Detection of hepatitis A virus from clotting factors implicated as a source of HAV infection among haemophilia patients in Korea

Abstract

To investigate the causal relationship of blood clotting factors and hepatitis A virus (HAV) infection in haemophilia patients during 1998-1999 in Korea, we performed a 1:3 matched case-control study and molecular detection of HAV from clotting factors and patients. The epidemiological investigation showed that one lot of clotting factor VIII was related epidemiologically to patients with hepatitis A with an odds ratio of 35.0, or 38.4 when adjusted for the interval between injections. We examined 17 sera collected from seven patients and 124 lots of blood clotting factors (factor VIII and factor IV) by HAV reverse transcriptase-polymerase chain reaction (RT-PCR). HAV RNA was detected in five clotting factors and six sera. The HAV sequence of one of the factor VIII samples was identical to the sequences found in three patients' sera. Findings from the laboratory and epidemiological studies suggested that the clotting factor was causally related to HAV infection in three haemophilia patients.

Fig

Nucleotide sequences of the HAV strains detected from clotting factors and patients. The phylogenetic analysis of HAV sequences detected from haemophiliac patients and blood products shows that the sequences of HAV from patient nos. 2, 4, 5 and one blood product (factor VIII, lot no. 1950177) are identical, as are HAV sequences from patient no. 6 and another product (factor IX, lot no. 1510039). The HAV sequence from patient no. 1 is closely related to that from factor IX (lot no. 1510043). MegAlign of the DNAstar aligns multiple sequences by drawing a histogram of consensus strength at the top of each alignment panel using one of two algorithms: the Jotun Hein method or the Clustal method. We used the Clustal method to group sequences into clusters by examining the distance between all pairs. The relationship of the sequences was shown in dendrograms. The length of each pair of branches represents the distance between sequences.