Data linkage to monitor hepatitis C-associated end-stage liver disease and hepatocellular carcinoma inpatient stays in England

Persons with chronic hepatitis C (HCV) infection are at increased risk of end-stage liver disease (ESLD) and hepatocellular carcinoma (HCC). The impact of hepatitis treatment scale-up and elimination strategies on ESLD and HCC incidence is a critical measure of progress towards WHO targets. Data from national laboratory surveillance of HCV diagnoses were linked to inpatient care records in Hospital Episode Statistics (HES). For persons first diagnosed with HCV between 1998-2016, we describe the characteristics of those with ESLD and HCC and estimate incidence. Of persons diagnosed with HCV between 1998 and 2016 (104,674), 9.1 % (9,525) had an admission for ESLD and 2.5% (2,610) for HCC. The majority of persons with ESLD and HCC were male (70.7% and 82.7%) and of white ethnicity (89.9% and 82.7%). Crude incidence of ESLD and HCC admission was 10.4 and 3.2 per 1,000 person years respectively. When compared to 2011-2013, incidence of ESLD and HCC admissions in 2014-2017 were lower [ESLD incidence rate ratio (IRR): 0.81; 95% Confidence interval (CI): 0.76-0.86; HCC IRR: 0.90; 95% CI: 0.82-1.00, p=0.045]. Data linkage showed considerable underreporting of HCV in HES coding for ESLD and HCC (16.0% and 11.3% respectively). In conclusion, we found a decline in incidence of ESLD and HCC-related inpatient admissions since 2011-2013. Linked analysis is required for the continued monitoring of ESLD and HCC inpatient incidence. However, HES data quality issues around completeness of identifiers contribute to uncertainty in linkage and may limit our ability to robustly monitor progress towards WHO elimination goals

Mark Garry : a New Quiet

A survey of ten years practice

Monitoring liver transplant rates in persons diagnosed with hepatitis C:a data linkage study, England 2008 to 2017

INTRODUCTION: Liver transplantation is an important measure of burden from hepatitis C virus (HCV)-associated liver disease. AIMS: To describe transplant rates and survival in individuals with HCV infection from 2008 to 2017 in England through data linkage. METHODS: This is a retrospective observational cohort study. Laboratory reports of HCV infection were linked to the Liver Transplant Registry for individuals aged 15 years and over, first diagnosed between 1998 and 2017. We estimated age-sex standardised incidence rates and used Poisson regression to investigate predictors of liver transplantation and test for a change in incidence after introduction of direct-acting antivirals (DAAs) in 2014. Kaplan-Meier survival analysis was used to calculate post-transplant survival rates. RESULTS: Of 124,238 individuals diagnosed with HCV infection, 1,480 were registered and 1,217 received a liver transplant. Of individuals registered, 1,395 had post-HCV cirrhosis and 636 had hepatocellular carcinoma (618 also had post-HCV cirrhosis). Median time from HCV diagnosis to transplant was 3.4 years (interquartile range: 1.3–6.8 years). Liver transplant rates were lower 2014–17 compared with 2011–13 (incidence rate ratio: 0.64; 95% confidence interval: 0.55–0.76). Survival rates were 93.4%, 79.9% and 67.9% at 1, 5 and 10 years, respectively. Data linkage showed minimal under-reporting of HCV in the transplant registry. CONCLUSION: In the post-DAA era, liver transplant rates have fallen in individuals with HCV infection, showing early impact of HCV treatment scale-up; but the short time from HCV diagnosis to liver transplant suggests late diagnosis is a problem

Cost-Effectiveness of One-Time Birth Cohort Screening for Hepatitis C as Part of the National Health Service Health Check Program in England.

BACKGROUND AND OBJECTIVES: Birth cohort screening for the hepatitis C virus (HCV) has been implemented in the US, but there is little evidence of its cost-effectiveness in England. We aim to evaluate the cost-effectiveness of one-time HCV screening for individuals born between 1950 and 1979 as part of the National Health Service health check in England, a health check for adults aged 40 to 74 years in primary care. METHODS: A Markov model was developed to analyze add-on HCV testing to the National Health Service health check for individuals in birth cohorts between 1950 and 1979, versus current background HCV testing only, over a lifetime horizon. The model used data from a back-calculation model of the burden of HCV in England, sentinel surveillance of HCV testing, and published literature. Results are presented from a health service perspective in pounds in 2017, as incremental cost-effectiveness ratios per quality-adjusted life years gained. RESULTS: The base-case incremental cost-effectiveness ratios ranged from £7648 to £24 434, and £18 681 to £46 024, across birth cohorts when considering 2 sources of HCV transition probabilities. The intervention is most likely to be cost-effective for those born in the 1970s, and potentially cost-effective for those born from 1955 to 1969. The model results were most sensitive to the source of HCV transition probabilities, the probability of referral and receiving treatment, and the HCV prevalence among testers. The maximum value of future research across all birth cohorts was £11.3 million at £20 000 per quality-adjusted life years gained. CONCLUSION: Birth cohort screening is likely to be cost-effective for younger birth cohorts, although considerable uncertainty exists for other birth cohorts. Further studies are warranted to reduce uncertainty in cost-effectiveness and consider the acceptability of the intervention

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 testing (SSBBV) between 2005-2014 we investigate the continuum of care of those tested for HCV in England. Persons ≥1 years old, with an anti-HCV test and subsequent RNA tests between 2005-2014 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 2005-2014, 2,390,507 samples were tested for anti-HCV, corresponding to 1,766,515 persons. 53,038 persons (35,190 men and 17,165 women) anti-HCV positive were newly reported to SSBBV. An RNA test, was conducted on 77.0% persons 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

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 testing (SSBBV) between 2005-2014 we investigate the continuum of care of those tested for HCV in England.Persons ≥1 years old, with an anti-HCV test and subsequent RNA tests between 2005-2014 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 2005-2014, 2,390,507 samples were tested for anti-HCV, corresponding to 1,766,515 persons. 53,038 persons (35,190 men and 17,165 women) anti-HCV positive were newly reported to SSBBV. An RNA test, was conducted on 77.0% persons 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

Factors associated with COVID-19 vaccine uptake in adolescents: a national cross-sectional study, August 2021-January 2022, England.

OBJECTIVES: To assess socioeconomic and geographical factors associated with COVID-19 vaccine uptake in pupils attending state-funded secondary schools in England. DESIGN: Cross-sectional observational study. SETTING: State-funded schools in England. PARTICIPANTS: Pupils aged 12-17 years attending state-funded schools in England for the academic year 2021/2022. OUTCOME MEASURES: Demographic, socioeconomic and geographical factors associated with vaccination uptake. We linked individual-level data from the English Schools Census to the National Immunisation Management System to obtain COVID-19 vaccination status of 3.2 million adolescents. We used multivariable logistic regression to assess demographic, socioeconomic and geographical factors associated with vaccination. RESULTS: By 9 January 2022, 56.8% of adolescents aged 12-17 years old had received at least one dose, with uptake increasing from 48.7% in those aged 12 years old to 77.2% in those aged 17 years old. Among adolescents aged 12-15 years old, there were large variations in vaccine uptake by region and ethnic group. Pupils who spoke English as an additional language (38.2% vs 55.5%), with special educational needs (48.1% vs 53.5%), eligible for free school meals (35.9% vs 58.9%) and lived in more deprived areas (36.1% in most deprived vs 70.3% in least deprived) had lower vaccine uptake. Socioeconomic variables had greater impact on the odds of being vaccinated than geographical variables. School-level analysis found wide variation in vaccine uptake between schools even within the same region. Schools with higher proportions of pupils eligible for free school meals had lower vaccine uptake. CONCLUSIONS: We found large differences in vaccine uptake by geographical region and ethnicity. Socioeconomic variables had a greater impact on the odds of being vaccinated than geographical variables. Further research is required to identify evidence-based interventions to improve vaccine uptake in adolescents

Implementation of COVID-19 Preventive Measures and Staff Well-Being in a Sample of English Schools 2020-2021.

BACKGROUND: We examined fidelity and feasibility of implementation of COVID-19 preventive measures in schools, and explored associations between adherence to these measures and staff well-being, to inform policy on sustainable implementation and staff wellbeing. METHODS: Surveys were conducted across 128 schools in England with 107 headteachers and 2698 staff-members with reference to autumn term 2020, examining school-level implementation of preventive measures, adherence, and teacher burnout (response rates for headteacher and staff surveys were 84% and 59%, respectively). RESULTS: The median number of measures implemented in primary and secondary schools was 33 (range 23-41), and 32 (range 22-40), respectively; most measures presented challenges. No differences were found regarding number of measures implemented by school-level socio-economic disadvantage. High adherence was reported for staff wearing face-coverings, staff regularly washing their hands, (secondary only) desks facing forwards, and (primary only) increased cleaning of surfaces and student hand-washing. Adherence to most measures was reported as higher in primary than secondary schools. Over half of school leaders and 42% (517/1234) of other teaching staff suffered from high emotional exhaustion. Higher teacher-reported school-wide adherence with measures was consistently associated with lower burnout for leaders and other teaching staff. CONCLUSIONS: Findings indicate a tremendous effort in implementing preventive measures and an urgent need to support investments in improving teacher wellbeing

Immunological imprinting of humoral immunity to SARS-CoV-2 in children

Omicron variants of SARS-CoV-2 are globally dominant and infection rates are very high in children. We measure immune responses following Omicron BA.1/2 infection in children aged 6-14 years and relate this to prior and subsequent SARS-CoV-2 infection or vaccination. Primary Omicron infection elicits a weak antibody response with poor functional neutralizing antibodies. Subsequent Omicron reinfection or COVID-19 vaccination elicits increased antibody titres with broad neutralisation of Omicron subvariants. Prior pre-Omicron SARS-CoV-2 virus infection or vaccination primes for robust antibody responses following Omicron infection but these remain primarily focussed against ancestral variants. Primary Omicron infection thus elicits a weak antibody response in children which is boosted after reinfection or vaccination. Cellular responses are robust and broadly equivalent in all groups, providing protection against severe disease irrespective of SARS-CoV-2 variant. Immunological imprinting is likely to act as an important determinant of long-term humoral immunity, the future clinical importance of which is unknown