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

• Published in: Clinical and molecular hepatology Vol. 26; no. 3; pp. 352 - 363
• Main Authors: Hyun Young Woo, Jun Yong Park, Si Hyun Bae, Chang Wook Kim, Jae Young Jang, Won Young Tak, Dong Joon Kim, In Hee Kim, Jeong Heo, Sang Hoon Ahn
• Format: Journal Article
• Language: Korean
• Published: 대한간학회 01.07.2020
• Subjects: Adefovir; Antiviral drug resistance; Entecavir; Lamivudine; Tenofovir
• ISSN: 2287-2728; 2287-285X

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 ETVassociated 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. Conclusions: 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). (Clin Mol Hepatol 2020;26:352-363)