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. AIM: 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.