Effect of virological response on post‐treatment durability of lamivudine‐induced HBeAg seroconversion

Abstract

Lamivudine‐induced HBeAg seroconversion may not be durable in Korean patients with hepatitis B virus (HBV) infection. It is unknown whether virological response during lamivudine treatment affects the post‐treatment outcome. We retrospectively analysed 124 consecutive HBeAg‐positive chronic hepatitis B (CHB) patients treated with lamivudine. Lamivudine was given at a dose of 100 mg per day. HBV DNA levels in sera obtained before and during therapy were measured by the Digene Hybrid Capture II assay and Digene Ultrasensitive Hybrid Capture II assay, respectively. HBeAg seroconversion was achieved in 42 of the 124 patients (33.8%) treated with lamivudine. Mean duration of treatment in HBeAg seroconverters was 12.86 ± 4.44 months. During the follow‐up period, the cumulative relapse rates at 3 months and 6 months post‐treatment in 42 patients with HBeAg seroconversion were 40.5% and 57.4%, respectively. Among 31 seroconverted patients whose sera were available at the second month of treatment, HBV DNA remained at > 4.7 × 103 genomes/mL in 15 patients and decreased to < 4.7 × 103 genomes/mL in the remaining 16 patients. HBV DNA levels at the second month of treatment was not related with relapse after discontinuation of treatment (66.7% vs. 43.8%, P= 0.2). At the time of HBeAg seroconversion, HBV DNA remained at > 4.7 × 103 genomes/mL in five patients and decreased to < 4.7 × 103 genomes/mL in the remaining 37 patients. Relapse rates were increased in patients who remained at > 4.7 × 103 genomes/mL compared with patients with HBV DNA levels < 4.7 × 103 genomes/mL (100% vs. 51.4%, P < 0.001). Thus, monitoring of serum HBV DNA at the time of HBeAg seroconversion may be helpful for predicting relapse in patients with lamivudine‐induced HBeAg seroconversion.

Determinants for sustained HBeAg response to lamivudine therapy

“…The high prevalence of genotype C HBV infection may be responsible for the high relapse rate in Korean studies. 7,8 Together with the observation that patients with genotype C HBV infection had higher hepatitis activities 27 and that patients with genotype B HBV infection had earlier spontaneous HBeAg seroconversion 27,29 or better response to interferon therapy, 16,30 our findings suggest that patients with genotype B HBV infection have more favorable clinical course and therapeutic outcome than those with genotype C HBV infection. The Korean study by Song et al 7 involving 34 patients followed up for 2 to 24 (median, 13 months) months showed that high pretreatment serum HBV DNA and short additional lamivudine therapy after HBeAg seroconversion were 2 independent predictive factors for posttreatment relapse.…”

“…6 However, it was not durable in Oriental countries such as Korea (62% [20/32] at 1 year; 50% [16/32] at 2 years) and Taiwan (69% at 24 weeks, 55% at 48 weeks, and 44% at 72 weeks). [7][8][9] The discrepancy between Oriental and Western patients is unknown. However, additional lamivudine treatment after HBeAg seroconversion, 7 serum HBV DNA at the time of HBeAg seroconversion, 8 and age 9 have been reported to be factors for durability.…”

“…[7][8][9] The discrepancy between Oriental and Western patients is unknown. However, additional lamivudine treatment after HBeAg seroconversion, 7 serum HBV DNA at the time of HBeAg seroconversion, 8 and age 9 have been reported to be factors for durability. Obviously, these inconsistent results need further studies to clarify the discrepancy.…”

Sustained response to peginterferon alfa-2a (40 kD) with or without lamivudine in Asian patients with HBeAg-positive and HBeAg-negative chronic hepatitis B

“…This is in contrast to CHB patients treated with lamivudine, where a higher sustained response has been previously noted in patients infected with genotype B (61%) than genotype C (25%, P = 0.009) [35]. This has particular importance for treating Asian patients, since genotype C was reported to have a high prevalence in studies of Korean patients and was associated with a lack of durability of HBeAg seroconversion [36,37]. Such lack of differentiation between genotypes in response to treatment in our study may be due to the more prolonged period of therapy with peginterferon alfa-2a and its superior efficacy, which has already been noted in comparison to conventional interferon in Asian patients [6].…”

Long-Term Results of Lamivudine Monotherapy in Korean Patients with HBeAg-Positive Chronic Hepatitis B: Response and Relapse Rates, and Factors Related to Durability of HBeAg Seroconversion

“…Although the endpoint of antiviral therapy in chronic hepatitis B is HBeAg seroconversion as well as HBV DNA negativity, previous reports have shown that the durability of lamivudine-induced HBeAg seroconversion may not persist [9,10,12] . Thus, despite the clinical benefi ts of lamivudine therapy, it is uncertain as to whether maximal antiviral potency has been achieved with lamivudine.…”