High efficacy of adefovir and entecavir combination therapy in patients with nucleoside-refractory hepatitis B

• Published in: The Korean journal of hepatology Vol. 18; no. 1; pp. 75 - 83
• Main Authors: Chae, Hee Bok, Kim, Mee Jin, Seo, Eui Geun, Choi, Yong Hyeok, Lee, Hee Seung, Han, Joung Ho, Yoon, Soon Man, Park, Seon Mee, Youn, Sei Jin
• Format: Journal Article
• Language: English
• Published: Korea (South) The Korean Association for the Study of the Liver 01.03.2012
• Subjects: Adenine - analogs & derivatives; Adenine - therapeutic use; Adult; Alanine Transaminase - blood; Antiviral Agents - therapeutic use; DNA, Viral - blood; Drug Resistance, Multiple, Viral; Drug Therapy, Combination; Female; Genotype; Guanine - analogs & derivatives; Guanine - therapeutic use; Hepatitis B Antibodies - blood; Hepatitis B e Antigens - blood; Hepatitis B, Chronic - drug therapy; Humans; Male; Middle Aged; Nucleosides - therapeutic use; Organophosphonates - therapeutic use; Original; Adefovir; Treatment efficacy; Drug resistance; Combination drug therapy; Entecavir
• ISSN: 1738-222X; 2093-8047
• DOI: 10.3350/kjhep.2012.18.1.75

Newly developed and potent antiviral agents suffer from the problem of drug resistance. Multidrug resistance is a major impediment in the treatment of patients with chronic hepatitis B (CHB). In line with American Association for the Study of Liver Diseases guidelines, adefovir dipivoxil (ADV) add-on therapy is recommended in the case of lamivudine resistance, while tenofovir disoproxil fumarate (TDF) is recommended for ADV or entecavir (ETV) resistance. TDF is currently not available in Korea. ADV+ETV combination therapy may be a viable alternative to TDF in patients with either ADV or ETV resistance. However, the efficacy of ADV+ETV combination therapy in patients with CHB and multidrug resistance is unclear. This study investigated the efficacy of ADV+ETV combination therapy in patients with multidrug resistance. Twenty-five patients were enrolled and were administered ADV+ETV combination therapy for at least 6 months. Blood was drawn at baseline and at 3, 6, 9, and 12 months after commencing treatment, and the following blood parameters were analyzed: alanine transaminase, hepatitis B e-antigen (HBeAg), anti-hepatitis B e-antigen, and hepatitis B virus (HBV) DNA levels. The initial virological response (IVR) was defined as an HBV DNA level of <4 log(10) copies/mL after 6 months of combination therapy. The IVR rate was 76%. The proportion of patients with a high viral load (≥5.0 log) dropped from 76% at baseline to only 5% after 6 months of treatment. The biochemical response rate during the first 6 months was 71%. HBeAg was lost in 2 patients (10%). ADV+ETV combination therapy induced a good IVR in CHB patients who were refractory to more than 2 antiviral agents. This regimen may be a good alternative to TDF in Korea, where that drug is not available.