Management of giant cell hepatitis associated with chronic lymphocytic leukemia – a case series and review of the literature

Abstract

Giant cell hepatitis (GCH) is a rare diagnosis in adults that is found in 0.25% of liver biopsies. GCH has been associated with multiple causes including drugs (6-mercaptopurine, methotrexate), toxins, viruses and autoimmune. GCH has been described in few patients with chronic lymphocytic leukemia (CLL). Here we describe three patients diagnosed with GCH thought to be related to underlying CLL and its management. All of our patients were treated with a combination of immunosuppression as well as CLL-directed therapy to address CLL and concomitant liver disease. GCH is a rare manifestation of active CLL and should be ruled out with prompt liver biopsy in patients with CLL with persistent transaminitis without another attributable cause. Prompt treatment of GCH with immunosuppression is required to prevent long-term liver toxicity. If transaminitis does not improve with immunosuppression alone, the addition of CLL directed therapy should be considered in patients who carry this diagnosis to prevent long-term liver toxicity.

Facing the Unknown: Idiopathic Giant Cell Hepatitis

“…Although most cases of GCH have a known underlying etiology amenable to targeted therapeutics, idiopathic cases are poorly understood and treatment strategies remain ill-defined. 3 , 4 Mortality upwards of 15% have been reported in idiopathic cases because of progressive cirrhosis and liver failure. 5 Supportive care lacks consistent clinical benefit, 5 , 6 and effective pharmacotherapy remains overall elusive.…”

“… 3 Prognosis ranges from spontaneous resolution to fulminant hepatic failure and death. 4 As such, identifying the underlying cause is important in preventing disease progression. To date, management of idiopathic cases remains uncertain.…”

Post-infantile Giant Cell Hepatitis: A Literature Review and Meta-analysis

“…52 In cases related to CLL, treatment usually includes a combination of immunosuppression (e.g., corticosteroids, cyclophosphamide, and azathioprine) and CLL directed therapy (anti-CD20 antibody, chemotherapy and/or ibrutinib). [59][60][61] For patients with rapid progression and a fatal process, liver transplantation is the last resort.…”

“…The most commonly associated malignancy with PIGCH appeared to be chronic lymphocyte leukemia (CLL). 37,43,44,51,[57][58][59][60][61][62] In addition, other malignancies seen in patients with PIGCH included Hodgkin's lymphoma, papillary thyroid carcinoma, 63 anaplastic carcinoma, 58 and primary myelofibrosis. 51 Some patients had more than one etiology, including autoimmune disorder and a viral infection, 28,29,33 autoimmune disorder and medication, 11 CLL with autoimmune hemolytic anemia, and CLL with a viral infection.…”

Autoimmune post-infantile giant cell hepatitis: a case report and review of the literature

“…However, similar favourable outcomes will likely be seen with DAAs. The clinical course for patients with CLL-related PGCH is usually favourable when they are treated with immunosuppressants with corticosteroids, intravenous immunoglobulin, anti-CD20 antibodies (ie, rituximab) and CLL-directed therapy (ibrutinib or equivalent) (8). In histiocyte-related disease,…”