Hepatic stem cells and their mesenchymal partners, angioblasts, g

Hepatic stem cells and their mesenchymal partners, angioblasts, give rise to daughter cells maturing into lineages

of parenchymal and mesenchymal cells with stepwise changes in cell size, morphology, ploidy, gene expression, growth potential, and signaling.1-4 Currently, there is buy Ponatinib evidence for at least eight intrahepatic lineage stages (Figs. 1, 2).5, 6 Continued efforts to characterize the liver’s lineage biology should result in recognition of additional stages. This overview focuses on early intrahepatic lineage stages in human livers and includes aspects of their regulation. Information on later lineage stages of cells, and additional background and references are included in the online supplement. Hepatic stem cells (hHpSCs) are multipotent stem cells located within the liver’s stem cell compartment, the ductal plates of fetal and neonatal livers, and canals of Hering in pediatric and adult livers.5, 7-12 The compartment represents the anatomic and physiological link between the intralobular

canalicular system of hepatocytes and the biliary tree and resides along sites that project starlike from the portal tracts. They constitute ≈0.5%-2% of the this website parenchyma of livers of all age donors. The hHpSCs cells range in size from 7-9 μm in diameter and have a high nucleus-to-cytoplasm AMPK inhibitor ratio. Tolerant of ischemia, they can remain viable in cadaveric livers for up to ≈6 days after asystolic death.11, 12 The hHpSC phenotypic profile includes epithelial cell adhesion molecule (EpCAM), neural cell adhesion molecule (NCAM), CD133, CXCR4, SOX9, SOX17, FOXA2,

cytokeratins (CK) 8/18/19, Hedgehog proteins (Sonic and Indian), intranuclear telomerase protein, claudin 3, MDR1, weak or negligible expression of albumin and major histocompatibility complex (MHC) antigens. They do not express α-fetoprotein (AFP), intercellular adhesion molecule (ICAM-1), P450s, or markers for hemopoietic (e.g., CD34/38/45/90, glycophorin), endothelial (e.g., vascular endothelial growth factor receptor [VEGFr], CD31, von Willebrand factor), or mesenchymal cells (e.g., CD146, desmin, vitamin A, CD105).6, 7, 13 It remains unclear whether C-kit (CD117), expressed in the liver’s stem cell niches,8, 14, 15 is on hHpSCs or associated angioblasts, as CD117+ flow cytometry selects for angioblasts.

Our previous study indicated that postoperative adjuvant transcat

Our previous study indicated that postoperative adjuvant transcatheter arterial chemoembolization (TACE) could improve the survival of patients with risk factors for residual tumor.34 In our study, patients with a high risk of recurrence, evidenced by clinical features such as vascular invasion and microsatellite lesions, were given one to three courses of prophylactic TACE

(doxorubicin, cisplatin, 5-fluorouracil, and iodized oil) 1 month after surgery.35 BMN 673 mouse We retrospectively collected the data of HCC patients with ≥2 CTCs who performed the prophylactic TACE and compared the antirecurrence results with those who did not perform TACE, and found that prophylactic TACE was selleck chemicals beneficial in preventing recurrence in patients with ≥2 CTCs (P = 0.006) (Supporting Fig. 4). However, randomized controlled trials are needed for further validation. The limitations of this study are its relatively small cohort size, short follow-up time, and data from a single study center. A prospective, multicenter, randomized clinical trial should be designed to further validate the prognostic significance of CTCs in HCC. To our knowledge, this is the first report to identify the stem cell–like characteristics of EpCAM+ CTCs and their prognostic significance using the standardized CellSearch system in HCC patients. A preoperative EpCAM+ CTC7.5 level of ≥2 is an independent prognostic

indicator for recurrence in

HCC patients undergoing curative resection. Monitoring dynamic changes of perioperative CTCs may be a promising predictor of the response of the therapeutic regimen. Eradicating these cells might open a therapeutic avenue toward preventing HCC recurrence. Additional Supporting Information may be found in the online version of this article. “
“The differentiation of embryonic or determined stem cell populations into adult liver fates under known conditions yields cells with some adult-specific genes but not others, aberrant regulation of one or more genes, and variations in the results from experiment to experiment. We tested the hypothesis that sets of signals produced by freshly isolated, lineage-dependent mesenchymal cell populations would yield greater efficiency and reproducibility in driving Adenosine triphosphate the differentiation of human hepatic stem cells (hHpSCs) into adult liver fates. The subpopulations of liver-derived mesenchymal cells, purified by immunoselection technologies, included (1) angioblasts, (2) mature endothelia, (3) hepatic stellate cell precursors, (4) mature stellate cells (pericytes), and (5) myofibroblasts. Freshly immunoselected cells of each of these subpopulations were established in primary cultures under wholly defined (serum-free) conditions that we developed for short-term cultures and were used as feeders with hHpSCs.

Proportions of DCs were determined in suspensions of cells from M

Proportions of DCs were determined in suspensions of cells from MLNs and lamina propria by five-color quantitative flow cytometry in a FACSAria cytometer using FACSDiva software (Becton Dickinson). Analyses Fludarabine were carried out using FlowJo software (TreeStar Inc., Ashland, OR). Cell suspensions were incubated with a combination of the following mAbs to define DCs: PE-OX62 (OX62) (Serotec), PE-cyanin 5-CD45RA (OX33) (BD Pharmingen), APC-RT1B (HIS19) (eBioscience), and Alexa Fluor 700-CD3 (1F4) (Serotec). After surface staining, cells were fixed, permeabilized, and stained with FITC-TNF-α (eBioscience). TNF-α production was

determined after culturing DCs in DMEM (BioWhittaker) or stimulated with lipolysaccharide (LPS) (055:B5; 25 μg/mL; Sigma-Aldrich). LBH589 research buy MLNs and blood samples were inoculated into thioglycollate medium (Scharlab, Barcelona, Spain) and incubated at 37°C for 48 hours. Microorganisms were identified by a manual biochemical test or an automated system (Microscan; Baxter, Irvine, CA).

GBT and bacteriemia were defined by the presence of viable organisms in the MLNs or blood culture, respectively (i.e., a positive bacteriological culture). Total intestinal aerobic count was defined as the sum of all the aerobic bacteria present in the ileal content sample expressed as log10 colony-forming units (CFU)/g of stool.6 MLNs were homogenized in PBS by sonication (UP100H Ultrasonic Processor; Hielscher, Teltow, Germany). Genomic DNA from homogenized MLNs was isolated using the QIAmp Tissue Kit (Qiagen, Hilden, Germany), as described elsewhere.7, 16 Bacterial DNA (Bact-DNA) was identified by running a broad-range polymerase chain reaction, followed by nucleotide sequencing of a conserved region of the 16SrRNA gene. Results are shown as mean ± standard deviation. Quantitative variables were compared using the unpaired Student t test with Bonferroni’s correction for multiple comparisons.

The level of statistical significance was set at P < 0.05. Statistical analyses were performed using SPSS 15.0 for Etofibrate Windows (SPSS, Inc., Chicago, IL). Sixty-six rats were entered into the protocol of cirrhosis with ascites induction, of which 41 survived (62%). On average, rats developed ascites 15 weeks (range, 12-20) after the initial CCl4 dose. The average amount of ascites was greater in cirrhotic rats with than in those without GBT (19.6 ± 10.8 versus 12.1 ± 8.4 mL; P < 0.05). Twenty-two of the forty-one (54%) rats with cirrhosis showed GBT to the MLNs. Bact-DNA fragments were present in the MLNs of all animals with GBT and in 14 of the 19 (74%) animals without GBT. None of the 14 healthy control rats showed GBT or Bact-DNA in MLNs. Enteric aerobic bacterial loads were significantly higher and serum total protein and albumin levels lower in cirrhotic rats with GBT than in those lacking GBT (Table 1). None of the studied animals had bacteremia.

Proportions of DCs were determined in suspensions of cells from M

Proportions of DCs were determined in suspensions of cells from MLNs and lamina propria by five-color quantitative flow cytometry in a FACSAria cytometer using FACSDiva software (Becton Dickinson). Analyses selleck chemicals were carried out using FlowJo software (TreeStar Inc., Ashland, OR). Cell suspensions were incubated with a combination of the following mAbs to define DCs: PE-OX62 (OX62) (Serotec), PE-cyanin 5-CD45RA (OX33) (BD Pharmingen), APC-RT1B (HIS19) (eBioscience), and Alexa Fluor 700-CD3 (1F4) (Serotec). After surface staining, cells were fixed, permeabilized, and stained with FITC-TNF-α (eBioscience). TNF-α production was

determined after culturing DCs in DMEM (BioWhittaker) or stimulated with lipolysaccharide (LPS) (055:B5; 25 μg/mL; Sigma-Aldrich). Selleckchem Navitoclax MLNs and blood samples were inoculated into thioglycollate medium (Scharlab, Barcelona, Spain) and incubated at 37°C for 48 hours. Microorganisms were identified by a manual biochemical test or an automated system (Microscan; Baxter, Irvine, CA).

GBT and bacteriemia were defined by the presence of viable organisms in the MLNs or blood culture, respectively (i.e., a positive bacteriological culture). Total intestinal aerobic count was defined as the sum of all the aerobic bacteria present in the ileal content sample expressed as log10 colony-forming units (CFU)/g of stool.6 MLNs were homogenized in PBS by sonication (UP100H Ultrasonic Processor; Hielscher, Teltow, Germany). Genomic DNA from homogenized MLNs was isolated using the QIAmp Tissue Kit (Qiagen, Hilden, Germany), as described elsewhere.7, 16 Bacterial DNA (Bact-DNA) was identified by running a broad-range polymerase chain reaction, followed by nucleotide sequencing of a conserved region of the 16SrRNA gene. Results are shown as mean ± standard deviation. Quantitative variables were compared using the unpaired Student t test with Bonferroni’s correction for multiple comparisons.

The level of statistical significance was set at P < 0.05. Statistical analyses were performed using SPSS 15.0 for Florfenicol Windows (SPSS, Inc., Chicago, IL). Sixty-six rats were entered into the protocol of cirrhosis with ascites induction, of which 41 survived (62%). On average, rats developed ascites 15 weeks (range, 12-20) after the initial CCl4 dose. The average amount of ascites was greater in cirrhotic rats with than in those without GBT (19.6 ± 10.8 versus 12.1 ± 8.4 mL; P < 0.05). Twenty-two of the forty-one (54%) rats with cirrhosis showed GBT to the MLNs. Bact-DNA fragments were present in the MLNs of all animals with GBT and in 14 of the 19 (74%) animals without GBT. None of the 14 healthy control rats showed GBT or Bact-DNA in MLNs. Enteric aerobic bacterial loads were significantly higher and serum total protein and albumin levels lower in cirrhotic rats with GBT than in those lacking GBT (Table 1). None of the studied animals had bacteremia.

Proportions of DCs were determined in suspensions of cells from M

Proportions of DCs were determined in suspensions of cells from MLNs and lamina propria by five-color quantitative flow cytometry in a FACSAria cytometer using FACSDiva software (Becton Dickinson). Analyses Selleck Maraviroc were carried out using FlowJo software (TreeStar Inc., Ashland, OR). Cell suspensions were incubated with a combination of the following mAbs to define DCs: PE-OX62 (OX62) (Serotec), PE-cyanin 5-CD45RA (OX33) (BD Pharmingen), APC-RT1B (HIS19) (eBioscience), and Alexa Fluor 700-CD3 (1F4) (Serotec). After surface staining, cells were fixed, permeabilized, and stained with FITC-TNF-α (eBioscience). TNF-α production was

determined after culturing DCs in DMEM (BioWhittaker) or stimulated with lipolysaccharide (LPS) (055:B5; 25 μg/mL; Sigma-Aldrich). Ceritinib in vitro MLNs and blood samples were inoculated into thioglycollate medium (Scharlab, Barcelona, Spain) and incubated at 37°C for 48 hours. Microorganisms were identified by a manual biochemical test or an automated system (Microscan; Baxter, Irvine, CA).

GBT and bacteriemia were defined by the presence of viable organisms in the MLNs or blood culture, respectively (i.e., a positive bacteriological culture). Total intestinal aerobic count was defined as the sum of all the aerobic bacteria present in the ileal content sample expressed as log10 colony-forming units (CFU)/g of stool.6 MLNs were homogenized in PBS by sonication (UP100H Ultrasonic Processor; Hielscher, Teltow, Germany). Genomic DNA from homogenized MLNs was isolated using the QIAmp Tissue Kit (Qiagen, Hilden, Germany), as described elsewhere.7, 16 Bacterial DNA (Bact-DNA) was identified by running a broad-range polymerase chain reaction, followed by nucleotide sequencing of a conserved region of the 16SrRNA gene. Results are shown as mean ± standard deviation. Quantitative variables were compared using the unpaired Student t test with Bonferroni’s correction for multiple comparisons.

The level of statistical significance was set at P < 0.05. Statistical analyses were performed using SPSS 15.0 for Avelestat (AZD9668) Windows (SPSS, Inc., Chicago, IL). Sixty-six rats were entered into the protocol of cirrhosis with ascites induction, of which 41 survived (62%). On average, rats developed ascites 15 weeks (range, 12-20) after the initial CCl4 dose. The average amount of ascites was greater in cirrhotic rats with than in those without GBT (19.6 ± 10.8 versus 12.1 ± 8.4 mL; P < 0.05). Twenty-two of the forty-one (54%) rats with cirrhosis showed GBT to the MLNs. Bact-DNA fragments were present in the MLNs of all animals with GBT and in 14 of the 19 (74%) animals without GBT. None of the 14 healthy control rats showed GBT or Bact-DNA in MLNs. Enteric aerobic bacterial loads were significantly higher and serum total protein and albumin levels lower in cirrhotic rats with GBT than in those lacking GBT (Table 1). None of the studied animals had bacteremia.

The internal structure of both lineages was different from the is

The internal structure of both lineages was different from the isolectotype of Lessonia nigrescens. It is therefore concluded that the name Lessonia nigrescens should not be used for the Chilean material. Chordaria spicata Suhr appears as the oldest available name for the central lineage, while Lessonia

berteroana Montagne is the oldest name for the northern lineage. In both cases, the type material consisted of small-sized, apical branches of larger plants. The new combination Lessonia spicata (Suhr) Santelices is proposed click here for the central lineage and we reinstate Lessonia berteroana for the northern lineage. Laminaria scissa Suhr is reduced to synonym of L. spicata. Representative specimens of Lessonia nigrescens were not found during new visits to its type locality in Cape Horn and along Chile. Future studies should verify the status of this species. “
“In the Ross Sea, the prymnesiophyte Phaeocystis antarctica G. Karst. dominates deeply mixed water columns, while diatoms dominate shallower mixed layers. Understanding what controls the dynamics of these two phytoplankton taxa is essential because they dominate virtually all coastal polar waters, have different CH5424802 clinical trial nutrient

utilization characteristics, and support dissimilar food webs. We cultured two strains of P. antarctica and one strain of the diatom Fragilariopsis cylindrus (Grunow) Willi Krieg under three dynamic PDK4 irradiance regimes that simulated different mixed-layer depths and measured their photosynthetic characteristics, cellular pigment concentrations, and cellular carbon and nitrogen content. In both species, chl a–normalized maximum carbon uptake rate (Pm* ) and specific growth rate were highest in the deeply mixed treatment that had a dark period.

In all irradiance treatments, both (Pm* ) and photosynthetic efficiency (α*) were greater for the two P. antarctica strains than for the F. cylindrus strain. In contrast, P. antarctica strains were more susceptible to photoinhibition (β*) than the F. cylindrus strain. When photosynthetic rates of each phytoplankton taxon were normalized by cellular particulate organic carbon (POC), the difference in the maximal photosynthetic rate () was generally reduced. In the dynamic irradiance treatment that simulated the shallowest mixed-layer irradiance, all three phytoplankton had similar ; however, the diatom had a 2-fold higher POC-normalized photosynthetic efficiency (αC). Finally, we performed calculations using the measured POC-normalized photosynthetic parameters to show that αC and can play a greater role than βC in determining the competitive outcome between P. antarctica and F. cylindrus in both shallow and deep mixed-layer environments of the Ross Sea. “
“The chl-specific short-term 14C-based production (Pb) measurement is a widely used tool to understand phytoplankton responses to environmental stresses.

The internal structure of both lineages was different from the is

The internal structure of both lineages was different from the isolectotype of Lessonia nigrescens. It is therefore concluded that the name Lessonia nigrescens should not be used for the Chilean material. Chordaria spicata Suhr appears as the oldest available name for the central lineage, while Lessonia

berteroana Montagne is the oldest name for the northern lineage. In both cases, the type material consisted of small-sized, apical branches of larger plants. The new combination Lessonia spicata (Suhr) Santelices is proposed Apoptosis Compound Library concentration for the central lineage and we reinstate Lessonia berteroana for the northern lineage. Laminaria scissa Suhr is reduced to synonym of L. spicata. Representative specimens of Lessonia nigrescens were not found during new visits to its type locality in Cape Horn and along Chile. Future studies should verify the status of this species. “
“In the Ross Sea, the prymnesiophyte Phaeocystis antarctica G. Karst. dominates deeply mixed water columns, while diatoms dominate shallower mixed layers. Understanding what controls the dynamics of these two phytoplankton taxa is essential because they dominate virtually all coastal polar waters, have different find more nutrient

utilization characteristics, and support dissimilar food webs. We cultured two strains of P. antarctica and one strain of the diatom Fragilariopsis cylindrus (Grunow) Willi Krieg under three dynamic GBA3 irradiance regimes that simulated different mixed-layer depths and measured their photosynthetic characteristics, cellular pigment concentrations, and cellular carbon and nitrogen content. In both species, chl a–normalized maximum carbon uptake rate (Pm* ) and specific growth rate were highest in the deeply mixed treatment that had a dark period.

In all irradiance treatments, both (Pm* ) and photosynthetic efficiency (α*) were greater for the two P. antarctica strains than for the F. cylindrus strain. In contrast, P. antarctica strains were more susceptible to photoinhibition (β*) than the F. cylindrus strain. When photosynthetic rates of each phytoplankton taxon were normalized by cellular particulate organic carbon (POC), the difference in the maximal photosynthetic rate () was generally reduced. In the dynamic irradiance treatment that simulated the shallowest mixed-layer irradiance, all three phytoplankton had similar ; however, the diatom had a 2-fold higher POC-normalized photosynthetic efficiency (αC). Finally, we performed calculations using the measured POC-normalized photosynthetic parameters to show that αC and can play a greater role than βC in determining the competitive outcome between P. antarctica and F. cylindrus in both shallow and deep mixed-layer environments of the Ross Sea. “
“The chl-specific short-term 14C-based production (Pb) measurement is a widely used tool to understand phytoplankton responses to environmental stresses.

A systematic review of the current literature showed only in vitr

A systematic review of the current literature showed only in vitro evidence that there is no consensus on the advantage of using an offset configuration implant compared to those in straight-line configuration, even though some studies present a slight improvement of bone stress distribution when an offset implant is under oblique loading (PICO). “
“Purpose: The aim of this study was to assess the role of obturating systems, dowel materials, and adhesive techniques on the resistance to

fracture of endodontically treated teeth. Material and Methods: Eighty maxillary central incisors were selected and randomly divided into two groups according to the obturating system (n = 40); group I: gutta-percha and Roeko sealer; group II: RealSeal. Both groups were further subdivided into two subgroups; subgroup A: using ceramic

Y-27632 chemical structure dowels (Cosmopost); subgroup B using fiber dowels (Easy Post). Each subgroup was assigned to two divisions according to the adhesive luting technique; division V (total-etch) Variolink II resin cement; division U (self-adhesive) RelyX Unicem. Composite core build-up was made using a core former. Each specimen was loaded 2 mm from its incisal edge on the palatal side at a 135° angle with the long axis of the tooth using a universal testing machine with a load cell of 5 KN at a crosshead speed of 0.5 mm/min until fracture. Selleckchem LY2157299 Failure loads were recorded in N. Scanning electron microscopic examination at the dentin/resin interface (1000x) was performed. Three-way ANOVA was used to test the effect of obturating system, dowel material, adhesive technique, and their interactions (obturating system * dowel material, obturating system * adhesive, dowel material * adhesive, obturating system * dowel material * adhesive). Duncan’s test was used for pairwise comparison. The significance level was set at p≤ 0.05. Statistical analysis was performed with SPSS 16.0. Results: The mean resistance to fracture (617.4 N) was statistically significantly higher in the ceramic

dowel with gutta-percha and Variolink (GP/C/V) group than in the other groups. The RealSeal and RelyX fiber dowel group’s mean resistance was the lowest and was significantly lower than the other groups. Conclusions: In this study, three factors played a Resminostat part in enhancing the resistance to fracture of endodontically treated teeth. High resistance to fracture was achieved when ceramic dowels were luted with total-etch technique in gutta-percha-obturated teeth. “
“Despite the excellent esthetics of veneered zirconia crowns, the incidence of chipping and fracture of veneer porcelain on zirconia crowns has been recognized to be higher than in metal ceramic crowns. The objective of this investigation was to study the effect of selected variations in core thickness on the post-fatigue fracture resistance of veneer porcelain on zirconia crowns.

[12, 13] DDI studies have been conducted with CNIs (tacrolimus an

[12, 13] DDI studies have been conducted with CNIs (tacrolimus and cyclosporine) and the protease inhibitors, telaprevir and http://www.selleckchem.com/products/Belinostat.html boceprevir.[11, 14, 15] Single-dose CNI exposure studies in healthy volunteers have demonstrated a several-fold augmentation of levels of CNIs after administration of boceprevir and telaprevir (cyclosporine 2.70- and 4.64-fold and tacrolimus 17.1- and 70.3-fold with boceprevir and telaprevir, respectively).[11] Thus, the doses of either cyclosporine or

tacrolimus are to be reduced several-fold while on a protease inhibitor and revamped back to their baseline after the protease inhibitor is removed from the treatment regimen. The management of anemia either with RBV dose reduction and with or without the addition of an ESA and/or the use of blood transfusions brings in another layer of complexity. Yet, the successful eradication of HCV in these patients who have a risk of progressive liver disease and graft failure is indeed rewarding and justifies intervention with protease inhibitor-based therapy. The main goal of treating the transplant recipient with recurrent infection with HCV is to achieve SVR (undetectable HCV RNA 12 weeks or more after the end of treatment). SVR preserves graft function, improves graft survival, and improves both patient Daporinad cost outcome and survival.

Today’s options for antiviral treatment are PEG-RBV alone or with either telaprevir or boceprevir (TT) for GT1. Most centers treat patients who are 6 months or more post-transplant and have aggressive HCV recurrence.[10] Dr. Reddy’s patient was transplanted in 2007 and had early recurrence of hepatitis C, which progressed rapidly to advanced fibrosis by 2009. Treatment to prevent disease progression and graft loss was clearly indicated. In nontransplant patients, next certain characteristics have been associated with a favorable response to TT:

responsiveness to IFN, defined by favorable IL28b polymorphism (genotype CC), decline in HCV RNA during lead-In with PEG-RBV, or achieving undetectable HCV RNA during a previous course of PEG-RBV; noncirrhotic stages of fibrosis; and in patients with cirrhosis, compensated disease (no complications and normal international normalized ratio, bilirubin, and albumin). Dr. Reddy’s patient was treated with PEG-RBV both pre- and post-transplant and achieved undetectable HCV RNA during post-transplant PEG-RBV, but relapsed. He demonstrated responsiveness to IFN, lacked cirrhosis or complications of liver disease, and thus was a good candidate for retreatment with TT. However, use of TT after transplant presents unique challenges. First, the treating physician must have a plan of management to define tolerability and response to PEG-RBV, DDIs, management of anemia and other side effects, and treatment duration. Our treatment protocols have been presented in a recent review.[10] Dr.

In renal transplantation, large randomized trials have shown that

In renal transplantation, large randomized trials have shown that both IL-2Ra reduce the incidence Temsirolimus purchase of acute rejection and have a relatively good toxicity and safety profile.5,

6 But there have also been some concerns about the long-term effects, especially regarding posttransplant lymphoproliferative disorders (PTLD) and other malignancies.3 The effects of IL-2Ra have also been evaluated in a meta-analysis of kidney transplant recipients.7 The results showed that induction with IL-2Ra significantly reduces the risk of acute rejection but has no effect on graft or patient survival. A first nonsystematic review of the literature showed that in liver transplant patients, IL-2Ra are not only used in addition to standard immunosuppression but are mainly used to reduce other immunosuppressive drugs, such as calcineurin inhibitors (CNI) and corticosteroids, thereby possibly decreasing the

incidence and severity of their adverse effects. We have therefore structured this meta-analysis into three separate comparisons as follows: (1) comparison of IL-2Ra versus placebo or no treatment; (2) comparison of IL-2Ra with reduced and/or delayed CNI versus placebo or no IL-2Ra treatment in combination with standard immunosuppression; and (3) comparison of IL-2Ra and reduced or no corticosteroids versus placebo or no IL-2Ra treatment in combination with standard immunosuppression. ACA, available-case-analysis; AE, adverse event; CMV, cytomegalovirus; INCB018424 mouse CNI, calcineurin inhibitor; eGFR, estimated glomerular filtration rate; GFR, glomerular filtration rate; HCV, hepatitis C virus; IL-2R, interleukin-2 receptor; IL-2Ra, interleukin-2 receptor antagonists; ITT, intention-to-treat analysis;

LOCF, last-observation-carried-forward; MD, mean difference; MDRD, modification of diet in renal disease; MMF, mycophenolate mofetil; NNT, number needed to treat; PTDM, post-transplant diabetes mellitus; PTLD, post-transplant lymphoproliferative disease; REML, restricted maximum likelihood; SAE, serious adverse event. The methods of literature search, the inclusion and exclusion criteria, outcome measures, and methods of statistical analysis were defined in a protocol according to the recommendations in the Cochrane Handbook for Systematic Reviews of Interventions.8 We also used the Preferred Items for Systematic Reviews and Meta-Analysis (PRISMA) and Meta-Analysis of Observational Studies in Epidemiology MycoClean Mycoplasma Removal Kit (MOOSE) recommendations for study reporting.9, 10 A systematic literature search was performed without language restrictions from inception to December 2010 in the following databases: Medline/PubMed, Embase, Transplant Library, and Cochrane Library. The keywords used were “liver transplantation,” “interleukin 2 receptor inhibitor/antagonist,” “basiliximab,” “daclizumab,” “simulect,” “zenapax,” and abbreviations thereof, combined with appropriate Boolean operators. The reference lists in all identified trials were examined for further relevant articles.