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Background  We analyzed whether difference exist in the clinical manifestations and outcomes of hepatocellular carcinoma (HCC) according to the two major etiologies of HCC from a nationwide, population-based, random HCC registry.    Methods  Of the 31,521 new HCC cases registered at the Korea Central Cancer Registry between 2003 and 2005, 4,630 (14.7%) were randomly abstracted, and followed up until December 2011. Of those, 2,785 hepatitis B virus (HBV)-related and 447 hepatitis C virus (HCV)-related HCC patients were compared.    Results  The mean annual incidence rates of HBV- and HCV-related HCC incidence per 100,000 persons were 20.8 and 4.9, respectively. The annual incidence rate of HBV-related HCC peaked at 50–59 age group (46.5 per 100,000 persons), while the annual incidence rate of HCV-related HCC increased gradually to the ≥70 year age group (13.2 per 100,000 persons). Large tumors (≥5 cm) and portal vein invasion at initial diagnosis were more frequent in HBV-related HCC, while multiple tumors were more frequent in HCV-related HCC. In outcome analysis, HBV-related HCC showed poorer survival than HCV-related HCC [median survival: 1.34 vs. 2.17 years, adjusted hazard ratio (95% confidence interval): 0.88 (0.78–0.98),  P  = 0.03, adjusted for age, gender, Child-Pugh class, AJCC/mUICC stage, and initial treatment modality]. However, when divided according to the AJCC/mUICC stage, survival difference was observed only for those with AJCC/mUICC stage IV tumor, but not for AJCC/mUICC stage I, II or III tumors. The treatment outcome of each modality (resection, ablation, and transartherial chemoeombolization) was comparable between the two etiologies.    Conclusion  HBV-related and HCV-related HCC have clear differences in clinical manifestation, requiring different screening strategy according to etiology to optimize HCC surveillance in HBV-endemic area. However, etiology did not affect treatment outcomes and long-term survival within the same stage except for far advanced tumors.

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Comparison of Clinical Manifestations and Outcomes between Hepatitis B Virus- and Hepatitis C Virus-Related Hepatocellular Carcinoma: Analysis of a Nationwide Cohort