{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T14:38:16Z","timestamp":1787841496841,"version":"build-2784847793"},"reference-count":29,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"5","content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2024,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>To delineate the levels of serum Hepatitis B virus (HBV) RNA in patients with HBV-related hepatocellular carcinoma (HCC) and study comparisons with those of individuals afflicted with cirrhosis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>Adult patients diagnosed with HBV-related cirrhosis or HCC (initial diagnosis) were enrolled in the cross-sectional study. Serum HBV DNA level was quantified through a real-time polymerase chain reaction assay with a lower limit of quantification (LLQ) of 20 IU\/ml. Additionally, serum HBV RNA was quantified employing RNA real-time fluorescence thermostatic amplification detection technology with LLQ of 100 copies\/ml. Propensity score matching (PSM) was conducted to ensure balance in between-group confounders.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>\n                      A total of 187 patients (47 with HCC and 140 with cirrhosis) were recruited, among whom 140 (74.9%) had undergone antiviral therapy prior to their inclusion, with varying durations. Serum HBV RNA was detectable in 89.4% of HCC patients at the time of carcinoma diagnosis. After PSM, individuals with HCC exhibited significantly elevated levels of serum HBV DNA and HBV RNA compared to those with cirrhosis (median lgHBV RNA 3.1 vs 2.0 copies\/ml,\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      = 0.001). Subgroup analysis, including 38 patients who exhibited ultrasensitive HBV DNA negativity, revealed similar results (median lgHBV RNA 3.0 vs 0.0 copies\/ml,\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      &lt; 0.001).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>Serum HBV RNA levels were significantly higher in HBV-related HCC patients compared to cirrhotic patients. The presence of serum HBV RNA positivity or elevated levels was associated with the onset of HCC.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.4103\/sjg.sjg_16_24","type":"journal-article","created":{"date-parts":[[2024,7,25]],"date-time":"2024-07-25T03:01:55Z","timestamp":1721876515000},"page":"294-301","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":3,"title":["Elevated Hepatitis B virus RNA levels in hepatocellular carcinoma patients compared to cirrhotic individuals: A propensity score matched analysis"],"prefix":"10.4103","volume":"30","author":[{"given":"Yuying","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Infectious Disease and Hepatology, The Second Hospital of Shandong University, Jinan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juanli","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Infectious Disease and Hepatology, The Second Hospital of Shandong University, Jinan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yushuang","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Infectious Disease and Hepatology, The Second Hospital of Shandong University, Jinan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Infectious Disease and Hepatology, The Second Hospital of Shandong University, Jinan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2548-5476","authenticated-orcid":false,"given":"Tao","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Infectious Disease and Hepatology, The Second Hospital of Shandong University, Jinan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2024,7,24]]},"reference":[{"key":"R1-20240913","doi-asserted-by":"crossref","first-page":"2029","DOI":"10.1111\/liv.15251","article-title":"Changing epidemiology of hepatocellular carcinoma in Asia","volume":"42","author":"Zhang","year":"2022","journal-title":"Liver Int"},{"key":"R2-20240913","doi-asserted-by":"crossref","first-page":"209","DOI":"10.3322\/caac.21660","article-title":"Global Cancer Statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"71","author":"Sung","year":"2021","journal-title":"CA Cancer J Clin"},{"key":"R3-20240913","doi-asserted-by":"crossref","first-page":"589","DOI":"10.1038\/s41575-019-0186-y","article-title":"A global view of hepatocellular carcinoma:trends, risk, prevention and management","volume":"16","author":"Yang","year":"2019","journal-title":"Nat Rev Gastroenterol Hepatol"},{"key":"R4-20240913","doi-asserted-by":"crossref","first-page":"616","DOI":"10.1136\/gutjnl-2020-323153","article-title":"Hepatitis B virus integrations promote local and distant oncogenic driver alterations in hepatocellular carcinoma","volume":"71","author":"P\u00e9neau","year":"2022","journal-title":"Gut"},{"key":"R5-20240913","doi-asserted-by":"crossref","first-page":"2454","DOI":"10.3390\/cancers13102454","article-title":"Unique features of hepatitis B virus-related hepatocellular carcinoma in pathogenesis and clinical significance","volume":"13","author":"Wang","year":"2021","journal-title":"Cancers (Basel)"},{"key":"R6-20240913","doi-asserted-by":"crossref","first-page":"2836","DOI":"10.1111\/liv.15065","article-title":"The association between hepatocarcinogenesis and intracellular alterations due to hepatitis B virus infection","volume":"41","author":"Tsuge","year":"2021","journal-title":"Liver Int"},{"key":"R7-20240913","doi-asserted-by":"crossref","first-page":"741","DOI":"10.1007\/s12072-022-10351-6","article-title":"Hepatitis B virus X protein mediated epigenetic alterations in the pathogenesis of hepatocellular carcinoma","volume":"16","author":"Yang","year":"2022","journal-title":"Hepatol Int"},{"key":"R8-20240913","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1056\/NEJMra2211764","article-title":"New approaches to chronic hepatitis B","volume":"388","author":"Dusheiko","year":"2023","journal-title":"N Engl J Med"},{"key":"R9-20240913","doi-asserted-by":"crossref","first-page":"370","DOI":"10.1016\/j.jhep.2017.03.021","article-title":"EASL 2017 Clinical Practice Guidelines on the management of hepatitis B virus infection","volume":"67","year":"2017","journal-title":"J Hepatol"},{"key":"R10-20240913","doi-asserted-by":"crossref","first-page":"1560","DOI":"10.1002\/hep.29800","article-title":"Update on prevention, diagnosis, and treatment of chronic hepatitis B: AASLD 2018 hepatitis B guidance","volume":"67","author":"Terrault","year":"2018","journal-title":"Hepatology"},{"key":"R11-20240913","first-page":"1425","article-title":"Guidelines for the prevention and treatment of chronic hepatitis B (version 2022)","volume":"11","author":"You","year":"2023","journal-title":"J Clin Transl Hepatol"},{"key":"R12-20240913","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1159\/000343857","article-title":"Quantitative levels of hepatitis B Virus DNA and Surface antigen and the risk of hepatocellular carcinoma in patients with hepatitis B receiving long-term nucleos(t)ide analogue therapy","volume":"3","author":"Kawanaka","year":"2014","journal-title":"Liver Cancer"},{"key":"R13-20240913","doi-asserted-by":"crossref","first-page":"1520","DOI":"10.1002\/hep.32479","article-title":"Circulating HBV RNA: From biology to clinical applications","volume":"76","author":"Deng","year":"2022","journal-title":"Hepatology"},{"key":"R14-20240913","doi-asserted-by":"crossref","first-page":"700","DOI":"10.1016\/j.jhep.2016.05.029","article-title":"Serum hepatitis B virus RNA is encapsidated pregenome RNA that may be associated with persistence of viral infection and rebound","volume":"65","author":"Wang","year":"2016","journal-title":"J Hepatol"},{"key":"R15-20240913","doi-asserted-by":"crossref","first-page":"760","DOI":"10.1111\/apt.17105","article-title":"Review article: Novel biomarkers in hepatitis B infection","volume":"56","author":"Lok","year":"2022","journal-title":"Aliment Pharmacol Ther"},{"key":"R16-20240913","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1002\/hep.31026","article-title":"Pregenomic HBV RNA and Hepatitis B core-related antigen predict outcomes in hepatitis B e antigen-negative chronic hepatitis B patients suppressed on nucleos(T)ide Analogue Therapy","volume":"72","author":"Carey","year":"2020","journal-title":"Hepatology"},{"key":"R17-20240913","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1007\/s12072-020-10015-3","article-title":"Rapidly decreased HBV RNA predicts responses of pegylated interferons in HBeAg-positive patients: A longitudinal cohort study","volume":"14","author":"Zhang","year":"2020","journal-title":"Hepatol Int"},{"key":"R18-20240913","doi-asserted-by":"crossref","first-page":"1480","DOI":"10.1002\/hep.31850","article-title":"HBV\/Pregenomic RNA increases the stemness and promotes the development of hbv-related hcc through reciprocal regulation with insulin-like growth factor 2 mRNA-binding protein 3","volume":"74","author":"Ding","year":"2021","journal-title":"Hepatology"},{"key":"R19-20240913","doi-asserted-by":"crossref","first-page":"e1008945","DOI":"10.1371\/journal.ppat.1008945","article-title":"Biogenesis and molecular characteristics of serum hepatitis B virus RNA","volume":"16","author":"Shen","year":"2020","journal-title":"PLoS Pathog"},{"key":"R20-20240913","doi-asserted-by":"crossref","first-page":"104925","DOI":"10.1016\/j.antiviral.2020.104925","article-title":"Hepatitis B virus biology and life cycle","volume":"182","author":"Tsukuda","year":"2020","journal-title":"Antiviral Res"},{"key":"R21-20240913","doi-asserted-by":"crossref","first-page":"706","DOI":"10.1016\/j.jhep.2021.05.013","article-title":"Covalently closed circular DNA:The ultimate therapeutic target for curing HBV infections","volume":"75","author":"Martinez","year":"2021","journal-title":"J Hepatol"},{"key":"R22-20240913","doi-asserted-by":"crossref","first-page":"972","DOI":"10.1136\/gutjnl-2022-328380","article-title":"Quantification of the hepatitis B virus cccDNA:Evidence-based guidelines for monitoring the key obstacle of HBV cure","volume":"72","author":"Allweiss","year":"2023","journal-title":"Gut"},{"key":"R23-20240913","doi-asserted-by":"crossref","first-page":"e00798","DOI":"10.1128\/JVI.00798-18","article-title":"Extracellular Hepatitis B Virus RNAs Are heterogeneous in length and circulate as capsid-antibody complexes in addition to virions in chronic Hepatitis B patients","volume":"92","author":"Bai","year":"2018","journal-title":"J Virol"},{"key":"R24-20240913","doi-asserted-by":"crossref","first-page":"e01275","DOI":"10.1128\/JCM.01275-19","article-title":"Diagnostic value of detection of pregenomic RNA in sera of Hepatitis B virus-infected patients with different clinical outcomes","volume":"58","author":"Lin","year":"2020","journal-title":"J Clin Microbiol"},{"key":"R25-20240913","doi-asserted-by":"crossref","first-page":"881","DOI":"10.1093\/infdis\/jiab597","article-title":"Association of serum Hepatitis B Virus RNA with hepatocellular carcinoma risk in chronic Hepatitis B patients under nucleos (t)ide Analogues Therapy","volume":"226","author":"Liu","year":"2022","journal-title":"J Infect Dis"},{"key":"R26-20240913","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1007\/s00535-021-01780-5","article-title":"Residual HBV DNA and pgRNA viraemia is associated with hepatocellular carcinoma in chronic hepatitis B patients on antiviral therapy","volume":"56","author":"Mak","year":"2021","journal-title":"J Gastroenterol"},{"key":"R27-20240913","doi-asserted-by":"crossref","first-page":"2261","DOI":"10.3748\/wjg.v24.i21.2261","article-title":"Hepatitis B virus pathogenesis:Fresh insights into hepatitis B virus RNA","volume":"24","author":"Sekiba","year":"2018","journal-title":"World J Gastroenterol"},{"key":"R28-20240913","doi-asserted-by":"crossref","first-page":"e00680","DOI":"10.1128\/AAC.00680-17","article-title":"Hepatitis B virus capsid assembly modulators, but not nucleoside analogs, inhibit the production of extracellular pregenomic RNA and spliced RNA Variants","volume":"61","author":"Lam","year":"2017","journal-title":"Antimicrob Agents Chemother"},{"key":"R29-20240913","doi-asserted-by":"crossref","first-page":"1249","DOI":"10.1016\/j.jhep.2021.11.024","article-title":"How to achieve functional cure of HBV:Stopping NUCs, adding interferon or new drug development?","volume":"76","author":"Wong","year":"2022","journal-title":"J Hepatol"}],"container-title":["Saudi Journal of Gastroenterology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ovid.com\/10.4103\/sjg.sjg_16_24","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T13:57:20Z","timestamp":1787839040000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ovid.com\/10.4103\/sjg.sjg_16_24"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,7,24]]},"references-count":29,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2024]]}},"URL":"https:\/\/doi.org\/10.4103\/sjg.sjg_16_24","relation":{},"ISSN":["1319-3767","1998-4049"],"issn-type":[{"value":"1319-3767","type":"print"},{"value":"1998-4049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,7,24]]},"assertion":[{"value":"2024-01-12","name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-06-30","name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}}]}}