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

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• 作者：Valentina Svicher ; Claudia Alteri ; Caterina Gori ; Romina Salpini ; Fabbio Marcuccilli ; Ada Bertoli ; Roberta Longo ; Martina Bernassola ; Valentina Gallinaro ; Sara Romano ; Michela Visca ; Antonella Ursitti
• 关键词：Drug resistance ; HBV ; Low viral replication
• 刊名：Digestive and Liver Disease
• 出版年：2010
• 出版时间：December 2010
• 年：2010
• 卷：42
• 期：12
• 页码：902-907
• 全文大小：283 K

文摘

Objective

To investigate lamivudine (LAM)-resistance profiles of hepatitis B virus (HBV) at the early stages of virological breakthrough (serum HBV-DNA 12–345 IU/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 345 IU/ml during first-line LAM-monotherapy; 24 were on LAM-monotherapy, and 15 were on LAM + adefovir dipivoxil (ADV) with undetectable serum HBV-DNA (<12 IU/ml).

Results

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