Prevalence of hepatitis B virus DNA polymerase mutations in treatment-naïve patients with chronic hepatitis B.
BACKGROUND
One of the most important factors in treatment failure using nucleos(t)ide analogues in chronic hepatitis B is anti-viral resistance. Primary drug resistance refers to amino acid changes in the hepatitis B virus polymerase/reverse transcriptase (rt) that result in reduced susceptibility to anti-viral agents. Pre-existing drug resistance mutations may occur in untreated patients and may affect their treatment outcomes.


OBJECTIVE
To determine the prevalence of hepatitis B DNA polymerase mutations in treatment-naïve patients.


METHODS
We used a direct PCR sequencing test to detect DNA polymerase mutations in 472 consecutive treatment-naïve patients at two community gastroenterology clinics in Northern California.


RESULTS
A majority of patients were Asians (>95%), had either genotype B or C (95%) and had no evidence of cirrhosis or liver cancer (94%). Mean age was 45 +/- 13 and mean hepatitis B virus DNA was 5.3 +/- 1.8 log(10) IU/mL. Most patients did not have any detectable mutations (82.4%). Some (16.7%) had mutations of unknown clinical significance (rtV207M/L/I) and only 4 patients had rtA181A/S, rtA194S or M250I.


CONCLUSIONS
No rtM204V/I or rtN236T mutations were observed in our study. Less than 1% of our patients had mutations that can be associated with primary resistance to existing anti-viral therapies for hepatitis B virus.
Division of Gastroenterology and Hepatology, Stanford University Medical Center, Stanford, CA 94304, USA. mindiehn@stanford.edu
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Levitt
D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use*; D003430:Cross-Sectional Studies; D004259:DNA-Directed DNA Polymerase / Q000235:genetics*; D005260:Female; D005838:Genotype; D006515:Hepatitis B virus / Q000187:drug effects / Q000235:genetics*; D019694:Hepatitis B, Chronic / Q000188:drug therapy / Q000235:genetics* / Q000821:virology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D015995:Prevalence; D012194:RNA-Directed DNA Polymerase / Q000235:genetics*; D016896:Treatment Outcome
D000998:Antiviral Agents; D012194:RNA-Directed DNA Polymerase; D004259:DNA-Directed DNA Polymerase