Entecavir Reduced Serum Hepatitis B Core-Related Antigen in Chronic Hepatitis B Patients With Hepatocellular Carcinoma
Lung-Yi Mak 1 , Kwan-Lung Ko 1 , Wai-Pan To 1 , Danny Ka-Ho Wong 1 2 , Wai-Kay Seto 1 2 3 , James Fung 1 2 , Man-Fung Yuen 1 2
Affiliations
Affiliations
1
Department of Medicine, Queen Mary Hospital, The University of Hong Kong, China.
2
State Key Laboratory of Liver Research, The University of Hong Kong, Hong Kong, China.
3
Department of Medicine, The University of Hong Kong-Shenzhen Hospital, Shenzhen, China.
PMID: 32457279 DOI: 10.5009/gnl19434
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Abstract
Serum hepatitis B core-related antigen (HBcrAg) was shown to predict the risk of hepatocellular carcinoma (HCC) in chronic hepatitis B (CHB) patients undergoing treatment. We investigated the longitudinal profile of HBcrAg in entecavir (ETV)-treated CHB patients with subsequent HCC development. We identified HCC cases diagnosed at ≥1 year after ETV initiation. CHB patients without HCC (matched for age, sex, cirrhosis status, baseline hepatitis B virus (HBV) DNA level, and ETV treatment duration) were identified as controls at an HCC:non-HCC ratio of 1:2. Serum samples were retrieved at baseline (ETV initiation) and at 3 and 5 years of ETV therapy for HBcrAg measurement (log IU/mL). In total, 180 patients (60 HCC patients matched with 120 CHB patients without HCC; median age, 56.5 years; 80.6% male; baseline HBV DNA, 5.9 log IU/mL; median follow-up, 6.8 years) were recruited. The median time from ETV initiation to HCC development was 3.2 years. HBcrAg levels were higher in HCC cases than in controls at all three time points: 5.69 log IU/mL versus 5.02 log IU/mL (p=0.025), 4.23 log IU/mL versus 3.36 log IU/mL (p=0.007), and 3.86 log IU/mL vs 3.36 log IU/mL (p=0.009), respectively. ETV led to similar rates of decline in HBcrAg from baseline to 3 years in both groups (0.34 log IU/mL/year vs 0.39 log IU/mL/year, p=0.774), although the decline from 3 to 5 years was slower in the non-HCC group (0.05 log IU/mL/year) than in the HCC group (0.09 log IU/mL/year, p=0.055). ETV time-dependently reduced HBcrAg in HCC and non-HCC patients. HBcrAg interpretation should consider the antiviral treatment duration.
血清乙型肝炎核心相关抗原（HBcrAg）被证明可预测接受治疗的慢性乙型肝炎（CHB）患者的肝细胞癌（HCC）风险。我们调查了恩替卡韦（ETV）治疗的CHB患者随后发生HCC的过程中HBcrAg的纵向分布。我们确定了ETV启动后≥1年诊断出的HCC病例。没有HCC（与年龄，性别，肝硬化状态，基线乙型肝炎病毒（HBV）DNA水平和ETV治疗持续时间相匹配）的CHB患者被确定为HCC：非HCC比为1：2的对照。在基线（ETV起始）以及ETV治疗3年和5年时（HB / mL）（log IU / mL）取血清。总共招募了180例患者（60例HCC患者与120例无HCC的CHB患者；中位年龄为56.5岁；男性为80.6％；基线HBV DNA为5.9 log IU / mL；中位随访时间为6.8年）。从开始ETV到肝癌发展的中位时间为3.2年。在所有三个时间点，HCC患者的HBcrAg水平均高于对照组：5.69 log IU / mL对5.02 log IU / mL（p = 0.025），4.23 log IU / mL对3.36 log IU / mL（p = 0.007），和3.86 log IU / mL分别为3.36 log IU / mL（p = 0.009）。在两组中，ETV导致HBcrAg从基线水平下降到3年的速率相似（0.34 log IU / mL /年vs 0.39 log IU / mL /年，p = 0.774），尽管在3年至5年的下降较慢。非HCC组（0.05 log IU / mL /年）比HCC组（0.09 log IU / mL /年，p = 0.055）。 ETV时间依赖性地降低了HCC和非HCC患者的HBcrAg。 HBcrAg的解释应考虑抗病毒治疗的持续时间。