.19, 20, 22, 31 We report here that the targeted disruption of Hjv in liver hepatocytes recapitulates the hemochromatotic phenotype of mice lacking Hjv ubiquitously.6, 7 Thus, the liver-specific ablation of Hjv leads to high transferrin saturation, hyperferremia, hyperferritinemia, hepatic iron overload, macrophage iron deficiency, and inappropriately low hepcidin expression, which are hallmarks of hereditary hemochromatosis. In addition, it is associated with increased hepatic BMP6 mRNA expression, as in ubiquitous Hjv−/− mice.