Eur J Gastroenterol Hepatol. 2019 Feb 15. doi: 10.1097/MEG.0000000000001351. [Epub ahead of print]
Risk factors for resistance development against lamivudine during long-term treatment of chronic hepatitis B virus infections.
Koukoulioti E1, Brodzinski A1, Mihm U2, Sarrazin C3, Jung MC4, Schott E5, Fülöp B1,6, Schlosser B7, Berg T1, van Bömmel F1.
Author information
1
Section of Hepatology, Department of Gastroenterology and Rheumatology, University Hospital Leipzig, Leipzig.
2
Medical Clinic I, University Hospital Frankfurt, Frankfurt.
3
Medical Clinic II, St Joseph's Hospital, Wiesbaden.
4
Liver Centre, Munich.
5
Helios Hospital Emil von Behring.
6
Department of Gastroenterology, Hepatology and Infectiology, Helios Hospital Berlin-Buch.
7
Praxis Jessen, Berlin, Germany.
Abstract
BACKGROUND/AIM:
The use of lamivudine for the treatment of chronic hepatitis B (CHB) is limited by high rates of lamivudine resistance. However, it is still in use in many regions. Factors associated with lamivudine resistance development have been studied in only a few European cohorts. The aim of our study was to assess the rate and risk factors for lamivudine resistance in a large real-life European cohort.
PATIENTS AND METHODS:
We retrospectively analyzed patients with CHB treated in three German University centers over up to 12 years. Lamivudine resistance was defined as virologic breakthrough and presence of genotypic lamivudine resistance. The probability of resistance was estimated by Kaplan-Meier analysis and resistance predictors by Cox regression.
RESULTS:
A total of 227 patients were included into the analysis (hepatitis B envelope antigen positive or negative). Rates of lamivudine resistance by years 1-7 were 7, 26, 35, 41, 46, 53, and 55%, respectively. Interestingly, two hepatitis B envelope antigen-negative patients developed resistance during the year 12 of treatment. Independent risk factors for resistance development were hepatitis B virus DNA levels of at least 10 copies/ml before and detectable hepatitis B virus DNA by month 6 of treatment.
CONCLUSION:
Even after long-term response to lamivudine more than 10 years, resistance may still develop. Our findings further discourage the use of lamivudine for the treatment of CHB.