CC BY-NC-ND 4.0 · J Lab Physicians 2012; 4(01): 010-016
DOI: 10.4103/0974-2727.98664
Original Article

Laboratory Evaluation of Three Regimens of Treatment of Chronic Hepatitis B: Tenofovir, Entecavir and Combination of Lamivudine and Adefovir

Rajeswari Jayakumar
Division of Clinical Microbiology, Department of Laboratory Medicine, All India Institute of Medical Sciences, New Delhi - 110 029, India
,
Yogendra Kumar Joshi
Department of Gastroenterology, All India Institute of Medical Sciences, New Delhi - 110 029, India
,
Sarman Singh
Division of Clinical Microbiology, Department of Laboratory Medicine, All India Institute of Medical Sciences, New Delhi - 110 029, India
› Author Affiliations
Source of Support: Nil

ABSTRACT

Background: Chronic hepatitis B is a disease of concern due to its life-threatening complications like cirrhosis, and hepatocellular carcinoma (HCC) in 20-40% of patients. There are about 400 million people affected worldwide with HBV, and over 300,000 die every year from HBV-related diseases. Oral antivirals like lamivudine, adefovir, entecavir, and tenofovir are commonly used to treat chronic hepatitis B. In this study, we tried to evaluate the comparative efficacy of these drugs alone and in combination.

Materials and Methods: Chronic hepatitis B patients with HBV-DNA more than 104 Copies/mL irrespective of their HBeAg status (n = 60) were enrolled in a prospective study. 21, 20, and 19 patients were treated with lamivudine (100 mg/day) plus adefovir (10 mg/day) combination entecavir monotherapy (0.5 mg/day) and tenofovir monotherapy (300 mg/day), respectively and were followed up for 24 weeks with their virological, serological, and biochemical markers measured at 12 and 24 weeks.

Results: After 24 weeks of treatment, there was no significant difference between the 3 groups in suppressing HBV-DNA to undetectable levels. The median decrease in HBV-DNA levels from baseline was better with tenofovir and entecavir monotherapies than lamivudine and adefovir combination, which was statistically significant. There was no significant difference between the 3 groups in HBsAg and HBeAg seroconversion and normalization of biochemical parameters.

Conclusion: Entecavir and tenofovir monotherapy were found to be more effective than lamivudine plus adefovir combination in reducing the HBV-DNA levels. However, lamivudine plus adefovir combination was not too inferior, especially when cost of treatment was taken into consideration.



Publication History

Article published online:
09 May 2020

© 2012.

Thieme Medical and Scientific Publishers Private Ltd.
A-12, Second Floor, Sector -2, NOIDA -201301, India

 
  • REFERENCES

  • 1 Kao JH, Chen DS. The natural history of Hepatitis B virus infection. In: Lai CL, Locarnini S, editors. Hepatitis B virus. London: International Medical Press; 2002. p. 161-72.
  • 2 Mason WS, Burrell CJ, Casey J, Gerlich WH, Howard CR, Kann M, et al. Hepadnaviridae. In: Fauquet CM, Mayo MA, Maniloff J, Desselberger U, Ball LA (editors). Virus taxonomy. Eighth report of the International Committee on Taxonomy of Viruses. Amsterdam: Elsevier; 2005.
  • 3 Fattovich G, Bortolotti F, Donato F. Natural history of chronic Hepatitis B: Special emphasis on disease progression and prognostic factors. J Hepatol 2008;48:335-52.
  • 4 Aggarwal R, Ghoshal UC, Naik SR. Treatment of chronic hepatitis B with interferon-alpha: Cost-effectiveness in developing countries. Natl Med J India 2002;15:320-7.
  • 5 Dienstag JL. Chronic Hepatitis (chapter 300). Harrison′s Principles of Internal Medicine. 17th ed. United states of America: McGraw-Hill companies; 2008. p. 1957-66.
  • 6 Liaw YF. Impact of YMDD mutations during lamivudine therapy in patients with chronic Hepatitis B. Antivir Chem Chemother 2001;12(Suppl 1):67-71.
  • 7 Akuta N, Suzuki F, Kawamura Y, Yatsuji H, Sezaki H, Suzuki Y, et al. Virological response and hepatocarcinogenesis in lamivudine-resistant Hepatitis B virus genotype C patients treated with lamivudine plus adefovir dipivoxil. Intervirology 2008;51:385-93.
  • 8 Chen EQ, Wang LC, Lei J, Xu L, Tang H. Meta-analysis: Adefovir dipivoxil in combination with lamivudine in patients with lamivudine-resistant Hepatitis B virus. Virol J 2009;6:163.
  • 9 Snow A, Thibault V, Qi X, Zhu Y, Westland CE, Arterbrun S. Combination of adefovir dipivoxil (ADV) and lamivudine (LAM) prevented emergence of ADV resistance mutations in chronic Hepatitis B (CHB) patients with LAM-resistant HBV. Gastroenterology 2005;128:M945.
  • 10 Cheng PN, Chang TT. Entecavir: A potent antiviral with minimal long-term resistance in nucleoside-naive chronic Hepatitis B patients. Expert Rev Anti Infect Ther 2008;6:569-79.
  • 11 Tenney DJ, Levine SM, Rose RE, Walsh AW, Weinheimer SP, Discotto L, et al. Clinical emergence of entecavir-resistant Hepatitis B virus requires additional substitutions in virus already resistant to lamivudine. Antimicrob Agents Chemother 2004;48:3498-507.
  • 12 Lacombe K, Gozlan J, Boelle PY, Serfaty L, Zoulim F, Valleron AJ, et al. Long-term Hepatitis B virus dynamics in HIV-Hepatitis B virus co-infected patients treated with tenofovir disoproxil fumarate. AIDS 2005;19:907-15.
  • 13 Jenh AM, Thio CL, Pham PA, Tenofovir for the treatment of Hepatitis B virus. Pharmacotherapy 2009;29:1212-27.
  • 14 Patterson SJ, George J, Strasser SI, Lee AU, Sievert W, Nicoll AJ, et al. Tenofovir disoproxil fumarate rescue therapy following failure of both lamivudine and adefovir dipivoxil in chronic hepatitis B. Gut 2011;60:247-54.
  • 15 Merican I, Guan R, Amarapuka D, ,Alexander MJ, Chutaputti A, Chien RN, et al. Chronic Hepatitis B virus infections in Asian countries. J Gastroenterol Hepatol 2000;15:1356-61.
  • 16 Carey I, Harrison PM. Monotherapy versus combination therapy for the treatment of chronic Hepatitis B. Expert Opin Investig Drugs 2009;18:1655-66.
  • 17 Lok AS, Lai CL, Leung N, Yao GB, Cui ZY, Schiff ER, et al. Long-term safety of lamivudine treatment in patients with chronic Hepatitis B. Gastroenterology 2003;125:1714-22.
  • 18 Kwon HC, Cheong JY, Cho SW, Choi JM, Hong SP, Kim SO, et al. Emergence of adefovir-resistant mutants after reversion to YMDD wild-type in lamivudine-resistant patients receiving adefovir monotherapy. J Gastroenterol Hepatol 2009;24:49-54.
  • 19 Ijaz S, Arnold C, Dervisevic S, Mechurova J, Tatman N, Tedder RS, et al. Dynamics of lamivudine-resistant Hepatitis B virus during adefovir monotherapy versus lamivudine plus adefovir combination therapy. J Med Virol 2008;80:1160-70.
  • 20 Pellicelli AM, Barbaro G, Francavilla R, Romano M, Barbarini G, Mazzoni E, et al. Adefovir and lamivudine in combination compared with adefovir monotherapy in HBeAg-negative adults with chronic Hepatitis B virus infection and clinical or virologic resistance to lamivudine: A retrospective, multicenter, nonrandomized, open-label study. Clin Ther 2008;30:317-23.
  • 21 Marcellin P, Heathcote EJ, Buti M, Gane E, de Man RA, Krastev Z, et al. Tenofovir disoproxil fumarate versus adefovir dipivoxil for chronic Hepatitis B. N Engl J Med 2008;359:2442-55.
  • 22 Colonno RJ, Rose R, Baldick CJ, Levine S, Pokornowski K, Yu CF, et al. Entecavir resistance is rare in nucleoside naive patients with Hepatitis B. Hepatology 2006;44:1656-65.
  • 23 Tenney DJ, Rose RE, Baldick CJ, Pokornowski KA, Eggers BJ, Fang J, 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;49:1503-14.
  • 24 Villet S, Ollivet A, Pichoud C, Barraud L, Villeneuve JP, Trépo C, et al. Stepwise process for the development of entecavir resistance in a chronic Hepatitis B virus infected patient. J Hepatol 2007;46:531-8.
  • 25 Guo JJ, Li QL, Shi XF, Zhang DZ, Zeng AZ, Feng T, et al. Dynamics of Hepatitis B virus resistance to entecavir in a nucleoside/nucleotide-naive patient. Antiviral Res 2009;81:180-3.
  • 26 Baldick CJ, Tenney DJ, Mazzucco CE, Eggers BJ, Rose RE,Pokornowski KA, et al. Comprehensive evaluation of Hepatitis B virus reverse transcriptase substitutions associated with entecavir resistance. Hepatology 2008;47:1473-82.
  • 27 Singh K, Bhat S, Shastry S. Trend in seroprevalence of Hepatitis B virus infection among blood donors of coastal Karnataka, India. J Infect Dev Ctries 2009;3:376-9.