Lamivudine Switching after Undetectable HBV DNA is Associated with High Rate of Virological Rebound in Entecavir-treated Chronic Hepatitis B Patients
Chainuvati S, MD1, Yingcharoen K, MD1, Tanwandee T, MD1
Affiliation : 1 Division of Gastroenterology, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
Objective : Current treatment of chronic hepatitis B includes oral nucleos[t]ides analogs which aim to suppress HBV DNA in order
to prevent HBV related complications and the treatment is likely to be lifelong. With the implementation of Thai National list of
essential medicine in late 2012, there are only lamivudine and tenofovir listed for treatment of chronic hepatitis B which can be
reimbursable. Many patients treated previously with high genetic barrier drug like entecavir had been switched to lamivudine. This
study aimed to investigate the outcome of lamivudine switching versus continuing entecavir in entecavir-treated chronic hepatitis
B patients who were undetectable HBV DNA at the time of switching.
Materials and Methods : This is a retrospective and prospective cohort design. The patients who were switched to lamivudine as
reimbursement policy were matched with similar patients who have continued entecavir. HBV DNA, liver biochemistry as well as
clinical data were observed every 3 to 6 months for 2 years. Virological rebound was defined as detectable HBV DNA at least twice,
one month apart.
Results : There were 73 chronic hepatitis B patients in both groups with similar baseline characteristics. The cumulative incidence
of virological rebound was significantly higher in lamivudine-switching group as compared to entecavir-continuing group, 31.6%
vs. 0% (p<0.001). The predictor for virological rebound in lamivudine-switching group was high baseline ALT. One hepatic
decompensation was found in the patients who had virological rebound during study and the patient died. All breakthroughs were
successfully rescued with tenofovir.
Conclusion : Switching from entecavir to lamivudine in the patients who have been treated with entecavir until undetectable HBV
DNA was associated with high rate of virological breakthrough (31.6% at 2 years), even in the patients with low baseline HBV DNA.
Switching to lamivudine is not safe since virological breakthrough can result in mortality. If practice lamivudine switching, closely
monitor the patients and rescue as soon as virological breakthrough is detected.
Keywords : Lamivudine switching, Virological rebound, Undetectable HBV DNA, Entecavir-treated chronic hepatitis B
