By this method we identified 1536 patients. Only patients with available clinical and biochemical components of the new simplified criteria at baseline were included.17 Thus, information on the presence of autoantibodies, immunoglobulin G (IgG) or gammaglobulins, viral serologies, and a liver biopsy were obtained before initiation of immunosuppressive therapy. Patients seen at the Mayo Clinic only for a second opinion, but who were diagnosed earlier and who had already started treatment, were excluded. Also, patients undergoing transplants for AIH and patients with decompensated liver disease at presentation Cabozantinib price were excluded as well

as pediatric cases (younger than 16 years of age). The reason for excluding patients with liver failure or those who required transplantation was because the diagnosis of AIH is more uncertain

in these conditions. Some features of AIH such as autoantibodies can be present in patients with liver failure and decompensated liver disease, probably secondary to the chronic liver injury. Furthermore, most patients with decompensated liver disease had been started on treatment for AIH elsewhere, and therefore AZD6738 there was often a lack of important biochemical parameters such as gammaglobulins or IgG and autoantibodies, making a diagnostic score almost impossible. Furthermore, patients with a diagnosis of primary biliary cirrhosis and primary sclerosing cholangitis were excluded, as were patients with clinical suspicion of overlap syndromes (AIH/primary biliary cirrhosis and AIH/primary sclerosing cholangitis). A retrospective review was performed on patients fulfilling the inclusion criteria. The following variables

were obtained by the chart review: age, sex, date of liver biopsy, titers of antinuclear antibodies, smooth muscle antibodies, liver kidney microsomal, antimitochondrial antibodies, antinuclear cytoplasmic antibodies, IgG, gammaglobulins, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, total bilirubin, albumin, and international normalized ratio at baseline. Furthermore, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, ifoxetine total bilirubin, albumin, international normalized ratio, IgG, gamma globulins at 1 to 2 weeks, 2 months, 6 months, 1 year, and at last follow-up after start of immunosuppressive treatment were recorded. The presence of a suspicion of drug etiology in triggering the AIH was recorded. The liver biopsy results were analyzed, and histology compared between the DIAH patients and age (±5 years of age at the diagnosis of AIH) and sex-matched patients (n = 24) randomly chosen from the rest of the AIH patients. Sex was balanced, and no significant age difference was found at diagnosis. Furthermore, patients with nitrofurantoin-induced and minocycline-induced AIH were compared. All biopsy materials were reviewed by a single liver pathologist (S.O.S.), blinded to the clinical context of the biopsy as well as the patient’s outcomes.

No stent migration was occurred in inoperable patients. Stent obstruction in inoperable patients was developed in 15.9% (7/44) during follow up period. Conclusion: The modified fully covered SEMS may be useful to prevent stent migration in patients with distal malignant biliary obstruction. Long-term learn more follow up and prospective comparative studies were demanded. Key Word(s): 1. distal malignant biliary obstruction; 2. covered self-expandable metallic stent Presenting Author: SOO KYUNG PARK Additional Authors: JONG HO MOON, HYUN JONG CHOI, YUN NAH

LEE, TAE HOON LEE, SANG WOO CHA, YOUNG DEOK CHO, SANG HEUM PARK, SUN JOO KIM Corresponding Author: SOO-KYUNG PARK Affiliations: Soonchunhyang University School of Medicine, Soonchunhyang University School of Medicine, Soonchunhyang University School of Medicine, Soonchunhyang University School of Medicine, Soonchunhyang University

School of Medicine, Soonchunhyang University School of Medicine, SoonChunHyang University School of Medicine, Soonchunhyang University School of Medicine Objective: Endoscopic bilateral metallic stenting has been introduced as feasible and effective palliative modality in patients with inoperable hilar malignant biliary strictures (MBS). However, repetitive endoscopic revision of occluded bilateral metallic stents may be challenging. The aim of this study was to selleck evaluate the feasibility and efficacy of repetitive endoscopic revision after first endoscopic revision for hilar MBS previously managed by bilateral stent-in-stent placement with cross-wired metallic stents. Methods: Total 6 patients (5 cholangiocarcinoma and one gallbladder cancer) who had previously managed by bilateral stent-in-stent placement with cross-wired metallic

stents (BONASTENT-M Hilar, Standard Sci Tech., Seoul, Korea) were required repetitive biliary reintervention because of stent occlusion after first endoscopic revision during follow up. Results: Total 19 repetitive endoscopic revision were performed. The mean number of repetitive endoscopic revision for each patient was 3.2 (range 1–8). Technical and clinical success rate of repetitive endoscopic revision after first endoscopic revision was 100.0% (19/19) and 78.9% (15/19), respectively. Bilateral revision was performed in 8 (42.1%) Interleukin-2 receptor endoscopic sessions. Early and late complication rate was 15.8% (3/19, cholangitis; 1, pancreatits; 2) and 21.1% (4/19, liver abscess; 4), respectively. And, stent occlusion rate was 68.4% (13/19). Mean stent patency period was 75 days (20–265), and became shorter than when first stenting (216 days, 43–481) and first revision (126 days, 34–316) (p = 0.006). Conclusion: Repetitive endoscopic revision for hilar MBS previously managed by bilateral metallic stenting was feasible. Cross-wired metallic stents for hilar MBS may facilitate repetitive endoscopic revision after stent occlusion. Key Word(s): 1. Hilar malignant biliary stricture; 2.

1C,D). Alcohol feeding to WT mice triggered expression of Type I IFN stimulated gene (ISG) 56, suggesting activation of Type I IFN signaling in alcohol-induced liver injury. In contrast, alcohol feeding of IRF3KO mice failed to up-regulate ISG56 (Fig. 1E). These data suggested a role of IRF3 and/or Type I IFNs in alcohol-induced liver injury. The liver functions

with a complex coexistence of parenchymal and nonparenchymal cells. To explore whether the protective effect of IRF3 in alcoholic liver injury is mediated by parenchymal cells or BM-derived immune cells, we generated IRF3-chimeric mice by transplanting WT BM into irradiated, IRF3-deficient mice (IRF3-KO/WT-BM mice), or by transplanting IRF3-deficient BM into irradiated WT mice (WT/IRF3KO-BM). WT mice with WT BM transplant served as controls (WT/WT-BM). As PD98059 purchase expected, WT/WT-BM mice developed ALD after 4 weeks of a Lieber-DiCarli diet, as indicated by liver steatosis, inflammatory infiltrate, and liver injury compared to pair-fed controls (Fig. 2A-C). In

sharp contrast to WT/WT-BM mice, IRF3-KO/WT-BM mice showed increased alcohol-induced liver injury, Gefitinib cell line as indicated by exaggerated steatosis and inflammatory infiltrate on histology (Fig. 2A). This finding was accompanied by a significant elevation in serum ALT and in liver triglycerides compared to WT/WT-BM ethanol-fed mice (Fig. 2B,C). Further, IRF3-KO/WT-BM mice showed significantly increased expression of inflammatory cytokines TNF-α and IL-1β compared to WT/WT-BM ethanol-fed mice (Fig. 2D-G). These Protein tyrosine phosphatase data suggested a protective role of IRF3 in parenchymal cells in ALD by limiting liver inflammation and injury. Furthermore, WT/IRF3KO-BM mice showed no protection against alcohol-induced liver damage and steatosis (Fig. 2A-C) compared to WT/WT-BM mice, in spite of deficient induction of proinflammatory cytokine TNF-α (Fig. 2D,E) and IL-1β

(Fig. 2G,F). These findings contrasted with the complete protection against alcohol-induced liver injury in global IRF3-KO mice (Fig. 1), and suggested that both parenchymal cell-specific and myeloid-specific IRF3 is required for the pathogenesis of alcohol-induced liver damage. More important, they indicated a protective role of parenchymal cell-specific IRF3 in alcohol-induced liver damage. Activation of IRF-3 leads to preferential induction of IFN-β.17 We identified that, in contrast to WT and to WT/IRF3KO-BM mice, IRF3-KO/WT-BM mice showed a significantly decreased expression of IFN-β (Fig. 3A) and of interferon-inducible gene ISG-56 (Fig. 3B). This finding indicated that aggravated liver injury in IRF3-KO/WT-BM mice is associated with deficiency in IRF3-dependent type I IFNs induction and signaling and suggested possible involvement of IRF3- and Type I IFN-dependent antiinflammatory factors in alcohol-induced liver injury.

Results: In contrast to ALT, plasma CatD was significantly increased in NASH patients compared to subjects with either steatosis or a normal liver. Whereas ALT demonstrated to be a late marker for NASH grade (grade 2 and 3), CatD was elevated at early inflammation (grade 1). The sensitivity and specificity of ALT for detecting hepatic inflammation improved markedly through addition of CatD. Conclusions: The combination of CatD and ALT in plasma is a potential, specific

non-invasive marker to assess Saracatinib NASH and to monitor disease progression. Disclosures: Jan-Willem Greve – Consulting: GI Dynamics; Grant/Research Support: GI Dynamics The following people have nothing to disclose: Sofie Walenbergh, Sander Rensen, Veerle Bieghs, Tim Hendrikx, Patrick van Gorp, Mike Jeurissen, Wim Buurman, Anita Vreugdenhil, Jogchum Plat, Marten H. Hofker, Patrick Lindsey, Ger H. Koek, Ronit Shiri-Sverdlov BACKGROUND AND AIMS: The

aim of this study was to compare the results of Fibroscan® and CAP™ versus liver biopsy in patients with Non Alcoholic Fatty Liver Disease (NAFLD). METHODS: We enrolled patients LBH589 manufacturer with NAFLD diagnosed by liver biopsy between May of 2011 and January of 2013 at Sao Paulo University Hospital. They underwent liver stiffness measurements to assess fibrosis by Fibroscan® using median and extra large probes according to their skin-liver distance. CAP™ was also used to assess steatosis when Fibroscan® measures were made with the median probe. The Fibroscan® was operated by 2 experts in the procedure. The time frame between liver

biopsy and Fibroscan® plus CAP™ was of sixty days at most. We considered failure fantofarone of Fibroscan® and CAP™ when: we couldn’t have ten valid measures; the total success rate was below 60% and/or the interquartile range (IQR) was above 30%. The results of these noninvasive methods were compared with liver histology (BRUNT criteria), used as the reference standard. The corresponding values of Fibroscan®(kPa) to fibrosis stages and of CAP™ (dBm-1) to steatosis grades considered were based in previous studies of these methods in NAFLD patients. The gamma distribution function was used to compare the results of Fibroscan® and CAP™ versus liver biopsy. RESULTS: A total of 65 patients were enrolled, 71 % female and 29% male with mean age of 56 years old (1 3-71 years). Mean body mass index (BMI) and abdominal circumference were 31.29Kg/m2 (19.6-47.7Kg/m2) and 102.3cm (77-135cm), respectively. Mean distance between skin surface and liver was 2.06cm (0.98-4.26cm). Patient’s comorbidities were: 46% diabetes; 73% dyslipidemia; 60% systemic arterial hypertension. The Fibroscan® was feasible in 83 %(95%CI: 0.7193 -0.9039) of a total of 65 patients and CAP™ was feasible in 74% (95%CI: 0.603 – 0.848) of a total of 47 patients, respectively. The results of comparison between Fibroscan®, CAP™ and liver biopsy (noninvasive methods evaluated separately) using gamma distribution function were: Fibroscan® gamma= 0.38(95%CI 0.09-0.

“
“p38α mitogen-activated protein kinases (MAPK) may be essential in the up-regulation of proinflammatory cytokines and can be activated by transforming growth factor β, tumor necrosis factor-α, interleukin-1β, and oxidative stress. p38 MAPK activation results in hepatocyte growth arrest, whereas increased proliferation has been considered a hallmark of p38α-deficient cells. Our aim was to assess the role of p38α in the progression of biliary cirrhosis induced by chronic cholestasis as an experimental model of chronic inflammation associated with hepatocyte proliferation, apoptosis, oxidative stress, and fibrogenesis. Cholestasis was induced

in wildtype and liver-specific p38α knockout Midostaurin order mice by bile duct ligation and animals were sacrificed at 12 and 28 days. p38α knockout mice exhibited a 50% decrease in mean life-span after cholestasis induction. Tamoxifen research buy MK2 phosphorylation was markedly reduced in liver of p38α-deficient mice upon chronic cholestasis. Hepatocyte

growth was reduced and hepatomegaly was absent in p38α-deficient mice during chronic cholestasis through down-regulation of both AKT and mammalian target of rapamycin. Cyclin D1 and cyclin B1 were up-regulated in liver of p38α-deficient mice upon chronic cholestasis, but unexpectedly proliferating cell nuclear antigen was down-regulated at 12 days after cholestasis induction and the mitotic index was very high upon cholestasis in p38α-deficient mice. p38α-knockout hepatocytes exhibited cytokinesis failure evidenced by an enhanced binucleation rate. As chronic cholestasis evolved the binucleation rate decreased in wildtype animals, whereas it remained high in p38α-deficient mice. Conclusion: Our results highlight a key role of p38α in hepatocyte proliferation, in the development of hepatomegaly, and in survival during chronic inflammation such as biliary cirrhosis. (HEPATOLOGY 2013) Mitogen-activated protein kinases (MAPKs) are essential for the cellular response against injury and for regulation of cell death and tissue homeostasis. p38 MAPKs are a family of serine/threonine

protein kinases activated by environmental and genotoxic stress that have key roles in the Oxymatrine control of cell proliferation, differentiation, and survival, as well as in the regulation of the inflammatory response.1 p38α is the most abundant kinase within the p38 MAPK family and displays relevant biological roles in pathophysiology. Increased proliferation and impaired differentiation have been considered hallmarks of p38α-deficient cells.2 Mice with liver-specific deletion of p38α exhibited enhanced hepatocyte proliferation after partial hepatectomy2 and developed more liver tumors with increased numbers of proliferative tumor cells.3 p38α may repress cell proliferation by antagonizing the c-Jun N-terminal kinase (JNK)/c-Jun pathway.

The total time per home per day spent giving medicines varied from 2.5 to 5.8 hours. A summary of medication activities at Table 1: Summary of medication-related activities and interruptions aggregated from four care homes Med. Round Residents (n) Time (mins) Interruptions (n) Doses administered (n) Mean no. doses per resident Mean no. interruptions per 100 doses Mean

no. interruptions per hour of med. round P *Mean was calculated only for 3 homes because consent from residents in one home was restricted to observing medicine rounds only – i.e. not for reviewing individual medication administration records. An average rate of http://www.selleckchem.com/products/PLX-4032.html one interruption every 12 minutes during medicine rounds seems alarmingly high considering the potential for making a mistake is greater when being distracted. However, carers may consider personal care and social interaction to be equally important to residents and therefore accept interruptions during medicine rounds as being a normal part of their caring role. In stark contrast with evidence cited in the CHUMS report, care staff subjectively believed that the risk of making an error was low

which may result in errors remaining undetected. However, some staff in our study experienced considerable anxiety over the possibility of making a mistake with medication. A worthy subject for future research would therefore be to appraise what is considered to be an appropriate balance between avoiding medication Birinapant supplier errors whilst taking into account the competing social care priorities that are important in care Grape seed extract homes. 1. Alldred DP et al (2009). Care Home Use of Medicines Study (CHUMS)). Medication errors in nursing and residential care homes – prevalence, consequences, causes and solutions. Universities of London, Leeds

and Surrey. Pamela Mills1,2, Anita Weidmann2, Derek Stewart2 1NHS Ayrshire and Arran, Ayrshire, UK, 2Robert Gordon University, Aberdeen, UK Semi-structured interviews were conducted with key hospital staff regarding their experiences of paper based prescribing systems and future expectations of electronic prescribing Multiple concerns and bad experiences were reported at every stage of the patient journey by all professional staff groups. The implementation of hospital electronic prescribing and medicine administration (HEPMA) was eagerly anticipated as a patient safety solution although many were cautious about impending changes to familiar practices. Hospital electronic prescribing and medicine administration (HEPMA) has been implemented into several UK hospitals with a lack of published formal evaluation. A recent systematic review advocates further research of information technology (IT) communication systems versus traditional, paper based systems, advising that organisations implementing such systems undertake formal research evaluation1.

7 and 27.1 find protocol for rs12980275 and rs8099917 with astronomical P values of 2.84 × 10−27 and 2.68 × 10−32, respectively. Ge et al.3 determined a combined OR of 3.1 for rs12979860, and Suppiah et al.2 found a combined OR of 1.98 for rs809917. It is challenging to ascertain the predictive value of a particular IL-28B allele in the first two studies cited; however, Suppiah et al. were careful to note that “according to a model of dominant inheritance, the rs8099917 G allele predicts non-response with 57% sensitivity and 63% specificity.” They also reported a negative predictive

value (NPV; i.e., a value indicating the correct prediction of treatment failure) Selleck PLX4720 of 64%. We recently reported data from a prospective cohort collected for plasma biomarker discovery.8 Although our cohort was considerably smaller than the populations used for genome-wide association studies, we found that the rs12979860 C/C genotype increased the odds of early virological response (EVR; OR = 2.53) with a positive predictive value (PPV) of 75% (Fig. 1A). Notably, biomarkers are used in the management of chronic patients with the intention of identifying those individuals who will fail to respond to therapy and thus can be directed to alternative treatment options (e.g., the failure to achieve EVR is used in the clinic

Carnitine palmitoyltransferase II as a negative predictor of sustained virological response). As such, the important index is the NPV, which was found to be 42% for the patients in our study (Fig. 1A). We thus argue the need for phenotypic markers to complement markers of genetic susceptibility. One plasma biomarker that has received attention is interferon induced protein 10 (IP-10 and also referred to as CXCL10), with higher concentrations

predicting treatment failure.9 We confirmed these data and found an NPV of 86% (Fig. 1B). One exciting possibility is the combination of assays; if they are taken together, predictions based on the C/C genotype or a low plasma concentration of CXCL10 yield an NPV of 100% (Fig. 1C). Our growing knowledge of epigenetics and the impact of environmental factors makes clear that phenotypic markers and/or functional assays (measured with validated assays) will be required to fully exploit the knowledge gained by genetic studies. We conclude that there is a real need to continue the effort to identify predictive biomarkers that will be clinically useful for managing patients with HCV disease. Matthew L. Albert M.D., Ph.D.* ‡, Armanda Casrouge* ‡, Stéphane Chevaliez Ph.D.§ ** ††, Christophe Hézode M.D., Ph.D.§ ** ††, Isabelle Rosa M.D§ ** ††, Philippe Renard M.D‡‡, Vincent Mallet M.D., Ph.D.¶ §§ ¶¶, Arnaud Fontanet M.D., Ph.D.†, Jean-Michel Pawlotsky M.D., Ph.D.§ ** ††, Stanislas Pol M.D., Ph.D.

[24] In the present study, we show the innervation pattern of these extracranially projecting afferents in more detail. We found labeled nerve fibers not only within the deep structures of the masticatory muscles and upper neck muscles but also within the connective tissue of the temporomandibular joint. Since we have never seen stained structures other than nerves in the dura

mater, as well as in sutures and emissary canals, we are Dasatinib cost sure that the tracer did not freely diffuse to these extracranial tissues. In the nuchal region, the trigeminal innervation territory seems to overlap with the territory of the occipital nerves. The innervation of pericranial muscles by collaterals of meningeal afferent fibers seems to be fairly substantial. The labeled extracranial nerve fibers in this region are certainly not of spinal origin because staining was completely lacking in the occipital nerves. Although we observed, both in humans and rats, nerves fibers in the posterior selleck kinase inhibitor part of the cranial cavity that penetrate the petrosquamous fissure, we could confirm labeled

nerve fibers in the upper neck muscles only in rats, due to the limited diffusion distance of the postmortem tracing technique. The electron microscopic sections of the spinosus nerve both in rat and human specimens showed numerous myelinated nerve fibers, which according to their diameter must partly be classified as Aβ-fibers, confirming previous observations.[9, 12, 20] Aβ-fibers subserve normally mechanoreceptive functions, but it seems difficult to attribute meningeal afferents a non-nociceptive function since there is no sensation but pain Carbohydrate that could be evoked by stimulation of the dura

mater during head surgeries.[5, 6] It has been speculated that these nerve fibers could be activated by mechanical stimuli, such as sudden head movements.[12, 36] This idea is particularly interesting in respect of their possible contribution to migraine and chronic tension-type headaches, if these nerve fibers belong to those that innervate pericranial muscles. To clarify the nociceptive nature of these afferents, combined labeling with nociceptive markers like neuropeptides may be useful, but first trials using antibodies against calcitonin gene-related peptide to label retrogradely traced nerve fibers have failed, probably due to the long duration of tissue fixation. Apart from the above hypothesis, there is an additional functional explanation for the extracranial innervation: Possibly part of the myelinated nerve fibers innervating pericranial muscles are not collaterals of meningeal afferents but proprioceptive fibers that travel through the trigeminal ganglion toward their somata located in the mesencephalic nucleus of the trigeminal nerve.

Hyperactivation of Akt but not Notch, signal transducer and activator of transcription 3 (STAT3), or mammalian target of rapamycin (mTOR) was detected in TGF-β-treated WB-F344 cells. Introduction of the dominant-negative mutant of Akt significantly attenuated T-IC properties of those transformed WB-F344 cells, indicating Akt was required in TGF-β-mediated-generation of hepatic T-ICs. We further demonstrate that TGF-β-induced Akt activation and LPC transformation was mediated by microRNA-216a-modulated phosphatase and tensin homolog deleted on chromosome 10 (PTEN) suppression. Conclusion: Hepatoma-initiating cells may derive from hepatic progenitor cells exposed to chronic and constant TGF-β stimulation

in cirrhotic liver, and pharmaceutical inhibition of microRNA-216a/PTEN/Akt signaling could be a novel

strategy for HCC prevention and therapy targeting hepatic T-ICs. (HEPATOLOGY 2012;56:2255–2267) Metformin cell line Liver cancer is the fifth most common cancer globally and the second leading cause of cancer death in men, among which hepatocellular find more carcinoma (HCC) accounts for 70% to 85% of total cancer burden.1 Despite the current advance in the diagnosis of HCC, the majority of patients are not eligible for surgical treatment due to late diagnosis.2 The high heterogeneity of HCC makes it difficult to eliminate the cancer cells with chemotherapy alone. Recurrence and metastasis result in a poor prognosis of HCC and the 5-year survival rate of patients undergoing surgical resection is disappointingly low.3 It is thereby urgent to elucidate the molecular pathogenesis of HCC so that a novel strategy for HCC prevention and treatment can be developed. Chronic infection of hepatitis B virus (HBV) or hepatitis C virus (HCV) is considered the major cause of cirrhosis and liver cancer.4 Epidemiological studies have revealed that cirrhosis with hepatitis

virus infection is the most predominant risk factor for HCC development, and only 10% to 20% of HCCs occur in patients without cirrhosis.5 Therefore, prevention of HCC in the high-risk population, particularly in those with established Ergoloid cirrhosis, would be highly desirable. Unfortunately, the molecular mechanism of hepatocarcinogenesis in those patients with cirrhosis remains elusive and effective approaches for HCC prevention and therapy are scarce to date. Liver regeneration normally counts on the proliferation of hepatocytes and cholangiocytes. In cirrhotic liver, however, the ability of those parenchymal cells to divide and repopulate damaged tissue is apparently compromised. Therefore, bipotential liver progenitor cells (LPCs), which reside quiescently within the canals of Hering in adults, are activated for compensative proliferation and differentiation into both hepatic and biliary lineages.6, 7 Recently, the concept that HCC originates from liver cancer stem cells (tumor-initiating cells) has captured much attention.

Hyperactivation of Akt but not Notch, signal transducer and activator of transcription 3 (STAT3), or mammalian target of rapamycin (mTOR) was detected in TGF-β-treated WB-F344 cells. Introduction of the dominant-negative mutant of Akt significantly attenuated T-IC properties of those transformed WB-F344 cells, indicating Akt was required in TGF-β-mediated-generation of hepatic T-ICs. We further demonstrate that TGF-β-induced Akt activation and LPC transformation was mediated by microRNA-216a-modulated phosphatase and tensin homolog deleted on chromosome 10 (PTEN) suppression. Conclusion: Hepatoma-initiating cells may derive from hepatic progenitor cells exposed to chronic and constant TGF-β stimulation

in cirrhotic liver, and pharmaceutical inhibition of microRNA-216a/PTEN/Akt signaling could be a novel

strategy for HCC prevention and therapy targeting hepatic T-ICs. (HEPATOLOGY 2012;56:2255–2267) selleck compound Liver cancer is the fifth most common cancer globally and the second leading cause of cancer death in men, among which hepatocellular CX-5461 manufacturer carcinoma (HCC) accounts for 70% to 85% of total cancer burden.1 Despite the current advance in the diagnosis of HCC, the majority of patients are not eligible for surgical treatment due to late diagnosis.2 The high heterogeneity of HCC makes it difficult to eliminate the cancer cells with chemotherapy alone. Recurrence and metastasis result in a poor prognosis of HCC and the 5-year survival rate of patients undergoing surgical resection is disappointingly low.3 It is thereby urgent to elucidate the molecular pathogenesis of HCC so that a novel strategy for HCC prevention and treatment can be developed. Chronic infection of hepatitis B virus (HBV) or hepatitis C virus (HCV) is considered the major cause of cirrhosis and liver cancer.4 Epidemiological studies have revealed that cirrhosis with hepatitis

virus infection is the most predominant risk factor for HCC development, and only 10% to 20% of HCCs occur in patients without cirrhosis.5 Therefore, prevention of HCC in the high-risk population, particularly in those with established Linifanib (ABT-869) cirrhosis, would be highly desirable. Unfortunately, the molecular mechanism of hepatocarcinogenesis in those patients with cirrhosis remains elusive and effective approaches for HCC prevention and therapy are scarce to date. Liver regeneration normally counts on the proliferation of hepatocytes and cholangiocytes. In cirrhotic liver, however, the ability of those parenchymal cells to divide and repopulate damaged tissue is apparently compromised. Therefore, bipotential liver progenitor cells (LPCs), which reside quiescently within the canals of Hering in adults, are activated for compensative proliferation and differentiation into both hepatic and biliary lineages.6, 7 Recently, the concept that HCC originates from liver cancer stem cells (tumor-initiating cells) has captured much attention.