Lamivudine treatment for viral hepatitis B is often accompanied by the development of resistance, which leads to a loss of therapeutic effect. According to the results of preclinical and phase II studies, entecavir has shown marked activity against the hepatitis B virus resistant to lamivudine.

In a randomized, double-blind, phase III study by M. Sherman et al. (Canada), HBE-positive patients with infection refractory to lamivudine treatment (persistent viremia or occurrence of documented YMDD mutations during treatment with lamivudine) were divided into two groups. In the study group, the drug was changed to entecavir at a dose of 1 mg / day (n = 141), patients in the control group continued to receive lamivudine at a dose of 100 mg / day (n = 145) for at least 52 weeks. After 48 weeks, the state of the infectious process was evaluated by the following indicators: the achievement of a histological improvement and a combined indicator (the amount of viral DNA in the DNA chain reaction is less than 0.7 meq / ml and the decrease in the level of alanine aminotransferase (ALT) is 1.25 times lower than the upper limit of normal)

According to the results, histological improvement was observed in 55% (68/124) of patients receiving entecavir, compared to 28% (32/116) in the control group (p less than 0.0001). The achievement rate of the combined score was also higher in patients receiving entecavir than in the control group (55% (77/141) vs 4% (6/145), respectively; p less than 0, 0001). The mean difference in viral DNA concentration since the start of the study was 5.11 log10 copies / ml in patients receiving entecavir, compared to 0.48 log10 copies / ml in patients in the control group (lower p at 0.0001). Deterioration in the course of the infectious process due to the development of resistance to entecavir occurred in 2 of 141 patients receiving this drug, and genotypic signs of resistance were detected in 10 patients. The safety profile of entecavir was comparable to that of lamivudine at a lower frequency of elevated ALT levels during treatment.

Thus, in patients with chronic viral hepatitis B refractory to lamivudine treatment, a change in treatment regimen to entecavir leads to a more pronounced histological improvement, a decrease in viral load and a normalization of ALT levels compared to continuing treatment with lamivudine with a comparable safety profile.