{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,4]],"date-time":"2025-12-04T14:35:33Z","timestamp":1764858933568,"version":"3.41.0"},"reference-count":29,"publisher":"Scientific Scholar","issue":"3","content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2016,9]]},"abstract":"\n Background & objectives:<\/jats:title>\n Reduction of viraemia in patients with chronic hepatitis B virus (HBV) infection using nucleoside\/nucleotide analogues reduces fatal liver disease-related events, but development of resistance in virus presents serious clinical challenge. Therefore, comparative evaluation of prolonged antiviral monotherapy and combination therapies was prospectively studied to assess their influence on viral suppression, rapidity of response, development of drug resistance and surfacing mutants in chronic liver disease (CLD) patients.<\/jats:p>\n <\/jats:sec>\n \n Methods:<\/jats:title>\n A total of 158 (62eAg-ve) chronic hepatitis B patients were prospectively studied for 24 months. Final analysis was performed on patients treated with lamivudine (LAM, n = 28), adefovirdipivoxil (ADV, n = 24), tenofovir disoproxil fumarate (TDF, n = 26), entecavir (ETV, n = 25), LAM + ADV (n = 28) and LAM + TDF (n = 27). Quantitative hepatitis B virus DNA was detected using real-time polymerase chain reaction. Multiple comparisons among drugs and genotypic mutations were analyzed.<\/jats:p>\n <\/jats:sec>\n \n Results:<\/jats:title>\n Progressive biochemical and virological response were noted with all the regimens at 24 months except LAM and ADV which were associated with viral breakthrough (VBT) in 46.4 and 25 per cent, respectively. Mutations: rtM204V (39.3%), M204V+L180M (10.7%) while rtA181V (8.1%) and rtN236T (8.3%) were observed with LAM and ADV regimen, respectively. LAM + ADV combination therapy revealed VBT in seven per cent of the cases without mutations whereas TDF, ETV and LAM + TDF therapies neither showed VBT nor mutations.<\/jats:p>\n <\/jats:sec>\n \n Interpretation & conclusions:<\/jats:title>\n LAM was the least potent drug among all therapeutic options followed by ADV. TDF and ETV were genetically stable antivirals with a strong efficacy. Among newer combination therapies, LAM + TDF revealed more efficacy in virological remission and acted as a profound genetic barrier on long term. Hence, newer generation molecules (TDF, ETV) and effective combination therapy should be a certain choice.<\/jats:p>\n <\/jats:sec>","DOI":"10.4103\/0971-5916.198674","type":"journal-article","created":{"date-parts":[[2017,1,20]],"date-time":"2017-01-20T07:49:15Z","timestamp":1484898555000},"page":"424-432","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":2,"title":["Comparative evaluation of long-term monotherapies & combination therapies in patients with chronic hepatitis B"],"prefix":"10.25259","volume":"144","author":[{"given":"Manjita","family":"Srivastava","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Neha","family":"Singh","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vinod Kumar","family":"Dixit","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gopal","family":"Nath","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ashok Kumar","family":"Jain","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"10894","reference":[{"key":"R1-16-20241212","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1016\/j.jhep.2012.02.010","article-title":"EASL clinical practice guidelines: Management of chronic hepatitis B virus infection","volume":"57","author":"Papatheodoridis","year":"2012","journal-title":"J Hepatol"},{"key":"R2-16-20241212","doi-asserted-by":"crossref","first-page":"617","DOI":"10.1053\/jhep.2001.27834","article-title":"Hepatitis B e antigen-negative chronic hepatitis B","volume":"34","author":"Hadziyannis","year":"2001","journal-title":"Hepatology"},{"key":"R3-16-20241212","doi-asserted-by":"crossref","first-page":"S52","DOI":"10.1002\/jmv.20608","article-title":"Hepatitis B virus mutations associated with antiviral therapy","volume":"78","author":"Bartholomeusz","year":"2006","journal-title":"J Med Virol"},{"key":"R4-16-20241212","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.antiviral.2004.07.003","article-title":"Mechanism of viral persistence and resistance to nucleoside and nucleotide analogs in chronic hepatitis B virus infection","volume":"64","author":"Zoulim","year":"2004","journal-title":"Antiviral Res"},{"key":"R5-16-20241212","doi-asserted-by":"crossref","first-page":"1503","DOI":"10.1002\/hep.22841","article-title":"Long-term monitoring shows hepatitis B virus resistance to entecavir in nucleoside-na\u00efve patients is rare through 5 years of therapy","volume":"49","author":"Tenney","year":"2009","journal-title":"Hepatology"},{"key":"R6-16-20241212","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1002\/hep.21534","article-title":"Adding-on versus switching-to adefovir therapy in lamivudine-resistant HBeAg-negative chronic hepatitis B","volume":"45","author":"Rapti","year":"2007","journal-title":"Hepatology"},{"key":"R7-16-20241212","doi-asserted-by":"crossref","first-page":"1414","DOI":"10.1002\/hep.20939","article-title":"Adefovir rapidly suppresses hepatitis B in HBeAg-negative patients developing genotypic resistance to lamivudine","volume":"42","author":"Lampertico","year":"2005","journal-title":"Hepatology"},{"key":"R8-16-20241212","doi-asserted-by":"crossref","first-page":"703","DOI":"10.1002\/hep.21290","article-title":"Evolution of multi-drug resistant hepatitis B virus during sequential therapy","volume":"44","author":"Yim","year":"2006","journal-title":"Hepatology"},{"key":"R9-16-20241212","doi-asserted-by":"crossref","first-page":"1711","DOI":"10.1002\/hep.510270634","article-title":"Emergence and takeover of YMDD motif mutant hepatitis B virus during long-term lamivudine therapy and re-takeover by wild type after cessation of therapy","volume":"27","author":"Chayama","year":"1998","journal-title":"Hepatology"},{"key":"R10-16-20241212","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1056\/NEJM199807093390201","article-title":"A one-year trial of lamivudine for chronic hepatitis B. 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