Geographical variation in hepatitis C-related severe liver disease and patient risk factors: a multicentre cross-sectional study.

Despite promising steps towards the elimination of hepatitis C virus (HCV) in the UK, several indicators provide a cause for concern for future disease burden. We aimed to improve understanding of geographical variation in HCV-related severe liver disease and historic risk factor prevalence among clinic attendees in England and Scotland. We used metadata from 3829 HCV-positive patients consecutively enrolled into HCV Research UK from 48 hospital centres in England and Scotland during 2012-2014. Employing mixed-effects statistical modelling, several independent risk factors were identified: age 46-59 y (ORadj 3.06) and ≥60 y (ORadj 5.64) relative to <46 y, male relative to female sex (ORadj 1.58), high BMI (ORadj 1.73) and obesity (ORadj 2.81) relative to normal BMI, diabetes relative to no diabetes (ORadj 2.75), infection with HCV genotype (GT)-3 relative to GT-1 (ORadj 1.75), route of infection through blood products relative to injecting drug use (ORadj 1.40), and lower odds were associated with black ethnicity (ORadj 0.31) relative to white ethnicity. A small proportion of unexplained variation was attributed to differences between hospital centres and local health authorities. Our study provides a baseline measure of historic risk factor prevalence and potential geographical variation in healthcare provision, to support ongoing monitoring of HCV-related disease burden and the design of risk prevention measures.

Population-level estimates of hepatitis C reinfection post scale-up of direct-acting antivirals among people who inject drugs.

BACKGROUND & AIMS: Scale-up of highly effective direct-acting antivirals (DAAs) for HCV among people who inject drugs (PWID) in Scotland has led to a reduction in the prevalence of viraemia in this population. However, the extent of reinfection among those treated with DAAs remains uncertain. We estimated HCV reinfection rates among PWID in Scotland by treatment setting, pre- and post-introduction of DAAs, and the potential number of undiagnosed reinfections resulting from incomplete follow-up testing. METHODS: Through linkage of national clinical and laboratory HCV data, a retrospective cohort of PWID who commenced treatment between 2000-2018 and achieved a sustained virological response (SVR) were followed up for reinfection to December 2019. Reinfection was defined as a positive HCV antigen or RNA test. RESULTS: Of 5,686 SVRs among 5,592 PWID, 4,126 (73%) had an HCV RNA or antigen test post-SVR. Of those retested, we identified 361 reinfections (3.9/100 person-years [PY]). The reinfection rate increased from 1.5/100 PY among PWID treated in 2000-2009 to 8.8/100 PY in 2017-2018. The highest reinfection rates were observed among those treated in prison (14.3/100 PY) and community settings (9.5/100 PY). Among those treated in the DAA era (2015-2018), 68% were tested within the first year post-SVR but only 30% in the second year; while 169 reinfections were diagnosed in follow-up, an estimated 200 reinfections (54% of the estimated total) had gone undetected. CONCLUSIONS: HCV reinfection rates among PWID in Scotland have risen alongside the scale-up of DAAs and broadened access to treatment for those at highest risk, through delivery in community drug services. Promotion of HCV testing post-SVR among PWID is essential to ensure those reinfected are identified and retreated promptly. LAY SUMMARY: Increased rates of hepatitis C reinfection in Scotland were observed following the rapid scale-up of highly effective direct-acting antiviral (DAA) treatments among people who inject drugs. This demonstrates that community-based treatment pathways are reaching high-risk groups, regarded vital in efforts to eliminate the virus. However, we estimate that less than half of reinfections have been detected in the DAA era because of inadequate levels of retesting beyond the first year following successful treatment. Sustained efforts that involve high coverage of harm reduction measures and high uptake of annual testing are required to ensure prompt diagnosis and treatment of those reinfected if the goals of elimination are to be met.

Population impact of direct-acting antiviral treatment on new presentations of hepatitis C-related decompensated cirrhosis: a national record-linkage study.

OBJECTIVE: Population-based studies demonstrating the clinical impact of interferon-free direct-acting antiviral (DAA) therapies are lacking. We examined the impact of the introduction of DAAs on HCV-related decompensated cirrhosis (DC) through analysis of population-based data from Scotland. DESIGN: Through analysis of national surveillance data (involving linkage of HCV diagnosis and clinical databases to hospital and deaths registers), we determined i) the scale-up in the number of patients treated and achieving a sustained viral response (SVR), and ii) the change in the trend of new presentations with HCV-related DC, with the introduction of DAAs. RESULTS: Approximately 11 000 patients had been treated in Scotland over the 8-year period 2010/11 to 2017/18. The scale-up in the number of patients achieving SVR between the pre-DAA and DAA eras was 2.3-fold overall and 5.9-fold among those with compensated cirrhosis (the group at immediate risk of developing DC). In the pre-DAA era, the annual number of HCV-related DC presentations increased 4.6-fold between 2000 (30) and 2014 (142). In the DAA era, presentations decreased by 51% to 69 in 2018 (and by 67% among those with chronic infection at presentation), representing a significant change in trend (rate ratio 0.88, 95% CI 0.85 to 0.90). With the introduction of DAAs, an estimated 330 DC cases had been averted during 2015-18. CONCLUSIONS: National scale-up in interferon-free DAA treatment is associated with the rapid downturn in presentations of HCV-related DC at the population-level. Major progress in averting HCV-related DC in the short-term is feasible, and thus other countries should strive to achieve the same.

Evaluating the effect of direct-acting antiviral agent treatment scale-up on Hepatitis C virus prevalence among people who inject drugs in UK.

BACKGROUND: There is limited empirical work assessing the effectiveness of treatment as prevention (TasP) in reducing HCV prevalence among people who inject drugs (PWID). Here, we used survey data from the UK during 2010-2020, to evaluate the impact of direct-acting antiviral agent (DAA) treatment scale-up, which started in 2015, on HCV prevalence among PWID. METHODS: We fitted a logistic regression to time/location specific data on prevalence from the Needle Exchange Surveillance Initiative in Scotland and Unlinked Anonymous Monitoring programme in England. For each post-intervention year and location, we quantified the effect of TasP as the difference between estimated prevalence and its counterfactual (prevalence in the absence of scale-up). Progress to elimination was assessed by comparing most recent prevalence against one in 2015. RESULTS: In 2015, prevalence ranged from 0.44 to 0.71 across the 23 locations (3 Scottish, 20 English). Compared to counterfactuals, there was an absolute reduction of 46% (95% credible interval [32%,59%]) in Tayside in 2020, 35% ([24%,44%]) in Glasgow in 2019, and 25% ([10%,39%]) in the Rest of Scotland in 2020. The English sites with highest estimated absolute reductions in 2021 were South Yorkshire (45%, [29%,58%]), Thames Valley (49%, [34%,59%]) and West London (41%, [14%,59%]). Compared to 2015, there was 80% probability that prevalence had fallen by 65% in Tayside, 53% in Glasgow and 36% in the Rest of Scotland. The English sites with highest % prevalence decrease compared to 2015, achieved with probability 80%, were Chesire & Merseyside (70%), South Yorkshire (65%) and Thames Valley (71%). Higher treatment intensity was associated with higher reductions in prevalence. CONCLUSION: Conclusion. Real-world evidence showing substantial reductions in chronic HCV associated with increase of HCV treatment scale-up in the community thus supporting the effectiveness of HCV treatmen as prevention in people who inject drugs.

Interventions to prevent HIV and Hepatitis C among people who inject drugs: Latest evidence of effectiveness from a systematic review (2011 to 2020).

BACKGROUND: Hepatitis C virus (HCV) and HIV remain prevalent among people who inject drugs (PWID) and transmission is usually associated with injecting risk behaviour (IRB). We update a 2011 review of reviews (RoR) to assess the latest evidence on the effectiveness of harm reduction interventions - drug treatment (including opioid agonist therapy [OAT]), needle and syringe programmes (NSP) and other interventions - in the prevention of HCV and HIV transmission, and related measures of infection risk (IRB and injecting frequency [IF]), among PWID. METHODS: We undertook an initial search for systematic reviews (i.e. an Overview of Reviews [OoR]) and subsequent systematic searches for primary studies where required. Where there was sufficient evidence based on synthesis of multiple robust studies for an intervention effect in the 2011 RoR, new evidence was not sought. Medline, CINAHL, The Cochrane Library, EMBASE, PsycINFO and Web of Science were searched (2011-2020). Two reviewers screened papers, extracted data, and graded reviews/studies. We classified evidence as 'sufficient', 'tentative', 'insufficient', or 'no evidence'. RESULTS: We screened 8513 reviews and 7133 studies, with 27 and 61 identified as relevant, respectively. The level of evidence increased since the 2011 RoR and is now 'sufficient' for OAT (regarding all outcomes), NSP (for reducing HIV transmission and IRB), and combination OAT/NSP (for reducing HCV transmission). There is also now sufficient evidence for in-prison OAT, psychosocial interventions, pharmacy-based NSP and provision of sterile drug preparation equipment for reducing IRB. CONCLUSION: There is now a strong body of empirical evidence for the effectiveness of OAT and NSP, alone and in combination, in reducing IRB, and HCV and HIV transmission. However, there is still a relative lack of evidence for other interventions, including heroin-assisted treatment, pharmacological treatment for stimulant dependence, contingency management, technology-based interventions, low dead space syringes and drug consumption rooms on HCV or HIV risk.

Reduction in the population prevalence of hepatitis C virus viraemia among people who inject drugs associated with scale-up of direct-acting anti-viral therapy in community drug services: real-world data.

BACKGROUND AND AIMS: There has been little empirical evidence to show the 'real-world' impact of scaling-up direct-acting anti-viral (DAA) treatment among people who inject drugs (PWID) on hepatitis C virus (HCV) viraemia at a population level. We aimed to assess the population impact of rapid DAA scale-up to PWID delivered through community services-including drug treatment, pharmacies, needle exchanges and prisons-in the Tayside region of Scotland, compared with Greater Glasgow and Clyde (GGC) and the Rest of Scotland (RoS). DESIGN, SETTING AND PARTICIPANTS: Natural experiment, evaluated using data from national biennial surveys of PWID and national clinical data. Services providing injecting equipment (2010-18) and HCV treatment clinics (2017-18) across Scotland. A total of 12 492 PWID who completed a questionnaire and provided a blood spot (tested for HCV-antibodies and RNA); 4105 individuals who initiated HCV treatment. INTERVENTION AND COMPARATOR, MEASUREMENTS: The intervention was rapid DAA scale-up among PWID, which occurred in Tayside. The comparator was GGC/RoS. Trends in HCV viraemia and uptake of HCV therapy over time; sustained viral response (SVR) rates to therapy by region and treatment setting. FINDINGS: Uptake of HCV therapy (last year) among PWID between 2013-14 and 2017-18 increased from 15 to 43% in Tayside, 6 to 16% in GGC and 11 to 23% in RoS. Between 2010 and 2017-18, the prevalence of HCV viraemia (among antibody-positives) declined from 73 to 44% in Tayside, 67 to 58% in GGC and 64 to 55% in RoS. The decline in viraemia was greater in Tayside [2017-18 adjusted odds ratio (aOR) = 0.47, 95% confidence interval (CI) = 0.30-0.75, P = 0.001] than elsewhere in Scotland (2017-18 aOR = 0.89, 95% CI = 0.74-1.07, P = 0.220) relative to the baseline of 2013-14 in RoS (including GGC). Per-protocol SVR rates among PWID treated in community sites did not differ from those treated in hospital sites in Tayside (97.4 versus 100.0%, P = 0.099). CONCLUSIONS: Scale-up of direct-acting anti-viral treatment among people who inject drugs can be achieved through hepatitis C virus (HCV) testing and treatment in community drug services while maintaining high sustained viral response rates and, in the Tayside region of Scotland, has led to a substantial reduction in chronic HCV in the population.

Global progress on the elimination of viral hepatitis as a major public health threat: An analysis of WHO Member State responses 2017.

In 2016, the World Health Assembly passed a resolution to eliminate viral hepatitis as a public health threat by 2030. We aimed to examine the status of the global viral hepatitis response. METHODS: In 2017, the World Health Organization (WHO) asked the Ministries of Health in all 194 Member States to complete a Country Profile on Viral Hepatitis policy uptake indicators, covering national plans/funding, engagement of civil society, testing guidance, access to treatment, and strategic information. RESULTS: Of 194 Member States, 135 (70%) responded, accounting for 87% of the global population infected with hepatitis B virus (HBV) and/or C virus (HCV). Of those responding, 84 (62%) had developed a national plan, of which, 49 (58%) had dedicated funding, and 62 (46%) had engaged with civil society; those engaged with civil society were more likely to have a funded plan than others (52% vs. 23%, p = 0.001). Guidance on testing pregnant women (for HBV) and people who inject drugs (for HCV) was available in 70% and 46% of Member States, respectively; 59% and 38% of Member States reported universal access to optimal therapies for HBV and HCV, respectively. CONCLUSIONS: Most people living with hepatitis B and C reside in a country with a national hepatitis strategy. Governments who engaged with civil society were more advanced in their response. Member States need to finance these national strategies and ensure that those affected have access to hepatitis services as part of efforts to achieve universal health coverage. LAY SUMMARY: The World Health Organization's goal to eliminate viral hepatitis as a public health threat by 2030 requires global action. Our results indicate that progress is being made by countries to scale-up national planning efforts; however, our results also highlight important gaps in current policies.

Evaluating sickness absence duration by musculoskeletal and mental health issues: a retrospective cohort study of Scottish healthcare workers.

OBJECTIVES: Sickness absence (SA) among healthcare workers is associated with occupational and non-occupational risk factors and impacts employee health, healthcare delivery and patient health. At the same time, healthcare is one of the employment sectors with the highest rates of work-related ill health in the UK. Musculoskeletal (MSK) and mental health (MH) issues are leading causes of SA, but there is a lack of research on how certain MSK/MH conditions impact on SA duration. The study aim is to determine differences in SA duration by MH and MSK disorders in healthcare employees. METHODS: Survival analyses were used to estimate SA duration due to MSK and MH problems over 6 years, and Cox's proportional hazards models to determine the HRs of returning to work, using a bespoke Scottish health board database with over 53 000 SA events. SA duration and time to return-to-work (RTW) were estimated for employees by age, gender, job and health conditions. RESULTS: MSK and MH conditions accounted for 27% and 6% of all SA events and 23.7% and 19.5% of all days lost, respectively. Average SA duration was 43.5 days for MSK and 53.9 days for MH conditions. For MSK conditions, employees with low back or neck pain had the fastest RTW (median P50: 7 days), whereas employees absent due to depression took the longest (P50: 54 days). The most influential sociodemographic variables affecting RTW were age, gender and job category. CONCLUSIONS: Using a unique and rich database, we found significant differences in SA duration by presenting condition in healthcare workers. MH conditions, and depression specifically, accounted for the most working days' absence. Significant variations in duration were also observed for MSK conditions. Our findings can inform public health practitioners and healthcare managers of the most significant factors impacting MSK-related and MH-related SA to develop and implement tailored and targeted workplace interventions.