A YIDD Mutation in a Case of Recurrent Hepatitis B after Liver Transplantation Induced by an S-escape Mutant

A 47-year-old woman underwent orthotopic liver transplantation (OLT) for hepatitis B virus (HBV)-related end-stage liver cirrhosis. The patient received hepatitis B immunoglobulin prophylaxis after OLT. Despite the protective level of the serum anti-hepatitis-B surface antibody, HBV recurred at 22 months post-OLT and induced subacute hepatic failure. The pre-OLT HBV genome contained a complex mutation pattern in overlapping frame regions of the surface (S) and polymerase (P) genes, which is the same mutation pattern as seen in post-OLT HBV DNA. G145R and K141R mutations in the "a" determinant were detected only in the post-OLT sample. Clevudine (30 mg once daily) was administered for recurrent hepatitis B. Hepatitis B was reactivated with a flare-up, and a M204I mutation (YIDD mutant type) appeared with a higher viral load at 9 months after clevudine treatment. We report here a case of a YIDD mutation that developed in recurrent hepatitis B after OLT induced by an S-escape mutant.

Detection of Hepatitis B Virus Surface Antigen Mutants / 대한진단검사의학회지

BACKGROUND: Mutation in the "a" determinant of HBsAg can alter the hepatitis B virus surface antigen (HBsAg) affinity to anti-HBs, which might escape detection by HBsAg immunoassays. This study was to evaluate the ability to detect the HBsAg mutants of diagnostic kits commonly used in laboratories in Korea. METHODS: Nine different recombinant HBsAg mutant panels provided by Abbott Laboratories (Abbott Park, USA) were assayed by Abbott AxSYM and Bayer ADVIA Centaur (Bayer HealthCare LLC, Tarrytown, USA). The performance of diagnostic kits was investigated through the External Quality Assurance Program of the Korean Association of Quality Assurance of Clinical Laboratory (KAQACL) using a recombinant HBsAg mutant (G145R) also kindly provided by Abbott Laboratories. HBsAg mutation was evaluated in patients' sera, whose results of HBV markers were unusual, using HBV DNA sequence analysis. RESULTS: Although Abbott AxSYM detected all of the nine recombinant mutants tested in this study, Bayer ADVIA Centaur failed to detect D144A and recombinant mutants with 2 mutations including G145R. Seven different diagnostic kits, such as Abbott Architect, AxSYM and IMx, Immulite (DPC, Los Angeles, USA), Cobas Core (Roche Diagnostics GmbH, Mannheim, Germany), BEP (Dade Behring, Marburg, Germany), and VIDAS (bioMerieux, France) used in 70 of the 142 participating laboratories of KAQACL could detect the recombinant HBsAg mutant, G145R. HBsAg mutants in native sera of 2 Korean patients with the concurrent presence of HBsAg and anti-HBs, were also detected easily by Elecsys (Roche Diagnostics GmbH, Mannheim, Germany), ADVIA Centaur, and Axsym. By sequence analysis, one of the patients was found to have I126S mutation and the other patient multiple mutations of Q54R, L98V, and Q101R. CONCLUSIONS: HBsAg mutants are probably more frequent even in normal diagnostic settings than previously believed. Detection of HBsAg needs to be improved by the introduction of new HBsAg assays able to recognize so far described HBsAg mutants and with a lower detection threshold than current immunoassays in order to detect the smallest amounts of HBsAg in low level carriers.