Preliminary study on the relationship between recurrence and quasispecies characteristics in P region of hepatitis B virus genome of chronic hepatitis B patients treated with lamivudine

Abstract

Purpose: To investigate the characteristics of quasispecies in the P region of hepatitis B viral (HBV) DNA of chronic hepatitis B (CHB) patients treated with lamivudine (LAM), and its effect on HBV relapse after drug withdrawal in CHB patients who met drug cessation criteria. Methods: A total of 43 patients with chronic HBV infection, who had undergone LAM therapy, were enrolled in this study. Treatment was discontinued for patients who met therapeutic criteria set by relevant Asian-Pacific regions. Polymerase chain reaction (PCR) was used to amplify the genome in P region of serum rcDNA before treatment, cccDNA during drug cessation period, and serum rcDNA at relapse. Quasispecies cloning and sequencing were performed to identify variable sites in HBV P region. Results: Mutations in P region of baseline serum rcDNA were detected in 30 CHB patients, with N/H238T (14/30), L/F/Q/R267H (12/30), V278T (12/30), D134E/I (11/30), and T222A (9/30) having highest rates. In hepatocellular cccDNA P region during drug withdrawal, most detectable mutations were L/F/Q/R267H (25/43), V278T (18/43), N/H238T (15/43), D134E/I (14/43), and T222A (11/43). During relapse, the highest detectable mutation rates in serum rcDNA P region were N/H238T (12/19), L/F/Q/R267H (10/19), T222A (10/19), and V278T (8/19). Conclusion: High mutation rates of T222A and N/H238T in P region of HBV DNA increase the risk of relapse in patients. As a result, patients are susceptible to relapse after drug withdrawal.