{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T03:26:08Z","timestamp":1792985168442,"version":"4.5.0"},"reference-count":22,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2024,1,31]],"date-time":"2024-01-31T00:00:00Z","timestamp":1706659200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2024,1,31]],"date-time":"2024-01-31T00:00:00Z","timestamp":1706659200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Medical Virology"],"published-print":{"date-parts":[[2024,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Serum hepatitis B virus (HBV) spliced RNAs (spRNAs) are ubiquitous in HBV\u2010infected 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\u2010type RNA (wtRNA) and spRNA levels were individually quantified in a cohort of 279 treatment\u2010na\u00efve, hepatitis B e antigen\u00a0positive CHB patients with or without cirrhosis. The spRNA proportion was determined as (spRNA\u2009\u00d7\u2009100%)\/(spRNAs\u2009+\u2009wtRNA). 20 patients'\u00a0serum samples underwent spRNA species profiling using next\u2010generation 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%,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.001). The spRNA proportion was positively associated with the alanine aminotransferase levels (\n                    <jats:italic>r<\/jats:italic>\n                    \u2009=\u20090.144,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.053) and significantly higher in cirrhotic than in non\u2010cirrhotic patients (1.69% vs. 1.04%,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.001). Multivariate analysis revealed a 2.566\u2010fold higher risk of cirrhosis in patients with elevated spRNA proportion (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.024). 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.\n                  <\/jats:p>","DOI":"10.1002\/jmv.29400","type":"journal-article","created":{"date-parts":[[2024,1,31]],"date-time":"2024-01-31T05:29:20Z","timestamp":1706678960000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Serum hepatitis B virus spliced RNA proportion increases with liver disease progression in patients with chronic hepatitis B"],"prefix":"10.1002","volume":"96","author":[{"given":"Xingyu","family":"Lu","sequence":"first","affiliation":[{"name":"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"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wanying","family":"Li","sequence":"additional","affiliation":[{"name":"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"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui","family":"Deng","sequence":"additional","affiliation":[{"name":"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"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bin","family":"Zhou","sequence":"additional","affiliation":[{"name":"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"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Digestive Diseases The First Affiliated Hospital of Zhengzhou University Zhengzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinlin","family":"Hou","sequence":"additional","affiliation":[{"name":"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"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheng","family":"Shen","sequence":"additional","affiliation":[{"name":"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"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian","family":"Sun","sequence":"additional","affiliation":[{"name":"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"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5669-1280","authenticated-orcid":false,"given":"Shi","family":"Liu","sequence":"additional","affiliation":[{"name":"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"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,1,31]]},"reference":[{"key":"e_1_2_10_2_1","unstructured":"WHO. 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