To determine the methylation profile of multiple tumor-related genes during multistep hepatocarcinogenesis, we investigated the methylation status of CpG islands of 9 genes, using methylation-specific polymerase chain reaction for 60 paired hepatocellular carcinoma (HCC) and non-HCC liver tissue samples, 22 dysplastic nodule (DN), 30 liver cirrhosis (LC), 34 chronic hepatitis (CH) and 20 normal liver samples. The methylation status of 9 genes was correlated to the clinicopathological findings of HCC patients. All HCC samples showed methylation of at least one gene, whereas it was shown in 72.7% of DN and 40% of LC, but was not shown in CH and normal liver samples (P < 0.001). The number of genes methylated showed a stepwise increase with the progression of stages (0 for normal liver and CH, 0.5 for LC, 1.5 for DN, and 3.7 for HCC (P < 0.001)). The genes frequently methylated in HCC were APC (81.7%), GSTP1 (76.7%), RASSF1A (66.7%), p16 (48.3%), COX-2 (35%), and E-cadherin (33.3%). COX-2, p16, RASSF1A, and TIMP-3 were not methylated in LC and CH from patients without concurrent HCC. Chronic liver diseases with concurrent HCC showed higher methylation frequencies of the tested genes, and a higher number of methylated genes than those without concurrent HCC. HCC patients with methylation of E-cadherin or GSTP1 showed poorer survival than those without (P = 0.034 and 0.043, respectively). In conclusion, our results indicated that CpG island methylation of tumor-related genes is an early and frequent event, and accumulates step-by-step during a multistep hepatocarcinogenesis. CpG island methylation of E-cadherin or GSTP1 might serve as a potential biomarker for prognostication of HCC patients.

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Nonalcoholic fatty liver disease (NAFLD) is related to risk factors of coronary artery disease, such as dyslipidemia, diabetes, and metabolic syndrome, which are closely linked with visceral adiposity. The aim of this study was to investigate whether NAFLD was associated with coronary artery calcification (CAC), which is used as a surrogate marker for coronary atherosclerosis independent of computed tomography (CT)-measured visceral adiposity. Out of 5,648 subjects who visited one of health screening centers between 2003 and 2008, we enrolled 4,023 (mean age 56.9 ± 9.4 years, 60.7% males) subjects without known liver disease or a history of ischemic heart disease. CAC score was evaluated by the Agatston method. In univariate analyses, the presence of CAC (score >0) was significantly associated with age, sex, body mass index, aspartate aminotransferase, alanine aminotransferase, high-density lipoprotein cholesterol, triglycerides and increased odds of diabetes, hypertension, smoking, and NAFLD. Increasing CAC scores (0, <10, 10-100, ≥100) were associated with higher prevalence of NAFLD (OR 1.84, 95% CI 1.61-2.10, P<0.001). Multivariate ordinal regression analysis adjusted for traditional risk factors, and CT-measured visceral adipose tissue area in a subgroup of subjects showed that the increased CAC scores were significantly associated with the presence of NAFLD (OR 1.28, 95% CI 1.04-1.59, P=0.023) independent of visceral adiposity. CONCLUSIONS Patients with NAFLD are at increased risk for coronary atherosclerosis independent of classical coronary risk factors, including visceral adiposity. These data suggest that NAFLD per se might be an independent risk factor for coronary artery disease.

Purpose:To determine the effi cacy and safety of transarterial chemoembolization (TACE) in patients with hepatocellular carcinoma (HCC) and main portal vein (MPV) invasion. Materials and Methods:This study was approved by the institutional review board, and the requirement to obtain informed consent was waived. The authors retrospectively assessed the electronic medical records of patients in whom HCC with MPV invasion was newly diagnosed from January 2004 to December 2007 at a single tertiary medical center. Patients with decompensated hepatic function were excluded. Outcomes of patients treated with TACE were compared with those of patients given supportive care according to Child-Pugh class. Results:One hundred twenty-fi ve patients (104 men and 21 women; mean age, 55.7 years; age range, 33.4-83.0 years) were included. The median overall survival was 3.7 months (range, 0.2-33.3 months). Eighty-three of the 125 patients (66.4%) were treated with TACE and 42 (33.6%) received supportive care. Repeated TACE showed significant survival benefi ts compared with supportive care in patients with Child-Pugh class A (median survival, 7.4 months vs 2.6 months, respectively; P , .001) and class B (median survival, 2.8 months vs 1.9 months, respectively; P = .002) disease. Results of multivariate analysis showed that treatment with TACE (hazard ratio, 0.263; 95% confi dence interval [CI]: 0.164, 0.424; P , .001) and Child-Pugh class A status (hazard ratio, 0.550; 95% CI: 0.368, 0.822; P = .004) were independent predictive factors of a favorable outcome. There were no procedurerelated deaths within 4 weeks after TACE, and patient morbidity was 28.9% (24 of 83 patients). Conclusion:TACE can be performed safely and may improve the overall survival of patients with HCC and MPV invasion.q RSNA, 2011