Lee Han Ah, Seo Yeon Seok, Park Seung Woon, Park Sang Jung, Kim Tae Hyung, Suh Sang Jun, Jung Young Kul, Kim Ji Hoon, An Hyunggin, Yim Hyung Joon, Yeon Jong Eun, Byun Kwan Soo, Um Soon Ho
Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea.
Department of Biostatistics, Korea University College of Medicine, Seoul, Korea.
Clin Mol Hepatol. 2016 Sep;22(3):382-389. doi: 10.3350/cmh.2016.0047. Epub 2016 Sep 25.
BACKGROUND/AIMS: Clear indicators for stopping antiviral therapy in chronic hepatitis B (CHB) patients are not yet available. Since the level of hepatitis B surface antigen (HBsAg) is correlated with covalently closed circular DNA, the HBsAg titer might be a good indicator of the off-treatment response. This study aimed to determine the relationship between the HBsAg titer and the entecavir (ETV) off-treatment response.
This study analyzed 44 consecutive CHB patients (age, 44.6±11.4 years, mean±SD; men, 63.6%; positive hepatitis B envelope antigen (HBeAg) at baseline, 56.8%; HBV DNA level, 6.8±1.3 log IU/mL) treated with ETV for a sufficient duration and in whom treatment was discontinued after HBsAg levels were measured. A virological relapse was defined as an increase in serum HBV DNA level of >2000 IU/mL, and a clinical relapse was defined as a virological relapse with a biochemical flare, defined as an increase in the serum alanine aminotransferase level of >2 × upper limit of normal.
After stopping ETV, virological relapse and clinical relapse were observed in 32 and 24 patients, respectively, during 20.8±19.9 months of follow-up. The cumulative incidence rates of virological relapse were 36.2% and 66.2%, respectively, at 6 and 12 months, and those of clinical relapse were 14.3% and 42.3%. The off-treatment HBsAg level was an independent factor associated with clinical relapse (hazard ratio, 2.251; 95% confidence interval, 1.076-4.706; =0.031). When patients were grouped according to off-treatment HBsAg levels, clinical relapse did not occur in patients with an off-treatment HBsAg level of ≤2 log IU/mL (n=5), while the incidence rates of clinical relapse at 12 months after off-treatment were 28.4% and 55.7% in patients with off-treatment HBsAg levels of >2 and ≤3 log IU/mL (n=11) and >3 log IU/mL (n=28), respectively.
The off-treatment HBsAg level is closely related to clinical relapse after treatment cessation. A serum HBsAg level of <2 log IU/mL is an excellent predictor of a sustained off-treatment response in CHB patients who have received ETV for a sufficient duration.
背景/目的：目前尚无慢性乙型肝炎（CHB）患者停止抗病毒治疗的明确指标。由于乙肝表面抗原（HBsAg）水平与共价闭合环状DNA相关，HBsAg滴度可能是停药反应的良好指标。本研究旨在确定HBsAg滴度与恩替卡韦（ETV）停药反应之间的关系。
本研究分析了44例连续的CHB患者（年龄44.6±11.4岁，均值±标准差；男性占63.6%；基线乙肝e抗原（HBeAg）阳性率为56.8%；HBV DNA水平为6.8±1.3 log IU/mL），这些患者接受ETV治疗足够长的时间，在测量HBsAg水平后停药。病毒学复发定义为血清HBV DNA水平升高>2000 IU/mL，临床复发定义为伴有生化复发的病毒学复发，生化复发定义为血清丙氨酸氨基转移酶水平升高>正常上限的2倍。
停止ETV治疗后，在20.8±19.9个月的随访期间，分别有32例和24例患者出现病毒学复发和临床复发。病毒学复发的累积发生率在6个月和12个月时分别为36.2%和66.2%，临床复发的累积发生率分别为14.3%和42.3%。停药时的HBsAg水平是与临床复发相关的独立因素（风险比，².²⁵¹；95%置信区间，¹.⁰⁷⁶ - ⁴.⁷⁰⁶；P = ⁰.⁰³¹）。根据停药时的HBsAg水平对患者进行分组，停药时HBsAg水平≤2 log IU/mL的患者（n = 5）未发生临床复发，而停药时HBsAg水平>2且≤3 log IU/mL（n = 11）和>3 log IU/mL（n = 28）的患者停药后12个月时临床复发的发生率分别为28.4%和55.7%。
停药时的HBsAg水平与停药后临床复发密切相关。血清HBsAg水平<2 log IU/mL是接受ETV治疗足够长时间的CHB患者持续停药反应的良好预测指标。
