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To the Editor:

The number of hepatitis E virus (HEV) infections reported within the organ-transplant population has dramatically increased within the last few years. In this population, HEV infection may evolve to chronic hepatitis (1). However, no HEV reactivation has been reported in organ-transplant patients who were HEV seropositive at the time of transplantation (2). Conversely, one case of HEV reactivation has been reported in a patient with acute lymphoblastic leukemia after allogenic stem-cell transplantation (3). In contrast, no relapse was observed in another patient with chronic myelomonocytic leukemia and chronic HEV infection, who was cleared of the virus after ribavirin monotherapy, despite chemotherapy being given for malignancy (4). In another case, recurrence of chronic HEV infection was observed after a second liver transplantation; the patient had developed HEV cirrhosis and was still viremic at retransplantation (5). Thus, it is still unknown whether kidney-transplant patients, who present with HEV infection and who are cleared of the virus during the first kidney-transplantation period, can suffer a relapse after retransplantation.

Between January 2004 and August 2011, at our department, 42 kidney-transplant recipients developed genotype-3 HEV infection, defined as detection of HEV–RNA in the serum and/or stools. Of these, three patients (two men, one woman) required hemodialysis and retransplantation (Table 1). The times between the first kidney transplantation and HEV infection were 48, 75 and 108 months. Patient 1 had spontaneous HEV clearance at 2 months after HEV infection. Patient 2 developed chronic HEV infection and was cleared of the HEV within 19 months after immunosuppressant dose was significantly reduced. Patient 3 remained viremic at 3 months after complete withdrawal of immunosuppressants, which was done when hemodialysis was initiated. This third patient was, then, successfully treated with a 3-month course of pegylated interferon. All three patients underwent a second kidney transplantation at, respectively, 22, 24 and 33 months after HEV clearance. The times on dialysis between kidney transplantations were 11, 23 and 30 months. After kidney transplantation, all three patients received induction therapy (one patient received rabbit antithymocyte globulin and the two others received basiliximab) associated with tacrolimus, mycophenolic acid and steroids. By 3, 3 and 36 months posttransplant, none of the three patients had recurrence of HEV. HEV–RNA was looked for in the serum and stools before the second transplantation, and very frequently thereafter. Of interest, patient 1 did not present with seroconversion after HEV infection. Alanine-aminotransferase levels were within normal ranges before retransplantation and remained stable at the last follow up.

Table 1.  Hepatitis E virus parameters
PatientsPatient 1Patient 2Patient 3
  1. KT = kidney transplantation; HEV = hepatitis E virus; ALT = alanine aminotransferase.

  2. 1Patient 3 received antiviral therapy after hemodialysis was started.

Time between first KT and HEV infection (months)10875 48
HEV-infection patternResolving hepatitisChronic hepatitisChronic hepatitis
Time between HEV infection and HEV clearance (months)  219 56
Mode of HEV clearanceSpontaneousImmunosuppressant dose reductionPegylated interferon
Time between HEV clearance and start of dialysis (months) 1011 –1
Time between dialysis and second KT (months) 2311 30
Time between HEV clearance and retransplantation (months) 3322 24
Time between retransplantation and last follow up (months) 36 3  3
Anti-HEV IgG at start of dialysisNegativePositiveNegative
Anti-HEV IgG at retransplantationNegativePositivePositive
Anti-HEV IgG at last follow upNegativePositivePositive
Anti-HEV IgM at start of dialysisNegativePositivePositive
Anti-HEV IgM at retransplantationNegativePositivePositive
Anti-HEV IgM at last follow upNegativePositivePositive
HEV–RNA at start of dialysisNegativeNegativePositive
HEV–RNA at retransplantationNegativeNegativeNegative
HEV–RNA at last follow upNegativeNegativeNegative
ALT level at start of dialysis (IU/L) 1412139
ALT level at retransplantation (IU/L) 1415 13
ALT level at last follow up (IU/L) 1815 15

These data are the first to show that kidney-transplant patients infected with HEV, who are then cleared of the virus and maintain sustained clearance, that is, HEV clearance for at least 6 months, do not relapse after retransplantation despite receiving an immunosuppressive regimen that includes an induction therapy. Hence, dialysis patients previously infected by HEV can be proposed for retransplantation. A larger series is needed to confirm our observations.

Disclosure

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The authors of this manuscript have no conflicts of interest to disclose as described by the American Journal of Transplantation.

References

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