Management of Clevudine-Resistant Chronic Hepatitis B: A Multicenter Cohort Study.

Abstract

BACKGROUND/AIMS:

Data are lacking regarding the management of chronic hepatitis B (CHB) with resistance to clevudine (CLV). This study evaluated the efficacy of different rescue therapies for CLV-resistant CHB.

METHODS:

Patients with CLV-resistant CHB were enrolled in the cohort, and all patients developed virologic breakthrough during CLV therapy and had confirmed-genotypic resistance to CLV (rtM204I mutation) before enrollment.

RESULTS:

Of the 107 patients, 12 received adefovir (ADV), 21 received a CLV plus ADV combination (CLV+ADV), 34 received a lamivudine plus ADV combination (LAM+ADV), and 40 received entecavir (ETV) therapy for 48 weeks. The CLV+ADV group had the lowest hepatitis B virus (HBV) DNA level (p<0.0001) and showed the greatest reduction of HBV DNA levels from baseline compared to all other groups (p=0.004) at week 48. HBV DNA was undetectable (<70 IU/mL) in 0%, 57.1%, 21.2%, and 27.5% (p=0.003) of the patients in each group, respectively, at week 48. At the end of the study, the mean alanine transaminase (ALT) level, rate of ALT normalization, and rate of hepatitis B envelope antigen loss or seroconversion did not differ between groups.

CONCLUSIONS:

CLV+ADV combination therapy in patients with CLV-resistant CHB more effectively suppresses HBV replication than ETV, ADV, or LAM+ADV therapy.

• Authors: Eun Young Cho, Hyung Joon Yim, Young Kul Jung, Sang Jun Suh, Yeon Seok Seo, Ji Hoon Kim, Hong Soo Kim, Sae Hwan Lee, Sang Hoon Ahn, Jeong Il Lee, Sook-Hyang Jeong, Jin-Wook Kim, Jin-Woo Lee, In Hee Kim, Hyoung Su Kim, Sang Jong Park, Jeong Mi Lee, Seong Gyu Hwang, Antiviral Resistance Study Group
• Journal: Gut and liver (Gut Liver) Vol. 11 Issue 1 Pg. 129-135 (Jan 15 2017) ISSN: 2005-1212 [Electronic] Korea (South)
• PMID: 27538443 (Publication Type: Journal Article, Multicenter Study)

Chemical References

• Antiviral Agents
• DNA, Viral
• Organophosphonates
• Lamivudine
• Arabinofuranosyluracil
• entecavir
• Guanine
• adefovir
• clevudine
• Adenine

Topics

• Adenine (analogs & derivatives, therapeutic use)
• Adult
• Aged
• Antiviral Agents (therapeutic use)
• Arabinofuranosyluracil (analogs & derivatives, therapeutic use)
• Cohort Studies
• DNA, Viral (blood)
• Disease Management
• Drug Resistance, Viral (genetics)
• Drug Therapy, Combination
• Female
• Genotype
• Guanine (analogs & derivatives, therapeutic use)
• Hepatitis B virus (genetics)
• Hepatitis B, Chronic (blood, drug therapy, virology)
• Humans
• Lamivudine (therapeutic use)
• Male
• Middle Aged
• Organophosphonates (therapeutic use)
• Viral Load