Reply:
Authors: Maria H Sjogren
Journal: Hepatology (2004)

I read with interest the letter from Amoroso et al. and appreciate their data, which I believe supports the case for more widespread vaccination against hepatitis A. The authors agree that in Italy as in the United States there has been an increased susceptibility to hepatitis A viral infection because of a decrease of natural immunity in the general population. They note that among 1,182 cases diagnosed at their hospital during the last 5 years, at least one-third (394 individuals) had severe clinical symptoms during the course of the illness, with complications such as aplastic anemia, coagulopathy, and pancreatitis. Four of their patients progressed to acute fulminant hepatitis (0.33%); one experienced a liver death (a pregnant woman required a liver transplantation). Indeed, these statistics, although reported from a single institution, underscore the need for prevention. Most, if not all, of these cases could have been prevented if the patients had received hepatitis A vaccine. As their 33% severe-symptom occurrence attests, hepatitis A is not a trivial infection. I would also note that surveillance systems are notoriously defective, and they underreport cases, morbidity, and mortality. One wonders about the expense incurred in treating the 394 individuals with severe symptoms—the direct costs of hospitalization and liver transplant, and the indirect costs of lost manpower and diverted resources. In the United States, the annual economic burden of hepatitis A in adolescents and adults was estimated at $488.8 million in a study that took into account the costs of medicines, hospitalization, physician visits, diagnostic studies, therapy for fulminant disease, liver transplantation, loss of income from missed work days, and mortality.1 The cost-effectiveness of routine immunization against hepatitis A vaccine was evaluated through meticulous review of studies, reviews, editorials, and letters published in 5 major languages (including Italian) between February 1992 and December 2001, and the conclusion was that the use of hepatitis A virus (HAV) vaccine in developed countries had cost-effectiveness comparable to that of other childhood vaccines.2 Indeed, we have recently witnessed the effects of the current U.S. policy of limited HAV vaccination in the outbreak of more than 600 symptomatic cases of HAV in the states of Georgia, Tennessee, and Pennsylvania. Thus far, 3 patients have died, and thousands of exposed individuals needed immediate passive immunization. None of the cities where the outbreak occurred were located in states that the Centers for Disease Control and Prevention recommends consideration for immunization because of high or intermediate rates of endemic HAV.3 Therefore, immunization directed to specific groups would not control the infection, in part because about half of the hepatitis A infections occur in patients without known factors. It is impossible to predict who would be at risk of infection with the hepatitis A virus. As I noted before, the rate of acute liver failure due to HAV has not decreased over the years; in contrast, the acute liver failure cases due to hepatitis B virus infection have substantially decreased, in part due to universal immunization.4 To suggest that the significant morbidity and mortality due to hepatitis A is an acceptable outcome in Italy or in the U.S. when cost-effective, safe, and highly immunogenic HAV vaccines are available would appear to this author to be the wrong strategy and it deserves urgent reconsideration.