Brianna Shinn, Charles Kistler, Christopher Roth and Hie Won Hann*
Since 1998 with the highly effective nucleos(t)ide analogues for Hepatitis B virus (HBV), we have witnessed successful viral suppression that has led to the delay or prevention of the development of hepatocellular carcinoma (HCC). Reduced incidence of HCC with anti-HBV treatment has been documented with lamivudine, entecavir and tenofovir. A number of investigators have observed that after the initial tumor was ablated, anti-HBV treatment could prevent or reduce the recurrent or subsequent new HCC. Nonetheless, as reported earlier, we are observing the persistent risk for HCC in patients in spite of successful viral suppression for over a decade with anti-HBV therapy. In this report, we present three cases who underwent initial tumor ablation and maintained negative HBV DNA with anti-HBV therapy and yet developed subsequent new or recurrent HCC at the intervals of 5,10,11 and 15 years. These persistent risks for new and recurrent HCC are attributed to the incomplete control of HBV due to the presence of cccDNA in the host’s hepatocytes. Current antiviral treatment can achieve a functional cure (suppression of HBV replication) while a complete cure of eliminating the cccDNA has not been possible. Therefore, even though HBV is not actively replicating, cccDNA remains in the nucleus of the hepatocytes and continues hepatocarcinogenic processes including HBV and host DNA integration. There is a need for HBV cure drugs.
