Molecular analysis of the interspousal transmission of hepatitis B virus in two Japanese patients who acquired fulminant hepatitis B after 50 and 49 years of marriage

Abstract

A 71-year-old (C1I) and 69-year-old (C2I) Japanese female contracted fulminant hepatitis B after 50 and 49 years of marriage, respectively. Both index cases exhibited high levels of anti-HBc IgM antibodies (24.2 and 31.5 S/CO, respectively), suggestive of acute hepatitis B virus (HBV) infection, although they had no discernible risk factors for HBV infection, except for chronically HBV-infected spouses with detectable HBV DNA (3.3 log copies/ml [C1S: 72-year-old] and 7.2 log copies/ml [C2S: 71-year-old]). The HBV genotype/subgenotype was identical in each couple (B/B1 or C/C2). The HBV isolates from the index cases and spouses shared a nucleotide sequence identity of 99.5% and 99.7%, respectively, over the entire genome, and these four isolates had the highest nucleotide sequence identity of only 97% to HBV isolates deposited in DNA databases. Phylogenetic trees confirmed a close relationship of the HBV isolates between C1I and C1S and between C2I and C2S, supported by a high bootstrap value of 100% within each couple, indicating the transfer of HBV infection between spouses. These four isolates shared a precore mutation of G1896A known to be associated with fulminant hepatitis B. Although the history of sexual contact within a reasonable incubation period was obscure for one stable, monogamous couple (C1I and C1S), the other couple had a monogamous sexual relationship within six months prior to disease onset. This study indicates that two elderly Japanese patients with fulminant hepatitis B acquired HBV infection via interspousal (most likely sexual) transmission during long-lasting marriages.

Risk factors of hepatitis B virus infection between vaccinated and unvaccinated groups among spouses in 2006 and 2014: a cross-sectional study in Beijing

“…40,41 Anti-HBc-positive rate was higher in older individuals owing to the decline of anti-HBs level with time or exposure to more risk factors with long duration of marriage. 34,42 Single anti-HBs decreased with age, which was similar to the result in the vaccinated group.…”

“…Numerous previous studies had found that infected spouse was one of the causes of HBV infection. 13,19,22,42 HBV vaccine immunization was an effective approach to prevent HBV transmission among infected spouses in some studies. 17,49 In our study, infected spouse was significantly associated with HBsAg and anti-HBc only in the unvaccinated group in 2006, which meant that individuals who were hepatitis B patients or carriers would be a threat to their unvaccinated spouses.…”

The Study of Hepatitis B Virus Using Bioinformatics

“…Sequencing and bioinformatics have played an important role in demonstrating transmission routes, for which previous evidence could only be anecdotal. For example, molecular characterization of HBV together with phylogenetic analysis was used to demonstrate inter-spousal transmission of HBV even after long marriages, in two Japanese patients, who developed acute liver failure [54]. Similarly, the first known case of transfusion-transmitted HBV infection by blood screened using individual donor nucleic acid testing was confirmed by the 99.7% sequence homology between the complete genome sequences of the donor and the recipient HBV strains [26].…”

Acute Liver Failure Caused by the Transmission of Hepatitis B Virus from the Spouse after 38 Years of Marriage

“…When these patients contract HBV infection, most present with a mild clinical course, with only 10.9% showing acute hepatitis (5). In contrast, although HBV transmission after 10 years of marriage is rare, fulminant hepatitis has been reported in the spouse (6).…”

“…For instance, G1896A coupled with G1889A mutations in the precore region has been reported to increase HBV replication (9). In addition, these mutations are observed in patients with fulminant hepatitis (6).…”