Antiviral Drug Resistance Testing in Patients with Chronic Hepatitis B
Rent the article at a discountRent now
* Final gross prices may vary according to local VAT.Get Access
Antiviral drugs against hepatitis B virus are limited by the emergence of drug resistance.
We aimed to study the impact of drug resistance testing on treatment decisions.
In part 1 of this study, consecutive patients with chronic hepatitis B who had antiviral drug resistance testing were studied. Part 2 was a two-step questionnaire survey including ten characteristic case scenarios. Hepatologists were asked about their treatment decisions before and after the knowledge of drug resistance results.
Fifty-one patients underwent drug resistance testing, most of whom were on lamivudine, adefovir dipivoxil or entecavir monotherapy. Thirty-four (67%) patients had drug-resistant mutants detected, 4 (8%) had low viral load, and 13 (25%) harboured wild-type virus. Twenty-nine of 34 (85%) patients harbouring drug-resistant mutants and 9 of 17 (53%) patients with no mutants detected changed their drug regimens (P = 0.038). In part 2, 18 hepatologists completed all two questionnaires. Overall, treatment decision was modified in 52% of cases upon receiving the drug resistance testing results. The detection of rtA181V/I resulted in decision changes in most hepatologists, with the preferred treatment switching from tenofovir to entecavir. When no mutants were detected in partial responders to entecavir monotherapy, most hepatologists chose to increase the dose of entecavir.
Drug-resistant mutations are detected in around two-thirds of chronic hepatitis B patients undergoing drug resistance testing. Drug resistance testing alters management in over half of the cases, and should be considered in all patients with virological breakthrough and suboptimal virological suppression.
- Chan HL, Sung JJ. Hepatocellular carcinoma and hepatitis B virus. Semin Liver Dis. 2006;26:153–161. CrossRef
- Chen CJ, Yang HI, Su J, et al. Risk of hepatocellular carcinoma across a biological gradient of serum hepatitis B virus DNA level. JAMA. 2006;295:65–73. CrossRef
- Wong VW, Chan SL, Mo F, et al. Clinical scoring system to predict hepatocellular carcinoma in chronic hepatitis B carriers. J Clin Oncol. 2010;28:1660–1665. CrossRef
- Sung JJ, Tsoi KK, Wong VW, Li KC, Chan HL. Meta-analysis: treatment of hepatitis B infection reduces risk of hepatocellular carcinoma. Aliment Pharmacol Ther. 2008;28:1067–1077. CrossRef
- Wong VW, Wong GL, Chim AM, et al. Surrogate end points and long-term outcome in patients with chronic hepatitis B. Clin Gastroenterol Hepatol. 2009;7:1113–1120. CrossRef
- Liaw YF, Leung N, Kao JH, et al. Asian-Pacific consensus statement on the management of chronic hepatitis B: a 2008 update. Hepatol Int. 2008;2:263–283. CrossRef
- European Association for the Study of the Liver. EASL clinical practice guidelines: management of chronic hepatitis B. J Hepatol. 2009;50(2):227–242.
- Lok AS, McMahon BJ. Chronic hepatitis B: update 2009. Hepatology. 2009;50:661–662. CrossRef
- Leung NW, Lai CL, Chang TT, et al. Extended lamivudine treatment in patients with chronic hepatitis B enhances hepatitis B e antigen seroconversion rates: results after 3 years of therapy. Hepatology. 2001;33:1527–1532. CrossRef
- Wong VW, Wong GL, Tsang SW, et al. Long-term follow-up of lamivudine treatment in patients with severe acute exacerbation of hepatitis B e antigen (HBeAg)-positive chronic hepatitis B. Antivir Ther. 2008;13:571–579.
- Hadziyannis SJ, Tassopoulos NC, Heathcote EJ, et al. Long-term therapy with adefovir dipivoxil for HBeAg-negative chronic hepatitis B for up to 5 years. Gastroenterology. 2006;131:1743–1751. CrossRef
- Lok AS, Lai CL, Leung N, et al. Long-term safety of lamivudine treatment in patients with chronic hepatitis B. Gastroenterology. 2003;125:1714–1722. CrossRef
- Liaw YF, Gane E, Leung N, et al. 2-Year GLOBE trial results: telbivudine Is superior to lamivudine in patients with chronic hepatitis B. Gastroenterology. 2009;136:486–495. CrossRef
- Lee YS, Suh DJ, Lim YS, et al. Increased risk of adefovir resistance in patients with lamivudine-resistant chronic hepatitis B after 48 weeks of adefovir dipivoxil monotherapy. Hepatology. 2006;43:1385–1391. CrossRef
- Chan HL, Chui AK, Lau WY, et al. Factors associated with viral breakthrough in lamivudine monoprophylaxis of hepatitis B virus recurrence after liver transplantation. J Med Virol. 2002;68:182–187. CrossRef
- Chan HL, Tsang SW, Liew CT, et al. Viral genotype and hepatitis B virus DNA levels are correlated with histological liver damage in HBeAg-negative chronic hepatitis B virus infection. Am J Gastroenterol. 2002;97:406–412. CrossRef
- Ayres A, Locarnini S, Bartholomeusz A. HBV genotyping and analysis for unique mutations. Methods Mol Med. 2004;95:125–149.
- Lampertico P, Vigano M, Manenti E, Iavarone M, Sablon E, Colombo M. Low resistance to adefovir combined with lamivudine: a 3-year study of 145 lamivudine-resistant hepatitis B patients. Gastroenterology. 2007;133:1445–1451. CrossRef
- Villet S, Pichoud C, Billioud G, et al. Impact of hepatitis B virus rtA181V/T mutants on hepatitis B treatment failure. J Hepatol. 2008;48:747–755. CrossRef
- Warner N, Locarnini S. The antiviral drug selected hepatitis B virus rtA181T/sW172* mutant has a dominant negative secretion defect and alters the typical profile of viral rebound. Hepatology. 2008;48:88–98. CrossRef
- Chang TT, Gish RG, de Man R, et al. A comparison of entecavir and lamivudine for HBeAg-positive chronic hepatitis B. N Engl J Med. 2006;354:1001–1010. CrossRef
- Tenney DJ, Rose RE, Baldick CJ, et al. Long-term monitoring shows hepatitis B virus resistance to entecavir in nucleoside-naive patients is rare through 5 years of therapy. Hepatology. 2009;49:1503–1514. CrossRef
- Karino Y, Toyota J, Kumada H, et al. Efficacy and resistance of entecavir following 3 years of treatment of Japanese patients with lamivudine-refractory chronic hepatitis B. Hepatol Int. 2010;4:414–422. CrossRef
- Ide T, Sata M, Chayama K, et al. Evaluation of long-term entecavir treatment in stable chronic hepatitis B patients switched from lamivudine therapy. Hepatol Int. 2010;4:594–600. CrossRef
- Degertekin B, Hussain M, Tan J, Oberhelman K, Lok AS. Sensitivity and accuracy of an updated line probe assay (HBV DR v.3) in detecting mutations associated with hepatitis B antiviral resistance. J Hepatol. 2009;50:42–48. CrossRef
- Ding C, Wong VW, Chow KC, et al. Quantitative subtyping of hepatitis B virus reveals complex dynamics of YMDD motif mutants development during long-term lamivudine therapy. Antivir Ther. 2006;11:1041–1049.
- Lui YY, Tsoi KK, Wong VW, et al. Cost-effectiveness analysis of roadmap models in chronic hepatitis B using tenofovir as the rescue therapy. Antivir Ther. 2010;15:145–155. CrossRef
- Antiviral Drug Resistance Testing in Patients with Chronic Hepatitis B
Digestive Diseases and Sciences
Volume 57, Issue 1 , pp 221-231
- Cover Date
- Print ISSN
- Online ISSN
- Springer US
- Additional Links
- Viral load
- Adefovir dipivoxil
- Industry Sectors
- Author Affiliations
- 1. Department of Medicine and Therapeutics, Prince of Wales Hospital, The Chinese University of Hong Kong, 30–32 Ngan Shing Street, Shatin, Hong Kong
- 2. Institute of Digestive Disease, The Chinese University of Hong Kong, Shatin, Hong Kong
- 3. Victorian Infectious Disease Research Laboratory, Melbourne, Australia