In this study, we utilized radiotelemetry data spanning 13 years to assess differences in home range use and habitat selection by houbara bustards in the Mahazat as-Sayd reserve in Saudi Arabia. The mean (±standard error of the estimate) annual home range size, estimated using the Kernel density method, was 307.76 ± 15.91 km2, and did not differ

significantly between genders. Annual home ranges of wild-born houbaras were however larger than those of their captive-born counterparts (wild-born: 423.77 ± 62.66 km2, captive-bred: 299.31 ± 16.39 km2). Rainy season home ranges were the largest (279.29 ± 27.75 km2) followed by winter home ranges (245.79 ± 19.19 km2) and summer home ranges (110.51 ± 8.91 km2) indicating larger-scale movements of houbaras when forage was available. Seasonal check details home ranges did not differ significantly between wild-born or captive-bred houbaras. Analysis of habitat selection patterns using the distance-based method revealed consistent patterns of habitat Y-27632 manufacturer preferences across years and seasons and between genders, ages and whether the bird was captive-bred or wild-born. Results indicate that scrub forms the most preferred habitat for houbaras, and should be conserved for the population welfare of the houbara in Saudi Arabia. “
“Resource exploitation and

behavioural interference underlie competition among carnivores. Competition is reduced by specializing on different prey and/or spatio-temporal separation, usually leading to different food habits. We predicted that two closely related species of large cats, the endangered snow leopard and the near-threatened common leopard, living see more in sympatry, would coexist through habitat separation and exploitation of different prey species. In central Himalaya, we assessed

(2006–2010) habitat and diet overlap between these carnivores. The snow leopard used grassland and shrubland, whereas the common leopard selected forest. Contrary to our prediction, snow leopard and common leopard preyed upon similar wild (Himalayan tahr, musk deer) and domestic species (Bos spp., dogs). Dietary overlap between snow leopard and common leopard was 69% (yearly), 76% (colder months) and 60% (warmer months). Thus, habitat separation should be the result of other factors, most likely avoidance of interspecific aggression. Habitat separation may not always lead to the use of different prey. Avoidance of interspecific aggression, rather than exploitation of different resources, could allow the coexistence of potentially competing large predators. “
“Perceptual range is one of the main determinants of dispersal success in fragmented landscapes, which are composed of scattered remnants of original habitat in a matrix of variable composition.

7A-C). See the Results section of the Supporting Materials for further details. EGI-1, TFK-1, and CCA1 were selected for experiments with human fibroblasts (Fig. 3 and Supporting Figs. 8 and 9).[8] Effects of conditioned media from CCA INCB018424 mw cells on fibroblast proliferation (MTS assay) and migration (Boyden chamber) were studied

before and after addition of imatinib, a PDGFRβ antagonist. Effects of EGI-1 cells on fibroblast recruitment were also tested after treatment with siRNA for PDGF-D, resulting in a significant down-regulation of PDGF-D secretion (of approximately 35%-40%, as compared with scramble, P < 0.01 with siRNA1, P < 0.05 with siRNA2) (Supporting Fig. 8). As compared with starved fibroblasts, or with

fibroblasts exposed to conditioned medium MG 132 derived from control cholangiocytes, human fibroblasts showed only a mild increase in proliferative activity after exposure to conditioned media from the different CCA cells (from 7% to 15%, as compared to control cholangiocytes) (Fig. 3A). PDGFRβ blockade induced a significant reduction in the rate of proliferating cells in fibroblasts stimulated by EGI-1 and TFK-1 (P < 0.01 and P < 0.05, respectively). As compared to control cholangiocytes, all conditioned media from the different CCA cells induced a potent migration of human fibroblasts (increase of approximately 73%-74%), which reduced significantly after PDGFRβ blockade (P < 0.05 for all CCA cells) (Fig. 3B). Notably, in EGI-1 cells, both PDGF-D siRNA showed a significant reduction in fibroblast recruitment of an extent similar to PDGFRβ blocker (P < 0.05, as compared with scramble). Human fibroblasts exposed to rhPDGF-D

exhibit a similar behavior. Effects of rhPDGF-D on migration were significantly reduced when fibroblasts were exposed to imatinib. These results are detailed in the Supporting Materials and shown in Supporting Fig. 9. To study the signaling pathways activated by PDGFRβ in response to PDGF-D, we stimulated human fibroblasts with rhPDGF-D at increasing doses (0.1, 1, 10, and 100 ng/mL), and then modulation of phosphorylated ERK1/2 (p-ERK1/2) and phosphorylated JNK (p-JNK) expression (by western blotting) Demeclocycline and activation of RhoA, Rac1, and Cdc42 (by G-LISA) were evaluated in the presence or absence of imatinib treatment (Figs. 4 and 5 and Supporting Fig. 10). To determine the kinetics of activation of RhoA, Rac1, and Cdc42, preliminary G-LISA experiments were run at 1, 10, 20, 30, and 60 minutes after stimulation with rhPDGF-D (100 ng/mL). PDGF-D induced a significant increase of p-ERK1/2 only at the highest doses (P < 0.05 at 10 and 100 ng/mL), those able to stimulate also fibroblast proliferation, and this effect was abrogated by imatinib (Fig. 4A). In contrast, increase of p-JNK was significant starting from the lowest doses of rhPDGF-D (0.1 ng/mL; P < 0.01) and was abolished by imatinib (P < 0.01) (Fig. 4B).

7A-C). See the Results section of the Supporting Materials for further details. EGI-1, TFK-1, and CCA1 were selected for experiments with human fibroblasts (Fig. 3 and Supporting Figs. 8 and 9).[8] Effects of conditioned media from CCA PCI-32765 solubility dmso cells on fibroblast proliferation (MTS assay) and migration (Boyden chamber) were studied

before and after addition of imatinib, a PDGFRβ antagonist. Effects of EGI-1 cells on fibroblast recruitment were also tested after treatment with siRNA for PDGF-D, resulting in a significant down-regulation of PDGF-D secretion (of approximately 35%-40%, as compared with scramble, P < 0.01 with siRNA1, P < 0.05 with siRNA2) (Supporting Fig. 8). As compared with starved fibroblasts, or with

fibroblasts exposed to conditioned medium see more derived from control cholangiocytes, human fibroblasts showed only a mild increase in proliferative activity after exposure to conditioned media from the different CCA cells (from 7% to 15%, as compared to control cholangiocytes) (Fig. 3A). PDGFRβ blockade induced a significant reduction in the rate of proliferating cells in fibroblasts stimulated by EGI-1 and TFK-1 (P < 0.01 and P < 0.05, respectively). As compared to control cholangiocytes, all conditioned media from the different CCA cells induced a potent migration of human fibroblasts (increase of approximately 73%-74%), which reduced significantly after PDGFRβ blockade (P < 0.05 for all CCA cells) (Fig. 3B). Notably, in EGI-1 cells, both PDGF-D siRNA showed a significant reduction in fibroblast recruitment of an extent similar to PDGFRβ blocker (P < 0.05, as compared with scramble). Human fibroblasts exposed to rhPDGF-D

exhibit a similar behavior. Effects of rhPDGF-D on migration were significantly reduced when fibroblasts were exposed to imatinib. These results are detailed in the Supporting Materials and shown in Supporting Fig. 9. To study the signaling pathways activated by PDGFRβ in response to PDGF-D, we stimulated human fibroblasts with rhPDGF-D at increasing doses (0.1, 1, 10, and 100 ng/mL), and then modulation of phosphorylated ERK1/2 (p-ERK1/2) and phosphorylated JNK (p-JNK) expression (by western blotting) Rebamipide and activation of RhoA, Rac1, and Cdc42 (by G-LISA) were evaluated in the presence or absence of imatinib treatment (Figs. 4 and 5 and Supporting Fig. 10). To determine the kinetics of activation of RhoA, Rac1, and Cdc42, preliminary G-LISA experiments were run at 1, 10, 20, 30, and 60 minutes after stimulation with rhPDGF-D (100 ng/mL). PDGF-D induced a significant increase of p-ERK1/2 only at the highest doses (P < 0.05 at 10 and 100 ng/mL), those able to stimulate also fibroblast proliferation, and this effect was abrogated by imatinib (Fig. 4A). In contrast, increase of p-JNK was significant starting from the lowest doses of rhPDGF-D (0.1 ng/mL; P < 0.01) and was abolished by imatinib (P < 0.01) (Fig. 4B).

40 Our findings are very different to those of Ueki et al.26 who showed that transient knockdown of SOCS3 using small interfering RNA in livers of obese db/db mice reduced steatosis and improved hepatic insulin sensitivity. Ueki et al.26 suggested that the reduced steatosis in db/db mice was attributed to enhanced STAT3 phosphorylation and reduction in SREBP1c expression. Instead, we found that liver STAT3 phosphorylation was not different between chow and HFD-fed WT and SOCS LKO mice. These data when combined with findings showing Selleck CB-839 that STAT3 LKO mice do not develop hepatic steatosis when challenged with

an HFD27 suggest that STAT3 may not be a critical regulator of lipogenesis under conditions of diet-induced obesity. The development of greater obesity in HFD-fed SOCS3 LKO mice was unexpected. To elucidate the mechanisms contributing to the increased adiposity we performed food intake studies and calorimetry

and found that SOCS3 LKO mice fed an HFD exhibited increased food consumption and reduced caloric expenditure compared with controls. Previous studies have shown that oligonucleotide inhibition Neratinib of SCD-1 in the liver of obese animals not only rescues hepatic steatosis but also reduces food intake, increases energy expenditure and improves hepatic insulin sensitivity.41, 42 One mechanism by which this may occur is by reducing inflammation,43 which as recent studies have shown,14, 29-31 plays an important role in the development of hypothalamic leptin resistance and obesity. Therefore, our findings of increased inflammation and elevated hypothalamic expression of SOCS3 and orexigenic neuropeptides, NPY and AgRP, in HFD-fed but not chow-fed SOCS3 LKO mice is consistent with the role of liver inflammation regulating appetite and energy expenditure. Another possibility for the increased weight gain in HFD SOCS LKO mice may be related to hyperinsulinemia which increases the expression of FASn, an important regulator of appetite and energy expenditure.34 Lastly, it remains possible 3-oxoacyl-(acyl-carrier-protein) reductase that energy expenditure and appetite could be altered by liver-specific

effects on the vagus nerve44, 45 or by altering the expression of a circulating factor such as the soluble leptin receptor,46 however we believe these possibilities are relatively unlikely because we only observed differences when SOCS3 LKO mice were fed an HFD. In conclusion, we have shown that hepatic SOCS3 is a physiological regulator of insulin signaling in vivo and that it is involved in the maintenance of hepatic insulin sensitivity even in the absence of overt inflammation as found in lean chow-fed mice and unstimulated hepatocytes. Although the deletion of liver SOCS3 enhances hepatic insulin sensitivity, in the presence of an obesogenic milieu of hyperglycemia and elevated fatty acids it promotes the development of NAFLD and inflammation, factors which may contribute to the development of obesity and systemic insulin resistance.

40 Our findings are very different to those of Ueki et al.26 who showed that transient knockdown of SOCS3 using small interfering RNA in livers of obese db/db mice reduced steatosis and improved hepatic insulin sensitivity. Ueki et al.26 suggested that the reduced steatosis in db/db mice was attributed to enhanced STAT3 phosphorylation and reduction in SREBP1c expression. Instead, we found that liver STAT3 phosphorylation was not different between chow and HFD-fed WT and SOCS LKO mice. These data when combined with findings showing NU7441 research buy that STAT3 LKO mice do not develop hepatic steatosis when challenged with

an HFD27 suggest that STAT3 may not be a critical regulator of lipogenesis under conditions of diet-induced obesity. The development of greater obesity in HFD-fed SOCS3 LKO mice was unexpected. To elucidate the mechanisms contributing to the increased adiposity we performed food intake studies and calorimetry

and found that SOCS3 LKO mice fed an HFD exhibited increased food consumption and reduced caloric expenditure compared with controls. Previous studies have shown that oligonucleotide inhibition buy Erlotinib of SCD-1 in the liver of obese animals not only rescues hepatic steatosis but also reduces food intake, increases energy expenditure and improves hepatic insulin sensitivity.41, 42 One mechanism by which this may occur is by reducing inflammation,43 which as recent studies have shown,14, 29-31 plays an important role in the development of hypothalamic leptin resistance and obesity. Therefore, our findings of increased inflammation and elevated hypothalamic expression of SOCS3 and orexigenic neuropeptides, NPY and AgRP, in HFD-fed but not chow-fed SOCS3 LKO mice is consistent with the role of liver inflammation regulating appetite and energy expenditure. Another possibility for the increased weight gain in HFD SOCS LKO mice may be related to hyperinsulinemia which increases the expression of FASn, an important regulator of appetite and energy expenditure.34 Lastly, it remains possible Protein tyrosine phosphatase that energy expenditure and appetite could be altered by liver-specific

effects on the vagus nerve44, 45 or by altering the expression of a circulating factor such as the soluble leptin receptor,46 however we believe these possibilities are relatively unlikely because we only observed differences when SOCS3 LKO mice were fed an HFD. In conclusion, we have shown that hepatic SOCS3 is a physiological regulator of insulin signaling in vivo and that it is involved in the maintenance of hepatic insulin sensitivity even in the absence of overt inflammation as found in lean chow-fed mice and unstimulated hepatocytes. Although the deletion of liver SOCS3 enhances hepatic insulin sensitivity, in the presence of an obesogenic milieu of hyperglycemia and elevated fatty acids it promotes the development of NAFLD and inflammation, factors which may contribute to the development of obesity and systemic insulin resistance.

5E). Although BMP signaling did not induce Hex, a functional Hex gene is required for establishment of the liver fate, because BMP-4 was unable to induce Alb expression in Hex−/− endoderm (Fig. 5F). In contrast, BMP-4 did induce Tcf1 expression in the absence of Hex, although the levels were not as high as those observed in the wild-type population (Fig. 5G). Findings from these analyses suggest that Hex and BMP-4 can regulate Tcf1 expression independently, but optimal levels of expression require both pathways. We also evaluate if Hex can induce

BMP-4 mRNA levels. However, Hex did not affect the gene expression levels of BMP-4 (data not shown). To determine if BMP-4 and Hex have an impact on the hepatoblast stage of development, we analyzed the different populations for expression of Dlk1. Tanimizu et al.26 have shown that Dlk1 is expressed GSK2118436 cost on progenitors with hepatoblast potential as fetal liver cells sorted for this marker displayed both hepatocyte and biliary epithelial potential. Dlk1 message was detected Birinapant in day 10 EBs cultured in the absence of BMP-4 and Dox induction. Addition of BMP-4, but not the induction of Hex, increased the levels of Dlk1 expression. The relatively high levels of Dlk1 observed in the absence of BMP-4 appear to be a result of activin signaling, because substantially lower levels were detected in cells differentiated in

the absence of activin. Induction with BMP-4 doubled the Grape seed extract expression levels of Dlk1 in either the absence of presence of activin. Finally, neither factor induced significant levels of Dlk1 in the absence of a functional Hex gene. The directed differentiation of ESCs in culture is emerging as a powerful model system for studying mammalian development in vitro as well as a renewable source of functional cell types for transplantation for future cell-based therapy and for drug discovery and toxicology testing.27 Of the different cell populations that can be generated

from these pluripotent stem cells, hepatocytes are of particular interest because hepatocyte-based therapy has been considered as a new generation and effective treatment mode for liver diseases28 and the liver is a primary target organ of drug toxicity.29 A number of reports have documented the efficient generation of immature hepatocytes from both mouse and human ESCs,16–18 demonstrating that specification of this lineage can be studied in this model system. The most successful approaches to date have translated developmental biology to the culture dish and recreated the key aspects of the normal hepatic developmental program in the differentiation cultures. Although these studies collectively show that it is possible to generate populations with hepatic characteristics, the cells that do develop in the cultures remain immature.

45; P < 0.001) and not serum storage duration MAPK inhibitor (beta = 0.03; P = 0.786) was significantly associated with MDA levels. We also recognize that this cross-sectional study cannot imply causation, and that additional mechanistic studies will be required to definitively establish the role of RES cell iron in the induction of various apoptotic pathways. In conclusion, we found that both HC and RES iron deposition are associated with increased OS, compared to patients without stainable iron. However, RES, but not HC iron deposition, in this disease is characterized by increased apoptosis in the liver, as shown by both in situ

TUNEL staining in the liver and circulating CK18 levels and suggests a mechanism for increased disease severity.

By contrast, our data suggest that selective HC iron deposition in NAFLD may preferentially promote cell necrosis versus apoptosis. Longitudinal studies will also help delineate the dynamic relationship of iron and OS and the role of these in NAFLD progression. The authors thank Andrew Rhieu and Jilene Chua for their work in TUNEL assay development and imaging and Priya Handa for her helpful discussions. “
“The role vitamin D playing in patients with chronic hepatitis C has been intensively studied. However, studies on the potential interaction between vitamin D level and chronic hepatitis B are still limited. This study aimed to explore whether any association existed between serum vitamin D level find more and liver histology or virological parameters in patients with chronic hepatitis B infection in Southern China. 25-hydroxyvitamin D serum levels

were determined in a cohort of 242 treatment-naïve chronic hepatitis B patients. Histologic assessment was based on Knodell histologic activity index and Ishak fibrosis staging. Predictors of vitamin D insufficiency were identified using multivariate analysis. Mean 25-hydroxyvitamin D value was 33.90ng/ml. The percentage of patients with different concentration of 25-hydroxyvitamin D (≥30ng/ml, 20-30ng/ml, <20ng/ml) were 59.9%, 31.4% and 8.7%, respectively. Gender, Dolichyl-phosphate-mannose-protein mannosyltransferase season, age and viral genotype were independent predictors of vitamin D insufficiency (<30ng/ml). Patients with genotype B virus infection had a lower mean 25-hydroxyvitamin D level (p=0.023) and higher prevalence of vitamin D insufficiency than those with genotype C (p=0.021) , while no association was found between vitamin D status and viral load. In addition, 25-hydroxyvitamin D level did not significantly vary according to activity grade or fibrosis stage. The prevalence of vitamin D insufficiency is relatively low in our cohort. Patients infected with genotype B had a higher prevalence of vitamin D insufficiency than genotype C. 25-hydroxyvitamin D serum level is not associated with viral load or fibrosis stage in chronic hepatitis B patients.

Undoubtedly, significant challenges remain; however, the remarkable progress in iPS technology through the effort of a large number of innovative investigators

will impact our ability to understand liver diseases and to develop novel therapeutic interventions for years to come. 1 “
“Post liver transplantation care begins with immunosuppression induction and maintenance and continues with close monitoring of graft function as well as renal, metabolic ATM inhibitor and infectious diseases complications. A number of recipient, donor and operative factors influence post-operative complications. Neurogenic, cardiovascular, renal, gastrointestinal and metabolic side effects may manifest early or later in the post-transplant period, while primary disease recurrence and malignancy issues most often manifest later in the course. With improvement selleck chemicals llc in survival rates after liver transplantation, due to advances in surgical techniques and immunosuppression

drugs, non-transplant related causes like cardiovascular disease and de novo malignancies are becoming responsible for most late deaths in the recipients. Liver transplant recipients hence require a multi-disciplinary team approach from day one after the transplant followed by a tailored screening and health maintenance regimen. “
“Lipin-1 regulates lipid metabolism by way of its function as an enzyme in the triglyceride synthesis pathway and as a transcriptional coregulatory protein and is highly up-regulated in alcoholic fatty liver disease. In the present study, using a liver-specific lipin-1-deficient (lipin-1LKO) mouse model, we aimed selleckchem to investigate the functional role of lipin-1 in the development of alcoholic steatohepatitis and explore the underlying

mechanisms. Alcoholic liver injury was achieved by pair feeding wild-type and lipin-1LKO mice with modified Lieber-DeCarli ethanol-containing low-fat diets for 4 weeks. Surprisingly, chronically ethanol-fed lipin-1LKO mice showed markedly greater hepatic triglyceride and cholesterol accumulation, and augmented elevation of serum liver enzymes accompanied by increased hepatic proinflammatory cytokine expression. Our studies further revealed that hepatic removal of lipin-1 in mice augmented ethanol-induced impairment of hepatic fatty acid oxidation and lipoprotein production, likely by way of deactivation of peroxisome proliferator-activated receptor γ coactivator-1alpha, a prominent transcriptional regulator of lipid metabolism. Conclusions: Liver-specific lipin-1 deficiency in mice exacerbates the development and progression of experimental alcohol-induced steatohepatitis. Pharmacological or nutritional modulation of hepatic lipin-1 may be beneficial for the prevention or treatment of human alcoholic fatty liver disease.

Undoubtedly, significant challenges remain; however, the remarkable progress in iPS technology through the effort of a large number of innovative investigators

will impact our ability to understand liver diseases and to develop novel therapeutic interventions for years to come. 1 “
“Post liver transplantation care begins with immunosuppression induction and maintenance and continues with close monitoring of graft function as well as renal, metabolic selleck chemical and infectious diseases complications. A number of recipient, donor and operative factors influence post-operative complications. Neurogenic, cardiovascular, renal, gastrointestinal and metabolic side effects may manifest early or later in the post-transplant period, while primary disease recurrence and malignancy issues most often manifest later in the course. With improvement Selleckchem NVP-BGJ398 in survival rates after liver transplantation, due to advances in surgical techniques and immunosuppression

drugs, non-transplant related causes like cardiovascular disease and de novo malignancies are becoming responsible for most late deaths in the recipients. Liver transplant recipients hence require a multi-disciplinary team approach from day one after the transplant followed by a tailored screening and health maintenance regimen. “
“Lipin-1 regulates lipid metabolism by way of its function as an enzyme in the triglyceride synthesis pathway and as a transcriptional coregulatory protein and is highly up-regulated in alcoholic fatty liver disease. In the present study, using a liver-specific lipin-1-deficient (lipin-1LKO) mouse model, we aimed find more to investigate the functional role of lipin-1 in the development of alcoholic steatohepatitis and explore the underlying

mechanisms. Alcoholic liver injury was achieved by pair feeding wild-type and lipin-1LKO mice with modified Lieber-DeCarli ethanol-containing low-fat diets for 4 weeks. Surprisingly, chronically ethanol-fed lipin-1LKO mice showed markedly greater hepatic triglyceride and cholesterol accumulation, and augmented elevation of serum liver enzymes accompanied by increased hepatic proinflammatory cytokine expression. Our studies further revealed that hepatic removal of lipin-1 in mice augmented ethanol-induced impairment of hepatic fatty acid oxidation and lipoprotein production, likely by way of deactivation of peroxisome proliferator-activated receptor γ coactivator-1alpha, a prominent transcriptional regulator of lipid metabolism. Conclusions: Liver-specific lipin-1 deficiency in mice exacerbates the development and progression of experimental alcohol-induced steatohepatitis. Pharmacological or nutritional modulation of hepatic lipin-1 may be beneficial for the prevention or treatment of human alcoholic fatty liver disease.

Flamm – Advisory Committees or Review Panels: Gilead, Bristol Myers Squibb, AbbVie, Janssen, Salix; Consulting: Merck, Janseen, Bristol Myers Squibb, AbbVie, Salix, Gilead; Grant/Research Support: Janssen, Bristol Myers Squibb, Merck, Vertex, Gilead, AbbVie, Boehringer Ingelheim; Speaking and Teaching: Salix Jill M. Denning – Employment: Gilead Sciences, Inc. Sarah Arterburn – Employment: Gilead Sciences Inc.; Stock Shareholder: click here Gilead Sciences Inc. Phillip S. Pang – Employment: Gilead Sciences John G. McHutchison

– Employment: Gilead Sciences; Stock Shareholder: Gilead Sciences Michael P. Curry – Grant/Research Support: Gilead Sciences, Mass Biologics, Merck, Salix, Conatus; Stock Shareholder: Achilion, Idenix The following people have nothing to www.selleckchem.com/products/Imatinib-Mesylate.html disclose: Theo Brandt-Sarif, Michael Charl-ton Background: The all-oral antiviral regimen using sofosbuvir (SOF) and simeprevir (SMV) with/without ribavirin (RBV) has been reported to lead to high sustained virologic response (SVR) rates along with minimal adverse events (AE) when treating patients with hepatitis C genotype 1 (HCV GT1). The efficacy of this regimen in liver transplant (LT) recipients has not been described to date. Objective: To report the virological response, safety, and tolerability of SOF+SMV with/ without RBV in treating LT recipients with HCV GT1 for

12 weeks. Results: To date, 77 patients met criteria to consider treatment and 55 patients (78% male, 29% non-white, 73% subtype 1a, 77% IL28B CT/TT, 87% HCV RNA >800,000 IU/mL, 24% F3-4 with 4% decompensation and 15% choles-tatic recurrence, 7% Protein tyrosine phosphatase status post kidney transplantation) have received SOF+SMV, being followed for a median of 11 weeks (range 1-23 weeks). 83% previously failed or did not tolerate peginterferon+RBV (PR)-based treatments (68% with PR, 13% with PR+telaprevir/boceprevir, and 2% with PR+SOF). Weight-based RBV was used in 14 patients (25%) at the discretion of the treating physicians. RBV dose reduction and/or erythro-poietin

administration was required in 64% of these patients. Median time from LT to treatment was 22 months (range 2-272 months). Tacrolimus was the primary immunosuppression (IS) in 86% of patients, the remainder were on cyclosporine. Minimal IS dose adjustments were required during treatment. 4 patients (7%) had estimated GFR <30 mL/min. On-treatment virolog-ical response rates are shown in the Table. Of 40 patients who received treatment ≥4 weeks, 39 patients achieved HCV RNA