Center for Database Research, E-Da Hospital, Kaohsiung City, Taiwan; Division of Gastroenterology, E-Da Hospital, Kaohsiung City, Taiwan; School of Medicine for International Students, I-Shou University, Kaohsiung City, Taiwan; Graduate Institute of Clinical Medicine, China Medical University, Taichung City, Taiwan.
Superintendent Office, Tainan Municipal Hospital, Tainan City, Taiwan.
Clin Gastroenterol Hepatol. 2016 Oct;14(10):1490-1498.e3. doi: 10.1016/j.cgh.2016.03.024. Epub 2016 Mar 24.
BACKGROUND & AIMS: This study investigated whether serum level of hepatitis B surface antigen (HBsAg) at the end of entecavir treatment was associated with risk of relapse.
We performed a prospective multicenter study of 161 consecutive patients with chronic hepatitis B in whom the hepatitis B virus was no longer detected after 3 years or more of entecavir therapy. Treatment ended between July 1, 2011 and July 1, 2015. Patients were monitored for clinical relapse (hepatitis B virus DNA >2000 IU/mL and level of alanine aminotransferase more than 2-fold the upper limit of normal) and virologic relapse (hepatitis B virus DNA >2000 IU/mL). Outcomes were calculated using the Kaplan-Meier method and risk factors were identified by Cox proportional hazards modeling.
Two years after therapy ended, 49.2% of patients in the entire cohort had a clinical relapse (95% confidence interval [CI], 40.9%-58.1%) and 81.7% had a virologic relapse (95% CI, 74.3%-88.0%). Among patients who were hepatitis B e antigen-negative at the end of therapy, 39.2% had a clinical relapse (95% CI, 30.3%-49.6%) and 77.4% had a virologic relapse (95% CI, 68.6%-85.2%). Serum level of HBsAg was associated with relapse in the hepatitis B e antigen-negative patients (Ptrend = .006 for clinical relapse; Ptrend = .0001 for virologic relapse). In multivariate Cox regression analysis, the hazard ratio (per log IU/mL increment) for clinical relapse was 2.47 (95% CI, 1.45-4.23) and for virologic relapse was 1.80 (95% CI, 1.33-2.45). The 11 (9%) patients with levels of HBsAg <10 IU/mL did not relapse.
Serum level of HBsAg is associated with risk of relapse in patients who are hepatitis B e antigen-negative after treatment with entecavir. A low titer of HBsAg might be used to identify patients at low risk for relapse after treatment.
本研究旨在探讨恩替卡韦治疗结束时血清乙型肝炎表面抗原（HBsAg）水平与复发风险的关系。
我们进行了一项前瞻性多中心研究，纳入了 161 例慢性乙型肝炎患者，这些患者在接受恩替卡韦治疗 3 年或更长时间后乙型肝炎病毒已不再被检测到。治疗于 2011 年 7 月 1 日至 2015 年 7 月 1 日结束。对患者进行临床复发（乙型肝炎病毒 DNA >2000 IU/mL，丙氨酸氨基转移酶水平超过正常值上限 2 倍以上）和病毒学复发（乙型肝炎病毒 DNA >2000 IU/mL）的监测。采用 Kaplan-Meier 法计算结局，采用 Cox 比例风险模型确定危险因素。
治疗结束后 2 年，整个队列中 49.2%（95%置信区间[CI]，40.9%-58.1%）的患者出现临床复发，81.7%（95%CI，74.3%-88.0%）的患者出现病毒学复发。在治疗结束时乙型肝炎 e 抗原阴性的患者中，39.2%（95%CI，30.3%-49.6%）出现临床复发，77.4%（95%CI，68.6%-85.2%）出现病毒学复发。血清 HBsAg 水平与乙型肝炎 e 抗原阴性患者的复发相关（临床复发 Ptrend =.006；病毒学复发Ptrend =.0001）。多变量 Cox 回归分析显示，临床复发的风险比（每 log IU/mL 增加）为 2.47（95%CI，1.45-4.23），病毒学复发的风险比为 1.80（95%CI，1.33-2.45）。11 例（9%）HBsAg 水平<10 IU/mL 的患者未复发。
恩替卡韦治疗后乙型肝炎 e 抗原阴性的患者，血清 HBsAg 水平与复发风险相关。低 HBsAg 滴度可能用于识别治疗后复发风险较低的患者。
