THE EFFECT OF LONG-TERM NUCLEOSIDE/TIDE ANALOGUE TREATMENT ON INTRAHEPATIC HBV DNA AND COVALENTLY CLOSED CIRCULAR DNA IN CHRONIC HEPATITIS B PATIENTS Print
D.K. Wong1,2, C.-L. Lai1,2, P. Ip3, M. Kopaniszen1, W.-K. Seto1, J. Fung1,2, F.-Y. Huang1, R. Wu1, C. Cheng1, V. Ngai1, M.-F. Yuen1,2
1Medicine, 2State Key Laboratory for Liver Research, 3Pathology, University of Hong Kong, Hong Kong, Hong Kong
Background and aims: Nucleoside/tide analogue (NA) treatment suppresses serum HBV DNA to very low levels. However, their long-term effects on intrahepatic HBV DNA (ihHBV-DNA) and covalently closed circular DNA (cccDNA) have never been documented.
Methods: Patients on long-term continuous (5 - 11 years) NA (lamivudine/adefovir/telbivudine/entecavir/tenofovir) were recruited. All patients had 3 liver biopsies: at baseline, after 1 year of treatment and at the last follow-up. Serum HBV DNA was measured by the COBAS TaqMan HBV Test (Roche Diagnostics). ihHBV-DNA and cccDNA were assayed by real-time PCR as previously described.1
Results: To date, 10 patients had undergone liver biopsies at the last follow-up, all of whom had either 100mg lamivudine or 0.5mg entecavir at baseline and had been switched to 1.0mg entecavir during follow-up (median follow-up: 11.4 years; range 10.7 - 11.5 years). At baseline, the median serum HBV DNA, ihHBV-DNA and cccDNA levels were 6.66 logIU/mL, 273 copies/cell, and 3.2 copies/cell, respectively. At the time of the last biopsies, although all 10 patients had serum HBV DNA levels below detection limit (< 20 IU/mL; p< 0.0001 comparing to baseline), all had detectable ihHBV-DNA and cccDNA. However, the ihHBV-DNA and cccDNA levels were greatly reduced, with median values of 0.45 and 0.04 copies/cell, respectively, and median percentage reductions of 99.9% and 98.2%, respectively (both p< 0.0001; compared to baseline levels).
Conclusions: Long-term NA treatment significantly reduced ihHBV-DNA and cccDNA, though small amount of these were still present. Whether more prolonged therapy can eradicate them is still unknown.
1. Wong et al, (2013) Clin. Gastro. Hepatol. 11:1004-10
Ching-Lung Lai , University of Hong Kong , Hong Kong , Hong Kong
Assigned in sessions:
12.04.2014, 09:00-18:00, Poster, 7C - VIRAL HEPATITIS: HEPATITIS B & D - CLINICAL (THERAPY, NEW COMPOUNDS, RESISTANCE), Poster Exhibition
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