PATHOGENESIS OF CHRONIC LIVER-DISEASE IN PATIENTS WITH CHRONIC HEPATITIS-B VIRUS-INFECTION WITHOUT SERUM HBEAG

Chronic hepatitis B in patients lacking hepatitis B e antigen has been attributed to a hepatitis B virus variant (G-to-A mutation at nucleot ide 1896 in the precore region of the genome). We therefore assessed t he frequency and significance of this variant among 43 United States p atients (10 with chronic hepatitis B seropositive for e antigen, 19 se ronegative for e antigen, and 14 healthy carriers). Sera were tested f or HBV DNA by polymerase chain reaction and branched DNA assay. The A( 1896) variant was detected by direct sequencing and ligase chain react ion. Serum HBV DNA was more frequently found among patients with e ant igen-positive than e antigen-negative chronic hepatitis B. Viral titer s were generally higher in those with e antigen. None of the e antigen -positive and only 24% of e antigen-negative patients harbored the A(1 896) variant. Patients infected with the variant were more often Asian , had had hepatitis B for longer and had higher levels of viral DNA th an HBeAg-negative patients with the wild-type virus. The A(1896) varia nt was found exclusively in patients infected with HBV genotypes C and D. Thus, the A(1896) variant is uncommon in the United States. The ac tivity of liver disease appears to be more closely related to the leve l of HBV replication than the presence of mutations at nucleotide 1896 in the genome.