Significant rate of hepatitis B reactivation following kidney transplantation in patients with resolved infection

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Abstract

Background

Limited data is available on the risk of hepatitis B virus (HBV) reactivation in patients with resolved infection undergoing kidney transplantation. It is generally thought that this risk is negligible.

Objectives

To evaluate the incidence of HBV reactivation in such patients, and the potential risk factors for reactivation.

Study design

Retrospective cohort study including 93 patients transplanted with a kidney between 1995 and 2007 who had evidence of resolved HBV infection (HBsAg negative, anti-HBc positive, anti-HBs positive or negative, and normal liver enzymes). HBV reactivation was defined as HBsAg reversion with HBV DNA > 2000 IU/mL.

Results

Six patients experienced HBsAg reversion followed by HBV reactivation, 3 within the first post-transplant year. Immunosuppression regimen was similar in patients with and without reactivation. Among patients with reactivation only one was positive for anti-HBs antibodies at time of transplantation; these were progressively lost before reactivation. The odds ratio for reactivation in patients without anti-HBs antibodies at transplantation compared to those with anti-HBs antibodies was 26 (95% CI [2.8–240.5], p = 0.0012). In patients with anti-HBs antibody titer above 100 IU/L, no reactivation was observed.

Conclusions

Reactivation rate of resolved hepatitis B is not negligible in patients without anti-HBs antibodies at transplantation. We suggest monitoring of liver tests and HBV serology including HBsAg and anti-HBs antibodies after transplantation as well as vaccination pre- and post-transplantation in all patients, including those with resolved hepatitis B, aiming at maintaining anti-HBs antibody level above 100 IU/L.

Section snippets

Background

Hepatitis B virus (HBV) infection entails a significant rate of morbidity and mortality in kidney transplant recipients (KTRs).1, 2 After successful renal transplantation, the rate of spontaneous hepatitis B surface antigen (HBsAg) clearance is decreased compared to the general population.3 Indeed, immunosuppression affects the T- and B-cell functions that are essential in the control of HBV infection, and steroids stimulate HBV replication by a direct effect on a glucocorticoid responsive

Objectives

The aims of our study were to evaluate the incidence of post-transplant HBV reactivation in patients who had previously cleared HBsAg and to identify potential risk factors for reactivation.

Study population

Retrospective cohort study included patients with previously resolved hepatitis B infection transplanted with a kidney at the Cliniques Universitaires Saint-Luc (Brussels, Belgium) between January 1995 and December 2007. Diagnostic criteria for resolved HBV infection at transplantation were: HBsAg negative, anti-HBc positive, anti-HBs positive or negative, and normal liver enzymes. HBsAg reversion was defined as the reappearance of HBsAg during follow-up. HBV reactivation was defined as HBsAg

Patient characteristics

The files of 764 KTRs were reviewed. Ninety-three patients (12%) were included (Table 1). All patients received 20 mg of prednisolone daily following transplantation, rapidly tapered to 5 mg/day at week 6.

Prophylaxis against cytomegalovirus was administered for a period of 3 months in seronegative patient receiving a seropositive graft. Patients did not receive prophylaxis against Pneumocystis.

Patient and graft survival

Patients were followed after transplantation for a median time of 73 [44–114] months. Five and 10-year

Discussion

Reactivation of HBV in patients with resolved infection could result from persisting occult HBV in the serum or the liver.16, 17, 18, 19, 20 In our 5 patients with HBV reactivation and available pre-transplant serum, HBV DNA was not detectable before transplantation in the serum of any of them. Reinfection with a different HBV strain seems improbable because neither patient received blood transfusion, underwent hemodialysis, or had other risk factors for hepatitis B in the post-transplant

Funding

None.

Competing interests

None declared.

Ethical approval

Ethical approval was provided by the Commission of Biomedical Ethics of the Université Catholique de Louvain in Brussels, Belgium.

References (38)

  • P. Romanet et al.

    Pitfall of hepatitis B surface antigen testing in a kidney transplant recipient presenting hepatitis B reactivation

    Clin Res Hepatol Gastroenterol

    (2011)
  • S. Barclay et al.

    Erratum to ‘The management of chronic hepatitis B in the immunocompromised patient: recommendations from a single topic meeting’

    J Clin Virol

    (2008)
  • P. Mathurin et al.

    Impact of hepatitis B and C virus on kidney transplantation outcome

    Hepatology

    (1999)
  • F. Fabrizi et al.

    HBsAg seropositive status and survival after renal transplantation: meta-analysis of observational studies

    Am J Transplant

    (2005)
  • S. Fornairon et al.

    The long-term virologic and pathologic impact of renal transplantation on chronic hepatitis B virus infection

    Transplantation

    (1996)
  • R. Tur-Kaspa et al.

    Hepatitis B virus DNA contains a glucocorticoid-responsive element

    Proc Natl Acad Sci U S A

    (1986)
  • J. Huskey et al.

    Chronic viral hepatitis in kidney transplantation

    Nat Rev Nephrol

    (2011)
  • G.K. Lau et al.

    Hepatic events after bone marrow transplantation in patients with hepatitis B infection: a case controlled study

    Bone Marrow Transplant

    (1997)
  • B.T. Duhart et al.

    Retrospective evaluation of the risk of hepatitis B virus reactivation after transplantation

    Transpl Infect Dis

    (2003)
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