21 Very recently, Spechler et al.4 have reported that the authors of a recently drafted Technical Review on BE commissioned by the American Gastroenterological Association

(AGA) considered the data summarized in the previous paragraph and, as a result, concluded that the “intestinal-type metaplasia only” definition should be discarded, in favor of the following: (Barrett’s esophagus is) . . . “the condition in which any extent of metaplastic columnar epithelium that predisposes to cancer development replaces the stratified squamous epithelium that normally lines the esophagus”.4 This circuitously worded definition still clings to the illogical concept that malignant potential should be a requirement for any definition of BE, but this selleck products is no longer of practical importance if

it is accepted Small molecule library that all types of BE mucosa carry a risk for malignant change. The wording of this new definition conveys more than a whiff of political struggle and will bamboozle some readers, especially those whose first language is other than English, but still, this is real progress! Oddly, at the time of finalizing this article, there is no indication when this review will be published in Gastroenterology, the established journal for publication of AGA Technical Reviews. The Montréal workshop12 recommended the term “endoscopically suspected esophageal metaplasia (ESEM)”, pending histological confirmation, rather than “suspected BE”. This was driven by concerns of participants from the USA that the word Terminal deoxynucleotidyl transferase “Barrett” causes major, unjustified loadings to life insurance premiums.12 This is a real issue that needs to be addressed, but this problem must not influence the clarity

of clinical terminology around the world; specifically, it is unjustified to coin yet another code term that would, in time, presumably be discovered and acted on with the same prejudice by insurance companies in the USA. This is a field that needs de-, rather than re-coding! There is now general acceptance that BE is an acquired abnormality. There remain major gaps in our understanding of factors that lead to its development and the factors that trigger progression to dysplasia and EA. Reflux disease is proven to be a major pathogenetic factor for development of BE,2–4 even though in some it is symptomatically mild or silent. In the minority of BE patients with metaplastic segments longer that 3 cm, gastroesophageal competence is usually severely impaired. Limited data also indicate that metaplastic segments shorter than 3 cm are associated with reflux disease. A careful search for BE (defined as at least 3 cm of metaplasia) in 733 unselected post-mortems revealed seven cases of which only two had been diagnosed during life. After adjustment, this was interpreted as showing that only 1 in 21 cases of BE is recognized during life.

There could be several reasons for these differences, including predator experience (Skelhorn & Rowe, 2007), availability of alternative see more prey or even light quality, which can affect target conspicuousness (Endler, 1993). We did not collect quantitative data on potential predator populations in our study sites, but based on personal observations, the most common species included black-capped chickadees (Poecile atricapillus), white-breasted nuthatches (Sitta carolinensis), northern cardinals (Cardinalis cardinalis), American crows (Corvus brachyrhynchos), American robins (Turdus migratorius) and yellow-bellied sapsuckers

(Sphyrapicus varius). Whatever the cause, the observed variation between sites and trials clearly reflects the diverse selection RXDX-106 mw pressures that are likely to be experienced by prey in the wild, at least in the short term. In contrast to the combined analysis, we found a significant effect of defensive treatment on predation rates when prey targets with pastry completely removed and partly removed were considered

separately. Previous experiments with wild avian predators have generally considered predation to have occurred if the edible portion of the prey target was either partly or entirely missing (Cuthill et al., 2005, 2006; Schaefer & Stobbe, 2006; Stevens et al., 2006; Rowland et al., 2008). In doing so, no distinction is made between

exploratory attacks and complete consumption by predators (but see Hossie & Sherratt, 2012), which is of considerable interest when comparing defensive strategies such as crypsis and aposematism. Indeed, when we analyzed our predation measures separately (i.e. predation was defined as the entire pastry being removed vs. part of the pastry being removed), they produced very different results. Specifically, when attacks were considered only if they resulted in the complete removal of the pastry, highly unpalatable prey experienced significantly less predation than high-crypsis, low-crypsis and white prey, but not significantly less than prey with low unpalatability. Conversely, when only partial tuclazepam removal of the pastry was considered, highly unpalatable prey experienced significantly more predation than low-crypsis and white prey, but not significantly more than high-crypsis prey or prey with low unpalatability. These results suggest that predators may have been sampling highly unpalatable prey at higher rates than cryptic prey and controls, but consuming them at a lower rate. It should be noted that we were not able to distinguish between single and multiple attacks by predators, and indeed, it is possible that completely ‘consumed’ prey targets were simply attacked multiple times by different predators.

Recognition memory (RM), familiarity, and recollection were examined in 21 patients with

mild-to-moderate PD (Hoehn and Yahr mean: 2.67). Patients were subdivided into two subgroups according to dopamine agonist (pramipexole [PPX] or ropinirole [RPR]), and completed matched versions of an RM test in a medicated and unmedicated condition (termed ON and OFF, respectively). Ten demographically matched healthy volunteers (HVs) also completed both RM tasks in two separate sessions. The PD group (PPX and RPR subgroups combined) Bcr-Abl inhibitor showed impairments in RM and recollection, but spared familiarity. When subdivided by dopamine agonist, the PPX subgroup’s ON-medication recollection performance was significantly lower than that of both the HVs and RPR subgroup. There was no evidence of decline in OFF-medication recollection or familiarity in either the PPX or RPR subgroups. Recollection in both PD subgroups correlated positively with a composite measure

of recall, but not prefrontally dependent measures of cognitive control. These findings suggest that mild-to-moderate PD patients may show relatively preserved recollection and familiarity, but that recollection is selectively disrupted by PPX, but not RPR and that this effect may depend on disrupted hippocampal function CH5424802 price rather than impaired pre-frontally dependent executive functions. “
“The ability to recognize and label emotional facial expressions is an important aspect of social cognition. However, existing paradigms to examine this ability present only static facial expressions, suffer from ceiling effects or have limited or no norms. A computerized test, the Emotion Recognition Task (ERT), was developed

to overcome these difficulties. In this study, we examined the effects of age, sex, and intellectual ability on emotion perception using the ERT. In this test, emotional facial expressions are presented as morphs gradually expressing one of the six basic emotions from neutral to four levels of intensity (40%, 60%, 80%, and 100%). The task Vitamin B12 was administered in 373 healthy participants aged 8–75. In children aged 8–17, only small developmental effects were found for the emotions anger and happiness, in contrast to adults who showed age-related decline on anger, fear, happiness, and sadness. Sex differences were present predominantly in the adult participants. IQ only minimally affected the perception of disgust in the children, while years of education were correlated with all emotions but surprise and disgust in the adult participants. A regression-based approach was adopted to present age- and education- or IQ-adjusted normative data for use in clinical practice. Previous studies using the ERT have demonstrated selective impairments on specific emotions in a variety of psychiatric, neurologic, or neurodegenerative patient groups, making the ERT a valuable addition to existing paradigms for the assessment of emotion perception.

A was dosed 100 mg BID and D 60 mg QD. Blood samples for drug assays were drawn during a dosing interval at day 0 (D0) before and 8 weeks (W8) after PR initiation (W8 = 4 weeks after AD initiation). Drugs were assayed by validated LC/MS/MS. Pharmacokinetic (PK) parameters, maximal concentration (Cmax), time to Cmax (Tmax) and predose concentration (Cmin) were VX-770 observed data; AUC during a dosing interval were estimated by non compartmental method (Win-NonLin®). Results are shown as median and (range).

Geometric mean ratio (GMR) W8/D0 and 90%CI were estimated for RAL parameters. Eighteen of 20 pts were male, median age was 49 (37-59), weight was 74 (65 – 78) kg, CD4 count was 849 (362 – 1994) /mm3, plasma HCV-RNA was 6.11 (4.987.41) log10 UI/mL, and HCV

genotype was 1a in 11 pts and 4 in 9 pts. In addition, 65% were IV drug users, all but 1 pt had plasma HIV-RNA<50 copies/mL, and 7 (35%) had Child A liver cirrhosis. Cmax, Cmin and AUC of A and D at W8 for the 20 pts were 305 (106-1100) ng/mL, 30 (12-144) ng/mL and 1025 (602-3436) ng.h/mL and 1140 (444-2880) ng/mL, 192 (104-641) ng/mL and 12008 (6026-32500) ng.h/mL respectively. For the 7 patients with liver cirrhosis, PK parameters are presented on the table. RAL PK data in the remaining non cirrhotic pts will be presented. All 20 patients had plasma HIV-RNA Lumacaftor mouse <50 copies/mL at W8. One neutropenia was reported as severe adverse event during the PK study. In conclusion, AD exposure in HIV-HCV co-infected patients was in the same range as in mono-infected patients, and RAL PK remained within a similar range after ADPR initiation in cirrhotic patients despite large inter- and intrapatient PK variabilities as previously reported. Disclosures: Eric Rosenthal - Board Membership: gilead, msd Hugues Aumattre - Speaking and Teaching: BMS, MSD, GS, VIIV, Janssen Francois Bailly - Board Membership: ABBVIE, MSD, BMS, GILEAD; Speaking and Teaching: JANSSEN Jean-Michel Molina - Board Membership: Gilead, BMS, Janssen, merck, Abbott, boehringer; Grant/Research Support: merck; Speaking

old and Teaching: merck, gilead, BMS The following people have nothing to disclose: Anne-Marie Taburet, Lionel Piroth, Hubert Paniez, Mélanie Simony, Valerie Furlan, Aurélie Barrail-Tran, Corine Vincent, Eric Billaud, Martine Resch, Laurence Meyer Purpose: Treatment responses to interferon-containing regimens with a protease inhibitor have historically been lower for black patients compared with white patients. The randomized phase 3 PEARL trials evaluated the safety and efficacy of the “3D” regimen of co-formulated ABT-450/ritonavir/ombitasvir and dasabuvir with or without ribavirin (RBV) in HCV genotype (GT) 1b treatment-experienced (PEARL-II) or treatment-naïve (PEARL-III) patients, and in GT1a treatment-naï;ve (PEARL-IV) patients. We assessed treatment response rates based on race or geographic location in a pooled analysis of results from the PEARL trials.

Serum markers of antioxidant status such as total, reduced (GSH) and oxidized (GSSG) glutathione as well as ferric reducing antioxidant power (FRAP) were measured according to the procedures reported selleck below. Ten percent formalin-fixed paraffin-embedded sections of liver samples were divided into 4-μm sections by using routine techniques and mounted onto slides with coverslips. Representative sections of each fixed sample were stained with standard hematoxylin-eosin and Sirius red/fast green according to standard protocols. All histological analyses were performed by an experienced histopathologist in a blinded manner. For the

detection and quantification of collagen, liver sections were stained with Picrosirius red solution. The extent of liver fibrosis was determined as the proportion of Picrosirius-stained area in each section. For each rat, 64 fields of a constant raster of 31 mm2 were analyzed at 100× final magnification. For semiautomated morphometry, a Sony 3CCD (model DXC-950P) videomicroscope equipped with a motor stage and the Quantimed 500MC (Leica, Germany) software were used. To detect the immunohistochemical

localization of adiponectin receptor 2 (adipo-R2), sections from formalin-fixed, paraffin-embedded specimens were deparaffinized and rehydrated in decreasing concentrations of ethyl alcohol. The detailed procedure, including antibody used Galunisertib purchase and all material specificities and provenience, is provided in the Supporting Information. Western blot analyses in tissue lysates prepared and quantified

for protein content were performed as described in the Supporting Information. Semiquantitative reverse-transcription polymerase chain reaction amplification of messenger RNA liver extracts was performed using the procedure and primers described in the Supporting Information. Markers of antioxidant status such as total, reduced (GSH), and oxidized (GSSG) glutathione in serum and liver samples; glutathione transferase activity in the liver; and plasma FRAP were measured according to the protocols described in the Supporting Information. Tumor necrosis factor α (TNF-α), interferon-γ (IFN-γ), interleukin (IL)-1α, IL-1β, IL-2, IL-4, IL-6, and IL-10 were quantified Casein kinase 1 in liver samples through the xMAP technology developed by Luminex (Austin, TX) and using a rat multiplex bead-based assay Bio-Plex Suspension Array System (Bio-Rad Laboratories, Hercules, CA) according to the manufacturer’s instructions. Data were analyzed using Bio-Plex Manager version 3.0 (Bio-Rad Laboratories) with five parameter logistic regression algorithm curve fits. Detection limits for the cytokines were 2-32,000 pg/mL. A detailed protocol for tissue preparation is described in the Supporting Information.

Adjunctive therapies are important, particularly where clotting factor concentrates are limited or not available, and may lessen the amount of treatment product required. First aid measures: In addition to increasing factor level with clotting factor concentrates

(or desmopressin in mild hemophilia A), protection (splint), rest, ice, compression, and elevation (PRICE) may be used as adjunctive management for bleeding in muscles and joints. Physiotherapy/rehabilitation is particularly important for functional improvement and recovery after musculoskeletal bleeds and for those with established hemophilic arthropathy (see ‘Principles of Physiotherapy/Physical Medicine in Hemophilia’). Antifibrinolytic drugs (e.g., tranexamic acid, epsilon aminocaproic acid) are effective as adjunctive treatment for mucosal bleeds and dental extractions (see ‘Tranexamic Acid’ and ‘Aminocaproic Acid’). Certain COX-2 inhibitors may be used judiciously Ibrutinib manufacturer for joint inflammation after an acute bleed and in chronic arthritis (see ‘Pain Management’). Prophylaxis is the treatment

by intravenous injection of factor concentrate to prevent anticipated bleeding (Table 1–4). Prophylaxis was conceived from the observation that moderate hemophilia patients with clotting factor level > 1 IU dL−1 seldom experience spontaneous bleeding and have much better preservation of joint function. [21-24] Prophylaxis prevents bleeding and joint destruction and should be the goal of therapy to preserve normal musculoskeletal function. (Level 2) [ [25-30] ] Prophylactic replacement ADAMTS5 of clotting

factor Tanespimycin solubility dmso has been shown to be useful even when factor levels are not maintained above 1 IU dL−1 at all times [27, 30, 31]. It is unclear whether all patients should remain on prophylaxis indefinitely as they transition into adulthood. Although some data suggest that a proportion of young adults can do well off prophylaxis [21, 31], more studies are needed before a clear recommendation can be made. [32] In patients with repeated bleeding, particularly into target joints, short-term prophylaxis for 4–8 weeks can be used to interrupt the bleeding cycle. This may be combined with intensive physiotherapy or synoviorthesis. (Level 3) [ [33, 34] ] Prophylaxis does not reverse established joint damage; however, it decreases frequency of bleeding and may slow progression of joint disease and improve quality of life. Prophylaxis as currently practiced in countries where there are no significant resource constraints is an expensive treatment and is only possible if significant resources are allocated to hemophilia care. However, it is cost-effective in the long-term because it eliminates the high cost associated with subsequent management of damaged joints and improves quality of life. In countries with significant resource constraints, lower doses of prophylaxis given more frequently may be an effective option.

These results directly link DLEU2 with TRIM13 transcriptional regulation in the presence of HBx. In silico analysis indicates that DLEU2 RNA species potentially binds the HBx protein and we confirmed the HBx-DLEU2 interaction using an anti-HBx RNA Immune Precipitation (RIP). Finally, we found that DLEU2 inac-tivation has a profound impact on HBV pgRNA transcription, thus unveiling a functional relevance of the DLEU2-HBx interaction in regulating HBV replication. Conclusion: Genome wide occupancy study revealed that HBx targets 39 lncRNA

promoters. HBx binding to the DLEU2 promoter modifies its splicing profile and affects the expression of the intragenic/overlapping TRIM13 gene, hsa-mir-15 and hsa-mir-16. Moreover, a direct interaction of DLEU2

with the HBx regulates HBV replication. Disclosures: Massimo Levrero – Advisory Committees or Review Panels: Gilead, Jansen Cilag; Speaking and Teaching: Roche, BMS, MSD The following buy ICG-001 people have nothing to disclose: Francesca Guerrieri, Safaa Jed-dari, Daniel D’Andrea, Anna Tramontano Backgrounds and Aims: Fc gamma receptors (FCGRs) are important in regulating immune responses. Most of the FCGRs are activating receptors including FCGR1, FCGR2A, FCGR3, whereas FCGR2B is the only inhibiting S1P Receptor inhibitor receptor. So far, there is no FCGRs study regarding hepatitis B virus (HBV) infection. Methods: whole-genome expression profiling of purified RNA of peripheral blood mononuclear cells (PBMC) from patients with acute self limiting hepatitis B (AHB) and treatment naive chronic HBV infection including immune tolerant(IT) and HBeAg positive(HBeAg+) chronic hepatitis B(CHB)and healthy control (HC) was performed using microarrays. Gene signatures Fenbendazole were developed through bioinformatics approaches and further evaluated and validated by real time RT-PCR and western blot. Results: Microarray data showed activating FCGRs namely FCGR1A and FCGR2A that were differentially expressed and validated by real time RT-PCR in the same patient

cohort, which revealed higher expression level of FCGR1A and FCGR2A in AHB compared with chronic HBV infection, in HBeAg+ CHB compared with IT and in AHB compared with HC(all, P<0.001). Subsequently studies with an independent patient cohort of 25 AHB, 40 IT, 50 HBeAg+ CHB showed that FCGR1A and FCGR2A had the similar expression pattern which was most significant for FCGR1A mRNA expression(P<0.001) and protein expres-sion(p<0.01), whereas FCGR3A expression was statistically insignificant. Also, we assessed mRNA expression of FCGR2B which revealed higher expression in IT compared with HBeAg+ CHB without statistical significance. The ratio of FCGR2A/ FCGR2B mRNA expression was calculated in 10 HBeAg+ CHB(10/50) before and after PEG-IFN therapy who achieved virological response. The result showed that the ratio FCGR2A/ FCGR2B was higher in those after treatment compared with those before treatment(5.88±5.12 vs 2.05±1.86, p<0.01).

69-73,400,401 LT is indicated for patients presenting with ABT-263 mouse acute liver failure, and it is the treatment of choice for patients progressing to decompensated cirrhosis with a MELD score of ≥15 or those with hepatocellular carcinoma meeting transplant criteria. Need for LT may result from a failure to diagnose and treat AIH as an etiology of cirrhosis, inadequate response or intolerance to immunosuppressive therapy or noncompliance with treatment.354,355 Untreated patients have a 10-year survival of <30%,69-73 and treatment failure requiring LT is often associated with the HLA genotype DRB1*0301.155,158 LT for AIH is very successful with 5-year and 10-year patient

survivals of approximately 75%.69-73,402-404 A combination of prednisone and a calcineurin inhibitor (tacrolimus more frequently than cyclosporine) is the most common immunosuppression regimen after LT.402-404 Recurrent AIH in transplant allografts occurs in approximately 30% of adult and pediatric patients (range 12%-46%) with an average time to recurrence of 4.6 years.404-413 The incidence increases with time after LT and accelerates after discontinuation of steroids.404 Diagnostic criteria

for recurrence include: (1) elevation of serum AST or ALT levels; (2) persistence of autoantibodies; (3) hypergammaglobulinemia Belinostat in vivo and/or elevation of IgG level; (4) compatible histopathological findings; (5) exclusion of alternative etiologies; and (6) responsiveness to steroids.404,412,413 Histopathological abnormalities compatible with recurrent AIH may precede laboratory or clinical evidence of recurrence.414 There is no prospectively validated scoring system for the diagnosis of recurrent AIH. Reported risk factors for recurrence included inadequate dosing of immunosuppression (especially discontinuation of prednisone), type 1 AIH and a recipient positive for either HLA-DRB1*03 or DRB1*04.412,414-421 The risk for recurrence has been associated with the HLA genotypes DRB1*03 or DRB1*04 in the recipients of some series, but not in all.412,414-421 Primary immunosuppression

with either tacrolimus or cyclosporine does not influence the risk of recurrence. Treatment of recurrent AIH has been empiric, and no controlled trials have been Baricitinib reported. Reintroduction of prednisone or prednisolone and optimization of calcineurin inhibitor levels is usually successful.403,419 A combination of prednisone and azathioprine has also been successful.419 Occasionally, substituting tacrolimus for cyclosporine may be useful.422 Sirolimus may also benefit patients unresponsive to steroids and calcineurin inhibitors.423 Based on these reports, recurrent AIH should be treated with prednisone and azathioprine in adjusted doses to suppress serum AST or ALT levels or increased doses of corticosteroids and optimization of calcineurin inhibitor levels (preferably, tacrolimus).

Information was obtained on the occurrence of death/hepatic transplantation and episodes of HE requiring in-hospital admission. Hospital admissions were qualified as HE-related if the reason for hospitalization was HE itself. Thus, inpatient stays during which an episode of HE occurred in an individual who had been admitted for a different reason or a major precipitant (i.e., gastrointestinal bleeding, sepsis) were not included. Differences between groups were examined using Mann-Whitney U or Kruskal-Wallis tests (post hoc comparisons: Mann-Whitney U test, applying the Bonferroni correction for multiple comparisons). Correlations were tested using the Spearman

coefficient. Survival analysis was performed with the Cox proportional hazards model or with the Kaplan-Meier cumulative survival method, as appropriate. Patients who underwent transplantation were qualified as alive and censored on the day of transplantation; the analysis was also conducted excluding FK506 transplanted patients. The predictive validity of different variables on the occurrence of HE-related hospitalizations was also assessed using survival analysis methods; patients who were hospitalized because of HE were qualified as complete

cases. The protocol was approved the Hospital of Padua Ethics Committee. All participating subjects provided written, informed consent. The study was conducted according to the Declaration of Helsinki (Hong find more Kong Amendment) and European Good Clinical Practice guidelines. The etiology of cirrhosis was viral (hepatitis C, B, or B plus D) in 38 (53%) patients, alcohol in 22 (30%) patients, primary biliary cirrhosis in 10 (14%) patient, and cryptogenic in two (3%) patients. Functionally, 14 patients (19%) were classified as Child-Pugh grade A, 38 (53%) as Child-Pugh grade B, and 20 (28%) as Child-Pugh grade C. The average MELD score mafosfamide was

12 ± 7. On average, patients with cirrhosis had significantly worse neuropsychiatric performance than healthy volunteers (Table 1). Patients with alcohol-related cirrhosis had significantly worse neuropsychiatric performance than their counterparts with non–alcohol-related cirrhosis (Table 2). On the day of study, 38 (53%) patients were classified as neuropsychiatrically unimpaired and 34 (47%) patients were classified as having grade I overt HE according to the West Haven criteria. Thirty-three (46%) patients had normal PHES and EEG performance, six (8%) had abnormal PHES, 18 (25%) had abnormal EEG, and 13 (18%) had both abnormal PHES and EEG. Of the 34 patients who were classified as having grade I overt HE, 11 (32%) had normal PHES and EEG performance, 5 (15%) had abnormal PHES, nine (26%) had abnormal EEG, and nine (26%) had both abnormal PHES and EEG. However, these 34 patients had significantly worse performance than their counterparts classified as clinically normal on most stand-alone psychometric and EEG indices (P < 0.

These interactions contribute to the navigation of monocytes into target tissues during their maturation into macrophages.5 The delivery of MCP-1 and MIP-1α-expressing BMMs to injured mice caused up-regulation of hepatic MCP-1 and MIP-1α and the recruitment of endogenous macrophages. These macrophages produced MMP-13, whose actions include the degradation of fibrillar collagens and gelatin as well activation of other MMPs (such as MMP-9).6 Donor BMMs also express MIP-2

and KC, which are examples of CXC chemokines that recruit neutrophils through the surface receptor CXCR2.5 One day after BMM delivery, hepatic expression of these neutrophil chemoattractants was markedly up-regulated, with elevated hepatic neutrophil selleck chemical numbers. This is in keeping with the role of macrophage-mediated neutrophil recruitment in fibrosis

resolution following cessation of cholestatic injury.24 In our model, recruited neutrophils produce MMP-9. MMP-9 overexpression reduces myofibroblast number and inhibits fibrogenesis during experimental liver injury.25 The simultaneous trend of increased MMP-12 (macrophage metalloelastase) and MMP-8 (neutrophil collagenase) expression following BMM therapy reinforces the fibrolytic role of recruited leukocytes. The markedly elevated hepatic IL-10 levels in BMM recipients may modify the behavior of resident and incoming leukocytes and the degree of injury.26 Simultaneous up-regulation of IL-10 and MMPs following BMM therapy may reduce myofibroblast activation26 and promote apoptosis.27 The chemokine-mediated recruitment of host effector cells to the injured Selleckchem Selumetinib liver, importantly at a time when the prevailing hepatic environment is antiinflammatory, represents a novel and realistic mechanism for the therapeutic actions of comparatively few donor

cells in the context of the whole organ. The improved liver function following BMM therapy is multifactorial. There is a less fibrotic cellular milieu, a proregenerative stimulus to LPCs, and elevated levels of cytokines such as CSF-1, VEGF, and IGF-1 that are involved in reparative processes during tissue injury.9, 28, 29 Hepatocyte proliferation was not significantly increased following BMM therapy. There was significant activation of the 4��8C LPC compartment, compatible with the recent observation that BM infusion transiently stimulated LPCs and improved serum albumin in a series of cirrhotic patients.30 We have previously noted the close spatial relationship between LPCs and endogenous macrophages in vivo.12 The cytokine TWEAK is a member of the TNF superfamily and is currently the only known mitogen that is selective for LPCs but not mature hepatocytes.13 TWEAK acts through its cognate receptor Fn14 to stimulate LPC proliferation. Interestingly, endogenous hepatic macrophages have recently been identified as a cellular source of TWEAK during chronic liver injury.