title: Hepatitis C virus seromarkers and subsequent risk of hepatocellular carcinoma: long-term predictors from a community-based cohort study.
abstract: OBJECTIVE
  Hepatitis C virus (HCV) contributes to one third of hepatocellular carcinoma cases worldwide. Long-term predictors for HCV-related hepatocellular carcinoma are essential for early intervention. Serum HCV RNA and ALT levels and HCV genotype were assessed for their predictability of hepatocellular carcinoma risk.
  
  
  METHODS
  A prospective cohort of 925 participants positive for antibodies against HCV and age 30 to 65 years was recruited and followed from 1991 to 2006. Serum HCV RNA and ALT levels and HCV genotypes at enrollment and during follow-up were examined. Newly developed hepatocellular carcinoma was identified by health examination and computerized linkage with national cancer registration and death certification profiles. Multivariate adjusted hazard ratios with 95% CIs were estimated using Cox regression models.
  
  
  RESULTS
  Fifty-five participants newly developed hepatocellular carcinoma during 8,476 person-years of follow-up, giving an incidence rate of 648.9 per 100,000 person-years. The cumulative hepatocellular carcinoma risk increased from 1.1% for HCV RNA seronegative status to 6.4% for low HCV RNA levels and to 14.7% for high HCV RNA levels (P < .001). The cumulative risk also increased with elevated serum ALT levels from 1.7% for persistently ≤ 15 U/L to 4.2% for ever more than 15 U/L but never more than 45 U/L and to 13.8% for ALT ever ≥ 45 U/L (P < .001). Having HCV genotype 1 was associated with a higher cumulative hepatocellular carcinoma risk (12.6%) than not having HCV genotype 1 (4.5%; P < .001).
  
  
  CONCLUSIONS
  Elevated serum levels of HCV RNA and ALT and HCV genotype 1 infection are independent risk predictors of hepatocellular carcinoma. These findings have strong implications for the management of chronic HCV.
authors.affiliation: National Taiwan University, Taipei, Taiwan.
authors.forename: Mei-Hsuan
authors.initials: MH
authors.lastname: Lee
authors.forename: Hwai-I
authors.initials: HI
authors.lastname: Yang
authors.forename: Sheng-Nan
authors.initials: SN
authors.lastname: Lu
authors.forename: Chin-Lan
authors.initials: CL
authors.lastname: Jen
authors.forename: Shiou-Hwei
authors.initials: SH
authors.lastname: Yeh
authors.forename: Chun-Jen
authors.initials: CJ
authors.lastname: Liu
authors.forename: Pei-Jer
authors.initials: PJ
authors.lastname: Chen
authors.forename: San-Lin
authors.initials: SL
authors.lastname: You
authors.forename: Li-Yu
authors.initials: LY
authors.lastname: Wang
authors.forename: Wei J
authors.initials: WJ
authors.lastname: Chen
authors.forename: Chien-Jen
authors.initials: CJ
authors.lastname: Chen
mesh_terms: D000328:Adult; D000368:Aged; D000410:Alanine Transaminase / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D006528:Carcinoma, Hepatocellular / Q000401:mortality / Q000821:virology*; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics* / Q000276:immunology; D018937:Hepatitis C Antibodies / Q000097:blood; D019698:Hepatitis C, Chronic / Q000097:blood / Q000150:complications / Q000175:diagnosis* / Q000401:mortality; D006801:Humans; D053208:Kaplan-Meier Estimate; D008113:Liver Neoplasms / Q000401:mortality / Q000821:virology*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012367:RNA, Viral / Q000097:blood*; D018570:Risk Assessment; D012307:Risk Factors; D013624:Taiwan; D013997:Time Factors; D015854:Up-Regulation; D019562:Viral Load
chemical_list: D015415:Biomarkers; D018937:Hepatitis C Antibodies; D012367:RNA, Viral; D000410:Alanine Transaminase