Oral Antiviral Therapy for Chronic Hepatitis B Virus Infection: Is Continuous Treatment Needed?

Abstract

AbbreviationsNA: Nucleos(T)Ide Analogue; HBV: Hepatitis B Virus; cccDNA: covalently closed circular DNA IntroductionLong-term usage of oral antiviral is highly effective in treating chronic hepatitis B virus (HBV) infection and can effectively suppress HBV proliferation which may prevent the progression of liver fibrosis and the development of HCC after long term use of NAs but cannot completely eradicate the virus. Furthermore, the safety of long-term usage of antivirals is still a concern that needs to be assessed and the increasing cost of antiviral treatments can be a serious financial burden. It is still unclear how long antiviral treatment needs to be continued and how to determine when discontinuation of the treatment is appropriate. The presence of covalently closed circular DNA (cccDNA) in hepatocytes correlates to immune activity and is used as a predictive factor to evaluate sustained viral suppression after termination of antiviral treatment [1]. Unlike pegylated interferon, oral antivirals do not have direct immunomodulatory effects and only temporarily induce a modest increase in immune function. Therefore, oral antiviral treatments are unlikely to provide continued viral suppression after termination. Discussion HBeAg-positive chronic HBV infectionPatients that reach sustained viral suppression (HBV DNA negativity and HBeAg loss or seroconversion) with lamivudine usage show a virologic relapse rate of 15.9-48%, 29-50%, 54-55.7%, and 44-64.8% 1, 2, 3, and 4 years after discontinuation of lamivudine respectively [2][3][4][5][6][7][8]. A considerable number of patients that undergo HBeAg seroconversion upon oral antiviral AbstractPotent nucleos(t)ide analogues (NAs) have improved patient prognosis via suppression of viral load, HBeAg seroconversion and in some cases, HBsAg seroconversion. However, the duration and end point of NA treatment are still debatable. Current international guidelines recommend that discontinuation of NA treatment can be considered when HBeAg seroconversion and undetectable HBV DNA status is maintained for at least 6-12 months for HBeAg-positive patients and undetectable HBV DNA status on 3 separate occasions 6 months apart for HBeAgnegative patients if they have been treated for at least 2 years. Durability of NA, particularly after off-treatment, remains uncertain. A proportion of patients who discontinue NA therapy after HBeAg seroconversion may require retreatment if sustained serological and/or virological response fails and high off-treatment virological relapse can develop in HBeAg-negative patients. Therefore, NA treatment may be continued until HBsAg clearance with or without antibodies to HBsAg, particularly in patients with severe fibrosis or cirrhosis.