Although Epstein-Barr virus (EBV) is not a hepatotrophic virus, hepatomegaly (10%) and mild liver enzyme abnormalities (40%) are not uncommon in patients with EBV infection [1]. Typically, the enzyme abnormalities are consistent with hepatocellular liver injury (hepatitis) rather than decreased bile flow (cholestasis) [1]. We report on two patients with acute infectious mononucleosis secondary to EBV infection whose predominant biochemical abnormalities were marked elevations in serum levels of alkaline phosphatase.

A 22-year-old woman working at a summer camp where three other campers had infectious mononucleosis developed lethargy, fever (body temperature, 102 °F), and sore throat that lasted 3 days. Her history was significant for a 10-year duration of Crohn disease of the distal ileum and colon that was in complete remission. Results of previous liver enzyme tests, including tests done 4 weeks previously, were normal. On physical examination, the patient seemed fatigued but was otherwise normal. She had one occipital lymph node and no hepatosplenomegaly or signs of active Crohn disease. Monospot and serum IgM anti-EBV tests had positive results. An abdominal ultrasonogram showed mild splenomegaly. By day 12 of her illness, the patient was feeling normal and remained well until her most recent review, 32 weeks after symptoms developed.

A 37-year-old woman presented with lethargy, myalgias, headache, and a low-grade fever of 2 weeks' duration. She had no history of hepatic disease or risk factors for hepatic disease. Physical examination was unremarkable. Monospot and serum IgM anti-EBV tests had positive results. One week later, while symptoms were improving, physical examination showed hepatosplenomegaly. Her symptoms continued to diminish and had completely abated by 8 weeks. Other data for both patients are shown in the (Table 1).

The clinical presentations and positive test results confirm the diagnosis of infectious mononucleosis in both cases. Furthermore, other potential viral and autoimmune causes were ruled out (data not shown). The markedly high levels of alkaline phosphatase seen in both patients were initially confusing because infectious mononucleosis is not typically associated with this kind of presentation. Markedly increased alkaline phosphatase levels have been reported in the past but only rarely [2]. Cholestasis can occur during the convalescent phase of any severe form of viral hepatitis, particularly hepatitis A, but patients more often present during the acute hepatocellular injury phase. The hepatitis C virus tends to be more trophic for biliary epithelial cells than other hepatotrophic viruses, but the cholestasis that develops tends to be mixed with a significant hepatocellular component [3] that was not seen in either case.

The mechanism whereby EBV might induce cholestasis remains to be determined. Other herpesviruses, such as cytomegalovirus, have been documented to infect bile duct epithelial cells (in addition to hepatocytes), but this is not a consistent finding for all viruses in the group [4]. Infections with EBV have been associated with hepatic granuloma, but granulomatous disease of the liver tends to be more insidious and protracted [5].

In summary, acute EBV infection should be considered in the differential diagnosis of patients presenting with transient cholestasis and that increased alkaline phosphatase levels typically peak in the second week after symptom onset.