EFFICACY OF ENTECAVIR AS RESCUE THERAPY IN LAMIVUDINE-RESISTANT PATIENTS WITH HBV LIVER CIRRHOSIS AND WAITING FOR ORTHOTOPIC LIVER TRANSPLANTATION

Background The efficacy of entecavir compared to adefovir or adefovir plus lamivudine in lamivudine resistant patients with HbeAg positive or negative hepatitis B virus (HBV) liver cirrhosis and waiting for orthotopic liver transplantation (OLT) is unknown. The main endpoint of pre-OLT antiviral treatment in lamivudine resistant patients is to suppress in a short time HBV replication before OLT and thus to decrease the risk of reinfection of the graft. Methods Patients with CHB who had histologically confirmed cirrhosis or advanced fibrosis with a demonstrated lamivudine resistance and waiting for OLT were randomly assigned in a 2:1:1 ratio to receive entecavir, or adefovir or adefovir plus lamivudine. Of the 82 patients with lamivudine-resistant HBV liver cirrhosis, 42 were assigned toreceive entecavir at the dosage of 1 mg/die (group 1), 20 adefovir at dosage of 10 mg/die (group 2) and 20 adefovir 10mg/die plus lamivudine 100 mg/die (group 3).The primary efficacy measure was a rapid reduction of HBVDNA levels in the first six months of treatment. Secondary efficacy measures included changes in serum ALT levels, and improvement in the Child score. Results By month 3, serum HBVDNA became undetectable (HBVDNA<15UI/ml, Taqman Roche) in 33 patients of group 1 (78.5%), in 7 of group 2 (35%) and in 10 of group 2 (50%). By month 6, HBVDNA became indetectable in 3 additional patients of group 1 (85%), in 1 additional patient of group 2 (40%) and in 2 additional patients of group 3 (60%). In group 1, 2 and 3 the rates of ALT normalization were respectively 80%, 65%, and 60% at month 3 and persisting up to 6 month. A more rapid reduction of HBVDNA levels was present in patients of group 1 compared to patients of group 2 respectively at 3 and 6 months (RR=2.24 p<0.0008 and RR=2.14 p<0.0002). On the contrary, there was not a statistically significant difference in the reduction of HBVDNA levels at 3 and 6 months in the patients of groups 2 and 3. Child Pugh class improved in the three groups without a statistically significant difference at 6 month of treatment. Conclusions These results suggest that Entecavir is highly effective to reduce HBVDNA and ALT levels in the first 6 month of treatment in patients with lamivudine resistance and waiting for OLT compared to adefovir or adefovir associated to lamivudine.