Du Yanan, Du Bingying, Fang Xiaoyan, Shu Meng, Zhang Yongjing, Chung Hsingwen, Sun Ye, Teng Jiaming, Visalath Phimphone, Qiu Hong, Cai Wei
Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Department of Epidemiology, Janssen Research and Development, Shanghai, China.
Front Oncol. 2021 Jan 21;10:615203. doi: 10.3389/fonc.2020.615203. eCollection 2020.
Alanine aminotransferase (ALT) level is one of the crucial indexes to evaluate disease status for chronic hepatitis B (CHB) patients. However, whether the ALT level after nucleos(t)ide analog (NA) treatment is associated with hepatocellular carcinoma (HCC) development remains unclear.
We evaluated the association between ALT level and HCC occurrence in NA-treated patients and investigated the predictive value of ALT flare for HCC. The associations between ALT level and HCC were analyzed by logistic regression and Cox proportional hazards models.
There were 21,223 CHB patients at Ruijin Hospital of China and 16,737 CHB patients in the Optum electronic health records (EHR) in the United States (US) treated with NAs between 2010 and 2018. Among them, 8,152 and 4,893 patients who achieved a normal ALT value were included in the study cohorts, respectively. A significant positive dose-dependent correlation between the peak ALT level and HCC was identified in both cohorts. Within the China cohort, ALT flare was significantly associated with increased risks of HCC compared to normal ALT (HR 2.55, 95%CI 1.45-4.50). Stronger increased risks associated with ALT flare were observed in the US cohort (HR 7.62, 95%CI 4.85-11.98).
ALT flare is a strong predictor for HCC occurrence in the CHB patients treated with NAs. Elevation of ALT, especially ALT flare warrants close monitoring for early HCC detection.
谷丙转氨酶（ALT）水平是评估慢性乙型肝炎（CHB）患者疾病状态的关键指标之一。然而，核苷（酸）类似物（NA）治疗后的ALT水平与肝细胞癌（HCC）发生之间的关系仍不明确。
我们评估了NA治疗患者中ALT水平与HCC发生之间的关联，并研究了ALT波动对HCC的预测价值。通过逻辑回归和Cox比例风险模型分析ALT水平与HCC之间的关联。
2010年至2018年期间，中国上海交通大学医学院附属瑞金医院有21,223例CHB患者，美国Optum电子健康记录（EHR）中有16,737例CHB患者接受了NA治疗。其中，分别有8,152例和4,893例ALT值恢复正常的患者被纳入研究队列。在两个队列中均发现ALT峰值水平与HCC之间存在显著的正剂量依赖性相关性。在中国队列中，与正常ALT相比，ALT波动与HCC风险增加显著相关（HR 2.55，95%CI 1.45 - 4.50）。在美国队列中观察到与ALT波动相关的风险增加更为明显（HR 7.62，95%CI 4.85 - 11.98）。
ALT波动是接受NA治疗的CHB患者发生HCC的有力预测指标。ALT升高，尤其是ALT波动，值得密切监测以早期发现HCC。
