Hepatitis B serology and DNA detection in multitransfused haemophiliacs and factor VIII and IX concentrates

Abstract

To assess the effect of HIV infection and the introduction of virus-inactivated concentrates, we conducted a retrospective 20-year longitudinal study of hepatitis B virus (HBV) serology and look for HBV DNA in recent serum samples of 63 multiply transfused haemophiliacs. Of 63 haemophiliacs, 51 had evidence of previous HBV infection and 12 vaccinees had anti-HBs only. Of 40 HIV-negative, two had persistent HBsAg but all were HBV DNA negative. All 23 HIV-positive were HBsAg-negative. Loss of anti-HBc(46% vs. 17.5%) and anti-HBs (32% vs. 14%) was more commonly seen in HIV-infected compared with noninfected individuals. One HIV-positive individual had HBV DNA detectable by PCR. Restrospective testing demonstrated that re-emergence was associated with loss of anti-HBs and advanced HIV infection (CD4<50 × 10(6-1) L CDC II), although eight other with CDC IV disease were HBV DNA negative. Forty-three batches of concentrates produced between 1965 and 1992 from both commercial and volunteer donors and subjected to different donor screening and virus inactivation methods were negative for HBV DNA. Some of these may have been infectious for HBV and therefore being negative for HBV may not equate with noninfectivity. We conclude that both HIV-positive and -negative haemophiliacs have lost protective antibodies against HBV since 1984 and that virus replication may re-emerge at least in the HIV-positive group. These observations may have implications for the management of their chronic liver disease and the risk of infection of sexual partners and medical attendants.

Reconstruction of the historic time course of blood‐borne virus contamination of clotting factor concentrates, 1974–1992

“…The infrequent detection of HBV DNA in the study samples (1 from 24) using a highly sensitive PCR 18 matches previously published findings of uniform negativity of clotting factors with expiry dates before 1990 in a study using a likely less sensitive PCR assay 45 . It was commented at the time that these negative results were inconsistent with remarkably high frequencies of past exposure to HBV in PWHs, with antihepatitis B core antibodies (anti‐HBc) reported in >80% receiving nonvirally inactivated concentrate, 45,46 substantially higher than the background population anti‐HBc seroprevalence in Western countries of typically <3%. However, frequent transmission of HBV from clotting factors manufactured from HBsAg‐negative‐screened plasma has been described, 46,47 potentially the outcome of including donors with occult HBV infections with undetectable HBsAg and low levels of infectious HBV particles 48 .…”

“…(1 from 24) using a highly sensitive PCR 18 matches previously published findings of uniform negativity of clotting factors with expiry dates before 1990 in a study using a likely less sensitive PCR assay. 45 It was commented at the time that these negative results…”

“…were inconsistent with remarkably high frequencies of past exposure to HBV in PWHs, with antihepatitis B core antibodies (anti-HBc) reported in >80% receiving nonvirally inactivated concentrate, 45,46 substantially higher than the background population anti-HBc seroprevalence in Western countries of typically <3%. However, frequent transmission of HBV from clotting factors manufactured from HBsAg-negative-screened plasma has been described, 46,47 potentially the outcome of including donors with occult HBV infections with undetectable HBsAg and low levels of infectious HBV particles.…”

Guidelines on the diagnosis, management and prevention of hepatitis in haemophilia

“…This is observed particularly in individuals infected with HIV. In these subjects, previous exposure to HBV infection may theoretically go unrecognized because the specific immune response may fail [28].…”

“…In some individuals previously exposed to HBV, the infection becomes latent; reactivation may occur, particularly in those who are immunosuppressed, e.g. with HIV [28].…”