BACKGROUND/AIMS: Liver transplantation for chronic liver disease due to hepatitis B virus infection is associated with a high risk of graft infection, graft failure and death. Many centres restrict this procedure to those seronegative for HBV-DNA (by hybridisation assay) and use prophylactic polyclonal human hepatitis B specific immunoglobulin to prevent infection of the graft, despite the very high cost. METHODS: We describe three patients who underwent liver transplantation for chronic HBV-related disease in whom death was due to fibrosing cholestatic hepatitis following graft infection with hepatitis B virus, despite receiving hepatitis B specific immunoglobulin. Variation within the immunodominant a epitope of HBsAg was sought by analysis of hepatitis B virus sequences and the use of a point mutation assay, following amplification from serum by the polymerase chain reaction. RESULTS: Prior to transplantation, Cases 1 and 2 had mutations at nucleotide 1902 (codon 145), resulting in G-C substitutions, which persisted at a low level after transplantation. In Case 2 a second mutant type with a G-A substitution at nucleotide 1902, became the predominant viral type post transplant. Case 3 had exclusively wild type virus before and after transplantation. The emergence of mutant type virus in Case 2 may have occurred because of immune pressure exerted by high titre anti-HBs detectable for more than 7 months. Cases 1 and 3 received only brief courses of anti-HBs therapy. The mutant viral surface antigen was not detected by a monoclonal antibody-based assay, and therefore the choice of HBsAg assay for post-transplant monitoring of patients who receive liver grafts for hepatitis B virus disease is important. CONCLUSIONS: A search for mutations affecting the a determinant prior to liver transplantation for HBV-related liver disease may help to identify those at risk of failure of prophylaxis. Monoclonal antibodies specific to the codon 145-mutant surface antigen might prevent graft infection, but other mutations might then emerge.
BACKGROUND/AIMS: Liver transplantation for chronic liver disease due to hepatitis B virus infection is associated with a high risk of graft infection, graft failure and death. Many centres restrict this procedure to those seronegative for HBV-DNA (by hybridisation assay) and use prophylactic polyclonal humanhepatitis B specific immunoglobulin to prevent infection of the graft, despite the very high cost. METHODS: We describe three patients who underwent liver transplantation for chronic HBV-related disease in whom death was due to fibrosing cholestatic hepatitis following graft infection with hepatitis B virus, despite receiving hepatitis B specific immunoglobulin. Variation within the immunodominant a epitope of HBsAg was sought by analysis of hepatitis B virus sequences and the use of a point mutation assay, following amplification from serum by the polymerase chain reaction. RESULTS: Prior to transplantation, Cases 1 and 2 had mutations at nucleotide 1902 (codon 145), resulting in G-C substitutions, which persisted at a low level after transplantation. In Case 2 a second mutant type with a G-A substitution at nucleotide 1902, became the predominant viral type post transplant. Case 3 had exclusively wild type virus before and after transplantation. The emergence of mutant type virus in Case 2 may have occurred because of immune pressure exerted by high titre anti-HBs detectable for more than 7 months. Cases 1 and 3 received only brief courses of anti-HBs therapy. The mutant viral surface antigen was not detected by a monoclonal antibody-based assay, and therefore the choice of HBsAg assay for post-transplant monitoring of patients who receive liver grafts for hepatitis B virus disease is important. CONCLUSIONS: A search for mutations affecting the a determinant prior to liver transplantation for HBV-related liver disease may help to identify those at risk of failure of prophylaxis. Monoclonal antibodies specific to the codon 145-mutant surface antigen might prevent graft infection, but other mutations might then emerge.
Authors: F J van Deursen; K Hino; D Wyatt; P Molyneaux; P Yates; L A Wallace; B C Dow; W F Carman Journal: J Clin Pathol Date: 1998-02 Impact factor: 3.411
Authors: V A Mbayed; J L López; P F Telenta; G Palacios; I Badía; A Ferro; C Galoppo; R Campos Journal: J Clin Microbiol Date: 1998-11 Impact factor: 5.948
Authors: Savio John; Karin L Andersson; Camille N Kotton; Martin Hertl; James F Markmann; A Benedict Cosimi; Raymond T Chung Journal: Therap Adv Gastroenterol Date: 2013-07 Impact factor: 4.409
Authors: R G Sawyer; R W McGory; M J Gaffey; C C McCullough; B L Shephard; C W Houlgrave; T S Ryan; M Kuhns; A McNamara; S H Caldwell; A Abdulkareem; T L Pruett Journal: Ann Surg Date: 1998-06 Impact factor: 12.969