Quantitative polymerase chain reaction assay for serum hepatitis B virus DNA as a predictive factor for post-treatment relapse after lamivudine induced hepatitis B e antigen loss or seroconversion

Abstract

Background and aims: Lamivudine induces favourable virological and biochemical responses but posttreatment relapses are frequent, even in patients with hepatitis B e antigen (HBeAg) loss or seroconversion. The aim of this study was to determine whether extended lamivudine therapy for up to 12 months after HBeAg loss/seroconversion could decrease the risk of post-treatment virological relapse. In addition, we monitored serum hepatitis B virus (HBV) DNA levels using a quantitative polymerase chain reaction (PCR) assay during extended lamivudine therapy and analysed predictive factors for post-treatment relapse. Patients and methods: A total of 49 patients who exhibited HBeAg loss/seroconversion during lamivudine therapy received extended lamivudine therapy for six months (group 1, n = 23) or 12 months (group 2, n = 26) after HBeAg loss/seroconversion. Serum HBV DNA levels were quantified by a PCR based assay at the time of HBeAg loss/seroconversion, and at cessation of therapy. Results: Post-treatment virological relapse rates at two years were 59% in group 1 and 50% in group 2. Age, time interval to HBeAg loss/seroconversion, and serum HBV DNA levels at the time of cessation of therapy were independent predictive factors for post-treatment relapse. The post-treatment relapse rate was 37% at two years in patients with serum HBV DNA levels of ,200 copies/ml but 73% in those with >10 3 copies/ml. Conclusions: Extended lamivudine therapy for up to 12 months did not decrease the rate of post-treatment virological relapse, and monitoring of serum HBV DNA by a quantitative PCR method was helpful in predicting post-treatment relapse.

Hepatitis B e Antigen Seroconversion: A Critical Event in Chronic Hepatitis B Virus Infection

“…Most of the information about HBeAg reversion after the cessation of NA treatment comes from follow-up studies of lamivudine therapy. In these studies, the cumulative HBeAg reversion rate at 2 years after treatment was approximately 50% in patients with HBeAg-positive CHB, most of whom were infected with genotype C HBV [48,[63][64][65]. In a study that evaluated HBeAg reversion in 108 patients who HBeAg seroconverted during a C24-week course of treatment with lamivudine or IFN, the 3-year cumulative reversion rate was 54% following lamivudine therapy and 32% following IFN [66].…”

Defining Virologic Relapse in Chronic Hepatitis B

“…Several studies have described the VR rate and factors affecting it [5][6][7][8][9][10][11][12][13][14]. However, different definitions of VR have been used in these studies, and as such, it is critically important to closely examine the definitions of VR in each study.…”

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

“…However, when consolidation treatment [2,4,5,8] was performed before termination of lamivudine treatment or when patients were young [4][5][6][7][8], the rate of virologic relapse was dramatically reduced. In 178 patients with HBeAg-positive chronic HBV infection that showed HBV DNA loss as well as HBeAg loss with lamivudine treatment, virologic relapse rates of 15.9% and 30.2% 1 and 5 years after stopping treatment, respectively were seen.…”

“…Patients 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…”