The relative risk started to increase at an entry HBV-DNA level of 2000 IU/mL (HR: 2.3; 95% CI: 1.1–4.9; P = 0.02). Those with HBV-DNA levels of 200 000 IU/mL or more had the greatest risk (HR: 6.1; 95% CI: 2.9–12.1; P < 0.001). Of particular note, the dose–response selleck relationship was most prominent for participants who were seronegative for HBeAg, with normal serum ALT levels, and no cirrhosis at study entry.[6, 49] Similarly, another prospective cohort study in adult HBV carriers
with 11 years of follow-up from Haimen City in China also showed that the relative risk for HCC mortality in carriers with low viral load (< 20 000 IU/mL) was 1.7 (95% CI: 0.5–5.7) and 11.2 (95% CI: 3.6–35.0) in those with high viral load (≥ 20 000 IU/mL) compared with the HBV carriers with undetectable viremia. In our recent study on 390 CHB patients with spontaneous HBeAg seroconversion, those with HBV-DNA levels > 2000 IU/mL at 1 year post HBeAg seroconversion had higher HR of HBeAg-negative chronic hepatitis, a precursor of cirrhosis and HCC, than patients Selleck Ku 0059436 with HBV-DNA
levels < 200 IU/mL (HR: 2.4; 95% CI: 1.3–4.4; P = 0.004). More importantly, the risk increased in a dose–response relationship. Ample evidence from all these studies indicates that hepatitis B viral load is what induces hepatitis activity and is the strongest factor associated with HCC development in patients with chronic HBV infection. Although a lower viral load is associated with favorable clinical outcomes such as inactive carrier state, our previous case–control study, including 183 HBV-related HCC patients and 202 HBV carriers, showed that young (≤ 40 years old) HCC patients had lower serum HBV-DNA level than old HCC patients (log10 copies/mL:
4.2 vs 4.8, P = 0.056). In addition, high serum HBV-DNA level was associated with the development of HCC in old patients (OR: 1.584; 95% CI: 1.075–2.333; P = 0.02), rather than in young patients (OR: Cyclic nucleotide phosphodiesterase 0.848; 95% CI: 0.645–1.116; P = 0.239). Thus, the host–virus interactions in association with the development of HCC in younger and older patients may be different, and this aspect needs further investigation. In addition to known hepatitis B viral factors associated with disease progression, the clinical significance of qHBsAg has become increasingly recognized. It is known for a long time that HBsAg is the hallmark of HBV infection and is qualitatively used for the diagnosis of HBV infection in clinical practice. However, this old biomarker has a new role in current management of chronic HBV infection. Serum HBsAg can be produced by three pathways: (i) the translation of transcriptionally active cccDNA molecules to form the envelope of HBV virion; (ii) subviral sepherical or filamentous form of noninfectious particles; and (iii) small HBsAg and truncated pre-S protein can also be generated from HBV-DNA integrated to host genome.