Homozygosity for KIR2DL3 in combination with group 1 HLA-C allotypes was more frequent in exposed seronegative aviremic individuals as compared to those with chronic HCV (25.0% versus 9.7%, P = 0.003, odds ratio [OR] = 3.1, 95% confidence interval [CI] = 1.3-7.1) in a model similar to that found for those spontaneously resolving HCV. In individuals undergoing treatment for HCV, those with KIR2DL3 and group 1 HLA-C were more likely to make a sustained virological response (SVR) (P = 0.013, OR = 2.3, 95% CI = 1.1-4.5). KIR and HLA-C protection in both

treatment response and spontaneously resolving HCV was validated at the allelic level, in which KIR2DL3-HLA-Cw*03 was associated with SVR (P = 0.004, OR = 3.4, 95% CI = 1.5-8.7) and KIR2DL3/KIR2DL3-HLA-Cw*03 was associated with spontaneous resolution of HCV infection Imatinib manufacturer (P = 0.01, OR = 2.3, 95% CI = 1.2-4.4). Conclusion: KIR and HLA-C genes are consistently beneficial determinants in the outcome of HCV infection. This advantage extends to the allelic level for both gene families. (HEPATOLOGY 2010.) “
“Aim:  The diagnosis of acute liver failure due to autoimmune hepatitis is often difficult because of atypical clinicopathological features. Patients with autoimmune acute liver failure are sometimes

resistant to immunosuppressive therapy and have poor prognosis. Although their survival rates are especially poor (5–20%) without liver transplantation in Japan, their clinicopathological features have remained uncertain. A major problem is that there is no gold standard for making www.selleckchem.com/products/BIBW2992.html the diagnosis of acute onset autoimmune hepatitis. If there are diagnosing tools supporting

clinicopathological features, they are of benefit to the patients. We examined computed tomography (CT) imaging features of autoimmune acute liver failure to clarify the usefulness of imaging for the diagnosis. Methods:  A retrospective analysis of 129 unenhanced CT scans of 68 patients MCE with acute hepatitis, consisting of 23 with autoimmune acute liver failure (ALF) (group 1), 25 with early admission-viral ALF (group 2) and 20 with late admission-viral ALF (group 3), was performed. Results:  Autoimmune acute liver failure showed heterogeneous hypoattenuating areas and viral ALF diffuse ones (P < 0.001). The diffuse hypoattenuating areas were present in none of group 1, 15 (60%) of group 2, and 7 (30%) of group 3. The heterogeneous hypoattenuating areas were present in 15 (65%) of group 1, none of group 2 and 1 (5%) of group 3. Conclusions:  Heterogeneous hypoattenuation on unenhanced CT was a characteristic CT imaging feature of autoimmune acute liver failure compared with viral ALF. This finding could be one of the tools for diagnosing autoimmune acute liver failure in combination with clinicopathological features.

The remaining 1,521 patients did not fulfill all three inclusion criteria and were excluded. The diagnosis of cirrhosis could rest on any combination of clinical, biochemical, imaging, hemodynamic, and liver biopsy findings, whereas the diagnosis of alcohol abuse was based on patients’ and relatives’ reports. Thus, patients were included in the cohort if the treating clinician was sufficiently confident of the diagnosis of alcoholic cirrhosis to record it in the medical chart. We did not negate clinicians’ diagnoses of alcoholic cirrhosis on the basis of information that became available later, e.g., autopsy findings, nor did

we include patients who were never believed to have cirrhosis until autopsy findings proved otherwise. The study inclusion date depended ATR inhibitor on the patient’s presentation: For patients who presented with ascites, variceal bleeding, or hepatic encephalopathy and who had a history of alcohol abuse in the absence of another probable cirrhosis cause (viral hepatitis, autoimmune hepatitis, primary biliary cirrhosis, primary sclerosing cholangitis, alpha-1-antitrypsin deficiency, hemochromatosis, or Wilson’s disease), Palbociclib datasheet it was usually the date of hospital admission. For patients without complications or with unclear cirrhosis etiology, it awaited clarification of the cirrhosis diagnosis and etiology. From the medical charts we obtained the date on which patients presented with the following three

complications: ascites, variceal bleeding, or hepatic encephalopathy. Ascites was defined as clinically detectable ascites, i.e., ascites seen only on ultrasound examination was excluded.

Variceal bleeding was defined as clinically unequivocal bleeding from esophageal or gastric varices with hematemesis, a heart rate >100 beats per minute and a systolic blood pressure <100 mmHg, or a need for blood transfusion. Hepatic encephalopathy was defined as clinically overt hepatic encephalopathy, i.e., minimal hepatic encephalopathy18 was excluded. In practice, the diagnosis of hepatic encephalopathy was based on the patient's clinical presentation, usually supported by the blood ammonia level and/or a continuous reaction time test,19 and with differential diagnoses deemed unlikely. Data on patients' alcohol consumption were extracted from http://www.selleck.co.jp/products/Fludarabine(Fludara).html the medical charts, as were data on liver transplantation, TIPS (transjugular intrahepatic portosystemic shunt) insertion, portosystemic shunt surgery, and spontaneous bacterial peritonitis, which was defined as >250 polymorphonuclear leukocytes per mm3 ascitic fluid.20 We recorded patients’ current alcohol drinking status (abstinent or drinking) as reported when they were seen in the hospital and assumed that it remained unchanged until the next hospital contact. “Abstinence” was defined as complete abstinence or consumption of small amounts of alcohol on rare occasions, and “drinking” was defined as nonabstinence.

The remaining 1,521 patients did not fulfill all three inclusion criteria and were excluded. The diagnosis of cirrhosis could rest on any combination of clinical, biochemical, imaging, hemodynamic, and liver biopsy findings, whereas the diagnosis of alcohol abuse was based on patients’ and relatives’ reports. Thus, patients were included in the cohort if the treating clinician was sufficiently confident of the diagnosis of alcoholic cirrhosis to record it in the medical chart. We did not negate clinicians’ diagnoses of alcoholic cirrhosis on the basis of information that became available later, e.g., autopsy findings, nor did

we include patients who were never believed to have cirrhosis until autopsy findings proved otherwise. The study inclusion date depended CHIR-99021 chemical structure on the patient’s presentation: For patients who presented with ascites, variceal bleeding, or hepatic encephalopathy and who had a history of alcohol abuse in the absence of another probable cirrhosis cause (viral hepatitis, autoimmune hepatitis, primary biliary cirrhosis, primary sclerosing cholangitis, alpha-1-antitrypsin deficiency, hemochromatosis, or Wilson’s disease), click here it was usually the date of hospital admission. For patients without complications or with unclear cirrhosis etiology, it awaited clarification of the cirrhosis diagnosis and etiology. From the medical charts we obtained the date on which patients presented with the following three

complications: ascites, variceal bleeding, or hepatic encephalopathy. Ascites was defined as clinically detectable ascites, i.e., ascites seen only on ultrasound examination was excluded.

Variceal bleeding was defined as clinically unequivocal bleeding from esophageal or gastric varices with hematemesis, a heart rate >100 beats per minute and a systolic blood pressure <100 mmHg, or a need for blood transfusion. Hepatic encephalopathy was defined as clinically overt hepatic encephalopathy, i.e., minimal hepatic encephalopathy18 was excluded. In practice, the diagnosis of hepatic encephalopathy was based on the patient's clinical presentation, usually supported by the blood ammonia level and/or a continuous reaction time test,19 and with differential diagnoses deemed unlikely. Data on patients' alcohol consumption were extracted from 6-phosphogluconolactonase the medical charts, as were data on liver transplantation, TIPS (transjugular intrahepatic portosystemic shunt) insertion, portosystemic shunt surgery, and spontaneous bacterial peritonitis, which was defined as >250 polymorphonuclear leukocytes per mm3 ascitic fluid.20 We recorded patients’ current alcohol drinking status (abstinent or drinking) as reported when they were seen in the hospital and assumed that it remained unchanged until the next hospital contact. “Abstinence” was defined as complete abstinence or consumption of small amounts of alcohol on rare occasions, and “drinking” was defined as nonabstinence.

The remaining 1,521 patients did not fulfill all three inclusion criteria and were excluded. The diagnosis of cirrhosis could rest on any combination of clinical, biochemical, imaging, hemodynamic, and liver biopsy findings, whereas the diagnosis of alcohol abuse was based on patients’ and relatives’ reports. Thus, patients were included in the cohort if the treating clinician was sufficiently confident of the diagnosis of alcoholic cirrhosis to record it in the medical chart. We did not negate clinicians’ diagnoses of alcoholic cirrhosis on the basis of information that became available later, e.g., autopsy findings, nor did

we include patients who were never believed to have cirrhosis until autopsy findings proved otherwise. The study inclusion date depended Selleckchem Compound Library on the patient’s presentation: For patients who presented with ascites, variceal bleeding, or hepatic encephalopathy and who had a history of alcohol abuse in the absence of another probable cirrhosis cause (viral hepatitis, autoimmune hepatitis, primary biliary cirrhosis, primary sclerosing cholangitis, alpha-1-antitrypsin deficiency, hemochromatosis, or Wilson’s disease), Birinapant order it was usually the date of hospital admission. For patients without complications or with unclear cirrhosis etiology, it awaited clarification of the cirrhosis diagnosis and etiology. From the medical charts we obtained the date on which patients presented with the following three

complications: ascites, variceal bleeding, or hepatic encephalopathy. Ascites was defined as clinically detectable ascites, i.e., ascites seen only on ultrasound examination was excluded.

Variceal bleeding was defined as clinically unequivocal bleeding from esophageal or gastric varices with hematemesis, a heart rate >100 beats per minute and a systolic blood pressure <100 mmHg, or a need for blood transfusion. Hepatic encephalopathy was defined as clinically overt hepatic encephalopathy, i.e., minimal hepatic encephalopathy18 was excluded. In practice, the diagnosis of hepatic encephalopathy was based on the patient's clinical presentation, usually supported by the blood ammonia level and/or a continuous reaction time test,19 and with differential diagnoses deemed unlikely. Data on patients' alcohol consumption were extracted from Decitabine the medical charts, as were data on liver transplantation, TIPS (transjugular intrahepatic portosystemic shunt) insertion, portosystemic shunt surgery, and spontaneous bacterial peritonitis, which was defined as >250 polymorphonuclear leukocytes per mm3 ascitic fluid.20 We recorded patients’ current alcohol drinking status (abstinent or drinking) as reported when they were seen in the hospital and assumed that it remained unchanged until the next hospital contact. “Abstinence” was defined as complete abstinence or consumption of small amounts of alcohol on rare occasions, and “drinking” was defined as nonabstinence.

[49] Neuroimaging showed that these reductions were associated with increased activity in the anterior cingulate cortex and anterior insula (ie, areas involved in the cognitive regulation of nociception) and with thalamic deactivation.[49] Meditation and other non-pharmacological practices may activate natural endogenous analgesic processes, or observed results could be attributable to distraction or altered expectations.[50] Yet the exact physiological

mechanisms of stress-reducing interventions on headache are not clearly elucidated. buy RO4929097 If stress-reducing interventions are effective because they alter autonomic reactivity, it is important to determine whether they alter autonomic responses to individual stressful events selleck inhibitor or the patient’s baseline autonomic levels. Stress reduction Decreased stress hormones (eg, cortisol) Altered autonomic arousal Changes in relevant psychological constructs Improved coping skills Increased self-efficacy Decreased external locus of control Decreased pain catastrophizing Decreased depression and anxiety Effects on other behaviors Improved sleep Improved diet, exercise, and other healthy behaviors Change in pain processing Change in neural pain processing

Activation of natural endogenous analgesic processes Placebo Altered expectations Common factors” (eg, ritual, empathy, alliance, etc.) Non-pharmacological interventions also may exert beneficial effects Pyruvate dehydrogenase lipoamide kinase isozyme 1 by affecting psychological constructs. An increased sense of headache “self-efficacy,” or confidence in one’s ability to persist with behavioral change efforts that one believes will manage headache symptoms, and a reduced external “locus of control,” or belief that nothing can exert control over the onset and course of headache, are potent predictors of behavioral treatment outcomes. Foundational research on evidence-based behavioral interventions decades ago identified increased self-efficacy as the key mediator of successful EMG biofeedback for TTH, regardless of whether the patient was taught to increase or decrease muscle tension.[51] More recent research has confirmed that both self-efficacy

and locus of control are important factors for the success of evidence-based behavioral headache treatments.[52] Evidence-based behavioral and mind/body interventions may be useful also because they improve psychiatric conditions commonly comorbid with headache, such as anxiety and depression, and are often associated with a poorer prognosis.53-55 Improvements in these affective conditions, even if present at a level not warranting a clinical diagnosis, in turn may improve the ability to cope with pain and enhance adherence to treatment recommendations. Even adults without formal psychiatric diagnoses may experience disabling anxiety related to the fear of individual attacks, the fear of triggers, or at the onset of prodrome or aura.

Key Word(s): 1. gastric

cancer; 2. serum proteomics; 3. iTRAQ; 4. D-LC-MS/MS; Presenting Author: MALU JUN Additional Authors: LINYAO GUANG Corresponding Author: LINYAO GUANG Affiliations: guangxi medical university Objective: To study the expression of S100A11 and Beclin1 in gastric carcinoma, precancerous lesion and chronic nonatrophic pangastritis, and the relationship between S100A11 and Beclin1 expression in gastric cancerous tissues and the biological behaviour of gastric carcinoma, investigate the mechanism and clinical significance of S100A11 and Beclin1 Enzalutamide clinical trial in the development of gastric carcinoma. Methods: The expression of S100A11 and Beclin1 proteins were determined by streptavidin-perosidase immunohistochemical method in 50 cases of gastric carcinoma from exairesis tissues, 30 cases of precancerous lesion and 20 cases of chronic nonatrophic pangastritis from endoscopic biopsy. Pathological image analysis system be used to analysis the grey level of S100A11 and Beclin1, then analyze the mechanism and clinical significance of S100A11 and Beclin1 in the development of gastric carcinoma.

Results: The positive expression grey level of S100A11 in gastric carcinoma was 132.9209 ± 5.649, and in precancerous lesion tissues was 133.6706 ± 5.8348, both of them were significantly lower than that of in chronic nonatrophic pheromone pangastritis tissues (138.048 ± 3.5902), SRT1720 clinical trial There were significant difference between the gastric carcinoma and chronic nonatrophic pangastritis tissues, precancerous lesion tissues and chronic nonatrophic pangastritis tissues (P < 0.05), But there was no difference between the gastric carcinoma and precancerous lesion tissues (P > 0.05). There was obvious correlation between the expression of S100A11 and the clinicopathological

factors, such as grading, infiltrating depth, lymph nodes metastasis, TNM degree (P < 0.05), but there was no correlation between the expression of S100A11 and position, knubbly diameter (P > 0.05). The positive expression grey level of Beclin1 in gastric carcinoma was 140.9705 ± 6.2019, which was significantly higher than those in precancerous lesion tissues (136.711 ± 5.5759) and in chronic nonatrophic pangastritis tissues (130.8024 ± 2.5363), there were significantly differences between two of the three tissues (P < 0.05). There was correlation between the expression of Beclin1 and grading, lymph nodes metastasis (P < 0.05), but there was no correlation between the expression of Beclin1 and position, diameter, infiltrating depth, TNM degree (P > 0.05), There existed a negative correlation between S100A11 and Beclin1 in gastric carcinoma (r = −0.156, P < 0.05).

Cells were then harvested with 0.025% trypsin/ethylenediaminetetraacetic acid, washed with PBS, and finally resuspended in PBS.

Samples were analyzed using the FACSCalibur flow cytometer with CellQuest software (BD Biosciences, Franklin Lakes, NJ). Mitochondrial membrane potential (MMP; Δψm) was determined using an MMP assay kit (Beyotime). Briefly, cultured cells were incubated with a buffer containing 5,5′,6,6′-tetrachloro-1,1′,3,3′-tetraethylbenzimidazolcarbocyanine iodide (JC-1; 1:200) for 20 minutes at 37°C. Cells were then washed twice with staining buffer on ice to remove excess probe. The ΔΨm was assessed Microtubule Associated inhibitor using the FACSCalibur flow cytometer (BD Biosciences). HepG2 cells were cultured in serum-free DMEM supplemented with free FAs (FFAs; 0.2 mM of OA, 0.1 mM of PA, and 0.075 mM of BSA)19 or FFA plus resistin (0.2 mM of OA, 0.1 mM of PA, 0.075 mM of BSA, and 25 ng/mL of resistin). TAG and glycerol were measured using a TAG assay kit and a glycerol assay kit Cisplatin in vitro (Applygen Technologies Co. Ltd., Beijing, China),

respectively. Values were normalized to protein concentrations using the Pierce BCA protein quantitative assay kit (Thermo-Fisher Scientific). Data are presented as means ± standard deviation (SD). Statistical analysis was performed using the unpaired two-tailed t test (for two groups) and analysis of variance (for multiple groups). P values <0.05 were considered statistically significant. Analysis of the ratio of mtDNA to nDNA in HepG2 cells showed that the direct addition of resistin markedly diminished

mitochondrial content in a dose-dependent manner (Fig. 1A). The time course studied indicated that the effect of resistin reached significance after incubation for 4 hours (Fig. 1B). Subsequently, the in vivo study also confirmed this finding. C57BL/6J mice were treated with or without resistin for 6 days. qPCR showed that mitochondrial content in livers of resistin-treated animals was significantly lower (Fig. 1C). Moreover, flow cytometry data verified the change of mitochondrial content (Fig. 1D). These data proved our hypothesis and confirmed that increased resistin signaling down-regulated mitochondrial content. The in vivo study Farnesyltransferase also indicated that resistin significantly stimulated levels of blood glucose, insulin, and TAG. Data of the homeostasis model assessment of IR (HOMA-IR) revealed resistin-induced IR (Table 1). To investigate the effect of resistin on mitochondrial function, HepG2 cells were cultured with or without 25 ng/mL of resistin for 24 hours, followed by measurement of Δψm and intracellular ROS and adenosine triphosphate (ATP) content. Resistin diminished Δψm and ATP levels substantially, but had little effect on ROS levels (Figs. 2A-C). The study of transcription levels indicated that resistin stimulated ucp2 expression, but did not influence sod2 RNA levels (Fig. 2D). Moreover, genes in the tricarboxylic acid (TCA) cycle and electron transport chain (ETC) were also assayed.

The more common sites for bleeding ectopic varices include gastrointestinal stomas (30%), duodenum (20%), jejunum and ileum (20%), colon and rectum (8%) and peritoneum (10%). Vaginal variceal bleeding appears to be rare as there are only 7 case reports in the medical literature. Most of these patients have had a hysterectomy, selleck chemicals llc presumably with

the development of post-surgical collaterals. The initial management of vaginal varices consists of resuscitation and local control with tamponade. This is the third patient in the medical literature who has been treated with TIPS but other options include balloon-occluded retrograde transvenous obliteration and liver transplantation. For patients with active bleeding who are not appropriate for TIPS, the transhepatic approach to the portal vein is usually preferred because of more rapid access into the mesenteric venous system. Contributed by “
“A 53-year-old man presented with a 4-month history of multiple subcutaneous tumors on his head, neck, and upper trunk. He drank more than 1 L of rice wine per day, beginning at age 16. Multiple ill-defined, variously sized tumors were noted on the scalp, neck, shoulders, and upper trunk (Fig. 1). The largest, 28 cm in length, was seen on the posterior neck and upper back (Fig. 2). These tumors were elastic firm on palpation Sorafenib manufacturer and showed no symptoms and signs of inflammation. Laboratory analyses revealed elevated aspartate aminotransferase,

83 U/L (<31); elevated alanine aminotransferase, 43 U/L (<31); and

elevated serum bilirubin level, 1.8 mg/dL (0.2–1.0). The complete Lonafarnib in vivo blood count with differential, blood glucose, and renal function tests were all unremarkable. Serologic tests ruled out viral hepatitis. Abdominal ultrasonography revealed fatty liver but no other abnormalities. Alcoholic liver disease was diagnosed. Skin biopsy and computed tomography of the tumors showed prominent fatty tissue (Fig. 3). These symmetrically distributed fatty tumors on the back, suboccipital region, and proximal extremities, with a characteristic “horse-collar” appearance, are typical of Madelung disease (benign symmetric lipomatosis), a rare disorder that usually affects middle-aged alcoholic men. The differential diagnosis includes Cushing’s syndrome, familial multiple lipomatosis, Dercum’s disease, and congenital lipomatosis. Madelung disease predominantly affects men between the ages of 30 and 60 years.1 The diagnosis is primarily dependent on clinical history and characteristic appearance. The masses are nonencapsulated, infiltrative, hypervascular. They can eventually reach very large sizes, diminish the range of motion of the neck and upper extremities, and even result in dysphagia or dyspnea.1 There is a strong correlation with alcohol abuse and liver disease.2, 3 Diabetes, polyneuropathy, hypothyroidism, and hyperlipidemia have also been reported to be associated.2, 3 However, the etiology is still not clearly known.

Results: Four pairs of liver tissues were selected for RNA extraction. miRNA microarray and FDR calculation were performed and four genes were selected due to the previous report on their correlation with HCC. The results of luciferase assay and transfection of HepG2 cells indicated that miRNA-128 indeed binds to the 3′ UTR of Axin1. In Western blotting study miR-128 indeed decreased Axin1 protein levels, demonstrating that Axin1 is indeed a target of miR-128 in HepG2 cells. Conclusion: In this study we report that miR-128 is up-regualted in clinical HCC tissues and that miR-128 binds to 3′ UTR of Axin1. The identification of miR-128 as oncomir and determination of its target gene Axin 1

will shed light on the pathogenesis of HCC. Key Word(s): 1. hepatocellular carcinoma; 2. microRNA; www.selleckchem.com/products/BKM-120.html 3. tumorigenesis Presenting Author: EUNAE CHO Additional Authors: MOON JONG HAN, CHAN YOUNG OAK, DONG IK KIM, MI YOUNG KIM, DU HYEON Selleckchem PI3K Inhibitor Library LEE, SHI HYUN YOO Corresponding Author: EUNAE CHO Affiliations: Chonnam National University Hospital, Chonnam National University Hospital, Chonnam National University Hospital, Chonnam National University Hospital, Chonnam National University Hospital, Chonnam National University Hospital Objective: 18F-fluorodeoxyglucose PET computed tomography (18F-FDG PET CT)

has been used widely in oncology part as a part of staging workup, prediction of treatment response and clinical outcomes in various malignancies. However, its use in hepatocellular carcinoma (HCC) has been limited to evaluation of extrahepatic metastasis. The aim of this study was to investigate the role of 18F-FDG PET CT as an independent prognostic factor in hepatocellular carcinoma. DNA ligase Methods: A total of 77 patients with newly diagnosed HCC who underwent 18F-FDG PET CT before treatment from January 2009 to December 2013 were reviewed retrospectively. Maximal standardized uptake values (SUVmax)

of the tumors were obtained. Results: Sixty-four patients were male (83.1%) and 13 patients were female (16.9%). Mean age of the enrolled patients was 61.73 years and mean duration of follow-up was 8.6 months. High SUVmax (≥5.0) was significantly associated with the tumor burden such as α-fetoprotein (P = 0.003), amino transaminase (AST) (P = 0.001), tumor size (P = 0.01), and TNM staging (P = 0.04). The overall survival rates in patients with high SUVmax (≥5.0) were 24.3% while those in patients with low SUVmax (<5.0) were 64.5% (P < 0.001). In subgroup analysis, among the 42 patients who received transarterial chemoembolization (TACE), patients with high SUVmax (≥5.0) were more likely to have earlier recurrence (P = 0.019). Conclusion: SUVmax of 18F-FDG PET CT can not only serve as an indicator of tumor burden and an independent prognostic factor in HCC but also predict recurrence after TACE. Key Word(s): 1. hepatocellular carcinoma; 2.

Gross areas of fibrosis were seen only in the duodenal lobe of pancreas in the CP group after the pancreas was harvested. The oxygen tension measurements between the two groups were compared by multi-level modeling using GLLAMM (Generalized Linear Latent and Mixed Models) program in STATA. Results: The mean oxygen tension in the CP group was less than that in the control group (5.3% ± 4.9 vs. 6.84% ± 4.27, p = 0.13) (Fig 2). Histologic evaluation selleck screening library confirmed glandular atrophy, inflammation and fibrosis in only 5–10% of the gland in the CP group. There was mild extra-pancreatic inflammation in the control group but no glandular features of chronic pancreatitis. Conclusion: A novel micro-oxygen sensor probe can detect

pancreatic oxygen tension in an experimental model of

chronic pancreatitis. Larger studies are needed in robust models of chronic pancreatitis to determine if significant pancreatic ischemia can be detected in chronic pancreatitis. The probe is endoscopy capable and may have utility in the detection of ischemic pathology in the gastrointestinal tract. M MELINO,1 V GADD,1 M MARTINEZ,2 K LINEBURG,2 K IRVINE,1 CH5424802 concentration AD CLOUSTON,3 EE POWELL,1,3 KP MACDONALD2 1Centre for Liver Disease Research, The University of Queensland, 2Antigen Presentation and Immunoregulation, QIMR Berghofer Medical Research Institute, 3Department of Gastroenterology and Hepatology, Princess Alexandra Hospital, Queensland Introduction: Most of the morbidity and mortality from chronic liver

disease (CLD) occurs in patients with advanced fibrosis or cirrhosis, who are at risk of developing complications of end stage liver disease including hepatocellular carcinoma. Currently, few anti-fibrotic therapies are in clinical trials and targeted strategies that modify progressive fibrosis are still required. Following liver injury, monocytes and macrophages contribute to fibrogenesis via the production of pro-inflammatory MYO10 cytokines and reactive oxygen species.1 Additionally, data from human CLD studies implicate the activation of bipotential hepatic progenitor cells (the “ductular reaction (DR)”) as an important precursor to fibrosis.2 However, the timing and mechanisms by which these lineages become activated and the interplay between macrophages and the ductular reaction during fibrogenesis remains unclear. To gain insight into temporal changes in monocytes, macrophages and hepatic progenitor cells we used a hepatotoxin induced liver injury model in which extensive fibrosis is induced over a 2-month period. Here we demonstrate the induction of fibrotic liver injury in two phases: an early monocyte mediated phase followed by a second progressive fibrotic phase accentuated by resident tissue macrophage and DR activity. Materials and Methods: Liver inflammation, DR and fibrosis were induced in 6–8-week-old C57BL/6 mice by oral administration of thioacetamide (TAA, 300 mg/L) in drinking water for up to 12 weeks.