Department of Clinical Laboratory, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.
Key Clinical Laboratory of Henan Province, Zhengzhou, Henan, China.
Microbiol Spectr. 2024 Apr 2;12(4):e0394123. doi: 10.1128/spectrum.03941-23. Epub 2024 Mar 1.
This study is to explore the proportion of significant liver histopathology in hepatitis B e antigen (HBeAg)-negative chronic hepatitis B virus (HBV)-infected patients with normal alanine aminotransferase (ALT) and investigate noninvasive indicators for predicting significant liver histopathology. A total of 201 HBeAg-negative chronic HBV-infected patients with normal ALT who underwent liver biopsy were involved in this study. Significant liver histological changes were defined as necroinflammation grade ≥2 (G ≥ 2) and/or fibrosis stage ≥2 (S ≥ 2). The results showed that 42.3% (85/201) and 45.8% (92/201) of the HBeAg-negative patients with normal ALT have significant liver necroinflammation (G ≥ 2) and fibrosis (S ≥ 2), respectively. High normal ALT (>22 U/L), high level of serum HBV DNA (>3.42 log IU/mL), and low level of prealbumin (PA) (<170 mg/L) were independent predictors for significant liver necroinflammation, and the predictive value of the combined indicators was 0.750 ( < 0.001), while high normal ALT (>24 U/L) and high level of FIB-4 (>1.53) were independent predictors for significant liver fibrosis, and the predictive value of the combined indicators was 0.740 ( < 0.001). In conclusion, more than 40% of HBeAg-negative patients with normal ALT have significant liver histopathology and require immediate antiviral treatment. ALT, PA, HBV DNA, and FIB-4 can independently predict significant liver inflammation and fibrosis for HBeAg-negative patients with normal ALT. Lowering the treatment threshold of ALT may benefit the HBeAg-negative chronic HBV-infected patients.
Hepatitis B e antigen (HBeAg)-negative chronic hepatitis B virus (HBV)-infected patients with normal alanine aminotransferase (ALT) were supposed to have a low risk of progression to cirrhosis or hepatocellular carcinoma, and it was recommended to regularly follow up or undergo liver biopsy to assess liver histopathology according to the major international guidelines. However, this study indicates that a considerable number of HBeAg-negative chronic HBV-infected patients with normal ALT have significant liver histopathology and require immediate antiviral treatment. Besides, several clinical commonly used noninvasive indicators were found that can be used to predict significant liver histopathology; thereby liver biopsy might be avoided for HBeAg-negative chronic HBV-infected patients with normal ALT.
本研究旨在探讨 ALT 正常的 HBeAg 阴性慢性乙型肝炎病毒（HBV）感染者中显著肝脏组织病理学的比例，并探讨预测显著肝脏组织病理学的非侵入性指标。方法：共纳入 201 例 ALT 正常的 HBeAg 阴性慢性 HBV 感染者行肝活检，将显著的肝脏组织学改变定义为坏死性炎症≥2 级（G≥2）和/或纤维化分期≥2 级（S≥2）。结果：42.3%（85/201）和 45.8%（92/201）的 ALT 正常的 HBeAg 阴性患者有显著的肝坏死性炎症（G≥2）和纤维化（S≥2）。高正常 ALT（>22 U/L）、高血清 HBV DNA（>3.42 log IU/mL）和低前白蛋白（PA）（<170mg/L）是显著肝坏死性炎症的独立预测因子，联合指标的预测价值为 0.750（<0.001），而高正常 ALT（>24 U/L）和高 FIB-4（>1.53）是显著肝纤维化的独立预测因子，联合指标的预测价值为 0.740（<0.001）。结论：超过 40%的 ALT 正常的 HBeAg 阴性患者有显著的肝脏组织病理学改变，需要立即进行抗病毒治疗。ALT、PA、HBV DNA 和 FIB-4 可独立预测 ALT 正常的 HBeAg 阴性患者的显著肝脏炎症和纤维化。降低 ALT 的治疗阈值可能对 HBeAg 阴性慢性 HBV 感染者有益。
根据主要国际指南，HBV 感染者 ALT 正常的 HBeAg 阴性慢性乙型肝炎患者被认为进展为肝硬化或肝细胞癌的风险较低，建议根据该指南定期随访或行肝活检以评估肝脏组织病理学。然而，本研究表明，相当数量的 ALT 正常的 HBeAg 阴性慢性 HBV 感染者存在显著的肝脏组织病理学改变，需要立即进行抗病毒治疗。此外，还发现了一些临床常用的非侵入性指标，可以用于预测显著的肝脏组织病理学，从而避免对 ALT 正常的 HBeAg 阴性慢性 HBV 感染者进行肝活检。
