Early on treatment detection of nucelos(t)ide analogue resistant minor variants of Hepatitis B virus (HBV) with ultra deep-pyrosequencing (UDPS) in chronic hepatitis B(CHB) patien…

Introduction: UDPS allows the detection of minor viral variants during the natural course and antiviral treatment in HBV-infected patients. It could be shown that double infections with two HBV genotypes and minor strains carrying resistance mutations not detected by clonal sequencing could be analyzed. Here we tested a method for analyzing multiple HBV genotypes in a single sample as well as its potential to identify resistance mutations in patients months before viral breakthrough. Patients and methods: A custom HBV sample was constructed by equimolar pooling of PCR amplicons derived from viral nucleic acid ex…