Alpha-fetoprotein above normal levels as a risk factor for the development of hepatocellular carcinoma in patients infected with hepatitis C virus.
BACKGROUND
Noninvasive risk factors are required for predicting the development of hepatocellular carcinoma (HCC) not only in patients with cirrhosis but also in those with chronic hepatitis who are infected with hepatitis C virus (HCV).


METHODS
A total of 707 patients with chronic HCV infection without other risks were evaluated for the predictive value of noninvasive risk factors for HCC, including age, sex, viral load, genotype, fibrosis stage, aspartate and alanine aminotransferase levels, bilirubin, albumin, platelet count, and alpha-fetoprotein (AFP) at entry to the study, as well as interferon (IFN) therapy they received.


RESULTS
The ten-year cumulative incidence rates of HCC for patients with fibrosis stages F0/F1, F2, F3, and F4 were 2.5, 12.8, 19.3, and 55.9%, respectively. Multivariate analysis identified age ≥57 years [hazard ratio (HR) 2.026, P = 0.004], fibrosis stage F4 (HR 3.957, P < 0.001), and AFP 6-20 ng/mL (HR 1.942, P = 0.030) and ≥20 ng/mL (HR 3.884, P < 0.001), as well as the response to IFN [relative risk (RR) 0.099, P < 0.001], as independent risk factors for the development of HCC. The ten-year cumulative incidence rates of HCC in the patients with AFP levels of <6, 6-20, and ≥20 ng/mL at entry were 6.0, 24.6, and 47.3%, respectively.


CONCLUSIONS
Not only high (>20 ng/mL), but also even slightly elevated (6-20 ng/mL) AFP levels, could serve as a risk factor for HCC to complement the fibrosis stage. In contrast, AFP levels <6 ng/mL indicate a low risk of HCC development in patients infected with HCV, irrespective of the fibrosis stage.
Tateyama
Masakuni
M
Clinical Research Center, National Nagasaki Medical Center, Nagasaki, 856-8562, Japan.
Yatsuhashi
Hiroshi
H
Taura
Naota
N
Motoyoshi
Yasuhide
Y
Nagaoka
Shinya
S
Yanagi
Kenji
K
Abiru
Seigo
S
Yano
Koji
K
Komori
Atsumasa
A
Migita
Kiyoshi
K
Nakamura
Minoru
M
Nagahama
Hiroyasu
H
Sasaki
Yutaka
Y
Miyakawa
Yuzo
Y
Ishibashi
Hiromi
H
D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000627:therapeutic use; D044963:Biopsy, Fine-Needle; D006528:Carcinoma, Hepatocellular / Q000175:diagnosis / Q000453:epidemiology / Q000209:etiology*; D015331:Cohort Studies; D005260:Female; D016174:Hepacivirus / Q000302:isolation & purification; D019698:Hepatitis C, Chronic / Q000097:blood* / Q000150:complications* / Q000188:drug therapy; D006801:Humans; D015994:Incidence; D007372:Interferons / Q000627:therapeutic use; D008099:Liver / Q000473:pathology; D008103:Liver Cirrhosis / Q000097:blood* / Q000145:classification / Q000150:complications / Q000473:pathology; D008113:Liver Neoplasms / Q000175:diagnosis / Q000453:epidemiology / Q000209:etiology*; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D012307:Risk Factors; D055815:Young Adult; D000509:alpha-Fetoproteins / Q000032:analysis*
D000998:Antiviral Agents; D000509:alpha-Fetoproteins; D007372:Interferons