Affiliation:
1. State Key Laboratory of Organ Failure Research; Key Laboratory of Infectious Diseases Research in South China, Ministry of Education; Guangdong Provincial Key Laboratory of Viral Hepatitis Research; Guangdong Provincial Clinical Research Center for Viral Hepatitis; Guangdong Institute of Hepatology; Department of Infectious Diseases, Nanfang Hospital Southern Medical University Guangzhou China
2. Department of Digestive Diseases The First Affiliated Hospital of Zhengzhou University Zhengzhou China
Abstract
AbstractSerum hepatitis B virus (HBV) spliced RNAs (spRNAs) are ubiquitous in HBV‐infected patients; however, their clinical significance remains unknown. Therefore, we aimed to explore the relationship between HBV spRNAs and liver disease progression in chronic hepatitis B (CHB) patients; in vitro cell line assessment was also performed. The serum HBV wild‐type RNA (wtRNA) and spRNA levels were individually quantified in a cohort of 279 treatment‐naïve, hepatitis B e antigen positive CHB patients with or without cirrhosis. The spRNA proportion was determined as (spRNA × 100%)/(spRNAs + wtRNA). 20 patients' serum samples underwent spRNA species profiling using next‐generation sequencing. Serum spRNA species 1, 2, 3, 4, and 5 were the most common variants. The spRNA proportion varied from 0.00% to 19.02%, with higher levels in HBV genotype C patients than in those with genotype B (1.76% vs. 0.84%, p < 0.001). The spRNA proportion was positively associated with the alanine aminotransferase levels (r = 0.144, p = 0.053) and significantly higher in cirrhotic than in non‐cirrhotic patients (1.69% vs. 1.04%, p = 0.001). Multivariate analysis revealed a 2.566‐fold higher risk of cirrhosis in patients with elevated spRNA proportion (p = 0.024). In vitro experiments confirmed that spRNAs contributed to hepatic stellate cell activation, which is critical in liver fibrosis development. Therefore, increased HBV spRNA expression poses a risk for liver disease progression. Quantifying serum HBV spRNAs can aid in monitoring liver disease progression. Furthermore, the therapeutic targeting of spRNAs may improve the prognosis of patients with CHB.
Subject
Infectious Diseases,Virology