Increased risk of hepatocellular carcinoma in male hepatitis B surface antigen carriers with chronic hepatitis who have detectable urinary aflatoxin metabolite M1

✍ Scribed by Zongtang Sun; Peixin Lu; Mitchell H. Gail; David Pee; Qinan Zhang; Lihua Ming; Jinbing Wang; Yan Wu; Guoting Liu; Yuying Wu; Yuanrong Zhu

• Publisher: John Wiley and Sons
• Year: 1999
• Tongue: English
• Weight: 54 KB
• Volume: 30
• Category: Article
• ISSN: 0270-9139
• DOI: 10.1002/hep.510300204

✦ Synopsis

We followed 145 men with chronic hepatitis B virus (HBV) hepatitis for 10 years to determine whether exposure to aflatoxin, or concomitant exposure to hepatitis C virus (HCV), or family history of hepatocellular carcinoma (HCC) increased the risk of developing HCC. We collected 8 monthly urine samples before beginning follow-up and pooled them to detect aflatoxin metabolite M1 (AFM1). AFM1 was detected in 78 (54%) of the subjects. The risk of HCC was increased 3.3-fold (with a 95% confidence interval of 1.2-8.7) in those with detectable AFM1 (above 3.6 ng/L). This relative risk was adjusted for age and for HCV status. The attributable risk from exposure to detectable AFM1 was 0.553 (0.087, 0.94). The relative risk of fatal cirrhosis for those with elevated AFM1 was 2.8 (0.6, 14.3), and the odds of having a persistently elevated alanine transaminase (ALT) were 2.5-fold greater in those with detectable AFM1 (P ‫؍‬ .007). Concomitant infection with HCV increased the risk of HCC 5.8-fold (2.0-17), adjusted for age and AFM1 status. A family history of HCC increased the risk of HCC 5.6-fold, adjusted for age and AFM1. Four men with detectable AFM1 and HCC all had missense mutation in codon 249 of the p53 gene in cancer tissues. This study shows that exposure to AFM1 can account for a substantial part of the risk of HCC in men with chronic HBV hepatitis and adds importantly to the evidence that HCV and family history of HCC increase the risk of HCC in men with chronic HBV hepatitis. (HEPATOLOGY 1999;30:379-383.)

PATIENTS AND METHODS

Population-based sampling was used to obtain a representative study cohort. In an earlier study of the prevalence of HBV infection sponsored by the Ministry of Public Health, China, from 1981 to 1982, 2 townships, formerly called communes, were selected at random from among 45 townships in Qidong. These 2 townships Abbreviations: HCC, hepatocellular carcinoma; HBV, hepatitis B virus; HBsAg, hepatitis B surface antigen; AFM1, metabolite M1 of aflatoxin; HCV hepatitis C virus; ALT, alanine transaminase; HPLC, high-pressure liquid chromatography.