Lamivudine-resistant HBV strain rtM204V/I in acute hepatitis B

Aims: To detect HBV rtM204V/I lamivudine-resistant strains in serum of patients with acute hepatitis B and to assess their biological and clinical significance. Methods: Eighty HBV DNA-positive patients with symptomatic acute hepatitis B observed from 1999 to 2010 were enrolled. A plasma sample obtained at the first observation was tested for HBV mutants in the polymerase region by direct sequencing; the antiviral drug-resistant rtM204V/I mutations, the most frequent HBV mutants in Italy, were also sought by the more sensitive allele-specific polymerase chain reaction (PCR). Results: No HBV mutation associated with resistance to nucleos(t)ide analogues was identified by direct sequencing, whereas allele-specific PCR identified HBV strains carrying the substitution rtM204V/I in 11 (13.7%) patients. Compared with those with the HBV wild strain, patients with rtM204V/I more frequently showed severe acute hepatitis B (36.4% vs 8.7%; p<0.05) and lower values of serum HBV DNA (1.77×106±4.76×106 vs. 1.68×108±5.46×108). In addition, a multivariate analysis identified the presence of a pre-existing HCV chronic infection as independently associated with severe acute hepatitis B (p<0.05). Conclusions: HBV rtM204V/I lamivudine-resistant strains were detected in serum of 11 (13.7%) patients with acute hepatitis B by allele-specific polymerase chain reaction. The frequent association of rtM204V/I with a more severe acute hepatitis B and with a lower viral load maysuggest that greater and/or more prolonged immune pressure might have induced their selection. © 2013.