Hepatitis C virus seromarkers and subsequent risk of hepatocellular carcinoma: long-term predictors from a community-based cohort study.
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.
Lee
Mei-Hsuan
MH
National Taiwan University, Taipei, Taiwan.
Yang
Hwai-I
HI
Lu
Sheng-Nan
SN
Jen
Chin-Lan
CL
Yeh
Shiou-Hwei
SH
Liu
Chun-Jen
CJ
Chen
Pei-Jer
PJ
You
San-Lin
SL
Wang
Li-Yu
LY
Chen
Wei J
WJ
Chen
Chien-Jen
CJ
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
D015415:Biomarkers; D018937:Hepatitis C Antibodies; D012367:RNA, Viral; D000410:Alanine Transaminase