Current research and challenges of low-level viremia in patients with chronic hepatitis B

Abstract

Abstract:

Although newborns are generally vaccinated against chronic hepatitis B virus, incidence of HBV infection decreases. However, in 2016, there were still 86 million cases of chronic HBV infection in China. In 2019, there were 296 million cases of chronic HBV infection worldwide, and approximately 820 000 people die from related diseases caused by HBV infection annually, such as liver failure, cirrhosis or HCC. Mostly, the clinical treatment of patients with chronic hepatitis B can achieve therapeutic effects of inhibiting virus replication and delaying disease progression after standar-dized antiviral treatments (such as entecavir, tenofovir, and propofol tenofovir). But with a deeper understanding of the di-sease and the improvement of detection technology, it has been found in clinical practice that some patients, after 48 weeks of standardized treatment, had serum HBV DNA levels below 2 000 IU/mL and continuously or intermittently exceeding the lower limit of detection， which indicates a state of low-level viremia（LLV）. The mechanism of LLV is currently unclear. Related studies have shown that LLV of HBV affects the clinical prognosis of patients, mainly manifesting as promoting liver inflammation, development of liver fibrosis, and an increased risk of decompensated cirrhosis, hepatocellular carcinoma, and drug resistance. In addition, there are no clear recommendations for the treatment of patients with HBV LLV. This article will review the definition, possible mechanisms, clinical significance, and clinical management strategies of HBV LLV, providing reference for clinical physicians.

Key words:Hepatitis B virus infection,Low level viremia,Nucleos(t)ide analogues

CLC Number:

WANG Jiaojiao, CAI Dachuan. Current research and challenges of low-level viremia in patients with chronic hepatitis B[J]. Journal of Diagnostics Concepts & Practice, 2024, 23(01): 23-29.

Figures/Tables3

作者	年份	总人数（n）	LLV患者HBV DNA水平（IU/mL）
Kim等^{[ 9 ]}	2017	875	12~2 000
Kim等^{[ 10 ]}	2019	565	9~2 000
Lee等^{[ 11 ]}	2020	894	12~2 000
Sun等^{[ 12 ]}	2021	212	100~2 000（抗病毒治疗过程中）
Li等^{[ 13 ]}	2021	211	20~2 000（ETV治疗≥48周）

Table 1

临床试验	年份	研究药物	研究终点HBV DNA水平
AI463022^{[ 20 ]}	2008	ETV	<300拷贝/mL
NCT00116805、NCT00117676^{[ 21 ]}	2008	TDF、阿德福韦酯	<400拷贝/mL（69 IU/mL)
NCT01940471、NCT01940341^{[ 22 ]}	2018	TDF、TAF	<29 IU/mL

Table 2

高灵敏度HBV DNA	HBV RNA	乙肝核心相关抗原
1.提高LLV检出率	1.不被NAs抑制	1.反映肝内cccDNA水平
2.反映病毒复制水平	2.反映肝内cccDNA的水平及转录活性	2.预测肝硬化与HCC发生的风险^{[ 30 ]}
3.评估抗病毒治疗疗效	3.联合HBV DNA预测HCC发生风险^{[ 31 ]}	3.联合HBV RNA预测病毒复发^{[ 2 ]}
	4.联合乙肝核心相关抗原预测病毒复发^{[ 2 ]}

Table 3

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