Pure Red Cell Aplasia Due To Parvovirus B19 Infection After Liver Transplantation

BackgroundOrthotopic liver transplantation is a well-established procedure in the treatment for the end-stage liver diseases. The graft and patient survival rates are increasing due to advanced surgical technique, successful immunosuppression and consummate perioperative management. However, the postoperative extrahepatic complications are becoming one of the critical causes of long-term mortality and frequently happened. These posttransplant complications are raising a worldwide concern toward the long-term survival of transplant recipients. Pure red cell aplasia (PRCA), as a relatively rare hematological complication characterized by the inhibition of bone marrow erythropoiesis, is one of these concerns. Manifested as normochromic normocytic anemia, reticulocytopenia and a striking erythroblastopenia in the bone marrow, acquired PRCA has been described in solid organ transplant recipients with an increasing number. However, there has been no such case described in liver transplant recipients in China. It is an unusual type of severe anemia after transplantation and requires special attention. On the other hand, viral infections after solid organ transplantation are becoming acommon recurrence due to the long-term state of immunosuppression. There have been relatively standard measures and experiences to deal with such infections due to common pathogens like cytomegalovirus, EB virus, hepatitis virus and nerpes vinrus hominis-6. However, dealing experiences are very inadequate to treat the relatively rare viral infections. Parvovirus B19 (PVB19) is one of these pathogens. PVB19 is the most common virus inducing PRCA after solid organ transplantation, and such cases were reported mainly in kidney transplant recipients and few reports on liver transplant recipients. Base on previous reports and related literature, sparse information on managing the easily recurring disease remains. Host-pathogen interactions of PVB19 after therapy, which are suggestive of complete cure or potential of recurrence, are still unclear.Patients and MethodsWe retrospectively described the Chinese first case of PRCA due to PVB19 infection after liver transplantation and summarized the cliniacal data of total 7 cases of such patients ever reported in the literature. Furthermore, an English-language literature search was conducted using MEDLINE (1974 to January 2007) on pure red cell aplasia, solid organ transplantation, immunosuppressant, parvovirus B19 and other related reports and reviews. Based on these clinical data and related literature, we systematically review the causes, diagnosis, therapy, prognosis and prevention of acquired PRCA after solid organ transplantation in this paper.ResultsMEDLINE search of English language articles published between 1974 and January 2007 revealed only 7 reports of PVB19 producing PRCA after liver transplantation. Herein, we describe the eighth liver transplant patient. To our knowledge, this is the first reported case associated with liver transplantation in China. Half of the 8 patients were children (4 cases), and 5 of them were male. The median age of the patients at the time of presentation with anemia was 13.7 years (range of 1.4 to 43 years) at a median time of 4 months (range of 11 days to 34 months) after liver transplantation. Six patients hadtacrolimus-based immunosuppression and 2 had cyclosporine-based immunosuppression. Severe anemia with reticulocytopenia was seen in all cases. The median lowest hemoglobin level was 69.5 g/L (range of 21 to 75 g/L). In addition, 2 patients had fever, one with leucopenia, one child with a typical rash of erythema infectiosum and one adult suffering from arthralgia. Bone marrow biopsies were performed on 4 patients and all revealed erythroid hypoplasia with presence of giant pronormoblasts. Four patients were positive for both PVB19-IgM and IgG at the time of evaluation, 2 were IgM positive and IgG negative and one was IgM negative and IgG positive. The patient we report was not tested for anti-viral antibodies at the time of making a diagnosis. Viral DNA detection using PCR technique was made in 4 patients and all showed positive results. All reports could not demonstrate the sources and routes of virus infection. Except one report did not offer the treatment information, all other 7 cases required treatment with commercial intravenous immunoglobulin (FVIG). Five patients had good response to the treatment and obtained long-term recovery from anemia, while recurrence of the disease appeared in 2 patients; one recovered after a second course of IVIG therapy, and another needed repeated IVIG infusion combined with plasmapheresis. Of the 4 patients detected for viral DNA, PVB19 viremia was successfully resolved in 2 patents after the treatment. Unlike the previous cases, our case held a persistent low-level viral load without recurrence of PRCA for 5 months' follow-up.ConclusionsSolid organ transplant recipients are at risk of developing PRCA. Acquired PRCA after solid organ transplantation may develop due to side effects of immunosuppressants and PVB19 infection. Diagnosis is made upon hemogram, bone marrow examination and further etiological identification including PCR techniques for viral DNA detection. Treatment includes drug substitution and high-dose IVIG therapy, respectively. Reffering to PRCA due to PVB19 infection, most patients can be successfully cured but the disease easily recurs. There is no proven specific and practical strategy available to preventPVB19 infection. Screening for potential virus and developing new strong virus inactivation methods in blood products and exploring PVB19 vaccines are being considered. Further research on exploring most effective modality of therapy without recurrence and preventative strategies are encouraged.