Hepatitis B virus reactivation after renal transplantation: report of two cases

Recovery from acute hepatitis B virus (HBV) infection is associated with the loss of HBV DNA and hepatits B surface antigen (HBsAg) together with the development of antibodies against HBsAg (anti-HBs), HB ‘e’ antigen (anti-HBe) and HBcore antigen (anti-HBc). Individuals with serological markers implying past exposure to HBV are generally believed to have cleared the virus and also to have acquired protective immunity. However, clinical observation has shown that individuals with such a constellation may nevertheless develop the reactivation of HBV infection spontaneously or under immunosuppression. We describe two recipients of a renal transplant who exhibited prior serologic resolution of HBV infection and in whom HBsAg reappeared 10 and 9 months after renal transplantation, respectively. A 35-year-old woman presented with chronic renal failure of unknown etiology requiring dialysis for 2 years. Serologic test results revealed a prior HBV infection that had apparently resolved (HbsAg-negative, anti-HBcIgG and anti-HBs-positive) on admission. The patient’s antiHBs titer was 12 IU/ml, and serum HBV DNA level was not assessed at the time of transplantation. She underwent kidney transplantation from her brother, whose serologic testing was negative for HBV. Ten months after transplantation, she demonstrated the elevated levels of aspartate-aminotransferase (AST) 87 IU/ml and alanineaminotransferase (ALT) 133 IU/ml. Viral markers became positive for HBsAg, HBeAg and HBV DNA (by hybridization) but became negative for anti-HBe and anti-HBs. Liver biopsy revealed a mild degree of active hepatitis without fibrosis and immunohistochemical staining indicated the presence of HBsAg in hepatocytes. Lamivudine treatment was initiated. After 2 months of lamivudine treatment, AST and ALT levels were increased to 105, 193 IU/ml respectively, HBeAg became negative, anti-HBe became positive. Two months later, AST and ALT levels returned to normal and serum HBV DNA became negative with hybridization (Fig. 1). A 24-year-old man exhibited renal failure that had been treated with hemodialysis for 4 years. On admission and also at the time of renal transplantation, the test results for HBsAg were negative and that for anti-HBs, and antiHBcIgG were positive. The patient’s anti-HBs titer was 33 IU/ml at the time of transplantation. Serum HBV DNA levels were not assessed before and at the time of transplantation. He underwent a kidney transplantation from his father, whose serologic results were negative for HBsAg, anti-HBs, and anti-HBcIgG. Early rejection of the transplant (detected by renal biopsy) was treated with pulse steroid treatment. On follow-up 9 months later, liver function and serologic test results were as follows: AST, 54 IU/ml and ALT, 58 IU/ml, HBsAg positive, antiHBs and HBV DNA negative. Thirteen months after transplantation, AST and ALT levels were increased to 60 and 105 IU/ml, respectively and serum HBV DNA level became positive with hybridization (quantitatively > 0.5 pg/ml was accepted as positive). Liver biopsy revealed a mild degree of chronic active hepatitis without fibrosis, and immunohistochemical staining revealed HBsAg in all hepatocytes. Lamivudine treatment was initiated. After 6 months of lamivudine treatment, serum testing for HBV DNA yielded a negative result, and liver function tests returned to normal range (Fig. 2). In our report, both patients had experienced the HBV infection in past silently and they were not treated for HBV infection before the transplantation. For both patients, immunosuppression was not tapered after the diagnosis of hepatitis B reactivation. The possibility of occult HBV infection after complete clinical recovery from acute hepatitis is a known entitity, which suggests possible viral reactivation from occult HBV infection in the presence of anti-HBc and anti-HBs during long-term immunosuppressive therapy after renal transplantation [1,2]. The re-emergence of HBV infection in our cases might have been caused by reactivation of a latent infection or by a new HBV infection. If we had performed HBV DNA measurements at the time of transplantation and if we had got positive HBV DNA levels with low titers, the problem with our cases would be easier with being occult HBV infection. But as we did not perform serum HBV DNA level measurements for both patients at the time of the transplantation, and we were not able to compare the HBV strain identified in each patient’s initial infection with the strain detected after