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Hepatitis virus (HCV) diagnosis and access to treatment in a UK cohort.

ABSTRACT: BACKGROUND:As direct acting antiviral (DAA) therapy is progressively rolled out for patients with hepatitis C virus (HCV) infection, careful scrutiny of HCV epidemiology, diagnostic testing, and access to care is crucial to underpin improvements in delivery of treatment, with the ultimate goal of elimination. METHODS:We retrospectively studied microbiology records from a large UK teaching hospital in order to compare the performance of HCV screening and diagnostic tests (antibody, antigen and HCV RNA detection). Having described a local cohort of adults with active HCV infection, we investigated the proportion who attended hospital appointments, were prescribed direct acting antiviral (DAA) therapy, and cleared HCV RNA following treatment. RESULTS:Over a total time period of 33 months between 2013 and 2016, we tested 38,509 individuals for HCV infection and confirmed a new diagnosis of active HCV infection (HCV-Ag + and/or HCV RNA+) in 353 (positive rate 0.9%). Our in-house HCV-Ab screening test had a positive predictive value of 87% compared to repeat HCV-Ab testing in a reference laboratory, highlighting the potential for false positives to arise using this test. HCV-Ag had 100% positive predictive value compared to detection of HCV RNA. There was a strong correlation between quantitative HCV-Ag and HCV RNA viral load (p < 0.0001). Among the cases of infection, genotype-1 and genotype-3 predominated, the median age was 37 years, 84% were male, and 36% were in prison. Hepatology review was provided in 39%, and 22% received treatment. Among those who received DAA therapy with 12 weeks of follow-up, 93% achieved a sustained virologic response (SVR12). CONCLUSIONS:HCV-Ag performs well as a diagnostic test compared to PCR for HCV RNA. Active HCV infection is over-represented among men and in the prison population. DAA therapy is successful in those who receive it, but a minority of patients with a diagnosis of HCV infection access clinical care. Enhanced efforts are required to provide linkage to clinical care within high risk populations.

SUBMITTER: Adland E

PROVIDER: S-EPMC6137907 | biostudies-other | 2018 Sep

REPOSITORIES: biostudies-other

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Hepatitis virus (HCV) diagnosis and access to treatment in a UK cohort.

Adland Emily E Jesuthasan Gerald G Downs Louise L Wharton Victoria V Wilde Gemma G McNaughton Anna L AL Collier Jane J Barnes Eleanor E Klenerman Paul P Andersson Monique M Jeffery Katie K Matthews Philippa C PC

BMC infectious diseases 20180914 1

<h4>Background</h4>As direct acting antiviral (DAA) therapy is progressively rolled out for patients with hepatitis C virus (HCV) infection, careful scrutiny of HCV epidemiology, diagnostic testing, and access to care is crucial to underpin improvements in delivery of treatment, with the ultimate goal of elimination.<h4>Methods</h4>We retrospectively studied microbiology records from a large UK teaching hospital in order to compare the performance of HCV screening and diagnostic tests (antibody, ...[more]

PMID: 30217169

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Project description:BACKGROUND: No recognized risk factors can be identified in 10-40% of hepatitis C virus (HCV)-infected patients suggesting that the modes of transmission involved could be underestimated or unidentified. Invasive diagnostic procedures, such as endoscopy, have been considered as a potential HCV transmission route; although the actual extent of transmission in endoscopy procedures remains controversial. Most reported HCV outbreaks related to nosocomial acquisition have been attributed to unsafe injection practices and use of multi-dose vials. Only a few cases of likely patient-to-patient HCV transmission via a contaminated colonoscope have been reported to date. Nosocomial HCV infection may have important medical and legal implications and, therefore, possible transmission routes should be investigated. In this study, a case of nosocomial transmission of HCV from a common source to two patients who underwent colonoscopy in an endoscopy unit is reported. RESULTS: A retrospective epidemiological search after detection of index cases revealed several potentially infective procedures: sample blood collection, use of a peripheral catheter, anesthesia and colonoscopy procedures. The epidemiological investigation showed breaches in colonoscope reprocessing and deficiencies in the recording of valuable tracing data. Direct sequences from the NS5B region were obtained to determine the extent of the outbreak and cloned sequences from the E1-E2 region were used to establish the relationships among intrapatient viral populations. Phylogenetic analyses of individual sequences from viral populations infecting the three patients involved in the outbreak confirmed the patient pointed out by the epidemiological search as the source of the outbreak. Furthermore, the sequential order in which the patients underwent colonoscopy correlates with viral genetic variability estimates. CONCLUSIONS: Patient-to-patient transmission of HCV could be demonstrated although the precise route of transmission remained unclear. Viral genetic variability is proposed as a useful tool for tracing HCV transmission, especially in recent transmissions.

Project description:The genome of hepatitis C virus (HCV) consists of seven functional regions: the core, E1, E2/NS1, NS2, NS3, NS4, and NS5 regions. The U. S. Food and Drug Administration-licensed 2.0G immunoassay for the detection of anti-HCV uses proteins from the core, NS3, and NS4 regions (McHutchinson et al., Hepatology 15:19-25, 1992). The 3.0G enzyme-linked immunosorbent assay includes the protein from the NS5 region (Uyttendaele et al., Vox Sang. 66:122-129, 1994). The necessity of detecting antibodies to viral envelope proteins (E1 and E2) and to different genotype samples has been demonstrated previously (Chien et al., Lancet 342:933, 1993; Lok et al., Hepatology 18:497-502, 1993). In this study we have attempted to improve the sensitivity of the anti-HCV assay by developing a single multiple-epitope fusion antigen (MEFA; MEFA-6) which incorporates all of the major immunodominant epitopes from the seven functional regions of the HCV genome. A nucleic acid sequence consisting of proteins from the viral core, E1, E2, NS3, NS4, and NS5 regions and different subtype-specific regions of the NS4 region was constructed, cloned, and expressed in yeast. The epitopes present on this antigen can be detected by epitope-specific monoclonal and polyclonal antibodies. In a competition assay, the MEFA-6 protein competed with 83 to 96% of genotype-specific antibodies from HCV genotype-specific peptides. This recombinant antigen was subsequently used to design an anti-HCV chemiluminescent immunoassay. We designed our assay using a monoclonal anti-human immunoglobulin G antibody bound to the solid phase. Because MEFA-6 is fused with human superoxide dismutase (h-SOD), we used an anti-human superoxide dismutase, dimethyl acridinium ester-labeled monoclonal antibody for detection. Our results indicate that MEFA-6 exposes all of the major immunogenic epitopes. Its excellent sensitivity and specificity for the detection of clinical seroconversion are demonstrated by this assay.

Project description:The hepatitis E virus (HEV) is the fifth known form of viral hepatitis and was first recognized as the cause of an epidemic of unexplained acute hepatitis in the early 1980s. Globally, it is one of the most frequent causes of acute viral hepatitis. The majority of HEV infections are asymptomatic and lead to the spontaneous clearance of the virus. Among the eight different genotypes identified to date, HEV genotype 1 (HEV1), HEV2, HEV3, and HEV4 are the most frequent genotypes causing infections in humans. HEV1 and HEV2 are prevalent in developing regions and able to result in large-scale outbreaks originating from contaminated water supplies. They are also responsible for severe hepatitis in pregnant patients and infants. In contrast, HEV3 and HEV4 are zoonotic, and the transmission of these genotypes to humans occurs mainly through the fecal contamination of water and consumption of contaminated meat from infected animals. Their main reservoir is the pig, and they are mostly encountered in developed countries. The major risk groups for HEV infection and its ensuing adverse consequences are pregnant women, infants, older people, immunocompromised individuals, patients with underlying chronic liver diseases, and workers that come into close contact with HEV-infected animals. In the clinical perspective, HEV infections have diverse clinical manifestations including acute and self-limiting hepatitis, acute-on-chronic liver disease, chronic hepatitis, cirrhosis, and liver failure. Although HEV mainly results in acute self-limiting infection, chronic HEV infection may occur among immunocompromised patients (e.g., solid-organ transplant recipients). Additionally, HEV-associated extrahepatic manifestations involving various organs have been reported in the last decade, although the causal link for many of them still needs to be proven. Ribavirin and interferon-alpha are the most widely used agents for the treatment of HEV infections with a certain level of success. However, ribavirin is contraindicated in pregnant patients, and interferon-alpha cannot be used in most transplant recipients. Therefore, there is an urgent need for novel antiviral compounds that are safe and effective particularly for patients having contraindications for ribavirin or interferon-alpha and infected by the ribavirin-resistant HEV. In this review article, a literature search using PubMed and MEDLINE databases was performed, up to March 2020. Only the articles published in English were reviewed.

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Hepatitis virus (HCV) diagnosis and access to treatment in a UK cohort.

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Hepatitis virus (HCV) diagnosis and access to treatment in a UK cohort.

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