Prevalence of naturally occurring surface gene variants of hepatitis B virus in nonimmunized surface antigen-negative Chinese carriers

Previous studies have suggested that hepatitis B virus (HBV) variants may a ccount for the presence of HBV DNA in hepatitis B surface antigen (HBsAg)-n egative patients (occult HBV infection). However, it is not known how wides pread these variants are and how they influence the course of liver disease . To determine the prevalence of variants within the major hydrophilic regi on (MHR) of HBsAg, we investigated 2,565 subjects, including subjects with chronic hepatitis, cryptogenic cirrhosis, hemodialysis patients, and blood donors. Fifty-one of them had occult HBV infection. The entire S gene from 46 of these patients was sequenced from amplified serum HBV DNA. Forty-thre e percent (20 of 46) had mutations in the MHR of HBsAg. Thirty-two amino ac id substitutions between positions 100-160 of the MHR of HBsAg were detecte d in 18 patients, and these ranged from 1 to 4 per patient. These changes i nvolved 11 positions inside and 5 outside of the historical first and secon d loops of the "a" determinant, and included the following: Q101K, T115A, K 122N, T123A, T126N, Q129N, G130R, T131i, M133T, F134L, C138Y, K141E, P142S, G145R, N146S, and C147F/R. Combinations of mutations were detected in 9 pa tients, and 7 of these have not been described before. Two further patients had insertion mutations immediately before the "a" determinant. Monoclonal antibody binding tests with the Royal Free hepatitis B surface (RFHBs) pan el of antibodies revealed decreased immunoreactivity in 6 novel variants of HBsAg. The existence of patients with occult HBV infection caused by HBsAg variants, therefore, has implications for their possible transmission thro ugh sexual contact and by blood transfusion.