HBV reactivation after kidney transplantation

doi:10.1016/j.jcv.2004.10.006

Journal of Clinical Virology

Volume 32, Issue 2, February 2005, Pages 162-165

https://doi.org/10.1016/j.jcv.2004.10.006 Get rights and content

Abstract

Recent studies suggest that reappearance of hepatitis B surface antigen (HBsAg) and loss of anti-HBs antibodies may be common events in bone marrow recipients and patients with chemotherapy. In this study, we reviewed the virologic laboratory records from kidney recipients. Out of 1512 patients, 228 had been diagnosed with resolved HBV infection (anti-HBc positive, HBsAg negative) but normal liver enzyme levels prior to kidney transplantation. Reappearance of HBsAg after kidney transplantation was observed in two (0.9%) of those patients, which may be attributed to reactivation of a latent infection or to a new HBV infection. In both of the patients, HBV infection may have been reactivated although immunosuppression was just on a low level over the whole period. We conclude that natural immunity to HBV may not protect against reactivation in patients with suppression of the immune system. Periodic follow-up of HBV serology for early diagnosis of reactivation is highly recommended in transplant recipients.

Introduction

In transplant recipients, hepatitis B virus (HBV) infection is associated with significant morbidity and mortality by cirrhosis or hepatocellular carcinoma. Immunosuppression increases the risk of HBV reactivation, defined as reappearance of the ‘e’ antigen (HBeAg) in the serum of hepatitis B surface antigen (HBsAg) positive patients. In bone marrow transplant recipients and patients undergoing chemotherapy with previously resolved HBV infection, reappearance of HBsAg and loss of anti-HBsAg were described in several case reports (Lok et al., 1991, Martin et al., 1995; Knöll et al., 2004). In solid organ recipients, however, reactivation seems to be a rather rare event and is not well described in the literature. Here, we report the occurrence of HBV reactivation in two kidney transplant recipients.

Section snippets

Case report

In this study, we reviewed virologic laboratory records of kidney recipients. Out 1512 patients, 228 had been diagnosed with resolved HBV infection (anti-HBc positive, HBsAg negative) but normal liver enzyme levels prior to kidney transplantation. Reappearance of HBsAg after kidney transplantation was observed in two (0.9%) of those patients.

The first patient was a 75-year old man who was dialysed from 1985 onwards because of polycystic kidneys. In 1988, he received a kidney from a donor who

Discussion

We describe two transplant patients with serological evidence of resolved HBV infection in whom HBsAg reappeared after transplantation. Reappearance of replicating HBV in patients with resolved infection may be caused by re-infection, especially in the setting of hemodialysis. In this study, we were not able to compare the sequences of the HBV strains responsible for the initial infection to those ones appearing after transplantation. It, however, may be most likely a result of viral

References (15)

A. Berger et al.
High frequency of HCV infection in individuals with isolated antibody to hepatitis B core antigen
Intervirology
(2000)
C. Blanpain et al.
Reactivation of hepatitis B after transplantation in patients with pre-existing anti-hepatitis B surface antigen antibodies: report on three cases and review of the literature
Transplantation
(1998)
B.T. Duhart et al.
Retrospective evaluation of the risk of hepatitis B virus reactivation after transplantation
Transpl Infect Dis
(2003)
W. Grotz et al.
Occurrence and management of hepatitis B virus reactivation following kidney transplantation
Clin Nephrol
(1998)
K. Kidd-Ljunggren et al.
Reappearance of hepatitis B 10 years after kidney transplantation
N Engl J Med
(1999)
A. Knöll et al.
Reactivation of resolved hepatitis B virus infection after allogeneic haematopoietic stem cell transplantation
Bone Marrow Transplant
(2004)
A. Larghi et al.
Hepatitis B virus reactivation after kidney transplantation and new onset lymphoma
J Clin Gastroenterol
(2003)

There are more references available in the full text version of this article.

Cited by (67)

Hepatitis B Virus Reactivation in Kidney Transplant Recipients Treated With Belatacept
2023, Kidney International Reports
Hepatitis B virus (HBV) reactivation in kidney transplant recipients has been reported in 3% to 9% of anti-HBc antibody (HBcAb)-positive HBs antigen (HBsAg)-negative patients. It has not been studied in patients receiving belatacept, a selective costimulation blocker.
We performed a retrospective study of all transplant recipients receiving belatacept in 2 kidney transplantation centers in France. Among HBcAb-positive patients, we analyzed HBV reactivation rate, outcomes, and risk factors.
A total of 135 patients treated with belatacept were included: 32 were HBcAb-positive and 2 were HBsAg-positive. Seven patients reactivated HBV (21.9% of HBcAb-positive patients), including 5 HBsAg-negative patients (16.7% of HBcAb-positive HBsAg-negative patients). Reactivation occurred 54.8 (± 70.9) months after transplantation. One patient presented with severe hepatitis and 1 patient developed cirrhosis. There was no significant difference in survival between patients that reactivated HBV and patients that did not: 5-year patient survival of 100% (28.6; 100) and 83.4% (67.6; 100), respectively (P = 0.363); and 5-year graft survival of 100% (28.6; 100) and 79.8% (61.7; 100), respectively (P = 0.335). No factor, including HBsAb positivity and antiviral prophylaxis, was statistically associated with the risk of HBV reactivation.
HBV reactivation rate was high in patients treated with belatacept when compared with previous transplantation studies. HBV reactivation did not impact survival. Further studies are needed to confirm these results. A systematic antiviral prophylaxis for these patients should be considered and evaluated.
Screening and Prophylaxis to Prevent Hepatitis B Reactivation: Transplant Recipients
2019, Clinics in Liver Disease
Hepatitis B virus reactivation after heart transplant: Incidence and clinical impact
2017, Journal of Clinical Virology
Occult hepatitis B infection consists of persistence of HBV genomes in hepatocytes,absence of serum HBsAg, low/undetectable serum HBVDNA. Reactivation of HBV infection may occur during immunosuppression, but few data are available in heart transplant.
We followed-up heart recipients with or without markers of previous HBV infection,evaluating prevalence of HBV markers, incidence of HBV reactivation and its virological and clinical features.
Heart failure patients listed for heart transplant (2007–2013) were screened for current or past HBV infection. Transplanted patients with past HBV infection (anti-HBc+/±anti-HBs+/HBVDNA−) were followed up as cases, and an equal number of HBV negative patients as controls. Virological reactivation was detected by standard real-time and home-made highly sensitive PCR (surface/core HBVDNA regions). Clinical status and progression were assessed by liver histology, ultrasound or elastography.
67 patients underwent heart transplant, including 4 (5.9%) HBsAg+ subjects. Cases were 11/67 (16.4%). During a median follow-up of 30 months, only one of these 11 patients presented viral reactivation (HBVDNA 209 IU/mL) at month 22, and started antiviral treatment. Four other recipients showed virological events of uncertain significance (sensitive PCR-only intermittently positive). Clinical signs of liver disease were observed in only one case at the last follow-up. A nonsignificant difference in survival was observed between cases and all other heart recipients without prior HBV contact (death rate 5/11 vs 15/52, respectively; p = 0.097).
HBV genotypic reactivation in HBsAg−/anti-HBc+/HBVDNA− heart recipients is uncommon. Virological events of uncertain significance occur more frequently; their clinical impact seems to be negligible.
Considerable decrease in antibodies against hepatitis B surface antigen following kidney transplantation
2015, Journal of Clinical Virology
Citation Excerpt :
Hepatitis B virus (HBV) infections still represent a significant cause of morbidity and mortality in kidney transplant recipients (KTRs) [1]. In addition to recipients with chronic HBV infection at the time of transplantation, other patients with past resolved HBV infection can experience HBV reactivation, mostly when they are devoid of anti-hepatitis B surface antigen antibodies (anti-HBsAb) [2–6]. Moreover, KTRs who are not immunized against HBV are at risk for de novo HBV infection through potential risks including graft, blood products transfusion and hemodialysis.
Immunization against hepatitis B virus (HBV) in kidney transplantation (KT) candidates and recipients is recommended. If anti-HBV surface antigen antibody (anti-HBsAb) titer of 10 IU/L is admitted to be protective, the optimal threshold, at and after KT, is unknown. In addition, the natural evolution of anti-HBsAb titers after KT is not reported.
To describe rates of protective immunity to HBV at time of KT (baseline) and evolution of anti-HBsAb titers during the following year.
We retrospectively analyzed HBV serology at baseline, 15 days, and 4 and 12 months post-KT. No patient received vaccination during the study period, but information about previous vaccination was unavailable.
At baseline 80% of 141 recipients had anti-HBsAb titer ≥10 IU/L. Among these 113 patients, 84 had subsequent HBV serologies at day 15 and month 4, and 67 had also serology at month 12. At month 12, 25% of patients had lost protective anti-HBsAb titers (p < 0.001). The duration of protective anti-HBsAb titers was significantly longer when the initial titer was ≥ 100 IU/L versus <100 IU/L (log-rank test p < 0.0001). Protective titers at month 12 persisted in 93% of patients with initial titer ≥100 IU/L compared to 33% with 10–100 IU/L titer (p < 0.0001). In contrast, duration of protective titers did not differ according to the anti-HBV core antigen antibody status at baseline.
Despite a high prevalence of protective anti-HBsAb titer at KT, the loss of protective immunity during the following year was considerable, particularly when initial anti-HBsAb titer was <100 IU/L.
Reactivation of Hepatitis B virus in kidney transplant recipients with previous clinically resolved infection: A single-center experience
2018, Nefrologia
Citation Excerpt :
This highlights the importance of assessing potential risk factors for reactivation since prophylaxis can prevent its occurrence. Only 4 retrospective studies addressed the risk of reactivation in HBsAg-negative and anti-HBc-positive KTR.7–9,13 The number of patients was small and reactivation rates varied from 0 to 6.5%.
Hepatitis B virus (HBV) reactivation in kidney transplant recipients (KTR) involves important morbidity and mortality. Despite being more common in patients who are HBsAg-positive, it may occur in patients with clinically resolved infection (HBsAg-negative and anti-HBc-positive), in whom the presence of the protective anti-HB antibody is thought to decrease the risk of reactivation. Data regarding reactivation rates in this population are scarce.
To retrospectively evaluate the risk of HBV reactivation in KTR with previously resolved infection.
Retrospective cohort study including patients who underwent a kidney transplant between January 1994 and December 2014 with resolved HBV infection at the time of transplantation (anti-HBc seropositivity without detectable HBsAg, with or without anti-HB-positive antibodies and normal liver enzymes).
Out of 966 patients, 95 patients with evidence of resolved HBV infection were analyzed, of which 86 had a titer of anti-HBs >10 mIU/ml. Mean follow-up time was 93 months; 12 patients had lost anti-HBs. Two patients showed evidence of reactivation. Risk factors associated with loss of anti-HBs were elderly age (>60) and occurrence of acute graft rejection (p < 0.05).
The risk of HBV reactivation in KTR with previously resolved infection is not negligible at 2%. Elderly age and acute rejection were associated with loss of anti-HBs, and these patients may benefit from closer monitoring of HBV DNA levels. Routine serology and/or HBV viral load monitoring in HBsAg-negative, anti-HBc-positive patients is recommended and should be emphasized in these patients.
La reactivación del virus de la hepatitis B (VHB) en receptores de trasplante renal (RTR) supone una importante morbilidad y mortalidad. A pesar de ser más frecuente en pacientes con HBsAg positivo, puede suceder en pacientes con infección clínicamente resuelta (HBsAg-negativo y anti-HBc-positivo). En estos casos, la presencia del anticuerpo protector anti-HBs parece disminuir el riesgo de reactivación. Existen escasos datos relativos a las tasas de reactivación en esta población.
Evaluación retrospectiva del riesgo de reactivación del VHB en RTR con infección previa resuelta.
Estudio de cohorte retrospectivo, incluyendo RTR entre enero de 1994 y diciembre de 2014, con infección VHB resuelta en el momento del trasplante (anti-HBc seropositivo, HBsAg indetectable, con o sin anticuerpo anti-HBs e enzimas hepáticas normales).
De un total de 966, 95 pacientes con evidencia de infección VHB resuelta fueron analizados; 86 tenían un título de anti-HBs > 10 mIU/ml. El tiempo medio de seguimiento fue de 93 meses, 12 pacientes habían perdido anti-HBs. Dos pacientes tuvieron evidencia de reactivación. Los factores de riesgo asociados a la pérdida de anti-HBs fueron la edad avanzada (>60) y la evidencia de rechazo agudo del injerto (p < 0,05).
El riesgo de reactivación del VHB en RTR con infección previamente resuelta (2%) no es despreciable. La edad avanzada y el rechazo agudo están asociados a la pérdida de anti-HBs, y estos pacientes podrían beneficiarse de una vigilancia de los niveles de DNA del VHB. Las serologías de rutina y/o la monitorización de la carga viral en pacientes HBsAg-negativo, anti-HBc-positivo está recomendado y debería ser enfatizado en estos pacientes.
Etiologies Associated With Elevated Liver Enzymes After Renal Transplant
2024, Experimental and Clinical Transplantation

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^☆: Presented in part at the fifth international symposium on molecular diagnostics in Laboratory Medicine, Graz, Austria, June 10–12, 2004.

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Short communicationHBV reactivation after kidney transplantation☆

Abstract

Introduction

Section snippets

Case report

Discussion

High frequency of HCV infection in individuals with isolated antibody to hepatitis B core antigen

Intervirology

Reactivation of hepatitis B after transplantation in patients with pre-existing anti-hepatitis B surface antigen antibodies: report on three cases and review of the literature

Transplantation

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

Transpl Infect Dis

Occurrence and management of hepatitis B virus reactivation following kidney transplantation

Clin Nephrol

Reappearance of hepatitis B 10 years after kidney transplantation

N Engl J Med

Reactivation of resolved hepatitis B virus infection after allogeneic haematopoietic stem cell transplantation

Bone Marrow Transplant

Hepatitis B virus reactivation after kidney transplantation and new onset lymphoma

J Clin Gastroenterol

Short communication
HBV reactivation after kidney transplantation☆