Jiang Hao, Yu Hongsheng, Huang Yinan, Li Mingkai, Yang Bilan, Xi Xiaoli, Lei Yiming, Wu Bin, Yang Yidong
Department of Gastroenterology, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, People's Republic of China.
Guangdong Provincial Key Laboratory of Liver Disease Research, Guangzhou, People's Republic of China.
J Gastroenterol Hepatol. 2025 Mar;40(3):720-730. doi: 10.1111/jgh.16849. Epub 2024 Dec 18.
In chronic hepatitis B (CHB), an indeterminate phase exists outside the typical predefined phases. Our study investigates this indeterminate phase's natural history and prognosis, focusing on antiviral treatment outcomes.
We conducted a retrospective cohort study to compare the risk of transitioning to immune active phase between inactive and indeterminate CHB and the incidence of hepatocellular carcinoma (HCC) and cirrhosis between untreated patients with indeterminate CHB (at baseline and throughout follow-up) and those who received treatment, following standard AASLD 2018 guidance.
The risk of transitioning to the immune active phase over 3, 5, and 10 years was 6.3%, 8.9%, and 14.2%, respectively, for inactive phase patients (n = 104). For HBeAg-negative indeterminate phase patients (n = 194), the risk was significantly higher at 23.0%, 31.9%, and 38.2%, and for HBeAg-positive indeterminate phase patients (n = 140), it was 40.4%, 52.0%, and 55.0% (p < 0.001). Inverse probability of treatment weighting (IPTW) was utilized to balance the groups of treated and untreated indeterminate patients. Following IPTW adjustment, the Kaplan-Meier curve analysis indicates that the risk of HCC and cirrhosis among untreated patients (n = 294) is higher than that among treated patients (n = 76), (p = 0.015 and 0.007, respectively). In the multivariable analysis, antiviral therapy remained an independent predictor of a reduced risk of HCC (aHR 0.128, 95% CI 0.031-0.522, p = 0.005) and cirrhosis (aHR 0.148, 95% CI 0.044-0.496, p = 0.002).
The indeterminate phase patients had a high-risk transition to active phase, and antiviral therapy can reduce the incidence of developing HCC and cirrhosis.
在慢性乙型肝炎（CHB）中，存在一个典型预定义阶段之外的不确定阶段。我们的研究调查了这个不确定阶段的自然史和预后，重点关注抗病毒治疗结果。
我们进行了一项回顾性队列研究，以比较非活动性和不确定型CHB患者转变为免疫活动期的风险，以及未治疗的不确定型CHB患者（基线时及整个随访期间）与接受治疗的患者之间肝细胞癌（HCC）和肝硬化的发生率，遵循2018年美国肝病研究学会（AASLD）的标准指南。
非活动性阶段患者（n = 104）在3年、5年和10年转变为免疫活动期的风险分别为6.3%、8.9%和14.2%。对于HBeAg阴性不确定阶段患者（n = 194），风险显著更高，分别为23.0%、31.9%和38.2%；对于HBeAg阳性不确定阶段患者（n = 140），风险分别为40.4%、52.0%和55.0%（p < 0.001）。采用治疗权重逆概率（IPTW）来平衡治疗组和未治疗组的不确定患者。经过IPTW调整后，Kaplan-Meier曲线分析表明，未治疗患者（n = 294）发生HCC和肝硬化的风险高于治疗患者（n = 76）（分别为p = 0.015和0.007）。在多变量分析中，抗病毒治疗仍然是HCC风险降低（aHR 0.128，95%CI 0.031 - 0.522，p = 0.005）和肝硬化风险降低（aHR 0.148，95%CI 0.044 - 0.496，p = 0.002）的独立预测因素。
不确定阶段患者向活动期转变的风险较高，抗病毒治疗可降低发生HCC和肝硬化的发生率。
