{"corpus_id":35926507,"paper_sha":"acea432fbb2e29937b24a81e6e3fb19ae86c69be","doi":"10.1056/NEJM199807093390201","arxiv_id":null,"pmid":9654535,"pmcid":null,"mag_id":2338794667,"dblp_id":null,"acl_id":null,"title":"A one-year trial of lamivudine for chronic hepatitis B. Asia Hepatitis Lamivudine Study Group.","year":1998,"publication_date":"1998-07-09","venue":"New England Journal of Medicine","journal":{"name":"The New England journal of medicine","pages":"\n          61-8\n        ","volume":"339 2"},"journal_issn":null,"journal_title":null,"publication_types":["JournalArticle","ClinicalTrial"],"pubmed_pub_types":["Clinical Trial","Journal Article","Randomized Controlled Trial","Research Support, Non-U.S. Gov't"],"s2_fields_of_study":["Medicine"],"reference_count":30,"citation_count":1570,"influential_citation_count":25,"is_open_access":true,"arxiv_categories":null,"arxiv_license":null,"arxiv_journal_ref":null,"mesh_headings":[{"d":"Adolescent","mj":false,"ui":"D000293"},{"d":"Adult","mj":false,"ui":"D000328"},{"d":"Aged","mj":false,"ui":"D000368"},{"d":"Alanine Transaminase","mj":false,"qs":[{"q":"blood","mj":false,"ui":"Q000097"}],"ui":"D000410"},{"d":"DNA, Viral","mj":false,"qs":[{"q":"blood","mj":false,"ui":"Q000097"}],"ui":"D004279"},{"d":"Double-Blind Method","mj":false,"ui":"D004311"},{"d":"Drug Administration Schedule","mj":false,"ui":"D004334"},{"d":"Female","mj":false,"ui":"D005260"},{"d":"Hepatitis B e Antigens","mj":false,"qs":[{"q":"blood","mj":false,"ui":"Q000097"}],"ui":"D006513"},{"d":"Hepatitis B virus","mj":false,"qs":[{"q":"genetics","mj":false,"ui":"Q000235"},{"q":"isolation & purification","mj":false,"ui":"Q000302"}],"ui":"D006515"},{"d":"Hepatitis B, Chronic","mj":false,"qs":[{"q":"drug therapy","mj":true,"ui":"Q000188"},{"q":"pathology","mj":false,"ui":"Q000473"},{"q":"virology","mj":false,"ui":"Q000821"}],"ui":"D019694"},{"d":"Humans","mj":false,"ui":"D006801"},{"d":"Lamivudine","mj":false,"qs":[{"q":"adverse effects","mj":false,"ui":"Q000009"},{"q":"therapeutic use","mj":true,"ui":"Q000627"}],"ui":"D019259"},{"d":"Liver","mj":false,"qs":[{"q":"pathology","mj":false,"ui":"Q000473"}],"ui":"D008099"},{"d":"Liver Cirrhosis","mj":false,"qs":[{"q":"drug therapy","mj":false,"ui":"Q000188"},{"q":"pathology","mj":false,"ui":"Q000473"}],"ui":"D008103"},{"d":"Male","mj":false,"ui":"D008297"},{"d":"Middle Aged","mj":false,"ui":"D008875"},{"d":"Mutation","mj":false,"ui":"D009154"},{"d":"Reverse Transcriptase Inhibitors","mj":false,"qs":[{"q":"adverse effects","mj":false,"ui":"Q000009"},{"q":"therapeutic use","mj":true,"ui":"Q000627"}],"ui":"D018894"}],"chemicals":[{"n":"DNA, Viral","ui":"D004279","reg":"0"},{"n":"Hepatitis B e Antigens","ui":"D006513","reg":"0"},{"n":"Reverse Transcriptase Inhibitors","ui":"D018894","reg":"0"},{"n":"Lamivudine","ui":"D019259","reg":"2T8Q726O95"},{"n":"Alanine Transaminase","ui":"D000410","reg":"EC 2.6.1.2"}],"comments_corrections":null,"source_flags":5,"s2_open_access_pdf_url":"https://www.nejm.org/doi/pdf/10.1056/NEJM199807093390201?articleTools=true","s2_open_access_landing_url":"https://www.semanticscholar.org/paper/acea432fbb2e29937b24a81e6e3fb19ae86c69be","s2_open_access_license":null,"s2_open_access_status":"BRONZE","pmc_open_access_pdf_url":null,"pmc_open_access_landing_url":null,"pmc_open_access_license":null,"pmc_open_access_status":null,"unpaywall_open_access_pdf_url":null,"unpaywall_open_access_landing_url":null,"unpaywall_open_access_license":null,"unpaywall_open_access_status":null,"abstract":"BACKGROUND AND METHODS: In preliminary trials, lamivudine, an oral nucleoside analogue, has shown promise for the treatment of chronic hepatitis B. We conducted a one-year, double-blind trial of lamivudine in 358 Chinese patients with chronic hepatitis B. The patients were randomly assigned to receive 25 mg of lamivudine (142 patients), 100 mg of lamivudine (143), or placebo (73) orally once daily. The patients underwent liver biopsies before entering the study and after completing the assigned treatment regimen. The primary end point was a reduction of at least two points in the Knodell necroinflammatory score. RESULTS: Hepatic necroinflammatory activity improved by two points or more in 56 percent of the patients receiving 100 mg of lamivudine, 49 percent of those receiving 25 mg of lamivudine, and 25 percent of those receiving placebo (P<0.001 and P=0.001, respectively, for the comparisons of lamivudine treatment with placebo). Necroinflammatory activity worsened in 7 percent of the patients receiving 100 mg of lamivudine, 8 percent of those receiving 25 mg, and 26 percent of those receiving placebo. The 100-mg dose of lamivudine was associated with a reduced progression of fibrosis (P=0.01 for the comparison with placebo) and with the highest rate of hepatitis B e antigen (HBeAg) seroconversion (loss of HBeAg, development of antibody to HBeAg, and undetectable HBV DNA) (16 percent), the greatest suppression of HBV DNA (98 percent reduction at week 52 as compared with the base-line value), and the highest rate of sustained normalization of alanine aminotransferase levels (72 percent). Ninety-six percent of the patients completed the study. The incidence of adverse events was similar in all groups, and there were few serious events. CONCLUSIONS: In a one-year study, lamivudine was associated with substantial histologic improvement in many patients with chronic hepatitis B. A daily dose of 100 mg was more effective than a daily dose of 25 mg.","claims":[{"public_id":"cl_472f4d210c4c3db2802ee3b8bf08cf14","status":"active","text":"A reduction of at least two points in the Knodell necroinflammatory score occurred in 56% of patients receiving 100 mg lamivudine, 49% receiving 25 mg, and 25% receiving placebo.","confidence":0.99,"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/claims/cl_472f4d210c4c3db2802ee3b8bf08cf14"},{"public_id":"cl_d77c0095b5f07487b3c0d4ce330968d0","status":"active","text":"Adverse events were similar across treatment groups, with few serious events.","confidence":0.95,"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/claims/cl_d77c0095b5f07487b3c0d4ce330968d0"},{"public_id":"cl_9a14f48c16fa4a3a5c39ff232222ab5a","status":"active","text":"Lamivudine produced substantial histologic improvement in many patients with chronic hepatitis B over one year.","confidence":0.98,"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/claims/cl_9a14f48c16fa4a3a5c39ff232222ab5a"},{"public_id":"cl_352809ee672af558cd4f030d611e2127","status":"active","text":"The 100 mg daily dose was more effective than the 25 mg daily dose.","confidence":0.97,"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/claims/cl_352809ee672af558cd4f030d611e2127"},{"public_id":"cl_e105139d57fd54d4c6ab9c9b3a26720f","status":"active","text":"The 100 mg dose was associated with reduced progression of fibrosis, the highest rate of HBeAg seroconversion, the greatest suppression of HBV DNA, and the highest rate of sustained normalization of alanine aminotransferase levels.","confidence":0.98,"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/claims/cl_e105139d57fd54d4c6ab9c9b3a26720f"}],"concepts":[{"public_id":"co_005d545da623ea5e895eb82dda176ae9","status":"active","name":"alanine aminotransferase levels","description":"Blood enzyme levels used as a marker of liver inflammation and injury.","types":["biomarker"],"aliases":["ALT levels"],"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/concepts/co_005d545da623ea5e895eb82dda176ae9"},{"public_id":"co_0381ac05a061bb6764a0fadbb8a7ca5b","status":"active","name":"Knodell necroinflammatory score","description":"A liver histology scoring system used to quantify necroinflammatory activity.","types":["score"],"aliases":[],"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/concepts/co_0381ac05a061bb6764a0fadbb8a7ca5b"},{"public_id":"co_0f5ae924b7450655fcfda168be5f83b8","status":"active","name":"adverse events","description":"Unwanted medical events occurring during treatment.","types":["safety outcome"],"aliases":[],"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/concepts/co_0f5ae924b7450655fcfda168be5f83b8"},{"public_id":"co_15085991a5d51d997710836273e3abc2","status":"active","name":"HBeAg seroconversion","description":"Loss of hepatitis B e antigen with development of antibody to HBeAg and undetectable HBV DNA.","types":["outcome"],"aliases":["hepatitis B e antigen seroconversion"],"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/concepts/co_15085991a5d51d997710836273e3abc2"},{"public_id":"co_1542c7c267fd5e3b2d6bacd3950700b8","status":"active","name":"histologic improvement","description":"A favorable change in liver biopsy findings used to assess treatment effect.","types":["outcome"],"aliases":[],"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/concepts/co_1542c7c267fd5e3b2d6bacd3950700b8"},{"public_id":"co_352ace11cc877b13e5a3c2741a5c3d0a","status":"active","name":"placebo","description":"An inactive control treatment used for comparison in the trial.","types":["control"],"aliases":[],"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/concepts/co_352ace11cc877b13e5a3c2741a5c3d0a"},{"public_id":"co_42a1b6fe711d2785d522dada5b03a9e9","status":"active","name":"25 mg daily dose","description":"The once-daily lamivudine regimen using 25 milligrams.","types":["dose"],"aliases":[],"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/concepts/co_42a1b6fe711d2785d522dada5b03a9e9"},{"public_id":"co_58a138534cbf2d01d287478742081252","status":"active","name":"HBV DNA","description":"Hepatitis B virus DNA measured as a marker of viral replication.","types":["biomarker"],"aliases":["hepatitis B virus DNA"],"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/concepts/co_58a138534cbf2d01d287478742081252"},{"public_id":"co_60420728e0bde9b69f6c770d77eafa92","status":"active","name":"chronic hepatitis B","description":"A persistent hepatitis B virus infection affecting the liver.","types":["disease"],"aliases":["CHB"],"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/concepts/co_60420728e0bde9b69f6c770d77eafa92"},{"public_id":"co_b87617beade29d4fca97a28c5b7c9ce8","status":"active","name":"lamivudine","description":"An oral nucleoside analogue evaluated as a treatment for chronic hepatitis B.","types":["drug"],"aliases":[],"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/concepts/co_b87617beade29d4fca97a28c5b7c9ce8"},{"public_id":"co_cb4b5f5b7dbbef7bf2950cb3eeeefa1c","status":"active","name":"100 mg daily dose","description":"The once-daily lamivudine regimen using 100 milligrams.","types":["dose"],"aliases":[],"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/concepts/co_cb4b5f5b7dbbef7bf2950cb3eeeefa1c"},{"public_id":"co_e9d05b14460da179550f4e933107d554","status":"active","name":"fibrosis progression","description":"Advancement of liver fibrosis measured as a treatment outcome.","types":["outcome"],"aliases":[],"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/concepts/co_e9d05b14460da179550f4e933107d554"}],"external_ids":{"DOI":"10.1056/NEJM199807093390201","ArXiv":null,"PubMed":9654535,"PubMedCentral":null,"MAG":2338794667,"DBLP":null,"ACL":null},"open_access":{"is_open_access":true,"pdf_url":"https://www.nejm.org/doi/pdf/10.1056/NEJM199807093390201?articleTools=true","landing_url":"https://www.semanticscholar.org/paper/acea432fbb2e29937b24a81e6e3fb19ae86c69be","source":"semantic_scholar","pdf_url_source":"semantic_scholar_open_access_pdf","license":null,"status":"BRONZE","reason":null},"reference_availability":{"status":"available","references_indexed":true,"full_text_available":false,"full_text_source":null,"count_basis":"semantic_scholar_metadata","extraction_status":"not_applicable","reason":null},"source":{"provider":"episteme2","base_corpus":"semantic_scholar_dump","freshness_mode":"unknown","basis":["semantic_scholar_metadata","postgres_metadata"],"limits":["paper metadata is based on indexed upstream scholarly datasets","claims and concepts are available only for extracted papers","absence of claims or concepts means no extracted graph data is available in this response"],"status":"available","degraded":false,"degraded_reasons":[],"diagnostics":{"status":"available","degraded":false,"degraded_reasons":[],"metadata_status":"available","graph_status":"available","abstract_status":"available"},"source_flags":5},"paper_id":631436,"paper_uid":"cdd8a7bc-89ef-47a6-9a66-a1620dc58a29","canonical_identity":{"paper_id":631436,"paper_uid":"cdd8a7bc-89ef-47a6-9a66-a1620dc58a29","identity_status":"available","lookup_basis":"semantic_scholar_external_id","compatibility_path":"corpus_id"},"url":"https://sah.borca.ai/papers/35926507"}