Original Article
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World J Gastroenterol. Nov 21, 2013; 19(43): 7671-7679
Published online Nov 21, 2013. doi: 10.3748/wjg.v19.i43.7671
Efficacy of switching to telbivudine plus adefovir in suboptimal responders to lamivudine plus adefovir
Hana Park, Jun Yong Park, Seung Up Kim, Do Young Kim, Kwang-Hyub Han, Chae Yoon Chon, Sang Hoon Ahn
Hana Park, Department of Internal Medicine, CHA Bundang Medical Center, CHA University, Seongnam-si 463-712, South Korea
Hana Park, Department of Internal Medicine, Yonsei University College of Medicine, Seoul 120-752, South Korea
Jun Yong Park, Seung Up Kim, Do Young Kim, Chae Yoon Chon, Department of Internal Medicine, Yonsei University College of Medicine, Seoul 120-752, South Korea
Jun Yong Park, Seung Up Kim, Do Young Kim, Chae Yoon Chon, Institute of Gastroenterology, Yonsei University College of Medicine, Liver Cirrhosis Clinical Research Center, Seoul 120-752, South Korea
Kwang-Hyub Han, Sang Hoon Ahn, Department of Internal Medicine, Yonsei University College of Medicine, Seoul 120-752, South Korea
Kwang-Hyub Han, Sang Hoon Ahn, Institute of Gastroenterology, Yonsei University College of Medicine, Seoul 120-752, South Korea
Kwang-Hyub Han, Sang Hoon Ahn, Liver Cirrhosis Clinical Research Center, Seoul 120-752, South Korea
Kwang-Hyub Han, Sang Hoon Ahn, Brain Korea 21 Project for Medical Science, Seoul 120-752, South Korea
Author contributions: Park H, Park JY and Ahn SH designed the research/study; Park H analyzed the data; Park H and Ahn SH performed the study; and Kim SU, Kim DY, Han KH, Chon CY and Ahn SH collected the data; Park JY reviewed the data of study population; Park H wrote the paper.
Supported by The Liver Cirrhosis Clinical Research Center, a grant from the Korea Healthcare Technology R and D project, Ministry of Health and Welfare, South Korea, No. HI10C2020; and a grant to the Bilateral International Collaborative R and D Program from the Ministry of Trade, Industry and Energy, South Korea
Correspondence to: Sang Hoon Ahn, MD, PhD, Department of Internal Medicine, Yonsei University College of Medicine, 150 Shinchon-dong 50 Yonsei-ro, Seodaemun-gu, Seoul 120-752, South Korea. ahnsh@yuhs.ac
Telephone: +82-2-3936884 Fax:+82-2-22281936
Received: June 9, 2013
Revised: September 14, 2013
Accepted: September 16, 2013
Published online: November 21, 2013
Processing time: 192 Days and 2.4 Hours
Abstract

AIM: To examine the efficacy of telbivudine (LdT) + adefovir (ADV) vs continuation of lamivudine (LAM) + ADV in patients with LAM-resistant chronic hepatitis B (CHB) who show a suboptimal response to LAM + ADV.

METHODS: This was a randomized, active-control, open-label, single-center, parallel trial. All eligible patients were enrolled in this study in Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea, between March 2010 and March 2011. Hepatitis Be antigen (HBeAg)-positive CHB patients whose serum hepatitis B virus (HBV) DNA remained detectable despite at least 6 mo of LAM + ADV therapy were included. Enrolled patients were randomized to either switching to LdT (600 mg/d orally) plus ADV (10 mg/d orally) (LdT + ADV group) or to continuation with LAM (100 mg/d orally) plus ADV (10 mg/d orally) (LAM + ADV group), and were followed for 48 wk. One hundred and six patients completed the 48-wk treatment period. Serum HBV DNA, HBeAg status, liver biochemistry and safety were monitored at baseline and week 12, 24, 36 and 48.

RESULTS: The duration of prior LAM + ADV treatment was 18.3 (LdT + ADV) and 14.9 mo (LAM + ADV), respectively (P = 0.131). No difference was seen in baseline serum HBV DNA between the two groups [3.66 (LdT + ADV) vs 3.76 (LAM + ADV) log10 IU/mL, P = 0.729]. At week 48, although there was no significant difference in the mean reduction of serum HBV DNA from baseline between LdT + ADV group and LAM + ADV group (-0.81 vs -0.47 log10 IU/mL, P = 0.167), more patients in the LdT + ADV group had undetectable HBV DNA levels compared to those in the LAM + ADV group (30.2% vs 11.5%, P = 0.019). Three patients with LdT + ADV treatment and 2 patients with LAM + ADV treatment achieved HBeAg loss. The patients in both groups tolerated the treatment well without serious adverse events. The proportion of patients with estimated glomerular filtration rate ≥ 90 mL/min per 1.73 m2 in the LdT + ADV group increased from 49.1% (26/53) at baseline to 58.5% (31/53) at week 48, while that in the LAM + ADV group decreased from 37.7% (20/53) at baseline to 30.2% (16/53) at week 48.

CONCLUSION: The switch to LdT + ADV in suboptimal responders to LAM + ADV showed a significantly higher rate of virologic response at week 48. These results suggest that LdT + ADV could be a therapeutic option for patients who are unable to use enofovir disoproxil fumarate for any reason.

Keywords: Chronic hepatitis B; Antiviral resistance; Suboptimal response; Telbivudine; Lamivudine

Core tip: A suboptimal response is common in patients treated with lamivudine (LAM) + adefovir (ADV) combination therapy and it has also become a new challenge for the management of chronic hepatitis B (CHB) patients. We commenced this study with the effect of telbivudine (LdT) + ADV combination therapy as a rescue therapeutic option in LAM-resistant CHB patients with suboptimal response to LAM + ADV. Our results demonstrated that switching from LAM + ADV to LdT + ADV resulted in superior virologic response, renoprotective effect and similar safety profiles at week 48. These results suggest that LdT + ADV could be a therapeutic option for patients who are unable to use enofovir disoproxil fumarate for any reason.