The Relationship Between Virological Factors And HBV Reinfection After Liver Transplantation

End-stage liver disease and fulminant hepatic failure associated with HBV infection have a very poor prognosis. Orthotopic liver transplantation (OLT) is often the only therapeutic option. But HBV reinfection decreased greatly the long survival of patients.Objective: To make an inquiry into the relationship between virological factors (HBV DNA quantity pre-OLT and HBV S gene mutation) and HBV reinfection after OLT.Methods: The HBV DNA quantity of pre-OLT sera was done in 11 patients who underwent OLT for HBV-related end-stage liver disease by the fluorescence-quantitate PCR (FQ-PCR) and compared in 3 groups of OLT. HBV DNA was detected with our established nested PCR method in sera from 11 OLT patients, including pre-OLT and post-OLT sera, and15 patients with chronic hepatitis B. Then HBV DNA fragments were sequenced. Some of them with mutations in 'a' determinant region from11 cases were cloned and further sequenced. We compared pre-OLT sequences with post-OLT sequences, and also summed up all mutants of different groups. Changes of determinants caused by mutation were analysed with Goldkey.Results: The reinfected patients had much more HBV DNA before transplantation than that of nonreinfection. All patients who underwent OLT were adr subtype, except one adw clone, and 14 of 15 chronic hepatitis B cases were adr subtype. In natural situation, HBV S gene mutations may appear in long time HBV infected patients, and these mutants could alter the conformation of major hydrophilic region(MHR), such as ThrHlAsn, Metl33Thr, Glyl45Ala, et al. Conversion from minority of the clones to dominance or emergence of a new amino acid substitution posttransplantation was observed during HBIg treatment (Cysl38Arg) . Nucleotide substitutions of S ORF also could interfere with the sequences of P ORF, even resulting in stop codon. Besides all that was mentioned above, nucleotides substitutions were investigated to scatter in S gene outside MHR. They were not only in OLT patients, but also in chronic hepatitis B patients (VaL117Ala, Leu213Ile, and so on).Conclusions: Whether HBV was replicating or not and HBV4DNA quantity level was one of the factors that could influence on HBV reinfection. HBV subtype results were accord with the regional distribution of adr subtype because most of patients came from the North of China. Even if there were enough anti-HBs in blood, some mutants could cause HBV reinfection after OLT, which was called 'antibody escape'. HBIg exerted immune pressure, leading to the emergence or selection of S gene mutation.None of P gene mutants caused by S gene mutation involved the high-conserved region (YMDD motif), so it may have no influence in the susceptibility to anti-viral treatment, for example lamivudine. But stop codon emerged in P ORF may play a role in HBV productive capability. Amino acid substitutions in HBV S gene outside MHR, especially Leu213Ile, may be something about HBV chronic infection.