1 Departments of Surgery, 2 Immunology, 3 Internal Medicine and 4 Medical Technology, Medical College, National Cheng Kung University, Tainan, Taiwan
Sir,
Recently, an expanding spectrum of clinical disease has been attributed to human parvovirus B19 (B19) infection with adult seroprevalence rates of around 50% [1]. In the majority of cases, B19 infections may be subclinical or produce symptoms such as erythema infectiosum, aplastic anaemia and thrombocytopenia and rarely as acute hepatic dysfunction. The common aetiologic factors of acute hepatic dysfunction following kidney transplantation include viral infection such as hepatitis B virus (HBV), hepatitis C virus (HCV) infection, cytomegalovirus (CMV), herpes simplex, varicella and Epstein-Barr virus, immunosuppressive drugs such as azathioprine, cyclosporin A and tacrolimus [2]. We report a kidney transplant with probable relapse of B19 infection associated with acute hepatic dysfunction and successfully treated with intravenous immunoglobulin.
Case.
In 1998, a 30-year-old woman underwent cadaveric kidney transplantation. Post-transplant immunosuppressive regimen included cyclosporin 10 mg/kg/day, mycophenolate mofetil 2 g/day p.o., in combination with methylprednisolone 120 mg/day intravenously for 4 days followed later by 20 mg/day p.o. Serum creatinine concentration was approximately in the range of 10 µmol/l after transplantation. Serum cyclosporin A trough concentration measured by Abbott TDX assay were maintained in the range of 350 ng/ml post-transplant. Five weeks later, AST and ALT progressively rise to 669 IU/l, 1086 respectively (Figure 1A) while platelet count and haemoglobin profile progressively decrease (Figure 1B
). Serological marker of hepatitis virus, pre- and post-transplant serum, were negative for HBsAg, HBeAg, IgM anti-HBc, HBV DNA, HCV RNA, HGV RNA and positive for anti-HBsAb and anti-HBeAb. There was no serological evidence of CMV, herpes simplex, varicella or Epstein Barr virus infection. B19 DNA, B19 IgG and IgM were all detected in the serum and bone marrow aspirate. B19-associated hepatitis was suspected and the dose of the immunosuppressive drugs were then reduced (cysclosporin 4 mg/kg/day, mycophenolate mofetil 1.5 g/day and prednisolone 5 mg/day). The IVIG was administered at a dosage of 0.4 g/kg/day for one week and patient responded promptly with hepatic enzyme, anaemia and thrombocytopenia returned to normal level (Figure 1A
,B
). She was doing well at 2-year follow up.
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Comment.
In our case, retrospective study of preserved serum using PCR analysis revealed that B19 DNA and IgG antibody were detected before transplantation indicating that a subclinical or chronic persistent B19 infection is present. Relapse or amplification of viral replication may have occurred following immunosuppressive therapy leading to hepatic dysfunction, which is rarely reported and may range from abnormal liver function to fulminant hepatic failure [3].
The initial immunological response to relapse of B19 infection is transitory production of IgM, typically present 5 days after relapse and which provides the greatest diagnostic value followed by a sustained production of IgG, detectable at 7 days which is long lived. Healthy immunocompetent patient may have detectable IgG but not viremic while many immunocomprised patients do not have detectable IgG or IgM antibody while in a state viraemia due to impaired humoral response [4].
IVIG contains high titer of B19 specific IgG. Its neutralizing antibodies can reduce but not eliminate the virus and has been proposed as a treatment modality for severe persistent anaemia in immunocompromised patients with B19 infection. This favourable prompt recovery of serum AST, ALT, haemoglobin and platelet count within 24 weeks following IVIG therapy in our case provides strong support for the hepatitis probably induced by relapse of chronic persistent or subclinical B19 infection. In this patient, we also reduced the immunosuppressive dosage given with IVIG therapy to treat PV B19 infection. The success of this regimen implies that immunosuppression plays an important role in the pathogenesis of the subclinical B19 infection [5].
In conclusion, clinical spectrum and manifestation of B19 infection is variable and its incidence should not be underestimated in kidney transplant patient undergoing immunosuppressive therapy, which may result in relapse of a chronic persistent or amplification of a subclinical infection. IVIG therapy, with reduced dosage of immunosuppressive therapy as described in this report, able to mount a satisfactory therapeutic response as shown by recovery of liver enzyme, anaemia and thrombocytopenia without enhancing acute rejection process.
References