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2015, Number 2

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Ann Hepatol 2015; 14 (2)

LAM add-on ADV combination therapy or ETV monotherapy for CHB patients with suboptimal response to ADV

Jia H, Ding F, Chen J, Zhang Y, Xiang D, Lian J, Zeng L, Yu L, Hu J, Li Y, Lu Y, Liu Y, Zheng L, Li L, Yang Y

Language: English
References: 20
Page: 175-180
PDF size: 94.95 Kb.


ABSTRACT

Introduction. Among the available nucleos(t)ide analogues adefovir dipivoxil (ADV) is relatively cheap and widely used in rural area in China. However, there are insufficient data on recommendation for patients with suboptimal response to ADV after 48 weeks of treatment in order to reduce the resistance rate in the long term. The aim of this study was to compare the efficacy and safety of LAM add-on combination therapy versus ETV monotherapy for patients with suboptimal response to ADV. Material and methods. 136 patients with suboptimal response to ADV were randomly assigned to the add-on LAM with ADV combination therapy (68 patients) group and the ETV monotherapy (68 patients) group. Patients in the add-on group were prescribed 100 mg LAM and 10 mg ADV per day, while the monotherapy group received 0.5 mg ETV per day for 48 weeks. Tests for liver and kidney function, HBV serum markers, HBV DNA load, were performed every 3 months. Results. The mean patient age in LAM add-on group and ETV monotherapy was 38.59 ± 7.65 and 37.56 ± 8.67 years respectively. The HBV DNA undetectable rate in the LAM add-on group and the ETV group were not significant difference at week 4, 12 and 24 (P › 0.05). However, the HBV undetectable rate in the ETV group was higher than that in the LAM add-on group at week 36 and 48 (P = 0.043 for week 36 and P = 0.038 for week 48). There was no significant difference both for HBeAg loss and HBeAg seroconversion between two groups (P › 0.05) at 48 weeks. Meanwhile, our study also demonstrated that the mean eGFR levels in LAM add-on group was decreased from 99.6 ± 8.71 at baseline to 86.4 ± 9.83 at the end of 48 weeks, which was significantly higher than that in the ETV monotherapy group (P ‹ 0.05). 8.8% of patients in LAM add-on group experienced eGFR reduction by 20-30% from baseline at 48 weeks. No patients developed hyposphosphatemia in our study. Conclusion. Our study clearly showed that switch to ETV monotherapy was the more effective and more safe than that of LAM add-on combination therapy for patients with suboptimal response to ADV.


REFERENCES

  1. Lee WM. Hepatitis B virus infection. N Engl J Med 1997; 337: 1733-45.

  2. Chen CJ, Yang HI, Su J, Jen CL, You SL, Lu SN, Huang GT, et al. REVEAL-HBV Study Group. Risk of hepatocellular carcinoma across a biological gradient of serum hepatitis B virus DNA level. JAMA 2006; 1: 65-73.

  3. Lai CL, Leung N, Teo EK, Tong M, Wong F, Hann HW, Han S, et al. Telbivudine Phase II Investigator Group. A 1-year trial of telbivudine, lamivudine, and the combination in patients with hepatitis B e antigen-positive chronic hepatitis B. Gastroenterology 2005; 2: 528-36.

  4. Yuen MF, Sablon E, Hui CK, Yuan HJ, Decraemer H, Lai CL. Factors associated with hepatitis B virus DNA breakthrough in patients receiving prolonged lamivudine therapy. Hepatology 2001; 4 :785-91.

  5. Kramata P, Votruba I, Otová B, Holý A. Different inhibitory potencies of acyclic phosphonomethoxyalkyl nucleotide analogs toward DNA polymerases alpha, delta and epsilon. Mol Pharmacol 1996; 6: 1005-11.

  6. Marcellin P, Chang TT, Lim SG, Tong MJ, Sievert W, Shiffman ML, Jeffers L, et al. Adefovir Dipivoxil 437 Study Group. Adefovir dipivoxil for the treatment of hepatitis B e antigen-positive chronic hepatitis B. N Engl J Med 2003; 9: 808-16.

  7. Hadziyannis SJ, Tassopoulos NC, Heathcote EJ, Chang TT, Kitis G, Rizzetto M, Marcellin P, et al. Adefovir Dipivoxil 438 Study Group. Adefovir dipivoxil for the treatment of hepatitis B e antigen-negative chronic hepatitis B. N Engl J Med 2003; 9: 800-7.

  8. Lee YS, Suh DJ, Lim YS, Jung SW, Kim KM, Lee HC, Chung YH, et al. Increased risk of adefovir resistance in patients with lamivudine-resistant chronic hepatitis B after 48 weeks of adefovir dipivoxil monotherapy. Hepatology 2006; 6: 1385-91.

  9. Locarnini S. Primary resistance, multidrug resistance, and cross-resistance pathways in HBV as a consequence of treatment failure. Hepatol Int 2008; 2: 147-51.

  10. Carrouée-Durantel S, Durantel D, Werle-Lapostolle B, Pichoud C, Naesens L, Neyts J, Trépo C, et al. Suboptimal response to adefovir dipivoxil therapy for chronic hepatitis B in nucleoside-naive patients is not due to preexisting drug-resistant mutants. Antivir Ther 2008; 3: 381-8.

  11. Gallego A, Sheldon J, García-Samaniego J, Margall N, Romero M, Hornillos P, Soriano V, et al. Evaluation of initial virological response to adefovir and development of adefovir-resistant mutations in patients with chronic hepatitis B. J Viral Hepat 2008; 5: 392-8.

  12. Hadziyannis SJ, Tassopoulos NC, Heathcote EJ, Chang TT, Kitis G, Rizzetto M, Marcellin P, et al. Adefovir Dipivoxil 438 Study Group. Long-term therapy with adefovir dipivoxil for HBeAg-negative chronic hepatitis B for up to 5 years. Gastroenterology 2006; 6: 1743-51.

  13. Colonno RJ, Rose R, Baldick CJ, Levine S, Pokornowski K, Yu CF, Walsh A, et al. Entecavir resistance is rare in nucleoside naïve patients with hepatitis B. Hepatology 2006; 6: 1656-65.

  14. Mukaide M, Tanaka Y, Shin-I T, Yuen MF, Kurbanov F, Yokosuka O, Sata M, et al. Mechanism of entecavir resistance of hepatitis B virus with viral breakthrough as determined by long-term clinical assessment and molecular docking simulation. Antimicrob Agents Chemother 2010; 2: 882-9.

  15. European Association For The Study Of The Liver. EASL clinical practice guidelines: Management of chronic hepatitis B virus infection. J Hepatol 2012; 57: 167-85.

  16. Liaw YF, Leung N, Kao JH, Piratvisuth T, Gane E, Han KH, Guan R, et al. Chronic Hepatitis B Guideline Working Party of the Asian-Pacific Association for the Study of the Liver Asian-Pacific consensus statement on the management of chronic hepatitis B: a 2008 update. Hepatol International 2008; 2: 263-83.

  17. Wang LC, Chen EQ, Cao J, Liu L, Wang JR, Lei BJ, Tang H. Combination of Lamivudine and adefovir therapy in HBe- Ag-positive chronic hepatitis B patients with poor response to adefovir monotherapy. J Viral Hepat 2010; 3: 178-84.

  18. Reijnders JG, Pas SD, Schutten M, de Man RA, Janssen HL. Entecavir shows limited efficacy in HBeAg-positive hepatitis B patients with a partial virologic response to adefovir therapy. J Hepatol 2009; 4: 674-83.

  19. Izzedine H, Hulot JS, Launay-Vacher V, Marcellini P, Hadziyannis SJ, Currie G, Brosgart CL, et al. Adefovir Dipivoxil International 437 Study Group; Adefovir Dipivoxil International 438 Study Group. Renal safety of adefovir dipivoxil in patients with chronic hepatitis B: two doubleblind, randomized, placebo-controlled studies. Kidney Int 2004; 3: 1153-8.

  20. Tanaka M, Suzuki F, Seko Y, Hara T, Kawamura Y, Sezaki H, Hosaka T, et al. Renal dysfunction and hypophosphatemia during long-term lamivudine plus adefovir dipivoxil therapy in patients with chronic hepatitis B. J Gastroenterol 2014; 3: 470-80.




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