Shimizu et al. showed that intrasplenically injected tumor cells migrated into the space of Disse at 2 days after injection, where they proliferated in close association with HSCs, suggesting that tumor cells may interact with and activate HSCs directly in vivo.17 Their hypothesis was later supported by data showing that conditioned medium of tumor cells was able to induce HSC activation in vitro.14 Conditioned medium of tumor cells promoted HSC proliferation in a dose-dependent manner and induced the expression of α-SMA and formation of α-SMA–positive stress find more fibers in HSCs, which are characteristic of transdifferentiated myofibroblasts.14 In our laboratory,

we found that treatment of quiescent HSCs with TGF-β1, a cytokine released by cancer cells that is abundant in the hepatic tumor microenvironment, induced myofibroblast transdifferentiation of HSCs in vitro.20 Taken together, these data suggest bidirectional interactions between tumor cells and HSCs in vivo. The activation of HSCs in the tumor microenvironment is a complex process that requires participation of paracrine stimuli of tumor cells and intracellular factors within HSCs. TGF-β and PDGF are the two most potent factors regulating HSC activation in vivo. The action of TGF-β on HSC activation is mediated by the canonical TGF-β/Smad-dependent signaling pathway.20 PDGF is one of most powerful mitogens and survival factors for

HSCs, which acts by MK-8669 cost activating key signaling pathways such as Ras/Erk (extracellular signal-regulated kinase) and phosphoinositide 3-kinase in HSCs.40, 41 In addition to TGF-β and PDGF, intracellular factors

promoting HSC responsiveness to external stimuli include receptor-mediated signaling cascades, ECM-mediated integrin activation signaling, the Rho family of small guanosine triphosphatases, and transcription factors. Their roles in HSC activation remain active research topics and are reviewed in detail medchemexpress elsewhere.40, 42, 43 Given the complex nature of the hepatic microenvironment, it is likely that other components of liver may interact with HSCs and tumor cells, thus contributing to HSC activation and metastatic growth. For example, Kupffer cells may regulate HSC activation and tumor growth by releasing TGF-β1,44 and endothelial cells may suppress HSC activation by producing nitric oxide,45, 46 a multifunctional signaling molecule that possesses antifibrotic activity. Current in vivo models that are employed to study the role of HSCs in liver metastases include subcutaneous coimplantation of tumor cells and HSCs/myofibroblasts in mice, portal vein implantation of tumor cells into the liver of mice, and portal vein coimplantation of tumor cells and HSCs/myofibroblasts into the liver of mice. Subcutaneous or portal vein coimplantation of HSCs/myofibroblasts and tumor cells in mice often resulted in larger tumors.

Less conclusive evidence of the importance of ER stress exists in viral and drug hepatitis, although it is likely to be so. It is important to recognize that the ER is in a pivotal position to both respond to and cause dysfunction in other cellular loci such as mitochondria,

cytoplasm, and nucleus. Thus, it is common to see ER stress response accompanied by ATP depletion, oxidative stress, mitochondrial dysfunction and lipid accumulation (Fig. 4). It is important to appreciate that cells such as hepatocytes exhibit the simultaneous appearance of numerous different stress responses—such as ER stress, mitochondrial KU-60019 in vivo dysfunction, mitogen-activated protein kinases, and so forth—in disease and there is a complex interplay among them in disease pathogenesis. The UPR/ER stress response is certainly a contributor to both dampening and worsening the outcome depending the ability of the ER to deal with disease promoting factors such as ROS, redox perturbations, client proteins( and their modifications), toxic chemicals/drugs, viruses and lipids. There is a complex cause-versus-effect interplay between all these pathophysiologic responses and ER stress response. Idelalisib We believe a key to interpreting the commonly observed association of liver diseases and ER stress response is the recognition that there is a vicious cycle between ER stress

and other adverse phenomena which are caused by ER stress response. Thus, it is the nature of such a vicious cycle that is the key pathophysiologic concept, and perhaps it is less important to resolve the difficult question as to whether ER stress is, so to speak, “the chicken or the egg.” From this standpoint, it is hoped that therapeutics aimed at blunting ER stress will interrupt the cycle. “
“Hepatocyte cell death via apoptosis and necrosis

are major hallmarks of ethanol-induced liver injury. However, inhibition MCE公司 of apoptosis is not sufficient to prevent ethanol-induced hepatocyte injury or inflammation. Because receptor-interacting protein kinase (RIP) 3–mediated necroptosis, a nonapoptotic cell death pathway, is implicated in a variety of pathological conditions, we tested the hypothesis that ethanol-induced liver injury is RIP3-dependent and RIP1-independent. Increased expression of RIP3 was detected in livers of mice after chronic ethanol feeding, as well as in liver biopsies from patients with alcoholic liver disease. Chronic ethanol feeding failed to induce RIP3 in the livers of cytochrome P450 2E1 (CYP2E1)-deficient mice, indicating CYP2E1-mediated ethanol metabolism is critical for RIP3 expression in response to ethanol feeding. Mice lacking RIP3 were protected from ethanol-induced steatosis, hepatocyte injury, and expression of proinflammatory cytokines. In contrast, RIP1 expression in mouse liver remained unchanged following ethanol feeding, and inhibition of RIP1 kinase by necrostatin-1 did not attenuate ethanol-induced hepatocyte injury.

Key Word(s): 1. Livin; 2. Caspase-3; 3. Caspase-3; 4. norcantharidin; Presenting Author: YU-HONG WANG Additional Authors: QIU-CHEN YANG, YUAN LIN, LING XUE, MIN-HU CHEN, JIE CHEN Corresponding Author: JIE CHEN Affiliations: Department of Gastroenterology, The First Affiliated Hospital of Sun Yat-Sen University; Department of Pathology, The First Affiliated Hospital of Sun Yat-Sen University Objective: To evaluate the significance of

serum chromogranin A (CgA) levels in patients with gastroenteropancreatic neuroendocrine neoplasm (GEP-NEN) in terms of diagnosis and curative effects. Methods: 1. Results of CgA immunohistochemical (IHC) staining in 213 cases of GEP-NEN were collected between January 1995 and December 2012 in The First Affiliated Hospital, Sun Yat-sen University. selleck compound Y-27632 supplier 2. Ninety GEP-NET patients comprising 50 patients with active disease and 40 postoperative patients were enrolled in this study from January 2011 to December 2012. Serum CgA levels were measured and clinicopathological factors were also collected. Results: 1. The overall expression rate of CgA was 62.4% (133/213). Over expression of CgA was associated with female patients, pancreas tumors, Functionality

and distant metastasis (P < 0.05), but not correlated with 上海皓元 prognosis (P = 0.07). 2. Serum CgA levels were significantly higher in GEP-NEN patients with active disease than in postoperative disease-free patients (P = 0.001) or healthy participants (P = 0.002). CgA values at 95 ng/ml distinguished healthy controls or disease-free patients from patients with active disease. Sensitivity and specificity rates were 54.0% and 90.1%, respectively. There was a significant difference in serum CgA levels between patients

with and without distant metastatic tumors (231 ng/ml vs. 46 ng/ml, P = 0.001); Patients (13/13, 100%) with stable disease and who showed complete remission and partial response after treatment had a more than 20% decrease in CgA levels compared with the baseline values. Patients (6/6, 100%) with progressive disease showed a more than 20% increase in CgA levels. CgA levels had not positive correlation with prognosis (P = 0.232). There was a positive correlation between the IHC expression and high serum levels of CgA (r = 0.280, P = 0.049). Conclusion: CgA can be used as a reliable biomarker not only for clinical diagnosis but also for the curative effects evaluation of GEP-NEN with high diagnostic value. Key Word(s): 1. gep; 2. CgA; 3. diagnosis; 4.

With JNK inhibitor sufficient nutrients, amino acids and insulin activate the mammalian target of rapamycin (mTOR) to down-regulate autophagy. The liver frequently serves as a model for the effects of starvation on autophagic function. Starvation-induced autophagy in mice decreases total hepatic protein content by 35% within 24 hours, 2 indicating that autophagy is a potent degradative pathway requiring strict regulation. Transcription

factor EB (TFEB) was first cloned from a human B-cell cDNA library by its ability to bind the adenoviral major late promoter. Sequence analysis demonstrated that TFEB has adjacent basic helix-loop-helix and leucine zipper domains, 3 which places it in the micropthalmia-transcription factor E (MiT/TFE) subfamily along with the genes, TFE3, TFEC, and MITF. 4 The function of TFEB remained unknown until Sardiello et al. 5 identified, by bioinformatics, a consensus DNA sequence in the promoters of 96 lysosomal genes termed the CLEAR (Coordinated Lysosomal Expression and Regulation) motif. The CLEAR element overlapped with the DNA target site for the MiT/TFE family, and expression studies demonstrated that TFEB specifically targeted the CLEAR motif to up-regulate genes essential for lysosomal biogenesis and function. 5 From these findings and knowledge of the existence of mTOR-independent

regulation of autophagy genes with starvation, 6 the present study by Settembre et al. 7 examined whether TFEB regulates autophagy. TFEB overexpression in several cell lines increased autophagosome formation and autophagic function, click here whereas a knockdown inhibited autophagy. 7 TFEB increased the expression of a number of autophagy genes containing a TFEB-binding site, and a subsequent study from the same laboratory confirmed and extended the list of TFEB-regulated autophagy genes. 8 In vivo TFEB overexpression also increased 上海皓元 autophagosome number and levels of lysosomal and autophagic TFEB target genes in liver. In vitro nutrient deprivation led to TFEB dephosphorylation at Ser142 and translocation to the nucleus to increase gene transcription. The mitogen-activated protein kinase (MAPK) extracellular

signal-regulated kinase 1/2 (ERK1/2) phosphorylated TFEB to maintain it in an inactive, cytosolic state. ERK1/2 is activated by growth factors, making it logical that this kinase down-regulates TFEB and autophagy in response to nutrients. Thus, the study demonstrates a central role for TFEB in controlling autophagosome formation, in addition to lysosomal biogenesis, to increase autophagy (Fig. 1). A weakness of the study is its reliance on ectopically expressed TFEB and failure to examine endogenous TFEB protein trafficking. The effects of mTOR signaling on TFEB were also not examined. Another recent study indicates that mTOR up-regulates TFEB. 9 Although TFEB phosphorylation regulated nuclear localization, Ser142 was not involved.

Genome-wide association studies have identified many non-coding variants

associated with common diseases and traits, like migraine. These variants are concentrated in regulatory DNA marked by deoxyribonuclease I hypersensitive sites. A role has been suggested for the two-pore domain potassium channel, TWIK-related spinal cord potassium channel. TWIK-related spinal cord potassium channel is involved in migraine by screening the KCNK18 gene in subjects diagnosed with migraine. “
“This review focuses on summarizing 2 pivotal articles in the clinical and pathophysiologic understanding of hemicrania continua (HC). The first article, a functional imaging project, identifies both the dorsal rostral pons (a region associated with the generation of migraines) and the posterior hypothalamus (a selleck screening library region associated with the generation of cluster and short-lasting

unilateral neuralgiform headache with conjunctival injection and tearing [SUNCT]) as active during this website HC. The second article is a summary of the clinical features seen in a prospective cohort of HC patients that carry significant diagnostic implications. In particular, they identify a wider range of autonomic signs than what is currently included in the International Headache Society criteria (including an absence of autonomic signs in a small percentage of patients), a high frequency of migrainous features, and the presence of aggravation and/or restlessness during attacks. Wide variations in exacerbation length, frequency, pain description, and pain location (including side-switching pain) are also noted. Thus, a case is made for widening and modifying the clinical diagnostic criteria used to identify patients with MCE HC. “
“A migraine attack is an extraordinarily complex brain event that takes place over hours to days. This review focuses on recent human studies that shed light on the evolution of a migraine attack. It begins with a constellation of premonitory symptoms that

are associated with activation of the hypothalamus and may involve the neurotransmitter dopamine. Even in the premonitory phase, patients experience sensitivity to sensory stimuli, indicating that central sensitization is a primary phenomenon. The migraine attack progresses to a phase that in some patients includes aura, which involves changes in cortical function, blood flow, and neurovascular coupling. The aura phase overlaps with the headache phase, which is associated with further changes in blood flow and function of the brainstem, thalamus, hypothalamus, and cortex. Serotonin receptors, nitric oxide, calcitonin gene-related peptide, pituitary adenylate cyclase-activating polypeptide, and prostanoids are demonstrated specific chemical mediators of migraine based on therapeutic and triggered migraine studies. A number of migraine symptoms persist beyond resolution of headache into a postdromal phase, accompanied by persistent blood flow changes in several brain regions.

27 These previous studies differed in sample size, technology used, and the major etiologic cause (i.e., hepatitis B virus [HBV], hepatitis C virus [HCV], and alcohol). The current study is the largest to date and is comprised of Taiwanese cases who are predominantly HBV positive. 5-HT, 5-hydroxytryptamine; AFB1, aflatoxin B1; bp, base pairs; HBC, hepatitis B virus; HBsAg, hepatitis B surface antigen; HCC, hepatocellular carcinoma; HCV, hepatitis C virus; NTU, National Taiwan University; PCR, polymerase chain

reaction; QC, quality control; SD, standard deviation; TSS, transcription start site. This study was approved by the institutional review boards of Columbia University (New York, LY2606368 NY) and National Taiwan University (NTU; Taipei, Taiwan). Written informed consent was obtained. Sixty-six frozen liver tissues collected in the Department of Surgery at AZD0530 cost NTU Hospital were assayed. Demographic data and clinicopathologic characteristics were obtained from hospital charts; HBV (hepatitis B surface

antigen; HBsAg) and HCV (anti-HCV) status were determined by immunoassay. For 39 subjects missing HCV status, liver tissues were stained with monoclonal antibody nonstructural protein 3 (Novocastra Laboratories Ltd., Newcastle upon Tyne, UK). Specimens were kept at −70°C until shipment to Columbia University, where pathologic analysis confirmed HCC status and indicated that adjacent tissues were primarily cirrhotic. Blood specimens were collected at the time of diagnosis for 30 patients and were plasma-frozen. Plasma from 8 additional cases from the same hospital was included in the analysis. DNA was extracted by standard proteinase K/RNase treatment and phenol/chloroform extraction. Plasma DNAs were extracted using DNeasy Blood and Tissue Kits (Qiagen, Valencia, CA). Bisulfite modification of 1 μg of DNA was conducted using an EZ DNA Methylation Kit (Zymo Research, Irvine, CA). The HumanMethylation27 DNA Analysis BeadChips (Illumina) were used to interrogate 27,578 highly informative CpG sites covering 14,495 genes, following their standard protocol. Paired samples

(e.g., HCC tumor and adjacent nontumor tissues) medchemexpress were processed on the same chip to avoid chip-to-chip variation; four pairs of tissues were repeat-assayed as a quality control (QC). Information on location of CpG sites in the promoter regions was provided by Dr. Kim.28 Pyrosequencing was carried out with primers designed with Pyromark Assay Design software (version 2.0; Qiagen). The region selected for interrogation included the CpG sites identified to be differentially methylated based on the array data, as well as surrounding sites. Polymerase chain reaction (PCR) was performed in a 25-uL reaction mix containing 50 ng of bisulfite-converted DNA, 1× Pyromark PCR Master Mix (Qiagen), 1× Coral Load Concentrate (Qiagen), and 0.

Carbamyl-palmitoyl trans-ferase 1a (CPT1a) and ATP synthase subunit ATP5G1 were strongly down-regulated implying defects in mitochondrial fatty acid transport and ATP synthesis. Electron microscopy showed mitochondrial swelling with abnormalities in shapes and numbers of cristae. Over

the next several weeks improvement of steatosis and apoptosis occurred, with increases in numbers of ALR-expressing cells and ATP levels. However, recovery was transient and was followed at 4-8 weeks by progressive inflammation, hepatocellular necrosis, ductular proliferation and fibrosis, and development of hepatocellular carcinoma by one year. In vitro, depletion of ALR from ALRfloxed/floxed hepatocytes with adeno-Cre infection increased lipid accumulation and decreased 3-Methyladenine cost CPT1a

expression/activity, and caused mitochondrial DNA AZD5363 in vivo damage, oxidative stress and death of the cells. Hepatic ALR levels were also found to be low in Ob/ Ob and alcohol-treated steatotic mice, and in humans with advanced alcoholic liver disease and nonalcoholic steatohepatitis. CONCLUSIONS: The results indicate that ALR is essential for normal mitochondrial function and lipid homeostasis in the liver. We conclude that the ALR-L-KO mouse provides a novel model to investigate not only mechanisms involved in the development of steatohepatitis but also complications arising from this disorder. Grant support: This work was supported by a VA Merit Review Award (1IO1BX001174) and grants from NIH (PO1AIO81678 and R21AA020846) to CRG. Disclosures: The following people have nothing to disclose: Chandrashekhar R. Gandhi, J. Richard Chaillet, Michael

A. Nalesnik, Sudhir Kumar, Anil Dangi, Robert Ferrell, Tong Wu, Senad Devanovic, Donna B. Stolz, Jiang Wang, Thomas Starzl Lipin family proteins (lipin 1, 2, and 3) act as phosphatidate phosphohydrolase (PAP) enzymes to catalyze diacylglycerol synthesis as the penultimate step in triglyceride synthesis. Though lipin 2 is highly expressed in fed liver, hepatic PAP activity and lipin 1 expression is markedly increased by stimuli that signal increased flux through the triglyceride synthetic pathway. However, the contribution of lipin 1-mediated PAP activity in hepatic fat accumulation in response to fasting or in chronic fatty liver disease is unknown. To examine this point, we developed mice deficient in lipin 1-mediated PAP activity in a liver-specific 上海皓元 manner by using a Cre-LoxP approach (Alb-Lpin1−/− mice). We evaluated hepatic PAP activity, triglyceride metabolism, liver histology, and hepatic insulin signaling in these mice under fed vs. fasting condition as well as after high fat feeding. All animal studies were approved by the institutional Animal Use and Care Committees of Washington University School of Medicine and fulfilled NIH requirements for humane care. Results: Hepatic PAP activity was reduced by 50% in mice with liver-specific lipin 1 deficiency and this deficit was exaggerated under fasted conditions.

51, −0.43). Conclusion: There were impaired function of proximal stomach in patients with DM. It presented as sensory threshold value declined and relax function reduction, the symptom will be gradually more serious when other complications appeared. Autonomic nervous damage existed

in diabetes, including abnormity of sympathetic nerve and parasympathetic nerve, parasympathetic nerve lesions are mainly appeared during the early stage. Proximal stomach dysfunction in diabetes mellitus was related to sympathetic nerve damage. Key Word(s): 1. diabetes mellitus; 2. autonomic selleck nervous; 3. stomach; 4. proximal; Presenting Author: NAGAP. MEKA Additional Authors: MEHUL ADHADUK, SWATHIB ANCHE, MYRIAM EDWARDS Corresponding Author: NAGAP. MEKA Affiliations: Hurley Medical Center; Internal Medicine Objective: Background-Motor nerve complications occur in about 3% of patients with Herpes Zoster. Colonic pseudoobstruction, severe constipation and obstipation have been reported with Herpes Zoster affecting thoracic (T6-T12) dermatomes. Methods: Case Description- She is a sixty-five year old white female with mixed connective tissue disorder, gastritis, chronic obstructive pulmonary disease, and no prior abdominal surgery

presented with severe abdominal pain and constipation for 5 days. Abdominal pain is diffuse, cramping, and severe. Patient was nauseous but no emesis and had flatus. Key Word(s): 1. Herpes Zoster; 2. Constipation; Presenting Author: RONAAGUILAR ATA

Corresponding Author: RONAAGUILAR ATA Affiliations: Makati Objective: Colonic diverticulosis is a disease Afatinib cell line affecting the elderly, with a high prevalence in Westernized countries. Marked by geographical variations, diverticular diseases differ in terms of site involvement, sex predilection and age distribution and local data is lacking in our setting. This study aims to determine the prevalence and distribution of colonic diverticulosis. Methods: A retrospective review of 6,357 patients who underwent colonoscopy between August 2009 and August 2012 was done. The age, gender and localization of diverticula were evaluated. Data analysis was presented using frequencies, Pearson’s chi-square and one-way analysis of variants. Key Word(s): 1. diverticulosis; 2. Prevalence; 上海皓元医药股份有限公司 3. Distribution; 4. Philippines; Presenting Author: RONA MARIEAGUILAR ATA Corresponding Author: RONA MARIEAGUILAR ATA Affiliations: Makati Objective: Colorectal cancer (CRC) ranks among the top five cancer morbidities in the world. Early-onset CRC is mostly genetic and thus behaves differently than late-onset colorectal cancer. This study aims to describe the clinical and histopathological profile of early-onset colorectal cancer (CRC) patients in contrast to that of late-onset colorectal cancer patients diagnosed via endoscopy in Cardinal Santos Medical Center.

The clinician must be familiar with potential drug interactions and side effects of the three treatment agents, especially those of telaprevir. In order to ensure compliance and safety as well as response-guided treatment decisions, close monitoring is essential. Additional Supporting Information may be found in the online version of this

article. “
“Background and Aim:  In Japan, patient acceptance of bowel preparation methods before colonoscopy remains unknown. This study was conducted to evaluate the patient acceptance of sodium Sorafenib phosphate (NaP) tablets and polyethylene glycol solution (PEG) with sodium Venetoclax nmr picosulfate. Methods:  One hundred patients were randomized into one of the following two groups:

the NaP tablet first-use group or the PEG with sodium picosulfate first-use group in a crossover design trial. Patient acceptance and incidence of adverse events were evaluated using a questionnaire. Colon-cleansing effectiveness was also evaluated. Results:  Patients’ overall impressions of the preparations were significantly different between the NaP tablet (77.9%, 67/86) and PEG with sodium picosulfate (60.5%, 52/86; P = 0.001). Nausea incidence as an adverse event was significantly different between the two regimens (P = 0.03). Colon-cleansing effectiveness was not significantly different between the two regimens. Conclusions:  The results of this crossover study showed that

patient acceptance was similar to those previously reported in a parallel-group comparison. In Japanese patients, preference for and acceptance of NaP tablets was significantly higher than that for PEG with sodium picosulfate solution. “
“Hans MCE Popper Laboratory of Molecular Hepatology, Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria The ABCB4 transporter mediates phosphatidylcholine (PC) secretion at the canalicular membrane of hepatocytes and its genetic defects cause biliary diseases. Whereas ABCB4 shares high sequence identity with the multidrug transporter, ABCB1, its N-terminal domain is poorly conserved, leading us to hypothesize a functional specificity of this domain. A database of ABCB4 genotyping in a large series of patients was screened for variations altering residues of the N-terminal domain. Identified variants were then expressed in cell models to investigate their biological consequences. Two missense variations, T34M and R47G, were identified in patients with low-phospholipid–associated cholelithiasis or intrahepatic cholestasis of pregnancy.

Of particular importance have been studies showing that EpCAM is a marker of the hepatobiliary stem cell niche and that when such cells develop into hepatocytes in culture, the new hepatocytes as well as the cells with intermediate features between stem/progenitor cells and hepatocytes also display membranous EpCAM.2, 16 These findings led us to hypothesize that EpCAM(+) hepatocytes are derived relatively recently from the stem cell niche http://www.selleckchem.com/products/AG-014699.html rather

than from other, preexisting hepatocytes. The goal of the present study was to investigate this possibility within intact tissue specimens from livers of patients with hepatitis B and C through several means. The first is by determining whether EpCAM(+) hepatocytes develop only in the context of ductular reactions, stage by stage, and exploring the topological relationships selleck chemicals llc of

these cells (Fig. 1 and Table 3). Four important points support our primary hypothesis: (1) EpCAM(+) hepatocytes, like ductular reactions, increase in frequency and extent with increasing stage of disease; (2) although ductular reactions sometimes do not have associated EpCAM(+) hepatocytes, EpCAM(+) hepatocytes, when present, are always associated with ductular reactions; (3) EpCAM(+) hepatocytes always appear as aggregates surrounding a core of ductular reaction cells; and (4) cells of intermediate morphology between the smallest progenitor cells of the ductular reaction and mature appearing, EpCAM(+) hepatocytes are always also EpCAM(+). Thus, morphologically, topographically, and immunophenotypically, EpCAM(+) hepatocytes 上海皓元医药股份有限公司 appear to derive from cells of the ductular reaction. Such data, although compelling, are incomplete. We thus hypothesized that if EpCAM(+) hepatocytes were stem cell–derived, they would have telomere lengths that were longer than those of the EpCAM(−) hepatocytes. This hypothesis is based on prior

data indicating that ductular reactions have increased telomerase activation22-25 and that senescent hepatocytes, after years of increased cell turnover, would have shortened telomeres.26-29 We would also expect that EpCAM(−) hepatocytes in cirrhosis would have telomeres that would be shorter than those in EpCAM(+) hepatocytes, and that telomere length of EpCAM(+) hepatocytes would be shorter than that in ductular reactions. These predictions were confirmed in a statistically meaningful way for hepatocytes in CHB cirrhosis. We also sought to explore issues of proliferation and senescence as previous studies had done,13-15, 20 but discriminating between hepatocytes that were EpCAM(+) and those that were EpCAM(−). However, there was no significant difference of PCNA and p21 labeling indices between EpCAM(+) hepatocytes and EpCAM(−) hepatocytes.