Risk and predictors of hepatocellular carcinoma for chronic hepatitis B patients with newly developed cirrhosis.
OBJECTIVE
Most studies on risk predictors of hepatocellular carcinoma (HCC) among cirrhotic chronic hepatitis B patients do not confirm the date at cirrhosis diagnosis. We examined HCC risk and predictors in chronic hepatitis B patients with newly diagnosed cirrhosis.


METHODS
4155 HBsAg seropositive participants were followed every 6-12 months with seromarker testing. Cirrhosis was ascertained through abdominal ultrasonography and computerized linkage with national health insurance profiles. Predictors included in Cox proportional hazards models were age, HBeAg serostatus, serum levels of HBsAg, alanine aminotransferase (ALT), alpha-fetoprotein (AFP), and ALDH2 rs671 genotypes.


RESULTS
A total of 301 patients developed cirrhosis, 76 of whom later developed HCC after 2462 person-years, showing an average annual incidence of 3.1%. The 15-year cumulative HCC risk among cirrhotics was 39.8% with a lifetime (30-80 years old) HCC risk of 78.5%. The adjusted HR's (95% CI, P-value) were 14.26 (3.17-64.08, P = 0.0005) for age at cirrhosis diagnosis of ≥60 years (vs 30-39 years), 2.85 (1.49-5.46, P = 0.0015) for HBeAg seropositivity (vs HBeAg seronegativity with HBsAg levels <1000 IU/mL), 0.35 (0.20-0.59, P < 0.0001) for AA/AG genotypes of rs671 (vs GG genotype), 3.68 (1.70-7.99, P = 0.0010) for ALT levels >45 U/L (vs <15 U/L), 3.52 (1.78-6.93, P = 0.0003) for AFP levels >20 ng/mL (vs <10 ng/mL), and 2.64 (1.38-5.07, P = 0.0035) for HBsAg levels ≥1000 IU/mL (vs <1000 IU/mL among HBeAg seronegatives).


CONCLUSIONS
Older age, GG genotype of ALDH2 rs671, HBeAg seropositivity, and elevated serum levels of ALT, AFP, and HBsAg at cirrhosis diagnosis were HCC risk predictors in cirrhotic chronic hepatitis B patients.
Department of Epidemiology, UCLA Fielding School of Public Health, Los Angeles, California, USA.
Justin
J
Chien
Genomics Research Center, Academia Sinica, Taipei, Taiwan.
Jessica
J
Liu
Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan.
Mei-Hsuan
MH
Lee
Genomics Research Center, Academia Sinica, Taipei, Taiwan.
Chin-Lan
CL
Jen
Roche Diagnostics, Ltd, Basel, Switzerland.
Richard
R
Batrla-Utermann
Department of Gastroenterology, Chang-Gung Memorial Hospital, Kaohsiung, Taiwan.
Sheng-Nan
SN
Lu
MacKay Medical College, New Taipei City, Taiwan.
Li-Yu
LY
Wang
Department of Public Health, College of Medicine, Catholic Fu-Jen University, New Taipei City, Taiwan.
San-Lin
SL
You
Genomics Research Center, Academia Sinica, Taipei, Taiwan.
Hwai-I
HI
Yang
Genomics Research Center, Academia Sinica, Taipei, Taiwan.|Graduate Institute of Epidemiology and Preventative Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan.
Chien-Jen
CJ
Chen
D000328:Adult; D000367:Age Factors; D000368:Aged; D000071396:Aldehyde Dehydrogenase, Mitochondrial / Q000235:genetics; D014408:Biomarkers, Tumor / Q000097:blood / Q000235:genetics; D006528:Carcinoma, Hepatocellular / Q000097:blood / Q000175:diagnosis / Q000453:epidemiology / Q000821:virology*; D018450:Disease Progression; D005260:Female; D020022:Genetic Predisposition to Disease; D006514:Hepatitis B Surface Antigens / Q000097:blood; D019694:Hepatitis B, Chronic / Q000097:blood / Q000150:complications* / Q000175:diagnosis / Q000453:epidemiology; D006801:Humans; D015994:Incidence; D008103:Liver Cirrhosis / Q000097:blood / Q000175:diagnosis / Q000453:epidemiology / Q000821:virology*; D008113:Liver Neoplasms / Q000097:blood / Q000175:diagnosis / Q000453:epidemiology / Q000821:virology*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011237:Predictive Value of Tests; D011379:Prognosis; D016016:Proportional Hazards Models; D011446:Prospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D013624:Taiwan / Q000453:epidemiology; D013997:Time Factors; D000509:alpha-Fetoproteins / Q000378:metabolism
C097353:AFP protein, human; D014408:Biomarkers, Tumor; D006514:Hepatitis B Surface Antigens; D000509:alpha-Fetoproteins; C096127:ALDH2 protein, human; D000071396:Aldehyde Dehydrogenase, Mitochondrial
epidemiology; polymorphism; prediction; viral load