Dose‐response association between hepatitis B surface antigen levels and liver cancer risk in Chinese men and women

Abstract

We aimed at evaluating the risk of liver cancer in different levels of HBsAg among Chinese men and women. We carried out a nested case-control study including 363 cases and 3,511 controls in two population-based cohorts in Shanghai. Plasma samples collected at enrollment were quantified for HBsAg levels using the Architect QT assay. Conditional logistic regression was performed to estimate the odds ratios (ORs) and 95% confidence intervals (95%CIs) for liver cancer, with adjustment for potential confounders. HBsAg was detected in 6.29% of control subjects overall (7.02% in men and 4.98% in women). HBsAg levels were positively associated with liver cancer risk in a dose-response manner (Ptrend<0.001). Such association showed a significant gender disparity. With increasing levels of HBsAg, liver cancer risks rose more steeply in men than in women. In men, the adjusted ORs increased from 7.27 (95%CI: 3.49–15.15) at the lowest detectable level of HBsAg (5–9 IU/ml) to 7.16 (95%CI: 3.21–15.96), 34.30 (95%CI: 16.94–69.44), and 47.33 (95%CI: 23.50–95.34) at the highest level of HBsAg (≥1,000 IU/ml) compared to those negative for HBsAg. The corresponding ORs were much lower for women, from 1.37 (95%CI: 0.25–7.47) to 3.81 (95%CI: 1.09–13.28), 7.36 (95%CI: 2.41–22.46), and 16.86 (95%CI: 7.24–39.27), respectively. HBsAg quantification has potential to distinguish individuals at different risks of liver cancer. Men with the lowest detectable level of HBsAg should still pay attention to their liver cancer risks, but those with a higher level may be given a higher priority in future liver cancer surveillance program.

HIV-hepatitis B virus coinfection

“…HBsAg is produced in large quantities in HBV infection and is generally considered to inhibit adaptive immunity and effective production of anti-HBV surface antibodies (HBsAb), which is required for long term HBV control [106] . Persistent high levels of HBsAg have been associated with elevated risk of HCC in untreated HBV mono-infection [107, 108] . Following antiviral treatment of HBV mono-infection, HBsAg loss is uncommon, and after 12 months treatment with NRTI or pegylated interferon (IFN), HBsAg loss occurs in of 0–3% and 3–7% of individuals respectively [109] .…”

Current but not past hepatitis B virus infection is associated with a decreased risk of nonalcoholic fatty liver disease in the Chinese population: A case‐control study with propensity score analysis

“…Increased serum HBsAg levels have been associated with increased risks of liver cancer 39 as well as recurrence of and death from HCC. 40 In the present study, we found that the magnitude of the association appeared to be comparable across HBsAg level categories, indicating that the protective effect of current HBV infection on NAFLD risk is not affected by serum HBsAg levels.…”

Pre‐diagnostic urinary 15‐F2t‐isoprostane level and liver cancer risk: Results from the Shanghai Women's and Men's Health Studies

“…Second, potential confounders such as intake of aflatoxin B1, hepatitis C virus infection and acceptance of antiviral therapy were not considered in our study, which may bias the association between 15‐F 2t ‐IsoP level and liver cancer risk. However, exposure rates for these two factors are low in our study participants …”

“…However, exposure rates for these two factors are low in our study participants. 22,23,26 In summary, we found a strong positive association between pre-diagnostic urinary level of 15-F 2t -IsoP and risk of liver cancer in the population-based cohorts of residents in urban Shanghai, indicating that higher level of oxidative stress may lead to higher liver cancer risk. With 15-F 2t -IsoP level increasing, liver cancer risk rises more steeply in men than in women, for both with and without HBV infection.…”

“…The laboratory personnel were blinded as to the disease or control status of study subjects. The design has been previously described in detail …”