INACTIVATION OF HEPATITIS-A VIRUS BY HEAT-TREATMENT IN AQUEOUS-SOLUTION

Hepatitis A virus infections have been reported recently among hemophi lic patients in Italy and Germany, leading to speculation that infecti ous hepatitis A virus (HAV) might have been present in some factor VII I concentrates. In both cases, the implicated factor concentrates had been treated by a solvent/detergent method, which inactivates envelope d viruses but which would not be expected to inactivate HAV, a nonenve loped picornavirus. To determine whether HAV would be inactivated duri ng pasteurization of factor VIII concentrate, an alternative method em ployed for virus inactivation, we determined the extent to which the i nfectivity of cell culture-adapted HAV, suspended either in cell cultu re medium or in a proprietary stabilizing buffer, was reduced by heat treatment at 60-degrees-C for 10 hr. The titer of infectious HAV decli ned rapidly at 60-degrees-C, but the stabilizer considerably delayed H AV inactivation. In cell culture medium, HAV was inactivated by >3.6 l og10 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, ind icating that <5.2 log10 infectious HAV particles are inactivated under these conditions. In the presence of the stabilizer, HAV was signific antly more stable than poliovirus type 1, which has been used to valid ate virus inactivation by pasteurization. We conclude that pasteurized factor VIII concentrate should pose little if any risk for transmissi on of HAV if pooled plasma used for its manufacture contained low leve ls of the virus. (C) 1993 Wiley-Liss, Inc.