Discussion
The clinical entities represented under the rubric of sickle hepatopathy (Table 1) encompass a disease spectrum; clinical manifestations vary depending on the relative degrees of cell trapping, ischemia, and intracanalicular cholestasis.1-6 There is overlap among these entities, so precise classification is often challenging. Patient 1 had a clinical course best classified as hepatic sequestration, whereas Patient 2 experienced intrahepatic cholestasis with multi-organ failure. Although illness severity differed between the two patients, there were several common features: 1) both individuals were teenagers with HbSC disease and primary EBV infection, as evidenced by atypical lymphocytosis and positive EBV IgM or PCR, 2) symptoms were initially attributed to sickle cell-related pain rather than infectious mononucleosis, 3) hepatomegaly, anemia, and thrombocytopenia progressed rapidly, 4) erythrocyte transfusions were required, 5) there was marked elevation of serum transaminases and bilirubin, and 6) a reactive thrombocytosis was noted during the recovery phase (Fig 1).
We surmise that EBV infection triggered sickle hepatopathy in these two cases. EBV-induced sickle hepatopathy has not been reported previously. EBV is known to cause acute hepatitis, although the degree of elevation of serum ALT or bilirubin is typically mild.11-13Occasionally EBV results in overt cholestatic hepatitis,14-20 and there is one noteworthy report of a 15-year-old with HbSC disease who developed EBV-induced cholestatic hepatitis without sickle hepatopathy (maximum serum ALT and total bilirubin of 770 U/L and 12.5 mg/dL, respectively).21We posit that the marked serum ALT elevation seen in Patient 1, which is not typical of hepatic sequestration crisis (Table 1), partly reflected EBV-induced hepatitis.