Acute hepatitis B infection associated with drug-resistant hepatitis B virus

BackgroundPre-existing antiviral-resistant hepatitis B virus (HBV) has been associated with primary non-response to lamivudine treatment in patients with chronic hepatitis B, but little is known of the capacity for resistant HBV to cause primary infection.ObjectiveThe study was to investigate if Beijing patients with acute hepatitis B (AHB) are infected with drug-resistant HBV.Study designSera were collected from 201 NA-untreated patients with AHB. Direct polymerase chain reaction (PCR) sequencing was used to screen HBV reverse-transcriptase (RT) domain and clonal sequencing were performed for all resistance-positive samples.ResultsDirect PCR sequencing showed that 14 samples (7.0%) were positive for drug-resistant HBV variants, comprised of 11 with the lamivudine-resistant pattern rtM204I and/or rtM204V in the presence and absence of compensatory mutations rtL80I, rtV173L, and rtL180M; two with the adefovir-resistant pattern rtA181V; and one with the entecavir-resistant pattern rtL180M + rtS202G + rtM204V. Concomitance of resistance variants with wild-type HBV was observed in samples from 13 patients. Clonal sequencing verified direct sequencing results. Furthermore, variants associated with resistance to adefovir or entecavir were found in 3 samples.ConclusionsDrug-resistant HBV strains, including those not resistant to lamivudine, are transmissible and can cause acute hepatitis B in China.