Anti-HBc Seroconversion after Transplantation of Anti-HBc Positive Nonliver Organs to Anti-HBc Negative Recipients

Abstract

With great interest we read the article by Hartwig and colleagues published in the August 2005 issue of Transplantation that reported a low risk for transmission of the hepatitis B virus (HBV) by transplantation of lungs from anti-HBc(+)/HBsAg(-) donors to anti-HBc(-) recipients (1). None of the 29 recipients became HBsAg positive and even more importantly, none developed anti-HBc antibodies. Lung transplant recipients at Duke University are reported to have been vaccinated against hepatitis B before transplantation. However, no information was given on the pretransplant anti-HBs status of the patients studied by Hartwig et al. Thus, we do not know whether recipients were protected by the vaccine or were just not exposed to HBV. This information might be of importance before recommending that the use organs from anti-HBc(+)/HBsAg(−) donors is really safe. Moreover, there had been some studies reporting HBsAg(+) and anti-HBc-seroconversion rates of after kidney transplantation of up to 5% and 13%, respectively (2). Therefore, we investigated virological and serological characteristics of lung (n=17) and kidney (n=43) transplant recipients who underwent transplantation at our centre between 1999 and 2004. All patients received organs from anti-HBc(+)/HBsAg(−) donors and were anti-HBc(−) at the time of transplantation. Identical methods as reported previously were applied (3). Importantly and in line with the Hartwig paper, none of our organ transplant recipients became HBsAg-positive after transplantation (follow-up 1 to 32 months). In contrast, however, 4 of the 17 lung transplant recipients (24%) developed persistently detectable anti-HBc antibodies without evidence for transfusion transmitted anti-HBc antibodies. Anti-HBc seroconversion rates were lower after kidney transplantation with 7% (3/43, Table 1). This difference was almost significant despite the relatively low number of patients investigated (lung vs. kidney P=0.07). Thus, our data suggest that the risk for HBV transmission could be slightly higher after lung transplantation than after kidney transplantation.TABLE 1: HBsAg and anti-HBc seroconversion rates in kidney and lung transplant recipients receiving organs from anti-HBc(+)/HBsAg(-) donorsImportantly, anti-HBc antibodies developed in five individuals who were anti-HBs negative at time of transplantation, whereas only two of the anti-HBs-positive recipients seroconverted to anti-HBc(+) (Table 1). To further investigate the risk for HBV-reactivation, we used a highly sensitive TaqMan PCR (Arthus HBV Real Time PCR, Abbott Molecular Diagnostics, Wiesbaden, Germany; detection limit 4 IU/ml) to investigate 20 kidney transplant with anti-HBs titers less than <100 IU/L for low levels of HBV-DNA in serum. Fortunately, none of these patients tested HBV-DNA positive 1–6 months after transplantation and thus did not show evidence for occult hepatitis B infection. In conclusion, transplantation of nonliver organs from anti-HBc(+) donors is safe and not associated with transmission of hepatitis B or occult HBV-DNA. However, the long-term detection of anti-HBc antibodies in 24% of lung recipients indicates an immunological response to the hepatitis B core antigen, suggesting that indeed very low levels of HBV antigens can be transmitted. Because this seems to be preventable in part by anti-HBs antibodies, HBV vaccination of all organs transplant candidates should be mandatory to reduce the remaining risk for HBV infection by receiving an anti-HBc-positive nonliver organ. This might be important in particular for lung transplant recipients. Paraskevi Fytili Sandra Ciesek Michael P. Manns Heiner Wedemeyer Department of Gastroenterology Hepatology, and Endocrinology Medical School of Hannover Hannover, Germany Michael Neipp Fabian Helfritz Jürgen Klempnauer Department of Visceral and Transplant Surgery Medical School of Hannover Hannover, Germany Christoph Bara Axel Haverich Department of Heart-Thoracical Surgery Medical School of Hannover Hannover, Germany