During the second pass, the cecum was reintubated and the same colonic segment was re-examined with NBI, and additional polyps were photographed and removed. In the back-to-back study

Bortezomib in vivo by East et al. in surveillance for hereditary non-polyposis cancer syndrome (HNPCC) patients, the number of adenomas detected on NBI almost doubled when performed by endoscopists who had experience with at least 100 colonoscopies with NBI.17 In a randomized tandem colonoscopy trial, 276 patients were randomized to undergo colonoscopy using NBI or white-light examination. All patients then underwent a second colonoscopy using white light as the reference standard. There were no significant differences in adenoma miss rates between

the NBI and the white-light techniques (12.6% vs 12.1%).14 In a small pilot study, 47 patients found to have neoplastic lesions during high-definition white-light colonoscopy underwent colonoscopy with NBI. The results of the first examination were blinded from the colonoscopist. NBI detected more lesions, particularly lesions in the right colon and flat lesions than high definition white-light colonoscopy.16 Blinding of endoscopists is not feasible in these studies. The disparity in results from randomized controlled trials and back-to-back studies may be attributed to several factors. Because of the difference in study methodology Ulixertinib clinical trial (Table 1), it is difficult to make direct comparison between tandem studies with the four randomized controlled studies. The use of high-definition monitors for white-light

endoscopy in Rex and Helbig’s study can potentially improve adenoma detection compared with standard monitor. Other confounding factors include differences in NBI systems and experience of colonoscopists. There is likely to be a learning curve with NBI for adenoma detection. learn more Behavior of colonoscopists may also be different when screening high-risk patients with a more thorough examination, particularly when looking for small lesions. Overall, pooled analysis showed that NBI was only marginally better than white-light endoscopy for adenoma detection.18 Patients with longstanding ulcerative colitis have an increased risk of developing colorectal cancer. In the only randomized crossover study of NBI in ulcerative colitis surveillance, NBI was not better than white-light endoscopy in dysplasia detection, although this study utilized an early NBI prototype system that was much darker than those currently available.15 The background inflammation in some patients with inflammatory bowel disease may potentially negate NBI contrast enhancement for hypervascular dysplastic lesions. A more positive report indicated that a third-generation NBI prototype plus magnification could reveal fine superficial vessels with increased diameter and densities as seen in neoplastic lesions compared with normal nucosa.

During the second pass, the cecum was reintubated and the same colonic segment was re-examined with NBI, and additional polyps were photographed and removed. In the back-to-back study

I-BET-762 purchase by East et al. in surveillance for hereditary non-polyposis cancer syndrome (HNPCC) patients, the number of adenomas detected on NBI almost doubled when performed by endoscopists who had experience with at least 100 colonoscopies with NBI.17 In a randomized tandem colonoscopy trial, 276 patients were randomized to undergo colonoscopy using NBI or white-light examination. All patients then underwent a second colonoscopy using white light as the reference standard. There were no significant differences in adenoma miss rates between

the NBI and the white-light techniques (12.6% vs 12.1%).14 In a small pilot study, 47 patients found to have neoplastic lesions during high-definition white-light colonoscopy underwent colonoscopy with NBI. The results of the first examination were blinded from the colonoscopist. NBI detected more lesions, particularly lesions in the right colon and flat lesions than high definition white-light colonoscopy.16 Blinding of endoscopists is not feasible in these studies. The disparity in results from randomized controlled trials and back-to-back studies may be attributed to several factors. Because of the difference in study methodology R788 datasheet (Table 1), it is difficult to make direct comparison between tandem studies with the four randomized controlled studies. The use of high-definition monitors for white-light

endoscopy in Rex and Helbig’s study can potentially improve adenoma detection compared with standard monitor. Other confounding factors include differences in NBI systems and experience of colonoscopists. There is likely to be a learning curve with NBI for adenoma detection. check details Behavior of colonoscopists may also be different when screening high-risk patients with a more thorough examination, particularly when looking for small lesions. Overall, pooled analysis showed that NBI was only marginally better than white-light endoscopy for adenoma detection.18 Patients with longstanding ulcerative colitis have an increased risk of developing colorectal cancer. In the only randomized crossover study of NBI in ulcerative colitis surveillance, NBI was not better than white-light endoscopy in dysplasia detection, although this study utilized an early NBI prototype system that was much darker than those currently available.15 The background inflammation in some patients with inflammatory bowel disease may potentially negate NBI contrast enhancement for hypervascular dysplastic lesions. A more positive report indicated that a third-generation NBI prototype plus magnification could reveal fine superficial vessels with increased diameter and densities as seen in neoplastic lesions compared with normal nucosa.

81; 95% CI 0.55-0.93). Conclusion: The findings illustrate a spatial variation in HCV exposure in Egypt. The observed clustering was suggestive of an array of iatrogenic

risk factors, besides past PAT exposure, and ongoing transmission. The role of PAT exposure in the HCV epidemic could have been overstated. Our findings support the rationale for spatially prioritized interventions. (Hepatology 2014;60:1150–1159) “
“In addition to its function as a neurotransmitter and vascular active molecule, serotonin is also a mitogen for hepatocytes and promotes liver regeneration. A possible role in hepatocellular cancer has not yet been investigated. Human hepatocellular cancer cell lines Huh7 and HepG2 were used to assess the

function of serotonin in these cell lines. Characteristics learn more of autophagy were detected with transmission electron microscopy, immunoblots of microtubule-associated protein light chain 3(LC3) and p62 (sequestosome 1). Immunoblots of the mammalian target of rapamycin (mTOR) and its downstream targets p70S6K and 4E-BP1 were used to investigate Selleckchem Pictilisib signaling pathways of serotonin. Two different animal models served as principle of proof of in vitro findings. Clinical relevance of the experimental findings was evaluated with a tissue microarray from 168 patients with hepatocellular carcinoma. Serotonin promotes tumor growth and survival in starved hepatocellular carcinoma cells. During starvation hepatocellular carcinoma cells exhibited characteristics of autophagy, which disappeared in serotonin-treated cells. Rapamycin, an inhibitor of mTOR, is known to induce autophagy. Serotonin could override rapamycin by an mTOR-independent pathway and activate common selleck kinase inhibitor downstream signals such as p70S6K and 4E-BP1. In two tumor models of the mouse, inhibition of serotonin signaling consistently impaired tumor growth. Human biopsies revealed expression of the serotonin receptor HTR2B, correlating with downstream signals,

e.g., phosphorylated p70S6K and proliferation. Conclusion: This study provides evidence that serotonin is involved in tumor growth of hepatocellular cancer by activating downstream targets of mTOR, and therefore serotonin-related pathways might represent a new treatment strategy. (HEPATOLOGY 2010.) Serotonin (5HT), a well-known neurotransmitter and vasoactive substance, also regulates a wide range of physiological actions in the gastrointestinal tract.1 5HT is a potent mitogen for many different cell types,2 including hepatocytes,3 and it is crucial for liver regeneration.4 On a cellular level 5HT acts predominately by way of G-protein-coupled receptors (GPCRs). Seven receptor classes including 14 subtypes of 5HT receptors (HTR) reflect the diversity of serotonergic actions.

81; 95% CI 0.55-0.93). Conclusion: The findings illustrate a spatial variation in HCV exposure in Egypt. The observed clustering was suggestive of an array of iatrogenic

risk factors, besides past PAT exposure, and ongoing transmission. The role of PAT exposure in the HCV epidemic could have been overstated. Our findings support the rationale for spatially prioritized interventions. (Hepatology 2014;60:1150–1159) “
“In addition to its function as a neurotransmitter and vascular active molecule, serotonin is also a mitogen for hepatocytes and promotes liver regeneration. A possible role in hepatocellular cancer has not yet been investigated. Human hepatocellular cancer cell lines Huh7 and HepG2 were used to assess the

function of serotonin in these cell lines. Characteristics Ribociclib research buy of autophagy were detected with transmission electron microscopy, immunoblots of microtubule-associated protein light chain 3(LC3) and p62 (sequestosome 1). Immunoblots of the mammalian target of rapamycin (mTOR) and its downstream targets p70S6K and 4E-BP1 were used to investigate BMS-354825 signaling pathways of serotonin. Two different animal models served as principle of proof of in vitro findings. Clinical relevance of the experimental findings was evaluated with a tissue microarray from 168 patients with hepatocellular carcinoma. Serotonin promotes tumor growth and survival in starved hepatocellular carcinoma cells. During starvation hepatocellular carcinoma cells exhibited characteristics of autophagy, which disappeared in serotonin-treated cells. Rapamycin, an inhibitor of mTOR, is known to induce autophagy. Serotonin could override rapamycin by an mTOR-independent pathway and activate common learn more downstream signals such as p70S6K and 4E-BP1. In two tumor models of the mouse, inhibition of serotonin signaling consistently impaired tumor growth. Human biopsies revealed expression of the serotonin receptor HTR2B, correlating with downstream signals,

e.g., phosphorylated p70S6K and proliferation. Conclusion: This study provides evidence that serotonin is involved in tumor growth of hepatocellular cancer by activating downstream targets of mTOR, and therefore serotonin-related pathways might represent a new treatment strategy. (HEPATOLOGY 2010.) Serotonin (5HT), a well-known neurotransmitter and vasoactive substance, also regulates a wide range of physiological actions in the gastrointestinal tract.1 5HT is a potent mitogen for many different cell types,2 including hepatocytes,3 and it is crucial for liver regeneration.4 On a cellular level 5HT acts predominately by way of G-protein-coupled receptors (GPCRs). Seven receptor classes including 14 subtypes of 5HT receptors (HTR) reflect the diversity of serotonergic actions.

In response to LPS, NICD1 translocates to mitochondria as demonstrated by confocal and electron microscopy, and enriches at the mtDNA D-loop comprising promoters of mitochondria genome as assessed by ChlP. Finally, systemic administration of DAPT attenuates Nos2 upregulation, nitrosative stress, and ASH in the model. [Conclusion] Our findings reveal a novel mechanism of MO M1 activation in ASH, which involves Notch activation buy Midostaurin to shift metabolism to glucose oxidation through induction of mtDNA and nuclear genes encoding mitochondrial complex proteins and consequent generation of mtROS enhancing M1 Nos2 activation. Disclosures: Hidekazu īsukamoto – Consulting: Shionogi & Co.,

S. P. Pharmaceutics; Grant/Research Support: The Toray

Co. The following people have nothing to disclose: Jun Xu, Feng Chi, Samuel W. French Background: Danger signals released from damaged cells trigger inflammatory response and tissue injury. N〇D-like receptors, such as NLRP3, are intracellular sensors of danger signals that activate the inflammasome, an intracellular complex which converts pro-interleukin (IL)−1β into mature IL-1β and perpetuates inflammation. Inflammasomes and IL-1β are key determinants of alcoholic liver disease (ALD), but the signals driving their activation are yet to be identified. CCI-779 chemical structure Aim: To determine the role of danger signals in activation of inflammasomes and IL-1β in ALD. Methods: We co-cultured primary hepatocytes with macrophages in vitro, or fed Lieber-DeCarli ethanol (EtOH) diet to wild-type (WT), ATp receptor 2×7 (P2rx7)- or NLRP3-deficient (KO) mice, and to two strains of transgenic mice overexpressing uricase (UOX-Tg). Some mice were treated with probenecid or allopurinol. Results: Administration of EtOH to WT mice caused hepatocyte damage and inflammasome selleck kinase inhibitor activation in the liver. Co-culture experiments revealed that damaged hepatocytes release signals that drive inflammasome activation and IL-1 β release in liver immune cells and identified extracellular adenosine triphosphate (ATP) as a mediator of this cross-talk.

Administration of EtOH to mice, or treatment of hepatocytes with EtOH resulted in extracellular ATP release. Absence of ATP receptors in P2rx7-K〇 mice or inhibition of ATP signaling in mice treated with probenecid prevented inflammasome activation in the liverand attenuated ALD. In addition to blocking ATP signaling, probenecid also depletes uric acid, another endogenous molecule released upon tissue injury. Indeed, we observed significantly increased hepatocyte-derived uric in vitro and in vivo, and found that depletion of uric acid in UOX-Tg mice or inhibition of uric acid synthesis with allopurinol prevented inflammasome activation and attenuated ALD. As the protection from ALD in P2rx7-K〇 or in UOX-Tg mice was substantial, yet incomplete, we asked whether ATP and uric acid activated inflammasomes in a complementary fashion.

Thirty-two full contour Y-TZP (Diazir®) specimens (hereafter referred to as zirconia sliders) (ϕ = 2 mm, 1.5 mm in height) were fabricated

using CAD/CAM and sintered according to the manufacturer’s instructions. Zirconia sliders were embedded in brass holders using acrylic resin and then randomly assigned (n = 16) according to the surface treatment received, that is, as-machined or glazed. Glass-ceramic antagonists, Empress/EMP and e.max/EX, were cut into tabs (13 × 13 × 2 mm3), wet-finished, and similarly embedded in brass holders. Two-body pin-on-disk wear testing was performed at 1.2 Hz for 25,000 cycles under a 3 kg load. Noncontact profilometry was used to measure antagonist height (μm) and volume loss (mm3). Qualitative data of the Sirolimus mouse zirconia testing surfaces and wear tracks were obtained using SEM. Statistics ICG-001 price were performed using ANOVA with a significance level of 0.05. As-machined yielded significantly higher mean roughness values (Ra = 0.83 μm, Rq = 1.09 μm) than glazed zirconia

(Ra = 0.53 μm, Rq = 0.78 μm). Regarding glass-ceramic antagonist loss, as-machined zirconia caused significantly less mean height and volume loss (68.4 μm, 7.6 mm3) for EMP than the glazed group (84.9 μm, 9.9 mm3), while no significant differences were found for EX. Moreover, EMP showed significantly lower mean height and volume loss than EX (p < 0.0001). SEM revealed differences on wear characteristics between the glass-ceramics tested. e.max wear was not affected by zirconia surface roughness; however, Empress wear was greater when opposing

glazed zirconia. Overall, surface glazing on full-contour zirconia did not minimize glass-ceramic wear when compared with as-machined zirconia. “
“This study evaluated the fatigue behavior of three fixed partial dentures (FPDs) before and after artificial fatigue testing. Sixty, three-unit zirconia-ceramic (ZC), galvano-ceramic (GC), and porcelain-fused-to-metal (PFM) FPDs (N = 20) were fabricated. Ten specimens from each group were exposed to fatigue testing by being thermocycled (5 to 55°C, 10,000 cycles) and loaded (100,000 cycles, 50 N, 0.5 Hz). All specimens were then subjected to occlusal loading in a universal testing machine until fracture. selleck chemicals The fractures were characterized using scanning electron microscopy. Data were analyzed using one-way ANOVA followed by Tukey’s significant difference post hoc test and the paired t-test. The chi-squared test was used to evaluate the type of fracture (α = 0.05). The mean fracture loads of non-fatigued and fatigued specimens for ZC were 2434.9 ± 154.3 and 2333.1 ± 183.0 N, respectively; for GC were 1678.1 ± 211.6 and 1475.8 ± 227.9 N, respectively; and 1878.5 ± 176.5 and 1687.8 ± 162.2 N, respectively, for PFM restorations. Significant differences were observed between fatigued and non-fatigued specimens of both the GC group and PFM group (p < 0.05), but not between fatigued and non-fatigued ZC specimens (p > 0.05).

Viability assays confirmed that these treatments did not significantly alter

selleckchem endothelial viability after 4 hours of treatment. WT mice and VAP-1–deficient mice (C57BL/6) expressing enzymatically active or inactive hVAP-1 on the endothelial cells under the control of the mouse tie 1 promoter have been described,24 and they were used to study the role of VAP-1 in MAdCAM-1 induction in vivo. All mice were handled in accordance with the institutional animal care policy of the University of Turku. MA [0.4% (wt/vol)] was administered in the drinking water of the animals (freshly made every day) for 14 days. After the mice were sacrificed, tissue samples from PPs and MLNs were excised and used for protein and RNA analysis. In order to study MAdCAM-1 induction in the intact

selleck products human liver, we used a Krumdieck tissue slicer (TCS Biologicals) to cut aseptic, 250-μm-thick slices of live liver tissue, which could be studied for up to 48 hours ex vivo. The liver tissue was incubated in Williams’ E media (Sigma) supplemented with 2% FBS, 0.1μM dexamethasone (Sigma), and 0.5μM insulin (Novo-Nordisk). Tissues were stimulated with MA (50 μM) and enzymatically active recombinant vascular adhesion protein 1 (rVAP-1) produced in Chinese hamster ovary cells (500 ng/mL; Biotie Therapies, Turku, Finland) before MAdCAM-1 protein and RNA analysis. The viability of the excised tissue slices was tested with a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay (Sigma) before and after the stimulation period (details are provided in the Supporting Information Materials

and Methods). Total RNA was extracted with the RNeasy mini Kit click here (Qiagen, United Kingdom) and analyzed as described in the Supporting Information Materials and Methods. MAdCAM-1 protein expression was determined by western blotting and immunoprecipitation techniques. The protocols and antibodies are described in the Supporting Information Materials and Methods. Multicolor fluorescence confocal microscopy was used to localize the expression of MAdCAM-1 in HECs. MAdCAM-1 expression in human liver tissue was investigated in formalin-fixed, sucrose-embedded tissues with NovaRED immunostaining. The presence of murine MAdCAM-1 in PPs and MLNs was examined by immunofluorescence. The protocols and antibodies are described in the Supporting Information Materials and Methods and Supporting Information Table 3. Formalin-fixed, sucrose-embedded sections (10 μm thick) were incubated with JY cells and PBLs from PSC patients (n = 3) for 30 minutes at room temperature. In certain experiments, tissue sections were incubated with an anti–MAdCAM-1 antibody (P1; 1 μg/mL; Pfizer), and JY cells and PBLs were blocked with anti-α4β7 [actin 1 (ACT-1); 1 μg/mL; a gift from M.

Both forms of MAVS, FL and cleaved, were detected in liver biopsy specimens from patients with CHC, whereas only FL MAVS was detected in controls (Fig. 1A, B). For all analyses, signal intensities of FL and cleaved MAVS were normalized to β-actin. The percentage of MAVS cleavage (cleaved/total MAVS × 100) varied widely among the

129 CHC patients, ranging from 0 to 76% (mean, 18%; standard deviation 21%) (Fig. 1B). Cleavage of MAVS was detected in 62 of the 129 patients (48%), and the percentage of cleavage in these 62 patients showed a normal distribution ranging from 7% to 76% (mean, 37%; standard deviation 16%). Only FL MAVS was detected in the remaining 67 patients. Because only the FL form of MAVS is functional, and because it is KU-57788 manufacturer unknown whether and how fast the cleaved MAVS product is degraded in PI3K inhibitors in clinical trials cells, we also performed all our analyses using the FL MAVS/beta-actin signal intensity ratio. The amount of FL MAVS showed strong negative correlation with the percentage of cleaved MAVS (Spearman r =-0.57, P < 0.0001; data not shown). There was a wide variation in the amount of functional FL MAVS within both the CHC and control patient groups (Fig. 1C), with the

median value being significantly lower in CHC compared with control samples (0.48 versus 0.77; P = 0.0007). Immunoblotting with the polyclonal MAVS antiserum AT107 yielded results similar to those obtained with mAb IID12 (Adri 1) (data not shown). We conclude that HCV-induced cleavage of MAVS reduces the amount of the functional FL MAVS in a considerable proportion of patients with CHC. Cleavage of MAVS was independent from the Metavir activity grade or fibrosis score (data not shown). All investigated HCV GTs were able to cleave MAVS. Samples from patients infected with the easier-to-treat GTs 2 or 3 had significantly lower

amounts of FL MAVS compared with the difficult-to-treat GTs 1 and 4 (P = 0.009; Fig. 1D). There was no significant difference between GT 2/3 and GT 1/4 patients with respect to viral load (VL), Metavir activity grade, or fibrosis score. Therefore, the difference most likely reflects different intrinsic properties of HCV GTs with respect to MAVS cleavage. Because in vitro studies demonstrated a very check details efficient cleavage of MAVS by the HCV NS3-4A protease,8, 16, 20 we assessed whether patients with a high VL show more MAVS cleavage in the liver. Indeed, there was a weak but statistically significant inverse correlation between the amount of FL MAVS and serum VL (Spearman r =-0.22, P = 0.011; Fig. 2A) and a strong positive correlation between the percentage of cleaved MAVS and serum VL (Spearman r = 0.53, P < 0.0001; Fig. 2B). The correlation remained significant when only the 62 samples with some detectable degree of MAVS cleavage were included in the analysis (Fig. 2C).

Both forms of MAVS, FL and cleaved, were detected in liver biopsy specimens from patients with CHC, whereas only FL MAVS was detected in controls (Fig. 1A, B). For all analyses, signal intensities of FL and cleaved MAVS were normalized to β-actin. The percentage of MAVS cleavage (cleaved/total MAVS × 100) varied widely among the

129 CHC patients, ranging from 0 to 76% (mean, 18%; standard deviation 21%) (Fig. 1B). Cleavage of MAVS was detected in 62 of the 129 patients (48%), and the percentage of cleavage in these 62 patients showed a normal distribution ranging from 7% to 76% (mean, 37%; standard deviation 16%). Only FL MAVS was detected in the remaining 67 patients. Because only the FL form of MAVS is functional, and because it is Quizartinib concentration unknown whether and how fast the cleaved MAVS product is degraded in Sotrastaurin price cells, we also performed all our analyses using the FL MAVS/beta-actin signal intensity ratio. The amount of FL MAVS showed strong negative correlation with the percentage of cleaved MAVS (Spearman r =-0.57, P < 0.0001; data not shown). There was a wide variation in the amount of functional FL MAVS within both the CHC and control patient groups (Fig. 1C), with the

median value being significantly lower in CHC compared with control samples (0.48 versus 0.77; P = 0.0007). Immunoblotting with the polyclonal MAVS antiserum AT107 yielded results similar to those obtained with mAb IID12 (Adri 1) (data not shown). We conclude that HCV-induced cleavage of MAVS reduces the amount of the functional FL MAVS in a considerable proportion of patients with CHC. Cleavage of MAVS was independent from the Metavir activity grade or fibrosis score (data not shown). All investigated HCV GTs were able to cleave MAVS. Samples from patients infected with the easier-to-treat GTs 2 or 3 had significantly lower

amounts of FL MAVS compared with the difficult-to-treat GTs 1 and 4 (P = 0.009; Fig. 1D). There was no significant difference between GT 2/3 and GT 1/4 patients with respect to viral load (VL), Metavir activity grade, or fibrosis score. Therefore, the difference most likely reflects different intrinsic properties of HCV GTs with respect to MAVS cleavage. Because in vitro studies demonstrated a very click here efficient cleavage of MAVS by the HCV NS3-4A protease,8, 16, 20 we assessed whether patients with a high VL show more MAVS cleavage in the liver. Indeed, there was a weak but statistically significant inverse correlation between the amount of FL MAVS and serum VL (Spearman r =-0.22, P = 0.011; Fig. 2A) and a strong positive correlation between the percentage of cleaved MAVS and serum VL (Spearman r = 0.53, P < 0.0001; Fig. 2B). The correlation remained significant when only the 62 samples with some detectable degree of MAVS cleavage were included in the analysis (Fig. 2C).

05). Thirst, pollakiuria were the main observed adverse drug reactions, and thirst could be improved by drinking water. Conclusion: Tolvaptan can effectively increase cirrhosis ascites patients’ 24-hour urine volume, decrease abdominal circumference by administering

15 mg once daily for 5 days, without renal function damage. Also, serum sodium, serum potassium, plasma colloid osmatic pressure can be improved in a steady process. So, it is a great option for those cirrhosis patients accompany with hyponatremia and hepatorenal symdrome. Key Word(s): 1. Tolvaptan; 2. cirrhosis ascites; 3. efficacy; 4. ACP-196 chemical structure safety; Presenting Author: YANJIE CHEN Additional Authors: JIMIN X-396 ZHU, HAO WU, JIA FAN, JIAN ZHOU, JIE HU, QIAN YU, TAOTAO LIU, LEI YANG, CHUNLEI WU, XIAOLING GUO, XIAOWU HUANG, XIZHONG SHEN Corresponding Author: XIAOWU HUANG, XIZHONG SHEN Affiliations: Department of Gastroenterology, Zhongshan Hospital of Fudan University; Liver Cancer Institute, Zhongshan Hospital of Fudan University; Department of Statistics, School of Public Health of Fudan University; Department of Molecular and Experimental Medicine, The Scripps Research Institute Objective: Sensitive and specific detection of liver cirrhosis is an urgent need for

optimal individualized management of disease activity. Substantial studies have identified circulation miRNAs as biomarkers for diverse diseases including chronic liver diseases. In this study, we investigated the plasma miRNA signature

to serve as a potential diagnostic biomarker for silent liver cirrhosis. Methods: A see more genome-wide miRNA microarray was first performed in 80 plasma specimens. Six candidate miRNAs were selected and then trained in CHB-related cirrhosis and controls by qPCR. A classifier, miR-106b and miR-181b, was validated finally in two independent cohort including CHB-related silent cirrhosis and controls, as well as non–CHB-related cirrhosis and controls as validation sets, respectively. Results: A profile of 2 miRNAs (miR-106b and miR-181b) was identified as liver cirrhosis biomarkers irrespective of etiology. The classifier constructed by the two miRNAs provided a high diagnostic accuracy for cirrhosis (AUC = 0.882 for CHB-related cirrhosis in the training set, 0.774 for CHB-related silent cirrhosis in one validation set, and 0.915 for non–CHB-related cirrhosis in another validation set). Conclusion: Our study demonstrated that the combined detection of miR-106b and miR-181b has a considerable clinical value to diagnose patients with liver cirrhosis, especially those at early stage. Key Word(s): 1. biomarker; 2. miR-106b; 3. miR-181b; 4.