Hematologic complications of hepatitis A: another reason for implementation of anti-HAV vaccination.

To the Editor: Hepatitis A virus (HAV) can produce asymptomatic or symptomatic infections in humans. In children aged <6 years of age, 70% of HAV infections are asymptomatic. Among older children and adults, jaundice occurs in >70% of patients. The overall case fatality ratio is approximately 0.5%, but is substantially higher in adults with underlying liver disease. Three atypical clinical manifestations of acute hepatitis A have been recognized that include prolonged cholestasis, relapsing hepatitis, and extrahepatic complications, with evanescent rash and arthralgias being the most common. Although frequently overlooked, HAV is associated with hematologic complications including severe aplastic anemia, virus-associated hemophagocytic syndrome (VAHS), and postinfectious thrombocytopenic purpura. Although thrombocytopenic purpura is usually a benign and selflimiting complication that may or may not deserve treatment, aplastic anemia and VAHS are 2 potentially lethal complications of HAV infection. Regarding aplastic anemia, positive association of seropositivity for HAV and aplastic anemia is uncommon in western countries, where aplastic anemia is either ‘‘idiopathic’’ or associated with seronegative hepatic infections, but is well established in epidemiologic studies performed in Thailand. More specifically, in a large population-based case-control study of aplastic anemia conducted in Thailand since the year 1989, the overall incidence of aplastic anemia ranged between 3 and 5 per million per year in various areas of the country, with a strong inverse association with socioeconomic status, as determined by total household income and years of education. In that study, exposure to HAV was a risk indicator for aplastic anemia and possibly a surrogate marker of poverty and low socioeconomic status. VAHS is also a rare but serious complication of HAV infection. Although the prognosis of posthepatitis A hemophagocytic lymphohistiocytosis seems to be better than that of the primary, familial form, we should not overlook this potential serious hematologic complication of a vaccine-preventable disease. Because the majority of children with hepatitis A have asymptomatic, mild, or unrecognized infections, they serve as a source of infection for adults. In adults, the average duration of work loss of those who become ill with hepatitis A has been estimated at 15 days for nonhospitalized and 33 days for hospitalized patients. Moreover, a 2005 Markov model analysis conducted by the Centers for Disease Control and Prevention in the United States estimated costs of 133.5 millionUSD during the lifetime of a single children cohort in the absence of anti-HAV vaccination. Hence, implementation of a nationwide antiHAV vaccination strategy is highly cost effective. Pediatric hematologists routinely recommend some immunizations for certain populations of children, like antipneumococcal vaccination for children with sickle cell anemia or who undergo elective splenectomy for hematologic indications. In our opinion, they should add hepatitis A into the group of diseases against which they recommend routine immunization, as this strategy is highly effective not only in eliminating the indigenous HAV transmission and the associated liver disease, but also its rare and potentially lethal hematologic complications.