{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T16:34:30Z","timestamp":1792427670730,"version":"4.5.0"},"reference-count":102,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2022,2,21]],"date-time":"2022-02-21T00:00:00Z","timestamp":1645401600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Hepatocellular carcinoma (HCC) is the fifth most common cancer and the second leading cause of cancer-related death worldwide. Hepatitis B virus (HBV) infection is among the main risk factors for HCC. The risk of HCC is not eliminated completely after viral suppression, due to HBV DNA integrated into human chromosomes. Cirrhosis, HBV viral DNA levels, age, male gender, the immune response of the host against HBV, and a combination of obesity and diabetes are among the main risk factors for HCC. Active viral replication and long-standing active disease with inflammation are associated with a higher risk of HCC. Treatment of HBV with nucleos(t)ide analogues (NAs) decreased HCC risk by effectively decreasing viral load and inflammation. Similar risk factors have been reported in hepatitis B patients after seroclearance. Studies have reported decreased risk of HCC after seroclearance, but there were also conflicting results from a few studies indicating no difference in risk of developing HCC. The difference in HCC rates could be because of other factors such as coinfection, occult HBV infection, family history, HBV genotype, and other comorbidities. Due to the persistent risk of HCC after seroclearance, HCC surveillance is critical for early detection, especially in high-risk patients. However, long-term studies might be needed to further validate the results.<\/jats:p>","DOI":"10.3390\/jcm11041126","type":"journal-article","created":{"date-parts":[[2022,2,21]],"date-time":"2022-02-21T20:47:45Z","timestamp":1645476465000},"page":"1126","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["Hepatocellular Carcinoma in Hepatitis B Virus-Infected Patients and the Role of Hepatitis B Surface Antigen (HBsAg)"],"prefix":"10.3390","volume":"11","author":[{"given":"Satinder P.","family":"Kaur","sequence":"first","affiliation":[{"name":"Liver Center, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arslan","family":"Talat","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, University of Massachusetts, Worcester, MA 01605, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6827-9496","authenticated-orcid":false,"given":"Hamidreza","family":"Karimi-Sari","sequence":"additional","affiliation":[{"name":"Middle East Liver Diseases Center, Tehran 1598976513, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"Grees","sequence":"additional","affiliation":[{"name":"Stony Brook Southampton Hospital, Southampton, NY 11968, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao Wei","family":"Chen","sequence":"additional","affiliation":[{"name":"Liver Center, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daryl T. Y.","family":"Lau","sequence":"additional","affiliation":[{"name":"Liver Center, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreea M.","family":"Catana","sequence":"additional","affiliation":[{"name":"Liver Center, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,2,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1683","DOI":"10.1001\/jamaoncol.2017.3055","article-title":"The burden of primary liver cancer and underlying etiologies from 1990 to 2015 at the global, regional, and national level: Results from the global burden of disease study 2015","volume":"3","author":"Akinyemiju","year":"2017","journal-title":"JAMA Oncol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"16018","DOI":"10.1038\/nrdp.2016.18","article-title":"Hepatocellular carcinoma","volume":"2","author":"Llovet","year":"2016","journal-title":"Nat. Rev. Dis. Primers"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1016\/S2468-1253(16)30161-3","article-title":"Characteristics, management, and outcomes of patients with hepatocellular carcinoma in Africa: A multicountry observational study from the Africa Liver Cancer Consortium","volume":"2","author":"Yang","year":"2017","journal-title":"Lancet Gastroenterol. Hepatol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1016\/j.jhep.2016.09.013","article-title":"Hepatocellular carcinoma in the absence of cirrhosis in patients with chronic hepatitis B virus infection","volume":"66","author":"Chayanupatkul","year":"2017","journal-title":"J. Hepatol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"422","DOI":"10.1016\/S0002-9343(96)00197-0","article-title":"Cost-effectiveness of screening for detection of small hepatocellular carcinoma in western patients with Child-Pugh class A cirrhosis","volume":"101","author":"Sarasin","year":"1996","journal-title":"Am. J. Med."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1159","DOI":"10.1111\/j.1365-2036.2004.01963.x","article-title":"Cost-effectiveness of screening for hepatocellular carcinoma in patients with cirrhosis due to chronic hepatitis C","volume":"19","author":"Lin","year":"2004","journal-title":"Aliment. Pharmacol. Ther."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1001\/jama.295.1.65","article-title":"Risk of hepatocellular carcinoma across a biological gradient of serum hepatitis B virus DNA level","volume":"295","author":"Chen","year":"2006","journal-title":"JAMA"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"454","DOI":"10.1007\/s12250-017-4009-4","article-title":"Recent advances in the study of hepatitis B virus covalently closed circular DNA","volume":"32","author":"Ji","year":"2017","journal-title":"Virol. Sin."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Guo, H., Xu, C., Zhou, T., Block, T.M., and Guo, J.-T. (2012). Characterization of the host factors required for hepadnavirus covalently closed circular (ccc) DNA formation. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0043270"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"872","DOI":"10.1111\/hepr.12427","article-title":"Risk of hepatocellular carcinoma in cirrhotic hepatitis B virus patients during nucleoside\/nucleotide analog therapy","volume":"45","author":"Orito","year":"2015","journal-title":"Hepatol. Res."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1093\/infdis\/jiy391","article-title":"Reduced incidence of hepatocellular carcinoma in cirrhotic and noncirrhotic patients with chronic hepatitis B treated with Tenofovir\u2014A propensity Score\u2013Matched study","volume":"219","author":"Nguyen","year":"2019","journal-title":"J. Infect. Dis."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1136\/gut.2007.119859","article-title":"Risk for hepatocellular carcinoma with respect to hepatitis B virus genotypes B\/C, specific mutations of enhancer II\/core promoter\/precore regions and HBV DNA levels","volume":"57","author":"Yuen","year":"2008","journal-title":"Gut"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"646","DOI":"10.1093\/infdis\/jiq096","article-title":"Association of hepatitis B virus pre-S deletions with the development of hepatocellular carcinoma in chronic hepatitis B","volume":"203","author":"Yeung","year":"2011","journal-title":"J. Infect. Dis."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"718","DOI":"10.1111\/jvh.13077","article-title":"Diabetes poses a higher risk of hepatocellular carcinoma and mortality in patients with chronic hepatitis B: A population-based cohort study","volume":"26","author":"Shyu","year":"2019","journal-title":"J. Viral Hepat."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2038","DOI":"10.1158\/1055-9965.EPI-19-0303","article-title":"The influence of metabolic syndrome on the risk of hepatocellular carcinoma in patients with chronic hepatitis B infection in mainland China","volume":"28","author":"Tan","year":"2019","journal-title":"Cancer Epidemiol. Prev. Biomark."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1002\/hep.510280130","article-title":"Sero-clearance of hepatitis B surface antigen in chronic carriers does not necessarily imply a good prognosis","volume":"28","author":"Huo","year":"1998","journal-title":"Hepatology"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1097\/MCG.0b013e3181dd558c","article-title":"HBsAg seroclearance in chronic hepatitis B: Implications for hepatocellular carcinoma","volume":"45","author":"Kim","year":"2011","journal-title":"J. Clin. Gastroenterol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1092","DOI":"10.1016\/j.jhep.2014.11.031","article-title":"Incidence of hepatocellular carcinoma after HBsAg seroclearance in chronic hepatitis B patients: A need for surveillance","volume":"62","author":"Kim","year":"2015","journal-title":"J. Hepatol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"902","DOI":"10.1016\/j.jhep.2017.06.019","article-title":"Impact of age and gender on risk of hepatocellular carcinoma after hepatitis B surface antigen seroclearance","volume":"67","author":"Yip","year":"2017","journal-title":"J. Hepatol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1192","DOI":"10.1053\/j.gastro.2008.07.008","article-title":"HBsAg Seroclearance in chronic hepatitis B in Asian patients: Replicative level and risk of hepatocellular carcinoma","volume":"135","author":"Yuen","year":"2008","journal-title":"Gastroenterology"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1016\/j.jhep.2012.03.004","article-title":"Why men are at higher risk for hepatocellular carcinoma?","volume":"57","author":"Keng","year":"2012","journal-title":"J. Hepatol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1016\/j.jhep.2004.10.026","article-title":"Long-term clinical and histological outcomes in patients with spontaneous hepatitis B surface antigen seroclearance","volume":"42","author":"Ahn","year":"2005","journal-title":"J. Hepatol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"e2995","DOI":"10.1097\/MD.0000000000002995","article-title":"Hepatitis B surface antigen loss and hepatocellular carcinoma development in patients with dual hepatitis B and C infection","volume":"95","author":"Yang","year":"2016","journal-title":"Medicine"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Hu, J., Liu, K., and Luo, J. (2019). HIV\u2013HBV and HIV\u2013HCV coinfection and liver cancer development. HIV\/AIDS-Associated Viral OncoGenesis, Springer.","DOI":"10.1007\/978-3-030-03502-0_9"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"765","DOI":"10.1016\/j.cgh.2017.12.009","article-title":"Effects of diabetes and glycemic control on risk of hepatocellular carcinoma after seroclearance of hepatitis B surface antigen","volume":"16","author":"Yip","year":"2018","journal-title":"Clin. Gastroenterol. Hepatol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1053\/j.gastro.2008.03.073","article-title":"Metabolic factors and risk of hepatocellular carcinoma by chronic hepatitis B\/C infection: A follow-up study in Taiwan","volume":"135","author":"Chen","year":"2008","journal-title":"Gastroenterology"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1204","DOI":"10.1016\/j.cgh.2018.08.019","article-title":"Spontaneous seroclearance of hepatitis B surface antigen and risk of hepatocellular carcinoma","volume":"17","author":"Song","year":"2019","journal-title":"Clin. Gastroenterol. Hepatol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/S0168-8278(03)00154-5","article-title":"Interferon-\u03b1 for HBeAg-positive chronic hepatitis B","volume":"39","year":"2003","journal-title":"J. Hepatol."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Zhuang, L., Zeng, X., Yang, Z., and Meng, Z. (2013). Effect and safety of interferon for hepatocellular carcinoma: A systematic review and meta-analysis. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0061361"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1111\/j.1365-2893.2009.01070.x","article-title":"Interferon therapy in chronic hepatitis B reduces progression to cirrhosis and hepatocellular carcinoma: A meta-analysis","volume":"16","author":"Yang","year":"2009","journal-title":"J. Viral Hepat."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"804","DOI":"10.1002\/hep.20128","article-title":"Long-term follow-up of alpha-interferon treatment of patients with chronic hepatitis B","volume":"39","author":"Honkoop","year":"2004","journal-title":"Hepatology"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"470","DOI":"10.1007\/s00535-009-0024-z","article-title":"Meta-analysis: The effect of interferon on development of hepatocellular carcinoma in patients with chronic hepatitis B virus infection","volume":"44","author":"Miyake","year":"2009","journal-title":"J. Gastroenterol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/j.jhep.2006.08.021","article-title":"Interferon therapy in HBeAg positive chronic hepatitis reduces progression to cirrhosis and hepatocellular carcinoma","volume":"46","author":"Lin","year":"2007","journal-title":"J. Hepatol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1053\/jhep.2001.25273","article-title":"Long-term follow-up of interferon alfa treatment in Chinese patients with chronic hepatitis B infection: The effect on hepatitis B e antigen seroconversion and the development of cirrhosis-related complications","volume":"34","author":"Yuen","year":"2001","journal-title":"Hepatology"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1136\/bmj.306.6870.107","article-title":"Fatal hepatic decompensation associated with interferon alfa. European concerted action on viral hepatitis (Eurohep)","volume":"306","author":"Janssen","year":"1993","journal-title":"Br. Med. J."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1067","DOI":"10.1111\/j.1365-2036.2008.03816.x","article-title":"Meta-analysis: Treatment of hepatitis B infection reduces risk of hepatocellular carcinoma","volume":"28","author":"Sung","year":"2008","journal-title":"Aliment. Pharmacol. Ther."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1177\/1756283X08093944","article-title":"Current status of antiviral therapy for hepatitis B","volume":"1","author":"Lau","year":"2008","journal-title":"Ther. Adv. Gastroenterol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1295","DOI":"10.1177\/135965350701200816","article-title":"Long-term lamivudine therapy reduces the risk of long-term complications of chronic hepatitis B infection even in patients without advanced disease","volume":"12","author":"Yuen","year":"2007","journal-title":"Antivir. Ther."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1016\/j.jhep.2010.02.026","article-title":"Risk assessment for the development of hepatocellular carcinoma: According to on-treatment viral response during long-term lamivudine therapy in hepatitis B virus-related liver disease","volume":"53","author":"Eun","year":"2010","journal-title":"J. Hepatol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1111\/j.1365-2893.2004.00564.x","article-title":"High risk of hepatocellular carcinoma in anti-HBe positive liver cirrhosis patients developing lamivudine resistance","volume":"11","author":"Andreone","year":"2004","journal-title":"J. Viral Hepat."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1016\/j.jhep.2012.10.025","article-title":"Effect of nucleos (t) ide analogue therapy on hepatocarcinogenesis in chronic hepatitis B patients: A propensity score analysis","volume":"58","author":"Kumada","year":"2013","journal-title":"J. Hepatol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1002\/hep.28156","article-title":"A ASLD guidelines for treatment of chronic hepatitis B","volume":"63","author":"Terrault","year":"2016","journal-title":"Hepatology"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1053\/j.gastro.2014.03.048","article-title":"Association of nucleos (t) ide analogue therapy with reduced risk of hepatocellular carcinoma in patients with chronic hepatitis B\u2014A nationwide cohort study","volume":"147","author":"Wu","year":"2014","journal-title":"Gastroenterology"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1002\/hep.26180","article-title":"Long-term entecavir treatment reduces hepatocellular carcinoma incidence in patients with hepatitis B virus infection","volume":"58","author":"Hosaka","year":"2013","journal-title":"Hepatology"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"2154","DOI":"10.1093\/jac\/dkt147","article-title":"Virological response to entecavir reduces the risk of liver disease progression in nucleos (t) ide analogue-experienced HBV-infected patients with prior resistant mutants","volume":"68","author":"Yang","year":"2013","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1537","DOI":"10.1002\/hep.26301","article-title":"Entecavir treatment reduces hepatic events and deaths in chronic hepatitis B patients with liver cirrhosis","volume":"58","author":"Wong","year":"2013","journal-title":"Hepatology"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1444","DOI":"10.1002\/hep.29320","article-title":"The risk of hepatocellular carcinoma decreases after the first 5 years of entecavir or tenofovir in Caucasians with chronic hepatitis B","volume":"66","author":"Papatheodoridis","year":"2017","journal-title":"Hepatology"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"3631","DOI":"10.1002\/cncr.29537","article-title":"Impact of long-term tenofovir disoproxil fumarate on incidence of hepatocellular carcinoma in patients with chronic hepatitis B","volume":"121","author":"Kim","year":"2015","journal-title":"Cancer"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1001\/jamaoncol.2018.4070","article-title":"Risk of hepatocellular carcinoma in patients treated with entecavir vs tenofovir for chronic hepatitis B: A Korean nationwide cohort study","volume":"5","author":"Choi","year":"2019","journal-title":"JAMA Oncol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1002\/hep.31267","article-title":"Comparative Effectiveness of Entecavir Versus Tenofovir for Preventing Hepatocellular Carcinoma in Patients with Chronic Hepatitis B: A Systematic Review and Meta-Analysis","volume":"73","author":"Dave","year":"2021","journal-title":"Hepatology"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"456","DOI":"10.1016\/j.jhep.2019.03.028","article-title":"A multicenter study of entecavir vs. tenofovir on prognosis of treatment-na\u00efve chronic hepatitis B in South Korea","volume":"71","author":"Kim","year":"2019","journal-title":"J. Hepatol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"784","DOI":"10.1007\/s10620-017-4448-7","article-title":"Effectiveness and safety of entecavir or tenofovir in a Spanish cohort of chronic hepatitis B patients: Validation of the page-B score to predict hepatocellular carcinoma","volume":"62","author":"Tabernero","year":"2017","journal-title":"Dig. Dis. Sci."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1016\/j.jhep.2014.08.045","article-title":"Incidence and predictors of hepatocellular carcinoma in Caucasian chronic hepatitis B patients receiving entecavir or tenofovir","volume":"62","author":"Papatheodoridis","year":"2015","journal-title":"J. Hepatol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1129","DOI":"10.1016\/j.jhep.2018.01.031","article-title":"Eight-year survival in chronic hepatitis B patients under long-term entecavir or tenofovir therapy is similar to the general population","volume":"68","author":"Papatheodoridis","year":"2018","journal-title":"J. Hepatol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1037","DOI":"10.1016\/j.jhep.2020.06.011","article-title":"Similar risk of hepatocellular carcinoma during long-term entecavir or tenofovir therapy in Caucasian patients with chronic hepatitis B","volume":"73","author":"Papatheodoridis","year":"2020","journal-title":"J. Hepatol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1774","DOI":"10.1111\/jgh.15031","article-title":"Comparison of the on-treatment risks for hepatocellular carcinoma between entecavir and tenofovir: A propensity score matching analysis","volume":"35","author":"Ha","year":"2020","journal-title":"J. Gastroenterol. Hepatol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1301","DOI":"10.1136\/gutjnl-2019-318947","article-title":"Comparison of tenofovir and entecavir on the risk of hepatocellular carcinoma and mortality in treatment-na\u00efve patients with chronic hepatitis B in Korea: A large-scale, propensity score analysis","volume":"69","author":"Lee","year":"2020","journal-title":"Gut"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1289","DOI":"10.1136\/gutjnl-2014-307023","article-title":"Entecavir treatment does not eliminate the risk of hepatocellular carcinoma in chronic hepatitis B: Limited role for risk scores in Caucasians","volume":"64","author":"Arends","year":"2015","journal-title":"Gut"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1223","DOI":"10.1038\/ajg.2014.145","article-title":"Effect of virological response to entecavir on the development of hepatocellular carcinoma in hepatitis B viral cirrhotic patients: Comparison between compensated and decompensated cirrhosis","volume":"109","author":"Kim","year":"2014","journal-title":"Off. J. Am. Coll. Gastroenterol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1053\/j.gastro.2019.09.025","article-title":"Tenofovir Is Associated with Lower Risk of Hepatocellular Carcinoma Than Entecavir in Patients with Chronic HBV Infection in China","volume":"158","author":"Yip","year":"2020","journal-title":"Gastroenterology"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1053\/j.gastro.2018.10.027","article-title":"Factors associated with rates of HBsAg seroclearance in adults with chronic HBV infection: A systematic review and meta-analysis","volume":"156","author":"Yeo","year":"2019","journal-title":"Gastroenterology"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1026","DOI":"10.1111\/jvh.12905","article-title":"Systematic review of risk factors of hepatocellular carcinoma after hepatitis B surface antigen seroclearance","volume":"25","author":"Kuang","year":"2018","journal-title":"J. Viral Hepat."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1197","DOI":"10.1111\/apt.13621","article-title":"Nested case\u2013control study: Hepatocellular carcinoma risk after hepatitis B surface antigen seroclearance","volume":"43","author":"Gounder","year":"2016","journal-title":"Aliment. Pharmacol. Ther."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"2155","DOI":"10.1002\/hep.31610","article-title":"Comparison of Long-Term Clinical Outcomes Between Spontaneous and Therapy-Induced HBsAg Seroclearance","volume":"73","author":"Choi","year":"2021","journal-title":"Hepatology"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"952","DOI":"10.1016\/j.jhep.2020.05.042","article-title":"Occult hepatitis B infection and hepatocellular carcinoma: Epidemiology, virology, hepatocarcinogenesis and clinical significance","volume":"73","author":"Mak","year":"2020","journal-title":"J. Hepatol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1016\/j.cgh.2019.06.029","article-title":"Among Patients with Undetectable Hepatitis B Surface Antigen and Hepatocellular Carcinoma, a High Proportion Has Integration of HBV DNA into Hepatocyte DNA and No Cirrhosis","volume":"18","author":"Wong","year":"2020","journal-title":"Clin. Gastroenterol. Hepatol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"608","DOI":"10.1007\/s00261-021-03343-x","article-title":"Contrast-enhanced US diagnostic algorithm of hepatocellular carcinoma in patients with occult hepatitis B","volume":"47","author":"Huang","year":"2022","journal-title":"Abdom. Radiol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"73","DOI":"10.3904\/kjim.2007.22.2.73","article-title":"Clinical outcomes of delayed clearance of serum HBsAG in patients with chronic HBV infection","volume":"22","author":"Nam","year":"2007","journal-title":"Korean J. Intern. Med."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"1325","DOI":"10.1136\/gutjnl-2013-305517","article-title":"HBsAg seroclearance after nucleoside analogue therapy in patients with chronic hepatitis B: Clinical outcomes and durability","volume":"63","author":"Kim","year":"2014","journal-title":"Gut"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1311","DOI":"10.1111\/apt.13630","article-title":"Clinical outcomes after spontaneous and nucleos (t) ide analogue-treated HB sAg seroclearance in chronic HBV infection","volume":"43","author":"Chen","year":"2016","journal-title":"Aliment. Pharmacol. Ther."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1111\/liv.12461","article-title":"Long-term outcome in Caucasian patients with chronic hepatitis B virus infection after HB sAg seroclearance","volume":"35","author":"Lauret","year":"2015","journal-title":"Liver Int."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1531","DOI":"10.1002\/hep.23464","article-title":"Clearance of hepatitis B surface antigen and risk of hepatocellular carcinoma in a cohort chronically infected with hepatitis B virus","volume":"51","author":"Simonetti","year":"2010","journal-title":"Hepatology"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"829","DOI":"10.1002\/hep.24551","article-title":"Occult hepatitis B infection and HBV replicative activity in patients with cryptogenic cause of hepatocellular carcinoma","volume":"54","author":"Wong","year":"2011","journal-title":"Hepatology"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"640","DOI":"10.1016\/j.aohep.2018.12.006","article-title":"Association of HBsAg mutation patterns with hepatitis B infection outcome: Asymptomatic carriers versus HCC\/cirrhotic patients","volume":"18","author":"Hosseini","year":"2019","journal-title":"Ann. Hepatol."},{"key":"ref_75","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":"ref_76","doi-asserted-by":"crossref","first-page":"191","DOI":"10.7326\/0003-4819-118-3-199302010-00006","article-title":"The natural history of asymptomatic hepatitis B surface antigen carriers","volume":"118","author":"Meucci","year":"1993","journal-title":"Ann. Intern. Med."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"696","DOI":"10.1007\/BF02347619","article-title":"Spontaneous hepatitis B surface antigen clearance in a long-term follow-up study of patients with chronic type B hepatitis. Lack of correlation with hepatitis C and D virus superinfection","volume":"31","author":"Madruga","year":"1996","journal-title":"J. Gastroenterol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"759","DOI":"10.7326\/0003-4819-135-9-200111060-00006","article-title":"Serologic and clinical outcomes of 1536 Alaska Natives chronically infected with hepatitis B virus","volume":"135","author":"McMahon","year":"2001","journal-title":"Ann. Intern. Med."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"1084","DOI":"10.1053\/gast.2002.36026","article-title":"Prognosis following spontaneous HBsAg seroclearance in chronic hepatitis B patients with or without concurrent infection","volume":"123","author":"Chen","year":"2002","journal-title":"Gastroenterology"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"1694","DOI":"10.1002\/hep.20240","article-title":"HBsAg seroclearance in chronic hepatitis B in the Chinese: Virological, histological, and clinical aspects","volume":"39","author":"Yuen","year":"2004","journal-title":"Hepatology"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"1019","DOI":"10.1093\/jnci\/djp146","article-title":"Hepatitis B virus infection and hepatocellular carcinoma among parous Taiwanese women: Nationwide cohort study","volume":"101","author":"Fwu","year":"2009","journal-title":"J. Natl. Cancer Inst."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"966","DOI":"10.1136\/gutjnl-2013-306247","article-title":"Serological and clinical outcomes of horizontally transmitted chronic hepatitis B infection in New Zealand M\u0101ori: Results from a 28-year follow-up study","volume":"64","author":"Lim","year":"2015","journal-title":"Gut"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"1648","DOI":"10.1136\/gutjnl-2013-305785","article-title":"Spontaneous seroclearance of hepatitis B seromarkers and subsequent risk of hepatocellular carcinoma","volume":"63","author":"Liu","year":"2014","journal-title":"Gut"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"762","DOI":"10.1016\/S1665-2681(19)30978-0","article-title":"Factors associated with spontaneous HBsAg clearance in chronic hepatitis B patients followed at a university hospital","volume":"13","author":"Ferreira","year":"2014","journal-title":"Ann. Hepatol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"e17537","DOI":"10.5812\/hepatmon.17537","article-title":"Prognostic values of fluctuations in serum levels of alanine transaminase in inactive carrier state of HBV infection","volume":"14","author":"Farzi","year":"2014","journal-title":"Hepat. Mon."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"949","DOI":"10.1111\/apt.13170","article-title":"Higher lifetime chance of spontaneous surface antigen loss in hepatitis B carriers with genotype C infection","volume":"41","author":"Tseng","year":"2015","journal-title":"Aliment. Pharmacol. Ther."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"9836","DOI":"10.3748\/wjg.v22.i44.9836","article-title":"Clinical features of HBsAg seroclearance in hepatitis B virus carriers in South Korea: A retrospective longitudinal study","volume":"22","author":"Park","year":"2016","journal-title":"World J. Gastroenterol."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"48","DOI":"10.3906\/sag-1411-156","article-title":"A persistently low HBV DNA level is a predictor of spontaneous HBsAg clearance in patients with chronic hepatitis B","volume":"46","author":"Ari","year":"2016","journal-title":"Turk. J. Med. Sci."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"390","DOI":"10.1111\/apt.13709","article-title":"Ethnic differences in incidence of hepatitis B surface antigen seroclearance in a real-life multicenter clinical cohort of 4737 patients with chronic hepatitis B infection","volume":"44","author":"Nguyen","year":"2016","journal-title":"Aliment. Pharmacol. Ther."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"896","DOI":"10.1111\/j.1572-0241.1998.00272.x","article-title":"Delayed clearance of serum HBsAg in compensated cirrhosis B: Relation to interferon alpha therapy and disease prognosis","volume":"93","author":"Fattovich","year":"1998","journal-title":"Am. J. Gastroenterol."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"71.e9-16","DOI":"10.1016\/j.amjmed.2005.02.033","article-title":"Long-term outcome after hepatitis B surface antigen seroclearance in patients with chronic hepatitis B","volume":"119","author":"Arase","year":"2006","journal-title":"Am. J. Med."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"889","DOI":"10.1016\/j.cgh.2009.04.012","article-title":"Development of hepatocellular carcinoma after seroclearance of hepatitis B surface antigen","volume":"7","author":"Tong","year":"2009","journal-title":"Clin. Gastroenterol. Hepatol."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"1084","DOI":"10.1016\/j.jhep.2009.01.016","article-title":"High rates of HBsAg seroconversion in HBeAg-positive chronic hepatitis B patients responding to interferon: A long-term follow-up study","volume":"50","author":"Moucari","year":"2009","journal-title":"J. Hepatol."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1111\/j.1365-2893.2011.01542.x","article-title":"Hepatitis B surface antigen seroconversion is associated with favourable long-term clinical outcomes during lamivudine treatment in HBeAg-negative chronic hepatitis B patients","volume":"19","author":"Idilman","year":"2012","journal-title":"J. Viral Hepat."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"814","DOI":"10.1007\/s00535-012-0548-5","article-title":"Long-term efficacy of interferon therapy in patients with chronic hepatitis B virus infection in Japan","volume":"47","author":"Suzuki","year":"2012","journal-title":"J. Gastroenterol."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"1943","DOI":"10.1136\/gutjnl-2013-306409","article-title":"Patients with chronic hepatitis B treated with oral antiviral therapy retain a higher risk for HCC compared with patients with inactive stage disease","volume":"63","author":"Cho","year":"2014","journal-title":"Gut"},{"key":"ref_97","first-page":"E89","article-title":"Hepatic flares promote rapid decline of serum hepatitis B surface antigen (HBsAg) in patients with HBsAg seroclearance: A long-term follow-up study","volume":"46","author":"Nagaoka","year":"2016","journal-title":"Hepatol. Res."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"1107","DOI":"10.1111\/jvh.12738","article-title":"HB sAg loss after peginterferon-nucleotide combination treatment in chronic hepatitis B patients: 5 years of follow-up","volume":"24","author":"Stelma","year":"2017","journal-title":"J. Viral Hepat."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"680","DOI":"10.1093\/cid\/cix353","article-title":"Durability of response after hepatitis B surface antigen seroclearance during nucleos (t) ide analogue treatment in a multiethnic cohort of chronic hepatitis B patients: Results after treatment cessation","volume":"65","author":"Chi","year":"2017","journal-title":"Clin. Infect. Dis."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"700","DOI":"10.1016\/j.cgh.2019.07.018","article-title":"Durability of spontaneous and treatment-related loss of hepatitis B s antigen","volume":"18","author":"Alawad","year":"2020","journal-title":"Clin. Gastroenterol. Hepatol."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1111\/jvh.13151","article-title":"Predictors of sustained functional cure in hepatitis B envelope antigen-negative patients achieving hepatitis B surface antigen seroclearance with interferon-alpha\u2013based therapy","volume":"26","author":"Li","year":"2019","journal-title":"J. Viral Hepat."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"514","DOI":"10.1016\/j.cgh.2019.04.020","article-title":"Durability of interferon-induced hepatitis B surface antigen seroclearance","volume":"18","author":"Wu","year":"2020","journal-title":"Clin. Gastroenterol. Hepatol."}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/11\/4\/1126\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T22:23:46Z","timestamp":1760135026000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/11\/4\/1126"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,2,21]]},"references-count":102,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2022,2]]}},"alternative-id":["jcm11041126"],"URL":"https:\/\/doi.org\/10.3390\/jcm11041126","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,2,21]]}}}