Background/aim: Non-alcoholic steatohepatitis (NASH) may progress to liver cirrhosis, and finally hepatocellular carcinoma. Recent study suggested that development of hepatic angiogenesis correlates the risk for hepatocarcinogenesis in liver cirrhosis patient. We therefore examined the role of angiogenesis in the hepatocarcinogenesis of NASH in both experimental and human study. Methods: As an experimental NASH model, Zucker (Z) rats, which naturally develop leptin receptor mutations, and their lean littermate (L) rats were fed a choline-deficient, amino acid-defined (CDAA) diet. In human study, 11 patients with NASH-related cirrhosis or pre-cirrhosis, regarded as high risk group of hepatocarcinogenesis, and 13 with simple fatty liver (FL) were enrolled and underwent clinico-pathological examinations. Immunohistochemical analysis of 4-hydroxy-2-noneal (4-HNE) and CD34 were employed for detection of reacrive oxidative stress (ROS) and angiogenesis in the liver tissues, respectively. Results: In experimental NASH model, both groups showed marked steatohepatitis by feeding CDAA diet. In sharp contrast, the development of glutathione-S-transferase placental form (GST-P)-positive pre-neoplastic lesions and HCC could be observed only in the L-rats. The hepatic neovascularization was also significantly increased only in the L-rats. In human study, Both NASH and FL exerted a marked elevation of ROS. In sharp contrast, significant development of hepatic neovascularization was observed only in NASH, whereas almost no neovascularization could be observed in FL. Conclusion: In conclusion, these results suggested that neovascularization might play a important role in hepatocarcinogenesis in NASH. Background: Paternally expressed gene 10 (PEG10), which was an imprinted gene with an active paternal allele but silent maternal allele, was highly expressed in a great majority of hepatocellular carcinoma(HCC). The aim of this study was to generate transgene mice expressing PEG10 in the liver under the control of mouse albumin (ALB) promoter and study the integration, transcription, expression of PEG10 gene in the transgenic mice Methods: The linearized 1716bp transgene fragments, which contained ALB promoter and structural gene of PEG10, were microinjected into fertilized eggs of mice. Then manipulated embryos were transferred into the oviducts of pseudo-pregnant female mice. All the newborn mice were screened and identified by PCR detecting genomic DNA in tail tissue. As the transgene was driven by the ALB promoter, we examined its expression in the liver of transgenic mice by RT-PCR and western blotting. Results: The transgene fragment was microinjected into the male pronucleus of 3741 fertilized oocytes. The injected eggs were implanted into oviducts of 94 pseudo-pregnant foster mothers, of which 22 mice became pregnant and give birth to 108 offspring. 65 of them died from unknown reason. Among the 43 offspring, 3 were identified to carry PEG10 cDNA as demonstrated by PCR, and PEG10 transgene could be expressed successfully in the liver of the established transgenic mice. The ratio of transgene integration were 6.97% (3/43) by PCR. Conclusions: The PEG10 transgenic mouse model should be valuable for studying the in viro function of this imprinted gene in HCC. Background/Aims: Brivanib alaninate is the L-alanine ester prodrug of BMS-540215, an oral selective dual inhibitor of vascular endothelial growth and fibroblast growth pathway receptors. It is being developed in treating hepatocellular carcinoma (HCC), a disease highly prevalent in Asia-pacific region. This analysis investigated whether BMS-540215 exposure was different between Asian and non-Asian subjects. Methods: A population pharmacokinetic (PPK) model was developed with data collected in 125 subjects (78 non-Asian, 47 Asian) with advanced and metastatic solid tumors (including HCC) from 2 clinical studies. Potential effects of the following covariates on model parameters were examined: age, gender, race, and baseline body weight. Model-based simulation was performed to examine BMS-540125 exposure in Asian and non-Asian patients following brivanib doses of 800 mg QD (Phase III dose). Results: The PPK of BMS-540215 was characterized by a 2-compartment model with first-order absorption and elimination. Clearance was found to slightly increase with body weight (p<0.01). However, effects of age, gender and race on clearance were not statistically significant. The median of apparent clearance in Asian was 9.5% lower than that of non-Asians, which was adequately explained by 16% lower body weight in Asians. There was substantial overlap in steady-state BMS-540215 AUC of Asian and non-Asian patients, simulated based on their observed body weight distributions in these patient groups. Conclusions: BMS-540215 PK can be adequately described by a linear 2-compartment model; exposures in Asian and non-Asian subjects are similar following brivanib doses of 800 mg QD. Background/aims: Hepatic resection is the standard treatment for hepatocellular carcinoma. In some patients with multiple HCC, one-block resection can not be feasible due to either the tumor location or the reserved liver function. In this study, we attempted to analyze the outcome of multiple-site resection or combined resection and RFA in patients with multiple HCC. The prognostic factors for postoperative survival were also investigated.