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

Abstract

Objective: The aim of this study was to evaluate retrospectively the long-term effects of lamivudine in 461 Korean patients with chronic hepatitis B who were treated for more than 12 months. Methods: The annual rates of virological response and breakthrough were examined and the predictive factors for post-treatment relapse in 114 patients who achieved hepatitis B e antigen (HBeAg) loss or seroconversion after lamivudine therapy were also analyzed. Results: During follow-up, the rates of HBeAg seroconversion after 1, 2, 3, 4 and 5 years of treatment were 22.9, 33.2, 47.6, 54.2 and 58.8%, respectively, while those for virological breakthrough at 1, 2, 3 and 4 years were 8.2, 41.7, 55.7 and 64.8%, respectively. Ninety-five patients (20.6%) had HBeAg seroconversion and 19 (4.1%) showed HBeAg loss alone with disappearance of hepatitis B virus DNA in serum. Seroconversion was higher with prolonged treatment in patients who had elevated serum alanine aminotransferase. The cumulative relapse rates in the seroconversion group were 52.0 and 55.7% 1 and 2 years after treatment, respectively. Age and the duration of additional treatment were significant predictive factors for post-treatment relapse. Patients aged ≤40 who had additional treatment for >12 months after seroconversion had the lowest relapse rate (p < 0.001). Conclusions: These results suggest that additional treatment for over 12 months after HBeAg seroconversion in younger patients may produce a better long-term outcome.

HBeAg seroconversion as an important end point in the treatment of chronic hepatitis B

“…In a study that examined determinants for sustained HBeAg responses to lamivudine therapy involving 82 HBeAg-positive CHB patients, an additional 8 months of lamivudine treatment (OR = 1.097; 95% CI = 1.028-1.171; P = 0.005), in addition to genotype B HBV (versus genotype C) and younger age, was an independent factor associated with sustained HBeAg response [66]. Similar findings were reported in a retrospective study that assessed factors predictive of posttreatment relapse after 12 months of lamivudine therapy in 461 Korean patients with CHB, mostly genotype C [67]. In this study, additional treatment for more than 12 months after HBeAg seroconversion was associated with a significantly lower relapse rate in patients 40 years and older (P \ 0.001).…”

“…The importance of a 6-to 12-month period of consolidation therapy to reduce the risk of relapse after HBeAg seroconversion has been demonstrated in patients with HBeAg-positive CHB [66,67]. In a study that examined determinants for sustained HBeAg responses to lamivudine therapy involving 82 HBeAg-positive CHB patients, an additional 8 months of lamivudine treatment (OR = 1.097; 95% CI = 1.028-1.171; P = 0.005), in addition to genotype B HBV (versus genotype C) and younger age, was an independent factor associated with sustained HBeAg response [66].…”

Efficacy and Safety of Tenofovir Disoproxil Furmarate for Patients with Lamivudine-Resistant Hepatitis B Virus Infection

“…However, the long-term treatment of LAM is associated with a high risk of drug resistance of HBV. LAM [4,5,21] . A combination treatment of LAM and ADV was recommended for the rescue therapy to prevent the development of ADV resistance during the second-line ADV monotherapy in patient with LAM-resistant HBV infection [10,22] .…”

Recent data on treatment of chronic hepatitis B with nucleos(t)ide analogues

“…Viral suppression is associated with serum ALT normalization and histological improvement. Relapse of disease occurred in up to 50% of responders within 5 years of stopping therapy [14][15][16].…”

“…Age and the duration of additional treatment were significant predictive factors for post-treatment relapse. Patients aged B40 who had additional treatment for [12 months after seroconversion had the lowest relapse rate (P \ 0.001) [15]. On the other hand, level of HBV corerelated antigen predicts relapse after cessation of lamivudine therapy [32].…”