高乙肝核心相关抗原水平与中等病毒载量慢性乙型肝炎病毒感染者肝细胞癌风险增加相关。
High Level of Hepatitis B Core-Related Antigen Associated With Increased Risk of Hepatocellular Carcinoma in Patients With Chronic HBV Infection of Intermediate Viral Load.
机构信息
Division of Gastroenterology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan.
Division of Gastroenterology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan; Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan.
出版信息
Gastroenterology. 2019 Dec;157(6):1518-1529.e3. doi: 10.1053/j.gastro.2019.08.028. Epub 2019 Aug 27.
BACKGROUND & AIMS: Chronic hepatitis B virus (HBV) infection is a risk factor for hepatocellular carcinoma (HCC). Serum levels of HB core-related antigen (HBcrAg) have been associated with active replication of HBV. We investigated whether HBcrAg levels are associated with development of HCC, especially in patients who do not require antiviral treatment.
METHODS
We collected data from 2666 adults positive for hepatitis B surface antigen (HBsAg), infected with HBV genotypes B or C, and without liver cirrhosis, who had long-term follow-up at the National Taiwan University Hospital from 1985 through 2000. None of the patients received antiviral treatment during the follow-up. Baseline levels of HBV DNA, HBsAg, and HBcrAg were determined retrospectively and participants were followed for a mean of 15.95 years. The primary end point was an association between serum level of HBcrAg and HCC development.
RESULTS
HCC developed in 209 patients in the cohort (incidence rate, 4.91 cases/1000 person-years). We found a positive association between baseline level of HBcrAg and HCC development; HBcrAg level was an independent risk factor in multivariable analysis. In the subgroup of hepatitis B e antigen-negative patients with HBV DNA levels from 2000 to 19,999 IU/mL (intermediate viral load [IVL]) and normal levels of alanine aminotransferase, HBcrAg levels of 10 KU/mL or more identified patients at increased risk of HCC (hazard ratio, 6.29; confidence interval, 2.27-17.48). Patients with an IVL and a high level of HBcrAg had a risk for HCC that did not differ significantly from that of patients with a high viral load (≥20,000 IU/mL). Patients with an IVL but a low level of HBcrAg had a low risk of HCC, with an annual incidence rate of 0.10% (95% confidence interval, 0.04%-0.24%).
CONCLUSIONS
In a long-term follow-up study of 2666 patients with chronic HBV infection (genotypes B or C), level of HBcrAg is an independent risk factor of HCC. Moreover, HBcrAg level of 10 KU/mL identifies patients with an IVL who are at high risk for HCC.
背景与目的
慢性乙型肝炎病毒（HBV）感染是肝细胞癌（HCC）的一个危险因素。血清 HB 核心相关抗原（HBcrAg）水平与 HBV 的复制活跃有关。我们研究了 HBcrAg 水平是否与 HCC 的发生有关，特别是在不需要抗病毒治疗的患者中。
方法
我们收集了 1985 年至 2000 年在台湾大学医院长期随访的 2666 名乙型肝炎表面抗原（HBsAg）阳性、感染乙型或丙型肝炎病毒且无肝硬化的成年人的数据。在随访期间，没有患者接受抗病毒治疗。回顾性检测了 HBV DNA、HBsAg 和 HBcrAg 的基线水平，平均随访 15.95 年。主要终点是血清 HBcrAg 水平与 HCC 发生之间的关系。
结果
该队列中有 209 名患者发生 HCC（发生率为 4.91 例/1000 人年）。我们发现 HBcrAg 基线水平与 HCC 发生呈正相关；HBcrAg 水平是多变量分析中的一个独立危险因素。在乙型肝炎 e 抗原阴性、HBV DNA 水平为 2000 至 19999 IU/mL（中间病毒载量[IVL]）且丙氨酸氨基转移酶正常的亚组中，HBcrAg 水平为 10KU/mL 或更高可识别出 HCC 风险增加的患者（危险比，6.29；95%置信区间，2.27-17.48）。IVL 且高水平 HBcrAg 的患者 HCC 风险与高病毒载量（≥20000 IU/mL）的患者无显著差异。IVL 但低水平 HBcrAg 的患者 HCC 风险较低，年发生率为 0.10%（95%置信区间，0.04%-0.24%）。
结论
在对 2666 名慢性 HBV 感染（B 型或 C 型）患者的长期随访研究中，HBcrAg 水平是 HCC 的一个独立危险因素。此外，HBcrAg 水平为 10KU/mL 可识别出 IVL 患者 HCC 风险较高。
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