Given the relationships of BCP double mutation with liver disease progression and HBeAg-negative infection (Kim, 2014), the possibility that C2(3) or C2(2) vs. C2(1) may cause more advanced liver diseases, including HCC in HBeAg-negative chronic HBV patients, cannot be excluded (Zhang et al., 2010; Alexopoulou and Karayiannis, 2014). Here, OPN1SW is linked to liver disorder.