Lamivudine-resistance mutations can be selected even at very low levels of hepatitis B viraemia

Svicher, Valentina; Alteri, Claudia; Gori, Caterina; Salpini, Romina; Marcuccilli, Fabbio; Bertoli, Ada; Longo, Roberta; Bernassola, Martina; Gallinaro, Valentina; Romano, Sara; Visca, Michela; Ursitti, Antonella; Feasi, Marcello; Micheli, Valeria; Angelico, Mario; Cassola, Giovanni; Parruti, Giustino; Gubertini, Guido; De Sanctis, Giuseppe Maria; Ceccherini-Silberstein, Francesca; Cappiello, Giuseppina; Spanò, Alberto; Perno, Carlo Federico

doi:10.1016/j.dld.2010.04.017

« Previous Next »Digestive and Liver Disease
Volume 42, Issue 12 , Pages 902-907, December 2010

Lamivudine-resistance mutations can be selected even at very low levels of hepatitis B viraemia

Valentina Svicher
- University of Rome “Tor Vergata”, Italy
- Equally contributed to the work.
Claudia Alteri
- University of Rome “Tor Vergata”, Italy
- Equally contributed to the work.
Caterina Gori
- I.N.M.I. “L. Spallanzani”, Rome, Italy
Romina Salpini
- University of Rome “Tor Vergata”, Italy
Fabbio Marcuccilli
- University of Rome “Tor Vergata”, Italy
Ada Bertoli
- University of Rome “Tor Vergata”, Italy
Roberta Longo
- “S. Pertini” Hospital, Rome, Italy
Martina Bernassola
- “S. Pertini” Hospital, Rome, Italy
Valentina Gallinaro
- University of Rome “La Sapienza”, Italy
Sara Romano
- “S. Pertini” Hospital, Rome, Italy
Michela Visca
- “S. Pertini” Hospital, Rome, Italy
Antonella Ursitti
- “S. Pertini” Hospital, Rome, Italy
Marcello Feasi
- “Galliera” Hospital, Genoa, Italy
Valeria Micheli
- “L. Sacco” Hospital, Milan, Italy
Mario Angelico
- University of Rome “Tor Vergata”, Italy
Giovanni Cassola
- “Galliera” Hospital, Genoa, Italy
Giustino Parruti
- “Spirito Santo” Hospital, Pescara, Italy
Guido Gubertini
- “L. Sacco” Hospital, Milan, Italy
Giuseppe Maria De Sanctis
- University of Rome “La Sapienza”, Italy
Francesca Ceccherini-Silberstein
- University of Rome “Tor Vergata”, Italy
Giuseppina Cappiello
- “S. Pertini” Hospital, Rome, Italy
Alberto Spanò
- “S. Pertini” Hospital, Rome, Italy
Carlo Federico Perno
- University of Rome “Tor Vergata”, Italy
- Corresponding author at: Department of Experimental Medicine, University of Rome “Tor Vergata”, Via Montpellier 1, 00133 Rome, Italy. Tel.: +39 06 72596566; fax: +39 06 72596039.

Received 21 January 2010; accepted 27 April 2010. published online 21 June 2010.

Abstract

Objective

To investigate lamivudine (LAM)-resistance profiles of hepatitis B virus (HBV) at the early stages of virological breakthrough (serum HBV-DNA 12–345IU/ml) or when HBV-DNA is undetectable.

Methods

Sixty-four HBV-mono-infected patients were enrolled: 25 had virological breakthrough with serum HBV-DNA ranging from 12 to 345IU/ml during first-line LAM-monotherapy; 24 were on LAM-monotherapy, and 15 were on LAM+adefovir dipivoxil (ADV) with undetectable serum HBV-DNA (<12IU/ml).

Results

HBV-reverse transcriptase was successfully sequenced in 22 (88.0%) LAM-treated patients with HBV-DNA between 12 and 345IU/ml, and in 12 (30.8%) patients receiving LAM (±ADV) with HBV-DNA<12IU/ml.

Drug-resistance mutations were observed in 17 (77.2%) LAM-treated patients with virological breakthrough: 8 M204V, 7 M204I, 1 M204I/V, and 1 A181T. One or ≥2 compensatory mutations were found in 10 (58.8%) and in 4 (23.5%) patients.

Drug-resistance mutations were present also in patients with undetectable serum HBV-DNA: M204I was detected in 2 patients receiving LAM-monotherapy, and V84M in 1 patient receiving LAM+ADV.

Conclusion

Overall findings support the existence of drug-resistance mutations even at very low levels of viral replication. The persistence of low-level HBV replication and consequent drug-resistance emergence should be considered when choosing therapeutic strategies.

Keywords: Drug resistance, HBV, Low viral replication