ENTECAVIR THERAPY FOR LAMIVUDINE RESISTANT HBV CIRRHOTIC PATIENTS WAITING FOR OLT: VIRAL AND BIOCHEMICAL OUTCOMES AT ONE YEAR

The efficacy of 48 weeks Entecavir (ETV) treatment in Lamivudine resistant (LAM-r) HBV cirrhotic patients waiting for OLT is unknown. We assess the efficacy and resistance profile of 48 weeks (w48) ETV treatment. Methods: Patients with demonstrated LAM-r were randomly assigned in a 2:1 ratio to receive ETV or Adefovir plus Lamivudine (ADV+LAM). Of the 62 patients with LAM-r, 42 were assigned to receive ETV 1 mg/day and 20 ADV+LAM (10mg+100mg/day). The primary end point was undetectability of HBVDNA at w48 of treatment. Secondary end points were the onset of ETV resistance and changed in serum ALT during the time. Results: In 2 ETV patients with detectable HBVDNA at w48, genotypic analysis showed an additional rt250V resistance with a baseline 204I/204V/180M resistance to LAM in both patients. In other 8 ETV patients, although HBVDNA was detectable at w48, no genotypic resistance was detected. A sub analysis has pointed out that in 9 out of 10 EVT patients with detectable HBVDNA at w48 there were at baseline multiple LAM-r mutations respect to 9 out of 25 ETV patients with not detectable HBVDNA at w48 (p<0.007). The results are reported in the table. Conclusions: Rescue therapy with ETV in LAM-r patients seems to be effective in the first 24 weeks of treatment compared to ADV+LAM. At w48 we assist to a reduced benefit of ETV treatment respect to ADV+LAM although this was not statistically significant. A suboptimal response at w48 in reducing HBVDNA levels and the onset of ETV resistance mutations is more frequent in a subset of ETV patients with baseline multiple LAM-r mutations compared to LAM-r patients with a single mutation at baseline.