Philip Vutien1, Huy N Trinh2, Ruel T Garcia2, Huy A Nguyen3, Brian S Levitt3, Khanh Nguyen3, Eduardo da Silveira3, Tami Daugherty4, Aijaz Ahmed4, Gabriel Garcia4, Glen A Lutchman4, Mindie H Nguyen5. 1. Case Western Reserve University School of Medicine, Cleveland, Ohio; Division of Gastroenterology and Hepatology, Stanford University Medical Center, Stanford, California. 2. Pacific Health Foundation, San Jose, California; San Jose Gastroenterology, San Jose, California. 3. San Jose Gastroenterology, San Jose, California. 4. Division of Gastroenterology and Hepatology, Stanford University Medical Center, Stanford, California. 5. Division of Gastroenterology and Hepatology, Stanford University Medical Center, Stanford, California. Electronic address: mindiehn@stanford.edu.
Abstract
BACKGROUND & AIMS: Prior studies have detected hepatitis B virus (HBV) DNA polymerase mutations in treatment-naive patients. However, most of these studies used either direct polymerase chain reaction sequencing, which detects these mutations with low levels of sensitivity, or patient cohorts that were not well-characterized. We investigated the prevalence of HBV mutations in DNA polymerase by using a line probe assay. METHODS: In a prospective, cross-sectional study, we enrolled 198 treatment-naive patients with chronic hepatitis B (52.5% male; mean age, 41 years) from February 2009 to May 2011 from 3 gastroenterology and liver clinics in Northern California. Exclusion criteria included infection with hepatitis C or D viruses or human immunodeficiency virus. All patients completed a questionnaire (to determine demographics, history of liver disease, prior treatments, family medical history, drug and alcohol use, and environmental risk factors for hepatitis) that was administered by a research coordinator; mutations in HBV DNA polymerase were detected by using the INNO-LiPA HBV DR v.3 assay. RESULTS: Most patients were Vietnamese (48.5%) or Chinese (36.4%) and were infected with HBV genotypes B (67.5%) or C (24.2%). Mutations in HBV DNA polymerase were found in 2 patients (1%), rtI233V (n = 1) and rtM250M/L (n = 1). CONCLUSIONS: In a multicenter prospective study of treatment-naive patients with chronic hepatitis B, we detected mutations in HBV DNA polymerase in only 1%. Because of the low prevalence of these mutations and the uncertain clinical significance of such quasispecies, routine HBV DNA polymerase mutation analysis cannot be recommended before initiation of antiviral therapy for treatment-naive patients with chronic hepatitis B. The analysis requires further molecular and clinical studies.
BACKGROUND & AIMS: Prior studies have detected hepatitis B virus (HBV) DNA polymerase mutations in treatment-naive patients. However, most of these studies used either direct polymerase chain reaction sequencing, which detects these mutations with low levels of sensitivity, or patient cohorts that were not well-characterized. We investigated the prevalence of HBV mutations in DNA polymerase by using a line probe assay. METHODS: In a prospective, cross-sectional study, we enrolled 198 treatment-naive patients with chronic hepatitis B (52.5% male; mean age, 41 years) from February 2009 to May 2011 from 3 gastroenterology and liver clinics in Northern California. Exclusion criteria included infection with hepatitis C or D viruses or human immunodeficiency virus. All patients completed a questionnaire (to determine demographics, history of liver disease, prior treatments, family medical history, drug and alcohol use, and environmental risk factors for hepatitis) that was administered by a research coordinator; mutations in HBV DNA polymerase were detected by using the INNO-LiPA HBV DR v.3 assay. RESULTS: Most patients were Vietnamese (48.5%) or Chinese (36.4%) and were infected with HBV genotypes B (67.5%) or C (24.2%). Mutations in HBV DNA polymerase were found in 2 patients (1%), rtI233V (n = 1) and rtM250M/L (n = 1). CONCLUSIONS: In a multicenter prospective study of treatment-naive patients with chronic hepatitis B, we detected mutations in HBV DNA polymerase in only 1%. Because of the low prevalence of these mutations and the uncertain clinical significance of such quasispecies, routine HBV DNA polymerase mutation analysis cannot be recommended before initiation of antiviral therapy for treatment-naive patients with chronic hepatitis B. The analysis requires further molecular and clinical studies.