Leemans Wilhelmus F, Flink Hajo J, Janssen Harry L A, Niesters Hubert G M, Schalm Solko W, de Man Robert A
Department of Gastroenterology & Hepatology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands.
J Hepatol. 2006 Mar;44(3):507-11. doi: 10.1016/j.jhep.2005.12.004. Epub 2006 Jan 19.
BACKGROUND/AIMS: To determine the response to pegylated interferon-alpha treatment of HBeAg-positive hepatitis B patients with proven lamivudine resistance.
Sixteen HBeAg-positive HBV patients with YMDD mutations were treated with pegylated interferon. Median treatment duration was 52 weeks (range 20-53), with a 26-week follow-up.
Two of 16 (12.5%) patients seroconverted to HBeAg negative and achieved sustained virological (HBV-DNA levels below 10log 5 copies/ml) together with biochemical (normalization of serum ALT levels) responses. Compared with the strong signal in all other patients, only these two patients had a faint signal in the lamivudine resistance assay. For all patients, the median viral load decreased from 10log 9.4 to 7.9 copies/ml (P = 0.001) during treatment but rebounded to a median of 10log 8.7 copies/ml after treatment cessation. Similarly, elevated median ALT levels at baseline decreased with treatment but rebounded after the end of treatment.
In the largest cohort study to date, pegylated interferon-alpha therapy showed marginal efficacy in the presence of lamivudine resistance but such therapy may be beneficial in patients with only small amounts of mutant virus. In our opinion, an analysis of the patient subgroup harbouring an YMDD-mutation should be included in all future studies of pegylated interferon-alpha in chronic hepatitis B.
背景/目的：确定聚乙二醇化干扰素-α治疗已证实对拉米夫定耐药的HBeAg阳性乙型肝炎患者的疗效。
16例HBeAg阳性且存在YMDD突变的HBV患者接受聚乙二醇化干扰素治疗。中位治疗持续时间为52周（范围20 - 53周），随访26周。
16例患者中有2例（12.5%）发生HBeAg血清学转换，达到持续病毒学应答（HBV - DNA水平低于10log5拷贝/ml）以及生化应答（血清ALT水平恢复正常）。与所有其他患者的强信号相比，仅这2例患者在拉米夫定耐药检测中信号较弱。所有患者在治疗期间病毒载量中位数从10log9.4降至7.9拷贝/ml（P = 0.001），但在停药后反弹至中位数10log8.7拷贝/ml。同样，基线时升高的ALT水平中位数随治疗下降，但在治疗结束后反弹。
在迄今为止最大规模的队列研究中，聚乙二醇化干扰素-α治疗在存在拉米夫定耐药的情况下显示出有限的疗效，但这种治疗可能对仅携带少量突变病毒的患者有益。我们认为，在未来所有关于聚乙二醇化干扰素-α治疗慢性乙型肝炎的研究中，都应纳入对携带YMDD突变患者亚组的分析。
