Xing T J, Zhao K Y, Li W T, Wang L J, Lu F M
Department of Infectious Diseases, Taizhou Hospital of Zhejiang Province, Linhai 317000, China.
Hepatology Institute, Peking University People's Hospital, Beijing 100044, China.
Zhonghua Gan Zang Bing Za Zhi. 2023 Sep 20;31(9):954-960. doi: 10.3760/cma.j.cn501113-20230820-00061.
To explore the relationship and dynamic changes between virological markers and hepatic pathological damage due to host anti-hepatitis B virus (HBV) immunity in the natural course of disease in chronic HBV infected patients. Two hundred and thirty-eight adult chronic HBV-infected patients who underwent liver biopsy from January 2016 to June 2022 in Taizhou Hospital, Zhejiang Province, were retrospectively selected. General clinical data such as age, gender, platelets, ALT, AST, albumin, HBV DNA, qHBsAg, HBeAg, and liver pathology diagnostic indexes such as the grade of liver necroinflammation and liver fibrotic stages of the patients were collected. The patients were grouped according to HBeAg status, and subgrouped according to different grades of liver necroinflammation and different HBV DNA loads. Statistical analyses were performed to compare the differences in HBV virologic marker levels between the groups, and the correlation between them and the indicators of hepatic inflammatory injury, such as ALT,AST, and the grade of liver necroinflammation in the patients. The levels of HBV virological markers in HBeAg-positive patients with moderate or higher liver necroinflammatory grade (G≥2) were significantly lower than those with mild (no) liver necroinflammatory grade (G < 2) ( < 0.01); whereas the opposite trend was observed in HBeAg-negative patients, with the levels of HBV DNA, and qHBsAg in the G≥2 subgroup being significantly higher than those in the G < 2 subgroup ( < 0.01). Correspondingly, HBV DNA level and qHBsAg showed weak to moderately strong negative correlation with liver necroinflammatory grade and AST which was an indicator of hepatic inflammatory injury in HBeAg-positive patients ( < 0.05); whereas in HBeAg-negative patients, they showed weak to moderately strong positive correlation with hepatic inflammatory activity and ALT, AST ( < 0.001), in which qHBsAg showed only a weak positive correlation with patients' liver necroinflammatory grade ( = 0.003). Further subgroup analyses of HBeAg-positive patients according to whether the HBV DNA level was > 2×10(6) IU/ml showed weak to moderate negative correlations between HBV virological markers and liver necroinflammatory grade as well as ALT and AST in the subgroup of patients with HBV DNA > 2×10(6) IU/ml ( < 0.05); however, the negative correlation disappeared in patients who were still HBeAg positive and had HBV DNA ≤ 2×10(6) IU/ml. Moreover, HBV DNA and ALT, HBeAg and AST showed moderate positive correlation ( < 0.05). We speculate that the activation of host anti-HBV immunity can efficiently inhibit HBV replication by targeting the infected hepatocytes, but only in the early phase of disease progression in HBeAg positive patients with HBV DNA high (> 2×10(6) IU/ml).
探讨慢性乙型肝炎病毒(HBV)感染患者自然病程中病毒学标志物与宿主抗HBV免疫所致肝脏病理损伤之间的关系及动态变化。回顾性选取2016年1月至2022年6月在浙江省台州医院接受肝活检的238例成年慢性HBV感染患者。收集患者的年龄、性别、血小板、ALT、AST、白蛋白、HBV DNA、定量HBsAg、HBeAg等一般临床资料,以及肝脏坏死炎症分级、肝纤维化分期等肝脏病理诊断指标。根据HBeAg状态对患者进行分组,并根据肝脏坏死炎症不同分级和不同HBV DNA载量进行亚组划分。进行统计分析以比较各组间HBV病毒学标志物水平的差异,以及它们与患者肝脏炎症损伤指标(如ALT、AST)和肝脏坏死炎症分级之间的相关性。HBeAg阳性且肝脏坏死炎症分级为中度或更高(G≥2)的患者,其HBV病毒学标志物水平显著低于轻度(无)肝脏坏死炎症分级(G<2)的患者(<0.01);而在HBeAg阴性患者中观察到相反趋势,G≥2亚组的HBV DNA和定量HBsAg水平显著高于G<2亚组(<0.01)。相应地,在HBeAg阳性患者中,HBV DNA水平和定量HBsAg与肝脏坏死炎症分级及作为肝脏炎症损伤指标的AST呈弱至中度负相关(<0.05);而在HBeAg阴性患者中,它们与肝脏炎症活动及ALT、AST呈弱至中度正相关(<0.001),其中定量HBsAg与患者肝脏坏死炎症分级仅呈弱正相关(=0.003)。根据HBV DNA水平是否>2×10⁶IU/ml对HBeAg阳性患者进行进一步亚组分析,结果显示在HBV DNA>2×10⁶IU/ml的患者亚组中,HBV病毒学标志物与肝脏坏死炎症分级以及ALT和AST呈弱至中度负相关(<0.05);然而,在仍为HBeAg阳性且HBV DNA≤2×10⁶IU/ml的患者中,这种负相关消失。此外,HBV DNA与ALT、HBeAg与AST呈中度正相关(<0.05)。我们推测宿主抗HBV免疫的激活可通过靶向感染的肝细胞有效抑制HBV复制,但仅在HBV DNA高(>2×10⁶IU/ml)的HBeAg阳性患者疾病进展的早期阶段如此。