INSERM U1052-Cancer Research Center of Lyon (CRCL), 69008, Lyon, France; University of Lyon, University Claude Bernard Lyon 1 (UCBL1), Lyon, France; Department of Virology, Croix Rousse Hospital, Hospices Civils de Lyon, Lyon, France.
INSERM U1052-Cancer Research Center of Lyon (CRCL), 69008, Lyon, France; University of Lyon, University Claude Bernard Lyon 1 (UCBL1), Lyon, France; Department of Hepatology, Croix Rousse Hospital, Hospices Civils de Lyon, Lyon, France.
Antiviral Res. 2019 Sep;169:104553. doi: 10.1016/j.antiviral.2019.104553. Epub 2019 Jul 6.
Chronic hepatitis B virus (HBV) infection remains a major health burden with over 250 million cases worldwide. This complex infection can lead to chronic hepatitis, liver cirrhosis and hepatocellular carcinoma. Complete recovery is seldom achieved due to the persistence in infected hepatocytes of covalently closed circular (ccc)DNA, which is not targeted by current antiviral therapies. Routine circulating biomarkers used for clinical monitoring of patients do not accurately reflect the cccDNA pool and transcriptional activity. New biomarkers, such as serum HB core-related Ag and circulating HBV RNAs, are under development. In this review, we discuss surrogate non-invasive biomarkers for evaluating intrahepatic cccDNA abundance and transcriptional activity. We also present their relevance for improving the classification of patients with regards to their natural history and for evaluating novel compounds to assess target engagement and to define new virological endpoints.
慢性乙型肝炎病毒（HBV）感染仍然是一个重大的健康负担，全球有超过 2.5 亿病例。这种复杂的感染可导致慢性肝炎、肝硬化和肝细胞癌。由于感染肝细胞中的共价闭合环状（ccc）DNA 持续存在，目前的抗病毒治疗并不能针对该 DNA 进行治疗，因此很少能完全恢复。用于临床监测患者的常规循环生物标志物不能准确反映 cccDNA 池和转录活性。新的生物标志物，如血清 HB 核心相关 Ag 和循环 HBV RNA，正在开发中。在这篇综述中，我们讨论了用于评估肝内 cccDNA 丰度和转录活性的替代非侵入性生物标志物。我们还介绍了它们在改善患者自然史分类方面的相关性，以及评估新型化合物以评估靶标结合和定义新的病毒学终点的相关性。
