Resistance issues in treating chronic hepatitis B.

HBV resistance is the main limitation of long-term therapy with oral HBV polymerase inhibitors, which represent the most common approach in the treatment of chronic hepatitis B. The complete suppression of HBV replication minimises the risk of resistance and therefore close monitoring with sensitive HBV DNA determinations at least every 6 months is required. Lamivudine monotherapy has the highest risk of selecting resistant mutations compared with other anti-HBV agents and is not currently considered as an optimal first-line treatment. Adefovir has a similar profile but less potency than the other nucleotide analog, tenofovir, whereas telbivudine selects for lamivudine resistance mutants and therefore its place is currently unclear. Entecavir and possibly tenofovir are the two most potent anti-HBV agents with the best resistance profile in nucleo(s)tide-naive patients, while tenofovir represents the optimal treatment for patients with lamivudine resistance. Combination of two agents without cross-resistance should be used in any patient with HBV resistance.