Sam Lattimore

Virology, serology, and demography of hepatitis E viremic blood donors in South East England

Hepatitis E virus (HEV) Genotype 3 (G3) in England comprises two principal phylogenetic groups (Group 1 and Group 2) and can be transmitted by transfusion. Unselected screening identified 79 viremic donors; 76 participated in a follow‐up study.

Clinical Care Pathways for Patients With Hepatitis C: Reducing Critical Barriers to Effective Treatment

New therapies with the potential to eradicate HCV are available. Engagement of infected individuals with care is the major barrier to realising this vision. We describe an enhanced care pathway leading to a sustained increase in indices of engagement.

Molecular epidemiology of newly acquired hepatitis C infections in England 2008–2011: Genotype, phylogeny and mutation analysis

BACKGROUND Analysis of laboratory testing data collected through the Sentinel Surveillance programme has provided a method for identifying individuals who have recently acquired their hepatitis C virus (HCV) infection. Access to samples from these individuals provided a rare opportunity to undertake molecular characterization studies. OBJECTIVES To describe the epidemiology and genetic diversity of hepatitis C in recent seroconverter infections and to predict how this will impact on HCV treatment and control. STUDY DESIGN One hundred and forty seven samples were available from individuals, identified to have recently acquired their HCV infection. Genotype determination with additional phylogenetic analysis was carried out on NS5B sequences. Analysis across the NS3 region investigated the presence of antiviral resistance mutations. Where possible, molecular data was linked to demographic and risk/behavioural factor information. RESULTS The majority of new infections occurred in males with a mean age of 37 years. The most commonly observed genotypes were 1a (49%) and 3a (42%) and injecting drug use (58%) was the most common risk factor. Genotype distribution differed between persons who inject drugs and those with other risk factors suggesting two possible epidemics. Phylogenetic analysis indicated possible transmission networks within specific risk groups. Amino acid changes associated with antiviral resistance were noted in the NS3 region in some samples. CONCLUSIONS Continued surveillance of linked molecular, virological, demographic and epidemiological information on recently acquired infections will contribute to understanding the on-going HCV epidemic in England.

Evaluation of hepatitis C testing in men who have sex with men, and associated risk behaviours, in Manchester, UK

Objective To determine the prevalence of newly diagnosed hepatitis C virus (HCV) and associated risk behaviours among men who have sex with men (MSM) in Manchester. Method A survey among MSM attending four genitourinary medicine clinics in Manchester was carried out over 9 months in 2013. Participants were asked about recent sexual behaviour, recreational drug use and HIV status. All men were offered an HCV test. Results Overall, 2030 MSM completed a questionnaire and accepted an HCV test. Of whom, 0.9% (18) were newly diagnosed with HCV, including 1.8% (13/735) of HIV-positive MSM, 0.7% (3/440) of MSM of unknown HIV status and 0.2% (2/855) of HIV-negative MSM. HCV positivity was significantly associated with HIV status (p<0.001). When compared with HIV-negative MSM, HIV-positive MSM had higher rates of sharing snorting drug equipment, injecting drugs/‘slamming’ and using recreational drugs (all p<0.05) but lower rates of five or more sexual partners and insertive unprotected anal intercourse (p<0.05). MSM newly diagnosed with HCV had significantly higher prevalence of unprotected sex, sex with someone HCV positive, fisting, group sex, ever injecting drugs/‘slamming’ and recreational drug use (p<0.002). Conclusions In this survey, HIV-positive MSM had significantly different drug use behaviour which may explain the higher HCV burden. However, HCV was also associated with HIV-negative MSM engaging in high-risk sexual practices. All MSM attending sexual health clinics must have a risk assessment and HCV screening should be offered based on the risk. Further studies are warranted to explore the interplay between HCV and HIV risk associated with drug use versus sexual practices.

Using surveillance data to determine treatment rates and outcomes for patients with chronic hepatitis C virus infection

The aim of this work was to develop and validate an algorithm to monitor rates of, and response to, treatment of patients infected with hepatitis C virus (HCV) across England using routine laboratory HCV RNA testing data. HCV testing activity between January 2002 and December 2011 was extracted from the local laboratory information systems of a sentinel network of 23 laboratories across England. An algorithm based on frequency of HCV RNA testing within a defined time period was designed to identify treated patients. Validation of the algorithm was undertaken for one center by comparison with treatment data recorded in a clinical database managed by the Trent HCV Study Group. In total, 267,887 HCV RNA test results from 100,640 individuals were extracted. Of these, 78.9% (79,360) tested positive for viral RNA, indicating an active infection, 20.8% (16,538) of whom had a repeat pattern of HCV RNA testing suggestive of treatment monitoring. Annual numbers of individuals treated increased rapidly from 468 in 2002 to 3,295 in 2009, but decreased to 3,110 in 2010. Approximately two thirds (63.3%; 10,468) of those treated had results consistent with a sustained virological response, including 55.3% and 67.1% of those with a genotype 1 and non‐1 virus, respectively. Validation against the Trent clinical database demonstrated that the algorithm was 95% sensitive and 93% specific in detecting treatment and 100% sensitive and 93% specific for detecting treatment outcome. Conclusions: Laboratory testing activity, collected through a sentinel surveillance program, has enabled the first country‐wide analysis of treatment and response among HCV‐infected individuals. Our approach provides a sensitive, robust, and sustainable method for monitoring service provision across England. (Hepatology 2014;59:1343‐1350)

Establishing the cascade of care for hepatitis C in England-benchmarking to monitor impact of direct acting antivirals

Little is known about engagement and retention in care of people diagnosed with chronic hepatitis C (HCV) in England. Establishing a cascade of care informs targeted interventions for improving case finding, referral, treatment uptake and retention in care. Using data from the sentinel surveillance of blood‐borne virus (SSBBV) testing between 2005 and 2014, we investigate the continuum of care of those tested for HCV in England. Persons ≥1 year old with an anti‐HCV test and subsequent RNA tests between 2005 and 2014 reported to SSBBV were collated. We describe the cascade of care, as the patient pathway from a diagnostic test, referral into care, treatment and patient outcomes. Between 2005 and 2014, 2 390 507 samples were tested for anti‐HCV, corresponding to 1 766 515 persons. A total of 53 038 persons (35 190 men and 17 165 women) with anti‐HCV positive were newly reported to SSBBV. An RNA test was conducted on 77.0% persons who were anti‐HCV positive, 72.3% of whom were viraemic (RNA positive) during this time period, 21.4% had evidence of treatment and 3130 49.5% had evidence of a sustained virological response (SVR). In multivariable models, confirmation of viraemia by RNA test varied by age and region/test setting; evidence of treatment varied by age, year of test and region/test setting; and SVR varied by age, year of test and region/setting of test. In conclusion, our findings provide HCV cascade of care estimates prior to the introduction of direct acting antivirals. These findings provide important baseline cascade estimates to benchmark progress towards elimination of HCV as a major public health threat.

Understanding hepatitis C intervention success: qualitative findings from the HepCATT study

The United Kingdom has committed to eliminating viral hepatitis as a public health threat. Innovative interventions for marginalized populations are required to realize this goal. In 2016, the HepCATT study team implemented a complex hepatitis C (HCV) intervention in three English drug treatment services, with five controls. We report qualitative study findings from two intervention sites to explore intervention success and transferability potential. The intervention comprised multiple components, including a nurse facilitator, peer support and education initiatives. Qualitative data were generated at baseline (2014) and post‐intervention (2016) at two sites through in‐depth interviews, focus groups and observations. The 96 participants comprised drug service and intervention providers and clients with an injecting history. Data were triangulated and thematically analysed. Client engagement with a HCV treatment service rose from 16 at baseline to 147 in 2016. There was no comparable increase at the five control sites. Baseline testing and treatment barriers included the following: limited HCV knowledge; fear of diagnosis and treatment; precarious living circumstances and service‐specific obstacles. Treatment engagement was aided by intervention timeliness; improved communication structures; personalized care; streamlined testing and treatment pathways; peer support. Multiple interrelated components influenced the increased levels of treatment engagement documented in HepCATT. The nurse facilitator, involved in implementation and innovation, was key to intervention success. Baseline barriers correspond with international literature—indicating transferability potential. Control data indicate that biomedical innovation alone is not sufficient to increase engagement among the most marginalized. Sustainable resourcing of community services is crucial to effect change.

Prevalence of diagnosed HIV infection among persons with hepatitis C virus infection: England, 2008-2014

In persons with hepatitis C virus (HCV) infection, HIV coinfection leads to faster progression to advanced liver disease. The aim of our study was to estimate diagnosed HIV prevalence among people with evidence of current HCV infection (polymerase chain reaction positive) and examine predictors of coinfection.

Consequences of screening English blood donors for HHV‐8 antibodies. Is it worth it?

Human herpesvirus 8 (HHV‐8) is the causative agent of Kaposis sarcoma which is of concern in organ transplantation due to transmission through either the donor organ or any associated blood components to immunologically susceptible patients. The prevalence of HHV‐8 in the UK has not been widely investigated. In this study, the seroprevalence of HHV‐8 in English blood donors was measured and the performance of confirmatory assays evaluated.

The Impact of HCV Infection Duration on HIV Disease Progression and Response to cART amongst HIV Seroconverters in the UK.

Introduction The effect of HCV infection on HIV disease progression remains unclear; the effect of HCV infection duration on HIV disease progression is unknown. Methods We used data from a cohort of HIV seroconverters to investigate the effect of HCV infection duration on time from HIV seroconversion to CD4 <350cells/mm3, AIDS or death, censoring at the earlier of cART initiation or last clinic visit, adjusting for confounders and splitting data into follow up periods from HIV seroconversion (<2, 2–4 and >4 years). We additionally compared CD4 cell decline following HCV infection to that of mono-infected individuals with similar HIV infection duration by fitting a random effects model. In a separate analysis, we used linear mixed models to we examine the effect of HCV infection and its duration on CD4 increase over 48 weeks following cART. Results Of 1655 individuals, 97 (5.9%) were HCV co-infected. HCV<1 year was associated with a higher risk of endpoint in each follow-up period from HIV seroconversion (HR [95% CI] 2.58 [1.51, 4.41], p = 0.001; 3.80 [1.20, 12.03], p = 0.023; 2.03 [0.88, 4.71], p = 0.098 for <2, 2–4 and >4 years respectively), compared to mono-infected individuals. However, we found no evidence of an association for those with HCV>2 years (all p>0.89). Individuals experienced a somewhat greater decrease in CD4 count following HCV infection lasting 13 months, relative to individuals with HIV alone, (estimate = -3.33, 95% CI [-7.29, 0.63] cells/mm3 per month, p = 0.099). Of 1502 initiating cART, 106 (7.1%) were HCV co-infected, with no evidence of HCV duration at cART being associated with immunological response (p = 0.45). Conclusions The impact of HCV co-infection on HIV disease progression appears to be restricted to the first year after HCV infection.