Entecavir (Baraclude) resistance is rare in nucleoside-naive patients receiving treatment for chronic hepatitis B virus (HBV) infection, but is not an infrequent event in patients with existing lamivudine (Epivir-HBV) resistance.

In vitro data, as well as anecdotal evidence in humans, suggest a beneficial effect of adefovir (Hepsera) in patients with entecavir resistance.

At 43rd annual meeting of the European Association for the Study of the Liver (EASL 2008) last month in Milan, Turkish researchers reported on a group of 10 lamivudine-refractory chronic hepatitis B patients (7 male, 3 female, median age 40 years) in BMS Study 026.

The study participants experienced virological breakthrough (> log10 copies/mL above nadir) while on entecavir. They were switched to lamivudine plus adefovir combination therapy and analyzed for drug resistance.

Results

• Genotypic resistance to entecavir was observed in all 10 patients.

• All patients had the L180M and M204V lamivudine resistance mutations.

• 6 patients had S202G, and 1 each had the T184A, T184A+M250I, T184F, and M250V mutations.

• The median HBV DNA levels at the time of viral breakthrough wase 8.43 log10 copies/mL (range 4.68-9.75).

• Viral breakthrough was first detected after a median duration of 108 weeks (range 36 to 216).

• 8 out of 10 patients finished at least 6 months of adefovir treatment.

• HBV DNA decreased compared with baseline (i.e., the time of viral breakthrough).

• None of the patients exhibited primary non-response to lamivudine plus adefovir therapy.

• At 6 months, the change in HBV DNA from baseline was -2.93 log10.

• In 6 patients who had samples 3- and 6-month samples available, the HBV DNA difference from baseline was -2.91 log10after 3 months and -3.46 log10 after 6 months of rescue therapy.

Conclusion

Based on these findings, the investigators concluded that treatment with lamivudine plus adefovir is an effective treatment strategy in lamivudine-refractory patients with entecavir resistance. They noted that the effect of this regimen starts to appear as early as 3 months after switching therapy.

University of Ankara Medical School, Gastroenterology Section, Ankara, Turkey;
University of Ankara, Hepatology Institute, Ankara, Turkey; Ege University Medical School, Gastroenterology Section, Izmir, Turkey; University of Istanbul, Istanbul Medical Faculty, Istanbul, Turkey.

5/09/08

Reference
C Yurdaydin, R Idilman, E Cevik, and others. Adefovir treatment of entecavir resistance in patients with lamivudine-refractory chronic hepatitis B. 43rd annual meeting of the European Association for the Study of the Liver (EASL 2008). Milan, Italy. April 23-27, 2008.