慢性乙型肝炎干扰素治疗后长期随访中复发与相关因素的研究

目的 观察和分析慢性乙型病毒性肝炎(CHB)经重组α干扰素(rIFN-α)治疗取得完全应答后,在长期随访过程中的复发情况,及其影响复发的相关因素.方法 523例经肝穿刺活检证实的CHB患者,给予rIFN-α 1 b治疗,疗程6～25个月,治疗中每1～3个月检测肝功能、HBVDNA、乙肝病毒e抗原(HBeAg).治疗后随访至少12个月,随访时每3～6个月检查肝功能、HBVDNA、HBsAg及HBeAg.结果 523例患者经rIFN-α治疗后,近期应答302例(57.7%).近期应答者经随访39.2±21.5个月,持续应答183例(35.0%),复发119例(39.4%).患者年龄、治疗前HBeAg状态、以及随访时间是影响复发的相关因素:复发组平均年龄(34.27±8.69岁)显著高于持续应答组的平均年龄(25.28±8.65)岁(P＜0.001);HBeAg( )组复发率76/225例(33.8%)显著低于HBeAg(-)组43/77例(55.8%)(P＜0.001);按随访每12个月为一时间段,分1～12个月、13～24个月、25～36个月、37～48个月、49～60个月和≥61个月6个时间段,各时间段复发的发生率有显著性差异(P＜0.001),累计复发率亦有显著性差异(P＜0.001),但25个月以后的4个时间段累计复发率差异无显著性(P=0.670).患者性别、治疗前ALT水平和HBVDNA水平、肝组织炎症活动度(G)、肝纤维化程度(S)及治疗疗程与复发无明显相关性,但在HBeAg( )组中,复发组的平均基线HBV DNA水平6.98±1.14 Log拷贝/ml高于持续应答组6.21±1.04 Log拷贝/ml(P=0.017).结论 CHB患者经rIFN-α治疗后,患者年龄、治疗前HBeAg状态以及随访时间是影响其在随访过程中复发的相关因素.在HBeAg( )CHB中,治疗前HBV DNA水平亦是影响复发的相关因素.

Factors related to chronic hepatitis B relapse after interferon-alpha treatment: a follow-up study

OBJECTIVE: To investigate the related to relapse of chronic hepatitis B (CHB) after recombinant interferon-alpha (rIFN-alpha) treatment. METHODS: This investigation involved 523 pathologically confirmed CHB patients including 403 HBeAg-positive and 120 HBeAg-negative patients, who were treated with 5 MU rIFN-alpha subcutaneously thrice a week for 6-25 months. For each patient, serum alanine aminotransferase (ALT) was measured biochemically, serum HBV DNA level detected with quantitative fluorescent PCR, and HBeAg level with enzyme immuoassay every 1-3 months during therapy and every 3-6 months during the follow-up period. RESULTS: Early response to rIFN-alpha treatment was observed in 302 (57.7%) patients at the end of treatment, among whom 39.4% (119/302) suffered relapse during the follow-up for 39.2-/+21.5 months. Age, HBeAg status before treatment, and follow-up duration were the predictive factors for post-treatment relapse. The mean age of patients with CHB relapse was significantly higher than that of the sustained responders (P<0.001), and the relapse rates in HBeAg-negative group (55.8%, 43/77) were significantly higher than that in HBeAg-positive group (33.8%, 76/225) at the end of follow up (P<0.001). The relapse rate and accumulative relapse rates at each year during the follow-up (for 5 years as the longest) differed significantly (P<0.001, P=0.000), but the accumulative relapse rates differed little between the years after the initial 2 of the follow-up (P=0.670). The relapse was not related to the patient's gender, pretreatment serum ALT, HBV DNA, grade of liver inflammation, stage of liver fibrosis, or duration of treatment. In HBeAg-positive patients, however, the mean HBV DNA was significantly higher in relapse group than in sustained response group (P=0.017). CONCLUSION: Age, pretreatment HBeAg status, and follow-up duration are independent predictive factors for post-treatment CHB relapse. In HBeAg positive patients, pretreatment serum HBV DNA is also one of the risk factors for relapse.