Baseline HBV DNA level is the most important factor associated with virologic breakthrough in chronic hepatitis B treated with lamivudine

Abstract

INTRODUCTIONA high incidence of virologic breakthrough (VBT) that results from viral resistance is a major disadvantage of lamivudine (LAM) treatment for patients with chronic hepatitis B (CHB). Data from a study of 592 patients who had undergone four years of LAM treatment indicated that resistance increased from 23% in year 1 to 71% in year 4 [1,2] . The clinical consequences of viral resistance can be severe, but early studies suggest that median HBV DNA and ALT levels continue to improve even as resistance develops [3] . LAM is known to have long-term therapeutic effects, with well-known resistance and side effects. LAM therapy for CHB patients with advanced fibrosis significantly reduced the incidence of hepatic decompensation and hepatocellular carcinoma (HCC) [4] . In addition, it is becoming increasingly clear that CHB management requires a long-term therapy, thus making the cost of treatment an important consideration. The need for long-term therapy and the consequent financial burden become significant in the economically disadvantaged regions of the world which also happen to be the hyperendemic areas for HBV. Furthermore, this cost issue presents a serious economic burden for CHB patients who immigrated to the US from the hyper-endemic regions. One study suggested that upfront LAM therapy may be highly cost-effective, assuming that patients who develop resistance begin a regimen of adefovir instead of continuing LAM treatment [5] . Our study sought to identify the factors associated with VBT in patients on LAM therapy and attempted to select a subgroup of patients who may respond well to LAM without developing VBT. MATERIALS AND METHODS PatientsWe reviewed the medical records of 208 CHB patients who were treated at the Liver Disease Prevention Center, Abstract AIM: To identify the factors associated with virologic breakthrough and to select a subgroup of patients who respond well to lamivudine without developing virologic breakthrough (VBT). METHODS:Of 79 patients who had received lamivudine therapy for 9-57 mo, 34 were HBeAg-positive and 45 were HBeAg-negative, 24 developed virologic breakthrough and 55 did not. Clinical and virologic factors were compared between the two groups. RESULTS:The median duration of therapy was 25 (9-57) mo. Virologic breakthrough was defined as a > 1 log HBV DNA increase following initial suppression. When several factors, including gender, duration of infection, baseline HBV DNA, and baseline ALT in HBeAg-positive chronic hepatitis patients were analyzed by logistic regression, the most important predictor of virologic breakthrough was the baseline HBV DNA (r 2 = 0.12, P < 0.05). When HBeAg-postitive chronic hepatitis patients were divided into two groups by a point of 6.6 log HBV DNA, the incidence of virologic breakthough between two groups was significantly different. CONCLUSION:Lamivudine may remain an effective first line therapy for those HBeAg-positive patients with a baseline HBV DNA < 6.6 log10 copies/mL.

Pretreatment and on-treatment predictors of viral breakthrough in lamivudine therapy for chronic hepatitis B

“…Duration of LAM therapy, HBeAg positivity at 1 year, and HBV DNA nonresponder at 6 months had high prediction of development for VBT with logistic regression analysis. Baseline HBV DNA level is significant predictor in other study [7]. But in comparison to on-treatment predictors, baseline HBV DNA is not significant in our study.…”

“…It is very important for Asian poor patients who cannot afford such treatment. Note: VBT, viral breakthrough was defined as[1 log 10 copies increase in HBV DNA from nadir after an initial virologic response or HBV DNA could be detected again after the previous report of under the detection limit [7] a P values were determined by student's t test and chi-square test…”

“…VBT was defined as [1 log 10 copies increase in HBV DNA from nadir after an initial virologic response or HBV DNA could be detected again after the previous report of under the detection limit [7].…”

“…Emergence of antiviral resistance may lead to viral and biochemical breakthrough and sometimes hepatitis flare-up and rapid decompensation [5,6]. A high incidence of viral breakthrough (VBT) that results from viral resistance is a major disadvantage of prolonged LAM therapy for CHB [7]. Selective amplification of resistant mutants is the main concern of long-term LAM therapy [8,9].…”

A review of the one-year incidence of resistance to lamivudine in the treatment of chronic hepatitis B

“…This is supported by a retrospective analysis of the emergence of virologic resistance among 79 patients treated with lamivudine for a median of 26 months [43]. In this study, Kaplan-Meier analysis of virologic response was performed for a subset of patients with HBeAg-positive CHB to determine the probability of developing virologic breakthrough according to baseline HBV DNA [43].…”