Inside and outside the liver: hepatitis-associated aplastic anaemia (haaa) in three paediatric cases.

Background: Hepatitis-associated aplastic anemia (HAAA) is a variant of aplastic anemia (AA) in which pancytopenia appears two to three months after an acute hepatitis [1]. The etiology of this syndrome is still uncompletely clarified: a role of various hepatitis and non hepatitis viruses (i.e. CMV, EBV and Parvovirus B19) has been detected; genetic predisposition and immune-mediated mechanisms (including imbalance of the T cell immune system and the response to immunosuppressive therapy) are also considered to have a pivotal role. Specific aim:We report three paediatric cases with HAAA who where successfully treated with haematopoietic stem cell transplantation (HSCT) or with administration of anti-lymphocyte globulins. Case serie: (1) A formerly healthy 9 year old boy was admitted to our Unit of Paediatric Gastroenterology and Hepatology for detection of elevated transaminases and GGT at blood tests prescribed for sudden appearance of hecchymoses and petechiae at his limbs, feet and face. No trauma had occurred. In the previous two months, asthenia had been referred. Blood tests showed pancytopenia and repeated transfusions of immunoglobulines and platelets were required. CRP-DNA for Parvovirus B19 was positive both on blood and on bone marrow aspirate. Bone marrow aspirate and bone biopsy confirmed AA. Given the absence of any recovery of the medullar function within one month of follow-up, a HSCT was successfully performed thank to the HLA compatibility of one sibling. (2) A 12 year old boy was evaluated at our Unit for jaundice with acute onset. A diagnosis of Type 1 Autoimmune Hepatitis (AIH 1) was based on both serologic profile and liver biopsy. The genetic screening for thiopurine methyltransferase excluded mutations, so a treatment with azathioprine was began to withdrawal corticosteroids. Pancytopenia was detected after two weeks of therapy. The CRPDNA for Parvovirus B19, initially negative at the time of AIH 1 diagnosis, turned out to be positive on both peripheral blood Oral Communications / Digestive and Liver Disease 44 Suppl. 4 (2012) S241–S257 S251 and bone marrow. Pancytopenia persisted with a worsening trend until the appearance of clinical signs (major epistaxis, ecchymoses) and repeated administrations of immunoglobulins, platelets and erythrocytes were needed. A bone biopsy evidenced AA. HSCT was finally required, and the existence of a HLA compatible twin made it feasible. (3) A 3 year old boy was admitted at our Unit for acute jaundice and detection of leucopenia, thrombocytopenia and elevated transaminases. Infusions of platelets and erythrocytes were required, given a progressive worsening of the bone marrow function. A bone biopsy evidenced AA. An immunosuppressive treatment with anti-lymphocyte globulins, cyclosporine, methylprednisolone was administered, together with G-CSF. No infective causes were detected. The bone marrow and liver function increased significantly until a final recovery, so that no bone marrow transplantation was needed. Discussion: Diagnosis of HAAA includes clinical manifestations, blood profiling, viral testing, immune functioning and bone marrow examination. Patients presenting the features of HAAA are mostly treated with HSCT from HLA matched donor. Immunosuppressive therapy has a minor efficacy, as far as it is currently demonstrated. Table Pts Clinical onset AST/ ALT (U/L) GGT (U/L) Parvovirus B19 DNA PCR on blood and bone marrow Ig adm. and blood component transfusions Anti-lymphocyte globulins and/or G-CSF Adm. Allogeneic HSCT Follow-up since diagnosis Current clinical and haemat. outcome Pt 1 Hecchymoses and petechiae at limbs, feet and face Asthenia 1284/ 2949 111 Positive Yes No Yes 1 year Good Pt 2 Jaundice major epistaxis ecchymoses at limbs 540/ 780 94 Positive Yes No Yes 5 months Good Pt 3 Jaundice 1357/ 2322 230 No Yes Yes No 10 years Good Pt: Patient, Adm.: Administration, Ig: Immunoglobulines, Transpl: Transplantation, Haemat.: Haematological, HSCT: Haematopoietic Stem Cell Transplantation. Reference(s) [1] Rauff B, Idrees M, Shah SA, Butt S, Butt AM, Ali L, Hussain A, Irshad- Ur-Rehman, Ali M. Hepatitis associated aplastic anemia: a review. Virol J. 2011 Feb 28;8: 87.