, 2012), multiple sclerosis (Henry et al., 2011), traumatic brain injury (Bornhofen & McDonald, 2008), Alzheimer’s disease (McCade, Savage, & Naismith, 2011), and Parkinson’s disease (Gray & Tickle-Degnen, 2010). While the Ekman 60 Faces Test has proven very useful in

clinical practice, it also has some limitations. First, a ceiling effect is present for the emotion happiness (mean performance of 9.9 from a maximum of 10 in healthy participants). Near-ceiling performances for recognition of this emotion are commonly found (see, e.g., Suzuki, Hoshino, & Shigemasu, 2006), as happy faces are easy to recognize in the absence of other positive emotions as possible distractors. However, although ceiling performances do not affect a test’s specificity, they do reduce a test’s sensitivity, which may be problematic in clinical practice. Second, only full-blown emotional

expressions are presented in the Ekman 60 Faces Test. It could selleck kinase inhibitor be argued that presenting facial expressions at lower intensities GSK1120212 solubility dmso would promote the detection of more subtle performance differences. Third, the stimuli are static photographs. It has been suggested that dynamic presentation of facial expressions (i.e., a neutral face gradually unfolding into an emotional expression) would, to a greater extent, resemble facial expression in everyday communication (Kamachi et al., 2001). Furthermore, movement is an important aspect of the perception of facial expressions that may even affect the accuracy of the perception (see Fiorentini & Viviani, 2011, for a discussion). To overcome these shortcomings, the Emotion Recognition Task (ERT) was developed, in which dynamically morphed facial expressions of the six basic emotions are presented at different levels of intensities (Montagne, Kessels, De Haan, & Perrett, 2007). This paradigm (sometimes

with slight variations in the administration selleck procedure) has been validated in various patient groups, such as Korsakoff’s amnesia (Montagne, Kessels, Wester, & De Haan, 2006), obsessive-compulsive disorder (Montagne et al., 2008), bipolar disorder (Gray et al., 2006), post-traumatic stress disorder (Poljac, Montagne, & De Haan, 2011), amygdalectomy (Ammerlaan, Hendriks, Colon, & Kessels, 2008), Huntington’s diseases (Montagne, Kessels, Kammers, et al., 2006), frontotemporal dementia (Kessels et al., 2007), schizophrenia (Scholten, Aleman, Montagne, & Kahn, 2005), autism spectrum disorder (Law Smith, Montagne, Perrett, Gill, & Gallagher, 2010), social phobia (Montagne, Schutters et al., 2006), depersonalisation disorder (Montagne, Sierra et al., 2007) and stroke (Montagne, Nys, Van Zandvoort, Kappelle, De Haan, & Kessels, 2007). To date, this test could not be used for neuropsychological assessment in clinical practice, but the ERT has recently been made available as part of the computerized DiagnoseIS neuropsychological assessment system (www.diagnoseis.com).

2 Similarly, increased VEGF is linked to earlier HCC recurrence and shorter overall survival.3-5 Both VEGF and IL-8 gene expression are regulated by the transcription factor activator protein 1 (AP-1). AP-1 binding sites were found in the promoter regions of VEGF and IL-8 genes.6, 7 AP-1 is supposed to be involved in tumor formation and angiogenesis8 and can be activated by oxidative stress.9 Oxidative stress is defined as an imbalance between production and antioxidative elimination of reactive oxygen species (ROS). Moreover, oxidative stress is a common feature of inflammatory

liver diseases that predispose to cancer10, 11 and is associated with a higher incidence of HCC recurrence in hepatitis C patients.10 Selenium counteracts oxidative stress because selenoproteins such as glutathione Selleck RG-7204 peroxidases (GPx) eliminate ROS.12, 13 Low selenium levels are associated with an increased cancer risk including HCC.14-18 The liver is particularly affected under selenium deficiency because other organs such as brain, testis, and endocrine tissues are supplied preferentially with selenium.19 GPx2 and GPx4 are supposed to attenuate cancer development.20 GPx4 is the only known enzyme that is efficiently able to reduce lipid peroxides13 formed through ROS-mediated oxidation of unsaturated lipids. Lipid peroxides elevate AP-1 activity and VEGF formation in colorectal cancer cells.21 Likewise, in cultured HCC

cells we found an increase of AP-1 components c-jun and c-fos by lipid peroxides.22 We hypothesized that Acalabrutinib AP-1 activation as well as expression of its target genes VEGF and IL-8 in HCC are controlled by the selenium/lipid peroxide antagonism. The results of the present study

support this hypothesis by evidence gathered from cell lines, an HCC animal model, and HCC patients. 2-AAF, 2-acetylaminofluoren; AP-1, activator protein 1; CXCL1, chemokine find more (C-X-C motif) ligand 1; DEN, diethylnitrosamin; DHFC, 2′,7′-dichlorofluorescin diacetate; IL-8, interleukin 8; HCC, hepatocellular carcinoma; HIF-1α, hypoxia inducible factor 1α; LH, linoleic acid; LOOH, linoleic acid hydroperoxides; LOOH-Ab, linoleic acid hydroperoxide related antibodies; ROS, reactive oxygen species; VEGF, vascular endothelial growth factor. Selenium was quantified by an inductively coupled plasma mass spectrometer (ICP-MS). Details are given in Supporting Methods. Twenty-nine adult patients with histologically confirmed HCC (Supporting Table 1) underwent orthotopic liver transplantation at the General Hospital of Vienna, Austria. HCC tissue arrays were constructed.23 Healthy persons from the local population without known liver disorders were used as controls. Data analysis was performed with the permission of the local Ethics Committee. Correlations were also calculated from published microarray human HCC data.24 HCC in Fisher-344 rats (Charles River) was initiated by 200 mg/kg intraperitoneal diethylnitrosamin (DEN) as described.25 Promotion was performed by 0.

After specifying important co-stimulatory interactions required for the re-stimulation of FVIII-specific memory B cells, we were interested to study the potential impact of different concentrations of FVIII on this process. We tested a range of concentrations between 1 pg mL−1 and 100 μg mL−1 of FVIII (Fig. 3a) [18]. Re-stimulation of memory B cells could be detected at concentrations of FVIII that were as small as 100 pg mL−1 (Fig. 3a)

[18]. Optimal re-stimulation was achieved at concentrations of 3–10 ng mL−1, which correspond to about 3–10% of the physiological plasma concentration (Fig. 3a) [18]. When we further increased the concentration of FVIII, inhibition of memory B-cell re-stimulation was observed. The MLN8237 solubility dmso inhibition started at a concentration of FVIII of 100–300 ng mL−1 with an almost complete inhibition at 1 μg mL−1 FVIII (Fig. 3a) [18]. The dose-response relation for T-cell re-stimulation was very different from the dose-response relation for memory B-cell re-stimulation. Optimal stimulation of FVIII-specific

T cells was observed at concentrations of 10–30 μg mL−1 FVIII (Fig. 3b,c). Inhibition of T-cell stimulation was seen at concentrations of 100 μg mL−1 FVIII. Based on these results, we conclude that the concentration of FVIII required for inhibition of memory B-cell OSI906 re-stimulation and the concentration required for inhibition of T-cell re-stimulation are very different (Fig. 3a–c), which makes it unlikely that the inhibition of memory B-cell re-stimulation is caused by an inhibition of T-cell stimulation. The major T-cell cytokines found in culture supernatants after stimulation of spleen cells with FVIII were IL-10 and IFN-γ (Fig. 3c), which is consistent with findings we reported previously [13,21]. To further support these results,

we analysed the frequency of FVIII-specific T cells by intracellular cytokine staining 3 days after re-stimulation of this website spleen cells. We compared concentrations of 10 ng mL−1, which re-stimulate, and 20 μg mL−1 FVIII which inhibit memory B-cell differentiation and observed a correlation between the frequency of FVIII-specific T cells producing IL-2, IL-10 or IFN-γ and the concentration of FVIII used for the re-stimulation (data not shown). We did not observe any inhibitory effects of 20 μg mL−1 of FVIII on T-cell stimulation despite the fact that this concentration of FVIII completely blocks the re-stimulation of FVIII-specific memory B cells [18]. Infections, particularly infections from the central venous catheter inserted in patients with haemophilia A and FVIII inhibitors during ITI therapy, commonly cause a rise in anti-FVIII antibody titres [22].

Furthermore, diet-control combined with the aforementioned drugs is probably a viable way to decrease HE risk after TIPS, and

GSI-IX nmr a novel adjustable stent system will improve the maneuverability of TIPS procedure. We are grateful to Ms. Jing Niu and technician Wengang Guo for data collection and helpful discussions. Ming Bai*, Guohong Han*, Xingshun Qi*, Zhanxin Yin*, Daiming Fan†, * Department of Digestive Interventional Radiology, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi’an, China, † State Key Laboratory of Cancer Biology, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi’an, China. “
“In their article in the September 2009 issue of HEPATOLOGY, Österreicher et al. conclude with a protective

role for angiotensin-converting enzyme 2 (ACE2) on liver injury.1 ACE2 acts to counterbalance up-regulation of the renin-angiotensin system (RAS) through degradation Regorafenib of angiotensin II to angiotensin 1-7. Based on previous reports on other disease models of RAS overactivity, we would like to highlight another potential anti-RAS mechanism. In these models, immunoassay studies have identified the presence of circulating antibodies against ACE and angiotensin II considered to exert a neutralizing effect.2, 3 Currently, no studies evaluating the levels of serum/tissue anti-RAS antibodies in chronic liver disease models are reported in the literature. It is possible that standardization of their titers could prove to be of prognostic significance. Michael G. Lenos M.D.*, Sofia-Maria Tsaniklidou M.D.†, * Department of Pathology, General Hospital of Athens ‘HIPPOCRATION’, Athens, Greece, † Department of Microbiology, General Hospital of Athens ‘GENNIMATAS’, Athens, Greece. “
” On behalf of the Japanese Society of Gastroenterology, Japan Society of Hepatology, and

Japan Digestive Disease Week, we are delighted to have sponsored the 6th International Symposium on Alcoholic Liver and Pancreatic click here Diseases (ALPD) and Cirrhosis as part of JDDW2011 in Fukuoka, Japan on 20–21 October 2011. Like the second symposium that our organizations also supported in Kobe 4 years ago, the event was very unique in assembling leading investigators in the field of ALPD and cirrhosis around the world. Dr Kenneth Warren, Acting Director of the NIAAA/NIH, delivered an enlightening opening lecture, followed by special tribute made in memory of the late Professor Hiromasa Ishii by Professors Helmut K. Seitz and Nobuhiro Sato. The level of science discussed was exceptionally high, as praised by many who attended the symposium, and this was attributable to outstanding lectures by prominent scientists, such as Michael Karin, Antonello Pietrangelo, and Arun Sanyal.

7% to 67.3% of subjects. This result indicates that atypical symptoms were not rare, but were more common than we expected in our subject population. The prevalence of asymptomatic RE in healthy individuals

has been reported as between 6% and 23%.10 Recently, some studies of subjects undergoing routine health checks in Asian countries have been published. A study from Korea reported that the Selleckchem Volasertib prevalence of RE was 6%, with 45.3% asymptomatic.8 Two studies from China and Taiwan reported that 4.3% and 33.6% of cases of erosive esophagitis were asymptomatic,11 and the prevalence of erosive esophagitis in asymptomatic subjects was 12%.9 Nozu and Komiyama reported that the frequency of asymptomatic RE was 26.4% in patients with RE.5 Murao et al., employing a QUEST cut-off score of 6 points, reported frequencies of asymptomatic esophageal reflux disease (ERD), symptomatic ERD and NERD were

34.8%, 13.6% and 51.6%, respectively among GERD patients.4 In this study, the prevalence of RE was 6.1% of all subjects undergoing EGD, with asymptomatic RE in ABT-737 solubility dmso 11.6% of subjects with RE. The frequency of asymptomatic RE was low compared with previous studies. A possible reason for this may be the fact that the subjects of this study were patients attending hospital with some complaint, our use of an FSSG score of zero to define asymptomatic RE. Obesity has been implicated in GERD,12 and some studies have identified a correlation between asymptomatic RE and BMI. Wang et al. stated that a high BMI is an independent risk factor for erosive

esophagitis in asymptomatic subjects.9 In contrast, another study stated that a low BMI is an independent risk factor associated with asymptomatic esophagitis.5 In this study, we found no association between asymptomatic RE and BMI. As there were only 14 subjects with RE who were also obese (BMI > 30), the contribution of BMI is selleck inhibitor necessarily obscure in this particular subject population. Our results indicate that asymptomatic RE was significantly more common in older subjects than symptomatic RE, in agreement with some earlier studies. In one study, elderly patients with endoscopically diagnosed RE had a significantly lower prevalence of typical gastroesophageal reflux symptoms than young and adult patients.13 Another large-scale study found that the prevalence of severe erosive esophagitis increases with age, but the severity of heartburn symptoms is an unreliable indicator of the severity of erosive disease.14 Franceschi et al. reported that in elderly patients with gastrointestinal disorders symptoms may be slight or atypical, resulting in a delayed diagnosis.15 Maekawa et al. compared reflux symptoms between elderly and younger patients with RE, concluding that since elderly patients with mild RE were less symptomatic than younger patients, mild RE in the elderly can go undiagnosed.16 These studies indicate that elderly patients are less likely to report symptoms than younger patients.

We report imaging findings of posterior fossa DVA with a thrombosed drainage vein

in a patient with nonhemorrhagic cerebellar infarct. We also review the relevant GW-572016 concentration literature on the subject. “
“The 2-deoxy-2-[18F] fluoro-D-glucose positron emission tomography (FDG-PET) scan is commonly used in detection and staging of many malignant neoplasms. However, several benign or non-neoplastic conditions avidly accumulate 18F-FDG, causing ambiguity in interpretation of results. It is unknown whether pituitary adenomas uptake 18F-FDG and appear positive in PET imaging. Here, we present 2 cases of benign pituitary adenoma with elevated metabolic activity in 18F-FDG PET scan. Medical, neurologic, and psychiatric histories; physical examination findings;

laboratory work up results; and pathologic and imaging studies were documented. The 18F-FDG-PET images revealed foci of marked PLX4032 clinical trial FDG uptake in pituitary adenomas of 2 patients. Pituitary micro- and macro-adenomas may present as hypermetabolic foci on 18F-FDG PET scan. “
“Primary intracranial malignant fibrous histiocytoma (MFH) is an extremely rare entity. A few reported cases have been associated with factors such as a previous history of radiation therapy or surgical trauma. We report on a rare case of intracerebral MFH in a previously healthy 47-year-old man, which was initially presumed to be a high-grade glioma. Conventional as well as advanced magnetic resonance sequences, including diffusion-weighted image and

perfusion-weighted image, were used in characterization of the mass. “
“A 31-year-old male patient admitted to another hospital for investigation of a localized painful hump in the medial surface of his left leg. The clinical examination revealed a painful palpable lump in the medial surface of left thigh that was initially thought to be a hematoma due to a history of recent trauma. However, an ultrasound was requested to find more exclude deep venous thrombosis (DVT). The US examination revealed a heterogeneous, fusiform lesion with elongated proximal and distal projections in close proximity to superficial femoral artery and vein and could not definitely exclude the DVT hypothesis. In a second ultrasound examination performed in our department, a neurogenic origin of the lesion was proposed. A consequent MRI examination confirmed the presence of a fusiform tumor in the anatomic path of the saphenous nerve. This was further confirmed intraoperatively, and pathologically was diagnosed as a malignant peripheral nerve sheath tumor (MPNST). In this present study the role of ultrasonography, the correlation between MRI and ultrasonographic findings are discussed and a review of the literature is presented. “
“It is still controversial whether intravenous (IV) thrombolysis for acute ischemic stroke increases the risk of aneurysmal bleeding.

[18] Another successful example of probiotics from mouse studies is a report that the Lactobacillus casei strain Shirota is able to protect mice against SCH 900776 the onset of NAFLD by way of an attenuation of the TLR4-signaling cascade in the liver and

an increased peroxisome proliferator-activated receptor (PPAR)-γ activity.[73] Another interesting candidate for the probiotic management of liver disease is Bifidobacterium pseudocatenulatum CECT 7765; a recent study demonstrates that the administration of this probiotic bacteria improves various metabolic alterations in the HFD-fed mouse model, and is interestingly able to reduce liver steatosis.[74] Of note, the changes in gut microbiota composition induced by polyunsaturated fatty acids-depletion and prebiotics administration (fructo-oligosaccharides) is able Selleck JNK inhibitor to modulate hepatic steatosis by changing gene expression in the liver, suggesting that a prebiotic approach could be conceivable in the management of liver disease.[75] Probiotics may also be promising way to restore the “leaky gut” state observed in numerous patients with liver

disease; Escherichia coli strain Nissle 1917 is able to restore normal mucosal permeability in the murine dextran sulfate sodium (DSS)-induced colitis model, as well as induce up-regulation of zonula occludens 1 expression in vitro.[76] Similarly, probiotic mixture VSL#3 is able to prevent the increased intestinal permeability induced by a DSS treatment, phenomena associated with a prevention of decreased expression and redistribution of the tight junction proteins occludin, zonula occludens-1, and claudin-1, -3, -4, and -5 normally observed in DSS-treated mice.[77] Antibiotics, by themselves, seem unlikely to be an effective means of promoting a healthful host-microbiota relationship, but could be part of approaches to transplant microbiotas. While, at present, the beneficial effects of microbiota transplant are only proven to prevent recurrent Clostridium

difficile colitis,[78] a recent study found that microbiota transplant ameliorated insulin resistance,[79] suggesting that the approach might be broadly applicable to various aspects of metabolic syndrome, click here including NAFLD. Thus, while further studies are warranted, it is the opinion of the authors that manipulation of the gut microbiota will ultimately be a helpful means of treating and/or preventing liver disease. It has long been appreciated that environmental factors, including diet and infection, are major determinants of liver disease. Herein we reviewed evidence supporting the more recently appreciated concept that another important environmental factor is the large microbial biomass living in the intestine. Being close the liver, the gut microbiota can influence liver phenotype in a number of ways.

Fields in which health care interventions are integrated with public health strategies appear to have the greatest potential for completing the National Institutes of Health (NIH) bench to bedside to community progression. We suggest that public health approaches and partnerships may facilitate the accomplishment of the objectives of the NIDDK 10-year plan targeting the prevention and care of viral and fatty liver conditions and their complications for all Americans. Despite the swift progression in our knowledge of hepatitis C from the identification of the virus in 198940 to the development of evidence-based guidelines for its management and treatment in 1997,41 the rates of

screening, access to treatment, and successful outcomes of treatment are unacceptably low.42, Selleckchem ABT-263 43 Indeed, the three primary recommendations of the recent Institute of Medicine report on the prevention and control of HCV are (1) to improve disease surveillance, (2) to improve patient and community education, and (3) to integrate and enhance Selleckchem KU-60019 viral hepatitis services.44

Furthermore, the AASLD and NIH recognize that it is especially difficult to initiate and manage antiviral treatment in several populations that are disproportionately affected by hepatitis C, including current or recent illicit drug users and patients without stable housing.45, 46 We have yet to establish health care models in the United States that effectively identify, treat, and manage the diverse individuals infected with HCV. With the advent of promising new HCV therapies, it is critical to improve the current health

care delivery systems for hepatitis C. We believe that improved viral hepatitis surveillance, management, and treatment outcomes will require the use of public health strategies and the adoption of disruptive selleck kinase inhibitor innovations, such as integrated care models or HCV treatment delivery within methadone or homeless clinics.47-49 It is incumbent upon hepatology investigators with health service research and implementation science expertise to develop effective strategies and models of viral hepatitis surveillance, management, and treatment. In contrast to HCV, fatty liver disorders are biologically more heterogeneous with a more complex pathophysiology. This may explain the longer interval between the characterization of the syndrome in 198050 and the only recent demonstration of efficacious therapies.51 Indeed, the development of specific treatments for these disorders is challenged by the fact that fatty liver conditions are typically only one manifestation of an underlying metabolic or toxic pathology. Despite concerted efforts to understand the pathophysiology of nonalcoholic fatty liver disorders, identify targets for therapy, and perform rigorous efficacy trials,4, 52, 53 the number of individuals with fatty liver disorders and their complications continues to swell.

1 ±2.30% vs. 36.4±2.37%, p<0.001). Overall participants with NAFLD had higher prevalence of H. pylori positivity in multivariable analysis (Odds ratio [OR]: 1.17; 95% confidence interval [CI]: 0.95-1.43) with marginal significance. With regard to presence of cagA protein, H. pylori and cagA positivity was not associated with NAFLD (OR: 1.05; 95% CI: 0.81-1.37) but, cagA negative H. pylori positivity was significantly associated with NAFLD in multivariable analysis (OR: 1.30; 95% CI: 1.01-1.67). CONCLUSIONS: The prevalence of NAFLD was higher in H. pylori positive subjects than in negative subjects. Especially,

cagA negative H. pylori positivity was significantly associated with NAFLD, independent of other known see more factors in the general population. Disclosures: The following people have nothing to disclose: Donghee Kim, Seung Joo Kang, Hwa Jung Kim, Won Kim, Yoon Jun Kim, Jung-Hwan Yoon Staging of hepatic fibrosis and steatosis is vital for prognosis and interventions in non-alcoholic steatohepatitis (NASH). Liver biopsy, the gold standard, is invasive, costly and prone to error. Non-invasive methods for hepatic fibrosis and steatosis have been proposed but their validation in NASH is unsatisfactory. We conducted a retrospective study

of consecutive patients with biopsy-proven buy Pifithrin-�� NASH seen between 2007 and 2012 in our Unit. APRI, FIB-4 and NAFLD fibrosis score were used to diagnose liver fibrosis (>F2) and cirrhosis (F4). Ultrasound, Xenon-133 scan and hepatic steatosis index (HSI) were used to diagnose severe hepatic steatosis (>66%, S3). The cut-off values of the original reports were selleck products applied. Non-invasive tests were done within 6 months from liver biopsy, used as gold standard. Variables associated with each outcome were determined by multivariate logistic regression. The performance of non-invasive methods was expressed as sensitivity, specificity, positive and negative predictive values (PPV, NPV), area under the curve (AUC). We also modelled the best combination

algorithm able to increase the accuracy of the single methods. Overall, 114 (mean age 49.6, 69.5% males) patients were included. Biopsy length range was 0.5-3.3cm, 57% of cases being >1.5cm. Fibrosis stages by Brunt were as follows: F0-F1=50%, F2=16.8%, F3 = 19.2%, F4=14%. Steatosis grades were as follows: S0-1=16%, S2=53.3%, S3=30.7%. The following variables were associated with the outcome measures: age (p<0.0001), diabetes (p=0.01) and steatosis (p=0.02) for >F2; female gender (p<0.05) and triglycerides (p=0.04) for F4; diabetes (p<0.05) and fibrosis (p=0.01) for S3. The performance of the non-invasive methods is depicted in the Table. Overall, the best method for detection of >F2 and F4 was FIB-4. Xenon scan outperformed the other methods but its AUC for S3 was <0.70. Notably, an algorithm combining gender and FIB-4 showed an AUC of 0.90, with 100% NPV to exclude cirrhosis.

14, 15 The present study confirms the safety profile of αPlGF (Supporting Information Results and Supporting Information Fig. 11). Furthermore, αPlGF did not compensatorily up-regulate the expression of VEGF; selleck such up-regulation has been suggested to represent a possible cause of resistance to antiangiogenic treatment (Supporting Information Results and Supporting Information Fig. 11). In conclusion, this experimental study characterized the pathophysiological mechanisms and molecular effects that PlGF exerts on murine and human cirrhotic livers and on HSCs. Blockade of the PlGF pathway in cirrhotic mice by monoclonal antibodies or by genetic deficiency of PlGF decreased

hepatic and mesenteric angiogenesis, mesenteric arterial blood flow, fibrosis, and inflammation, as well as portal pressure. Also because of its safety profile, αPlGF may be considered as an attractive candidate for treating patients with chronic liver disease. We thank Julien Dupont and Huberte Moreau for technical assistance,

Kin Jip Cheung for compiling the demographic data of the patients, and Susana Kalko for technical assistance with bioinformatic analysis. LX-2 cells were generously supplied by Scott L. Friedman; αPlGF was kindly provided by ThromboGenics NV. Additional Supporting Information may be found in the online Antiinfection Compound Library cell line version of this article. “
“Background and Aim:  Patients with hepatocellular carcinoma (HCC) that is refractory to repeated transarterial chemoembolization

(TACE) are considered for systemic therapy, but TACE refractoriness is not well defined. The aim of this study was to determine the characteristics of patients whose HCC is refractory to repetitive TACE. Methods:  We evaluated 264 patients with intermediate-stage HCC who underwent TACE between January 2006 and September 2009. We designated the development of vascular invasion or extrahepatic see more spread during follow up as “stage progression” (SP), and hypothesized that SP might be the surrogate end-point for TACE refractoriness. Results:  The median follow up was 18.2 months, and median number of TACE was 3.0 (range, 1–13). Median time-to-progression was 5.5 months (95% confidence interval, 4.8–6.2), and median overall survival was 25.3 months (95% confidence interval, 21.6–29.0). We classified the patients according to disease course as: no progressive disease (PD(−); n = 33); PD without SP (PD(+)SP(−); n = 113); PD followed by SP (PDSP; n = 47); and simultaneous PD and SP (PD&SP; n = 64). PD(−) and PD(+)SP(−) groups showed no difference in overall survival, PDSP group had worse overall survival than PD(−) and PD(+)SP(−) groups, and PD&SP group had the worst overall survival. The significant prognostic factors for SP-free survival were development of PD and need for three sessions of TACE during the first 6 months.