TY - JOUR
T1 - Hepatitis B virus with antigenically altered hepatitis B surface antigen is selected by high-dose hepatitis B immune globulin after liver transplantation
AU - Protzer-Knolle, U.
AU - Naumann, U.
AU - Bartenschlager, R.
AU - Berg, T.
AU - Hopf, U.
AU - Zum Buschenfelde, K. H.M.
AU - Neuhaus, P.
AU - Gerken, G.
AU - Locarnini, S. A.
PY - 1998
Y1 - 1998
N2 - 'Escape' variants of hepatitis B virus (HBV) can cause infection despite previous immunization. These viruses show alterations of the immunogenic major hydrophilic loop of the HBV small surface protein (s-protein). We studied whether HBV 'escape' variants were selected in patients with graft infection after liver transplantation for HBV-related diseases who received passive immunoprophylaxis with high-dose polyclonal hepatitis B hyperimmune globulin (HBIG). For that, pre- and posttransplantation sera of 34 patients were analyzed for the occurrence of HBV S-gene variants. In addition, binding of in vitro-translated variant s-proteins to HBIG was studied. Variants with exchanges of amino acid (aa) 144 (s144) in HBV genotype A and 145 in genotype D (s145) were found to emerge, persist, and predominate during HBIG, and thus fulfilled criteria of 'escape' variants selected. In addition to already- known variants sG145R/K/E, we could demonstrate that newly described variants sX144G and sG145A were antigenically altered and showed impaired recognition by polyclonal HBIG in vitro. Diminished recognition of variant s-proteins correlated with the failure of HBIG to prevent infection of the liver graft with antigenically altered variant HBV. Patients infected with 'escape' variants s144 or s145 showed a worse clinical outcome compared with the other patients on high-dose, long-term HBIG prophylaxis (44% vs. 23% graft failure caused by HBV infection). Our results suggest that antigenically altered HBV variants s144 and s145 can be selected by HBIG and can influence clinical outcome after liver transplantation.
AB - 'Escape' variants of hepatitis B virus (HBV) can cause infection despite previous immunization. These viruses show alterations of the immunogenic major hydrophilic loop of the HBV small surface protein (s-protein). We studied whether HBV 'escape' variants were selected in patients with graft infection after liver transplantation for HBV-related diseases who received passive immunoprophylaxis with high-dose polyclonal hepatitis B hyperimmune globulin (HBIG). For that, pre- and posttransplantation sera of 34 patients were analyzed for the occurrence of HBV S-gene variants. In addition, binding of in vitro-translated variant s-proteins to HBIG was studied. Variants with exchanges of amino acid (aa) 144 (s144) in HBV genotype A and 145 in genotype D (s145) were found to emerge, persist, and predominate during HBIG, and thus fulfilled criteria of 'escape' variants selected. In addition to already- known variants sG145R/K/E, we could demonstrate that newly described variants sX144G and sG145A were antigenically altered and showed impaired recognition by polyclonal HBIG in vitro. Diminished recognition of variant s-proteins correlated with the failure of HBIG to prevent infection of the liver graft with antigenically altered variant HBV. Patients infected with 'escape' variants s144 or s145 showed a worse clinical outcome compared with the other patients on high-dose, long-term HBIG prophylaxis (44% vs. 23% graft failure caused by HBV infection). Our results suggest that antigenically altered HBV variants s144 and s145 can be selected by HBIG and can influence clinical outcome after liver transplantation.
UR - http://www.scopus.com/inward/record.url?scp=0031983151&partnerID=8YFLogxK
U2 - 10.1002/hep.510270138
DO - 10.1002/hep.510270138
M3 - Article
C2 - 9425945
AN - SCOPUS:0031983151
SN - 0270-9139
VL - 27
SP - 254
EP - 263
JO - Hepatology
JF - Hepatology
IS - 1
ER -
