Instead, antigen cross-presentation in the liver may expand a CD8+ T-cell population with an atypical phenotype, the purpose of which has yet to be understood. Taken together, these results help to explain how the liver can be a primary site for T-cell proliferation, and yet liver-activated T cells are check details prone to deliver ineffective immunity. We thank Ms. Rebekah Brown and Mr. Dat Mai as well as flow core facilities at Seattle BioMed and the University of Washington for their technical support during this study. We also thank Ms. JoAnne Dyer for help with preparation of the article. Additional Supporting Information

may be found in the online version of this article. “
“Aim:  This study explored recent improvements in the management of hepatocellular carcinoma (HCC) diagnosed during surveillance. Methods:  The subjects were 1074 patients with HCC, subdivided into three groups. Group A comprised 211 patients for whom HCC was Pexidartinib order detected during periodic follow-up examinations at Kurume University School of Medicine, Group B comprised 544 patients diagnosed with HCC during periodic follow-up examinations at other institutions, and, Group C comprised 319 patients with HCC detected incidentally or because of symptoms. Results:  In 1995–2000 and 2001–2006, 91% and 91% of group A, 68% and 70% of group B, and 27% and 26% of group C patients with HCC, respectively, met

the Milan criteria. For groups A and B, the proportions of patients with Child–Pugh class A and use of promising treatment increased in the later periods compared to those diagnosed during the earlier periods (group A, Child–Pugh class A, 72% vs 58% [P = 0.040], receiving treatment, 90% vs 70% [P < 0.0001]; group B, Child–Pugh class A, 71% vs 62% [P = 0.031]; receiving treatment, 72% vs 52% [P < 0.0001], respectively). The cumulative survival rates of the 405 patients with HCC detected in the latter 6 years tended medchemexpress to be better than those for patients diagnosed in the former 6 years (350 patients) (4 years, 58% vs 50% [P = 0.0349]).

Conclusion:  The use of promising treatment and prognosis have improved in the last 6 years for patients with HCC diagnosed through surveillance relative to those identified in 1995–2000. “
“Recently, the association of the dysfunction of programmed cell death (PD)-1 expressed on activated lymphocytes with the pathogenesis of autoimmune hepatitis (AIH) has been speculated. This study aimed to investigate the association of serum anti-PD-1 antibodies with clinical characteristics of type 1 AIH. Serum samples before the initiation of prednisolone treatment were obtained from 52 type 1 AIH patients, 24 patients with drug-induced liver injury (DILI), 30 patients with acute viral hepatitis (AVH), 11 patients with primary sclerosing cholangitis (PSC), and 62 healthy volunteers.

“
“Zinc-fingers and homeoboxes 2 (ZHX2) and zinc-finger and BTB domain containing 20 (ZBTB20) repress the postnatal expression click here of α-fetoprotein (AFP) by interacting with the AFP gene promoter regions. ZHX2 inhibits the expression of AFP and cyclins A and E. ZBTB20 is negatively regulated by CUX1, which promotes cell-cycle

progression, suggesting that AFP reactivation is closely linked to hepatocyte proliferation. A slight elevation in the serum AFP level often occurs in patients with chronic hepatitis C in the absence of hepatocellular carcinoma (HCC) and is an independent risk factor for HCC development to complement the fibrosis stage. In addition, the sustained elevation of AFP after interferon therapy is a risk factor of HCC development. AFP levels are clinically useful in predicting the outcomes of liver transplantation and sorafenib therapy for HCC patients. A low preoperative AFP level is a predictor of long-term survival and is associated with a low recurrence rate of HCC after liver transplantation. AFP response (≥20% decrease in AFP during 6–8 weeks of treatment) rather than radiological outcomes is a significant prognostic factor for survival in sorafenib-treated HCC patients. Highly sensitive Lens culinaris agglutinin-reactive AFP (AFP-L3) is 5–10 times more sensitive than conventional

AFP-L3, and useful for early detection of HCC in patients Autophagy Compound Library chemical structure with total AFP below 20 ng/mL. “
“Background and Aim:  Donor liver steatosis can impact on liver allograft outcomes. The aim of the present study was to comprehensively report on the impact of type and grade

上海皓元医药股份有限公司 of donor steatosis, as well as donor and recipient factors, including the reported Donor Risk Index (DRI), on liver allograft outcomes. Methods:  A review of unit data for all adult liver transplant procedures from 2001 to 2007, as well as donor offers. Donor liver biopsies were regraded for steatosis by an experienced histopathologist. Results:  Steatosis was detected in 184/255 (72%) of biopsies, of which 114 (62%) had microvesicular steatosis (MiS; 68 mild, 22 moderate, 24 severe) and 70 (38%) macrovesicular steatosis (MaS; 59 mild, 7 moderate, 4 severe). The majority (66/70, 94%) of biopsies with MaS also contained MiS. Allograft steatosis was associated with increasing donor body mass index (P = 0.000), plus donor male sex (P < 0.05). Primary non function (P = 0.002), early renal failure (P = 0.040), and requirement for retransplantation (P = 0.012) were associated only with severe MaS. Early biliary complications were associated with moderate MaS (P = 0.039). Only severe MaS was significantly associated with inferior allograft survival at 3 months (relative risk = 12.09 [8.75–19.05], P = 0.000) and 1 year (P = 0.000).

RBC MTXPG1–5 were measured using high-performance

liquid chromatography. Clinical status (active disease or remission) was assessed by 2 IBD physicians blinded to [MTXPG], using combination of prospectively recorded clinical activity indices (Simple Colitis Activity Index, Harvey Bradshaw Index), endoscopy, fecal calprotectin and C-reactive protein (CRP). Pearson correlation coefficient, r was calculated to assess relationship between MTX dose and [MTXPG]. Association between [MTXPG] and clinical response was analyzed with unpaired t-test. Results: Patient demographics are shown in Table 1: Table 1. Median Age (years, range) 35 (22–59) Male, n (%) 12 (57) Crohn’s disease / ulcerative colitis n(%) / IBD-unclassified 16 (76)/3 (14)/2 (10) Disease duration Buparlisib concentration years, mean PI3K Inhibitor Library molecular weight (SD) 7.6+/–4.3 Concomitant biologic, n (none/infliximab/adalimumab) 6/12/3 MTX route administration (oral/subcutaneous) 19/2 MTX dose, mg, mean (SD) 17.2+/–1.2 4/21(22%) patients (3 of whom admitted non-adherence) had undetectable MTXPGs and were excluded from further analysis. MTXPG2–4 were detected in all

adherent patients. PG3 was the predominant polyglutamate accounting for a mean of 43% of total MTXPG. A linear relationship between dose of MTX and PG1–5 was observed. 12/21(57%) patients were assessed as having active disease. No significant difference in mean [MTXPGn] was observed between those with active disease and remission, (Table 2). For each

MTXPGn, a non-significant trend towards a higher concentration was observed in patients with active disease. Table 2 MTX PG Correlation between MTX dose and MTXPG r, (p) Active disease: [ PGn] (nmol/RBC medchemexpress 8 × 1012), mean, SD Remission [PGn] (nmol/RBC 8 × 1012) mean, SD p value PG1 0.96 (p = 0.01) 22 ± 16 15 ± 10 0.28 PG2 0.92 (p = 0.008) 24 ± 3.6 17 ± 2.3 0.17 PG3 0.98 (p = 0.003) 51 ± 9.8 36 ± 6.7 0.26 PG4 0.94 (p = 0.019) 19 ± 4.9 12 ± 1.7 0.25 PG5 0.67 (p = 0.219) 4.5 ± 1.5 1.3 ± 0.73 0.09 Conclusions: In this study, the largest to date in IBD, measuring RBC MTXPG was useful in assessing adherence to MTX. A trend towards higher PG concentrations was associated with active disease confirming the findings in the only other study in IBD. Whether this is confounded by higher doses being used in patients with more active disease warrants further study in larger, prospective trials. 1. Dervieux T et al, Annals of the Rheumatic Diseases, 2005;64:1180–1185. 2. Stamp LK et al, Arthritis Rheumatism. 2010;3:359–368. 3. Alenka JB et al. Theraputic Drug Monitoring, 2007;29:619–625. M RADOJCIC,1 F MACRAE, B VINEY Department of Colorectal Medicine and Genetics, The Royal Melbourne Hospital and The University of Melbourne Medical School, Melbourne, Australia Introduction: Up to 40% of patients with an attack of severe, acute ulcerative colitis (UC) fail to respond to intravenous corticosteroids.

Therefore, GTP-bound Rac1 is necessary for the activation of Nox1 and Nox2 NAPDH oxidases. GDP and GTP are generated from guanosine monophosphate (GMP) by transferring phosphate groups from adenosine triphosphate (ATP). In animal cells, GMP is synthesized through two distinct pathways: the de novo synthesis and

salvage pathways.[12] Since the salvage pathway is energetically more efficient, it is believed to be the primary supplier of guanine nucleotides. GTP is necessary for NOX2 NAPDH oxidase activation in vitro,[13] but it is unclear how Rac1 and NADPH oxidase-mediated ROS generation is affected when guanosine nucleotides are reduced in vivo. In this study we implemented a forward genetic approach in zebrafish, which has proved to be a valuable strategy for identifying new genes and pathways that influence hepatic steatosis.[14-18] We identified GMP synthetase mutant larvae as showing Selleck MK2206 a hepatic steatosis phenotype, and subsequently found that they also show down-regulation of Rac1 activation and ROS generation. Accordingly, artificially reducing ROS levels through Alectinib mw multiple mechanisms was sufficient to induce hepatic steatosis in wild-type zebrafish larvae, which were then subsequently rescued by artificially increasing ROS levels. These and other data suggest that physiological levels of

ROS generation are required to protect the liver from accumulating excess lipid. Zebrafish (Danio rerio) larvae were obtained from crosses of wild-type AB/TL strain or heterozygous mutant

fish and raised as described.[19] The following transgenic and mutant lines were used: GMP synthetases850, Tg (fabp10:GFP-CAAX)lri1, and Tg (fabp10:GFP-DNRac1)lri4. The following molecules were used: Mycophenolic acid (Sigma Aldrich, Product #5255), Rac1 inhibitor (EMD Biosciences, Product #553502), diphenyleneiodonium chloride (DPI, Sigma Aldrich, Product #D2926), dimethyl p-nitrophenylphosphate 上海皓元医药股份有限公司 (E600, Sigma Aldrich, Product #PS613) and N-acetyl-L-cystein (NAC, Sigma Aldrich, Product #A9165). All pharmacological treatments were administered with 1% dimethyl sulfoxide (DMSO) by volume. Concentrations of molecules used in this study are listed in Supporting Table 2. Embryos were fixed at 7 days postfertilization (dpf) and treated as described.[17] The Rac1 Activity Assay Kit (Millipore) was used. Embryos were lysed and incubated with PAK-1 Pak1-binding domain (PBD)-bound beads. After washing, beads were loaded on sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) gels and blotted with anti-Rac1 (BD Transduction Laboratories, Cat. 610650) and β-tubulin (Abcam, Cat. 75123) antibodies. Electron microscopy was performed as described.[19] Embryos were fixed at 7 dpf in 4% paraformaldehyde (PFA) overnight. Livers were removed and soaked in Nile Red (500 ng/mL) along with TO-PRO3 Iodide nuclear stain for 2 hours at room temperature.

38). Due to this possible confound, years in school was included as a covariate in our performance analysis; again, this did not change our findings. Ethical approval of the study was obtained from the head of the research department at the regional hospital. All participants gave Venetoclax written consent after detailed information was provided to them. To characterize the TBI population and highlight those areas in which the patients were experiencing cognitive difficulties, a battery of neuropsychological tests were administered. As can be seen in Table 1, consistent with typical

cognitive sequelae of moderate-to-severe TBI, the TBI participants performed poorly compared with normative data on measures assessing attention and speeded processing (Trail Making Test – Part A, Reitan, 1958) and executive functioning (Trail Making Test – Part B, Reitan, 1958; the Danish version of the semantic (animals) and phonemic (s-words) fluency tasks, Mortensen, Nielsen, & Rune, 1994; perseverative errors on the modified Wisconsin Card Sorting Test [mWCST], Nelson, 1976). In contrast to the above performance, the group performed within normal range on immediate and delayed verbal memory (Verbal Paired Associates [VPA] subscale of the Wechsler memory Scale-III [WMS-III], Wechsler, 1997), an attention task (digit

span) and two executive functioning tasks (Stroop, Stroop, 1935; Zoo Map Test from the Behavioural assessment of Dysexecutive Syndrome battery, Wilson, Alderman, Burgess, Emslie, & Evens, 1996). Standard deviations and the ranges

of scores indicated a degree of heterogeneity in the patients’ selleck chemicals performances. Of note, severity and characteristics of cognitive impairments after TBI are known to be extremely variable (Ponsford, 1995). Our design distinguished between two different forms of mental time travel – past versus future, each of which was examined for three different time periods. Thus, a 2 (Temporal Direction: future versus past) × 3 (Temporal Distance: 1 month, 5 years and 10 years) × 2 (Group: TBI versus controls) mixed design was used. Participants generated one event in each condition making it a total of six event representations for each participant. The participants’ ability to simulate representations 上海皓元医药股份有限公司 of specific past and future events was assessed using a standard method adopted from D’Argembeau and Van der Linden (2004). The task was divided into two parts – one for recording memories for past events and the other for recording representations of future events. The order in which the past and future condition were completed was counterbalanced across participants. Prior to commencing each condition, participants were provided with detailed written instructions, presented in large writings on a printed text card. The instructions for the past and future recording were the same – except for temporal reference.

4A, middle panel). In contrast, as compared with regular chow (CHD), none of the fatty liver–inducing diets (HSD, HFD, and MCD) affected the level of ATGL mRNA expression (Fig. 4A, right panel). It is noteworthy that although MCD diet induced the largest TG accumulation in the liver compared with feeding with other diets (Table 1), it did not have any effect on the mRNA HM781-36B expression of the three different patatin-like

family members (Fig. 4A). In any case, there was no evidence of compensatory adjustment in hepatic Pnpla5 or ATGL expression in the absence of Pnpla3 in the liver (Fig. 4A, middle and right panels). We next examined the mRNA expression of PNPLA family genes in perigonadal Everolimus ic50 WAT in wild-type and Pnpla3−/− mice. As reported previously22 and confirmed by us, Pnpla3 expression in the WAT of wild-type mice was significantly induced by HSD diet (∼2.5-fold) and slightly up-regulated by HFD diet (∼1.5-fold,

not significant; Fig. 4B, left panel). Under the same conditions, the expression of Pnpla5 was not significantly affected (Fig. 4B, open bars, middle panel). The mRNA expression of ATGL was not altered under the different diets in the wild-type WAT; furthermore, the diets did not affect ATGL mRNA in WAT in the two genotypes (Fig. 4B, right panel). Interestingly, the mRNA level of Pnpla5, normally expressed in WAT at very low level compared with the other two paralogs (Lake et al.23 and our own data), was up-regulated by ∼5-fold in Pnpla3−/− mice fed regular chow (CHD). This up-regulation of Pnpla5 was also observed in the gonadal fat of

Pnpla3−/− mice fed HSD or HFD, although a little less in the HFD group (Fig. 4B, solid bars, middle panel). It thus appears that increased mRNA expression of another patatin-like family member, Pnpla5, may partly compensate for the loss of Pnpla3 in mice, specifically in WAT, but not in liver. Genome-wide association studies have identified the Pnpla3/adiponutrin gene to be associated with obesity and insulin sensitivity,13, 21, 24 and more recently with nonalcoholic,3-5 as well as alcoholic, fatty liver disease6 and elevated AST and ALT,3, 5 implicating PNPLA3 in the control of body fat, liver fat, and whole-body glucose and lipid homeostasis. However, 上海皓元医药股份有限公司 to our surprise, we found that loss of Pnpla3 in mice does not have any effect on body weight, adiposity, or plasma lipid or glucose levels (Fig. 1 and Supporting Table 1), nor does it cause detectable alterations in hepatic TG content or serum ALT and AST levels (Table 1). Furthermore, the whole-body glucose homeostasis and insulin sensitivity remained normal. These were evident whether the Pnpla3-null mice were fed CHD, HFD, HSD, or MCD regimens or in mice bred into a genetic obesity Lepob/ob background. We conclude that Pnpla3 appears dispensable for liver TG metabolism and normal adipose development in mice.

However, these preliminary conclusions are based on only 13 subjects and therefore need to be confirmed in a larger cohort. Detection and validation of inhibitors to haemophilia treatment products selleck chemical are important for clinical care, evaluation of product safety, and assessment of population trends. In clinical practice, the diagnosis of an inhibitor is usually based on more than a single positive inhibitor titre; it includes the patient’s historical response to therapy and often PK studies. In clinical trials and surveillance programmes, however, such information may not be

available, and there is a risk of miscounting of cases and mislabelling of patients due to false positive results. Alternative methods for measuring inhibitors can be used to minimize that risk. Because inhibitors are antibodies, they can be measured in two different ways, through inhibition of functional assays and through detection of binding to the protein that stimulated their

formation. The NA is the gold standard for measurement of inhibitors directed against FVIII. Clot-based assays, however, have several drawbacks. They are based on the endpoint of formation of a fibrin clot in a milieu containing many plasma proteins from multiple individuals and rely on the presence of adequate amounts of key plasma components. They may be influenced by the presence of other antibodies, such as lupus anticoagulants and non-specific inhibitors of coagulation, or by heparin contamination from venous access devices, and they are relatively insensitive. Alternative methods, such as chromogenic assays, enzyme-linked immunosorbent assays (ELISA), Venetoclax and fluorescence-based immunoassays (FLI) can be used to improve on the sensitivity and specificity of clot-based assays. ELISA for FVIII inhibitors have been used for many years, and kits for their performance are commercially available. Although they have a high sensitivity, MCE公司 they lack specificity when compared with clot-based assays, because they detect both inhibitory and non-inhibitory (so-called ‘non-neutralizing’) antibodies. ELISA methods used to screen

for inhibitors must be followed when positive by clot-based assays for confirmation and quantitation. More recently, FLI have been developed for the popular Luminex platform; these also detect both inhibitory and non-inhibitory antibodies. Chromogenic tests for FVIII activity have been used in inhibitor assays and have the advantage of insensitivity to lupus anticoagulants. They depend upon FVIII activation by a standard amount of thrombin and measure generation of FXa in an artificial system, a specific end point. To determine how to define and validate a true positive inhibitor, the prospectively collected data of the Hemophilia Inhibitor Research Study (HIRS), conducted by the Centers for Disease Control and Prevention (CDC) at 17 US haemophilia treatment centres, were examined.

CD56dim NK cells represent approximately 90% of the circulating NK-cell population and predominantely mediate cytotoxic effector functions. CD56bright NK cells contribute up to 10% of the peripheral blood NK-cell population and their primary function is cytokine production. However, recent studies have challenged this simple dichotomy by showing that CD56bright, as well as CD56dim, cells are capable of exerting both functions.3 NK-cell activation and function is tightly regulated by multiple activating

and inhibitory receptors. NK receptors include (1) the killer cell immunoglobulin-like receptors (KIRs) that recognize human leukocyte antigen (HLA) class RG-7388 cell line I molecules, (2) the C-type lectin receptors, including the activating receptors, NKG2C, NKG2D, and NKG2E, and the inhibitory receptor, NKG2A, and (3) the activating natural cytotoxicity receptors, such as NKp30, NKp44, and

NKp46. In hepatitis C virus (HCV) infection, the essential role of NK cells has been shown in several studies. For example, Khakoo et GSK126 al. found that KIR2DL3, an inhibitory NK-cell receptor, and its HLA-C1 ligand directly influence the outcome of HCV infection.4 During acute infection, NK cells are activated, irrespective of the later outcome of infection,5 and they produce higher amounts of IFN-γ and are more cytotoxic, compared to NK cells obtained from healthy controls. Peak NK-cell activity either precedes or coincides with peak T-cell responses, supporting an indirect role of NK cells in priming and regulating adaptive immune responses.6 During chronic HCV infection, 上海皓元 pertubations in NK-cell frequency, phenotype, and function have been reported, as reviewed elsewhere.7, 8 Indeed, peripheral blood NK-cell frequencies are reduced in chronic HCV infection, compared to healthy individuals. In addition, an impaired production of the TH1

polarizing cytokine, IFN-γ, and an increased production of immunoregulatory cytokines, such as interleukin (IL)-10 and transforming growth factor beta, has been reported.9, 10 In contrast, cytotoxicity of NK cells is increased and correlates with the degree of liver inflammation.10, 11 This polarization toward cytotoxicity may be induced by IFN-α.11, 12 Given their important role in the regulation of NK cells, several studies have analyzed the expression of inhibitory and activating receptors on NK cells during acute and chronic HCV infection. Most, but not all, of these studies have revealed an increase in the expression of the inhibitory receptor, NKG2A, and the activating receptors, such as NKp30, NKp44, and NKp46.13, 14 NKp46 is a particularly interesting molecule.

1, 2 miRNAs can function as tumor suppressors or oncogenes, depending on whether they specifically target oncogenes or tumor suppressor genes.3-5 Recently, studies on tumor invasion, metastasis, and adhesion have revealed a critical role of miRNAs in these processes.6-9 Some studies have also focused on the effect of miRNAs on the migration and invasion of hepatocellular carcinoma (HCC) cells. miR-34a and Let-7g inhibit, whereas miR-30d, miR-17-5p, and miR-151 promote cell migration and invasion in HCC cells.10-14 miR-10b, a member of the miRNA family that contains miR-10, miR-51, miR-57, miR-99, and miR-100

(miBase website) can regulate metastasis of breast cancer.15 selleck inhibitor We asked whether miR-10a is involved in the process of cancer metastasis. In this study we investigated whether miR-10a also contributed to the metastasis of HCC cells. HCC is a highly malignant tumor with very poor prognosis, and invasion and migration to other tissue sites are the primary causes of mortality in patients with solid tumors.16, 17 Recent studies have suggested that CX-4945 chemical structure the specific site of cancer cell metastasis does not depend on the anatomic location of the primary tumor or its proximity to secondary sites, but rather, it involves interactions between tumor cells and the local microenvironment at the secondary site, such as cell-matrix adhesion.18 Epithelial-mesenchymal

transition (EMT) is the key process that drives cancer metastasis and it is characterized by loss of the epithelial marker E-cadherin, increased expression of the mesenchymal marker vimentin, and enhanced migratory and invasive behaviors.19 Barrios et al.20 indicated that Eph tyrosine kinase receptor A4 (EphA4) regulates the mesenchymal-to-epithelial transition (MET) of the paraxial mesoderm during somite morphogenesis. The Eph receptors represent the largest family of receptor protein tyrosine kinases and they interact with their ligands, ephrins. Most recently, the genes for Eph receptors and ephrins have been demonstrated to be differentially expressed in various

human tumors.21-27 EphA4 is a member of the Eph receptor tyrosine kinase family and has been reported to play roles in different types of human cancers. EphA4 promotes cell proliferation MCE公司 and migration through an EphA4-FGFR1 signaling pathway in the human glioma U251 cell line.28 Overexpression of the EphA4 gene and reduced expression of the EphB2 gene correlate with liver metastasis in colorectal cancer.29 However, EphA4 has never been described in association with HCC. In this study we found that miR-10a promoted the migration and invasion of the human HCC cell lines QGY-7703 and HepG2 but suppressed the metastasis of HCC cells in in vivo metastasis assays. We identified EphA4 as a direct target of miR-10a.

72 (range: 0.62-0.82) and 0.71 (range: 0.61-0.81) (P > 0.2 for all comparisons). Finally, assessment of the IDI (i.e., the average improvement in the predicted probability of decompensation) indicated that the LS and the MELD including models yielded a better performance than the CTP one. Thus, the net improvement of the LS model versus the CTP one was 11% (P = 0.01), whereas the

MELD model improved the CTP one by 9% Pexidartinib cell line (P = 0.02). LS and MELD models showed a similar performance, as the respective figure for the comparison between them was 1.8% (P = 0.4). As the CTP score showed a strong impact on the emergence of decompensations, we performed analyses restricted to 215 patients harboring class A CTP stage at baseline. In these patients, a higher baseline LS tended to be associated with the occurrence of liver events. Namely, 10 (6%) out of 171 patients with an LS < 40 kPa developed a hepatic decompensation versus 7 (16%) out 44 with an LS ≥ 40 kPa (P = 0.1). Unfortunately, the

relative low number of events precluded to perform reliable multivariate analyses. Fifteen (6%, 95% CI: 3.5%-9.9%) patients died during follow-up. The mortality rate was 3.6 deaths per 100 person-years learn more (95% CI: 2.2%-5.8%). In 10 patients, death was liver-related. Two patients died due to HE, two due to PHGB, two due to HRS, two due HCC, one due to SBP, and one due to liver failure following portal thrombosis. Five

patients died to non liver-related causes: two patients due to cerebral bleeding, one patient due to a non-acquired immune deficiency syndrome (AIDS)-related neoplasm, one patient due to bacteremic pneumococcal pneumonia, and one patient suffered from sudden death. One patient underwent liver transplant. Thus, 11 patients, 10 with ESLD-related deaths and one undergoing a liver transplant, developed a liver-related death and/or transplantation. The rate of 上海皓元 this outcome was 2.4 per 100 person-years (95% CI: 1.4%-4.4%). Higher baseline LS values were associated with developing a liver-related death and/or transplantation (Table 3, Fig. 2). Liver-related mortality and/or transplantation tended to be lower in those patients who achieved SVR during follow-up (Table 3). Cox regression analyses did not yield statistical interactions between LS, CTP stage, and MELD score. Thus, these variables were included simultaneously into multivariate models. After multivariate analyses, baseline LS, CTP stage, and previous exposure to anti-HCV therapy before enrolment were independently associated with liver-related mortality and/or transplantation (Table 3). Baseline LS was associated with overall mortality (Supporting Fig. 2). Table 4 shows univariate and multivariate analyses of the predictors of overall mortality.