Prevalence and characteristics of hepatitis B virus (HBV) mutations in chronic hepatitis B (CHB) patients on oral antiviral therapy (AVT): The CHARM study.

Abstract

AVT resistance in CHB can cause viral rebound and disease progression however early AVT modification can prevent resistance. The CHARM study reports the prevalence and characteristics for hepatitis B virus (HBV) mutations in patients receiving AVT in clinical practice. In this large Australian, multi-centre, cross-sectional study, CHB patients on AVT for >=6 mo had serum HBV DNA measured (Versant v3.0; LOD > 351 IU/mL) and direct sequence analysis of the polymerase catalytic region (amino acids 1-257) performed if HBV DNA was detectable. Demographics, clinical and serological information, patient compliance, and prior AVT history and mutations were collected. To date 483 patients have been enrolled, these were predominantly male (74%), Asian (76%), overseas born (94%), HBeAg negative (64%), median ALT 34 U/L (range 5-395) and age 49 yrs. Median total duration of AVT was 50 months (range 6-156) and 62% had received a prior AVT; 13% of patients had missed >=1 dose in the last 28 days. Current AVT was predominantly LAM (25%), ADV + LAM (24%) and ETV 0.5 mg (22%) with a median duration of 43, 12 and 13 mo respectively. HBV DNA was detectable in 25% (123/483) of patients with 72% (89/123) having >=1 resistance mutation, a genotypic resistance prevalence of 18%. M204V/I was most frequently reported (14%); L180M (9%), A181V/T (3%), N236T (2%), V173L (2%), T184 (1%) and S202 (<1%) were also reported. The majority of patients with mutations had received a prior AVT (83%) and were currently on ADV + LAM (39%), LAM (16%), ADV + ETV (12%) or ETV 1 mg (11%). They were predominantly HBeAg positive (60%), with a mean ALT 45 U/L and 31% had ALT>ULN (40 U/L); 27% had a history of resistance mutations. The majority of CHB patients with detectable HBV DNA on AVT, including combination AVT, had genotypic resistance. A significant proportion had accompanying biochemically active liver disease. These data highlight the need for early adaption of AVT in patients with a sub-optimal response.