Woo Jungreem, Choi Youkyung
Division of Viral Hepatitis, National Center for HIV, Viral Hepatitis, STD and TB Prevention, US Centers for Disease Control and Prevention (CDC), Atlanta, GA 30329-4018, USA.
Pathogens. 2024 Apr 17;13(4):331. doi: 10.3390/pathogens13040331.
The hepatitis C virus (HCV) infection affects 58 million people worldwide. In the United States, the incidence rate of acute hepatitis C has doubled since 2014; during 2021, this increased to 5% from 2020. Acute hepatitis C is defined by any symptom of acute viral hepatitis plus either jaundice or elevated serum alanine aminotransferase (ALT) activity with the detection of HCV RNA, the anti-HCV antibody, or hepatitis C virus antigen(s). However, most patients with acute infection are asymptomatic. In addition, ALT activity and HCV RNA levels can fluctuate, and a delayed detection of the anti-HCV antibody can occur among some immunocompromised persons with HCV infection. The detection of specific biomarkers can be of great value in the early detection of HCV infection at an asymptomatic stage. The high rate of HCV replication (which is approximately 10 to 10 virions per day) and the lack of proofreading by the viral RNA polymerase leads to enormous genetic diversity, creating a major challenge for the host immune response. This broad genetic diversity contributes to the likelihood of developing chronic infection, thus leading to the development of cirrhosis and liver cancer. Direct-acting antiviral (DAA) therapies for HCV infection are highly effective with a cure rate of up to 99%. At the same time, many patients with HCV infection are unaware of their infection status because of the mostly asymptomatic nature of hepatitis C, so they remain undiagnosed until the liver damage has advanced. Molecular mechanisms induced by HCV have been intensely investigated to find biomarkers for diagnosing the acute and chronic phases of the infection. However, there are no clinically verified biomarkers for patients with hepatitis C. In this review, we discuss the biomarkers that can differentiate acute from chronic hepatitis C, and we summarize the current state of the literature on the useful biomarkers that are detectable during acute and chronic HCV infection, liver fibrosis/cirrhosis, and hepatocellular carcinoma (HCC).
丙型肝炎病毒（HCV）感染在全球影响着5800万人。在美国，自2014年以来，急性丙型肝炎的发病率翻了一番；在2021年期间，这一比例从2020年的水平上升至5%。急性丙型肝炎的定义为出现任何急性病毒性肝炎症状，同时伴有黄疸或血清丙氨酸氨基转移酶（ALT）活性升高，并检测到HCV RNA、抗-HCV抗体或丙型肝炎病毒抗原。然而，大多数急性感染患者没有症状。此外，ALT活性和HCV RNA水平可能会波动，并且在一些丙型肝炎病毒感染的免疫功能低下者中可能会出现抗-HCV抗体检测延迟的情况。检测特定生物标志物对于在无症状阶段早期检测丙型肝炎病毒感染具有重要价值。HCV的高复制率（每天约10至10个病毒粒子）以及病毒RNA聚合酶缺乏校对功能导致了巨大的基因多样性，这给宿主免疫反应带来了重大挑战。这种广泛的基因多样性增加了发生慢性感染的可能性，进而导致肝硬化和肝癌的发生。针对丙型肝炎病毒感染的直接抗病毒（DAA）疗法非常有效，治愈率高达99%。与此同时，由于丙型肝炎大多无症状，许多丙型肝炎病毒感染患者并不知道自己的感染状况，因此在肝脏损伤进展之前他们一直未被诊断出来。为了寻找用于诊断感染急性期和慢性期的生物标志物，人们对丙型肝炎病毒诱导的分子机制进行了深入研究。然而，对于丙型肝炎患者尚无经过临床验证的生物标志物。在本综述中，我们讨论了能够区分急性和慢性丙型肝炎的生物标志物，并总结了关于在急性和慢性丙型肝炎病毒感染、肝纤维化/肝硬化以及肝细胞癌（HCC）期间可检测到的有用生物标志物的文献现状。
