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Hepatocarcinogenesis is a multistep process that evolves from cirrhosis or dysplastic nodule (DN), and eventually leads to overt hepatocellular carcinoma (HCC). Differentiation between early HCC and DN is an important issue in the clinical setting. This study aims to investigate the potential of circulating microRNA (miRNA) levels in the diagnosis of early HCC. RNA was extracted from sera of 30 chronic hepatitis B patients with pathologically proven DN and 120 age- and sex-matched patients with early HCC. Paired samples were collected from ten patients with DN who developed overt HCC in the follow-up. A panel of ten cancer-associated miRNAs was analyzed by quantitative real-time reverse-transcription polymerase chain reaction. Serum levels of miR-16, miR-122, miR-221, let-7b and miR-15b were significantly lower in patients with DN than in the HCC group. When DN progressed to overt HCC, serum miR-122, miR-let-7b and miR-15b levels increased significantly (p50.046, 0.043 and 0.044, respectively). As a single marker, α-fetoprotein (AFP) and miR-122 as well as let-7b had the similar performance for differentiate HCC from DN. As limited to subjects with normal AFP, let-7b resulted in a sensitivity of 84.8% and a specificity of 50% in separating HCC and DN with a cutoff value of 3.5 (p50.001). In conclusion, miR-122 and let-7b, which are upregulated in the serum of early-HCC patients, can be useful markers for differentiating early HCC from DN in chronic hepatitis B patients. [ABSTRACT FROM AUTHOR]

Background and Aim Based on up-to-seven criteria and Child- Pugh score, four substages of Barcelona Clinic Liver Cancer ( BCLC) intermediate hepatocellular carcinoma ( HCC) were proposed. The purpose of this study was to validate and modify this proposal. Methods Between January 2002 and February 2011, newly diagnosed intermediate HCC patients underwent transarterial embolization ( TAE) were enrolled. Patients were stratified into four ( B1- B4) substages and followed up until death or end of 2012. Patients' survivals and discriminatory ability of substaging systems were compared. Results Five-hundred and eighty patients were enrolled. There were 56.6%, 33.8%, 7.4%, and 2.2% in substage B1, B2, B3, and B4. The 5-year survival rate was 21.4%, 13.9%, 7.4%, and 7.7% with median survival time of 2.4, 1.3, 0.5, and 0.8 years ( P < 0.001). In addition to substage B1- B4, α-fetoprotein ( AFP) level was an independent factor associated with survival in multivariate analysis. According to AFP < or > 200 ng/mL, B1 was classified into B1a and B1b, and B2 into B2a and B2b. There were no differences in survivals between B1b and B2a ( P = 0.174), and B2b and B3 ( P = 0.785). Patients were re-classified into modified (m) B1 ( B1a), mB2 ( B1b + B2a), m B3 ( B2b + B3). The modified substages (m B1-m B3) showed a more desirable substaging system. Conclusions For BCLC intermediate HCC patients, substages B1- B4 were useful in predicting survival after TAE. However, modified substaging system provided better prognostic prediction. [ABSTRACT FROM AUTHOR]

Background and Aims: Hepatitis C virus (HCV) infection is reported to be associated with or to cause type 2 diabetes mellitus (T2DM). Our study aimed to elucidate the role of triglyceride (TG) and cholesterol (CHOL) levels in the association between anti-HCV seropositivity and T2DM in an HCV-endemic area. Methods: We analyzed a computerized dataset of 56 338 residents from a community-based comprehensive screening program in Tainan County in southern Taiwan. Fasting glucose, anti-HCV status, hepatitis B surface antigen (HBsAg) status, platelet counts, TG levels, CHOL levels, age, gender, and body mass index were included in the analyses. Multivariate logistic analysis was used to identify factors independently associated with T2DM. Results: Older age, being overweight, thrombocytopenia, hypertriglyceridemia, hypercholesterolemia, anti-HCV seropositivity, and HBsAg seronegativity were common factors independently associated with diabetes. Among all models of multiple logistic regression analysis used for identifying factors independently associated with T2DM, anti-HCV seropositivity was only identified in the models that included either hypertriglyceridemia or hypercholesterolemia. When subjects were divided into hyperlipidemia (CHOL, > 200 or TG, > 150 mg/dL; n = 33 393) or non-hyperlipidemia subgroups (CHOL, < 200 and TG, < 150 mg/dL; n = 22 945), anti-HCV seropositivity was identified as an independent factor only in the non-hyperlipidemia subgroup. The odds ratio was 1.35, with a 95% confidence interval of 1.17-1.55. Conclusions: This study demonstrates that the lipid level is associated with the relationship between T2DM and anti-HCV seropositivity in non-hyperlipidemic individuals. However, the relationship between HCV and T2DM did not exist when the lipid level was not included in the analysis. [ABSTRACT FROM AUTHOR]

Background and Aim: Long-term trends of anti-hepatitis C virus (HCV) antibody titer and their associated factors in patients with sustained virological response (SVR) were investigated. Methods: From May 1999 to July 2005, a total of 166 SVR consecutive patients (M/F: 86/80) were enrolled. Anti-HCV titer, samples to cut-off (S/CO) ratios, were measured with AxSYM HCV version 3.0. Their S/CO ratios were followed every 6 months after SVR and the patterns over time were identified by trajectory analyses. Changes of recombinant immunoblot assay (RIBA) pattern before treatment and end of follow-up were compared ( n = 64). Results: The mean duration of follow-up was 4.7 ± 1.5 years (median 4.3; range 3-9 years). The rates of S/CO ratios decreased annually ( P < 0.001). Two of them (1.2%) achieved seroreversion. Trajectory groups included lower pretreatment S/CO ratios (LAB, n = 83), rapid decrease (RD, n = 62) and slow decrease (SD, n = 21) groups. Comparing LAB to RD group, odds ratio (OR) of increased platelet count per 1 unit and interferon regimen was 1.12 (95% confidence interval [CI] 1.04-1.20) and 2.17 (95% CI 1.04-4.52) respectively. Comparing SD to LAB and RD groups, the OR of advanced fibrotic stage, using mild fibrotic stage as a reference, was 4.33 (95% CI 1.49-12.63). Reaction strength of all four RIBA bands decreased significantly at the end of follow-up. Conclusions: Anti-HCV titers decreased annually during long-term follow-up after SVR. Higher pretreatment platelet count, interferon regimen and mild fibrosis were associated with decreased anti-HCV titers. However, only a few cases achieved seroreversion. All RIBA bands decreased significantly after long-term follow-up. [ABSTRACT FROM AUTHOR]

This study was aimed to validate the 5th and 6th editions of tumor-node-metastasis (TNM) system for patients with hepatocellular carcinoma (HCC), and attempted to improve prognostic stratification by modifying the 6th edition according to vascular invasion and tumor size. From 1986 to 2002, a total of 5,613 HCC cases from Kaohsiung Chang Gung Memorial Hospital in southern Taiwan were enrolled. The 6th edition was modified by dividing stage I into stages IA (single tumor, ≤2cm) and IB (single tumor, >2cm), and by dividing stage II into IIA (multiple tumors, none >5cm) and IIB (tumor with segmental macro vascular invasion). The Akaike information criteria (AIC), within a Cox proportional hazard regression model were used; lower AIC value indicated a better discriminatory ability for staging system. The 1-, 3-, 5-, and 7-year overall survival rates were 45.6, 25.9, 17.9, and 13.4%, respectively. Significant differences in survival curve existed in the 5th, 6th, and modified 6th edition TNM systems. For the modified 6th edition TNM, survival differed significantly between stages IA and IB, and between stage IIA and IIB. The AIC values of 5th (72,328), 6th (72,188), modified 6th (71,991) edition TNM system were decreasing. This investigation demonstrated better prognostic stratifications for the 6th edition than the 5th edition TNM staging system. Moreover, the modified 6th edition staging system demonstrated better prognostic prediction than the former two. Pretreatment staging and simple classification of current modified 6th edition TNM staging can be applied to all HCC patients and are clinically useful. © 2007 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

Background: The Cancer of the Liver Italian Program (CLIP) staging system for hepatocellular carcinoma (HCC) was subdivided into 36 subgroups. We aimed to validate the prognostic value of CLIP scoring., Methods: This study included 3868 HCC cases treated between 1986 and 2002. Survival and prognostic impact of all subgroups were analysed., Results: In primary CLIP, comparisons of each score showed a significant difference (P<0.001) and exhibited a linear trend (P<0.001). A CLIP score of 0 was used as control group. Portal vein thrombosis, Child-Pugh B, alpha-fetoprotein (AFP) > or =400 ng/ml and multinodular with tumour extension < or =50% of the four subgroups with a CLIP score of 1 exhibited decreasing univariate hazard ratios and 95% confidence intervals, with values of 2.99 (2.05-4.37), 2.39 (2.00-2.86), 1.66 (1.40-1.96) and 1.39 (1.18-1.63) respectively. Homogeneity in the same score was evaluated by comparing subgroup survival curves. For scores 1-5, 83.3% (5/6), 57.1% (16/28), 24.4% (11/45), 3.6% (1/28) and 16.7% (1/6) pairs of survival curves significantly differed, respectively, with decreasing linear trend (P<0.001)., Conclusion: Different prognostic weighting of four predictive factors caused intrascore heterogeneity. Lower CLIP scores were associated with increased differences in intrascore. In conclusion, the CLIP staging scoring system is a reasonable ordinal scale, but the clinician must be aware of the heterogeneity of mortality risk within a given score.