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Randomized Controlled Trial
. 2020 Jul;26(3):352-363.
doi: 10.3350/cmh.2019.0044n. Epub 2020 May 28.

Entecavir+tenofovir vs. lamivudine/telbivudine+adefovir in chronic hepatitis B patients with prior suboptimal response

Hyun Young Woo  1   2 , Jun Yong Park  3 , Si Hyun Bae  4 , Chang Wook Kim  4 , Jae Young Jang  5 , Won Young Tak  6 , Dong Joon Kim  7   8 , In Hee Kim  9 , Jeong Heo  1   2 , Sang Hoon Ahn  3
Affiliations
Randomized Controlled Trial

Entecavir+tenofovir vs. lamivudine/telbivudine+adefovir in chronic hepatitis B patients with prior suboptimal response

Hyun Young Woo et al. Clin Mol Hepatol. 2020 Jul.

Abstract

Background/aims: Suboptimal responses to lamivudine or telbivudine plus adefovir (LAM/LdT+ADV) rescue therapy are common in patients with LAM-resistant hepatitis B virus (HBV) infections. We compared patients switched to entecavir plus tenofovir (ETV+TDF) to those maintained on LAM/LdT+ADV.

Methods: This prospective randomized controlled trial examined 91 patients whose serum HBV DNA levels were greater than 60 IU/mL after at least 24 weeks of treatment with LAM/LdT+ADV for LAM-resistant HBV. Patients were randomized to receive a new treatment (ETV+TDF, n=45) or maintained on the same treatment (LAM/LdT+ADV, n=46) for 48 weeks. Patients with baseline ADV resistance were excluded.

Results: Compared to LAM/LdT+ADV group, ETV+TDF group had more patients with a virologic response (42/45 [93.33%] vs. 3/46 [6.52%], P<0.001) and had a greater mean reduction in serum HBV DNA level from baseline (-4.16 vs. -0.37 log10 IU/mL, P<0.001). Multivariate analysis indicated that high baseline HBV DNA level (P=0.005) and LAM/LdT+ADV maintenance therapy (P=0.001) were negatively associated with virologic response. At week 48, additional ADV- or ETV-associated mutations were cleared in ETV+TDF group, but such mutations were present in 4.3% of patients in LAM/LdT+ADV group (P=0.106). The two groups had similar rates of adverse events.

Conclusion: ETV+TDF combination treatment led to a significantly higher rate of virologic response compared to LAM/LdT+ADV combination treatment in patients with LAM-resistant HBV who had suboptimal responses to LAM/LdT+ADV regardless of HBV genotypic resistance profile (NCT01597934).

Keywords: Adefovir; Antiviral drug resistance; Entecavir; Lamivudine; Tenofovir.

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Conflict of interest statement

Conflicts of Interest: The authors have no conflicts to disclose.

Figures

Figure 1.
Figure 1.
Study design. LAM, lamivudine; LdT, telbivudine; ADV, adefovir; ETV, entecavir; TDF, tenofovir.
Figure 2.
Figure 2.
Cumulative virologic responses in the two groups. Solid line: TDF+ETV group; dotted line: LAM/LdT+ADV group. ETV, entecavir; TDF, tenofovir; LAM, lamivudine; LdT, telbivudine; ADV, adefovir.
Figure 3.
Figure 3.
Reduction of HBV DNA level (mean log10 IU/mL) in the two groups from baseline to week 48. Solid line: TDF+ETV group; dotted line: LAM/LdT+ADV group. HBV, hepatitis B virus; LAM, lamivudine; LdT, telbivudine; ADV, adefovir; ETV, entecavir; TDF, tenofovir.
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