Liver disease and sickle cell disease: autoimmune hepatitis more than a coincidence; a systematic literature review

In patients with SCD, chronic liver damage is a common manifestation. More than 50% of SCD patients have elevated liver enzymes.  Common underlying aetiologies include sickle cell hepatic crisis, viral hepatitis, sickle cell intrahepatic cholestasis and hepatic sequestration in the acute  setting,  and  cholelithiasis  and  iron  overload  in  the  chronic  setting.  Autoimmune  hepatitis (AIH)  is  a  rare  disease  that  appears  to  occur  more  commonly  in  the  sickle  cell  disease  (SCD) population than in the general population. There are many schools of thought as to why this is the case,  including  the  phosphatidylserine  hypothesis,  the  heme  inflammatory  hypothesis,  the complement generation hypothesis, and the transfusion alloimmunization hypothesis.Due  to  the  natural  history  of  the  two  illnesses,  SCD  is  almost  always diagnosed  first  in  cases  of dual pathology. Symptoms such as jaundice, fatigue, and abdominal pain are common in SCD, as are  abnormal  liver  function  tests  (LFTs).  These  abnormalities,  attributed  to  the  other  more frequent liver involvements in SCD, can lead to delays in AIH diagnosis in this population.Corticosteroids,  sometimes  with  other  immunosuppressive  agents,  such  as  azathioprine,  are the cornerstone of acute AIH treatment. However, corticosteroid use in the SCD population has been shown to carry an increased risk of vaso-occlusive crises,providing a treatment dilemma.The following is a review of AIH in the SCD population, where we explore the pathophysiology behind the association between the two disorders, discuss an approach to investigating abnormal LFTs in SCD, and examine treatment options in this population with co-existing diseases.