Failure to diagnose recent hepatitis C virus infections in London injecting drug users

Abstract

Hepatitis C virus (HCV) infection results in chronic liver disease in a substantial proportion of those infected. Most new cases of HCV infection in the UK are associated with intravenous drug use. It is important to identify these infections because of the implications for the future health of the individuals concerned and for the control of further spread of infection. However, as hepatitis C infection is characterised by a relatively long asymptomatic period of seronegative viraemia, a laboratory diagnostic protocol that does not test HCV seronegative samples for the presence of HCV RNA may wrongly designate HCV viraemic seronegative individuals as uninfected. Amongst 424 injecting drug users whose serum was sent to our diagnostic laboratory for "HCV screening" over a 14-month period, the prevalence of HCV seropositivity was 48.4%. We retrospectively identified seven individuals for whom there was evidence of recent acquisition of HCV infection. Three of these infections were identified using our routine diagnostic protocol: testing for the presence of HCV-specific antibody and performing HCV RNA testing only on seropositive and seroindeterminate specimens. However, four cases were only identified by HCV RNA testing of HCV seronegative serum. On the basis of these observations, we estimate the incidence of HCV infection amongst London injecting drug users as being 14.3 per 100 person-years. We advocate that all HCV seronegative blood samples obtained from injecting drug users should be tested for the presence of HCV RNA, and suggest that this could be done efficiently by nucleic acid testing the specimens in small pools. .

Hepatitis C infection among recent initiates to injecting in England 2000–2008: Is a national hepatitis C action plan making a difference?

“…High HCV incidences have been reported in a London cohort study (32–55 per 100 pyrs [15]) and in Bristol (38–47 per 100 pyrs [16]) using HCV RNA testing of anti‐HCV‐negative participants in a community survey. Lower incidences, comparable to the crude estimate among recent initiates here, have been reported in other UK studies: nine per 100 pyrs in a community‐recruited cohort study in south Wales [17]; 28 per 100 pyrs from a retrospective cohort study using residual samples from diagnostic testing in Glasgow [18]; and 14 per 100 pyrs in Greater London from the HCV RNA testing of anti‐HCV‐negative diagnostic samples [19]. These variations in naïve incidence in part reflect the different methodologies, settings and recruitment approaches used; however, these are unlikely to account fully for the differences seen.…”

“…The HCV prevalence has been relatively stable among recent initiates since 2004, the year the Hepatitis C Action Plan was launched, suggesting that this has so far had no detectable There have been a small number of studies that have investigated the naïve incidence of HCV infection among IDUs in the United Kingdom, and these have reported a wide range of incidences. High HCV incidences have been reported in a London cohort study (32-55 per 100 pyrs [15]) and in Bristol (38-47 per 100 pyrs [16]) using HCV [19]. These variations in naïve incidence in part reflect the different methodologies, settings and recruitment approaches used; however, these are unlikely to account fully for the differences seen.…”

Diagnosis of acute hepatitis C virus infection and estimated incidence in low‐ and high‐risk English populations

“…Incidence was estimated at 41.8 per 100 person‐years among recent initiates into injecting in London [12] and ranged from 11.9 to 28.4 per 100 person‐years among Scottish IDUs [15]. Among another cohort of London IDUs, the overall incidence estimate was 14.3 per 100 person‐years [11]. This study combined a prospective cohort study with retrospective testing of stored samples – our approach.…”

Occult hepatitis B virus and hepatitis C virus infections

“…HCV-seronegative individuals have been identified after exposure to HCV as shown by detection of virus-specific cell-mediated immunity in persons who otherwise had no evidence of HCV infection, that is negative for anti-HCV and HCV-RNA [110]. HCV infection is a frequent event amongst injecting drug users but recent acquisition of infection is not diagnosed in anti-HCVseronegative serum unless there is testing for HCV-RNA [111]. Indeed, the existence of the seronegative HCV carrier state had been documented in the chimpanzee animal model where exposure to low infective HCV-RNA doses induces cellular immune responses without consistently detectable viremia or anti-HCV seroconversion [112].…”