Inactivation of hepatitis A virus by heat treatment in aqueous solution

Hepatitis A virus infections have been reported recently among hemophilic patients in Italy and Germany, leading to speculation that infectious hepatitis A virus (HAV) might have been present in some factor VIII concentrates. In both cases, the implicated factor concentrates had been treated by a solvent/detergent method, which inactivates enveloped viruses but which would not be expected to inactivate HAV, a nonenveloped picornavirus. To determine whether HAV would be inactivated during pasteurization of factor VIII concentrate, an alternative method employed for virus inactivation, we determined the extent to which the infectivity of cell culture-adapted HAV, suspended either in cell culture medium or in a proprietary stabilizing buffer, was reduced by heat treatment at 60 degrees C for 10 hr. The titer of infectious HAV declined rapidly at 60 degrees C, but the stabilizer considerably delayed HAV inactivation. In cell culture medium, HAV was inactivated by > 3.6 log10 within 30 min, but 3.6 log10 inactivation of HAV was reached only after 6 hr in the presence of the stabilizer. Residual infectious HAV was present after even 10 hr of heat treatment in the stabilizer, indicating that < 5.2 log10 infectious HAV particles are inactivated under these conditions. In the presence of the stabilizer, HAV was significantly more stable than poliovirus type 1, which has been used to validate virus inactivation by pasteurization. We conclude that pasteurized factor VIII concentrate should pose little if any risk for transmission of HAV if pooled plasma used for its manufacture contained low levels of the virus.