Schiefke Ingolf, Klecker Chris, Maier Melanie, Oesen Ute, Etzrodt Gunnar, Tannapfel Andrea, Liebert Uwe G, Berr Frieder
Department of Medicine II, University of Leipzig, Leipzig, Austria.
Liver Int. 2004 Apr;24(2):98-104. doi: 10.1111/j.1478-3231.2004.0889.x.
BACKGROUND/AIMS: Hepatitis B e antigen-negative/hepatitis B virus (HBV) DNA-positive chronic hepatitis B (CHBe-) exhibits a high relapse rate on monotherapy with lamivudine or interferon-alpha (IFN-alpha). We investigated, whether sequential therapy with famciclovir or lamivudine followed by combination with IFN-alpha-2a improves durable virologic response in CHBe- characterized by mutation analysis of the HBV precore genome region.
Fourteen patients were treated with famciclovir (n=3) or lamivudine for 4 weeks to reduce the viral load, and subsequently with the combination of the nucleoside analogue and IFN-alpha-2a until 16 weeks beyond the loss of serum HBV-DNA.
Median duration of therapy was 29.0 weeks (range 20.6-48.3 weeks). Serum HBV-DNA was undetectable and alanine aminotransferase had normalized in all patients at the end of treatment. Seven (50%) patients maintained a sustained response 12 months after end of treatment. Only two of them had been infected by HBV with the G1896A mutation. Most patients (5/7) with the G1896A mutation relapsed within 4 months after therapy.
Sequential combination therapy can induce sustained virologic response in a subgroup of CHBe-, but most with the G1896A precore mutant HBV relapse. Trials of CHBe- should be based on characterization of HBV mutants.
背景/目的：乙肝e抗原阴性/乙肝病毒（HBV）DNA阳性的慢性乙型肝炎（CHBe-）患者接受拉米夫定或α干扰素（IFN-α）单药治疗时复发率较高。我们通过对HBV前核心基因组区域进行突变分析，研究了先用泛昔洛韦或拉米夫定序贯治疗，随后联合α-2a干扰素治疗是否能改善CHBe-患者的持久病毒学应答。
14例患者先用泛昔洛韦（n = 3）或拉米夫定治疗4周以降低病毒载量，随后使用核苷类似物与α-2a干扰素联合治疗，直至血清HBV-DNA消失后16周。
治疗的中位持续时间为29.0周（范围20.6 - 48.3周）。治疗结束时所有患者血清HBV-DNA均检测不到，丙氨酸转氨酶均恢复正常。7例（50%）患者在治疗结束后12个月维持持续应答。其中仅2例感染的HBV存在G1896A突变。大多数携带G1896A突变的患者（5/7）在治疗后4个月内复发。
序贯联合治疗可在部分CHBe-患者中诱导持续病毒学应答，但大多数携带G1896A前核心突变型HBV的患者会复发。CHBe-患者的试验应基于HBV突变体的特征。
