Kosaka Masanari, Fujino Hatsue, Tsuge Masataka, Yamaoka Kenji, Fujii Yasutoshi, Uchikawa Shinsuke, Ono Atsushi, Murakami Eisuke, Kawaoka Tomokazu, Miki Daiki, Hayes Clair Nelson, Kashiyama Seiya, Mokuda Sho, Yamazaki Shinichi, Oka Shiro
Department of Gastroenterology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
Liver Center, Hiroshima University Hospital, Hiroshima, Japan.
J Gastroenterol. 2025 Apr;60(4):469-478. doi: 10.1007/s00535-025-02211-5. Epub 2025 Jan 22.
Hepatitis B virus (HBV) RNA is an important serum biomarker of hepatic covalently closed circular DNA (cccDNA) transcriptional activity; however, its clinical characteristics remain unclear. This study evaluated the clinical utility of HBV RNA levels in patients with chronic hepatitis B (CHB).
We studied 87 CHB patients with serum HBV DNA levels ≥ 5.0 log IU/mL who initiated entecavir (ETV) treatment between 2000 and 2018. Serum HBV RNA levels were measured at three-time points: before ETV treatment, at 12 weeks, and at 48 weeks after starting ETV treatment. Clinical markers associated with the antiviral effects of ETV treatment were analyzed.
Serum HBV RNA levels decreased in both HBeAg-positive and -negative patients during the observation period. In HBeAg-positive patients, multivariable analysis showed that lower HBV RNA levels at 48 weeks of ETV treatment were independently associated with HBeAg seroconversion. Additionally, lower baseline HBV RNA levels significantly predicted virologic response in those patients. In contrast, among HBeAg-negative patients, lower HBV core-related antigen (HBcrAg) levels and the FIB-4 index were independently associated with virologic response. In HBeAg-positive patients, those with higher baseline HBV RNA levels showed a more significant reduction in hepatitis B surface antigen levels.
Serum HBV RNA levels predicted HBeAg seroconversion and early HBV DNA reduction in HBeAg-positive patients, while HBcrAg was significantly associated with virologic response in HBeAg-negative patients. These findings highlight the different predictive roles of HBV RNA and HBcrAg based on HBeAg status, which may provide individualized treatment strategies.
乙型肝炎病毒（HBV）RNA是肝共价闭合环状DNA（cccDNA）转录活性的重要血清生物标志物；然而，其临床特征仍不清楚。本研究评估了慢性乙型肝炎（CHB）患者中HBV RNA水平的临床应用价值。
我们研究了87例血清HBV DNA水平≥5.0 log IU/mL且在2000年至2018年期间开始接受恩替卡韦（ETV）治疗的CHB患者。在三个时间点测量血清HBV RNA水平：ETV治疗前、治疗12周时以及开始ETV治疗后48周时。分析与ETV治疗抗病毒效果相关的临床标志物。
在观察期内，HBeAg阳性和阴性患者的血清HBV RNA水平均下降。在HBeAg阳性患者中，多变量分析显示，ETV治疗48周时较低的HBV RNA水平与HBeAg血清学转换独立相关。此外，较低的基线HBV RNA水平显著预测了这些患者的病毒学应答。相比之下，在HBeAg阴性患者中，较低的HBV核心相关抗原（HBcrAg）水平和FIB-4指数与病毒学应答独立相关。在HBeAg阳性患者中，基线HBV RNA水平较高的患者乙肝表面抗原水平下降更为显著。
血清HBV RNA水平预测了HBeAg阳性患者的HBeAg血清学转换和早期HBV DNA降低，而HBcrAg与HBeAg阴性患者的病毒学应答显著相关。这些发现突出了基于HBeAg状态的HBV RNA和HBcrAg的不同预测作用，这可能为个体化治疗策略提供依据。
