Early-onset Hepatocellular Carcinoma Research Articles

Risk Factors for Early-Onset and Late-Onset Hepatocellular Carcinoma in Asian Immigrants With Hepatitis B in the United States

Routine screening for hepatocellular carcinoma (HCC) is recommended in chronic hepatitis B (HBV) patients with cirrhosis and select non-cirrhotic HBV populations including Asian males ages 40 and older and females ages 50 and older. However, many younger HBV patients develop HCC and there have been few studies examining this group. Additionally, studies of HCC in the Asian immigrant population in the United States have been limited. The objective of this study was to determine the associated risk factors for the development of early-onset (males and females under ages 40 and 50, respectively) and late-onset HCC in immigrants with chronic HBV in the United States. Clinical, demographic, and laboratory data were retrospectively collected on all Asian immigrants with HBV at Bellevue Hospital Center from 2003 to 2009. Patients with HCC were identified within this cohort. Features of early-onset and late-onset HCC cases were compared with age-matched HBV controls without HCC. We identified 168 cases of HCC in Asians with HBV. In all, 74% (124/168) of cases were late-onset, and 26% (44/168) were early-onset. When comparing the 124 late-onset HCC cases with 199 age-matched HBV controls, gender (odds ratio (OR)=4.4; P<0.05) and cirrhosis (OR=9.6; P<0.05) or surrogate labs (i.e., platelets, international normalized ratio, total bilirubin, albumin) were found to be associated with HCC development. When comparing the 44 early-onset HCC cases with 432 age-matched HBV controls, family history of HCC (OR=2.7; P<0.05), and smoking history (OR=3.4; P<0.05) were independently associated risk factors in addition to gender (OR=2.7; P<0.05), and cirrhosis (OR=19.5; P<0.05) or surrogate labs. In all, 54.8% of late-onset HCC cases were cirrhotic and 29.5% of early-onset HCC cases were cirrhotic. HCC occurs in Asian immigrant HBV patients younger than currently recommended screening guidelines. A large majority of these early-onset patients did not have cirrhosis at the time of their HCC diagnosis; therefore, factors other than cirrhosis need to be considered when evaluating HCC risk in young patients. Factors associated with HCC development across all ages include cirrhosis and male gender, while family history and smoking history may identify younger Asian immigrant HBV patients at risk for HCC. Prospective validation, including cost-effectiveness evaluation, is necessary, but our results suggest that younger Asian HBV patients, especially those with a smoking history or family history of HCC, appear to have an increased risk for HCC and should be considered for enrollment in early screening programs regardless of their age.

Polymorphisms in XRCC1 and glutathione S-transferase genes and hepatitis B-related hepatocellular carcinoma.

Chronic infection with hepatitis B virus (HBV) causes DNA damage. An arginine (Arg)-to-glutamine (Gln) polymorphism at codon 399 in the XRCC1 gene is putatively associated with DNA damage. In a case-control study of 577 HBV surface antigen carriers with hepatocellular carcinoma (HCC) and 389 HBV carrier control subjects, we investigated the association between this polymorphism and the risk of HCC and assessed whether this association varied with glutathione S-transferase (GST) status; GSTs are involved in carcinogen metabolism. All statistical tests were two-sided. The XRCC1 Gln allele was associated with a dose-dependent increased risk of early-onset HCC (<50 years) but not with the risk of late-onset HCC (P(trend) =.01). The GSTT1-null genotype alone did not affect risk, but the GSTM1-null genotype was associated with a decreased risk for early-onset HCC. Various combinations of GSTM1 and GSTT1 genotypes differentially modified the association of XRCC1 with HCC (P(interaction) =.005); e.g., for individuals with the GSTT1-null/GSTM1-present genotype, the risk of HCC was greater for those with the Gln/Gln genotype (odds ratio = 8.07, 95% confidence interval = 1.67 to 38.93) than for those with the Arg/Arg genotype. Thus, GST status appears to affect the risk of HCC associated with this XRCC1 polymorphism.