[184-186] In cases where the HBV DNA levels during lamivudine therapy remained <2.6 log copies/mL, HBV DNA continued negative after switching to entecavir, and entecavir-resistant virus was not detected. On the other hand, when the HBV DNA levels is ≥2.6 log copies/mL at the time of switching, entecavir-resistant HBV may appear irrespective of whether lamivudine-resistant virus

was already present. Concerning problems with safety, almost no adverse reactions of clinical importance XAV-939 nmr were reported. Points to keep in mind are that entecavir is not suitable for long term continuous therapy for women desiring to bear children due to the risk of teratogenesis, GSK126 and the safety of long term administration has not been established. Recommendations Favourable results are obtained with entecavir in patients naïve to NAs, with

a low incidence of resistant virus, currently making entecavir the first-choice NA. Switching to entecavir is recommended in patients in whom the HBV DNA negative conversion occurs with lamivudine therapy. It has been reported that if lamivudine-resistant HBV appears and the viral load increases, onset of hepatitis is likely; furthermore, in some cases the hepatitis may become severe.[157, 187] Accordingly, treatment with an antiviral agent is required if lamivudine-resistant HBV appears. IFN, adefovir selleck screening library and entecavir have been confirmed effective against lamivudine-resistant HBV, and are currently approved for Japanese medical insurance. Although IFN can be used to a certain extent to treat hepatitis associated with lamivudine-resistant HBV, there are problems with adverse reactions and a limited treatment duration.[188,

189] On the other hand, adefovir has good long term efficacy against lamivudine-resistant HBV, with mild adverse reactions and suitable for long term therapy, so currently adefovir is recommended. Rather than switch from lamivudine to adefovir, lamivudine and adefovir in combination provides a stronger antiviral effect.[190] The long term effect of lamivudine+adefovir combination therapy against lamivudine-resistant HBV has been reported as an HBV DNA negative conversion rate (<2.6 log copies/mL) using the Amplicor testing of 56–82% at 1 year, 74–84% at 2 years, 81–86% at 3 years, 80–92% at 4 years, and 85–86% at 5 years.[158, 159, 161, 164, 165, 167] Reported factors relating to the antiviral effect of lamivudine+adefovir combination therapy include DNA load (low value), albumin level (low), ALT level (high), HBeAg (negative), and HBV DNA negative conversion during lamivudine therapy.[159, 165, 166, 168] Reported ALT normalization rates were 67–81% at 1 year, 75–83% at 2 years, 80–92% at 3 years, 82–90% at 4 years, and 85% at 5 years.