De novo infection of hepatitis B virus in patients with orthotopic liver transplantation: Analysis by determining complete sequence of the genome

Abstract

De novo infection of hepatitis B virus (HBV) occurs after liver transplantation from donors with HBV markers that suggest past infection. In the present study, the complete nucleotide sequences of HBV derived from a donor and recipients were determined to determine the clinical and virological characteristics. A total of 57 donor-recipient pairs, which underwent living-related orthotopic liver transplantation, were enrolled in the present study; all were negative for HBsAg before transplantation. HBV DNA was tested in serum, liver tissue, and peripheral blood mononuclear cells (PBMCs) by the polymerase chain reaction (PCR). The nucleotide sequence of HBV was determined based on PCR products and the phylogenetic analysis. De novo infection of HBV was found in 3 of the 57 recipients. Anti-HBc was positive in all donors of 3 recipients with the de novo infection but was positive only in 4 donors of the remaining 54 recipients (P=0.001). HBV DNA was detected in the liver but not in the serum or PBMCs in donor 3 whose recipient developed de novo HBV infection. The nucleotide sequence covering entire genome of HBV (3,215 bases) derived from the liver of donor 3 had a homology of 99.8-100% with that derived from the serum of corresponding recipient 3. The strain of recipient 3 showed the closest association with that of the donor 3 by phylogenetic analysis. Complete sequences from two recipients with de novo HBV infection including recipient 3 conserved the basic organisation of HBV genome. Analysis of the entire nucleotide sequence of HBV genome proved that HBV existed in the liver of the donor with anti-HBc, and it caused de novo infection in the corresponding recipient.

Molecular Epidemiology and Evolution in an Outbreak of Fulminant Hepatitis B Virus

“…The complete genome sequences derived from the source and the two infected patients present a small number of differences (eight and nine differences for patients 15 and 16, respectively, from a total of 3,218 nt), many of which correspond to polymorphic sites in the source that are resolved in the recipients (five cases). Similar or even higher numbers of differences (ranging from 0 to 43) have been found by full-genome comparisons between HBV isolates from source and recipient pairs in several analyses (4,7,25,32). Our statistical analyses provide strong, additional support for a link between the three full genome sequences considered in the outbreak and additional full genome sequences obtained from HBV-infected individuals from the same population.…”

Are we ready for marginal hepatitis B core antibody-positive living liver donors?

“…Although clinical outcomes of a limited number of recipients of HBcAb ϩ living donor liver grafts have been reported previously, the short-and long-term safety of partial hepatectomy in HBcAb ϩ adult living liver transplant donors has not been described previously. 22,23 The majority of right-lobe liver donors in this series were women (65%), and mean donor graft weight was 574 g. The 24 HBcAb ϩ donors were significantly older than the 29 HBcAbϪ donors (median age, 42 v 31 years). Interestingly, 80% of the HBcAbϪ group were HBsAb ϩ , suggesting either previous HBV vaccination or exposure to HBV.…”

Current use of hepatitis B immune globulin for prevention of de novo hepatitis B in recipients receiving anti-HBc-positive livers

“…It is therefore difficult to differentiate DNH from recurrent HBV infection. Such a problem can be resolved by complete sequencing of the isolated viral genome [19]. Nonetheless, anti-HBc positivity in recipients offers some protection against DNH.…”

“…Overall, DNH rarely occurred with variable onset time in recipients positive for both serological markers. Among the 47 cases positive for both, anti-HBs and anti-HBc before LT in 10 studies, only 2 of them (4.3%) developed DNH after receiving liver allografts from anti-HBc-positive donors, even without prophylaxis (Table 1) [7,16,19,21,22,26,27,29,31,32]. Nevertheless, Takemura et al [33] reported a single case positive for both anti-HBs and anti-HBc before transplant, developing DNH at 35 months after LT.…”