The natural history and antiviral treatment of hepatitis C in haemophilia

Abstract

People with haemophilia who received non-virucidally treated large-pool clotting factor before 1986 were infected with hepatitis C virus (HCV), previously referred to as non-A, non-B hepatitis. Approximately one-tenth of patients have been shown to clear infection naturally and shown persistently negative HCV PCR. Patients have been infected with genotypes 1, 2 and 3 reflecting the plasma donors in Northern Europe and the United States. Several studies have shown that HCV mono-infection has a very slow progression. Co-infection with human immunodeficiency virus (HIV), however, can hasten the progression to cirrhosis and liver failure. Genotype 1 and older age at first infection also increase the progression rate. Candidates with detectable HCV RNA are candidates for therapy. The combination of standard interferon-alpha and ribavirin doubles the effectiveness of interferon-alpha alone and is the current standard of care for the treatment of chronic hepatitis C. The duration of therapy depends on the genotype and level of viraemia. Patients with genotypes 2 or 3 should have 6 months' therapy while those with genotype 1 and > 2 million copies mL-1 should have 1 year of therapy. Pegylated interferon is an emerging therapy. Patients co-infected with HIV, in whom treatment has stabilized the HIV infection, may be able to tolerate therapy for HCV infection. Liver transplantation is indicated for patients with haemophilia who have decompensated hepatitis C infection.

Current status of Japanese HIV-infected patients with coagulation disorders: coinfection with both HIV and HCV

“…This infection with HCV in the present subjects is thought to have occurred before 1989, as observed by Taki et al [27]. Therefore, the recent increase in the number of deaths from hepatic disease may be a natural consequence of infection with HCV [28]. Although the emerging risk of mortality from liver disease and liver cancer had already been observed among hemophiliacs with or without HIV-1 in the United Kingdom just before 1997 [29], it became evident after 1997 in Japan.…”

Managing Occupational Risks for Hepatitis C Transmission in the Health Care Setting

“…Several studies have suggested that the course of hepatitis C infection is accelerated and that the disease may produce more severe hepatic damage in HIVcoinfected patients (10,30,196,204,254,319,324,(337)(338)(339)(340). These studies also demonstrate that patients infected with both viruses generally have higher circulating HCV viral burdens than do patients who are not HIV infected.…”

Mixed Genotypes in Hepatitis C Virus Infection

“…Heat-inactivated factor concentrates were not available until November 1985. Virtually, all hemophiliacs who received clotting factor concentrates prior to implementation of viral inactivation techniques became infected with hepatitis C virus at the time of the first infusion (Morfini et al, 1994;Lee C et al, 2002;Ragni et al, 2010). Prevalence rates of HCV infection up to 100% were reported in hemophilia patients treated with concentrates before 1985 (Yee et al, 2000;Lee C, 2009;Manucci, 2008;Arnold et al, 2006).…”

“…Prevalence rates of HCV infection up to 100% were reported in hemophilia patients treated with concentrates before 1985 (Yee et al, 2000;Lee C, 2009;Manucci, 2008;Arnold et al, 2006). Even though the introduction of heat-treated factor concentrates progressively decreased HCV transmission, the true risk ended when new regulations in blood donor screening together with the implementation of second and third generation immunoassays for the detection of antibodies against HCV was introduced in 1991 in Europe, in 1992 in the US and 1993 in Argentina (Morfini et al, 1994;Franchini et al, 2001;Lee and Dusheiko, 2002;Tagliaferri et al, 2010;Argentinean Ministry of Health resolution #1077, 1993. However, it is important to notice that clotting factor concentrates used for Argentinean hemophilic patient treatments were never manufactured in the country but brought from the US or Europe.…”