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.