4 During the 1990s, evidence of a linkage between OCs and hepatocellular carcinoma (HCC) increased with experimental proof. Dunsford and Sell5 and Hixson et al.6 attempted to analyze the phenotypic relationships between OCs, bile duct cells, and adult and fetal cells. They found that OCs, preneoplastic foci, early tumor nodules, and primary HCC express both OC and hepatocyte antigens. This suggests a cause-effect relationship between OCs and HCC. Their results corroborated

the idea that OCs appear and proliferate in the liver as previously reported by Farber7 and Hewitt8 in the late 1950s, and they were confirmed by Dumble et al.9 nearly a half-century later. Rodent models of liver tumorigenesis have been based on chemical induction, which yields HCC almost exclusively and cholangiocarcinoma PLX3397 datasheet (CC) only rarely. Unfortunately, animal models of CC have been limited www.selleckchem.com/products/chir-99021-ct99021-hcl.html primarily to the Syrian hamster model, murine models of gallbladder adenocarcinoma, and the administration of furan to rats.10 Thus, liver-specific neurofibromatosis type 2 (Nf2−/−)–deleted mice11 not only represent an excellent model of liver

tumorigenesis for both HCC and CC but also offer an excellent tool for studying the involvement of OCs in liver malignancies. These mice develop a great variety of histopathological types of HCC (including trabecular, solid, pseudoductular,

and acinar HCC) and early CC that resemble human tumorigenesis.11 NF2 is an inherited disorder characterized by the development of Schwann cell tumors of the vestibulocochlear nerve. Several tumors of the nervous system, including schwannomas, meningiomas, and ependymomas, have been associated with mutations in the NF2 locus.12 The NF2 gene codes for a 595–amino acid protein called Merlin; Merlin is highly related to the ezrin, radixin, FER and moesin proteins, which are actively involved in the regulation of the cytoskeleton and signal transduction pathways.13 Merlin caught the attention of cancer researchers because it was found to be a negative regulator of the Hippo/Warts/Yorkie tumor suppressor pathway in Drosophila. However, the function of Merlin in the regulation of the analogous macrophage stimulating 1 (Mst)/large tumor suppressor (Lats)/yes-associated protein (Yap) pathway in mammals is not clear yet.14 In the actual study, McClatchey’s group11 used different experimental approaches to investigate whether NF2/Merlin regulates Mst/Lats/Yap. They observed that the absence of NF2/Merlin does not change the phosphorylation, localization, or expression of Yap1-related genes after the endogenous or exogenous administration of Merlin or short hairpin RNA knockdown in liver-specific NF2-deleted OCs.

25, 26 Kan et al.26 proposed that SOX1 suppresses β-catenin-mediated TCF/LEF signaling by interacting with β-catenin to promote neurogenesis. These results suggest that SOX family member exertion of their functions through manipulation of Wnt signaling is a common tactic.

In previous studies, we identified that SOX1 was hypermethylated in cervical and ovarian cancers.27, 28 Moreover, we selleck chemicals llc recently demonstrated that SOX1 and secreted frizzled-related proteins were concomitantly hypermethylated in HCC tissues by QMS-PCR analysis (unpublished data). These results suggest that Wnt antagonists might be attenuated or shut down simultaneously during the progression of HCC. However, the expression and functional role of SOX1 in the development of HCC are not Inhibitor Library price clear. In this study, our data demonstrated that SOX1 was frequently downregulated through promoter hypermethylation. Furthermore, ectopic expression of SOXl led to significant repression of HCC growth, which is mediated through interaction with β-catenin,

thereby interfering with the Wnt signaling pathway. These results indicate SOX1 to be a novel tumor suppressor in hepatocarcinogenesis. Eight HCC cell lines (SK-Hep-1, HepG2, Hep3B, Huh6, Huh7, HA22T, TONG, and Mahlavu) were used in this study. Sixty paired HCC samples, including HCC tissues and DNA and RNA samples, were provided by the Taiwan Liver Cancer Network (TLCN). The TLCN is funded by the National Science Council to provide researchers in Taiwan with primary liver cancer tissues

and their associated clinical information (Supporting Table 1). The use of the 60 HCC tissues, paired nontumor parts, and hepatic hemangioma tissues (as control livers) in this study was approved by our Institutional Review Board and the TLCN User Committee. Bisulfite conversion and quantitative methylation-specific polymerase chain reaction (QMS-PCR) were performed as described.29, 30 The primer sequence for QMS-PCR has been described.30 All QMS-PCR data were obtained P-type ATPase from at least three independent modifications of DNA to ensure reproducibility. RNA isolation and RT-PCR were performed according to the manufacturer’s protocol. Complementary DNA was amplified via PCR with primers specific for SOX1.27 Quantitative RT-PCR analysis was performed based on our previous report.29 Detailed information is given in the Supporting Information. HCC cells transfected with vector or SOX1 were injected subcutaneously into the left and right flanks of 6-week-old nonobese diabetic/severe combined immunodeficiency (NOD/SCID) mice. For the tet-on system, NOD/SCID mice were injected with Hep3B cells and randomly divided into two groups, with or without 0.2 μg/mL doxycycline (DOX) administration in 5% sucrose drinking water. The tumor volume was calculated as 0.

16 Cells were incubated with BV, BR, or FeCl2 for 24 to 48 hours in Dulbecco’s modified essential medium containing 5% fetal bovine serum. The detailed procedure is described in Supporting Methods, available online. Cells were fixed in absolute methanol, washed in phosphate-buffered

saline, and incubated with positive HCV genotype 2A polyvalent human serum. On western blots, this antiserum specifically MEK inhibitor recognized core, NS3, and NS5A at their appropriate mobilities. Antibody binding was evaluated after labeling with anti-human secondary antibody–alkaline phosphatase conjugate and results recorded by photomicroscopy. Western blots (WB) were performed as previously described using enhanced chemiluminescence for signal detection (Amersham).17 Signal intensities were quantified by using Image J software (National Institutes of Health, Bethesda, MD). BVR small interfering RNA and control (scrambled) small interfering RNA were purchased from Santa Cruz Biotechnology (sc-44650 and sc-37007). BVR knockdown was performed as described previously.9 Efficiency of the knockdown was monitored by MAPK inhibitor semiquantitative densitometry of BVR WB. Protease activity was determined fluorometrically with the SensoLyte 620 HCV Protease Assay (AnaSpec), using a wide wavelength excitation/emission (591 nm/622 nm, respectively) fluorescence energy transfer peptide according to the manufacturer’s

instructions. Control incubations with BV or metabolite only were performed to eliminate or correct for autofluorescence or quenching. A competitive inhibitor of the NS3/4A protease, AnaSpec #25346, was used as a positive control. For assays employing endogenous NS3/4A protease, the detailed procedure is described in Supporting Oxymatrine Methods, available online. The detailed procedure is described in Supporting Methods, available online. These assays were performed as described in detail in Supporting Methods, available online. Data from individual experiments as well as combined data from separate experiments were expressed as mean ± standard error of the

mean. The significance between means was determined by using Student t test and, when applicable, with analysis of variance, using pooled variances. P values less than 0.05 were considered significant. All experimental findings, whether performed singly or in parts, were repeated at least three times. We have previously shown that induction of HO-1 with hemin results in decreased HCV replication in vitro9; however, it was not known whether physiological concentrations of heme exert antiviral effects. Incubation of replicons with various amounts of hemin demonstrated a concentration-dependent antiviral effect of hemin, apparent at levels as low as 5 μM (Table 1). These concentrations are well within the physiological range of heme in human circulation (10-16 μM) and, in the presence of HO-1, would be expected to yield equimolar quantities of BV, Fe, and carbon monoxide.

Rosen, Ann K. Daly, Lucy Golden-Mason “
“The purpose of this study was to evaluate the usefulness of liver stiffness measurement (LSM) for assessing the risk of hepatocellular carcinoma (HCC) in chronic hepatitis C (CHC) patients receiving interferon (IFN) therapy. One hundred fifty-one CHC patients who underwent LSM and received IFN therapy were included in the estimation

cohort, and 56 were included in the validation study. The cumulative HCC incidences were evaluated using Venetoclax supplier Kaplan–Meier plot analysis and the log-rank test. Multivariate Cox proportional hazard analyses were used to estimate the hazard ratios (HRs) of variables for HCC. In the estimation cohort, 9 of 151 patients developed HCC during the median follow-up time of 722 days. Multivariate

analysis identified three independent risk factors for HCC: LSM (≥ 14.0 kPa, HR 5.58, P = 0.020), platelet count (< 14.1 × 104/μL, HR 5.59, P = 0.034), and non-sustained virological response (HR 8.28, P = 0.049). The cumulative incidence of HCC development at 3 years was 59.6%, 8.2%, and 0.0% in patients with all three risk factors, one to two risk factors, and none of these risk factors, respectively. The click here incidence of HCC was significantly different between these groups (P < 0.001). In the validation cohort, HCC incidence was also significantly different with respect to these risk factors (P = 0.037). LSM, platelet count, and IFN-therapeutic effect could be used to successfully stratify the risk of HCC in patients receiving IFN therapy and demonstrate the usefulness of LSM before IFN therapy for the management of CHC patients. Persistent hepatitis C virus

(HCV) infection is one of the major causes of chronic liver disease leading to the development of HCC, the fifth most common cancer, and the third most common cause of cancer-related death worldwide.[1] HCV is responsible for 27–75% of the HCC cases in Europe and the United States and > 80% of the HCC cases in Japan.[2, 3] In fact, HCV-positive Etofibrate patients have a 20-fold higher risk of developing HCC than HCV-negative patients,[4] indicating a significant carcinogenic role for persistent HCV infection. Because of this connection, many chronic hepatitis C (CHC) patients are treated with interferon (IFN)-based antiviral therapy because it not only eradicates HCV but also reduces the rate of HCC development. IFN therapy is most effective at decreasing the risk of developing HCC in patients that achieve a sustained virological response (SVR);[5-7] however, the risk of HCC development persists after IFN therapy even in patients who do achieve SVR.[8] HCC might develop immediately after IFN therapy in some cases, or during long-term IFN therapy in others.[9, 10] Because assessing the risk of developing HCC is clinically important in the management of CHC patients, it is necessary to establish predictors for HCC development in patients who receive IFN therapy.

Recently, a fixed combination of

sumatriptan 85 mg and naproxen 500 mg (32% pain-free [PF]) was superior to placebo (10% PF) and sumatriptan 85 mg (24% PF) in 2 very large RCTs (n = 1461 and n = 1495) and sustained PF for 24 hours was 24%, 8% and 15%, respectively.143 From a clinical perspective it is the evaluation that despite highly statistically significant results in very large RCTs, the majority of the migraine patients are not treated satisfactorily with triptans, with 30-40% PF response at 2 hours with most triptans142 Migraine and Calcitonin Gene-Related Peptide (CGRP) (1990).— In 1983, a novel neuropeptide, CGRP, was demonstrated in neural tissue144 and its presence in perivascular nerves of cerebral arteries was demonstrated with immunocytochemistry ABT-263 purchase and radioimmunoassay.145 CGRP was LEE011 price found to be a potent vasodilator of cerebral vessels.146,147 Stimulation of the human trigeminal ganglion in the treatment of trigeminal neuralgia resulted in flushing and the release of vasoactive peptides, substance P, and CGRP, in the external jugular vein (EJV).148 In 1990 it was shown that CGRP, but not neuropeptide Y, vasoactive intestinal peptide, and substance P, was considerably increased in the EJV during migraine attacks both in migraine with and without aura.17 Three years later, the effect of trigeminal

ganglion stimulation on CBF and jugular vein peptides in cats was studied before and after administration of sumatriptan and dihydroergotamine.149 The increase of CBF and release of CGRP

Diflunisal in EJV in cats was reduced by both drugs. Treatment of migraine patients with sumatriptan also led to a decrease of elevated CGRP in the EJV and relief of headache in most cases.149 The finding of increased CGRP in the EJV led to the development of new migraine drugs based on CGRP receptor blockade.150 However, in a Danish study (n = 17) with intra-patient comparison, in which blood samples from the EJV were taken in the patients’ home, there was no tendency for an increase of CGRP during an attack of migraine without aura.151 In a later study, also with intra-patient comparisons, 8 migraine patients were investigated in the laboratory during, and outside, attacks of migraine without aura. No increase of CGRP in EJV was found.152,153 Furthermore, in one nitroglycerin-induced migraine attack study, CGRP in EJV was not increased.153 In contrast, saliva CGRP was increased during migraine attacks in patients responding to rizatriptan154 whereas there was a nonattack-related increase in CGRP in saliva in migraine in another study.155 The important role of CGRP in migraine pathophysiology is shown by 2 sets of facts. First, infusion of CGRP induced delayed migraine attacks in migraine patients.156 Second, CGRP receptor antagonists were effective in the treatment of migraine attacks.

In vitro, HSCs-derived TGF-β could suppress NK cytolytic activity, and blockade of TGF-β significantly enhanced NK cell-derived CD107a and IFN-γ production. The immunohistochemical BI 6727 manufacturer staining showed that NKp46-positive cells

were more enriched in the α-SMA-negative area in livers from LC patients. Finally, NK cell cytolytic activity was also correlated negatively with liver fibrosis scores in HBV infected patients, which is further confirmed by the longitudinal follow-up of LC patients. Our findings may facilitate the rational development of immunotherapeutic strategies to enhance NK activity while limiting or abolishing liver fibrosis in chronic HBV infection. Disclosures: The following people have nothing to disclose: Juanjuan Zhao, Zheng Zhang, Yonggang Li, Fu-Sheng Wang Purpose Patients with chronic

hepatitis C infection (HCV) have low serum 25Hydroxyvitamin D (25(OH)D) levels which are associated with advanced fibrosis and low SVR. However, the impact of 25(OH)D levels on post transplant HCV fibrosis is unknown. Methods A total of 73 HCV cirrhosis patients who underwent protocol liver biopsies at Cleveland Clinic 6-12 months post transplant between January 201 1 and 2012 were retrospectively reviewed. A time-to-fibrosis analysis was performed and Kaplan-Meier plot was constructed to compare subject’s vitamin D levels. Univariable and multivariable AZD6738 research buy Cox regression was also performed. Results A majority (74%) had genotype 1 infection. Average vitamin D levels were 25.8 ± 13.3 ng/mL and deficiency (< 20 ng/mL) was observed in 31.1% of subjects. Thirty-one percent developed stage 1 or greater and 12% had stage 2 or more post-LT fibrosis. On univariable analysis, Caucasian subjects had 66% lower hazard of post-LT fibrosis compared to non-Caucasians

(HR=0.34; p=0.019). No evidence suggested vitamin D levels (p=0.52) nor vitamin D deficiency (p=0.28; Figure 1) contributed to post-LT fibrosis. On multivariable analysis non-Caucasians had 3.6 higher hazard of developing fibrosis post liver transplant than Caucasians (p=0.011); females had 4 times higher risk than males (p=0.01). Adjusting for ethnicity and gender, no evidence Amisulpride suggested 25 (OH) D levels contributed to post-LT fibrosis (p=0.73). Conclusion 25 (OH) D level deficiency is commonly seen in cirrhotics transplanted for HCV cirrhosis. We found that post-LT fibrosis was more common in non-caucasians and females. Vitamin D deficiency at the time of transplantation was not associated with post-liver transplant fibrosis in patients transplanted for hepatitis C virus related cirrhosis. Multi-center studies with larger number of patients are needed to further evaluate this relationship. Disclosures: The following people have nothing to disclose: Matthew J. Skomorowski, Rocio Lopez, Binu V.

All patients participated in either a sparse population-pharmacokinetic (PK) cohort or in an optional intensive-PK cohort, which involved a more intensive schedule of sample collection. Patients who participated in the population-PK cohort were stratified based on HCV genotype (i.e., 1a versus other genotype 1 subtypes). Plasma concentrations of vaniprevir were determined Ixazomib in vitro using liquid-liquid extraction, followed by high-performance liquid chromatography/tandem mass

spectrometry analysis. The lower limit of quantitation (LOQ) for the plasma assay was 1 ng/mL (1.32 nM) and the linear calibration range was 1-1,000 ng/mL. Sparse population PK samples were collected on selected days up to week 72. In addition, samples were also collected at multiple time points over the 12- or 24-hour dosing period for the subset of patients (∼4-8 patients per treatment group) included in the intensive-PK cohort. For all patients, the concentration

of drug in the plasma at 2 hours after dose and the trough concentration of drug in the plasma (Ctrough: concentration of drug in the plasma at 12 hours after dose for BID regimens and concentration of drug in the plasma at 24 hours after dose [C24h] for QD regimens) were assessed. The following additional plasma PK parameters were assessed for the intensive-PK cohort: area under the plasma-concentration versus time curve (AUC0-12h see more for the BID regimens and AUC0-24h for the QD regimens), time to reach maximum concentration (Cmax) (Tmax), and accumulation ratio, as appropriate. The accumulation of vaniprevir was determined by calculating the ratio of the PK parameter value (i.e., AUC, Cmax, and Ctrough) on days 28 and 1. WinNonlin (Pharsight Corporation, Mountain

View, CA) was used to determine PK parameters. The primary efficacy endpoint was the proportion of patients achieving RVR, defined as plasma HCV RNA below the limit of detection (LOD) at week 4. Exploratory efficacy endpoints included the proportion of patients achieving EVR (defined as plasma HCV RNA below the LOD at week 12) and the proportion of patients achieving SVR Thymidine kinase (defined as plasma HCV RNA below the LOD 24 weeks after completing treatment with Peg-IFN and RBV). The per-protocol (PP) population was predefined as the primary efficacy-analysis population. This excluded patients who had important deviations from the protocol, such as those taking prohibited medications or who fell below predetermined levels of compliance required for each component of the treatment. Only patients with HCV RNA results at week 4 were included in the analysis of RVR using the predefined missing primary data approach of data as observed (i.e., missing data were not replaced).

The ability of conventional ITI protocols involving high-dose FVIII infusion to reduce inhibitor titres may relate

to inhibiting the re-stimulation Selleck FK506 of FVIII-specific memory B cells and their differentiation into antibody-secreting plasma cells. In vitro and in vivo experiments in a mouse model of haemophilia A indicated that inhibition of memory B cell responses correlated with FVIII dose (Fig. 11) and that inhibition was irreversible at an FVIII dose of 20 μg mL−1 [37]. Elimination of B cells with rituximab is a feasible approach to inhibitor eradication but is not a permanent solution in all patients. Although long-term inhibitor eradication has been reported in patients following successful ablation of B cell with rituximab, it is expected that most patients will experience inhibitor relapse after B-cell repopulation [43]. Application of anti-idiotypic antibodies presents another means of interfering with the B-cell-mediated immune response. In recent experiments, mice were infused with an inhibitory monoclonal antibody against FVIII (GMA8021; Green Mountain Antibodies, Burlington, VT, USA). Addition of a highly specific anti-idiotype (JkH5) blocked the effects of GMA8021in a concentration-dependent fashion such that FVIII residual activity increased in line with higher concentrations of JkH5. Is it possible go even further

and translate these findings into clinical applications? Currently, collaborations with investigators from several Y-27632 cost major ITI studies including the International ITI Study and RES.I.ST allow the analysis of epitopes and IgG subclasses. The aim is to correlate molecular biology data with clinical outcomes and ITI course to increase understanding of the immune response, establish relevant biomarkers and improve prognosis for the patient. The success of ITI therapy depends largely on the inhibitor titre at the start of treatment. Other possible factors include genetic risk, type of concentrate (recombinant or plasma-derived), presence of danger signals (e.g. infections, surgery, immunizations etc). Data are also accumulating

which point to the influence of antibody signature on ITI course and success. Antibody epitopes have been shown to affect the reactivity of a patient’s plasma with different FVIII concentrates Astemizole in vitro [21-23, 25] as well as influence the course and success of ITI therapy [21, 24, 44, 45]. Van Helden and coworkers characterized the domain specificity of FVIII inhibitors in 11 patients with haemophilia receiving ITI [45]. In five patients, the relative contribution of anti-light chain or A2 inhibitors changed during the course of treatment. Antibodies directed towards the A2 domain of FVIII were observed in more patients who failed ITI, whereas antibodies exclusively directed towards the light chain were seen predominantly in patients who achieved successful tolerization.

The ability of conventional ITI protocols involving high-dose FVIII infusion to reduce inhibitor titres may relate

to inhibiting the re-stimulation Hydroxychloroquine ic50 of FVIII-specific memory B cells and their differentiation into antibody-secreting plasma cells. In vitro and in vivo experiments in a mouse model of haemophilia A indicated that inhibition of memory B cell responses correlated with FVIII dose (Fig. 11) and that inhibition was irreversible at an FVIII dose of 20 μg mL−1 [37]. Elimination of B cells with rituximab is a feasible approach to inhibitor eradication but is not a permanent solution in all patients. Although long-term inhibitor eradication has been reported in patients following successful ablation of B cell with rituximab, it is expected that most patients will experience inhibitor relapse after B-cell repopulation [43]. Application of anti-idiotypic antibodies presents another means of interfering with the B-cell-mediated immune response. In recent experiments, mice were infused with an inhibitory monoclonal antibody against FVIII (GMA8021; Green Mountain Antibodies, Burlington, VT, USA). Addition of a highly specific anti-idiotype (JkH5) blocked the effects of GMA8021in a concentration-dependent fashion such that FVIII residual activity increased in line with higher concentrations of JkH5. Is it possible go even further

and translate these findings into clinical applications? Currently, collaborations with investigators from several EPZ-6438 chemical structure major ITI studies including the International ITI Study and RES.I.ST allow the analysis of epitopes and IgG subclasses. The aim is to correlate molecular biology data with clinical outcomes and ITI course to increase understanding of the immune response, establish relevant biomarkers and improve prognosis for the patient. The success of ITI therapy depends largely on the inhibitor titre at the start of treatment. Other possible factors include genetic risk, type of concentrate (recombinant or plasma-derived), presence of danger signals (e.g. infections, surgery, immunizations etc). Data are also accumulating

which point to the influence of antibody signature on ITI course and success. Antibody epitopes have been shown to affect the reactivity of a patient’s plasma with different FVIII concentrates GPX6 in vitro [21-23, 25] as well as influence the course and success of ITI therapy [21, 24, 44, 45]. Van Helden and coworkers characterized the domain specificity of FVIII inhibitors in 11 patients with haemophilia receiving ITI [45]. In five patients, the relative contribution of anti-light chain or A2 inhibitors changed during the course of treatment. Antibodies directed towards the A2 domain of FVIII were observed in more patients who failed ITI, whereas antibodies exclusively directed towards the light chain were seen predominantly in patients who achieved successful tolerization.

Aim: To describe our centers http://www.selleckchem.com/products/ly2606368.html experience with NTZ in post LT HCV recurrence.

Methods: When used at our center, NTZ was prescribed off-label in prior non-responders or in patients with aggressive disease, such as early cholestatic HCV recurrence. NTZ was mainly used as lead in therapy for PEG-IFN/RBV. Demographics, clinical, immunosuppression and virologic data in LT recipients treated with NTZ/PEG-IFN/RBV were collected for descriptive analysis. The primary endpoint was sustained virologic response (SVR). Results: Nineteen patients were treated with NTZ, 2 were excluded for introduction of telaprivir to the course of treatment. The study group included 17 patients, mean age 50±4 years, including 13 (76%) males (13 (76% ) Caucasian, 2 (12%) Black, and 2 (12%) Hispanic), all had HCV genotype 1. NTZ was used in 13 (76%) prior non-responders and in 4 (23%) patients as part of their first course of HCV treatment post LT. Of the 13 non-responders, 9 (69%) were converted from tacrolimus to cyclosporine due to severity of HCV recurrence and 6 (46%) had advanced fibrosis prior to NTZ therapy. NTZ was introduced at 4.9±3.4 years post LT, as 4 week lead-in 10 (77%) and extended a further 4-16 weeks in 3 (23%) cases. Five (38%) patients previously had a <1 log and 4 (31%) had a >2log drop in viral

Kinase Inhibitor Library load, none had cleared virus on prior PEG-IFN/RBV, and 5 (38%). With NTZ/PEG-IFN/RBV 1 (8%) patient had <1 log and 5 (38%) had >2 log drop in viral load, with the latter 5 clearing HCV on treatment and 4 achieving SVR (31%), 2 with advanced fibrosis. Of the 4 treatment naive patients post-LT

receiving 4 week lead-in NTZ and PEG-IFN/RBV, 2 (cyclosporine) were treated for cholestatic HCV infection with <2 log response. Two patients (on tacrolimus) were treated 4-5 years post LT, without advanced fibrosis. Both cleared HCV on therapy, but 1 died before completing therapy (due to de novo malignancy) and 1 died after completing therapy but before SVR was established (due to pulmonary hemorrhage). Conclusion: LT recipients with HCV genotype 1 recurrence but without access to or success of direct acting agents, who are being considered for PEG-IN/ RBV may benefit from NTZ lead-in therapy. Disclosures: Paul Y. Kwo - Advisory Committees or Review Panels: Abbott, Novartis, Merck, Gilead, BMS, Janssen; Consulting: Diflunisal Vertex; Grant/Research Support: Roche, Vertex, GlaxoSmithKline, Merck, BMS, Abbott, Idenix, Vital Therapeutics, Gilead, Vertex, Merck, Idenix; Speaking and Teaching: Merck, Merck Marwan Ghabril – Grant/Research Support: Salix The following people have nothing to disclose: Marshall E. McCabe, Saurabh Agrawal, Marco A. Lacerda, A. Joseph Tector Introduction: Treatment (Tx) of Hepatitis C Virus (HCV) infection in kidney transplant (KT) recipients with interferon (IFN)-based regimens has been contra-indicated. IFN-free therapies with good safety profiles offer the opportunity of HCV Tx after KT for the first time.