Published online Jan 27, 2019. doi: 10.4254/wjh.v11.i1.65
Peer-review started: September 27, 2018
First decision: October 16, 2018
Revised: November 14, 2018
Accepted: December 31, 2018
Article in press: January 1, 2019
Published online: January 27, 2019
Processing time: 122 Days and 9.4 Hours
Hepatitis B virus (HBV) is one of the most significant hepatocarcinogens. The ultimate goal of anti-HBV treatment is to prevent the development of hepatocellular carcinoma (HCC). During the last two decades, with the use of currently available anti-HBV therapies (lamivudine, entecavir and tenofovir disoproxil fumatate), there has been a decrease in the incidence of HBV-associated HCC (HBV-HCC). Furthermore, several studies have demonstrated a reduction in recurrent or new HCC development after initial HCC tumor ablation. However, during an observation period spanning 10 to 20 years, several case reports have demonstrated the development of new, subsequent new and recurrent HCC even in patients with undetectable serum HBV DNA. The persistent risk for HCC is attributed to the presence of covalently closed circular DNA (cccDNA) in the hepatocyte nucleus which continues to work as a template for HBV replication. While a functional cure (loss of hepatitis B surface antigen and undetectable viral DNA) can be attained with nucleos(t)ide analogues, these therapies do not eliminate cccDNA. Of utmost importance is successful eradication of the transcriptionally active HBV cccDNA from hepatocyte nuclei which would be considered a complete cure. The unpredictable nature of HCC development in patients with chronic HBV infection shows the need for a complete cure. Continued support and encouragement for research efforts aimed at developing curative therapies is imperative. The aims of this minireview are to highlight these observations and emphasize the need for a cure for HBV.
Core tip: Despite the advances in the management of hepatitis B virus (HBV) infection and HBV-associated hepatocellular carcinoma (HCC), the risk for new, subsequent new and recurrent HCC persists even after over a decade of antiviral therapy and initial tumor ablation. This is due to the inability of the current antiviral therapy to eliminate the covalently closed circular DNA from the hepatocyte nucleus. There is a great need for an HBV cure drug.