Acute hepatitis B infection associated with drug-resistant hepatitis B virus.
BACKGROUND
Pre-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.


OBJECTIVE
The study was to investigate if Beijing patients with acute hepatitis B (AHB) are infected with drug-resistant HBV.


METHODS
Sera 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.


RESULTS
Direct 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.


CONCLUSIONS
Drug-resistant HBV strains, including those not resistant to lamivudine, are transmissible and can cause acute hepatitis B in China.
Xu
Zhihui
Z
Viral Hepatitis Research Laboratory, Institute of Infectious Diseases, Beijing 302 Hospital, 100 Xi Si Huan Middle Road, Beijing 100039, China.
Liu
Yan
Y
Xu
Teng
T
Chen
Li
L
Si
Lanlan
L
Wang
Yao
Y
Ren
Xiaoqiang
X
Zhong
Yanwei
Y
Zhao
Jingmin
J
Xu
Dongping
D
D000225:Adenine / Q000031:analogs & derivatives / Q000494:pharmacology; D000328:Adult; D019943:Amino Acid Substitution / Q000235:genetics; D000998:Antiviral Agents / Q000494:pharmacology*; D002681:China; D004279:DNA, Viral / Q000737:chemistry / Q000235:genetics; D024882:Drug Resistance, Viral; D006147:Guanine / Q000031:analogs & derivatives / Q000494:pharmacology; D006509:Hepatitis B / Q000821:virology*; D006515:Hepatitis B virus / Q000187:drug effects* / Q000302:isolation & purification*; D006801:Humans; D019259:Lamivudine / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D063065:Organophosphonates / Q000494:pharmacology; D016133:Polymerase Chain Reaction; D012194:RNA-Directed DNA Polymerase / Q000235:genetics; D017422:Sequence Analysis, DNA; D014764:Viral Proteins / Q000235:genetics
D000998:Antiviral Agents; D004279:DNA, Viral; D063065:Organophosphonates; D014764:Viral Proteins; D019259:Lamivudine; C413685:entecavir; D006147:Guanine; C053001:adefovir; D012194:RNA-Directed DNA Polymerase; D000225:Adenine