Due to the lack of neutralizing anti-CLDN1 antibodies, the role of CLDN1 in the viral entry process is poorly understood. In this study, we produced antibodies directed against the human CLDN1 extracellular loops by genetic immunization and used these antibodies to investigate

the mechanistic role of CLDN1 for HCV entry in an infectious HCV cell culture system and human hepatocytes. Antibodies specific for cell surface–expressed CLDN1 specifically inhibit HCV infection in a dose-dependent manner. Antibodies specific for CLDN1, scavenger receptor B1, and CD81 show an additive neutralizing capacity compared with either agent used alone. Kinetic studies with anti-CLDN1 and anti-CD81 antibodies www.selleckchem.com/products/CP-673451.html demonstrate that HCV interactions with both entry factors occur at a similar time in the internalization process. Anti-CLDN1 antibodies inhibit the binding of envelope glycoprotein E2 to HCV permissive cell lines in the absence of detectable

CLDN1-E2 interaction. Using fluorescent-labeled entry factors and fluorescence resonance energy transfer methodology, we demonstrate selleck chemicals llc that anti-CLDN1 antibodies inhibit CD81-CLDN1 association. In contrast, CLDN1-CLDN1 and CD81-CD81 associations were not modulated. Taken together, our results demonstrate that antibodies targeting CLDN1 neutralize HCV infectivity by reducing E2 association with the cell surface and disrupting CD81-CLDN1 interactions. Conclusion: These results further define the function of CLDN1 in the HCV entry process and highlight new antiviral

strategies targeting E2-CD81-CLDN1 interactions. (HEPATOLOGY 2010.) With an estimated 170 million infected individuals, hepatitis C virus (HCV) has a major impact on public health. HCV is a hepatotropic virus that causes persistent 上海皓元医药股份有限公司 infection in the majority of infected individuals.1 Therapeutic options for chronic infection are limited, and a vaccine is not available.2 HCV entry into hepatocytes is the first step of the viral life cycle resulting in productive viral infection.3, 4 Furthermore, HCV entry is a major target of host neutralizing responses5–7 and a target for antiviral immunopreventive and therapeutic strategies (for review, see Timpe and McKeating4 and Zeisel8). Viral entry is believed to be mediated by the viral envelope glycoproteins E1 and E2 and several host entry factors. These include heparan sulfate, tetraspanin CD81, scavenger receptor class B type I (SR-BI),3 and the tight junction (TJ) proteins claudin-1 (CLDN1)9 and occludin.10, 11 Because none of these host cell surface factors alone is able to promote HCV entry, the interaction of HCV and its target cells leading to the internalization of the virus is believed to be a multistep process involving the interplay of several host cell factors.3, 4, 8 Evans and colleagues9 reported that CLDN1 is essential for HCV infection.

Rabies control measures have seen significant numbers of carnivores killed (e.g. Tischendorf et al., 1998; Guerra et al., 2003; Bourhy et al., 2005) at substantial economic cost (Curtis & Hadidian, 2010). The greatest fear has been that rabies presence in established urban species is likely to increase the chance of transmission to pets or humans. Parasite transmission is also a significant risk. EX527 For example, raccoons carry a roundworm Baylisascaris procyonis, which causes no symptoms in the primary host but can be fatal to intermediate hosts (including humans) through visceral, neural or ocular larva migrans.

As raccoons leave faeces in latrines in the open, risk of infection can be high for small children. Roussere et al. (2007) recorded that almost half of California residences surveyed had least one raccoon latrine containing B. procyonis eggs. Similarly, Gefitinib cost there is a high prevalence of Echinococcus multilocuralis in foxes in Zürich; this might be a source of infection for domestic carnivores and urban inhabitants (Stieger et al., 2002). Carnivores carry many other parasite diseases (see review by Soulsbury et al., 2010), which may have economic

importance through transmission to domestic pets in urban environments. Carnivores may damage houses and gardens due to their diggings and residing in locations that may be problematic (e.g. roof spaces, where their movements are noisy and defecation or urination can cause

damage) (e.g. Herr et al., 2010). Stone martens in Luxembourg climb into car engine compartments and, as part of territorial behaviour, destroy cables and rubber components and scent mark them (Herr et al., 2009b). In terms of general nuisance value, bin-raiding is a commonly reported problem with urban carnivores (Harris, 1984; Clark, 1994) (discussed medchemexpress in the section: ‘Refuse’). Digging activities may also cause damage; for example, badger setts can be extensive (e.g. have 80 entrance holes and 360 m of tunnels, Delahay et al., 2009, and references therein), and while badgers in Europe do not often use buildings, their excavations cause significant damage to roads, buildings and waterways (Delahay et al., 2009). Larger carnivores using urban areas might also increase the chance of direct attacks upon humans and companion animals (e.g. Gehrt & Riley, 2010). Löe & Röskaft (2004) suggested that tiger attacks on humans are more likely when there is less natural prey (a situation typical of urban areas). Also, as some carnivores become used to human presence, they lose their fear, resulting in direct attacks. Non-threatening behaviour by humans and the presence of anthropogenic waste food may have contributed to the death of a geologist in Canada, allegedly due to grey wolves (Geist, 2007).

Increased field strength translates to enhanced quantification of the metabolite of interest, allowing more fundamental studies on underlying pathophysiology. CEST contrast is affected by several tissue properties, such as the concentrations of exchange partners and their rate of proton exchange, whose effects have been examined and explored in this review. We have highlighted the background

of CEST MRI, typical implementation strategy, and complications at 7 T. “
“Sensory neuronopathies (SN) are peripheral nervous system disorders associated with degeneration NVP-BEZ235 in vivo of dorsal root ganglion neurons. Magnetic resonance imaging (MRI) studies have shown abnormalities limited to T2-weighted high signal intensity in the posterior columns. A 65-year-old woman with Sjögren syndrome had slowly progressive unsteadiness of gait and limb paresthesias. A blink reflex examination suggested a paramedian brainstem lesion, confirmed by MRI. Sjögren’s syndrome-related SN may be associated with a more diffuse immune-mediated aggression, involving also the brainstem, and leading to some of the blink reflex abnormalities

observed in nonparaneoplastic SN. “
“Impairment of orientation for time (OT) Opaganib cost is a characteristic symptom of Alzheimer disease (AD). However, the brain regions underlying OT remain to be elucidated. Using single photon emission MCE computed tomography (SPECT), we examined the brain regions exhibiting hypoperfusion that

were associated with OT. We compared regional cerebral blood flow (rCBF) differences between AD and amnesic mild cognitive impairment (aMCI) or normal subjects using 3-dimensional stereotactic surface projection (3D-SSP) analysis. AD patients were divided into OT good and poor groups according to their mean OT scores, and rCBF then compared between the groups to elucidate OT-specific brain areas. 3D-SSP analysis showed reduced rCBF in the left superior parietal lobule (SPL) and bilateral inferior parietal lobule (IPL) in AD patients. In the poor OT group, 3D-SSP analysis revealed hypoperfusion in the bilateral SPL, IPL, posterior cingulated cortex (PCC), and precuneus. Among these areas, region of interest analysis revealed a significant higher number of hypoperfused pixels in the left PCC in the OT poor AD group. Our SPECT study suggested that hypoperfusion in the left SPL and bilateral IPL was AD specific, and reduced rCBF in the left PCC was specifically associated with OT. “
“Evidence from animal models and examination of human epilepsy surgery specimens indicates that inflammation plays an important role in epilepsy. Positron emission tomography (PET) using [C11]PK11195, a marker of activated microglia, provides a means to visualize neuroinflammation in vivo in humans.

Increased field strength translates to enhanced quantification of the metabolite of interest, allowing more fundamental studies on underlying pathophysiology. CEST contrast is affected by several tissue properties, such as the concentrations of exchange partners and their rate of proton exchange, whose effects have been examined and explored in this review. We have highlighted the background

of CEST MRI, typical implementation strategy, and complications at 7 T. “
“Sensory neuronopathies (SN) are peripheral nervous system disorders associated with degeneration GDC-973 of dorsal root ganglion neurons. Magnetic resonance imaging (MRI) studies have shown abnormalities limited to T2-weighted high signal intensity in the posterior columns. A 65-year-old woman with Sjögren syndrome had slowly progressive unsteadiness of gait and limb paresthesias. A blink reflex examination suggested a paramedian brainstem lesion, confirmed by MRI. Sjögren’s syndrome-related SN may be associated with a more diffuse immune-mediated aggression, involving also the brainstem, and leading to some of the blink reflex abnormalities

observed in nonparaneoplastic SN. “
“Impairment of orientation for time (OT) AZD2281 purchase is a characteristic symptom of Alzheimer disease (AD). However, the brain regions underlying OT remain to be elucidated. Using single photon emission MCE公司 computed tomography (SPECT), we examined the brain regions exhibiting hypoperfusion that

were associated with OT. We compared regional cerebral blood flow (rCBF) differences between AD and amnesic mild cognitive impairment (aMCI) or normal subjects using 3-dimensional stereotactic surface projection (3D-SSP) analysis. AD patients were divided into OT good and poor groups according to their mean OT scores, and rCBF then compared between the groups to elucidate OT-specific brain areas. 3D-SSP analysis showed reduced rCBF in the left superior parietal lobule (SPL) and bilateral inferior parietal lobule (IPL) in AD patients. In the poor OT group, 3D-SSP analysis revealed hypoperfusion in the bilateral SPL, IPL, posterior cingulated cortex (PCC), and precuneus. Among these areas, region of interest analysis revealed a significant higher number of hypoperfused pixels in the left PCC in the OT poor AD group. Our SPECT study suggested that hypoperfusion in the left SPL and bilateral IPL was AD specific, and reduced rCBF in the left PCC was specifically associated with OT. “
“Evidence from animal models and examination of human epilepsy surgery specimens indicates that inflammation plays an important role in epilepsy. Positron emission tomography (PET) using [C11]PK11195, a marker of activated microglia, provides a means to visualize neuroinflammation in vivo in humans.

Thus, VhlF/F;AlbERcre mice may be a valuable model of spontaneous steatohepatitis for use in preclinical drug development. Although the direct effectors

that increase inflammation are not known, it is possible that HIF-2α can directly activate inflammatory mediators in the liver. Indeed, it was shown that Il-6 is a direct HIF-2α target learn more gene in macrophages.34 However, our data clearly show that HIF-2α can bind to the promoters of several profibrogenic genes, consistent with data demonstrating that hypoxia can activate fibrogenesis in hepatocytes and stellate cells.35-37 Hepatic stellate cells initiate the fibrotic process. In the liver, quiescent stellate cells are critical in the storage of vitamin A. During liver injury, stellate cells become activated, proliferate, and express a fibrogenic gene program.38 After Vhl disruption, a robust activation of stellate cells is observed in the liver resulting from high activation of collagen gene expression and an increase in SMA, both markers of stellate cell activation. The initiating factor in the activation of stellate cells after Vhl loss is thought to be the result of a sustained increase in lipid accumulation and inflammatory genes. In addition,

the increase in fibrosis mediated by HIF-2α may be caused by collagen matrix stabilization. P4HA1, P4HA2, and PLOD2 are required for hydroxylation of lysyl and prolyl residues on collagen.23, PLX3397 price 26 The resultant hydroxylysyl and hydroxyproline groups are critical for the stability and synthesis of collagen matrixes. Loxl1 and loxl2 gene expression were also increased in the livers of tamoxifen-treated VhlF/F;AlbERcre mice, and their respective promoters were occupied by HIF-2α. Lysyl oxidase

activity is critical in the formation of insoluble collagen fibers, and HIF-1α has been shown to increase MCE公司 renal fibrosis through a lysyl oxidase-mediated mechanism.21, 22 Moreover, TGM2, a multifunction enzyme that covalently cross-links collagen matrices, has been shown to be critical in inducing apoptosis by inactivation of SP1 and c-met in injured livers after alcohol administration.24, 25 HIF-2α can directly regulate the promoter of Tgm2 in a distinct manner, as observed with HIF-1α.39 It is not clear whether Tgm2 is the key enzyme that regulates fibrosis, because Tgm2-null mice are not protected in the carbon tetrachloride and the thioacetamide-induced fibrosis models.40 However, it is likely that the cumulative increase in several profibrogenic genes are needed to increase liver fibrosis, and HIF-2α may be the critical transcription factor to integrate these signals. The present study demonstrates that activation of HIF-2α in the liver regulates liver homeostasis and disease progression and establishes that steatosis, inflammation, and fibrosis are direct responses initiated by the liver after HIF-2α activation.

Results:  Splenectomy induced thrombocytosis, and increased serotonin content in cirrhotic liver. Stimulation of liver regeneration was indicated by the following parameters: hepatocyte ratio to the entire liver area, Ki67-positive hepatocyte count, and expression of phosphorylated extracellular signal-regulated kinases. This enhancement of liver regeneration was negated by ketanserin. Conclusion:  Our results showed that splenectomy promoted liver regeneration by increasing serotonin content in liver even under cirrhotic conditions.

“
“Background and Aims:  The 3′ region of the cagA gene, the most well-known virulence factor of Helicobacter pylori, contains Glu-Pro-Ile-Tyr-Ala (EPIYA) motifs. Four segments flanking the EPIYA motifs, EPIYA-A, -B, -C, or -D, were reported to play important roles

in H. pylori-related gastroduodenal pathogenesis. The aim was to determine the roles MAPK inhibitor of EPIYA segments in gastroduodenal pathogenesis in an Iranian population. Methods:  A total of 92 cagA-positive Iranian strains isolated from dyspepsia patients with non-ulcer dyspepsia (n = 77), peptic ulcer (n = 11) and gastric cancer (n = 4) were studied. The EPIYA motif genotyping was determined by polymerase chain reaction and sequencing. Results:  A total of 86 (93.5%) strains had three copies of EPIYA (ABC type), three (3.3%) had four copies (ABCC type) and three (3.3%) had two copies (AB type). The alignment of the deduced protein sequences

confirmed MCE that there were no East Asian type EPIYA-D sequences ABT-263 in vitro (EPIYATIDFDEANQAG) in Iranian strains. When the prevalence of strains with multiple EPIYA-C segments in Iran was compared with previously published data, it was much lower than that in Colombia and Italy, but was higher than that of Iraq, and the patterns were parallel to the incidence of gastric cancer in these countries. Conclusion:  The structure of the 3′ region of the cagA gene in Iranian strains was Western type. Although we could not find differences between EPIYA types and clinical outcomes, low prevalence of strains with multiple EPIYA-C segments might be reasons for low incidence of gastric cancer in Iran. “
“The aim of this study was to clarify the relationship between the expression of micro-RNAs (miRNAs) in peripheral blood mononuclear cells (PBMCs) and clinical presentation in patients with primary biliary cirrhosis (PBC). This study involved 58 patients with PBC, patients with control diseases including 25 patients with autoimmune hepatitis (AIH), six patients with PBC-AIH overlap syndrome, 23 patients with systemic lupus erythematosus (SLE), and 30 healthy controls. After miRNA was extracted from PBMCs, the expressions of miR-26a, miR-328, miR-299-5p, miR-146a, miR-155, miR-16, miR-132 and let7a were quantified by real-time PCR. The relationships between all miRNA expressions and clinical test parameters were also examined.

2F). Quantification of the fluorescence of CFP-MxA in this region demonstrated a more than 1.22-fold Rapamycin supplier increase after YFP-HBcAg photobleaching,

whereas no increase was found in the two control groups YFP/CFP-MxA and YFP-HBcAg/CFP (data not shown), indicating an evident energy transfer between the two proteins in the perinuclear compartment. Taken together, our data suggest that MxA interacts with HBcAg in living animal cells. To further dissect the biochemical properties of MxA-HBcAg interaction and determine the relevance of the interaction to the anti-HBV activity of MxA, we created different truncated mutants of MxA (Fig. 3A) and tested their association with HBcAg. Huh7 cells were transfected with Flag-HBcAg and Myc-tagged full-length MxA

or each of the truncated mutants, and the associations were checked by coimmunoprecipitation. We found that MxA deletion mutants either lacking the N-terminal GTP-binding domain, which contains the self-assembly sequence (MxAΔN, 359-662aa), or lacking the C-terminal leucine zipper region (MxAΔC, 1-574 aa), retained the ability to interact with HBcAg as demonstrated by coprecipitation with Flag-HBcAg (Fig. 3B). Interestingly, a MxA deletion mutant lacking the central interactive region (MxAΔCID) was not precipitated by Flag-HBcAg, indicating an essential role of this domain in mediating the MxA-HBcAg association (Fig. 3B). We also coexpressed YFP-HBcAg and CFP-tagged each of the truncated mutants Selleck HDAC inhibitor to observe the formation of the protein aggregates. We found that, well-correlated with the results of immunoprecipitation, CFP-MxAΔC and CFP-MxAΔN, but not the CFP-MxAΔCID, colocalized with YFP-HBcAg to form large perinuclear aggregates (Fig. 3C), indicating morphologically a requirement for the CID

domain in the generation of MxA-HBcAg complexes. Finally, MCE we assessed the effects of the truncated MxA mutants on HBV replication by measuring the encapsulated viral DNA in the culture medium of HepG2.2.15 cells. Clearly, overexpression of either Myc-MxAΔC or Myc-MxAΔN dramatically decreased HBV DNA level, mimicking that of wild-type Myc-MxA. In contrast, no evident suppression was detected in cells expressing Myc-MxAΔCID (Fig. 3D). Therefore, our results suggest that the CID domain of MxA is the responsive region in mediating the interaction with HBcAg, and MxA-HBcAg interaction is essential to the anti-HBV function of MxA. Given that MxA interacts with HBcAg to form a complex in the perinuclear compartment, and this interaction is required for the anti-HBV activity of MxA, we then aimed at investigating the effect of MxA on the intracellular kinetics of HBcAg. To address this, we performed fluorescence recovery after photobleaching (FRAP) in living cells.

This is important information,

because NASH can also be observed in NAFLD patients with normal aminotransferases.40, 41 A composite model including both ALT and caspase-cleaved CK-18 revealed higher accuracy for prediction of NAFLD activity compared with detection of CK-18 fragments alone.47 Intriguingly, we found an even better diagnostic accuracy of the M65 marker to predict NASH compared with the diagnostic value of the M30 ELISA in a previous validation study.26 This observation has been supported Selleckchem Selinexor in a small patient cohort, which already indicated a higher predictive value to diagnose NASH for the M65 compared with M30 biomarker.48 Thus, total CK-18 levels might be superior to discriminate between healthy and minimal and between minimal and significant disease conditions. Whether the differential sensitivity of the M30 and M65 markers reflect different cell

death modes remains to be investigated. So far, no appropriate biomarkers for the detection of necrosis or necroptosis have been established. Furthermore, it is clear that various intermediate forms of cell death exist. Moreover, different serum stabilities of the CK-18 forms might account for the different sensitivity of the assays. The Tyrosine Kinase Inhibitor Library lower values obtained with the M30 assay, especially in patients with mild liver disease, might further compromise the accuracy of this test. In summary, measurement of total CK-18 is superior to detection of caspase-cleaved CK-18 to determine relevant stages of fibrosis and steatosis, in particular at low disease stages. Further large cohort studies in NAFLD patients analyzing the mode of cell death and the value of cell death biomarkers to correctly predict NASH are warranted. “
“The aim of this study 上海皓元医药股份有限公司 was to evaluate the effect and molecular mechanism of albumin infusion on cardiac contractility in experimental cirrhosis with ascites. Cardiac contractility was recorded ex vivo in rats with cirrhosis and ascites and in control rats after the injection in the caudal vein of albumin, saline, or hydroxyethyl starch (HES). Gene and protein expression

of β-receptors and pathways involved in their intracellular signaling such as Gαi2 protein (Gαi2), adenylate cyclase 3 (Adcy3), protein expression of tumor necrosis factor alpha (TNF-α) and inducible nitric oxide synthase (iNOS), were evaluated in cardiac tissue in both groups. Phosphorylation and membrane-translocation of the cytosolic components of nicotinamide adenine dinucleotide phosphate (NAD(P)H)-oxidase and translocation of nuclear factor kappa B (NF-κB) were also evaluated. After saline intravenous injection, cardiac contractility was significantly reduced in rats with cirrhosis as compared to control rats (P < 0.01). This was associated with: (1) increased expression of protein Gαi2 (P < 0.05), TNF-α (P < 0.05), iNOS (P < 0.05); (2) increased NAD(P)H-oxidase activity (P < 0.

29 In this context, Tregs are likely to have synergistic regulatory effects on different arms of the immune system based on the stages of bile duct injury. Collectively, our in vitro and in vivo studies in a well-established murine model of BA provide compelling evidence that Treg deficiency leads to unopposed DC-dependent costimulation and aberrant activation of effector

T-lymphocytes in the neonatal liver conferring susceptibility to BA. Furthermore, our study revealed cellular and molecular candidates for future investigations to elucidate whether costimulatory blockade of T-cell activation by targeting Tregs or Treg-dependent pathways may prevent progression of bile click here duct obstruction in BA. Additional Supporting Information may be found in the online version of this GDC-0199 research buy article. “
“In a recent article in HEPATOLOGY, Kremer et al. explored the association between steatosis, cytokines, and natural killer T (NKT) cell numbers. Elegant experiments suggest that increased interleukin-12 (IL12) secretion, in part by Kupffer

cells, leads to NKT depletion in mice and humans with liver steatosis.1 Recent data suggests that steatosis (consisting mainly of triglycerides) per se is a benign condition and reflects the body’s strategy to cope with excessive fatty acid flux.2 Progressive fatty liver disease that develops in a minority of individuals may stem from MCE dysregulated repair responses.3 The hedgehog pathway has been shown to modulate such responses, and overactivation of the hedgehog pathway leads to fibrogenesis. Furthermore, exposure of primary liver NKT cells to increasing concentrations of Sonic hedgehog, a hedgehog ligand, promotes NKT cell viability and proliferation, and enhances IL13 (a T helper 2 [Th2]cytokine) secretion.4 Mice with excessive hedgehog signaling also harbor increased NKT cells and develop increased

fibrosis in diet-induced nonalcoholic steatohepatitis (W. K. Syn et al., manuscript submitted). Indeed, Tajiri et al. noted increased NKT numbers among individuals with greater nonalcoholic steatohepatitis activity scores.5 In contrast to benign hepatic steatosis, there is increasing data supporting the concept that NKT cells accumulate with progressive fatty liver disease. In this study, NKT cell depletion was associated with elevated IL12 levels; conversely, NKT population was preserved in IL12 knockout mice. As suggested, additional factors are likely to be involved in determining the size of the hepatic NKT population. For example, NKT cells express cysteine-X-cysteine receptor 3 (CXCR3) and CXCR6; recruitment of NKT cells in steatotic liver is likely to be regulated by their associated ligands. In addition, because NKT cell viability is modulated by IL15,6 it would be important to determine if expression of IL15 alters with steatosis.

If biliary complications develop at a younger age, they are less likely to be successfully treated by non-surgical approaches. Disclosures: The following people have nothing to

disclose: Nicholas Fidelman, Andrew Lee, Robert Kerlan, John P. Roberts Purpose: Although the Milan criteria have been accepted as standard selection criteria for liver PF-6463922 in vivo transplantation (LT) candidates with hepatocellular carcinoma (HCC), many transplant centers have accepted some extended criteria and focus on the patient selection. The purpose of this study is to evaluate whether neurtophil-lymhocyte ratio (NLR) and C-reactive protein (CRP) predict survival of patients with HCC who undergo LT. Methods: From October 2000 to November 2011, 224 patients underwent living donor liver transplantation (LDLT) for HCC at our institution. Results: selleck chemical 37 patients (16.5%) experienced HCC recurrence during the study period. The 5 yrs disease free survival (DFS) and overall survival (OS) were 81.6% and 76.6% respectively. In multivariate analysis, DFS and OS were significantly related to AFP > 100 (P=0.017, P=0.048), maximal tumor size > 5cm (P<0.001, P=0.001), NLR >6 (P=0.049, P=0.003),

CRP >1.0 (P=0.010, P<0.001). The patients with NLR <6 or CRP <1.0 were significantly better DFS and OS than the patients with NLR >6 or CRP >1.0, especially in beyond Milan criteria group. The scoring system with NRL and CRP were correlated with prediction of DFS and OS. Conclusion: Preoperative NLR and CRP are useful biomarkers for predicting DFS and OS, especially in beyond Milan criteria. Combined with the Milan criteria, NLR and CRP may be new selection criteria for LDLT candidates with HCC. Disclosures: The following people have nothing to disclose: Dong Goo Kim Background. There are no studies measuring the impact of tumor morphological staging, microvascular

invasion (mVI), and model-for-end-stage-liver-disease (MELD) score on the benefit of liver transplantation (LT) over hepatic resection (HR) for hepatocellular carcinoma (HCC). Methods. Exclusion criteria: very large (>10 cm) tumours, macrovascular invasion and extra-hepatic metastases. Study population: 1106 HCC cir-rhotic 上海皓元 patients undergoing HR from one Eastern (n=424) and two Western (n=682) surgical units. We identified 3 tumor stages: I (within Milan, n=806), II (beyond Milan within Up-to-7, n=123), III (beyond Milan and Up-to-7, n=177). Patient survival observed after HR by proportional hazard regression model was compared to that predicted after LT by the Metroticket calculator. The benefit obtainable from LT compared to resection was analyzed in relationship with staging, mVI, and MELD using Monte Carlo simulation. Results. MELD score had the most important effect on transplant benefit independently form tumor characteristics: mean 5-year LT benefit was −2.22 months (95% CI, −2.45 – −1.98) for patients with MELD score < 10, and 6.32 months (95% CI, 6.08–6.