Platelet MP and VWF-bearing MP were significantly increased after DDAVP. MP depletion by magnetic Cell Cycle inhibitor bead selection led to a significant reduction in VWF:Ag (−18.0%) and VWF:RCo (−27.7%) plasma levels without changes in VWF multimer composition. As results were similar for DDAVP control

subjects, the amount of VWF bound to circulating microparticles was significantly higher after DDAVP administration compared with healthy controls (reduction −11.7%). DDAVP leads to a release of microparticles and increases the amount of VWF bound to microparticles which might explain the clinical efficacy of DDAVP in platelet disorders. “
“The risk of bleeding in patients with hereditary bleeding disorders (HBD) undergoing gastro-intestinal (GI) endoscopic procedures is unknown but guidelines generally recommend correction of factor deficiency. Investigate the safety of oral tranexamic acid (TA) without prophylactic factor replacement to prevent bleeding complications in patients with HBD undergoing elective GI endoscopic procedures. A prospective single-arm pilot study testing the feasibility of using TA, without prophylactic factor replacement

or desmopressin preprocedure, for prevention of bleeding complications following elective standard risk (<1% risk of bleeding) endoscopic procedures in patients learn more with HBD. Baseline factor levels, haemoglobin and iron studies (IS) were measured preprocedure. Primary outcome of bleeding (NCI CTCAE Cyclic nucleotide phosphodiesterase v3.0 Bleeding Scale) was undertaken by patient review and repeat Hb, IS on day 21. Twenty-eight patients underwent

32 GI endoscopic procedures from September 2010 until June 2012. The median age was 53 years (range 24–75 years) and disease types included mild haemophilia A/B (n = 12), severe haemophilia A/B (n = 9), von Willebrand disease (n = 5), FXI deficiency (n = 1) and FVII deficiency (n = 1). Procedures performed included 11 gastroscopies, 12 colonoscopies, 8 gastroscopies and colonoscopies and 1 flexible sigmoidoscopy. Fourteen standard risk procedures and two high risk procedures were performed. Two patients experienced Grade 1 bleeding and one patient experienced Grade 2 bleeding. This study suggests that TA without prophylactic factor replacement may be a safe approach for mild and moderate HBD patients undergoing standard risk endoscopic procedures, particularly where no biopsy is performed. These findings should be confirmed in a larger study. “
“Congenital factor XIII (FXIII) deficiency is a severe bleeding disorder. We previously identified an Arg260Cys missense mutation and an exon-IV deletion in patients’ A subunit genes, F13A. To characterize the molecular/cellular basis of this disease, we expressed a wild type and these mutant A subunits in baby hamster kidney (BHK) cells. The mutant proteins were expressed less efficiently than the wild type.

The incision site was closed, and animals were given 0.1 mg/kg buprenorphine (Reckitt Benckiser Pharmaceuticals, Richmond, VA) every 12 hours for 48 hours. Past studies have indicated that transplanting mice with hHpSCs first and then establishing liver failure results in survival of all the transplanted mice, whereas the reverse results in significant loss of mice.25 For liver injury models,

a one-time dose of carbon tetrachloride (CCl4; Sigma-Aldrich, St. Louis, MO) was administered intraperitoneally at 0.6 μL/g. Experiments were repeated at least three times with duplicate or triplicate samples for each condition. Data from representative experiments are presented where similar trends were seen in multiple trials. Results are presented as the mean ± SEM. Statistical analysis of data was performed Metabolism inhibitor PLX4032 order by a one-way ANOVA. Significant findings were followed with pair-wise t tests corrected for multiple comparisons using the step-down Bonferroni method. Additional methods can be found in the Supporting Information. The hHpSCs survived and maintained

a stable stem cell phenotype for more than 3 weeks in cultures when fed KM and when embedded within composite matrix biomaterials (HA, type III collagen, laminin), conditions found in stem cell niches. In both forms of hyaluronan hydrogels used (HA versus HA + collagen III + laminin), messenger RNA expression levels (Fig. 1A) show a significant (P < 0.05) fold increase in EpCAM (7.72 ± 1.42, 9.04 ± 1.82) and albumin (5.57 ± 0.73, 4.84 ± 0.84) when compared with cells on plastic. There was also a significant decrease in AFP (0.55 ± 0.11, 0.17 ± 0.03) and an increase in NCAM, the combination of which indicates that cells maintain a stem cell phenotype. When the hHSC was lineage restricted to hHBs, they lost NCAM and dramatically increased their expression of AFP.14 At the protein expression level, cells in hyaluronans with or without other matrix components demonstrated coexpressed EpCAM and NCAM (Fig. 1B). In

hydrogels supplemented with type III collagen and laminin, the EpCAM signal Bay 11-7085 was the strongest compared with that in HA hydrogel alone. Immunosorbent assays on regularly collected media showed that normalized albumin, transferrin, and urea concentrations were stably synthesized by cells in both HA hydrogel conditions (Fig. 2). We used luciferin-marked cells transplanted into livers of immunocompromised mice, and used bioluminescent signal acquisition to test cell localization and engraftment efficiency with grafting versus other transplantation strategies. The marking was achieved using an adenoviral vector, Ad-CMV-Luc, that does not integrate in the genome and provides intense but only transient expression enabling whole animal imaging. The expression is terminated at a time point between 48 and 72 hours or soon thereafter due to silencing of the promoter by methylation mechanisms.

The incision site was closed, and animals were given 0.1 mg/kg buprenorphine (Reckitt Benckiser Pharmaceuticals, Richmond, VA) every 12 hours for 48 hours. Past studies have indicated that transplanting mice with hHpSCs first and then establishing liver failure results in survival of all the transplanted mice, whereas the reverse results in significant loss of mice.25 For liver injury models,

a one-time dose of carbon tetrachloride (CCl4; Sigma-Aldrich, St. Louis, MO) was administered intraperitoneally at 0.6 μL/g. Experiments were repeated at least three times with duplicate or triplicate samples for each condition. Data from representative experiments are presented where similar trends were seen in multiple trials. Results are presented as the mean ± SEM. Statistical analysis of data was performed check details Metformin in vivo by a one-way ANOVA. Significant findings were followed with pair-wise t tests corrected for multiple comparisons using the step-down Bonferroni method. Additional methods can be found in the Supporting Information. The hHpSCs survived and maintained

a stable stem cell phenotype for more than 3 weeks in cultures when fed KM and when embedded within composite matrix biomaterials (HA, type III collagen, laminin), conditions found in stem cell niches. In both forms of hyaluronan hydrogels used (HA versus HA + collagen III + laminin), messenger RNA expression levels (Fig. 1A) show a significant (P < 0.05) fold increase in EpCAM (7.72 ± 1.42, 9.04 ± 1.82) and albumin (5.57 ± 0.73, 4.84 ± 0.84) when compared with cells on plastic. There was also a significant decrease in AFP (0.55 ± 0.11, 0.17 ± 0.03) and an increase in NCAM, the combination of which indicates that cells maintain a stem cell phenotype. When the hHSC was lineage restricted to hHBs, they lost NCAM and dramatically increased their expression of AFP.14 At the protein expression level, cells in hyaluronans with or without other matrix components demonstrated coexpressed EpCAM and NCAM (Fig. 1B). In

hydrogels supplemented with type III collagen and laminin, the EpCAM signal Baricitinib was the strongest compared with that in HA hydrogel alone. Immunosorbent assays on regularly collected media showed that normalized albumin, transferrin, and urea concentrations were stably synthesized by cells in both HA hydrogel conditions (Fig. 2). We used luciferin-marked cells transplanted into livers of immunocompromised mice, and used bioluminescent signal acquisition to test cell localization and engraftment efficiency with grafting versus other transplantation strategies. The marking was achieved using an adenoviral vector, Ad-CMV-Luc, that does not integrate in the genome and provides intense but only transient expression enabling whole animal imaging. The expression is terminated at a time point between 48 and 72 hours or soon thereafter due to silencing of the promoter by methylation mechanisms.

Experiments were performed as described by the manufacturer. For quantification of serum levels of CCL2 and CCL5,

Mouse MCP-1 Flex Set and Mouse RANTES Flex Set (BD) were used. Instrument set-up and experiments were performed with Mouse/Rat Soluble Protein Master Buffer Kit (BD) on the BD FACSArray bioanalyzer software. Data analysis was done on BD FCAP Array software. All experimental procedures were done as recommended by the manufacturer. Hepatic collagen levels were quantified by way of C59 wnt determination of hydroxyproline content as described.21 Briefly, liver samples were homogenized in distilled water. The homogenates were hydrolyzed in 6 N HCl (final concentration) by incubating at 110°C for 18 hours. The hydrolysates were filtered (Millex-HV, Millipore) and evaporated by speed vacuum centrifugation. The sediments or 10-100 μg of standards (high-purity trans-4-hydroxy-L-proline, Sigma-Aldrich) were dissolved in 50 μL of distilled water, then mixed with 450 μL of 56 mM chloramines-T (Sigma-Aldrich) in acetate-citrate buffer (pH 6.5) and incubated for 25 minutes

at room temperature. Subsequently, 500 μL of Ehrlich’s solution (Fluka) was added, mixed, and incubated at 65°C for 20 minutes, followed by reading the absorbance at 562 nm. Control liposome and clodronate liposome were synthesized as described22 and injected intraperitoneally (10 Fluorouracil μL/g mouse) from the age of 3 weeks on. At the age of 12 weeks all animals were sacrificed and analyzed further. Data are shown as means ± standard deviation (SD). Statistical Rebamipide significance was determined using a two-tailed Student’s t test. P < 0.05 was considered significant. To understand the effect of NF-κB activation in the liver, we crossed mice carrying a constitutively active IKK2 (CAIKK2) allele17 under the control of a tetracycline-regulated promoter with animals expressing tTA under the control of the LAP promotor.14 The resulting double

transgenic mice were termed CAIKK2LAP (Supporting Fig. 1A). Given the known critical role of NF-κB in hepatocytes during embryonic development, we repressed transgenic IKK2 expression by DOX administration in the drinking water to the pregnant mothers. Using this strategy, double transgenic mice were born at the expected Mendelian frequency. Measurements of luciferase, which was used as a reporter gene, confirmed the absence of transgene expression in the DOX-administered animals (Supporting Fig. 2A). Removal of DOX at birth led to induction of luciferase, whereas no luciferase activity was observed in animals continuously treated with DOX (Supporting Fig. 1B). In vivo imaging and luciferase assays revealed that expression of the transgene reporter luciferase was restricted to the liver both in vivo and in vitro (Supporting Figs. 1B, 2A). Furthermore, expression of CAIKK2 transgene was detectable in the liver, but not in isolated HSCs or Kupffer cells (Supporting Fig. 1C).

Percentage necrosis in explanted tumors was correlated with imaging findings. 100%, 50%-99% and <50% pathological necrosis was observed in 6 (67%), 1 (11%), and 2 (22%) tumors in Group A and 3 (42%), 2 (28%), and 2 (28%) in Group B, respectively (P = 0.81). While ADC (P = 0.46) did not change after treatment, WHO (P = 0.06) and RECIST (P = 0.08) response at 1 month failed to reach significance,

but significant responses by EASL (P < 0.01/0.03) and mRECIST (P < 0.01/0.03) SB525334 at 1 and 3 months were observed. Response was equivalent by EASL or mRECIST. No difference in response rates was observed between groups A and B at 1 and 3 months by WHO, RECIST, EASL, mRECIST or ADC measurements. Despite failing to reach significance, smaller baseline size was associated with complete pathological necrosis (CPN) (RECIST: P = 0.07; WHO: P = 0.05). However, a cut-off size of 35 mm was predictive of CPN (P = 0.005). CPN could not be predicted by WHO (P = 0.25 and 0.62), RECIST (P = 0.35 and 0.54), EASL (P = 0.49 and 0.46), mRECIST (P = 0.49 and 0.60) or ADC (P = 0.86 and 0.93). Conclusion: The adjunct of Sorafenib did not augment radiological or pathological response to Y90 therapy for HCC. Equivalent significant reduction in enhancement at 1 and 3 months

by EASL/mRECIST was noted. Neither EASL nor mRECIST could reliably predict CPN. (HEPATOLOGY 2013;58:1655–1666) The development of surrogate markers for locoregional therapies (LRTs) in hepatocellular carcinoma (HCC) is www.selleckchem.com/products/dabrafenib-gsk2118436.html desirable to improve treatment planning and accelerate design and endpoints in clinical trials. Before validation, early imaging surrogate markers face different challenges, including methodological considerations, reproducibility, accuracy to detect real treatment response, and, potentially most important, detection of a survival benefit. In comparison with survival, surrogate endpoints (time to progression [TTP] and progression-free survival) offer the advantage of potentially less-confounding effect by concomitant liver (i.e., cirrhosis, fibrosis) or systemic diseases as well as previous or subsequent locoregional or systemic

treatment.[1] The European Association for the Study of the Liver (EASL) guidelines (2011) advocate the use of enhancing tissue to assess imaging response of HCC.[2] Modified Response Evaluation Criteria in Solid Tumors (mRECIST) were TCL devised with keeping this concept in mind and are currently being proposed as the standard methodology of radiological response in HCC.[3] However, few radiological-pathological studies support these criteria; our research group has previously highlighted the relevance of these important correlative concepts for both chemo- and radioembolization.[4-6] Uni- and bidimensional measurements of the entire treated tumor (Response Evaluation Criteria in Solid Tumors [RECIST] and World Health Organization [WHO] criteria) are often criticized, given their lack of correlation with viable tumor.

For this study, we selected miR-20a, miR-92a, miR-122, miR-21, miR-146a, miR-221 because of their implication in liver fibrosis. Their expression was assessed INCB024360 by RT-qPCR in serums and biopsies samples. Results In liver biopsies, a higher expression of hepatic miR-122 (p<0,0001), miR-92a (p=0,026) and miR-20a (p=0,024) was observed in patients with mild (F1) and moderate fibrosis (F2) compared to those with severe fibrosis (F3-F4). There were no significant differences in the expression of miR-21, miR-146a and miR-221 in liver biopsies. The

expression of mir-122, mir-92a and mir-20a was decreased in 5 patients whose fibrosis stage increased from mild to moderate fibrosis. Decreased hepatic miR-122 and miR-20a have been previously described in patients with hepatocellular carcinoma. There was no significant difference in the level of expression of mir-122, mir-92a and mir-20a in the serum of patients with mild and moderate fibrosis and those with severe fibrosis. While mir-122 in the serum was correlated with ALT, no significant association

was found for mir-92a and mir-20a. Conclusions Interestingly, the expression of hepatic miR-122, miR-92a and miR-20a was higher in patients with mild and moderate fibrosis as compared to those with more advanced fibrosis. The study of the five paired biopsies confirmed the importance of those miRNAs during fibrosis progression. Disclosures: Nathalie Boyer – Board Membership: MSD, JANSSEN, Gilead, Abbvie; Speaking Everolimus and Teaching: BMS Patrick Marcellin – Consulting: Roche, Gilead, BMS, Vertex, Novartis, Janssen, MSD, Abbvie, Alios BioPharma, Idenix, Akron; Grant/Research Support: Roche, Gilead, BMS, Novartis, Janssen, MSD, Alios BioPharma; Speaking and Teaching: Roche, Gilead, BMS, Vertex, Novartis, Janssen, MSD, Boehringer, Pfizer, Abbvie Tarik Asselah – Advisory Committees or Review Panels: AbbVie, Boerhinger-Ingelheim, Gilead, BMS, Roche, Janssen The following people have nothing to disclose:

Kevin Appourchaux, Emilie Estrabaud, Philippe Broet, Martine Amoxicillin Lapalus, Michelle Martinot-Peignoux, Michel Vidaud, Pierre Bedossa Background: Recent therapeutic advances promise greater convenience (oral therapies) with higher efficacy (>90% sustained viral response (SVR), and shorter duration of treatment than current standard of care in Europe. The implementation of these higher-cost agents to abrogate the escalating disease burden of untreated HCV infection requires robust epidemiological data and country-specific mathematical modeling to assess the potential impact of improved HCV treatment strategies. Methods: Disease progression was modeled using age-and gender-defined cohorts to track HCV incidence, prevalence, morbidity and mortality. Baseline assumptions were derived from published literature and unpublished data.

The coauthors of this article were all involved with this conference and consequently created an international group to overcome this shortcoming by working on a new staging system. Recently, a group of experts16 proposed a new staging system for IHC; the various grades were validated with a large database available in the United States. In this article, we focus on PHC, the most common and challenging form of CCA. Our aim is to propose a simple, reproducible, easily applicable, find protocol and informative staging system. To achieve

this goal and enable international acceptance, the staging will be established by the consensus of a group of international experts in the field. First, we discuss the need for a staging system. Next, we review the currently available staging systems. Then, we present the information needed to establish a valuable staging system. Finally, we submit our proposal for a new staging system. In contrast to IHC, it is currently not possible to test the ability of the new staging system to predict the natural history of the disease or the outcome after surgery because this information is not available in any large database. Our goal, therefore, is to offer a descriptive

system that will enable us to test correlations of various tumor characteristics with survival or other outcomes once a prospective database is available. Upon the publication of this article, we will open a professionally designed, online-based registry for PHC that is based on the new proposal www.cholangioca.org. A staging system PARP inhibitor for patients with cancer must ideally (1) provide information about the prognosis and natural history of the disease, (2) serve as a guide for therapy, and (3) enable convincing comparisons of therapies among various institutions and over time.17 In so-called surgical diseases, a staging system is crucial for deciding between an aggressive approach (i.e., chance for cure) and only palliative alternatives. Another criteria for a good

staging system is its ability to identify patients for the best type of surgery (e.g., local resection versus extensive Quinapyramine resection or even liver transplantation). Staging systems for cancer usually describe the extent of the disease according to the primary tumor and its spread. The tumor-node-metastasis (TNM) classification is the gold standard for many cancers because it is simple to understand, applies to many types of cancers, and provides information on the primary tumor (T), the lymph node status (N), and distant metastases (M).17, 18 Unfortunately, this system is of little help when local factors, such as the precise localization of the tumor along the bile duct, are crucial to predicting the natural history of the disease and choosing the therapy.

Disruption of the epithelial barrier Cobimetinib clinical trial is often associated with the increase of cell shedding. This study aims to investigate the mechanisms how mucosal protectants maintain the integrity of intestinal epithelial barrier in

indomethacin-induced enteropathy by observing real-timely the gap density using confocal laser endomicroscopy (CLE). Methods: A method to evaluate real-timely the intestinal epithelial barrier damage after administration of indomethacin in rats were established using a new technique CLE by investigating the gap density in small intestine. Then the mucosal protectant teprenone and proton pump inhibitor rabeprazole were given by gavage before and after the administration of indomethacin. Then, the mechanisms of how these medicines affect the intestinal epithelial barrier were investigated by investigating gap density and TNF- α pathway. Results: Gaps could be clearly observed by CLE, Gap density increased after indomethacin administration. During this process, the expressions of TNF- α, NF-kB and Caspase-3 were up-regulated while the expressions of tight junction were down-regulated. Teprenone and rabeprazole could interfere in the damage process and protect the integrity of the epithelial

barrier. Conclusion: CLE can be more objective, accurate and real-time to Doxorubicin in vitro investigate gap density. Teprenone and rabeprazole could prevent indomethacin-induced intestinal demage and improve the integrity of the epithelial barrier mediated by the intervention of TNF-α pathway. Key Word(s): 1. Epithelial barrier; 2. endomicroscopy; 3. Gap density; 4. TNF- α; Presenting Author: YING KIT LEUNG Corresponding Author: YING KIT LEUNG Affiliations: Precious Blood Hospital Objective: We have previously demonstrated that the vasculature in villi are of the reverse fountain pattern, one-uo, one down pattern or the reticular pattern. Whether these pertain to a arteriole-venule pattern

or mainly comprise of capillaries is not yet confirmed about scientifically. The aim of this study is to visualize how blood elements flow in the vasculature of the villi in a living human under sedation, hence infer the basic characteristic of such blood vessels. Methods: Ten subjects underwent colonoscopy and probe-based confocal laser endomicroscopy (pCLE) were included into the study. The indications of the procedure being: inflammatory bowel disease, familial adenomatous polyposis, colonic polyps and abdominal pain. Fluorescein was injected after the small intestine was entered, and the villi examined with pCLE which took video images at 12/sec. The velocities of cellular movement in the vessels were determined during playback of the videos, and compared with similar measurement of flow around colonic crypts. Results: Blood elements of diameter around 7–10 microns, move in the vessels in an episodic manner.

Disruption of the epithelial barrier Buparlisib order is often associated with the increase of cell shedding. This study aims to investigate the mechanisms how mucosal protectants maintain the integrity of intestinal epithelial barrier in

indomethacin-induced enteropathy by observing real-timely the gap density using confocal laser endomicroscopy (CLE). Methods: A method to evaluate real-timely the intestinal epithelial barrier damage after administration of indomethacin in rats were established using a new technique CLE by investigating the gap density in small intestine. Then the mucosal protectant teprenone and proton pump inhibitor rabeprazole were given by gavage before and after the administration of indomethacin. Then, the mechanisms of how these medicines affect the intestinal epithelial barrier were investigated by investigating gap density and TNF- α pathway. Results: Gaps could be clearly observed by CLE, Gap density increased after indomethacin administration. During this process, the expressions of TNF- α, NF-kB and Caspase-3 were up-regulated while the expressions of tight junction were down-regulated. Teprenone and rabeprazole could interfere in the damage process and protect the integrity of the epithelial

barrier. Conclusion: CLE can be more objective, accurate and real-time to XAV939 investigate gap density. Teprenone and rabeprazole could prevent indomethacin-induced intestinal demage and improve the integrity of the epithelial barrier mediated by the intervention of TNF-α pathway. Key Word(s): 1. Epithelial barrier; 2. endomicroscopy; 3. Gap density; 4. TNF- α; Presenting Author: YING KIT LEUNG Corresponding Author: YING KIT LEUNG Affiliations: Precious Blood Hospital Objective: We have previously demonstrated that the vasculature in villi are of the reverse fountain pattern, one-uo, one down pattern or the reticular pattern. Whether these pertain to a arteriole-venule pattern

or mainly comprise of capillaries is not yet confirmed 4��8C scientifically. The aim of this study is to visualize how blood elements flow in the vasculature of the villi in a living human under sedation, hence infer the basic characteristic of such blood vessels. Methods: Ten subjects underwent colonoscopy and probe-based confocal laser endomicroscopy (pCLE) were included into the study. The indications of the procedure being: inflammatory bowel disease, familial adenomatous polyposis, colonic polyps and abdominal pain. Fluorescein was injected after the small intestine was entered, and the villi examined with pCLE which took video images at 12/sec. The velocities of cellular movement in the vessels were determined during playback of the videos, and compared with similar measurement of flow around colonic crypts. Results: Blood elements of diameter around 7–10 microns, move in the vessels in an episodic manner.

Chronic injury of C57BL/6 mice led to advanced fibrosis (fibrosis

scoring 3 on Sirius red–stained sections) associated with highly elevated numbers of α-SMA+ HSCs at peak injury (day 1) (Fig. 4A,B). Both the grade of fibrosis (score 2) and numbers of α-SMA–positive cells were reduced for c-rel−/− mice. Quantification of Sirius red staining by densitometric analysis confirmed a significantly reduced level of collagen deposition at peak injury in c-rel−/− compared to Wt livers (Fig. 4B). BDL-induced fibrosis HKI 272 was also attenuated in c-rel−/− mice (Fig. 5A) with reduced collagen deposition again being confirmed by densitometric analysis (Fig. 5B). The observation of reduced fibrosis in both the CCl4 and BDL models indicates an important and previously unreported role for c-Rel in fibrogenesis. Activation of HSCs and fibrogenesis is influenced by the inflammatory response25 and RANTES, which are both defective in c-rel−/− livers and may therefore partly explain the attenuated fibrosis. However, we also observed intrinsic AZD6244 mouse differences in the phenotype of in vitro culture-activated c-rel−/− HSCs, with reduced expression of collagen I (Fig. 5C), suggesting a direct influence of c-Rel on fibrogenesis. We also observed a trend

toward reduced expression of α-SMA in c-rel−/− HSCs, although this did not reach statistical significance. Of note, levels of TIMP-1 were similar between L-NAME HCl Wt and c-Rel–deficient HSCs. These data suggest selective influences of c-Rel on fibrogenic gene expression and that the decreased fibrosis observed in injured c-rel−/− mice may primarily be due to reduced collagen expression, despite similar levels of TIMP-1. Toxic injury of the liver is associated with loss of hepatocytes that

triggers compensatory hepatocyte proliferation.26 Proliferating hepatocytes were detected in chronic CCl4-injured livers using antibodies recognizing PCNA and by hematoxylin counterstaining to visualize mitotic bodies (Fig. 6A). The proliferative markers were most abundant at day 3 after injury, indicating a burst of replicative activity occurs during the early phase of recovery from fibrotic disease (Fig. 6B). The c-Rel–deficient livers displayed low numbers of PCNA-positive hepatocytes, indicating a defect in hepatocyte DNA synthesis. The “gold standard” model for study of hepatocyte regeneration is partial hepatectomy (PHx) which induces synchronized compensatory hepatocyte proliferation in the remnant liver.27 BrdU and PCNA were widely detected at 36 hours after PHx in Wt hepatocytes and were 14-fold and 4-fold lower, respectively, in c-rel−/− livers at this time point (Fig. 7A). This dramatic effect on hepatocyte DNA synthesis was associated with a modest reduction in recovery of liver mass at 72 hours (Supporting Fig. 4).