Fulminant hepatitis related to transmission of hepatitis B variants with precore mutations between spouses

A precore defective variant of hepatitis B virus has been indicated to cause fulminant hepatitis in various instances such as intrahospital outbreaks or mother-to-child transmission of hepatitis B virus. To learn whether similar variants are involved in interspouse transmission, we analyzed three cases of fulminant hepatitis B that developed in formerly healthy subjects whose only exposure to hepatitis B virus was contact with their longtime spouses, who were carriers of HBV and positive for antibody to HBe. The DNA clones for precore and S genes were propagated from patients and spouses and sequenced. Because of the conservation of S-gene sequences and the identity of subtypes between patient and spouse, it was suggested that patients were infected with hepatitis B virus from their spouses, not from other sources. A TGG-to-TAG mutation at the 28th codon of the precore gene of hepatitis B virus was commonly observed in all DNA clones from patients with fulminant hepatitis and from their spouses. A 29th-codon GGC-to-GAC mutation was additionally evident in DNAs from one patient-and-spouse couple. A significant rise in the circulating hepatitis B virus concentration was transiently observed in the index spouse of this case just before development of fulminant hepatitis in her husband. The increase in circulating HBV DNA was associated with a rise in abundancy of variants with mutations at both the 28th and 29th codons, compared with variants with only a 28th-codon mutation. The double mutation in hepatitis B virus DNA may either help the virus escape immune surveillance or replicate at a higher rate than before.