Sickle Hepatopathy

Abstract

Sickle hepatopathy is an umbrella term describing various pattern of liver injury seen in patients with sickle cell disease. The disease is not uncommon in India; in terms of prevalence, India is second only to Sub-Saharan Africa where sickle cell disease is most prevalent. Hepatic involvement in sickle cell disease is not uncommon. Liver disease may result from viral hepatitis and iron overload due to multiple transfusions of blood products or due to disease activity causing varying changes in vasculature. The clinical spectrum of disease ranges from ischemic injury due to sickling of red blood cells in hepatic sinusoids, pigment gall stones, and acute/chronic sequestration syndromes. The sequestration syndromes are usually episodic and self-limiting requiring conservative management such as antibiotics and intravenous fluids or packed red cell transfusions. However, rarely these episodes may present with coagulopathy and encephalopathy like acute liver failure, which are life-threatening, requiring exchange transfusions or even liver transplantation. However, evidence for their benefits, optimal indications, and threshold to start exchange transfusion is limited. Similarly, there is paucity of the literature regarding the end point of exchange transfusion in this scenario. Liver transplantation may also be beneficial in end-stage liver disease. Hydroxyurea, the antitumor agent, which is popularly used to prevent life-threatening complications such as acute chest syndrome or stroke in these patients, has been used only sparingly in hepatic sequestrations. The purpose of this review is to provide insights into epidemiology of sickle cell disease in India and pathogenesis and classification of hepatobiliary involvement in sickle cell disease. Finally, various management options including exchange transfusion, liver transplantation, and hydroxyurea in hepatic sequestration syndromes will be discussed in brief.

Keywords: AASLD, American Association for the Study of Liver Diseases; ACLF, Acute on chronic liver failure; ALF, Acute liver failure; ALT, Alanine transaminase; AST, Aspartate transaminase; FFP, Fresh frozen plasma; GIT, Gastrointestinal tract; HAV, Hepatitis A virus; HBV, Hepatitis B virus; HCV, Hepatitis C virus; HEV, Hepatitis E virus; HIC, Hepatic iron content; HbS, Sickle hemoglobin; HbSS, Sickle cell disease homozygous; INR, International normalized ratio; PT, Prothrombin time; RUQ, Right upper quadrant; SC, Scheduled caste; SCD, Sickle cell disease; SCIC, Sickle cell intrahepatic cholestasis; ST, Scheduled tribe; TJLB, Transjugular liver biopsy; UDCA, Ursodeoxycholic acid; cholelithiasis; intrahepatic cholestasis; sickle cell hepatopathy; sickle cholangiopathy; sickle hepatic crisis.

Figure 1

An overview of the prevalence of the sickle cell gene in tribal population in different states of India. HbS, sickle hemoglobin.

Figure 2

Suggested outline for management of sickle cell intrahepatic cholestasis (SCIC). Severity of jaundice should be carefully assessed as Gilbert's syndrome or G6PD deficiency–associated hemolysis may make the disease appear more severe than the degree of liver damage. Comorbid diseases as outlined in the text should be carefully ruled out. If patient shows features of acute liver failure, liver transplantation as an option should be considered. In all cases receiving multiple transfusions and having chronic hemolysis, management of iron overload should be part of treatment. The need for liver biopsy should be carefully assessed in view of risks involved, and lastly, some people have suggested use of ursodeoxycholic acid (UDCA) to improve biliary sludging in cholestasis. ACLF, acute on chronic liver failure; ALF, acute liver failure; SCD, sickle cell disease; SCIC, sickle cell intrahepatic cholestasis; EBT, Exchange Blood Transfusion.