Second, the potential interactive Tanespimycin mw effects of known hepatitis B viral factors on the development of HCC are not incorporated into this model. In a prospective study, Yu et al. provide strong evidence that male patients with both HBV genotype C and very high HBV viral loads had a 26-fold higher risk of HCC than those with other genotypes and low or undetectable viral loads.[72] Our case–control studies also revealed

that BCP A1762T/G1764A mutation combined with high viral load was independently associated with the risk of HCC, irrespective of the presence of cirrhosis.[22, 23] In addition, combination of mutations of pre-S, precore, and BCP regions, rather than single mutation, was significantly associated with the development of progressive liver diseases and HCC.[33, 37, 73] Furthermore, the relationships between HCC risk and dynamic changes of serum HBV-DNA, HBsAg, and ALT levels were determined in the ERADICATE-B study. Compared with patients with persistently low levels of HBV-DNA, HBsAg, or ALT, those with persistently high levels of these three factors were at a higher risk of HCC.[64] Therefore, it is essential to incorporate qualitative and

quantitative hepatitis B viral factors in risk calculation model to make it more comprehensive and to be clinically NU7441 research buy useful in various forms of chronic liver disease, including inactive carrier state, chronic hepatitis, and cirrhosis (Fig. 3). Over the past decade, extensive research on HBV has identified several hepatitis B viral factors

such as serum HBsAg level, viral load, genotype, and mutants as powerful contributors to disease progression of CHB patients. According to several population and hospital-based cohort studies, risk stratification for HCC in patients with chronic HBV infection has been established in a preliminary manner. Low risk factors for HBV-related HCC include female gender, younger age (≦ 50 years old), HBV genotype A/B, and low serum levels of ALT, HBV-DNA, and HBsAg. In contrast, high risk factors for HBV-related HCC include male gender, advanced age (> 50 years mafosfamide old), HBV genotype C/D, BCP A1762T/G1764A mutations, pre-S deletion mutations, and high serum levels of ALT, HBV-DNA, and HBsAg. Among them, the modifiable risk factors are serum levels of ALT, HBV-DNA, and HBsAg. In the future, multivariate risk assessment profiles for HCC should be integrated with current HBV treatment guidelines to enable practicing physicians to have better management of HBV carriers with different HCC risks. Finally, risk modification through antiviral therapy may lead to the prevention of disease progression and eventually reduce the risk of HCC development even among those who start treatment with substantial risk (Fig. 4).