Department of Gastroenterology and Hepatology, Erasmus MC, University Medical Center Rotterdam’s Gravendijkwal 230, Rm Ha 204, 3015 CE Rotterdam, The Netherlands.
Clin Infect Dis. 2013 Jan;56(1):100-5. doi: 10.1093/cid/cis859. Epub 2012 Oct 5.
Alanine aminotransferase (ALT) flares occur frequently during peginterferon (PEG-IFN) therapy. We related occurrence of flares to presence of precore (PC) and/or basal core promoter (BCP) mutants and studied kinetics of hepatitis B e antigen (HBeAg) and hepatitis B surface antigen (HBsAg) levels during flares.
Fifty of 214 (23%) patients treated with PEG-IFN ± lamivudine for 52 weeks experienced flares. Flares were host-induced (ALT elevation followed by HBV DNA decline, n = 19), virus-induced (HBV DNA increase with subsequent ALT elevation, n = 17) or indeterminate (n = 14). Presence of wild-type (WT) or non-WT (detectable PC/BCP mutants) was studied by lineprobe assay.
Fifty-eight percent of host-induced flares occurred in WT HBV patients, whereas 94% of virus-induced flares occurred in patients with PC and/or BCP mutants (P = .003). HBsAg loss was only achieved in patients with a host-induced flare, and WT patients with a host-induced flare cleared HBsAg in 64% of cases. Serum HBsAg levels declined after a host-induced flare, whereas virus-induced flares were accompanied by stable or increasing levels of HBsAg. Patients with a host-induced flare achieved a mean HBsAg reduction of 3.24 log IU/mL, compared with 0.25 log IU/mL in virus-induced flares (P < .001). Patients who achieved a decline in HBsAg of >0.5 log IU/mL within 4 weeks after the flare cleared HBsAg in 64% (7 of 11) of cases.
Host-induced flares are associated with WT virus and may result in decline and clearance of HBV DNA, HBeAg, and HBsAg. Monitoring of HBsAg levels during and after flares may help predict a favorable treatment outcome.
聚乙二醇干扰素（PEG-IFN）治疗期间常发生丙氨酸氨基转移酶（ALT） flares。我们将 flares 的发生与前核心（PC）和/或基本核心启动子（BCP）突变体的存在相关联，并研究了 flares 期间乙型肝炎 e 抗原（HBeAg）和乙型肝炎表面抗原（HBsAg）水平的动力学。
在接受 PEG-IFN ±拉米夫定治疗 52 周的 214 名患者中，有 50 名（23%）经历了 flares。Flare 分为宿主诱导型（ALT 升高后 HBV DNA 下降，n = 19）、病毒诱导型（HBV DNA 增加后 ALT 升高，n = 17）或不确定型（n = 14）。通过线探针分析研究了野生型（WT）或非 WT（可检测到 PC/BCP 突变体）的存在。
58%的宿主诱导型 flares 发生在 WT HBV 患者中，而 94%的病毒诱导型 flares 发生在 PC 和/或 BCP 突变体患者中（P =.003）。只有在发生宿主诱导型 flare 的患者中才能实现 HBsAg 丢失，而在发生宿主诱导型 flare 的 WT 患者中，有 64%的患者清除了 HBsAg。在发生宿主诱导型 flare 后，血清 HBsAg 水平下降，而病毒诱导型 flares 则伴有 HBsAg 水平稳定或升高。发生宿主诱导型 flare 的患者 HBsAg 平均降低 3.24 log IU/mL，而病毒诱导型 flares 为 0.25 log IU/mL（P <.001）。在 flare 后 4 周内 HBsAg 下降 >0.5 log IU/mL 的患者中，有 64%（7/11）清除了 HBsAg。
宿主诱导型 flares 与 WT 病毒相关，可能导致 HBV DNA、HBeAg 和 HBsAg 的下降和清除。在 flares 期间和之后监测 HBsAg 水平可能有助于预测有利的治疗结果。
