Prevalence of hepatitis B virus DNA polymerase mutations in treatment-naïve patients with chronic hepatitis B


Dr M. H. Nguyen, Division of Gastroenterology and Hepatology, 750 Welch Road, Suite 210, Palo Alto, CA 94304, USA.


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 log10 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.