BACKGROUND.: The objective of this study was to examine the usefulness of platelet counts in the diagnosis of cirrhosis and for identifying high‐risk individuals in a community‐based hepatocellular carcinoma (HCC) screening program.METHODS.: Pilot Study 1 determined the correlation between platelet counts and pathologic hepatic fibrosis scores among individuals with chronic hepatitis B virus (HBV) infection (n = 122 patients) and hepatitis C virus (HCV) infection (n = 244 patients). Pilot Study 2 investigated proportions of individuals with thrombocytopenia (<150 × 10³/mm³) among patients with HCC (n = 4042 patients). Pilot Study 3 demonstrated the correlation between platelet counts and ultrasonographic (US) parenchyma scores among anti‐HCV‐positive individuals (n = 75 patients). The core study was a 2‐stage, community‐based screening for HCC among residents age 40 years or older in townships with a high prevalence of anti‐HCV (n = 4616 individuals) and in townships with a low prevalence of anti‐HCV (n = 1694 individuals). Patients with thrombocytopenia were identified for US and α‐fetoprotein screening.RESULTS.: Among the individuals who were positive for anti‐HCV, platelet counts decreased according to increased pathologic fibrosis scores or US scores for liver parenchyma disease: The best cutoff platelet count was 150 × 10³/mm³ for a diagnosis of cirrhosis. The sensitivity and specificity were 68.2% and 76.4%, respectively, for pathologic cirrhosis and 76.2% and 87.8%, respectively, for US cirrhosis. Forty‐eight percent of patients with HCC were thrombocytopenic. The proportion of thrombocytopenia was significantly greater in patients with HCV‐related HCC (63%) than in patients with HBV‐related HCC (42%). In the townships with high and low anti‐HCV prevalence, the prevalence of thrombocytopenia was 17.9% and 6.1%, respectively, (P < .001), respectively. Twenty‐five patients were diagnosed with HCC, and all of those patients resided in the high‐prevalence township.CONCLUSIONS.: Thrombocytopenia was a valid surrogate of cirrhosis and a valid marker for the identification of individuals at high‐risk for HCC, especially in areas that had a high prevalence of HCV. Cancer 2006. © 2006 American Cancer Society.

There is strong evidence linking chronic hepatitis C virus (HCV) infection and Type 2 diabetes mellitus (DM). Recent studies have suggested that DM is associated with increased risk of developing hepatocellular carcinoma (HCC). The aim of our cohort study was to assess whether DM influence the incidence of HCC in chronic hepatitis C patients treated with interferon (IFN)‐based antiviral therapy. A total of 1,470 chronic hepatitis C patients treated with IFN or pegylated‐IFN plus ribavirin therapy were enrolled. Of them, 253 (17%) patients had DM at entry. Evaluation of HCC incidence was performed by Kaplan–Meier method and Cox proportional hazards analysis. Patients with baseline DM were significantly older and had higher body mass index, serum transaminase levels and fibrosis scores and lower platelet counts compared to non‐DM subjects. Sustained virological response (SVR) was achieved in 160 (63%) of DM and 867 (71%) of non‐DM patients (p = 0.008). During a median follow‐up period of 4.3 years, HCC developed in 21 (8.3%) of DM and 66 (5.4%) of non‐DM patients (p = 0.017). However, DM was not an independent covariate by Cox proportional hazards analysis. In a subgroup analysis, DM (hazard ratio, 4.32; 95% confidence interval, 1.23–15.25; p = 0.023) was an independent predictor of HCC in the SVR patients without baseline cirrhosis, despite a low HCC incidence. In conclusion, DM has a selective impact on HCC development among chronic hepatitis C patients after IFN‐based therapy. DM may increase the HCC risk in chronic hepatitis C without cirrhosis after eradication of HCV.

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.