The implementation of a hepatitis C testing service in community pharmacies: I-COPTIC consensus statement.

OBJECTIVES: This aimed to develop a blueprint for an effective community pharmacy Hepatitis C virus (HCV) testing service by producing a consensus statement. STUDY DESIGN: This was a modified Delphi process. METHODS: We recruited a heterogenous panel of experts (who had been involved in the setup or delivery of a community pharmacy HCV testing service) by purposive and chain referral methods. We had three rounds of a modified Delphi process. The first was a series of questions with free text responses and was analysed using thematic analysis, and the second and third were statements for the respondents to rate using a 7-point Likert scale. Consensus was predefined in a published protocol, and the results were reviewed by a public and patient involvement panel before the statement was finalised. RESULTS: We had 24 participants, including community and hospital-based pharmacists, local pharmaceutical committee members, charity representatives (Hepatitis C Trust), local clinical service lead, nurse specialists and doctors. The response rate of the first, second and third rounds were 100%, 96% and 88%, respectively. After the third round, we had 60 statements that reached consensus. We discussed the accepted statements with a patient and public involvement group. We used these statements to produce the I-COPTIC statement and a graphical summary. CONCLUSIONS: We developed a blueprint for the design of a gold standard community pharmacy HCV testing service. We believe this will support the successful implementation of community pharmacy testing for HCV. Community pharmacy testing is an important service to help achieve and maintain HCV elimination.

Increased case-finding and uptake of direct-acting antiviral treatment essential for micro-elimination of hepatitis C among people living with HIV: a national record linkage study.

OBJECTIVES: Micro-elimination of hepatitis C virus (HCV) in people living with HIV (PLHIV) and co-infected with HCV has been proposed as a key contribution to the overall goal of HCV elimination. While other studies have examined micro-elimination in HIV-treated cohorts, few have considered HCV micro-elimination among those not treated for HIV or at a national level. METHODS: Through data linkage of national and sentinel surveillance data, we examined the extent of HCV testing, diagnosis and treatment among a cohort of PLHIV in Scotland identified through the national database of HIV-diagnosed individuals, up to the end of 2017. RESULTS: Of 5018 PLHIV, an estimated 797 (15%) had never been tested for HCV and 70 (9%) of these had undiagnosed chronic HCV. The odds of never having been tested for HCV were the highest in those not on HIV treatment [adjusted odds ratio (aOR) = 7.21, 95% confidence interval (CI): 5.15-10.10). Overall HCV antibody positivity was 11%, and it was at its highest among people who inject drugs (49%). Most of those with chronic HCV (91%) had attended an HCV treatment clinic but only half had been successfully treated (54% for those on HIV treatment, 12% for those not) by the end of 2017. The odds of never having been treated for HCV were the highest in those not on HIV treatment (aOR = 3.60, 95% CI: 1.59-8.15). CONCLUSIONS: Our data demonstrate that micro-elimination of HCV in PLHIV is achievable but progress will require increased effort to engage and treat those co-infected, including those not being treated for their HIV.

We know DAAs work, so now what? Simplifying models of care to enhance the hepatitis C cascade.

Globally, some 71 million people are chronically infected with hepatitis C virus (HCV). Marginalized populations, particularly people who inject drugs (PWID), have low testing, linkage to care and treatment rates for HCV. Several models of care (MoCs) and service delivery interventions have the potential to improve outcomes across the HCV cascade of care, but much of the relevant research was carried out when interferon-based treatment was the standard of care. Often it was not practical to scale-up these earlier models and interventions because the clinical care needs of patients taking interferon-based regimens imposed too much of a financial and human resource burden on health systems. Despite the adoption of highly effective, all-oral direct-acting antiviral (DAA) therapies in recent years, approaches to HCV testing and treatment have evolved slowly and often remain rooted in earlier paradigms. The effectiveness of DAAs allows for simpler approaches and has encouraged countries where the drugs are widely available to set their sights on the ambitious World Health Organization (WHO) HCV elimination targets. Since a large proportion of chronically HCV-infected people are not currently accessing treatment, there is an urgent need to identify and implement existing simplified MoCs that speak to specific populations' needs. This article aims to: (i) review the evidence on MoCs for HCV; and (ii) distil the findings into recommendations for how stakeholders can simplify the path taken by chronically HCV-infected individuals from testing to cure and subsequent care and monitoring.

Impact of previous hepatitis B infection on the clinical outcomes from chronic hepatitis C? A population-level analysis.

Chronic coinfection with hepatitis C virus (HCV) and hepatitis B virus (HBV) is associated with adverse liver outcomes. The clinical impact of previous HBV infection on liver disease in HCV infection is unknown. We aimed at determining any association of previous HBV infection with liver outcomes using antibodies to the hepatitis B core antigen (HBcAb) positivity as a marker of exposure. The Scottish Hepatitis C Clinical Database containing data for all patients attending HCV clinics in participating health boards was linked to the HBV diagnostic registry and mortality data from Information Services Division, Scotland. Survival analyses with competing risks were constructed for time from the first appointment to decompensated cirrhosis, hepatocellular carcinoma (HCC) and liver-related mortality. Records of 8513 chronic HCV patients were included in the analyses (87 HBcAb positive and HBV surface antigen [HBsAg] positive, 1577 HBcAb positive and HBsAg negative, and 6849 HBcAb negative). Multivariate cause-specific proportional hazards models showed previous HBV infection (HBcAb positive and HBsAg negative) significantly increased the risks of decompensated cirrhosis (hazard ratio [HR]: 1.29, 95% CI: 1.01-1.65) and HCC (HR: 1.64, 95% CI: 1.09-2.49), but not liver-related death (HR: 1.02, 95% CI: 0.80-1.30). This is the largest study to date showing an association between previous HBV infection and certain adverse liver outcomes in HCV infection. Our analyses add significantly to evidence which suggests that HBV infection adversely affects liver health despite apparent clearance. This has important implications for HBV vaccination policy and indications for prioritization of HCV therapy.

Multidisciplinary managed care networks-Life-saving interventions for hepatitis C patients.

Successful hepatitis C virus (HCV) therapy depends on effective pathways of care. Over two decades, we have developed four sequential models of care latterly using a multidisciplinary managed care network to improve HCV testing, care and treatment. This was a cohort study to evaluate the effectiveness of care pathways, carried out using all HCV antibody-positive individuals tested in a geographical region between 1994 and 2014. The study involved 3122 HCV-positive patients. They were divided into four subgroups representing different care pathways defined by their date of HCV antibody diagnosis. The number who accessed treatment services within 1 year of diagnosis increased from 77 of 292 (26.3%) to 521 of 821 (72.9%). The rate of treatment starts within 1 year of diagnosis increased from 6 of 292 (2.0%) to 133 of 821 (16.2%), and the sustained viral response rate improved from 61.6% to 77.4%. All-cause mortality decreased from 232 of 688 (33.7%) in subgroup A to 55 of 1207 (4.5%) in subgroup D, and multivariate analysis showed that pathway type was an independent predictor of mortality irrespective of age, sex, SVR status or HIV co-infection with pathway in D having an odds ratio of 0.53(0.40-0.77; P<.001) compared to pathway in A. At study end, 78% (3122) of an estimated 4000 HCV positive had been diagnosed. In total, 97.5% of HCV caseload was referred to specialist services and 89% attended for assessment. The introduction of a managed care network increased access to care and reduced all-cause mortality.

Limited impact of awareness-raising campaigns on hepatitis C testing practices among general practitioners.

The global hepatitis strategy calls for increased effort to diagnose those infected, with a target of 90% diagnosed by 2030. Scotland's Action Plan on Hepatitis C included awareness-raising campaigns, undertaken during 2008-2011, to promote testing by general practitioners. We examined hepatitis C virus (HCV) testing practice among general practitioners before and following these campaigns. Scottish general practitioners were surveyed, using Dillman's method, in 2007 and 2013; response rates were 69% and 60%, respectively. Most respondents offer testing when presented with a risk history (86% in 2007, 88% in 2013) but only one-fifth actively sought out risk factors (19% in 2007, 21% in 2013). Testing was reportedly always/almost always/usually offered to people who inject drugs (84% in 2007, 87% in 2013). Significant improvements in the offer of testing were reported in patients with abnormal LFTs (41% in 2007, 65% in 2013, P<.001) and who had received medical/dental treatment in high prevalence countries (14% in 2007, 24% in 2013, P=.001). In 2013, 25% of respondents had undertaken HCV-related continued professional development. This group was significantly more likely to actively seek out risk factors (P=.009) but only significantly more likely to offer a test to patients who had received medical/dental treatment in high prevalence countries (P=.001). Our findings suggest that government-led awareness raising campaigns have limited impact on general practitioners' testing practices. If the majority of the HCV-infected population are to be diagnosed, practitioner-based or physician-centred interventions should be considered alongside educational initiatives targeted at professionals.

A matched comparison study of hepatitis C treatment outcomes in the prison and community setting, and an analysis of the impact of prison release or transfer during therapy.

Prisoners are a priority group for hepatitis C (HCV) treatment. Although treatment durations will become shorter using directly acting antivirals (DAAs), nearly half of prison sentences in Scotland are too short to allow completion of DAA therapy prior to release. The purpose of this study was to compare treatment outcomes between prison- and community-based patients and to examine the impact of prison release or transfer during therapy. A national database was used to compare treatment outcomes between prison treatment initiates and a matched community sample. Additional data were collected to investigate the impact of release or transfer on treatment outcomes. Treatment-naïve patients infected with genotype 1/2/3/4 and treated between 2009 and 2012 were eligible for inclusion. 291 prison initiates were matched with 1137 community initiates: SVRs were 61% (95% CI 55%-66%) and 63% (95% CI 60%-66%), respectively. Odds of achieving a SVR were not significantly associated with prisoner status (P=.33). SVRs were 74% (95% CI 65%-81%), 59% (95% CI 42%-75%) and 45% (95% CI 29%-62%) among those not released or transferred, transferred during treatment, or released during treatment, respectively. Odds of achieving a SVR were significantly associated with release (P<.01), but not transfer (P=.18). Prison-based HCV treatment achieves similar outcomes to community-based treatment, with those not released or transferred during treatment doing particularly well. Transfer or release during therapy should be avoided whenever possible, using anticipatory planning and medical holds where appropriate.

HCV treatment rates and sustained viral response among people who inject drugs in seven UK sites: real world results and modelling of treatment impact.

Hepatitis C virus (HCV) antiviral treatment for people who inject drugs (PWID) could prevent onwards transmission and reduce chronic prevalence. We assessed current PWID treatment rates in seven UK settings and projected the potential impact of current and scaled-up treatment on HCV chronic prevalence. Data on number of PWID treated and sustained viral response rates (SVR) were collected from seven UK settings: Bristol (37-48% HCV chronic prevalence among PWID), East London (37-48%), Manchester (48-56%), Nottingham (37-44%), Plymouth (30-37%), Dundee (20-27%) and North Wales (27-33%). A model of HCV transmission among PWID projected the 10-year impact of (i) current treatment rates and SVR (ii) scale-up with interferon-free direct acting antivirals (IFN-free DAAs) with 90% SVR. Treatment rates varied from <5 to over 25 per 1000 PWID. Pooled intention-to-treat SVR for PWID were 45% genotypes 1/4 [95%CI 33-57%] and 61% genotypes 2/3 [95%CI 47-76%]. Projections of chronic HCV prevalence among PWID after 10 years of current levels of treatment overlapped substantially with current HCV prevalence estimates. Scaling-up treatment to 26/1000 PWID annually (achieved already in two sites) with IFN-free DAAs could achieve an observable absolute reduction in HCV chronic prevalence of at least 15% among PWID in all sites and greater than a halving in chronic HCV in Plymouth, Dundee and North Wales within a decade. Current treatment rates among PWID are unlikely to achieve observable reductions in HCV chronic prevalence over the next 10 years. Achievable scale-up, however, could lead to substantial reductions in HCV chronic prevalence.

Attendance at specialist hepatitis clinics and initiation of antiviral treatment among persons chronically infected with hepatitis C: examining the early impact of Scotland's Hepatitis C Action Plan.

Primary goals of the Hepatitis C Action Plan for Scotland Phase II (May 2008-March 2011) were to increase, among persons chronically infected with the hepatitis C (HCV) virus, attendance at specialist outpatient clinics and initiation on antiviral therapy. We evaluated progress towards these goals by comparing the odds, across time, of (a) first clinic attendance within 12 months of HCV diagnosis (n = 9747) and (b) initiation on antiviral treatment within 12 months of first attendance (n = 5736). Record linkage between the national HCV diagnosis (1996-2009) and HCV clinical (1996-2010) databases and logistic regression analyses were conducted for both outcomes. For outcome (a), 32% and 45% in the respective pre-Phase II (before 1 May 2008) and Phase II periods attended a specialist clinic within 12 months of diagnosis; the odds of attendance within 12 months increased over time (OR = 1.05 per year, 95% CI: 1.04-1.07), but was not significantly greater for persons diagnosed with HCV in the Phase II era, compared with the pre-Phase II era (OR = 1.1, 95% CI: 0.9-1.3), after adjustment for temporal trend. For outcome (b), 13% and 28% were initiated on treatment within 12 months of their first clinic attendance in the pre-Phase II and Phase II periods, respectively. Higher odds of treatment initiation were associated with first clinic attendance in the Phase II (OR = 1.9, 95% CI: 1.5-2.4), compared with the pre-Phase II era. Results were consistent with a positive impact of the Hepatitis C Action Plan on the treatment of chronically infected individuals, but further monitoring is required to confirm a sustained effect.

Prevalence estimates of diagnosed viral hepatitis B, liver condition outcomes and hospitalization costs: a population record-linkage study in Tayside, Scotland.

We estimated prevalence and incidence of liver condition outcomes, and costs to the health service of diagnosed hepatitis B virus (HBV) in Tayside, UK. HBV patients were identified from electronic virology data between 1989 and 2003. The health resource costs of HBV for surface antigen-positive (HBsAg+) patients and HBV (HBsAg+ or immune, i.e. recovered) patients were calculated. A total of 633 patients had HBV (275 HBsAg+), and were more likely to be male (62% vs. 48%), older (mean age 42.6 vs. 39 . 2 years) and deprived than the general population. The prevalence of immune individuals increased steadily. Post-HBV diagnosis, 24% of immune and 13% of HBsAg+ patients were diagnosed with a liver condition. The median cost per immune patient (£3023) was greater than per HBsAg+ patient (£1498) (P=0.02). While increasing prevalence of immune HBV patients highlights an increase in screening and treatment, the costs associated with this group are high.

Intravenous drug use: not a barrier to achieving a sustained virological response in HCV infection.

Hepatitis C virus (HCV) is commonly transmitted by intravenous drug use (IDU) but drug users are under represented in many treatment cohorts, this is because of the assumption of lowered treatment success. We assessed HCV treatment outcomes in active intravenous drug users and patients on opiate substitution therapy. The Tayside HCV treatment database was retrospectively analysed for consecutively treated patients based on risk factor for acquisition of HCV. Primary end point was sustained virological response (SVR). Two hundred and ninety-one consecutively treated patients were assessed. The overall SVR rate was 55.3%. The SVR rates by risk factor were; Non-IDU 61.4%, Ex-IDU 54.8% and Active IDU 47.1% (P = n/s). In the groups G1 patients SVR was; Non-IDU 52.7%, Ex-IDU 30.7% and active IDU 35.4% (P = n/s). In the non-G1 patients: non-IDU 65.1%, Ex-IDU 76.7% and active IDU 53.5%. Ex-IDU had a significantly better SVR than active IDU, other differences were not significant. Our results demonstrate that SVR rates in the active drug users and those on opiate substitution therapy can be achieved which are comparable with non-IDU infected individuals. Intravenous drug use in those engaged with treatment services should not be seen as a barrier to treatment of HCV.

The effectiveness of outreach testing for hepatitis C in an immigrant Pakistani population.

In Scotland, an estimated 1% of the population is infected with hepatitis C virus (HCV). There is ethnic diversity in Scotland, with a large Pakistani sub-population. Our aim was to investigate the prevalence of HCV in an immigrant Pakistani population and effectiveness of an outreach testing intervention. We arranged a series of HCV awareness meetings at the mosques and Pakistani Women's centre in the city of Dundee. Thereafter short-term outreach HCV testing clinics were set up in the same venues. Venous blood samples were obtained and tested for HCV IgG and HbsAg. A short questionnaire was also completed. In total, 177 individuals volunteered for testing, out of an estimated 250 who attended meetings and a total Pakistani population in Dundee of 1723. Of those tested 170 were Scottish Pakistanis (159 first generation, 11 second generation). There were 145 (85.2%) men. The mean age was 45.11 (± S.D. 16.7) years. Seven (4.1%) individuals in the cohort were anti-HCV positive. Five (2.9%) were found to have HCV RNA by PCR. Only one patient had chronic hepatitis B infection. All patients with positive results were seen in the liver clinic for consideration of treatment. We have demonstrated that immigrant Pakistanis retain a higher prevalence of HCV compared to the population of their adopted country. Outreach targeted testing in this group can be achieved using religious and cultural gatherings, with only modest investment in staff time.

Cost-effectiveness of pharmacy-led versus conventionally delivered antiviral treatment for hepatitis C in patients receiving opioid substitution therapy: An economic evaluation alongside a pragmatic cluster randomised trial.

BACKGROUND: Elimination targets for hepatitis C have been set across the world. In the UK almost 90% of infections are in people who inject drugs. Evidence shows community case-finding is effective at identifying and treating undiagnosed patients. The aim of this analysis was to assess, from a healthcare provider perspective, the cost-effectiveness of a new pharmacist-led test and treat pathway for hepatitis C in opioid agonist treatment (OAT) patients attending community pharmacies compared to conventional care. METHODS: In a cluster randomised controlled trial, pharmacies were randomised to the pharmacist-led or conventional care pathway. Mean cost per OAT patient and per patient initiating treatment was identified for each pathway. A Markov model tracking disease progression was developed, with a 50-year time horizon and 3·5% time discount rate, to estimate the incremental cost-effectiveness ratio (ICER) per quality-adjusted life-year (QALY) gained and the probability of being cost-effective at a £30,000 per QALY willingness-to-pay threshold. Probabilistic sensitivity analysis was performed for a range of drug discounts, re-infection rates, and model assumptions. FINDINGS: Mean cost per OAT patient (£3,674 vs £1,965) and per patient initiating treatment (£863 vs £404) was higher in the pharmacist-led pathway, due to higher uptake of testing and pharmacist time requirements. Over a 50-year time horizon the ICER per QALY gained was £31,612 at NHS indicative price for treatment (£38,979 for 12 weeks) and 12·1/100 person-years re-infection rate, reducing to £21,027/£10,220/-£501 per QALY gained with 30%/60%/90% drug price discounts and £25,373/£21,738/£14,912 per QALY gained at re-infection rates of 8/5/2 per 100 person-years. At 30%/60%/90% drug discount rates, the pharmacist-led pathway has an 80%/98%/100% probability of being cost-effective. INTERPRETATION: The pharmacist-led pathway is effective at increasing testing and treatment uptake, with cost-effectiveness being highly dependent on drug price discounts. FUNDING: Trial funding provided by the Scottish Government, Gilead Sciences, and Bristol-Myers Squibb.

The influence of hepatitis C and alcohol on liver-related morbidity and mortality in Glasgow's injecting drug user population.

Infection with the hepatitis C virus (HCV) is associated with the development of severe liver disease, but cofactors--namely alcohol abuse--in Scotland's HCV-positive population complicate estimation of the unique contribution of HCV. We compared the risk of hospital admission/death for a liver-related cause in a large cohort of Glasgow's injecting drug users (IDUs) testing HCV-positive with IDUs testing HCV negative. Data for 6566 current/former IDUs who had been tested for anti-HCV and/or HCV RNA by polymerase chain reaction in Greater Glasgow health board between 1993 and 2007 were linked to the national hospitalization database and deaths registry to identify all admissions and deaths from a liver-related condition. Relative risks were estimated using Cox proportional hazards regression for recurrent events. Time at risk was censored at 2 years following an HCV test to address bias owing to unobserved seroconversion. The risk of hospitalization/death from a liver-related or an alcoholic liver-related condition following HCV testing was greater for those IDUs with no prior alcohol-related hospitalization who tested positive [adjusted hazard ratio (HR) = 3.2, 95% CI: 1.5-6.7; 4.9, 95% CI: 1.8-13.1, respectively], compared with those who tested anti-HCV negative, but not for those IDUs with a prior alcohol admission (HR = 0.8, 95% CI: 0.4-1.5; 0.8, 95% CI: 0.4-1.6). There was little evidence for an increased risk of hospitalization/death for an exclusively nonalcoholic liver condition for those testing positive (HR = 1.5, 95% CI: 0.8-2.7), after adjustment for previous alcohol-related admission. Within Glasgow's IDU population, HCV positivity is associated with an increased risk of a liver-related outcome, but this is not observed for those IDUs whose problem alcohol use already increases their risk.

Excess morbidity in the hepatitis C-diagnosed population in Scotland, 1991-2006.

We estimated the excess risk of in-patient hospitalization in a large cohort of persons diagnosed with hepatitis C virus (HCV) infection, controlling for social deprivation. A total of 20 749 individuals diagnosed with HCV in Scotland by 31 December 2006 were linked to the Scottish hospital discharge database, and indirectly standardized hospitalization rates, adjusting for sex, age, year and deprivation were calculated. We observed significant excess morbidity considering episodes for: any diagnosis [standardized morbidity ratio (SMR) 3·4, 95% CI 3·3-3·5]; liver-related diagnoses (SMR 41·3, 95% CI 39·6-43·0); and only non-liver-related diagnoses (SMR 2·14, 95% CI 2·08-2·19). Cox regression analyses of the 2000-2006 data indicated increased relative risks of hospitalization for males [hazard ratio (HR) 1·1, 95% CI 1·0-1·2], older age (per 10 years) (HR 1·55, 95% CI 1·5-1·6), and those testing HIV-positive (HR 1·6, 95% CI 1·3-1·8). This study has revealed substantial excess all-cause and liver-related morbidity in the Scottish HCV-diagnosed population, even after allowing for deprivation.

The impact of a managed care network on attendance, follow-up and treatment at a hepatitis C specialist centre.

Infection with the hepatitis C virus commonly occurs in patient groups who have difficulty accessing conventional medical care, reducing their chance of successful antiviral therapy. Managed care networks (MCNs) have been suggested as a mechanism of improving access to care; however, there is little evidence to support their use in patients with hepatitis C. The aim of this study was to evaluate the impact of a MCN for patients with hepatitis C. This was a retrospective cohort study of all individuals in our area who had received a positive hepatitis C antibody test between August 1994 and June 2008. The MCN introduced a new referral pathway, which included nonmedical referrals and outreach nurse-led clinics. These interventions were introduced in 2004 and evaluated in 2008. After the introduction of the MCN, the proportion of individuals who accessed care increased from 61% (280/430) to 82.4% (721/875). There was an increase in nonmedical referrals with 81 (18.3%) being directly referred from Drug Problem Services and 75 (17%) from the Prison Service. The changes to referral did not have a negative impact on treatment outcomes as the number who completed treatment increased from 66.1% (43/65) to 73.7% (98/133) and the sustained virological response increased from 50.7% (33/65) to 60.9% (81/133). This study provides evidence that the collaboration of health care professionals within a network can have a radical effect in improving access to care in a traditionally hard to reach population. This has been achieved with little additional resource, but rather working smarter with existing staff.

Diagnosis of hepatitis C virus infection in Scotland's injecting drug user population.

We estimated the extent of undiagnosed hepatitis C virus (HCV) infection in injecting drug users (IDUs) in Scotland. We used record-linkage to determine HCV diagnosis status for 41 062 current/former IDUs attending drug treatment and support services between 1 April 1995 and 31 March 2006; the extent of undiagnosed HCV infection was estimated by comparing the number HCV-diagnosed to the number HCV-infected (estimated from an unlinked anonymous testing survey of 2141 current/former IDUs). In all, 9145 IDUs (22%) were diagnosed HCV antibody-positive since first attendance at drug services (diagnosis rate of 33.6/1000 person-years, 95% CI 32.7-34.4). By 31 March 2006, of the 19 632 current/former IDUs who had attended drug services and were determined to be living with HCV, an estimated 58% (95% CI 45-62) had not been HCV-diagnosed. It is essential that the deployment of resources for identifying at-risk IDUs with a view to offering antiviral therapy is guided by evidence.

The growing contribution of hepatitis C virus infection to liver-related mortality in Scotland.

The large number of individuals in Scotland who became infected with the hepatitis C virus (HCV) in the 1970s and 1980s leads us to expect liver-related morbidity and mortality to increase in the coming years. We investigated the contribution of HCV to liver-related mortality in the period January 1991 to June 2006. The study population consisted of 26,861 individuals whose death record mentioned a liver-related cause (underlying or contributing). Record-linkage to the national HCV Diagnosis database supplied HCV-diagnosed status for the study population. The proportion diagnosed with HCV among people dying from a liver-related cause rose from 2.8% (1995-1997) to 4.4% (2004-June 2006); the largest increase occurred in those aged 35-44 years at death (7% to 17%). Among all deaths from a liver-related cause, an HCV-positive diagnosis was more likely in those who died in 2001 or later than those who died in 1995-1997 (2001-2003: odds ratio (OR)=1.4, 95% confidence interval (CI): 1.1-1.7; 2004-June 2006: 1.6, 1.3-2.0), and in those who died at under 55 compared with at least 55 years of age. HCV infection represents a significant, growing, public health burden in Scotland in terms of early deaths from liver disease.

A record-linkage study of the development of hepatocellular carcinoma in persons with hepatitis C infection in Scotland.

We investigated trends in first-time hospital admissions and deaths attributable to hepatocellular carcinoma (HCC) in a large population-based cohort of 22 073 individuals diagnosed with hepatitis C viral (HCV) infection through laboratory testing in Scotland in 1991-2006. We identified new cases of HCC through record-linkage to the national inpatient hospital discharge database and deaths registry. A total of 172 persons diagnosed with HCV were admitted to hospital or died with first-time mention of HCC. Hepatocellular carcinoma incidence increased between 1996 and 2006 (average annual change of 6.1, 95% confidence interval (CI): 0.9-11.6%, P=0.021). The adjusted relative risk of HCC was greater for males (hazard ratio=2.7, 95% CI: 1.7-4.2), for those aged 60 years or older (hazard ratio=2.7, 95% CI: 1.9-4.1) compared with 50-59 years, and for those with a previous alcohol-related hospital admission (hazard ratio=2.5, 95% CI: 1.7-3.7). The risk of individuals diagnosed with HCV developing HCC was greatly increased compared with the general Scottish population (standardised incidence ratio=127, 95% CI: 102-156). Owing to the advancing age of the Scottish HCV-diagnosed population, the annual number of HCC cases is projected to increase, with a consequent increasing burden on the public healthcare system.