AN OUTBREAK OF HEPATITIS-A AMONG SOUTH-AFRICAN PATIENTS WITH HEMOPHILIA - EVIDENCE IMPLICATING CONTAMINATED FACTOR-VIII CONCENTRATE AS THE SOURCE

We report an outbreak of hepatitis A in nine South African hemophiliac s treated exclusively with infusions of factor VIII concentrate. The s olvent/detergent (S/D) method (which does not inactivate nonenveloped viruses) was used for virus eradication. In three of six patients stud ied at a molecular level hepatitis A virus (HAV) complementary DNA (cD NA) amplified from serum by reverse transcription-polymerase chain rea ction (RT-PCR) was identical to HAV cDNA in 1 of 14 lots (no. 53) of f actor VIII tested. The plasma for lot 53 was obtained from donors in t he United States: 1 of 12 samples of this source material contained th e same HAV cDNA sequences. In another two patients receiving lot 53, t he degree of identity between HAV cDNA in serum and that in factor VII I was only 88% and 89%, respectively, and in the sixth patient, who di d not receive lot 53, it was 90%. The degree of HAV cDNA homology amon g five patients in an independent point-source outbreak of hepatitis A was 100%, and that in nine patients who acquired this infection spora dically in Johannesburg, Egypt, or Russia, was 93% to 100%. Whether th e three hemophiliacs with low HAV cDNA homology with lot 53 acquired t he infection from other unidentified virus strains contaminating faste r VIII or from extraneous sources is unknown. This-study provides furt her evidence that factor VIII concentrate prepared by the S/D method m ay be contaminated by the HAV, in this instance at source, and may cau se hepatitis in recipients. Proof of a cause-and-effect relationship w ill, however, depend on animal inoculation studies.