PH triggers activation of the immediate early genes (i e , genes

PH triggers activation of the immediate early genes (i.e., genes that are rapidly, but transiently, activated) within approximately the first 4 hours,1 and

thereby hepatocytes reenter the cell-division cycle. Immediate early genes encode proteins that regulate later phases in G1 and play an important role in cell growth in the regenerating liver.1, 2 The process of liver www.selleckchem.com/products/azd9291.html regeneration after hepatectomy is coordinated by both pro- and antiproliferative factors. Transforming growth factor-beta1 (TGF-β1) is a potent inhibitor of mitogen-stimulated DNA synthesis in cultured hepatocytes.3 Therefore, it has been thought that TGF-β1 is a potent candidate to limit or stop liver regeneration after PH hepatectomy.4 Because TGF-β is synthesized and secreted as a latent complex, the important step in regulating its biological activity is the conversion of the latent www.selleckchem.com/autophagy.html form into the active one. However, the contribution of TGF-β to the liver’s regenerative response after PH hepatectomy is still poorly understood. TGF-β1 messenger RNA

(mRNA) induction occurs within 4 hours, and levels of TGF-β1 remain elevated until 72 hours after PH hepatectomy.5, 6 In sharp contrast, in the model of complete lack of TGF-β signaling using hepatocyte-specific TGF-β type II receptor knockout

mice, the lack of TGF-β signaling does not result in prolonged hepatocyte proliferation; rather, only transiently up-regulated proliferation of hepatocytes is shown in the later phase after hepatectomy, with a peak at ∼36 hours.7 These Wilson disease protein differences raise an open question about whether locally activated TGF-β1 is indeed essential for the inhibition of hepatocyte proliferation in vivo. Furthermore, the time course of locally activated TGF-β1 and its activation mechanism after PH hepatectomy still remain largely unknown. The matricellular protein, thrombospondin-1 (TSP-1), was first shown as a component of the α-granule in platelets and can act as a major activator of latent TGF-β1.8, 9 TSP-1 is induced in response to tissue damage or stress and plays a role as a transient component of extracellular matrix during tissue repair.8, 10, 11 However, the roles of TSP-1 and of TSP-1/TGF-β1 interdependence during liver regeneration have not yet been addressed. We hypothesize that the initiation of local TGF-β activation occurs much earlier after PH hepatectomy, and TSP-1 plays a critical role in this process. Here, using a TSP-1-deficient mouse model, we investigated whether TSP-1 would be a suitable molecular target for accelerating liver regeneration after PH.

ERK inhibitors, PD98059 and U0126, and NF-κB pathway inhibitors,

ERK inhibitors, PD98059 and U0126, and NF-κB pathway inhibitors, sulfasalazine and N-acetyl-l-cysteine, also inhibited MMP-9 expression. Conclusion:  These results support a model whereby the EPIYA Selleck Buparlisib motif of CagA is phosphorylated by Src family kinases in gastric epithelial cells, which initiates activation of SHP-2. In addition, they suggest that the resultant activation of ERK pathway along with CagA-dependent NF-κB activation is critical for the induction of MMP-9 secretion. “
“The Helicobacter heilmannii sensu

lato (H. heilmannii s.l.) group consists of long, spiral-shaped bacteria naturally colonizing the stomach of animals. Moreover, bacteria belonging to this group have been observed in 0.2–6% of human gastric biopsy specimens, and associations have been made with the development of chronic gastritis, peptic ulceration, and gastric MALT lymphoma in humans. To gain insight into the prevalence of H. heilmannii s.l. infections in patients suffering from gastric disease in China, H. heilmannii s.l. species-specific PCRs were performed on DNA extracts from rapid urease test (RUT)-positive gastric biopsies from 1517 patients followed by nucleotide sequencing. At the same time, Helicobacter pylori cultivation and specific PCR was

performed to assess H. pylori infection in these patients. In total, H. heilmannii s.l. infection was detected in 11.87% (178/1499) of H. pylori-positive patients. The prevalence of H. suis, H. felis, H. bizzozeronii, www.selleckchem.com/products/kpt-330.html H. heilmannii sensu stricto (s.s.), and H. salomonis in the patients was 6.94%, 2.20%, 0.13%, 0.07%, and 2.54%, respectively. Results revealed that all patients with H. heilmannii s.l. infection were co-infected with H. pylori, and some patients were co-infected with more than two different Helicobacter species. Helicobacter heilmannii s.l. infections are fairly common in Chinese patients. This should be kept in mind when diagnosing the cause of gastric pathologies in patients. Helicobacter suis was shown to be by far the most prevalent H. heilmannii s.l.species. “
“Background:  FER Studies comparing new

monoclonal fecal tests for evaluating cure of Helicobacter pylori infection after treatment are scarce. The objective was to compare the diagnostic accuracy of three monoclonal stool tests: two rapid in-office tools –RAPID Hp StAR and ImmunoCard STAT! HpSA – and an EIA test – Amplified IDEIA Hp StAR. Materials and methods:  Diagnostic reliability of the three tests was evaluated in 88 patients at least 8 weeks after H. pylori treatment. Readings of immunochromatographic tests were performed by two different observers. Sensitivity, specificity, positive and negative predictive values and 95% confidence intervals were calculated. Results:  All tests presented similar performance for post-eradication testing. Sensitivity for detecting persistent infection was 100% for both Amplified IDEIA and RAPID Hp StAR and 90% for ImmunoCard STAT! HpSA. Respective specificities were 94.

2 The cells can be clonogenically expanded ex vivo in a serum-fre

2 The cells can be clonogenically expanded ex vivo in a serum-free medium tailored for endodermal progenitors [Kubota's medium (KM)]9 and have the potential to differentiate

into mature functional hepatocytes and cholangiocytes in vivo. The microenvironment of stem cell niches modulates stem cell proliferation, influences symmetric division versus asymmetric division, controls differentiation, protects cells from physiological stresses, and helps them to contribute to tissue formation in development and in regeneration in adult life.7 The components of the stem cell microenvironment regulating these processes include distinct cell-cell interactions and paracrine signals, which comprise both soluble and extracellular Small molecule library matrix factors, as well as the three-dimensional Everolimus solubility dmso (3D) architecture, which shapes and dictates the delivery of these cues. The studies reported here are focused on mesenchymal companion cells and their provision of critical paracrine signals regulating the parenchymal lineage stages. Paracrine signals were identified with purified subpopulations of mesenchymal cells cultured under serum-free conditions. A set of these signals was then used to regulate precisely the growth and/or fates of hHpSCs under feeder-free conditions. In a separate report, we are focusing on studies of lineage-dependent

soluble signals (J. Uronis and L. Reid, unpublished data, 2010). 3D, three-dimensional; AFP, α-fetoprotein; ALB, albumin; ASMA, α-smooth muscle actin; BC, bile canaliculus; C1A1, ADAMTS5 collagen 1A1; C3A1, collagen

3A1, C4A5, collagen 4A5; C5A2, collagen 5A2; CK, cytokeratin; CS-PG, chondroitin sulfate proteoglycan; DAPI, 4′,6-diamidino-2-phenylindole; ELS, elastin; EpCAM, epithelial cell adhesion molecule; ER, endoplasmic reticulum; FN, fibronectin; GFAP, glial fibrillar acidic protein; GAG, glycosaminoglycan; GPYC, glypican; HA, hyaluronan; HDM, hormonally defined medium; hHB, human hepatoblast; hHpSC, human hepatic stem cell; hHpSTC, human hepatic stellate cell; hMSC, human mesenchymal stem cell; HP-PG, heparin proteoglycan; HS-PG, heparan sulfate proteoglycan; HUVEC, human umbilical cord vein endothelial cell; ICAM, intercellular cell adhesion molecule; ICG, indocyanine green; IF, intermediate filament; KDR, kinase insert domain receptor; KM, Kubota’s medium; LA4, laminin A4; LB2, laminin B2; LB3, laminin B3; MCM, mesenchymal cell medium; MKM, modified Kubota’s medium; MKM-C, modified Kubota’s medium for cholangiocytes; MKM-H, modified Kubota’s medium for hepatocytes; mRNA, messenger RNA; NCAM, neural cell adhesion molecule; NPC, nonparenchymal cell; qRT-PCR, quantitative reverse transcription polymerase chain reaction; SDC2, syndecan 2; SR, secretin receptor; TEM, transmission electron microscopy; VEGF, vascular endothelial growth factor; vWF, von Willebrand factor.

” Both authors1, 12 mentioned some awareness about the quality of

” Both authors1, 12 mentioned some awareness about the quality of the meta-analysis and the studies included in it. We think that conclusion must be interpreted both in light of the included trials and considering the effects of other factors, such as baseline HCV level, sex, race, and genotype. We strongly believe more research is needed before it is concluded one peginterferon is better than the other. David Kershenobich M.D., Ph.D.*, Linda Muñoz†, René Malé‡, Jesús Gaytan§, Francisco Sánchez¶, * Laboratorio de Hígado, Páncreas y Motilidad, Departamento de Medicina Experimental, Facultad de Medicina de la UNAM, Hospital General

de México, México DF, México, † Unidad de Hígado, Departamento de Medicina Interna, Hospital Universitario

“Dr. José E. González” Universidad Autónoma de Nuevo León, Monterrey, Nuevo León, México, Selleck AG 14699 ‡ Centro de Enfermedades Digestivas y Hepáticas SC, Instituto de Salud Digestiva y Hepáticas SC, Guadalajara, Jalisco, México, § Hospital de Infectología. Centro Médico Nacional “La Raza”. Instituto Mexicano del Seguro Social, México DF, México, ¶ Departamento de Gastroenterología. Instituto Nacional de Ciencias Médicas y Nutrición “Salvador Zubirán,” México DF, México. Lapatinib supplier
“A 61-year-old woman presented with fever and right upper quadrant discomfort of 4 weeks’ duration. She lived on a farm with her husband, and they had several dogs. The husband hunted wild animals, and they ate garden-grown vegetables.

A physical examination revealed hepatomegaly. Computed tomography of the abdomen (Panel A) showed a large cystic lesion in the right hepatic lobe with internal Sitaxentan septations. Laboratory studies showed peripheral eosinophilia and abnormal liver chemistries (less than 2 times the upper limit of normal). Serology for echinococcosis was equivocal. PAIR, puncture, aspiration, injection of a scolicidal agent, and re-aspiration. Echinococcusgranulosus was strongly suspected because of the unilocular nature of the cystic lesion. Other infectious cystic diseases of the liver include Echinococcusmultilocularis and Echinococcusvogeli. These two infections were considered less likely on the basis of cyst characteristics, with E.multilocularis causing multilocular cysts and E.vogeli causing polycystic lesions. Therapy for cystic echinococcosis is based on considerations of the size, location, and manifestations of the cysts. Surgery has traditionally been the principal definitive method of treatment. In this case, surgical resection was considered; however, it was determined that because of the large size of the cyst, right hepatectomy would be required. For uncomplicated echinococcal lesions, puncture, aspiration, injection of a scolicidal agent, and re-aspiration (PAIR) constitute an alternative to surgery.

Four days after an uneventful surgery the

patient develop

Four days after an uneventful surgery the

patient developed confusion, seizures, and was admitted to the ICU. CT perfusion revealed reduced ispilateral time-to-peak and mean-transient-time and increased cerebral blood volume and cerebral blood flow, confirming the diagnosis of cerebral hyperperfusion syndrome. We thus propose CT perfusion as a diagnostic means for cerebral hyperperfusion syndrome, a syndrome that remains underdiagnosed. “
“We describe a left-handed patient selleck screening library with transient aphasia and bilateral carotid stenosis. Computed tomography (CT) arteriography showed a 90% stenosis of the right and 30% stenosis of the left internal carotid artery. Head CT and magnetic resonance www.selleckchem.com/products/voxtalisib-xl765-sar245409.html imaging (MRI) of the brain showed no recent ischemic changes. As only the symptomatic side would require surgical intervention, and because hemispheric dominance for language in left-handed patients may be either left or right sided, a preoperative assessment of hemispheric dominance was required. We used functional MRI to determine hemispheric dominance for language and hence to establish the indication for carotid endarterectomy surgery. Functional MRI demonstrated right hemispheric dominance for language and right-sided carotid endarterectomy was

performed. We propose that the clinical use of functional MRI as a noninvasive imaging technique for the assessment of hemispheric language dominance may be extended to the assessment of hemispheric language dominance prior to carotid endarterectomy. “
“To describe diffusion-weighted imaging and diffusion tensor imaging variations in spinal cord infarctions. We studied the apparent diffusion coefficient (ADC) and fractional anisotropy

(FA) local variations in 2 patients with spinal cord infarcts in the conus region at days 3–4, 9–10, and 15–22 after clinical onset, and correlated them with the clinical outcome. Both patients (19 and 53 years-old) presented spinal cord infarction unraveled by paraparesis and bladder dysfunction. Although initial clinical and radiological presentations were similar, the first patient early and fully recovered whereas the second kept severe bladder dysfunctions. Pregnenolone Early absolute values of FA and ADC did not seem to correlate with outcome. At day 9–10, the second patient, who presented definitive sequel, had decreasing values of FA in the ischemic region whereas they had increased in the first patient, who fully recovered. FA values could be an interesting prognosis marker in spinal cord ischemia, which needs to be confirmed by a larger study. “
“We present the first case of cerebral infarction due to idiopathic reversible vasospasm of the extracranial internal carotid artery without headache or identifiable cause in a patient who subsequently suffered acute myocardial infarction due to vasospasm of the coronary artery.

In comparison with lobar TACE, selective/superselective TACE led

In comparison with lobar TACE, selective/superselective TACE led to significantly higher mean levels of necrosis (75.1% versus this website 52.8%, P = 0.002) and a higher rate of complete necrosis (53.8% versus 29.8%, P = 0.013). A significant direct relationship was observed between the tumor diameter and the mean tumor necrosis level (59.6% for lesions < 2 cm, 68.4% for lesions of 2.1-3 cm, and 76.2% for lesions > 3 cm). Histological necrosis was maximal for tumors > 3 cm: 91.8% after selective/superselective TACE and 66.5% after lobar procedures. Independent predictors

of complete tumor necrosis were selective/superselective TACE (P = 0.049) and the treatment of single nodules (P = 0.008). Repeat sessions were more frequently needed for nodules treated with lobar TACE (31.6% versus 59.3%, P = 0.049). Conclusion: Selective/superselective TACE was more successful than lobar procedures in achieving complete histological necrosis, and TACE was more effective in 3- to 5-cm tumors than in smaller ones. (Hepatology 2011;) Transarterial chemoembolization (TACE) is the recommended treatment strategy for patients with intermediate-stage hepatocellular carcinoma (HCC) according to the American Association for the Study of Liver Diseases guidelines.1, 2 In the setting of liver transplantation (LT), TACE is applied both to reduce the dropout rate for patients on the waiting list (bridge therapy) and to downstage patients with HCC not initially meeting

the transplantability criteria DMXAA nmr (downstaging protocols).3 The capability of TACE to induce extensive tumor necrosis is still under debate, and this technique is considered to be a noncurative modality. Staurosporine price Whether this belief derives from the real potential

of the technique or from the fact that it has mainly been applied to tumors that are large and are, consequently, more difficult to treat is still a matter of discussion. Similarly, the role of the various technical modalities of TACE procedures in determining the final rate of necrosis has not been adequately investigated in Western countries. The recommendation for TACE as the standard of care for intermediate-stage HCC is based on the demonstration of improved survival in comparison with the best supportive care or suboptimal therapies in a meta-analysis of six randomized control trials.4 However, there was considerable heterogeneity between the individual study designs of the six trials, and the differences included the patient populations and TACE techniques. More specifically, the oldest trials of the meta-analysis included lobar or whole liver embolization (i.e., the injection of a mixture of Lipiodol, a chemotherapeutic agent, and an embolizing material into either the main lobar artery or the hepatic artery itself), whereas more recently, selective treatments have been used (i.e., the injection of agents into the segmental or subsegmental branches feeding the tumors) with apparently better survival results.

[2] These bacterial species belong mostly to genera that are plac

[2] These bacterial species belong mostly to genera that are placed in one of the four phyla, namely Firmicutes, Bacteroidetes, Palbociclib purchase Proteobacteria, and Actinobacteria,[3] with little representation from the other bacterial phyla. GI tract is sterile at birth. Colonization begins soon thereafter, initially with flora acquired from the mother’s vaginal canal and thereafter from the surrounding environment. An individual’s gut microbiota is generally well established by 1 year

of age and remain unchanged through life except for minor temporary fluctuations.[4] The composition of adult gut microbiota varies widely between individuals and depends on several factors, including host genetics, diet, and other environmental factors. Thus, a particular individual’s gut harbors

a subset of about 150–200 bacterial species from among those referred to above.[2] Gut microbiota plays several important roles in the host’s health. It supplements the host’s nutritional needs through breakdown and absorption of complex dietary carbohydrates, which human enzymes cannot digest, as also synthesis of some essential substances, for example vitamin K. In addition, it helps maintain the integrity of intestinal epithelial barrier through production of short-chain fatty acids, particularly butyrate, that BAY 57-1293 molecular weight are trophic for colonic epithelial cells and help epithelial restitution,[5] and contributes to maturation of host immune system, including development of Peyer’s patches, mucosal lymphoid follicles, and antibody-secreting plasma cells.[6] In addition, these organisms protect the host against pathogenic microbes through competition for adhesion sites and nutrients, and production of antimicrobial agents. Liver develops as a bud from the embryonic foregut and maintains

a close two-way liaison with the GI tract throughout life. Venous blood from the gut reaches the liver via portal vein, carrying with it products of gut flora and of host’s immunological responses to these organisms. In turn, the liver produces bile that flows to the gut to affect the abundance and distribution of various organisms in the latter’s lumen. This close relationship of liver and Isoconazole gut implies that gut flora may play a role in the pathogenesis of liver diseases, and their study may allow identification of newer preventive and therapeutic strategies against these diseases. This article reviews in brief the techniques used to study gut microbiota and current knowledge about the role of microbiota in liver disease. Initial studies on composition of gut microbiota were based on culture of intestinal biopsy specimens, luminal contents, or feces. In recent years, these have largely been replaced by molecular methods.

In contrast, in the injured or fibrotic liver, HSC exist in a pre

In contrast, in the injured or fibrotic liver, HSC exist in a predominantly activated state and acquire proliferative capacity themselves.5 We hypothesize that HSC activated in

vivo also up-regulate B7-H4 expression, and then dominate Sirolimus ic50 the liver environment with T cell inhibitory signals leading to attenuation of the immune response. T cell responses can be divided into two major stages: (1) primary and (2) recall responses. Antigen-specific primary T cell responses have been shown in the liver.38 Similarly, T cells activated in the peripheral lymphoid tissues that traffic through the liver have poor survival, earning the liver the reputation as a graveyard for activated T cells.39 It has been shown that the coinhibitory molecule B7-H1 expressed on hepatocytes promotes priming but inhibits recall T cell responses.40 In contrast, we report here that B7-H4 on AHSC inhibits both priming and recall CD8+ T cell responses. Inhibiting https://www.selleckchem.com/products/LBH-589.html T cell responses at different stages highlights the key role of HSC in modulating intrahepatic immunity in fibrosis. Here we provide evidence that B7-H4 expression on AHSC-induced T cell inactivation or anergy that could be reversed

by exogenous IL-2. The rescue mechanism from B7-H4 is similar to B7-H1-mediated T cell inhibition because the B7-H1 (PD-L1)-PD-1 inhibitory pathway can also be overcome by provision of exogenous IL-2.41 This may have interesting implications in chronic viral diseases such as HCV

infection, as the inhibitory effects of B7-H4 on T cells may be perpetuated or amplified by a relative deficiency of IL-2.42, 43 Still unknown is the cellular regulation of B7-H4 in AHSC, although our studies are starting to offer some intriguing clues. In tumor macrophages the upregulation of B7-H4 is dependent on IL-6 and IL-10.32 Janus kinase (JAK) Interestingly, AHSC also secrete IL-6; however, whereas QHSC can be isolated from IL-6 knockout mice, these cells do not seem to proliferate or transition to an activated state (data not shown). Altogether, it will be of further interest to investigate whether B7-H4 expression on HSC results in, is coincidental with, or is a consequence of HSC proliferation and activation. In summary, our results demonstrate that AHSC inhibit T cell responses in a B7-H4-dependent manner. In the tumor microenvironment, B7-H4 attenuates T cell responses and the tumors use this mechanism to evade the T cell immunity. In the present study, our results suggest that AHSC proliferate, perpetuate fibrosis, and inhibit intrahepatic T cell immunity. AHSC expressed B7-H4 provides a novel link between liver fibrosis and impaired intrahepatic immunity and highlights the potential importance of targeting interventions toward the AHSC in hepatotropic infections such as HCV.

Among the 34 patients who added FTC, 12 remained viremic on their

Among the 34 patients who added FTC, 12 remained viremic on their last evaluable visit through week 144 (median duration of combination therapy = 59 weeks, range = 25-70 weeks); PCR amplification failed for 1; 5 showed no change in the pol/RT versus the last observation while they were on TDF monotherapy; 4 harbored distinct polymorphic site changes; and 2 developed

conserved site changes (rtL180L/M, rtA181T, and rtM204M/V and rtR192H; Table 3). Clonal analysis of the baseline sample for the patient harboring the rtL180L/M, rtA181T, and rtM204M/V mutations demonstrated the presence of these mutations as subpopulations on separate genomes (rtL180M and rtM204V at 3.7% and rtA181T at 7.4%). Phenotypic analysis of the viral pool containing the rtA181T mutation demonstrated that the virus was fully sensitive to inhibition by tenofovir CT99021 nmr (Table 2). Clones containing the rtL180M and rtM204V mutations could not be obtained with the PCR primers used for phenotyping. For patient 026, the viral quasispecies pool, individual clones (n = 7), and an rtR192H site-directed mutant in the pCMVHBV backbone were all replication-defective in a cell

culture (Table 2). Thirteen patients experienced a confirmed virological breakthrough (10 and 3 in the TDF and ADV-TDF arms, respectively) during the 144 weeks of cumulative exposure to TDF monotherapy; nonadherence Rucaparib to the study medication contributed to the majority of the virological breakthrough events (11/13, 85%), and all patients experiencing virological breakthrough remained phenotypically sensitive to inhibition by tenofovir (Table 4). Four patients experienced virological breakthrough while they were on combination FTC/TDF therapy (three and one in the TDF and ADV-TDF arms, respectively), virological breakthrough could be attributed to nonadherence in two of the however four patients, and the virus obtained from these patients remained

phenotypically sensitive to inhibition by tenofovir and FTC (Table 4). We performed extensive genotypic and phenotypic analyses of 641 HBeAg+ and HBeAg− patients who received up to 144 weeks of TDF therapy. We identified six previously undescribed conserved site changes in the HBV pol/RT. These novel conserved site changes were located in areas of high variability within the HBV genome.19 None of these changes appeared to be related to tenofovir resistance, as demonstrated by the lack of phenotypic resistance to tenofovir in vitro, nor were they associated with a confirmed virological breakthrough. Phenotypic analysis was also performed for patients who experienced virological breakthrough because this can be a hallmark of resistance development. All of the viruses tested remained phenotypically sensitive to inhibition by tenofovir; this is consistent with the genotypic findings, which demonstrated no changes in the pol/RT among these patients.

78, p=0 005), older donor age (HR 1 26, p<0 0001), male donor gen

78, p=0.005), older donor age (HR 1.26, p<0.0001), male donor gender (HR 1.54, p=0.006), number of corticosteroids bolus selleck kinase inhibitor received (HR 1.31, p=0.02) and aspirin intake (HR 0.74, p=0.03) were associated with fibrosis progression to stage F≥2.HCV genotype, preservation injury, cold ischemia time, post LT diabetes were not associated with fibrosis progression. Multivariate analysis showed that

male donor gender (HR 1.7, p=0.002) and older donor age (HR 1.3, p=0.0001) were associated with rapid fibrosis progression whereas aspirin intake (HR 0.66 [0.47-0.91], p=0.01) and older recipient age (HR 0.8, p=0.02) were associated with slow fibrosis progression. After adjustment on immunosuppressive therapy, aspirin intake was still associated with decreased fibrosis progression (HR 0.71 [0.51-0.99], p=0.05). Conclusion: Low dose aspirin reduces liver fibrosis progression in HCV recurrence after liver transplantation. These results are in line with the concept of an association between thrombosis and liver fibrosis.

Disclosures: Francois Durand – Advisory Committees or Review Panels: Astellas, Novartis; Speaking and Teaching: Gilead Christophe Duvoux – Advisory Committees or Review Panels: Novartis, Roche, Novartis, Roche, Novartis, Roche, Novartis, Roche; Speaking and Teaching: Astellas, Astellas, Astellas, Astellas Vincent Mackiewicz – Speaking and Teaching: Abbott Diagnostics The following people have nothing to disclose: Armelle Poujol-Robert, Pierre-Yves Boëlle, Filomena Conti, Dominique ABT-263 chemical structure Wendum, Valerie Paradis, Olivier Chazouilleres, Raoul Poupon Introduction and Aim: Hepatitis C (HCV) related liver disease and hepatoma continue as the leading indication for liver transplantation (LT). Sustained virological response (SVR) rates to PEG-IFN/Ribavirin (P/R) therapy of recurrent HCV in Genotype 1(G1) LT recipients have been disappointing (30-40%. Experience with triple therapy using protease inhibitors

(PI; Boceprevir (BOC), Telaprevir (TPV)) in these patients is limited. OSBPL9 This report summarizes the results in a large cohort of patients treated for recurrent HCV using triple therapy in 6 Canadian adult liver transplant centres. Methods: 76 pts (64 male, mean age 56y) were treated for G1 HCV (55 G1a) with either BOC (2/3) or TPV at a mean of 44.7 mo. post LT. 2/3 pts were either prior non-responders or relapsers; the rest were treatment naϊve. Two pts had fibrosing cholestatic HCV; the balance chronic disease with mean fibrosis stage 2.55 pts were on cyclosporine based immunotherapy; the remainder on tacrolimus or neither. All BOC and the majority of TPV pts had a P/R lead-in phase of 4-24wks. Results: 69/76 total pts have had viral load (VL) measured on triple therapy; 56 (81%) were undetectable. 39 pts remain on treatment, 90% with undetectable VL. Of 37 pts off therapy, 28 had undetectable VL at treatment end, with VL pending in two others.