NF-κB is the central transcriptional regulator of inflammatory an

NF-κB is the central transcriptional regulator of inflammatory and immune responses.39 Constitutive NF-κB activation has been implicated in the malignant progression of numerous human inflammatory

diseases, metabolic diseases, cancers, and diabetes.40 Inhibiting the aberrant activation of NF-κB signaling can slow down or stop these disease processes.41, 42 In this study, our analysis results of inflammatory gene expression revealed that TGR5 has anti-inflammatory properties in the mouse liver. Our data show that TGR5 activation prevents the phosphorylation of IκBα, nuclear translocation of p65, and NF-κB DNA-binding activity. Activation of NF-κB in Kupffer cells promotes liver cancer development through IL-6 and liver-inflammatory responses.43 Blockage of NF-κB by deletion of GSK3235025 IKKβ in Kupffer cells, in addition to hepatocytes, strongly inhibited diethylnitrosamine-induced HCC development.43 Thus, the suppression of NF-κB might be a therapeutical strategy for treating liver cancer, because the loss of NF-κB in Kupffer cells might suppress cancer. TGR5 is highly expressed in Kupffer cells of the liver.13, 14 In this study, we demonstrated that TGR5 activation is able to strongly suppress NF-κB-induced Mitomycin C supplier inflammation in vitro and in vivo, which suggests that TGR5 may be a

desirable therapeutic target for liver cancer treatment. It has been reported that TGR5 could be a potential target for the treatment of diabesity and associated metabolic disorders.10, 12, 44, 45 For example, Watanabe et al. reported that TGR5 activation by bile acids induces energy expenditure in muscle and brown adipose tissue.10 Thomas et al. found that TGR5 activation improves glucose tolerance and insulin sensitivity in fat-fed mice.12 These diseases, such as obesity, insulin resistance, and type 2 diabetes, are also closely associated with chronic inflammation, characterized by abnormal cytokine production, increased acute-phase reactants, and activation of a network of inflammatory signaling pathways.4,

46, 47 Inhibition of NF-κB-related inflammation is able to improve glucose metabolism in vivo.48, 49 Here, our data show that TGR5 is a negative modulator of NF-κB-mediated inflammation. Therefore, there is a potential link between anti-inflammation and Sclareol treatment of obesity and diabetes through TGR5. TGR5 may be an attractive therapeutic target for metabolic disorders through not only regulation of energy and glucose homeostasis, but also suppression of NF-κB signaling. In conclusion, our results reveal that TGR5 is a negative regulator of NF-κB-mediated hepatic inflammation, and indicate that TGR5 ligands have utility in anti-inflammation. These findings suggest that TGR5 is a potential target for anti-inflammatory drug design, and its agonist ligands offer possible therapies to prevent and treat inflammatory liver diseases. The authors thank Dr.

NF-κB is the central transcriptional regulator of inflammatory an

NF-κB is the central transcriptional regulator of inflammatory and immune responses.39 Constitutive NF-κB activation has been implicated in the malignant progression of numerous human inflammatory

diseases, metabolic diseases, cancers, and diabetes.40 Inhibiting the aberrant activation of NF-κB signaling can slow down or stop these disease processes.41, 42 In this study, our analysis results of inflammatory gene expression revealed that TGR5 has anti-inflammatory properties in the mouse liver. Our data show that TGR5 activation prevents the phosphorylation of IκBα, nuclear translocation of p65, and NF-κB DNA-binding activity. Activation of NF-κB in Kupffer cells promotes liver cancer development through IL-6 and liver-inflammatory responses.43 Blockage of NF-κB by deletion of PD0325901 datasheet IKKβ in Kupffer cells, in addition to hepatocytes, strongly inhibited diethylnitrosamine-induced HCC development.43 Thus, the suppression of NF-κB might be a therapeutical strategy for treating liver cancer, because the loss of NF-κB in Kupffer cells might suppress cancer. TGR5 is highly expressed in Kupffer cells of the liver.13, 14 In this study, we demonstrated that TGR5 activation is able to strongly suppress NF-κB-induced CX-4945 inflammation in vitro and in vivo, which suggests that TGR5 may be a

desirable therapeutic target for liver cancer treatment. It has been reported that TGR5 could be a potential target for the treatment of diabesity and associated metabolic disorders.10, 12, 44, 45 For example, Watanabe et al. reported that TGR5 activation by bile acids induces energy expenditure in muscle and brown adipose tissue.10 Thomas et al. found that TGR5 activation improves glucose tolerance and insulin sensitivity in fat-fed mice.12 These diseases, such as obesity, insulin resistance, and type 2 diabetes, are also closely associated with chronic inflammation, characterized by abnormal cytokine production, increased acute-phase reactants, and activation of a network of inflammatory signaling pathways.4,

46, 47 Inhibition of NF-κB-related inflammation is able to improve glucose metabolism in vivo.48, 49 Here, our data show that TGR5 is a negative modulator of NF-κB-mediated inflammation. Therefore, there is a potential link between anti-inflammation and Oxymatrine treatment of obesity and diabetes through TGR5. TGR5 may be an attractive therapeutic target for metabolic disorders through not only regulation of energy and glucose homeostasis, but also suppression of NF-κB signaling. In conclusion, our results reveal that TGR5 is a negative regulator of NF-κB-mediated hepatic inflammation, and indicate that TGR5 ligands have utility in anti-inflammation. These findings suggest that TGR5 is a potential target for anti-inflammatory drug design, and its agonist ligands offer possible therapies to prevent and treat inflammatory liver diseases. The authors thank Dr.

It plays an important role in the process of maturity and differe

It plays an important role in the process of maturity and differentiation of B cells. There are not available that BAFF expression and the predictive value on treatment outcome in patients with ZD1839 chronic hepatitis C (CHC). Methods: 175 CHC patients were enrolled with PEG-IFNα-2a (180 μg, qw) / RBV (800-1200mg/d) treatment for at least 12w. IL28B SNP rs12979860 and rs8099917 and HCV genotype were detected

at baseline, while serum ALT, AST, TBIL, HCV RNA loads and BAFF levels were detected before and 4w, 12w after treatment. BAFF levels were assessed on 58 health blood donors (HBD). To compare BAFF levels among these three groups, and analyze predictors to RVR in patients after antivirus treatments. Results: 1.BAFF levels in patients with RVR (median 2400.0pg/ml) were higher than that in patients without (median 1731.6pg/ml) and than that in HBD (median 1095.9pg/ml), successively, P<0.05. The lowest BAFF level was 724pg/ml in this study. 2. HCV genotype, IL28BSNP rs12979860 and rs8099917 genotype, HCV RNA and BAFF baseline were included in the logistic regression analysis

and ROC was drawn to evaluate predict value of BAFF to RVR. After calculation IL28B SNP rs12979860 genotype and BAFF become influence factors to RVR. This was a logistic regression equation: Y=2.427-0.001 xBAFF-2.013×lL28BSNP rs12979860 (coded CC Genotype as 1 and non-CC as 0, Y=0.3614 according to the ROC cut-off point) . If a patient with CC genotype or non-CC genotype whose BAFF baseline were above L-gulonolactone oxidase 52.5pg/ml or 2065.5pg/ml, the AUROC achieved 79.6% (Figure 1). Conclusions: 1. BAFF expression Z-VAD-FMK purchase in patients with hepatitis C-infected is higher than HBD.

2. BAFF is a predictor to RVR in patients with IL28BSNP rs12979860 non-CC genotype after antivirus therapy. There is higher RVR rate in patients with CC genotype regardless of others indexes. Figure l: ROC curve in prediction on BAFF to 1^ R after logistic regression analysis-Note: AUROC curve values (95% CI) were 0.796(0.684-0.908), cut-off point is 0.361, sensitivity is 0.904, specificity is 0-696, negative predictive value is 0.762,.P=0.000 Disclosures: The following people have nothing to disclose: Jing Liu, Zhen Xu, Wen-Xiong Xu, Zhi-Shuo Mo, Xiang Zhu, Zhi-liang Gao Although recent studies indicate that supplementation of vitamin D significantly improves a sustained viral response by IFN-based therapy to chronic hepatitis C, detailed mechanisms for the role of vitamin D are not fully elucidated. Previously, we demonstrated that the metabolite of vitamin D, 25-hydroxyvita-min D, has the direct anti-viral effect against hepatitis C virus (HCV) targeting infectious virus production. Since vitamin D is known to be multi-functional, we reasoned that other anti-viral functions of vitamin D, especially through immunomodulatory activity, should be considered.

Strikingly, some of the HCV-mediated mitochondrial dysfunctions c

Strikingly, some of the HCV-mediated mitochondrial dysfunctions could even be rescued by alisporivir. Conclusion:

These observations provide new insights into the pathogenesis of HCV-related liver disease and reveal an additional mechanism of action of alisporivir that is likely beneficial in the treatment of chronic hepatitis C. (HEPATOLOGY 2012) Hepatitis C virus (HCV)-related liver disease represents a major health burden worldwide.1 Treatment with pegylated interferon-α and ribavirin has limited efficacy and numerous adverse effects.2 While a first generation of directly acting antivirals have entered clinical application, targeting host factors essential for the HCV life cycle represents an attractive alternative therapeutic approach. In this context, non-immunosuppressive analogues of the cyclophilin (Cyp) inhibitor cyclosporine A (CsA) represent a new class selleckchem of potent anti-HCV agents,3 with efficacy both in vitro as well as in clinical studies in patients with chronic hepatitis C.4-6 Alisporivir (also known as Debio-025 or DEB025) is the prototype and most advanced molecule in this novel class of antivirals. It efficiently inhibits Cyps but, unlike CsA, does click here not interact with calcineurin, explaining the lack of immunosuppressive effect.7 At least 16 Cyp isoforms are expressed in

human cells, and these are involved in diverse cellular processes and pathways, many of which may influence the HCV life cycle.8 The respective roles of Cyp isoforms in the HCV life cycle remains controversial. However, the peptidyl-prolyl cis-trans isomerase activity of cyclophilin A (CypA)

is crucial for HCV replication, and its inhibition mediates the antiviral activity of alisporivir.9, 10 CypA may interact with different viral proteins and favor a particular conformation that is required for efficient viral replication find more and/or could have a role in facilitating the processing of the HCV polyprotein.3 Cyclophilin D (CypD) is a member of the family that has been receiving growing attention because of its role in controlling cell fate.11 It is localized within the mitochondrial matrix and interacts with the mitochondrial permeability transition pore (MPTP), sensitizing its opening by physiological inducers.12, 13 Activation of the MPTP allows the rapid passage of low molecular weight molecules and ions (up to 1.5 kDa) and, when persistent, the release of proapoptotic mitochondrial intermembrane proteins, i.e., proteins located between the outer and inner mitochondrial membranes.12 This last event, whose mechanism has not yet been completely clarified, induces adaptive cellular responses that can lead to mitophagy, apoptosis, or necrotic cell death.

Conclusion: Insulin, promotes HepaRG-hepatocyte differentiation a

Conclusion: Insulin, promotes HepaRG-hepatocyte differentiation and proliferation, however maintained high levels of signaling through this pathway impair maturation and lead to aberrant lipid accumulation. These results may facilitate refinement of current strategies designed to produce mature cells from various progenitor sources in vitro. Disclosures: The following people have nothing to disclose: Luke A. Noon, Alicia MartinezRomero, Jose E. O’Connor, Talazoparib Anne Comlu, Pascale Bouillé, Christiane Guillouzco, Deborah J. Burks Aim: To assess the utility of autologous mesenchymal stem cells (MSCs) peripheral vein infusion as a possible therapeutic modality and to confirm the supportive role of the stem

cell (SC) treatment for patients with end-stage liver diseases Methods: Forty patients with post-HCV end-stage liver diseases were randomized into 2 groups. Group 1, comprising 20 patients

and they have received granulocyte colony stimulating factor (GCSF) for 5 days followed by autologous MSC peripheral veins infusion. Group 2, comprising 20 patients and they have received regular liver supportive treatment and have served as Tofacitinib order a control group. Results: In the infused group (Gr. I), There was near normalization of liver enzymes and improvement in liver synthetic function (S. Albumin, Prothrombin time and concentration) in 54%. There was significant changes in albumin (p=0.000), bilirubin (p=0.002), INR (p=0.017), prothrombin conc. (p=0.029), AST (p=0.156) and ALT levels (p=0.029). Also, in Gr. I, there Methocarbamol was stabilization of the clinical and biochemical status in 13% of cases. None of the patients in the control group (Gr. II) showed any significant improvement. Hepatic fibrosis was assessed in the treated group by detection of procollagen Ill C peptide level (PIIICP) (9.4 ± 4.2) and procollagen Ill N peptide level (PIIINP) (440 ± 189) (Pre treatment Value) in the patients’ serum. It was reported a decrease in the level of PIIICP (8.1 ± 2.6) and PIIINP (388 ± 102) after stem cell therapy (three months treatment Value) but they have not reached the significant value (6

months treatment Value) (p=0.7), however there was a significant correlation coefficient after three months between the serum level of the PIIINP and prothrombin concentration (p=-0.5) and between the serum level of the PIIICP and ascites (p=0.550) Conclusion: Our data showed that autologous mesenchymal stem cells infusion into the peripheral veins was effective and showed the same result as intrahepatic infusion from our previous studies (Salama et al, 2011) and confirmed the supportive role of mesenchymal stem cell treatment for end-stage liver disease with satisfactory tolerability and beneficial effects on liver synthetic functions and hepatic fibrosis. We have also observed in this study that the serum albumin has been improved within the first two weeks and prothrombin concentration improvement was delayed for almost one month.

Conclusion: Insulin, promotes HepaRG-hepatocyte differentiation a

Conclusion: Insulin, promotes HepaRG-hepatocyte differentiation and proliferation, however maintained high levels of signaling through this pathway impair maturation and lead to aberrant lipid accumulation. These results may facilitate refinement of current strategies designed to produce mature cells from various progenitor sources in vitro. Disclosures: The following people have nothing to disclose: Luke A. Noon, Alicia MartinezRomero, Jose E. O’Connor, Apoptosis inhibitor Anne Comlu, Pascale Bouillé, Christiane Guillouzco, Deborah J. Burks Aim: To assess the utility of autologous mesenchymal stem cells (MSCs) peripheral vein infusion as a possible therapeutic modality and to confirm the supportive role of the stem

cell (SC) treatment for patients with end-stage liver diseases Methods: Forty patients with post-HCV end-stage liver diseases were randomized into 2 groups. Group 1, comprising 20 patients

and they have received granulocyte colony stimulating factor (GCSF) for 5 days followed by autologous MSC peripheral veins infusion. Group 2, comprising 20 patients and they have received regular liver supportive treatment and have served as check details a control group. Results: In the infused group (Gr. I), There was near normalization of liver enzymes and improvement in liver synthetic function (S. Albumin, Prothrombin time and concentration) in 54%. There was significant changes in albumin (p=0.000), bilirubin (p=0.002), INR (p=0.017), prothrombin conc. (p=0.029), AST (p=0.156) and ALT levels (p=0.029). Also, in Gr. I, there Buspirone HCl was stabilization of the clinical and biochemical status in 13% of cases. None of the patients in the control group (Gr. II) showed any significant improvement. Hepatic fibrosis was assessed in the treated group by detection of procollagen Ill C peptide level (PIIICP) (9.4 ± 4.2) and procollagen Ill N peptide level (PIIINP) (440 ± 189) (Pre treatment Value) in the patients’ serum. It was reported a decrease in the level of PIIICP (8.1 ± 2.6) and PIIINP (388 ± 102) after stem cell therapy (three months treatment Value) but they have not reached the significant value (6

months treatment Value) (p=0.7), however there was a significant correlation coefficient after three months between the serum level of the PIIINP and prothrombin concentration (p=-0.5) and between the serum level of the PIIICP and ascites (p=0.550) Conclusion: Our data showed that autologous mesenchymal stem cells infusion into the peripheral veins was effective and showed the same result as intrahepatic infusion from our previous studies (Salama et al, 2011) and confirmed the supportive role of mesenchymal stem cell treatment for end-stage liver disease with satisfactory tolerability and beneficial effects on liver synthetic functions and hepatic fibrosis. We have also observed in this study that the serum albumin has been improved within the first two weeks and prothrombin concentration improvement was delayed for almost one month.

Disease patterns vary in areas of differing endemicity and correl

Disease patterns vary in areas of differing endemicity and correlate with socioeconomic status and access to clean water and sanitation. In many parts of the world, economic development and improved sanitation and living standards have resulted in significant shifts in the acquisition of HAV infection from infancy and childhood to older ages.4 In developing countries, where infection is endemic, most persons are infected in early childhood when asymptomatic infection is likely. In developed

countries, where the incidence rate is lower, infection typically occurs at older ages when clinical symptoms become more apparent.5 Community-wide epidemics contribute significantly to the burden of disease in developed countries. In these settings, disease tends to occur http://www.selleckchem.com/products/KU-60019.html in circumscribed groups, such as travelers to hepatitis A endemic areas, or as outbreaks among high-exposure groups such as intravenous drug users or men who have sex with men.5-7 Prior to the introduction of vaccines against HAV in the United States, hepatitis A occurred as large nationwide epidemics approximately every 10 years. The last epidemic occurred during the mid-1990s and affected particularly adolescents and young adults,8 causing substantial morbidity and economic losses estimated at $489 million annually.9 Since the introduction of an HAV vaccine in 1995, the incidence of hepatitis

A has decreased markedly for all age groups; many however, an estimated 25,000 new infections still occurred in 2007.10 Approximately 50% of all reported signaling pathway hepatitis A cases have no specific risk factors identified.11 In cases where risk factors have been identified, the majority of adults

are international travelers, men who have sex with men, or intravenous drug users.6, 7 Host genetic factors have played an important role in determining the differential susceptibility to infectious diseases such as hepatitis B and C, malaria, HIV/AIDS, tuberculosis, and invasive pneumococcal disease.12 In outbreaks of hepatitis A, some people are infected while others remain uninfected after exposure, suggesting that people vary in their susceptibility to HAV infection.5, 6 However, to date, the number of studies of human genetic variation and HAV infection are few, except for two small candidate gene studies,13, 14 and twin studies showing that genetic factors accounted for ≈36% of the total variability in HAV-specific immune response to vaccination.15, 16 There are no reports investigating host genetic factors for hepatitis A in the United States population, though many public health researchers have focused on behavior, environment, and viral factors. Examining host factors may provide insight into pathogenesis and susceptibility to HAV infection and also help to identify and target high-risk populations for vaccination.

Important practicalities relevant to interpretation of reports on

Important practicalities relevant to interpretation of reports on biopsies from BE patients are www.selleckchem.com/products/3-methyladenine.html commonly poorly understood in routine clinical practice. The quality of surveillance endoscopy and decision-making on the need for intervention is frequently impaired by this poor understanding (Fig. 2). A terminological soup unfortunately adds to the interpretative challenge. This article uses the relatively simple terminology of low and high-grade dysplasia and EA for describing biopsy findings, an approach also used in the 1990 review.1 Other categories of dysplasia that have been and still may be used are “indefinite” and “moderate”, but

these are not usually considered useful by pathologists

working in centers with a special interest in BE.46,47 More recently, “low” and “high grade intraepithelial neoplasm” (LGIN and HGIN) have been introduced in the belief that they are technically better terms that are more Proteases inhibitor consistent with terminology used for other mucosae than “high” and “low grade dysplasia”, respectively. LGIN and HGIN are clumsy terms (like the growing use of “at this time”, instead of “now”), but more importantly, they are confusing for at least gastroenterologists. Probably, as a consequence, these terms are used by only a few, most being pathologists. Use of the abbreviations LGIN and HGIN is worse, Amino acid since they add to the already daunting code that burdens the understanding of BE-related matters. The diagnosis of low-grade dysplasia is unfortunately usually very inaccurate when this is made by pathologists who are not highly expert in BE.47 In one US study, 65% of 20 general pathologists misdiagnosed a case of low-grade dysplasia; 25% classified it as normal and the other 40% as either moderate or high-grade dysplasia, in equal proportions.48 A more recent US study found that general pathologists had only poor to fair interobserver agreement on the diagnosis

of low-grade dysplasia (Kappa value 0.32).49 In a study from the Netherlands, 85% of low-grade dysplasia cases diagnosed by general pathologists were downgraded to “not dysplasia” on review by pathologists highly expert in BE.50 This experience, consistent with that of Vieth in Germany,47 highlights the important role that centers expert in BE are playing in refining the diagnosis of low-grade dysplasia. So, given these diagnostic problems, should the clinician ignore low-grade dysplasia? No—because as explained below, this finding, when confirmed by an expert BE pathologist, should change management, because it indicates a substantially higher risk for EA when compared to those whose BE is diagnosed as free of dysplasia.

Serial immunostaining showed that ∼43% of these cells were CD103+

Serial immunostaining showed that ∼43% of these cells were CD103+ and that ∼63% were CD11c+ (Table 1; Fig. 2C); some were also CD25+ and/or CD86+ (Fig. 2D). The mean Acalabrutinib cost survival time of the Irr(−) and Irr(+) groups were 10.3 ± 1.6 (n = 9) and 8.8 ± 1.0 days (n = 4) after LT, respectively (Fig. 5A), indicating that irradiation enhanced rejection slightly, but not significantly. The ratio of the sinusoidal area to the total surface area was significantly higher in the Irr(+) group than in the Irr(−) group’s on day 5, but became

comparable by day 7 (Fig. 5B). The CD8+ T-cell responses were comparable in the Irr(+) and Irr(−) groups, as shown by the kinetics of BrdU+CD8β+ cell numbers in the graft portal and sinusoidal areas (Fig. 5C-F). In both the Irr(−) and Irr(+) groups, donor MHCII+ DC-like cells were observed in clusters with BrdU+ cells that were found in the graft portal and hepatic vein areas on days 2-4 after LT (Fig. 6A). FACS analysis to detect nonparenchymal cells on day 3 after LT showed that the sessile donor DCs were mainly in the CD172a+CD11b+

population in both groups and that they expressed similar levels of CD25 and CD86 (Fig. 6B-D). Immunostained serial sections showed that of these donor MHCII+ cluster-forming cells, ∼65% were CD103+ and ∼82% were CD11c+ (Table 1; Fig. 6E,F). Furthermore, some also coexpressed CD86 (Fig. 6F). Cytosmears of FACS-sorted Pritelivir liver DC subsets showed their DC cytology (Fig. 7A). The positive stimulator control of the donor splenic DCs induced a dose-dependent proliferation

of responder T cells. The CD172a+CD11b+ DCs (3 × 103/well) that were isolated from the donor liver with or without irradiation and from the irradiated donor hepatic lymph induced high proliferation comparable to the control splenic DCs (3 × 103/well) (Fig. 7B). In contrast, CD172a−CD11b+ DCs isolated from the nonirradiated donor liver (3 × 103/well) showed a lower Megestrol Acetate stimulation index (Fig. 7B). The CD172a+CD11b+ DCs formed huge clusters in vitro that were larger than clusters formed by the CD172a−CD11b+ DCs (Fig. 7C). The number of BrdU+FoxP3+ regulatory T cells was suppressed slightly on day 2 in both the spleen and graft portal areas in the Irr(+) group, compared to the Irr(−) group (Supporting Fig. 3A,B); however, suppression was not significantly different over the entire examination period. The total number of FoxP3+ cells in the portal areas was also comparable (Supporting Fig. 3C). The 35,129-element oligonucleotide microarray of graft tissues used to analyze the Irr(+) group identified 117 up-regulated and 79 down-regulated genes on day 2 and 95 up-regulated and 79 down-regulated genes on day 3 after LT, compared to the Irr(−) group. Among these, several genes were related to immune responses.

Conclusion: The routine second-look endoscopy may be beneficial f

Conclusion: The routine second-look endoscopy may be beneficial for selected patients who have presence of fibrosis on endoscopic finding. Key Word(s): 1. ESD; 2. second look; 3. high risk; 4. bleeding; Table 1. Univariate analysis of factors associated with risk of bleeding   Post ESD bleeding (n = 14) Post ESD non-bleeding (n = 602) P value Male Sex 8 (60.0%) 411 (68.4%) 0.332 Age (years) 54.42 ± 10.02 52.40 ± 12.15 0.333 Body mass index (kg/m2) 24.29 ± 3.30 24.47 ± 2.92 0.742 Hypertension 3 (24.0%) 131 (21.9%) 0.787 Diabetes 1 (0.7%) 57 (9.6%) 0.474 Mucosal Fibrosis 13 (92.8%) 24 (3.9%) 0.076 Mucosal atrophy 6 (42.8%) 245 (40.6%)

0.708 H. pylori infection 4 (28.5%) 102 (4.1%) 0.633 GDC-0973 in vitro Intestinal metaplasia 3 (21.4%) 55 (9.1%) 0.140 Presenting Author: WEI CAI Additional Authors: YUZHENG ZHUGE Corresponding Author: YUZHENG ZHUGE Affiliations: Nanjing Drum Tower Hospital Objective: To assess the clinical efficacy and safety of transjugular intrahepatic portosystemic shunt (TIPS) in treating cirrhotic patients

with esophageal gastric varices bleeding. Methods: This prospective study included 105 consecutive patients who were enrolled into three groups. We observed success rates, shunt insufficiency rates, rebleeding rates, survival rates, and major complications of overall and different stent groups. Results: (1) The overall success CYC202 rate was 95%. The success rates were 87%, 100%, and 100% in bare stent group, covered stent-grafts group, and combined stent group, respectively (P = 0.01). (2) The overall 6-month, 12-month and 24-month shunt insufficiency rates were 8%, 9%, and 16%, respectively. The overall 6-month, 12-month, and 24-month rebleeding rates were 2%, 6%, and 17%, respectively. Erastin concentration The overall 6-month, 12-month

and 24-month survival rates were 100%, 97%, and 94%. Shunt insufficiency rate was 26% in bare stent group, 14% in covered stent-grafts group, and 5% in combined stents group (P = 0.61). The rebleeding rate was 33% in bare stent group, 7% in covered stent-grafts group, and 3% in covered stent-grafts group (P = 0.43). The survival rate was 92% in bare stent group, 93% in covered stent-grafts group, and 100% in combined stents group (P = 0.39). (3) Shunt insufficiency rates were higher in patients with splenectomy than those without splenectomy (P = 0.04). (4) The intraperitoneal hemorrhage rates in covered stent-grafts group and combined stents group were significantly lower than that in bare stent group (P = 0.01). Conclusion: TIPS could treat and prevent esophageal gastric varices bleeding in patients with cirrohsis effectively. TIPS with covered stent-grafts could significantly decrease intraperitoneal hemorrhage caused by TIPS, and improve the safety and success rates of treatment. However, the influence of TIPS with covered stent-grafts toward clinical efficacy needs more furthur study. Key Word(s): 1.