Lin Weijia, Ding Rongrong, Sun Shuangshuang, Lu Wei, Wang Yanbin, Zhou Xinlan, Huang Dan, Li Xiufen, Zhang Zhanqing, Chen Liang
Department of Hepatobiliary Medicine, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China.
Department of Hepatology Center, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China.
BMC Infect Dis. 2025 Mar 19;25(1):385. doi: 10.1186/s12879-025-10790-0.
The natural history of chronic hepatitis B virus (HBV) infection is usually divided into four phases: immune tolerant (IT), immune active (IA), immune carrier (IC), and immune reactive (IR). Many patients still cannot be classified into the four phases, called "Grey Zone (GZ)". This study aimed to analyze the liver histological features of the GZ patients to guide antiviral therapy.
We retrospectively analyzed the 1454 patients with chronic HBV infection who underwent liver biopsy. GZ patients with identical serum hepatitis Be antigen (HBeAg) and alanine aminotransferase (ALT) levels as those in the IT, IA, IC, and IR phases were categorized into the IT-GZ, IA-GZ-1, IA-GZ-2, IC-GZ, and IR-GZ groups, respectively. We analyzed and compared the histological distribution of liver in these patients. We evaluated independent influencing factors for significant liver histological changes (SLHC) in patients in the GZ subgroups.
Among the 1454 patients, 690(47.5%) patients in GZ. Among the 690 patients of the GZ, 322(46.7%) patients for whom histological examinations indicated SLHC. The proportion of SLHC within the GZ subgroups was as follows: IT-GZ (50.5%), IA-GZ-1 (75.0%), IA-GZ-2 (48.4%), IC-GZ (32.1%), and IR-GZ (59.6%). In the IT-GZ group, the proportion of patients aged ≤ 30 years with SLHC was 47.1%, and in the IC-GZ group, this proportion was 42.1%.
46.7% of GZ patients had significant liver histological changes. For HBeAg-negative patients with ALT ≤ 40U/L, HBV DNA ≥ 2000IU/mL, and an age of ≤ 30 years old, antiviral therapy was recommended; if they expressed concern, a liver biopsy was suggested.
慢性乙型肝炎病毒(HBV)感染的自然史通常分为四个阶段:免疫耐受期(IT)、免疫活动期(IA)、免疫携带期(IC)和免疫反应期(IR)。许多患者仍无法归入这四个阶段,称为“灰色地带(GZ)”。本研究旨在分析灰色地带患者的肝脏组织学特征,以指导抗病毒治疗。
我们回顾性分析了1454例接受肝活检的慢性HBV感染患者。将血清乙肝e抗原(HBeAg)和丙氨酸氨基转移酶(ALT)水平与IT、IA、IC和IR期相同的灰色地带患者分别归入IT-GZ、IA-GZ-1、IA-GZ-2、IC-GZ和IR-GZ组。我们分析并比较了这些患者肝脏的组织学分布。我们评估了灰色地带亚组患者显著肝脏组织学改变(SLHC)的独立影响因素。
在1454例患者中,690例(47.5%)处于灰色地带。在690例灰色地带患者中,322例(46.7%)患者的组织学检查显示有显著肝脏组织学改变。灰色地带亚组中显著肝脏组织学改变的比例如下:IT-GZ(50.5%)、IA-GZ-1(75.0%)、IA-GZ-2(48.4%)、IC-GZ(32.1%)和IR-GZ(59.6%)。在IT-GZ组中,年龄≤30岁且有显著肝脏组织学改变的患者比例为47.1%,在IC-GZ组中,这一比例为42.1%。
46.7%的灰色地带患者有显著肝脏组织学改变。对于HBeAg阴性、ALT≤40U/L、HBV DNA≥2000IU/mL且年龄≤30岁的患者,建议进行抗病毒治疗;如果他们表示担忧,建议进行肝活检。