Standard liver biochemistry selleckchem (alanine aminotransferase, aspartate aminotransferase, total bilirubin, gamma-glutamyltranspeptidase, and alkaline phosphatase [ALP]) along with other standard laboratory investigations (creatinine, hemoglobin, and thyroid-stimulating hormone levels) were retrieved. Serum immunoglobulin G, immunoglobulin M, and titer of serum AMA (routine immunofluorescence) or AMA-M2 (Pharmacia Diagnostics, Dorval, Quebec) were recorded. Serum biochemical data were available for all subjects at the time of questionnaire and from within the year immediately before symptom assessment. Data from liver biopsy, abdominal ultrasound, as well as upper endoscopy,

were also collected. PBC-40 is a 40-item scale measuring health-related quality of life in PBC, readily applicable to routine clinic practice, as a way of patients evaluating their symptoms.26 It consists of specific symptom domains (Cognition,

Itch, Fatigue, Social, Emotional, and Symptoms) and is designed for self-completion. Participants Selleck AG-14699 rate items on a five-point scale (1 = ‘never’ to 5 = ‘always’), with high scores denoting greater symptoms impact and poorer quality of life. A previous study defined ranges of severity for the symptom domains contained in the PBC-40.21 By using these clinically meaningful cutoff values applied to the scores from the PBC-40 Fatigue domain, no fatigue was a score of 11 or less, mild was a score of MCE 12 to 28, moderate was a score of 29 to 39, and severe was a score of 40 or greater. To test the reliability of the questionnaire in our PBC patient population, the PBC-40 questionnaire was applied twice, at a 1-year interval, to a random sample of 196 patients. Data were analyzed using SAS. Results are reported as mean ± standard deviation. Categorical variables were analyzed using a series of t tests and chi-squared test (or Fisher’s exact test where appropriate). Pearson correlation coefficient (or analysis of variance where appropriate) was performed to analyze correlations between fatigue scores and various biological, demographic,

and clinical variables. Finally, variables that were found to be statistically significant were further analyzed with multivariate analysis using a backward selection procedure to determine predictive factors for fatigue. A P value < 0.05 was considered significant. ALP, alkaline phosphatase; AMA, antimitochondrial antibody; BMI, body mass index; PBC, primary biliary cirrhosis; QOL, quality of life; UDCA, ursodeoxycholic acid. Three hundred twenty-seven unselected patients with PBC were included in the review. Clinical, biochemical, and histological stage of disease in the participants are summarized in Table 1. At the time of questionnaire, 94% of the participating cohort were women, and the mean age was 57.3 ± 11.5 (range, 24-90).

Methods: 438 patients were categorized as non-responders if they had a <40% drop in ALP after one year of UDCA. A time-dependent propensity score was derived to determine the probability of patients receiving feno-fibrates. Primary outcome measure: transplant-free survival, reaching minimal listing criteria or decompensated cirrhosis. Secondary outcome: biochemical response and change in bilirubin. Results: Of 387 eligible patients, 133/387 (34.4%) were nonresponders: 49/133 (36.8%) were on a fenofibrate and UDCA (FF) and 84/133 (63.2%) on UDCA alone (UDCA).

The propensity score was derived from Small molecule library baseline age, time from diagnosis, cirrhosis, bilirubin and ALT. Time on lipidil was 336±402 days. Those with decompensated cirrhosis had a lower mean bilirubin over time in the FF group compared to the UDCA group. In the FF group, 25/33 (75.8%) of patients had >40% drop in ALP after >100 days of treatment. Similar number of patients decompensated (19.0% UDCA; 18.4% FF, p=1.00), died/underwent transplant (14.3% both FF & UDCA groups, p=1.00) Nutlin-3 manufacturer (Figure 1). 8/49 (16.3%) stopped fenofibrate due to adverse events (most common: hepatitis &

abdominal pain). Conclusion: Fenofibrates lead to biochemical response, but do not have a clear impact on transplant-free survival or decompensated cirrhosis in PBC. Disclosures: E. Jenny Heathcote – Consulting: Axcan Pharma, Gilead Sciences, Hoffman-La-Roche, Merck, Tibotec (Johnson & Johnson), Axcan Pharma, Gilead Sciences, Hoffman-LaRoche, Merck, Tibotec (Johnson & Johnson), Axcan Pharma, Gilead Sciences, Hoffman-LaRoche, Merck, Tibotec (Johnson & Johnson), Axcan Pharma, Gilead Sciences, Hoffman-LaRoche, Merck, Tibotec (Johnson & Johnson); Grant/ Research Support: Axcan Pharma, Boehringer Ingelheim, Bristol-Myers Squib, Gilead Sciences, MCE公司 GlaxoSmithKline, Hoffman-LaRoche, Intercept Pharma, Merck, Tibotec (Johnson & Johnson), Vertex, Axcan Pharma, Boehringer Ingelheim, Bristol-Myers Squib, Gilead Sciences, GlaxoSmithKline, Hoffman-LaRoche, Intercept Pharma, Merck, Tibotec

(Johnson & Johnson), Vertex, Axcan Pharma, Boehringer Ingelheim, Bristol-Myers Squib, Gilead Sciences, GlaxoSmithKline, Hoffman-LaRoche, Intercept Pharma, Merck, Tibotec (Johnson & Johnson), Vertex, Axcan Pharma, Boehringer Ingelheim, Bristol-Myers Squib, Gilead Sciences, GlaxoSmithKline, Hoffman-LaRoche, Intercept Pharma, Merck, Tibotec (Johnson & Johnson), Vertex; Speaking and Teaching: Axcan Pharma, Gilead Sciences, Hoffman-LaRoche, Merck, Tibotec (Johnson & Johnson), Axcan Pharma, Gilead Sciences, Hoffman-LaRoche, Merck, Tibotec (Johnson & Johnson), Axcan Pharma, Gilead Sciences, Hoffman-LaRoche, Merck, Tibotec (Johnson & Johnson), Axcan Pharma, Gilead Sciences, Hoffman-LaRoche, Merck, Tibotec (Johnson & Johnson) Harry L.

We think that an explanatory strategy for building the Cox model, using time-dependent covariates and a propensity score to adjust for the potential confounding factors, would have enriched the study.3–5 In this way, instead of being Selleck Dasatinib driven by significance tests, covariates would have entered and remained in the explanatory model as a result of their modification effect on the association of therapy and mortality.3 Moreover, they could have checked for confounding and likely interactions to explore whether the observed effect was the same in different subsets of patients, as the editorialists claimed. Besides, the use of time-dependent covariates would have allowed fine-tuning of the

beta-blocker therapy duration and would have better addressed its influence on outcomes.4 Finally, a propensity score, which defines the probability that an individual will receive a specific treatment based on his or her pretreatment characteristics, is useful for overcoming the imbalance

between www.selleckchem.com/products/r428.html groups when treatment assignment is not random.5 Specifically, in Serstè et al.’s study, the propensity score would have corrected the effect of beta-blockers for patient characteristics such as the presence of varices, which heavily conditions their prescription. With such an analysis, the focus of the model would have been the influence of beta-blockers on survival rather than the identification of factors influencing survival; hence, it would have offered more clues to the causal effect. The proposed approach would add robustness to the interesting results provided by Serstè et al. Agustín Albillos M.D., Ph.D.* ‡, Javier

Zamora M.D., Ph.D.† §, * Departments of Gastroenterology and Hepatology, Ramón y Cajal Institute of Health Research, University of Alcalá, Madrid, Spain, † Clinical Biostatistics, Ramón 上海皓元医药股份有限公司 y Cajal University Hospital, Ramón y Cajal Institute of Health Research, University of Alcalá, Madrid, Spain, ‡ Network Centers for Biomedical Research in Hepatic and Digestive Diseases Carlos III Institute of Health, Madrid, Spain, § Epidemiology and Public Health, Carlos III Institute of Health, Madrid, Spain. “
“The hepatitis C virus (HCV) is a small, parenterally transmitted RNA virus that is acquired today almost exclusively by the use of unsterile needles. It occurs in sixdistinct genotypes, genotype 1 being the most prevalent in North America, Europe, and Japan. HCV causes an acute hepatitis that is clinically silent in most cases and persists in the majority (80%) of patients leading to chronic hepatitis. Chronic hepatitis C remains clinically silent, and progresses to cirrhosis in about 10% of patients within 20 years. Once cirrhosis is established, morbidity and mortality from hepatic decompensation and hepatocellular carcinoma ensues. Concomitant alcohol consumption, male gender, co-infection with HIV or HBV, and older age at time of infection accelerates the progression to cirrhosis.

We describe the clinical presentation and endovascular management of an end-stage renal disease patient with a left upper extremity arteriovenous graft who developed intracranial venous hypertension, left-sided subdural

and subarachnoid intracranial hemorrhage, and left-sided cerebral infarcts related to a left brachiocephalic vein occlusion. “
“Tolosa-Hunt syndrome (THS) is a very rare, relapsing, and remitting painful ophthalmoplegia caused by nonspecific granulomatous inflammation learn more in the cavernous sinus. To our knowledge, bilateral complete, simultaneous palsies of all 3 cranial nerves associated with extraocular movement have not been reported. We describe the first such patient with bilateral THS that responded quickly to corticosteroid therapy. A 54-year-old man presented with a periorbital and frontal headache with acute bilateral severe blepharoptosis and

fixed eyes, which dramatically responded to corticosteroid therapy. He had diabetes mellitus type II. Brain MRI showed granulomatous inflammation in both cavernous sinuses and thickening of the surrounding selleckchem dura mater of the cranial base, suggesting the coexistence of focal hypertrophic cranial pachymeningitis. Our experience indicates that steroid therapy with strict control of blood sugar should be considered in patients with THS complicated by diabetes. MRI is a valuable tool for serially monitoring the response of lesions to treatment in THS. “
“Artery-to-artery embolism generally occurs in patients with not only moderate to severe arterial stenosis but also plaque vulnerability. Two 上海皓元 unique cases with free-floating thrombi at the distal side of the small plaque in the internal carotid artery without stenosis are presented and its clinical implications are discussed. Two middle-aged men suffered embolic stroke. Initial duplex ultrasonography revealed small plaques and vortex flow without significant stenosis or plaque vulnerability in their internal carotid arteries. Continuous examination by duplex ultrasonography showed that free-floating thrombi developed and regressed at the

distal side of the small plaques. Histological examination disclosed plaque erosion at the distal side of the plaques without lipid core rupture. In these two cases, duplex ultrasonography revealed free-floating thrombi developed at the distal region of small plaques. Aggressive treatment should be considered in a patient with thromboembolic stroke who has the small plaque presenting “snake fang” sign even if there is no stenosis or plaque vulnerability. “
“Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) is a recently defined inflammatory central nervous system disorder responsive to steroids with characteristic magnetic resonance imaging (MRI) features.

Furthermore, in vivo immortalization and in vitro cultivation presumably led to a dedifferentiated phenotype, characterized by low miR-122 and ApoE levels. Nevertheless, these results indicate that mouse liver cells can support vigorous HCV RNA replication in the absence of any human cofactors (Fig. 3C). Given that mature mouse miR-122 is highly expressed in mouse livers (Fig. 2), and since the mouse miR-122 supported Quizartinib ic50 HCV replication in mouse

liver cells as efficiently as the human ortholog (Fig. 3), we consider it unlikely that HCV replication in mouse liver is limited by availability of miR-122. Collectively, these findings raise the hope that establishment of robust HCV RNA MK 2206 replication in vivo may require only little genetic manipulation of mice, possibly not involving ectopic expression of human replication cofactors. Clearly, for construction of fully HCV permissive mice it is crucial that mouse liver cells not only permit efficient RNA replication but also virus production and cell entry. Using the MLT-MAVS−/−miR-122 cells we show that reconstitution

of ApoE expression is necessary and sufficient to allow production of infectious HCV progeny from full-length genomes (Fig. 5). This observation underscores the important role of ApoE during virus production and extends the findings of Long et al.,[8] who recently reported that trans-complemented HCV particles can be produced in a stable mouse replicon cell line. Similar to those authors, we did not find a striking difference between HCV usage of human or mouse MCE公司 ApoE, suggesting that endogenous ApoE expression in mouse liver should sustain HCV assembly. However, the efficiency of virus production from MLT-MAVS−/−miR-122-derived cells was generally lower compared to human Huh-7.5 cells. While this may suggest that other mouse assembly cofactors are not efficiently used by HCV, it is also possible that attenuated replication of

full-length HCV in mouse liver cells indirectly reduced virus production. In fact, human liver cells that are also less permissive for HCV RNA replication than Huh-7.5 cells (e.g., HepG2 and HuH6 cells) produce much lower levels of infectious virus.[14, 20] Regarding cell entry, expression of the complete or minimal set of absolutely essential human HCV entry cofactors rendered MLT-MAVS−/−miR-122 cells permissive to HCVcc infection (Fig. 6). Notably, infection of these mouse cells was more efficient for the mouse-tropic Jc1 variant[2] although both viruses displayed comparable infectiousness on Huh-7.5 cells (Fig. 6). However, since upon dilution of these virus stocks Luc-Jc1mCD81 was also more infectious than Luc-Jc1 in Huh-7.

Furthermore, in vivo immortalization and in vitro cultivation presumably led to a dedifferentiated phenotype, characterized by low miR-122 and ApoE levels. Nevertheless, these results indicate that mouse liver cells can support vigorous HCV RNA replication in the absence of any human cofactors (Fig. 3C). Given that mature mouse miR-122 is highly expressed in mouse livers (Fig. 2), and since the mouse miR-122 supported Selleckchem CHIR-99021 HCV replication in mouse

liver cells as efficiently as the human ortholog (Fig. 3), we consider it unlikely that HCV replication in mouse liver is limited by availability of miR-122. Collectively, these findings raise the hope that establishment of robust HCV RNA DNA Damage inhibitor replication in vivo may require only little genetic manipulation of mice, possibly not involving ectopic expression of human replication cofactors. Clearly, for construction of fully HCV permissive mice it is crucial that mouse liver cells not only permit efficient RNA replication but also virus production and cell entry. Using the MLT-MAVS−/−miR-122 cells we show that reconstitution

of ApoE expression is necessary and sufficient to allow production of infectious HCV progeny from full-length genomes (Fig. 5). This observation underscores the important role of ApoE during virus production and extends the findings of Long et al.,[8] who recently reported that trans-complemented HCV particles can be produced in a stable mouse replicon cell line. Similar to those authors, we did not find a striking difference between HCV usage of human or mouse medchemexpress ApoE, suggesting that endogenous ApoE expression in mouse liver should sustain HCV assembly. However, the efficiency of virus production from MLT-MAVS−/−miR-122-derived cells was generally lower compared to human Huh-7.5 cells. While this may suggest that other mouse assembly cofactors are not efficiently used by HCV, it is also possible that attenuated replication of

full-length HCV in mouse liver cells indirectly reduced virus production. In fact, human liver cells that are also less permissive for HCV RNA replication than Huh-7.5 cells (e.g., HepG2 and HuH6 cells) produce much lower levels of infectious virus.[14, 20] Regarding cell entry, expression of the complete or minimal set of absolutely essential human HCV entry cofactors rendered MLT-MAVS−/−miR-122 cells permissive to HCVcc infection (Fig. 6). Notably, infection of these mouse cells was more efficient for the mouse-tropic Jc1 variant[2] although both viruses displayed comparable infectiousness on Huh-7.5 cells (Fig. 6). However, since upon dilution of these virus stocks Luc-Jc1mCD81 was also more infectious than Luc-Jc1 in Huh-7.

Furthermore, in vivo immortalization and in vitro cultivation presumably led to a dedifferentiated phenotype, characterized by low miR-122 and ApoE levels. Nevertheless, these results indicate that mouse liver cells can support vigorous HCV RNA replication in the absence of any human cofactors (Fig. 3C). Given that mature mouse miR-122 is highly expressed in mouse livers (Fig. 2), and since the mouse miR-122 supported IDH inhibitor HCV replication in mouse

liver cells as efficiently as the human ortholog (Fig. 3), we consider it unlikely that HCV replication in mouse liver is limited by availability of miR-122. Collectively, these findings raise the hope that establishment of robust HCV RNA find protocol replication in vivo may require only little genetic manipulation of mice, possibly not involving ectopic expression of human replication cofactors. Clearly, for construction of fully HCV permissive mice it is crucial that mouse liver cells not only permit efficient RNA replication but also virus production and cell entry. Using the MLT-MAVS−/−miR-122 cells we show that reconstitution

of ApoE expression is necessary and sufficient to allow production of infectious HCV progeny from full-length genomes (Fig. 5). This observation underscores the important role of ApoE during virus production and extends the findings of Long et al.,[8] who recently reported that trans-complemented HCV particles can be produced in a stable mouse replicon cell line. Similar to those authors, we did not find a striking difference between HCV usage of human or mouse medchemexpress ApoE, suggesting that endogenous ApoE expression in mouse liver should sustain HCV assembly. However, the efficiency of virus production from MLT-MAVS−/−miR-122-derived cells was generally lower compared to human Huh-7.5 cells. While this may suggest that other mouse assembly cofactors are not efficiently used by HCV, it is also possible that attenuated replication of

full-length HCV in mouse liver cells indirectly reduced virus production. In fact, human liver cells that are also less permissive for HCV RNA replication than Huh-7.5 cells (e.g., HepG2 and HuH6 cells) produce much lower levels of infectious virus.[14, 20] Regarding cell entry, expression of the complete or minimal set of absolutely essential human HCV entry cofactors rendered MLT-MAVS−/−miR-122 cells permissive to HCVcc infection (Fig. 6). Notably, infection of these mouse cells was more efficient for the mouse-tropic Jc1 variant[2] although both viruses displayed comparable infectiousness on Huh-7.5 cells (Fig. 6). However, since upon dilution of these virus stocks Luc-Jc1mCD81 was also more infectious than Luc-Jc1 in Huh-7.

Immunohistochemistry was performed using standard procedures. In short, liver tissues were removed and fixed in 10% neutral buffered formalin and embedded in paraffin wax. Five-micrometer sections were prepared for hematoxylin and eosin staining and immunofluorescence

analyses. After deparaffinization, antigen unmasking was performed in a decloaking chamber (Biocare Medical, San Diego, CA) using BORG Decloaker Solution (Biocare Medical, San Diego, CA) for 5 minutes at 125°C. The sections were blocked for 30 minutes in Tris-buffered saline/Tween 20 buffer containing 3% goat serum. Primary antibodies used in this study included click here rabbit anti–phospho-STAT5 (Tyr694), anti-cleaved caspase-3 (Cell

Signaling Technology), MG132 rabbit anti-NOX4 (Novus Biologicals, Littleton, CO), rabbit anti-PUMA (Abcam, Cambridge, MA), anti-BIM (Cell Signaling Technology), anti–phospho-histone H3 (Upstate Biotechnology, Lake Placid, NY), and anti-Ki 67 (Santa Cruz Biotechnology) in addition to mouse anti-β-catenin (BD Transduction Laboratories, San Jose, CA). For double-labeling immunofluorescence analyses, sections exposed to a pair of primary antibodies were incubated in a 1:400 dilution of goat anti-rabbit immunoglobulin G (IgG) conjugated with a red fluorophore (Alexa Fluor 594; Molecular Probes, Eugene,

OR) and goat anti-mouse IgG conjugated with a green fluorophore (Alexa Fluor 488; Molecular Probes, Eugene, OR) for 30 min at room temperature. Images were obtained with a Retiga Exi camera on a Olympus BX51 microscope (Olympus America, Center Valley, PA) using Image-Pro 5.1 software. For GH stimulation, mice were injected with 2 μg/g body weight of GH intraperitoneally. They were sacrificed 45 minutes after injection, and liver tissue was harvested. Noninjected mice were used as controls. Liver tissue was cross-linked in 1.5% formaldehyde for 15 minutes MCE at 37°C and sonicated using the Misonix Sonicator 3000 (Misonix, Farmingdale, NY). Immunoprecipitation was carried out in TE buffer containing protease inhibitors (Sigma, St. Louis, MO). Chromatin was incubated with protein A Dynabeads (Invitrogen, Carlsbad, CA), which were preincubated with STAT5A or IgG antibody (R&D Systems, Minneapolis, MN). Immunoprecipitated DNA was eluted and amplified by real-time polymerase chain reaction (PCR) using a 7900 HT fast real-time PCR system (Applied Biosystems, Foster City, CA) and analyzed using SDS2.3 Software (Applied Biosystems, Foster City, CA).

Immunohistochemistry was performed using standard procedures. In short, liver tissues were removed and fixed in 10% neutral buffered formalin and embedded in paraffin wax. Five-micrometer sections were prepared for hematoxylin and eosin staining and immunofluorescence

analyses. After deparaffinization, antigen unmasking was performed in a decloaking chamber (Biocare Medical, San Diego, CA) using BORG Decloaker Solution (Biocare Medical, San Diego, CA) for 5 minutes at 125°C. The sections were blocked for 30 minutes in Tris-buffered saline/Tween 20 buffer containing 3% goat serum. Primary antibodies used in this study included selleck screening library rabbit anti–phospho-STAT5 (Tyr694), anti-cleaved caspase-3 (Cell

Signaling Technology), ITF2357 in vitro rabbit anti-NOX4 (Novus Biologicals, Littleton, CO), rabbit anti-PUMA (Abcam, Cambridge, MA), anti-BIM (Cell Signaling Technology), anti–phospho-histone H3 (Upstate Biotechnology, Lake Placid, NY), and anti-Ki 67 (Santa Cruz Biotechnology) in addition to mouse anti-β-catenin (BD Transduction Laboratories, San Jose, CA). For double-labeling immunofluorescence analyses, sections exposed to a pair of primary antibodies were incubated in a 1:400 dilution of goat anti-rabbit immunoglobulin G (IgG) conjugated with a red fluorophore (Alexa Fluor 594; Molecular Probes, Eugene,

OR) and goat anti-mouse IgG conjugated with a green fluorophore (Alexa Fluor 488; Molecular Probes, Eugene, OR) for 30 min at room temperature. Images were obtained with a Retiga Exi camera on a Olympus BX51 microscope (Olympus America, Center Valley, PA) using Image-Pro 5.1 software. For GH stimulation, mice were injected with 2 μg/g body weight of GH intraperitoneally. They were sacrificed 45 minutes after injection, and liver tissue was harvested. Noninjected mice were used as controls. Liver tissue was cross-linked in 1.5% formaldehyde for 15 minutes MCE at 37°C and sonicated using the Misonix Sonicator 3000 (Misonix, Farmingdale, NY). Immunoprecipitation was carried out in TE buffer containing protease inhibitors (Sigma, St. Louis, MO). Chromatin was incubated with protein A Dynabeads (Invitrogen, Carlsbad, CA), which were preincubated with STAT5A or IgG antibody (R&D Systems, Minneapolis, MN). Immunoprecipitated DNA was eluted and amplified by real-time polymerase chain reaction (PCR) using a 7900 HT fast real-time PCR system (Applied Biosystems, Foster City, CA) and analyzed using SDS2.3 Software (Applied Biosystems, Foster City, CA).

10, 12, 14, 16 More recently, Ning et al.11 reported that overexpression of HNF4α suppresses diethylnitrosamine (DEN)-induced HCC in rats. These data suggest that HNF4α may have the ability to inhibit hepatocyte proliferation within the liver; however, the mechanisms are yet to be determined. Because of its fundamental role in liver development and homeostasis, whole-body deletion of HNF4α results in an embryonic lethal phenotype.18 Liver-specific deletion of HNF4α under an albumin promoter-driven cre recombinase

results in severe hepatic metabolic disruption and lethality between 6 and 8 weeks of age.4, 18 In these mice produced using constitutively active albumin-cre, HNF4α is deleted during early postnatal development, making it difficult to decipher the effect of improper hepatic differentiation and aberrant hepatic proliferation on the observed phenotype. To overcome RAD001 these issues, we developed Saracatinib in vivo an inducible knockout (KO) of HNF4α where HNF4α is deleted in the mature mouse liver using a tamoxifen (TAM)-inducible cre recombinase (ERT2-Cre), first described by Bonzo et al.17 Using this novel mouse model of hepatocyte specific HNF4α deletion in the adult liver combined with RNA sequencing mediated transcriptomics, we investigated the mechanism of HNF4α-mediated inhibition of hepatocyte proliferation. We also studied the significance of the role of HNF4α-mediated regulation

of hepatocyte proliferation using a chemical carcinogenesis model. Our studies indicate that apart from its role in hepatic differentiation, HNF4α actively inhibits hepatocyte proliferation and plays a critical role in maintenance of hepatic homeostasis. The HNF4αFl/Fl mice (provided by Dr. Frank Gonzalez of NCI-NIH)

and the TAM-inducible albumin cre mice (AlbCreERT2+, provided by Dr. Pierre Chambon, IGBMC-France) used in these studies have been described.4 The HNF4αFl/Fl, AlbCreERT2+ mice were produced by standard animal breeding and identified using polymerase chain reaction (PCR)-based genotyping of tail biopsies. All animals were housed in 上海皓元医药股份有限公司 Association for Assessment and Accreditation of Laboratory Animal Care-accredited facilities at the University of Kansas Medical Center under a standard 12-hour light/dark cycle with access to chow and water ad libitum. The Institutional Animal Care and Use Committee approved all of the studies. Three-month-old male, HNF4αFl/Fl, AlbERT2-Cre+ mice were treated with TAM (6 μg/mouse, intraperitoneal, referred to as HNF4α-KO), or with vehicle alone (corn oil, intraperitoneal, referred to as Control) subcutaneously. To account for changes induced by TAM, 3-month-old male, HNF4αFl/Fl, AlbERT2-Cre− mice were treated with TAM (6 μg/mouse, intraperitoneal, referred to as TAM Control). Mice were killed by cervical dislocation under isoflurane anesthesia and livers were collected 7 days postinjection.