Severe Aplastic Anemia following Acute Hepatitis from Toxic Liver Injury: Literature Review and Case Report of a Successful Outcome

Abstract

Hepatitis associated aplastic anemia (HAAA) is a rare syndrome in which severe aplastic anemia (SAA) complicates the recovery of acute hepatitis (AH). HAAA is described to occur with AH caused by viral infections and also with idiopathic cases of AH and no clear etiology of liver injury. Clinically, AH can be mild to fulminant and transient to persistent and precedes the onset SAA. It is assumed that immunologic dysregulation following AH leads to the development of SAA. Several observations have been made to elucidate the immune mediated injury mechanisms, ensuing from liver injury and progressing to trigger bone marrow failure with the involvement of activated lymphocytes and severe T-cell imbalance. HAAA has a very poor outcome and often requires bone marrow transplant (BMT). The findings of immune related myeloid injury implied the use of immunosuppressive therapy (IST) and led to improved survival from HAAA. We report a case of young male who presented with AH resulting from the intake of muscle building protein supplements and anabolic steroids. The liver injury slowly resolved with supportive care and after 4 months of attack of AH, he developed SAA. He was treated with IST with successful outcome without the need for a BMT.

Sequential transplantation and implications for clinical management: OLT followed by HCT and consequent RT in a pediatric patient

“…However, as in this case, if an HLA‐matched sibling is not available, literature suggests a trial of immunotherapy with citations of 50%‐80% response rates when using ATG and CNI therapy . If SAA then does not respond to immunotherapy, HLA‐matched, unrelated donor HCT is the next feasible therapeutic option . Overall evidence demonstrates that the liver graft tolerates the process of HCT (sibling or unrelated donor) well, with functioning of the original liver graft largely maintained after HCT .…”

“…19 It has been well documented that SAA is a complication of non-A-E hepatitis in children, with success reported both in immunotherapy treatment and undergoing HCT after resolution of hepatitis. [1][2][3][4][5][6][7][8][9][10]19 Table 1 summarizes the various reports published on patients with SAA complicating non-A-E hepatitis. [1][2][3][5][6][7][20][21][22][23][24][25][26] It is hypothesized that the complication of SAA is likely associated with the original mechanism of hepatic failure, rather than due to the transplantation, 6 and is likely mediated by immunopathologic mechanisms and inappropriate cytotoxic T-cell activation, as evidenced by response to immunotherapy.…”

“…[1][2][3][5][6][7][20][21][22][23][24][25][26] It is hypothesized that the complication of SAA is likely associated with the original mechanism of hepatic failure, rather than due to the transplantation, 6 and is likely mediated by immunopathologic mechanisms and inappropriate cytotoxic T-cell activation, as evidenced by response to immunotherapy. 3,4,9 This disease association has a high mortality rate, estimated in the 30%-50% range. Mortality is likely associated with systemic infections due to neutropenia and severe bleeding.…”

“…28 If SAA then does not respond to immunotherapy, HLAmatched, unrelated donor HCT is the next feasible therapeutic option. 2,4 Overall evidence demonstrates that the liver graft tolerates the process of HCT (sibling or unrelated donor) well, with functioning of the original liver graft largely maintained after HCT. 28 Doney et al demonstrated that 85% of patients who underwent HCT after SOT for SAA were alive 0.5-23 years after HCT.…”

“…SAA associated with hepatitis has a high mortality rate and is felt to be likely secondary to abnormal immunological activation. While there have been case reports of successful treatment with immunotherapy, these patients have also required HCT for continued bone marrow failure . Fortunately, despite the need for an additional transplant procedure, the process of undergoing HCT has been typically well tolerated by the liver graft…”