Fulminant hepatitis is a severe complication of hepatitis A virus infection. Its mechanism is unknown. Liver transplantation can be necessary, but spontaneous recovery is frequent. There are no data on the level of viral replication according to the clinical form of hepatitis A. We reviewed the files of 50 patients with acute hepatitis A. Nineteen patients had fulminant hepatitis (defined by encephalopathy and factor V <50%), and, from them, 10 patients underwent transplantation. Hepatitis A virus (HAV) RNA was quantified by real-time PCR on sera obtained at admission. The genotype was determined by phylogenetic analysis of HAV RNA. HAV RNA was detected in serum by RT-PCR in 39 out of 50 patients. Encephalopathy and low factor V level were significantly related to female gender, HAV PCR negativity (9/19 vs. 5/31, respectively; P ؍ .03), a low serum HAV RNA level (log, 3.6 ؎ 0.6 vs. 4.4 ؎ 0.9, respectively; P ؍ .02), genotypes other than IA, and acetaminophen intake. In multivariate analysis, low or undetectable HAV viral load and a high bilirubin level were independently associated with both low factor V levels and fulminant hepatitis and also with death or transplantation. In conclusion, HAV-related liver failure is due to an excessive host response associated with a marked reduction in viral load. The infection is spread chiefly by fecal-oral transmission and is a public health problem throughout the world. The main complication of HAV infection is fulminant hepatitis (FH), i.e., acute liver failure with encephalopathy, which occurs in less than 1% of cases. It appears to be more frequent in adults than in children. 1 In the United States, about one third of adults have anti-HAV antibodies, and 100 deaths per year are attributed to HAV-related acute liver failure. 1 This is also a frequent cause of death among children in developing countries. 2 Liver transplantation has markedly changed the prognosis of HAV-related acute liver failure in industrialized countries 3 and is currently indicated for patients with deep coma and low factor V levels. However, HAV-related FH resolves spontaneously more frequently than FH of other origins, and the decision to transplant or not to transplant is thus particularly difficult. Auxiliary liver transplantation may be appropriate in this setting, pending possible regeneration of the native liver. 4,5 Few data have been published on viral replication during acute hepatitis A, and viral load in patients with FH A has not yet been studied. There are several HAV genotypes, IA being most prevalent in industrialized countries. 6 Little information is available on the possible relation between the severity of hepatitis A and the infecting genotype. We applied real-time quantitative polymerase chain reaction (PCR) to stored sera from 50 patients with acute hepatitis A, of whom 19 had FH, to examine the possible relation between HAV viral load, HAV genotype, and the clinical course.
