Sequential liver and haematopoietic stem cell transplantation in a case of fulminant hepatitis associated liver failure and aplastic anaemia

Abstract

Hepatitis-associated aplastic anaemia (HAAA) is a potentially lethal complication of acute hepatitis where pancytopenia develops a few months after the acute hepatitis episode. As with severe aplastic anaemia (SAA), the pathogenic mechanism is thought to be immune-mediated destruction of haematopoietic stem cells (HSCs) leading to bone marrow failure and pancytopenia. Acute hepatitis may progress to fulminant hepatic failure (FHF) necessitating liver transplantation as a life-saving measure. The optimal management of SAA in young patients is an allogeneic haematopoietic stem cell transplantation (HSCT) from a suitably matched donor. Both modalities are associated with considerable morbidity.We present the case of a patient treated with deceased donor liver transplantation for FHF secondary to acute hepatitis who subsequently developed SAA that was successfully treated with a matched unrelated donor (MUD) allogeneic HSCT. To our knowledge, this is the first reported adult case of post-liver transplant SAA treated with MUD HSCT. | C A S E REP ORTA previously healthy 19-year-old female presented with jaundice, lethargy and abdominal pain in October 2017. Initial laboratory analysis revealed elevated aspartate aminotransferase (AST) 1809 U/L, alanine aminotransferase (ALT) 2303 U/L, bilirubin 505 μmol/L and INR 1.54. Complete blood count and renal function were normal with haemoglobin (Hb) 133 g/L, white blood count (WBC) Abstract The management of severe aplastic anaemia is particularly challenging when it occurs in the context of recent liver transplantation. Rapid identification of a suitable donor followed by allogeneic haematopoietic stem cell transplantation is the only curative option. This scenario is often complicated by potentially life-threatening infections that develop as a consequence of immunosuppression. Alternative donor transplantation using suitably matched unrelated donors can be potentially life-saving when suitably matched sibling donors are unavailable. Above all, a dedicated interdisciplinary approach with seamless communication between hepatology, transplant surgery, haematology, and stem cell transplant services is essential to achieving optimaloutcomes. Herein, we describe a case of severe hepatitis leading to hepatic failure who was treated with liver transplantation from a deceased donor, and later received an allogeneic haematopoietic stem cell transplantation from a matched unrelated donor for hepatitis-associated aplastic anaemia. K E Y W O R D Sallogeneic blood and marrow transplantation, aplastic anaemia, liver transplantation

A case of hepatitis‐associated aplastic anaemia following living‐donor liver transplantation for fulminant hepatitis showing loss of heterozygosity in the 6p chromosome in the affected liver

“…On the other hand, FH did not recur after LDLT even though the donor's liver shared the HLA haplotype that was lost in the recipient liver as a result of 6pLOH. Previous studies that reported successful treatment of HAAA after LDLT with IST did not observe a recurrence of FH in the donor's liver either 5,9,10,12–14 . Although the reason for the non‐recurrence of FH in our patient is unclear, the target antigen of pathogenic CD8 + T cells may be a polymorphic protein unique to the recipient.…”

“…Previous studies that reported successful treatment of HAAA after LDLT with IST did not observe a recurrence of FH in the donor's liver either. 5,9,10,[12][13][14] Although the reason for the non-recurrence of FH in our patient is unclear, the target antigen of pathogenic CD8 + T cells may be a polymorphic protein unique to the recipient.…”

“…Although there are several reports about the development of HAAA following LDLT for FH, 5,[9][10][11] none have highlighted the aetiological association between HAAA and FH. Our findings demonstrated the presence of 6pLOH(+) hepatocytes in the excised liver tissue obtained during LDLT and the 6pLOH responsible for the lack of HLA-A31 in the patient's PB leucocytes after LDLT for the first time (Figure S4).…”

Successful Treatment of a 19-Month-Old Boy with Hepatitis Associated Aplastic Anemia by Infusion of Umbilical Cord-Derived Mesenchymal Stromal Cells: A Case Report

“…The cause of hepatitis appears to be an undetermined virus, and the underlying pathological mechanism may be immune-mediated 1 . Several cases of HAAA have been successfully treated by allogeneic hematopoietic stem cell transplantation (HSCT) or immunosuppressive treatment [2][3][4] . However, HSCT is not feasible for all patients.…”