Follow ing its identification in 1989, HCV was identified as the m ajor cause o f non-A, non- B post-transfusion hepatitis. The advent o f a serological assay for the detection o f IgG antibody to HCV (anti-H C V ) and reverse transcriptase-polym erase chain reactions (RT- PCR) for the detection o f viral RNA, together with w orldw ide epidem iological surveys has identified HCV as being a m ajor cause o f m orbidity and mortality.
Transm ission o f HCV is prim arily by the parenteral route but less effective transm ission through bodily secretions is possible as HCV has been identified in saliva, urine, semen and ascitic fluid [Liou et al, 1992]. Rates o f infection can be divided into those o f high-risk groups and those o f healthy populations. Those included in the high-risk populations include recipients o f blood products prior to the introduction o f HCV screening and intravenous drug users (IV D U ’s).
1.2.3.2 Incidence
T he incidence o f transfusion related HCV prior to 1986 was 5 to 13%, declining to 1.5-9% from 1986-1990, and declining further to < 1% after 1990 with the introduction o f anti- HCV screening o f donors [D onahue et al, 1992]. In Am erican studies o f com m unity acquired HCV, an estim ated 21% o f acute hepatitis is due to HCV, how ever the annual incidence rates have fallen by over 50% since the identification o f the virus [A lter et al, 1990]. A definable risk factor is present in 60% o f cases and in a large proportion o f the rem aining 40% a low socio-econom ic level has been associated. A cute HCV infection is also m ore com m on am ong young adults due most probably to the patterns o f exposure [A lter et al, 1990]. In high-risk populations, incidence rates o f 10% am ongst IV D U ’s in A m sterdam [Van A m eijden et al, 1993], 1% o f Am erican prison inm ates [V alhov et al,
1993] and 3% o f B elgian hem odialysis patients [Jadoul et al, 1993] have been reported. 1.2.3.3 Prevalence
T he highest prevalence rates o f up to 90% exist for those at high risk; IV D U ’s o f more than 10 years and m ultiple transfusion recipients [Donahue et al, 1991], that is haem ophiliacs in receipt o f m ultiple transfusions o f non-treated factor concentrates [Rumi et al, 1990]. H aem odialysis patients have prevalence rates varying according to geographic region, from 1-2% in the U nited K ingdom to 10-30% in the U nited States and to 20-91% in Eastern E urope [A lter et al, 1995]. In healthy control populations, the prevalence o f HCV again varies by geographic region, from less than 0.08% in the United Kingdom , 0.3% in the U nited States and 3% in South A m erica [Alter, 1995]. However, these studies are based on analysis o f blood donors and therefore probably underestim ate the general population prevalence rates, as blood donors are a highly selected group o f pre-screened individuals.
HCV w as identified as the m ajor cause o f post-transfusion hepatitis in retrospective studies follow ing its identification [D onahue et al, 1992]. Intravenous drug use is also a
docum ented route o f infection by the sharing o f contam inated needles and drug
paraphernalia [Van A m eijden et al, 1993]. H ealth care w orkers are also at risk for HCV m fection with prevalence rates o f up to 1.6% reported in the U nited States [C ooper et al, 1992] am ong high-risk w orkers and 9% am ong dentists practising oral surgery [K lein et al, 1991]. Sexual and household contacts o f patients w ith HCV are also at risk o f acquiring HCV, w ith prevalence rates averaging 5% and 3.6% respectively [Alter, 1995]. T he risk o f sexual transm ission has been associated w ith the num ber o f sexual partners, not using a condom , history o f other sexually transm itted diseases and having partners at risk o f hum an im m unodeficiency virus. Perinatal prevalence rates o f HCV in children bom to anti-H C V positive, anti-HIV negative wom en vary betw een 0-13% . T he highly variable results are thought to be due to small sam ple sizes, variable serologic tests and variable follow-up periods.
In Ireland, the prevalence o f HCV in the general population is estim ated at 0.05 -0.1%. T here are three cohorts o f subjects w here there prevalence is considerably higher. The first relates to post-transfusion hepatitis that pre-dates the introduction o f HCV screening into the Irish Blood Transfusion service in 1994. Patients with high transfusion requirem ents, notably haem ophiliacs, who received blood products pre-1994, have a prevalence o f HCV approaching 90% [Nolan, personal com m unication 2003]. T he second cohort consists o f people with a history o f intravenous drug use. In D ublin currently, there are an estim ated
13,000 drug users, with a seroprevalence o f 52% to 81% and an estim ated 62% o f these are chronically infected [Keating, personal com m unication 2003], Sim ilarly, 37% o f prisoners are estim ated to be anti-H C V positive, rising to 81% in those w ith a history o f IVDU [Irish G overnm ent stationary office, 1999]. The third cohort relates to tw o outbreaks o f HCV that occurred follow ing the adm inistration o f H C V -contam inated anti-D im m unoglobulin to pregnant women. The first occurred in 1977 and the second over the period o f 1991 to
1994.
1.2.3.4 G eographical variation
Epidem iological studies have also m apped the geographical distribution o f the HCV genotypes and subtypes [Fom s et al, 1998]. G enotype la and lb are the m ost prevalent type in N orth A m erica each accounting for m ore than 40% o f infections. In N orthern Europe genotype la is highly prevalent w hereas genotype lb is most prevalent in Southern and E astern Europe. However, genotype 3 is most prevalent am ong younger patients, particularly IV D U ’s in Europe [Silini et al, 1995]. W orldw ide, genotype 3 has a high prevalence in Thailand, South-East Asia and India [Davidson et al, 1995]. G enotype lb is
most prevalent throughout Japan and China. G enotype 4 is the principal genotype in the M iddle East, Egypt and C entral A frica [Davidson et al, 1995], genotype 5 in South Africa [Sim m onds et al, 1993] and genotype 6 in H ong Kong [M cO m ish et al, 1994]. T he variants o f genotype 6, genotypes 7 to 9 are prevalent in V ietnam [Tokita et al, 1994] and genotypes
10 and 11, variants o f 3 and 6 respectively, in T hailand [Tokita et al,1996].