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.