Interestingly, many of the genes up-regulated are involved in cell cycle control and cancer (Table 2). IPA-mediated functional analysis reveals that the major classes of genes changed following HNF4α deletion are in the cancer and cell proliferation category. The up-regulation of promitogenic genes explains the significant increase in proliferation within the liver of HNF4α-KO mice. This observation also raises questions

regarding the mechanism by which HNF4α is regulating promitogenic genes. Whereas beyond the scope of this study, a closer look at the up-regulated genes in HNF4α-KO mice raises the possibility that HNF4α inhibits hepatocyte proliferation by way of both direct and CH5424802 indirect inhibition for select subpopulations of genes. Bonzo et al.17 first reported the observation that deletion of HNF4α results in an increase in hepatocyte proliferation due to an increase in promitogenic gene expression. The data obtained in this study further confirmed that HNF4α inhibits proliferation through the inhibition of genes involved in cell cycle control. Analysis within the Bonzo et al. study was performed 19 days following initial TAM exposure. Our study strengthens their findings by showing that hepatocyte proliferation and changes in promitogenic gene expression occur as early as 7 days after HNF4α deletion. This suggests that the increased promitogenic gene expression and hepatocyte proliferation

may be due directly to the loss of HNF4α as opposed to another factor that HNF4α may regulate. We have recently made similar observation using an adeno-associated PLX3397 chemical structure virus 8-mediated Cre system.19 Our analysis revealed that a large number of the genes up-regulated after

HNF4α deletion are regulated by c-Myc. The RNA-Seq data showed a 3.8-fold increase in c-Myc gene expression, corroborating these results. Previous studies have indicated that HNF4α competes with c-Myc for binding on the promoter of cell cycle inhibitor p21/WAF1.27 Further analysis revealed that several genes up-regulated in the c-Myc gene network are involved in stimulation of cell proliferation and cancer Abiraterone ic50 pathogenesis including the set oncoprotein, fus, ccnb1, and ccnb2. These data indicate that HNF4α may indirectly down-regulate these genes by way of suppressing c-Myc activation in normal adult hepatocytes. It has been speculated that deletion of HNF4α will result in rapid liver failure, making it difficult to directly study its role in the pathogenesis of HCC.17 Whether HNF4α deletion itself can result in hepatocarcinogenesis is not known and may be difficult to study due to limitations of the model system; therefore, we decided to investigate whether HNF4α deletion can promote existing tumors in the liver and can be tested using the two-stage DEN-induced chemical carcinogenesis model. Our studies indicate that HNF4α deletion during the late stage of HCC progression can substantially promote DEN-induced hepatic tumor formation.

Tumor histology was abstracted by cancer registrars.

The first preference was to obtain this information p38 MAPK cancer from pathology reports, followed by other sources. Stage, histological confirmation, and first-course primary-site surgery data were all available for 1998-2008. Incidence trends by stage and histological confirmation were examined for the years from 1992 through 2008. Linear regression models were used to fit trend data (Joinpoint software, version 3.3.1; IMS, Silver Spring, MD).13 Annual percent change (APC) in regression-line slopes were considered statistically significant when the trend differed from zero (P < 0.05). Incidence trends were examined by histological confirmation, stage, and reported first-course surgical and ablative therapy. Five-year cause-specific survival was estimated during the most recent decade of surveillance with follow-up of vital status (1998-2007). Cause-specific survival was selected because life tables were MLN8237 mw unavailable for most racial and ethnic groups included in this analysis, and because life tables may not reflect mortality differentials between HCC cases and the population related to screening, socioeconomic status, or health behavior.14 Cause of death was

defined as cancer, with other causes of death censored at time of death. Survival analyses were restricted to 16,020 of 18,894 reported HCC cases (85%) diagnosed in SEER-13 registries during the most recent decade of surveillance (1998-2007). Cases were excluded from survival analysis because HCC was a second or later primary cancer diagnosis (n = 2,409; 13%), case information was limited to death certificate or autopsy reports (n = 418; 2%), or because the case was alive without information on survival time (n = 47; <0.5%). For historical context, 5-year cause-specific survival of HCC cases diagnosed in SEER-9 registries was calculated for 1975-1977. Overall, race- and ethnicity-specific survival and

95% confidence intervals (CIs) were estimated by first-course therapies in descending order of survival: liver transplantation, NADPH-cytochrome-c2 reductase RFA of tumors less than 3 cm (potentially curative5), resection, local tumor destruction, all cases, and cases with no reported surgery. Stage distributions were presented by group, based on “reason no surgery performed,” “SEER historic stage A,” and “first-course primary-site surgery.” Among 1,249 cases with local tumor destruction, 75 (6%) underwent resection. Their 38% 5-year survival was similar to all cases with local tumor destruction (35%). Groups were combined for analysis. Of 21,390 HCCs diagnosed during 1998-2008, 4,727 (22%) reported liver surgery or local tumor destruction (Table 1). Interventions were reported more often among localized (39%) than regional (16%) or distant/unstaged cases (4%).

However, a large majority progress

to chronic active gastritis, where from thenceforth the fork in the road develops. A proportion of patients will develop antral predominant gastritis which may subsequently be complicated by duodenal ulcer(s) and/or rarely Acalabrutinib in vivo lymphoma, whilst another proportion will develop multifocal atrophic gastritis and subsequently become at risk for developing gastric ulcer(s), gastric cancer and rarely lymphoma. Why one individual during the course of their HP infection should clear the infection without the use of antibiotics is uncertain, and why individuals should arrest at any stage of this “pathway” without progressing to develop complications again is unresolved. The nature of acute infections with HP are understood due to a small number of cases where investigators and/or volunteers have been intentionally infected with the bacteria.29,30 Acute gastritis results histologically in a neutrophilic gastritis followed by a gradual infiltration by all classes

of inflammatory cells, including prominently lymphocytes and coupled with a transient hypochlorhydria. Post-acute gastritis, two patterns of chronic gastritis are observed and this difference in topography is associated with different diseases. Antral predominant gastritis is seen usually in conjunction with little or no gastric atrophy in duodenal selleck chemical ulcer disease, with normal or increased acid secretion.30–33 This is in comparison to the extensive pattern of gastritis with corpus (usually with antral) atrophy which tends to progress through intestinal metaplasia, to intestinal-type gastric cancer with hypochlorhydria, or achlorhydria. Carbohydrate The location of a peptic ulcer, when considered in association with HP infection gives the clinician the pattern and topography of HP-associated inflammation in the stomach. Duodenal ulcers are associated with antral predominant gastritis of the non-atrophic variety, hypergastrinaemia and hypersecretion of acid.30 Patients with duodenal ulcer virtually never develop body atrophic gastritis and consequently retain robust acid secretion.34,35

Conversely, gastric ulcers are thought to be associated with a chronic non-atrophic gastritis initially which progresses to chronic atrophic gastritis which involves both corpus and, invariably, the antrum and decreased acid output.36,37 Importantly, in patients with CAG, some studies have found that eradication of HP infection partially reverses the hypochlorhydria/achlorhydria seen resulting in an improvement in inflammation histologically.38–43 Annibale et al. report only 20% of their study patients reversed gastric body atrophy after HP eradication, whilst the remaining 80% retained gastric atrophic change or IM that was initially observed.44 Of note, patients with CAG may progress to intestinal metaplasia (IM).

Aim: To characterise the association between small intestinal mucosal permeability and hepatic fibrosis, using a plasma-based assay and transient elastography. Methods: A cohort of patients with chronic liver disease (CLD) of mixed aetiology (hepatitis B, C and non-alcoholic fatty liver) was compared to healthy volunteers (HV). Subjects were excluded if they drank alcohol within 24 hours, had gastro-intestinal

pathology or were taking potentially confounding medications within 4 weeks. Small intestinal permeability was assessed by an enteral lactulose:rhamnose probe. Subjects ingested 100 ml water containing 5 g lactulose and 1 g rhamnose and blood was collected 90 minutes later, for analysis of the lactulose:rhamnose (L:R) ratio by high performance liquid chromatography. All subjects underwent transient elastography to stratify them by fibrosis stage (no/mild BAY 80-6946 supplier <7.5 kPa, see more significant > 7.5 kPa). Increased permeability was defined as L:Rx100 > 8.86 (Tran, 2012). Statistical analysis was performed by GraphPad Prism v 5.0). Results: 32 subjects met inclusion criteria; 20 with CLD (9 with no/mild fibrosis, 11 with significant fibrosis) and 12 HV (all had no fibrosis). Small intestinal permeability (median L:R x 100, IQR) was elevated in CLD with significant fibrosis (20.9, 16.9–46.3), compared to HV (6.3, 5.3–15.7) p = 0.02,

but not in CLD with no/mild fibrosis (12.4, 6.7–36.7) p = 0.33. Median transient elastography values were 4.3 (3.4–4.7) for HV, 5.7(4.7–6.1) for no/mild fibrosis, and 12.5 (11.1–35.8) for advanced fibrosis. Median age, body mass index and HBA1c were similar. No patients had any adverse effects. Conclusion: Utilising non-invasive techniques, our results show that

significant hepatic fibrosis is associated with increased small intestinal permeability. AT ST JOHN,1,2 EH CHENG1 & M HAQUE1,2 Department of Gastroenterology, Mater Adult Hospital, Brisbane, Australia1, School of Medicine, University of Queensland, Brisbane, Australia2 Background and aims: The combination of a low hepatitis B surface antigen (HBsAg) titre and a low HBV DNA level appears to be associated with a reduced risk of hepatocellular carcinoma (HCC) development.1 We evaluated the cost effectiveness of a risk stratification system utilising HBsAg quantification and HBV DNA levels to Miconazole determine HCC surveillance intervals in HBsAg positive patients at a tertiary referral centre in Brisbane. Methods: We identified all patients who had at least one HBsAg quantification performed in the preceding two years at the Mater Adult Hospital in Brisbane. Treatment experienced and treatment naïve patients were included in the analysis. Demographic and clinical data were used to identify those patients who qualified for HCC surveillance. A modified version of the AASLD criteria for HCC surveillance was used. Patients with HBsAg titres <1000 IU/mL and HBV DNA <2000 IU/mL were identified and considered for a less intensive surveillance strategy.

Methods Liver biopsies were collected from 12 DNVH-B-OLT, 12 acute Hepatitis B Virus Infected patients (AVH-B) and 12 health controls (HC). Use Flow cytometry and ELISA kit to detect Tregs, IL-10, TGF-β and IFN-γ in peripheral blood. Immunohistochemistry was used to analyze intrahepatic T lymphocyte subsets. Results Compared to AVH-B patients, Tregs, TGF-β and selleck chemicals IL-10 clearly increased, IFN-γ decreased in peripheral blood, and intrahepatic CD3+, CD4+, CD8+T cells decreased and Tregs expression

enhanced in DNVH-B-OLT patients. The differences were statistically significant. Tregs were positively correlated with HBV DNA load, and negatively correlated with HAI scores and ALT. The Tregs level in HBV-clearance patients was obviously lower than that in non-HBV-clearance patients. Conclusion Galunisertib molecular weight In DNVH-B-OLT patients, the quantity of Tregs increased in liver tissues and peripheral blood, which suppressed immune inflammation reaction; the number of CD3+, CD4+, CD8+T cells decreased, which on the other hand inhibited

ability of specific HBV clearance and led to immune escape and chronicity. Disclosures: The following people have nothing to disclose: Yinjie Gao, Min Zhang, Jingmin Zhao, Hanwei Li Aim and Background: The aim of the present study was to determine the long-term efficacy of nucleos(t)ide analogue (NUC) treatment and low dose hepatitis B immunoglobulin (HBIG) combination therapy for preventing posttransplant hepatitis B virus (HBV) recurrence. Material and Methods: Between January 1, 1990 and December 31, 2012, a total of 296 HBV-infected patients (M/F: 246/50; median age: 52 years), who underwent liver transplantation (LT) in two different Transplantation Units, was included. Immunosuppressive protocol consisted of tacrolimus, mycophenolate mofetil and steroid. Steroids were gradually tapered for 24 weeks and discontinued for 48 weeks

after LT. HBV recurrence was defined as reappearance of HBsAg positivity and HBV DNA detectability during post-LT period. A combination find more of a daily single NUC treatment and intravenous (i.v.) hepatitis B immunoglobulin (HBIG) was used in an attempt to eliminate the HBV recurrence. HBIG was initiated at a dose of 4.000-10.000 IU i.v during anhepatic phase maintained at dose of 1.000-2.000 IU for 7 days, followed 2.000 IU weekly. After the patient discharged, HBIG was adjusted to maintain the hepatitis B surface antibody (antiHBs) titer at more than 100 IU/L (average doses of 2.000 IU monthly). Results: Median follow-up period after liver transplantation was 46 months. Causes of LT were HBV-induced cirrhosis in 191 patients (65%), HBV-induced acute liver failure in 10 patients (3%), and delta virus-induced cirrhosis in 95 patients (32%).

Eight-week-old male wildtype C57Bl/6 mice (Jackson Laboratory) were used for analysis of miRNA expression changes BMS-907351 chemical structure after 2/3 PH. Liver samples were obtained at 0, 1.5, 6, and 18 hours after surgery. Five mice were analyzed for each timepoint. Total RNA was isolated using Trizol and purified with the miRNeasy mini kit (Qiagen). miRNA expression profiling including labeling, hybridization, scanning, normalization, and data analysis was performed at Exiqon. Profiling was conducted with total RNA with RNA integrity number (RIN) values close to 8 measured with an Agilent

2100 Bioanalyzer. One μg total RNA of each sample and a common reference pool were labeled with Hy3 and Hy5 fluorescent label, respectively, using the miRCURY LNA Array power labeling kit (Exiqon). Hy3-labeled samples and Hy5-labeled common reference pool were mixed pairwise and hybridized to miRCURY LNA arrays v. 9.2 (Exiqon), which have a 61% coverage of the mouse miRNAs listed in miRBase v. 14.0. Hybridization was performed using a Tecan HS4800 hybridization

station. Slides were scanned using an Agilent G2565BA Microarray Scanner System and image analysis was carried out with ImaGene 7.0 software (BioDiscovery). Background correction was performed to remove nonbiological contributions to the measured signal.14 Quantified signals were normalized using the global Lowess (locally weighted scatterplot smoothing) regression algorithm.15 Log2 transformed median Hy3 (sample)/Hy5 (common reference pool) ratios were calculated for each capture probe (present Z-VAD-FMK datasheet in four replicates on the array). A two-tailed Student’s t test was performed between the samples obtained at 0 hours and the samples obtained at 1.5, 6, and 18 hours after 2/3 PH. Clustering was performed on miRNAs corresponding to capture probes with log2 Hy3/Hy5 ratios which passed filtering criteria of P < 0.001. The heatmap

was generated using the Euclidean metric. The log2 median ratio values were standardized Mannose-binding protein-associated serine protease by subtracting the mean followed by dividing by the standard deviation.16 miRIDIAN miRNA Mimics or Hairpin Inhibitors (Dharmacon) were introduced into Hepa1,6 mouse hepatoma cells (ATCC) at a final concentration of 20, 40, or 80 nM. Five × 104 cells were plated in 24-well plates (Corning) and transfected using Lipofectamine 2000 (Invitrogen) 24 hours later. Hepa1,6 cells transfected with chemically modified double-stranded or single-stranded oligonucleotides based on the sequence of miR-67 from C. elegans (both Dharmacon) were used as controls for miRNA mimics or inhibitors, respectively. For luciferase assays, cells were cotransfected with 30 ng of the pMIR-REPORT vector (Ambion) modified to contain the B-cell translocation gene 2 (Btg2) or ornithine decarboxylase 1 (Odc1) 3′ untranslated region (UTR) and 30 ng of the pSV-β-Galactosidase Control Vector (Promega) to monitor transfection efficiencies.

PUBMED, MEDLINE, EMBASE and the Cochrane Database were searched for articles published from 1990 to December 2012. Our results showed that the presence of high viral load significantly increased overall HCC recurrence risk after curative therapy. Pooled data from four studies on the recurrence rate among patients with genotype C infection compared with genotype B showed an increased risk of recurrence. Basal core promoter (BCP) mutation was associated with a significant risk in the recurrence of HCC. The pooled estimate of treatment effect was significantly

in favor of a preventive effectiveness of antiviral therapy. The present study suggested that HCC patients with high viral load, genotype C and BCP mutation had a significantly higher risk of recurrence. Antiviral therapy has potential beneficial effects

Palbociclib supplier after the curative treatment of HCC in terms of tumor recurrence. ”
“The etiology of KPT-330 manufacturer biliary atresia (BA) is unknown. Given that patterns of anomalies might provide etiopathogenetic clues, we used data from the North American Childhood Liver Disease Research and Education Network to analyze patterns of anomalies in infants with BA. In all, 289 infants who were enrolled in the prospective database prior to surgery at any of 15 participating centers were evaluated. Group 1 was nonsyndromic, isolated BA (without major malformations) (n = 242, 84%), Group 2 was BA and at least C59 cell line one malformation considered major as defined by the National Birth Defects Prevention Study but without laterality defects (n = 17, 6%). Group 3 was syndromic, with laterality defects (n = 30, 10%). In the population as a whole, anomalies (either major

or minor) were most prevalent in the cardiovascular (16%) and gastrointestinal (14%) systems. Group 3 patients accounted for the majority of subjects with cardiac, gastrointestinal, and splenic anomalies. Group 2 subjects also frequently displayed cardiovascular (71%) and gastrointestinal (24%) anomalies; interestingly, this group had genitourinary anomalies more frequently (47%) compared to Group 3 subjects (10%). Conclusion: This study identified a group of BA (Group 2) that differed from the classical syndromic and nonsyndromic groups and that was defined by multiple malformations without laterality defects. Careful phenotyping of the patterns of anomalies may be critical to the interpretation of both genetic and environmental risk factors associated with BA, allowing new insight into pathogenesis and/or outcome. (Hepatology 2013;58:1724–1731) The etiology of biliary atresia (BA) is unknown. In a large series of European infants reported by Davenport et al.,[1] infants with BA were catalogued by two different presentations: acquired/perinatal/nonsyndromic (∼90%) versus embryonal/syndromic (∼10%).

The majority of included sources employed convenience sampling, and so sampled detainees may not have been representative of the broader detainee population. Reinforcing this point, sources reporting data from random samples of general population detainees had significantly lower anti-HCV prevalence than sources with convenience samples. We used all identified data sources to estimate the summary prevalence of anti-HCV; however, older

studies this website reported higher anti-HCV prevalence than more recent studies. As a result, our summary prevalence estimates may overestimate the true anti-HCV burden. In evaluating our estimates, it is also important to note that very few data sources were located for some regions known to have high prevalence of anti-HCV among people who inject drugs, such as East

and Southeast Asia.[5] Despite a broad-based search strategy, no data were located for several countries with large incarcerated populations, including Russia, which has the world’s second largest prisoner population, and China, which, as noted above, operates a large network of extrajudicial detention centers for people who use drugs in addition to correctional facilities operating under the criminal GS-1101 in vivo justice system. No data could be located for countries of the Caribbean and the Pacific Islands. Even in well-represented regions, such as Western Europe and North America, Arachidonate 15-lipoxygenase data frequently related to single

institutions or institutions within a defined geographical area. Systematic data collection at the country or jurisdictional level is urgently required to allow for accurate appraisal of the scale of this issue, and to inform policy and clinical responses. The burden of HCV in detained populations, particularly in areas where IDU is highly prevalent among detainees, is a major public health concern. Despite this, epidemiologic data on the extent of HCV infection in detained populations is lacking in many countries. The global response to HCV in closed settings has been limited, with few countries implementing the necessary preventive interventions or providing treatment for HCV-infected detainees. Greater attention towards HCV prevention, diagnosis, and effective delivery of treatment to detained populations is urgently required. We thank the following individuals and organizations for assistance in completing this review: Mary Kumvaj, National Drug and Alcohol Research Centre, University of New South Wales, for assistance with developing search strings and locating literature; Paul Nelson, National Drug and Alcohol Research Centre, University of New South Wales, for methodological advice; Christine Reavis, student intern, for assisting with the literature search; and Annette Verster, HIV/AIDS Department, World Health Organization, for funding support and assisting with identification of gray literature.

58%) in only 1 case. Conclusions: The increased frequency of AA changes in S gene unrelated to LMV resistance suggests enhanced immune escape; further studies are needed to clarify whether this is related to Nuc pressure or natural history of the disease. In “a” determinant, immune escape variants other than the common sG1 45R were detected, suggesting a different pattern in our area. Study funded by Instituto de Salud Carlos III, grant PI 11/01973,

cofinanced by the European R428 price Regional Development Fund (ERDF). Disclosures: Rafael Esteban – Speaking and Teaching: MSD, BMS, Novartis, Gilead, Glaxo, MSD, BMS, Novartis, Gilead, Glaxo, Janssen Maria Buti – Advisory Committees or Review Panels: Boerhinger Inghelm, Boer-hinger Inghelm; Speaking and Teaching: MSD, Bristol-Myers Squibb, Novartis, Gilead, Janssen, MSD, Bristol-Myers Squibb, Novartis, Gilead, Janssen The following people have nothing to disclose: David Tabernero, Francisco Rodriguez-Frias, Rosario Casillas, Josep Gregori, Irene Belmonte Mula, Maria Homs, Maria Blasi, Josep Quer, Leonardo

Nieto, Silvia Camos, Andrea Caballero, Carolina Gonzalez Background: The role of quantitative hepatitis B surface antigen (HBsAg) after hepatitis B e-antigen (HBeAg) seroclearance is not well defined Aim: To determine the role of HBsAg levels in predicting significant viremia and hepatitis flares after HBeAg seroclearance, and to describe the trend of HBsAg levels and its correlation with HBV DNA in a longitudinal study. Methods: 228 chronic hepatitis B patients with spontaneous HBeAg seroclearance were Y 27632 included, with a minimum of 5 years follow-up after seroclearance. Patients were followed up regularly at 3-6 monthly intervals with routine liver biochemistry and hepatitis B serology. Levels of HBV DNA and HBsAg were measured at yearly intervals for up to 5 years after HBeAg seroclearance. Results: The median age at the time of seroclearance was 38 years (range, 14-77), with a similar male:female ratio (51%:49%). Of the 228 patients, 218 (95.6%) had evidence of seroconversion with detectable anti-HBe, with the remaining 1 0 (4.4%) patients remaining anti-HBe negative. The median log HBsAg and HBV DNA level

after HBeAg seroclearance was 3.52 IU/mL and 4.13 IU/mL Fenbendazole respectively, with no significant correlation (p=0.572). There was a gradual but significant decline in HBV DNA with increasing time from HBeAg seroclearance. The HBV DNA at HBeAg seroclearance was 4.13 log IU/mL, compared with 3.12 log IU/mL after 5 years (p<0.001). In contrast, the level of HBsAg remained consistent throughout each time-point after HBeAg seroclearance in non-treated patients. At the time of HBeAg seroconversion, the median HBsAg level was 3.52 log IU/mL, and this was comparable to the level of 3.50 log IU/mL (p=0.991) at 5 years. Hepatitis B flares occurred in 103 (45.2%) patients. Patients who developed hepatitic flares compared with those without hepatitic flares were older (39 vs 35 years, p=0.

7 Similarly, small amounts selleck products of albumin are synthesized and are not packaged as in later lineage stages, implicating lineage-dependent

distinctions in posttranscriptional and translational protein processing. The hHpSCs are isolated by dual immunoselection for EpCAM+/NCAM+ cells from livers of all donor ages. In adult livers, which have scarce hepatoblast populations, EpCAM+ selection alone results in isolation of predominantly hHpSCs.7, 16 In culture, the hHpSCs form colonies capable of self-replication17 and of differentiation to mature cells in culture and in vivo.7, 18 Cells expand ex vivo if cultured in Kubota’s medium, a serum-free medium containing only insulin, transferrin/fe,

lipids, no copper, and low calcium19, 20 and if cocultured with angioblasts. These feeders are replaceable with purified type III collagen substrates, embedding into weakly crosslinked hyaluronan hydrogels, or a mixture of both.13, 21 If transplanted in vivo, they yield mature liver tissue. If cultured under distinct conditions (see below) they lineage-restrict into hepatoblasts.13 Hepatoblasts (hHBs) are diploid bipotent cells giving rise to hepatocytic and cholangiocytic lineages, associated with precursors of both endothelia and hepatic stellate cells, and the liver’s probable transit amplifying cells.13 They reside throughout parenchyma of fetal and neonatal FK228 livers or as single cells and small cell aggregates tethered to the ends of canals of Hering in adult livers.8 With donor age, hHBs decline to <0.01% of the parenchymal cells in postnatal livers.7, 8 They expand during regenerative processes associated with certain diseases such as cirrhosis. Previously, hHBs were referred to as “intermediate hepatobiliary cells of the ductular reactions”22; extensive characterization enabled us to refer to them, as hepatoblasts.8

They can be isolated by dual immunoselection for EpCAM+/ICAM-1+. They have enormous expansion potential cultured in Kubota’s medium, especially if supplemented with epidermal growth factor (EGF) and hepatocyte growth factor (HGF), or on feeders of stellate cell precursors Acyl CoA dehydrogenase replaceable by substrata of type IV collagen, laminin, hyaluronans, or mixtures of these expansion is without proven self-replication.13, 23, 24 The hHBs, larger (10-12 μm) and with higher amounts of cytoplasm than hHpSCs, have an antigenic profile that overlaps with hHpSCs.6, 7, 15 Shared phenotypic traits include CXCR4, CD133, SOX17, MDR1, cytokeratins (CK) 8/18 and 19, Hedgehog proteins (Sonic and Indian), and null expression of late P450s (e.g., P450-3A) or markers for hemopoietic, endothelia, or mesenchymal cells (as for hHpSCs).