{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T06:19:48Z","timestamp":1790489988703,"version":"4.1.0"},"reference-count":62,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2020,7,28]],"date-time":"2020-07-28T00:00:00Z","timestamp":1595894400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Hepatitis B virus (HBV) infection and its related liver diseases are important health problems worldwide, particularly in the Asia-Pacific region. For the past 4\u20135 decades, Taiwan\u2019s government and scientists have cooperated together to control this virus infection and its related liver diseases. These efforts and achievements have made progress toward the elimination of HBV. Taiwan\u2019s government initiated the Viral Hepatitis Control Program (VHCP) in the1970s, and then launched the national vaccination program in 1984. This universal vaccination program effectively decreased the rate of hepatitis B carriage and the development of hepatocellular carcinoma (HCC) in the younger generation. Since 2003, approved anti-HBV treatments were reimbursed nationwide. This reimbursement program resulted in a higher uptake of anti-HBV treatments, which contributed to a decrease in liver-related disease progression and subsequently reduced attributable mortality in Taiwan. This experience can be shared by countries in other parts of the world regarding the control of chronic viral hepatitis B.<\/jats:p>","DOI":"10.3390\/v12080815","type":"journal-article","created":{"date-parts":[[2020,7,28]],"date-time":"2020-07-28T10:16:49Z","timestamp":1595931409000},"page":"815","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":52,"title":["Elimination of Hepatitis B in Highly Endemic Settings: Lessons Learned in Taiwan and Challenges Ahead"],"prefix":"10.3390","volume":"12","author":[{"given":"Chun-Jen","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, National Taiwan University Hospital, Taipei 10002, Taiwan"},{"name":"Hepatitis Research Center, National Taiwan University Hospital, Taipei 10002, Taiwan"},{"name":"Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei 10002, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pei-Jer","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, National Taiwan University Hospital, Taipei 10002, Taiwan"},{"name":"Hepatitis Research Center, National Taiwan University Hospital, Taipei 10002, Taiwan"},{"name":"Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei 10002, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,7,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1126\/science.325649","article-title":"Australia antigen and the biology of hepatitis B","volume":"197","author":"Blumberg","year":"1977","journal-title":"Science"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1001\/jama.1965.03080070025007","article-title":"A \u2018\u2018new\u2019\u2019 antigen in leukemic sera","volume":"191","author":"Blumberg","year":"1965","journal-title":"JAMA"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1002\/hep.24500","article-title":"Fighting against viral hepatitis: Lessons from Taiwan","volume":"54","author":"Chen","year":"2011","journal-title":"Hepatology"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1036","DOI":"10.1007\/BF02233264","article-title":"Clinical study on primary carcinoma of the liver in Taiwan","volume":"12","author":"Sung","year":"1967","journal-title":"Am. J. Dig. Dis."},{"key":"ref_5","first-page":"697","article-title":"Hepatitis-associated antigen and antibody in Taiwan","volume":"70","author":"Shih","year":"1971","journal-title":"J. Formos. Med. Assoc."},{"key":"ref_6","first-page":"505","article-title":"Hepatitis-associated antigen in hepatocellular carcinoma in Taiwan","volume":"71","author":"Sung","year":"1972","journal-title":"J. Formos. Med. Assoc."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"687","DOI":"10.7326\/0003-4819-75-5-687","article-title":"Hepatitis-associated antigen and hepatocellular carcinoma in Taiwan","volume":"75","author":"Tong","year":"1971","journal-title":"Ann. Intern. Med."},{"key":"ref_8","first-page":"908","article-title":"A seroepidemiologic survey of hepatitis B virus infection in Taiwan","volume":"77","author":"Chen","year":"1978","journal-title":"J. Formos. Med. Assoc."},{"key":"ref_9","first-page":"423","article-title":"Hepatitis B virus infection and chronic liver disease in Taiwan","volume":"25","author":"Chen","year":"1978","journal-title":"Acta Hepatogastroenterol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"321","DOI":"10.3109\/00365528009181477","article-title":"Maternal transmission of hepatitis B surface antigen in patients with hepatocellular carcinoma in Taiwan","volume":"15","author":"Sung","year":"1980","journal-title":"Scand. J. Gastroenterol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1129","DOI":"10.1016\/S0140-6736(81)90585-7","article-title":"Hepatocellular carcinoma and hepatitis B virus. A prospective study of 22,707 men in Taiwan","volume":"2","author":"Beasley","year":"1981","journal-title":"Lancet"},{"key":"ref_12","first-page":"65","article-title":"Combined passive and active immunization for interruption of perinatal transmission of hepatitis B virus in Taiwan","volume":"32","author":"Lo","year":"1985","journal-title":"Hepatogastroenterology"},{"key":"ref_13","unstructured":"Hsu, H.M. (1989). Hepatitis B control and its implementation, Epidemiology of Hepatitis B and Implementation of Immunoprophylaxis in Taiwan, (In Chinese)."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2597","DOI":"10.1001\/jama.1987.03390190075023","article-title":"A mass vaccination program in Taiwan against hepatitis B virus infection in infants of hepatitis B surface antigen carrier-mothers","volume":"257","author":"Chen","year":"1987","journal-title":"JAMA"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2231","DOI":"10.1001\/jama.1988.03410150079034","article-title":"Efficacy of a mass hepatitis B vaccination program in Taiwan. Studies on 3464 infants of hepatitis B surface antigen-carrier mothers","volume":"260","author":"Hsu","year":"1988","journal-title":"JAMA"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1002\/jmv.1890180402","article-title":"Base-line seroepidemiology of hepatitis B virus infection in children in Taipei, 1984: A study just before mass hepatitis B vaccination program in Taiwan","volume":"18","author":"Hsu","year":"1986","journal-title":"J. Med. Virol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1002\/jmv.1890340205","article-title":"Seroprevalence of hepatitis B virus infection in children in Taiwan, 1989: Five years after a mass hepatitis B vaccination program","volume":"34","author":"Tsen","year":"1991","journal-title":"J. Med. Virol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"906","DOI":"10.1001\/jama.1996.03540110060032","article-title":"Seroepidemiology of hepatitis B virus infection in children: Ten years of mass vaccination in Taiwan","volume":"276","author":"Chen","year":"1996","journal-title":"JAMA"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"796","DOI":"10.7326\/0003-4819-135-9-200111060-00009","article-title":"Hepatitis B virus infection in children and adolescents in a hyperendemic area: 15 years after mass hepatitis B vaccination","volume":"135","author":"Ni","year":"2001","journal-title":"Ann. Intern. Med."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1287","DOI":"10.1053\/j.gastro.2007.02.055","article-title":"Two decades of universal hepatitis B vaccination in Taiwan: Impact and implication for future strategies","volume":"132","author":"Ni","year":"2007","journal-title":"Gastroenterology"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1324","DOI":"10.1016\/j.cgh.2016.04.030","article-title":"Continuing decrease in hepatitis B virus infection 30 years after initiation of infant vaccination program in Taiwan","volume":"14","author":"Ni","year":"2016","journal-title":"Clin. Gastroenterol. Hepatol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1855","DOI":"10.1056\/NEJM199706263362602","article-title":"Universal hepatitis B vaccination in Taiwan and the incidence of hepatocellular carcinoma in children","volume":"336","author":"Chang","year":"1997","journal-title":"N. Engl. J. Med."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1348","DOI":"10.1093\/jnci\/djp288","article-title":"Decreased incidence of hepatocellular carcinoma in hepatitis B vacinees: A 20-year follow-up study","volume":"101","author":"Chang","year":"2009","journal-title":"J. Natl. Cancer Inst."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1928","DOI":"10.1056\/NEJMoa061760","article-title":"Quadrivalent vaccine against human papillomavirus to prevent anogenital diseases","volume":"356","author":"Garland","year":"2007","journal-title":"N. Engl. J. Med."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1111\/j.1440-1746.2009.06165.x","article-title":"Toward elimination and eradication of hepatitis B","volume":"25","author":"Chen","year":"2010","journal-title":"J. Gastroenterol. Hepatol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"771","DOI":"10.1056\/NEJM197504102921503","article-title":"Vertical transmission of hepatitis B antigen in Taiwan","volume":"292","author":"Stevens","year":"1975","journal-title":"N. Engl. J. Med."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1099","DOI":"10.1016\/S0140-6736(83)90624-4","article-title":"Prevention of perinatally transmitted hepatitis B virus infection with hepatitis B immune globulin and hepatitis B vaccine","volume":"2","author":"Beasley","year":"1983","journal-title":"Lancet"},{"key":"ref_28","unstructured":"(2020, July 17). Available online: https:\/\/www.mohw.gov.tw\/dl-48435-4f5e5141-5b04-4e49-8f96-0642ec0771c9.html."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1067\/mpd.2001.116277","article-title":"Universal hepatitis B vaccination and the decreased mortality from fulminant hepatitis in Taiwan","volume":"139","author":"Kao","year":"2001","journal-title":"J. Pediatr."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1002\/hep.20006","article-title":"Pediatric fulminant hepatic failure in endemic areas of hepatitis B infection: 15 years after universal hepatitis B vaccination","volume":"39","author":"Chen","year":"2004","journal-title":"Hepatology"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1126\/science.8211155","article-title":"From hepatitis to hepatoma: Lessons from type B viral hepatitis","volume":"262","author":"Chen","year":"1993","journal-title":"Science"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"260","DOI":"10.1016\/S0168-8278(87)80030-2","article-title":"Childhood hepatocellular carcinoma develops exclusively in hepatitis B surface antigen carriers in three decades in Taiwan. Report of 51 cases associated with rapid development of liver cirrhosis","volume":"5","author":"Hsu","year":"1987","journal-title":"J. Hepatol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"472","DOI":"10.1053\/j.gastro.2016.05.048","article-title":"Long-term effects of hepatitis B immunization of infants in preventing liver cancer","volume":"151","author":"Chang","year":"2016","journal-title":"Gastroenterology"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"805","DOI":"10.1016\/j.jhep.2009.01.002","article-title":"Hepatitis B vaccination: The key towards elimination and eradication of hepatitis B","volume":"50","author":"Chen","year":"2009","journal-title":"J. Hepatol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"974","DOI":"10.1001\/jama.2013.276701","article-title":"Thirty-year outcomes of the national hepatitis B immunization program in Taiwan","volume":"310","author":"Chiang","year":"2013","journal-title":"JAMA"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1056\/NEJMoa013215","article-title":"Hepatitis B e antigen and the risk of hepatocellular carcinoma","volume":"347","author":"Yang","year":"2002","journal-title":"N. Engl. J. Med."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1093\/jnci\/dji043","article-title":"Hepatitis B virus genotype and DNA level and hepatocellular carcinoma: A prospective study in men","volume":"97","author":"Yu","year":"2005","journal-title":"J. Natl. Cancer Inst."},{"key":"ref_38","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_39","doi-asserted-by":"crossref","first-page":"594","DOI":"10.1086\/505883","article-title":"Role of hepatitis B virus precore\/core promoter mutations and serum viral load on non-cirrhotic hepatocellular carcinoma: A case-control study","volume":"194","author":"Liu","year":"2006","journal-title":"J. Infect. Dis."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"678","DOI":"10.1053\/j.gastro.2005.11.016","article-title":"Predicting cirrhosis risk based on the level of circulating hepatitis B viral load","volume":"130","author":"Iloeje","year":"2006","journal-title":"Gastroenterology"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1007\/s12072-015-9675-4","article-title":"Asian-Pacific clinical practice guidelines on the management of hepatitis B: A 2015 update","volume":"10","author":"Sarin","year":"2016","journal-title":"Hepatol. Int."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1016\/j.jfma.2018.11.008","article-title":"Taiwan consensus statement on the management of chronic hepatitis B","volume":"118","author":"Chien","year":"2019","journal-title":"J. Formos. Med. Assoc."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"742","DOI":"10.1002\/hep.21100","article-title":"Interferon a-2b with and without ribavirin in the treatment of hepatitis B e antigen-positive chronic hepatitis B: A randomized study","volume":"43","author":"Liu","year":"2006","journal-title":"Hepatology"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1521","DOI":"10.1056\/NEJMoa033364","article-title":"Lamivudine for patients with chronic hepatitis B and advanced cirrhosis","volume":"351","author":"Liaw","year":"2004","journal-title":"N. Engl. J. Med"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1001","DOI":"10.1056\/NEJMoa051285","article-title":"A comparison of entecavir and lamivudine for HBeAg-positive chronic hepatitis B","volume":"354","author":"Chang","year":"2006","journal-title":"N. Engl. J. Med."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1002\/hep.23952","article-title":"Tenofovir disoproxil fumarate (TDF), emtricitabine\/TDF, and entecavir in patients with decompensated chronic hepatitis B liver disease","volume":"53","author":"Liaw","year":"2011","journal-title":"Hepatology"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1755","DOI":"10.1111\/liv.13253","article-title":"Four-year entecavir therapy reduces hepatocellular carcinoma, cirrhotic events and mortality in chronic hepatitis B patients","volume":"36","author":"Su","year":"2016","journal-title":"Liver Int."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1154","DOI":"10.1002\/hep.27630","article-title":"Significant reduction in end-stage liver diseases burden through the national viral hepatitis therapy program in Taiwan","volume":"61","author":"Chiang","year":"2015","journal-title":"Hepatology"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1946","DOI":"10.1002\/ijc.22045","article-title":"Secular trends and geographic variations of hepatitis B virus and hepatitis C virus-associated hepatocellular carcinoma in Taiwan","volume":"119","author":"Lu","year":"2006","journal-title":"Int. J. Cancer"},{"key":"ref_50","unstructured":"(2020, July 17). Available online: www.who.int\/hepatitis\/publications\/hep-elimination-by-2030."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"648","DOI":"10.1097\/MPG.0000000000002483","article-title":"Survey of impediments to prevention of mother-to-infant transmission of hepatitis B virus by international societies","volume":"69","author":"Chang","year":"2019","journal-title":"J. Pediatr. Gastroenterol. Nutr."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1016\/j.jpeds.2018.08.017","article-title":"Hepatitis B virus infection and the progress toward its elimination","volume":"205","author":"Hsu","year":"2019","journal-title":"J. Pediatr."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1002\/hep.27048","article-title":"Incomplete hepatitis B immunization, maternal carrier status, and increased risk of liver diseases: A 20-year cohort study of 3.8 million vaccinees","volume":"60","author":"Chien","year":"2014","journal-title":"Hepatology"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1016\/j.jhep.2013.02.015","article-title":"Mother-to-infant transmission of hepatitis B virus infection: Significance of maternal viral load and strategies for intervention","volume":"59","author":"Wen","year":"2013","journal-title":"J. Hepatol."},{"key":"ref_55","first-page":"CD003510","article-title":"Antivirals for reducing the risk of mother-to-child transmission of HIV infection","volume":"7","author":"Volmink","year":"2007","journal-title":"Cochrance Database Syst. Rev."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1111\/j.1365-2893.2008.01067.x","article-title":"Role of antiviral therapy in the prevention of perinatal transmission of hepatitis B virus infection","volume":"16","author":"Chotiyaputta","year":"2009","journal-title":"J. Viral Hepat."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"2324","DOI":"10.1056\/NEJMoa1508660","article-title":"Tenofovir to prevent hepatitis B transmission in mothers with high viral load","volume":"374","author":"Pan","year":"2016","journal-title":"N. Engl. J. Med."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1002\/hep.27837","article-title":"Efficacy of maternal tenofovir disoproxil fumarate in interrupting mother-to-infant transmission of hepatitis B virus","volume":"62","author":"Chen","year":"2015","journal-title":"Hepatology"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"911","DOI":"10.1056\/NEJMoa1708131","article-title":"Tenofovir versus placebo to prevent perinatal transmission of hepatitis B","volume":"378","author":"Jourdain","year":"2018","journal-title":"N. Engl. J. Med."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1016\/j.gtc.2020.01.003","article-title":"Hepatitis B: Current status of therapy and future therapies","volume":"49","author":"Spyrou","year":"2020","journal-title":"Gastroenterol. Clin. N. Am."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1146\/annurev-pathol-011110-130246","article-title":"Pathogenesis of liver fibrosis","volume":"6","author":"Friedman","year":"2011","journal-title":"Annu. Rev. Pathol."},{"key":"ref_62","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"}],"container-title":["Viruses"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4915\/12\/8\/815\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T09:52:22Z","timestamp":1760176342000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4915\/12\/8\/815"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,7,28]]},"references-count":62,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2020,8]]}},"alternative-id":["v12080815"],"URL":"https:\/\/doi.org\/10.3390\/v12080815","relation":{},"ISSN":["1999-4915"],"issn-type":[{"value":"1999-4915","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,7,28]]}}}