Search

Introduction: We assessed the prevalence of prescribing of certain medications for alcohol dependence and the extent of any inequalities in receiving prescriptions for individuals with such a diagnosis. Further, we compared the effectiveness of two of the most prescribed medications (acamprosate and disulfiram) for alcohol dependence and assessed whether there is inequality in prescribing either of them. Methods: We used a nationwide dataset on prescriptions and hospitalisations in Scotland, UK (N = 19,748). We calculated the percentage of patients receiving alcohol dependence prescriptions after discharge, both overall and by socio‐economic groups. Binary logistic regressions were used to assess the odds of receiving any alcohol‐dependence prescription and the comparative odds of receiving acamprosate or disulfiram. Comparative effectiveness in avoiding future alcohol‐related hospitalisations (N = 11,239) was assessed using Cox modelling with statistical adjustment for potential confounding. Results: Upto 7% of hospitalised individuals for alcohol use disorder received prescriptions for alcohol dependence after being discharged. Least deprived socio‐economic groups had relatively more individuals receiving prescriptions. Inequalities in prescribing for alcohol dependence existed, especially across sex and comorbidities: males had 12% (odds ratio [OR] 0.88, 95% confidence interval [CI] 0.81–0.96) and those with a history of mental health hospitalisations had 10% (OR 0.90, 95% CI 0.82–0.98) lower odds of receiving prescriptions after an alcohol‐related hospitalisation. Prescribing disulfiram was superior to prescribing acamprosate in preventing alcohol‐related hospitalisations (hazard ratio ranged between 0.60 and 0.81 across analyses). Disulfiram was relatively less likely prescribed to those from more deprived areas. Discussion and Conclusions: Inequalities in prescribing for alcohol dependence exists in Scotland with lower prescribing to men and disulfiram prescribed more to those from least deprived areas. [ABSTRACT FROM AUTHOR]

INTRODUCTION: Risk scores estimating a patient's probability of a hepatocellular carcinoma (HCC) diagnosis are abundant but are difficult to interpret in isolation. We compared the predicted HCC probability for individuals with cirrhosis and cured hepatitis C with the general population (GP). METHODS: All patients with cirrhosis achieving sustained viral response (SVR) in Scotland by April 2018 were included (N = 1,803). The predicted 3-year probability of HCC at time of SVR achievement was determined using the aMAP prognostic model. GP data on the total number of incident HCCs in Scotland, stratified by demographics, were obtained from Public Health Scotland. Predicted HCC risk of cirrhosis SVR patients was compared with GP incidence using 2 metrics: (i) incidence ratio: i.e., 3-year predicted probability for a given patient divided by the 3-year probability in GP for the equivalent demographic group and (ii) absolute risk difference: the 3-year predicted probability minus the 3-year probability in the GP. RESULTS: The mean predicted 3-year HCC probability among cirrhosis SVR patients was 3.64% (range: 0.012%–36.12%). Conversely, the 3-year HCC probability in the GP was much lower, ranging from <0.0001% to 0.25% depending on demographics. The mean incidence ratio was 410, ranging from 5 to >10,000. The mean absolute risk difference was 3.61%, ranging from 0.012% to 35.9%. An online HCC-GP comparison calculator for use by patients/clinicians is available at https://thrive-svr.shinyapps.io/RShiny/. DISCUSSION: Comparing a patient's predicted HCC probability with the GP is feasible and may help clinicians communicate risk information and encourage screening uptake. [ABSTRACT FROM AUTHOR]

Background & aims: The impact of interferon (IFN)‐free therapies on the epidemiology of hepatitis C virus (HCV) related hepatocellular carcinoma (HCC) is not well understood at a population level. Our goal was to bridge this evidence gap. Methods: This study included all patients in Scotland with chronic HCV and a diagnosis of cirrhosis during 1999‐2019. Incident cases of HCC, episodes of curative HCC therapy, and HCC‐related deaths were identified through linkage to nationwide registries. Three time periods were examined: 1999‐2010 (pegylated interferon‐ribavirin [PIR]); 2011‐2013 (First‐generation DAA); and 2014‐2019 (IFN‐free era). We used regression modelling to determine time trends for (i) number diagnosed and living with HCV cirrhosis, (ii) HCC cumulative incidence, (iii) HCC curative treatment uptake and (iv) post‐HCC mortality. Results: 3347 cirrhosis patients were identified of which 381 (11.4%) developed HCC. After HCC diagnosis, 140 (36.7%) received curative HCC treatment and there were 202 deaths from HCC. The average annual number of patients diagnosed and living with HCV cirrhosis was approximately seven times higher in the IFN‐free versus the PIR era, whereas the number of incident HCCs was four times higher. However, the cumulative incidence of HCC was significantly lower in the IFN‐free versus PIR era (sdHR: 0.65; 95%CI:0.47‐0.88; P =.006). Among HCC patients, diagnosis in the IFN‐free era was not associated with improved uptake of curative treatment (aOR:1.18; 95%CI:0.69‐2.01; P =.54), or reduced post‐HCC mortality (sdHR: 0.74; 95%CI:0.53‐1.05; P =.09). Conclusions: The cumulative incidence of HCC is declining in HCV cirrhosis patients, but uptake of curative HCC therapy and post‐HCC survival remains suboptimal. [ABSTRACT FROM AUTHOR]

Summary: Background: Primary measures for preventing morbidity and mortality associated with bleeding gastroesophageal varices in cirrhotic patients include endoscopic screening. Aim: To identify factors associated with (a) screening and (b) first hospital admission for variceal bleeding among cirrhotic hepatitis C virus (HCV) patients attending specialist care in Scotland. Methods: The Scottish Hepatitis C Clinical Database was linked to national hospitalisation and deaths records to identify all chronic HCV patients diagnosed with compensated cirrhosis in 2005‐2016 (n = 2741). The adjusted odds of being screened by calendar year period were estimated using logistic regression, and the adjusted hazard ratio (HR) of a first variceal bleed using Cox regression. Results: About 34% were screened within the period starting 12 months before and ending 12 months after cirrhosis diagnosis. The proportion screened was stable in 2005‐2010 at 42%, declining to 37% in 2011‐2013 and 26% in 2014‐2016. Odds of screening were decreased for age‐groups <40 (OR = 0.61, 95% CI: 0.48‐0.77) and 60+ years (OR = 0.67, 95% CI: 0.48‐0.94), history of antiviral therapy (OR = 0.70, 95% CI: 0.55‐0.89), and cirrhosis diagnosis in 2014‐2015, compared with 2008‐2010 (OR = 0.67, 95% CI: 0.52‐0.86). Compared with 2008‐2010, there was no evidence for an increased/decreased relative risk of a first variceal bleed in any other period, but viral clearance was associated with a lower risk (HR = 0.56, 95% CI: 0.32‐0.97). Conclusions: Overall screening uptake following cirrhosis diagnosis was low, and the decline in recent years is of concern. The stable bleeding risk over time may be attributable both to ongoing prevention initiatives and to changing diagnostic procedures creating a patient pool with milder disease in more recent years. [ABSTRACT FROM AUTHOR]

Background: Although people who inject drugs (PWID) are an important group to receive Hepatitis C Virus (HCV) antiviral therapy, initiation onto treatment remains low. Concerns over reinfection may make clinicians reluctant to treat this group. We examined the risk of HCV reinfection among a cohort of PWID (encompassing all those reporting a history of injecting drug use) from Scotland who achieved a sustained virological response (SVR).Methods: Clinical and laboratory data were used to monitor RNA testing among PWID who attained SVR following therapy between 2000 and 2009. Data were linked to morbidity and mortality records. Follow-up began one year after completion of therapy, ending on 31st December, 2012. Frequency of RNA testing during follow-up was calculated and the incidence of HCV reinfection estimated. Cox proportional hazards regression was used to examine factors associated with HCV reinfection.Results: Among 448 PWID with a SVR, 277 (61.8%) were tested during follow-up, median 4.5 years; 191 (69%) received one RNA test and 86 (31%) received at least two RNA tests. There were seven reinfections over 410 person years generating a reinfection rate of 1.7/100py (95% CI 0.7-3.5). For PWID who have been hospitalised for an opiate or injection related cause post SVR (11%), the risk of HCV reinfection was greater [AHR=12.9, 95% CI 2.2-76.0, p=0.002] and the reinfection rate was 5.7/100py (95% CI 1.8-13.3).Conclusion: PWID who have been tested, following SVR, for HCV in Scotland appear to be at a low risk of reinfection. Follow-up and monitoring of this population are warranted as treatment is offered more widely. [ABSTRACT FROM AUTHOR]

Seven years have elapsed since the Scottish Government launched its Hepatitis C Action Plan - a Plan to improve services to prevent transmission of infection, particularly among people who inject drugs (PWID), identify those infected and ensure those infected receive optimal treatment. The Plan was underpinned by industrial scale funding (around £100 million, in addition to the general NHS funding, will have been invested by 2015), and a web of accountable national and local multi-disciplinary multi-agency networks responsible for the planning, development and delivery of services. Initiatives ranged from the introduction of testing in specialist drug services through finger-prick blood sampling by non-clinical staff, to the setting of government targets to ensure rapid scale-up of antiviral therapy. The Plan was informed by comprehensive national monitoring systems, indicating the extent of the problem not just in terms of numbers infected, diagnosed and treated but also the more penetrative data on the number advancing to end-stage liver disease and death, and also through compelling modelling work demonstrating the potential beneficial impact of scaling-up therapy and the mounting cost of not acting. Achievements include around 50% increase in the proportion of the infected population diagnosed (38% to 55%); a sustained near two-and-a-half fold increase in the annual number of people initiated onto therapy (470 to 1050) with more pronounced increases among PWID (300 to 840) and prisoners (20 to 140); and reversing of an upward trend in the overall number of people living with chronic infection. The Action Plan has demonstrated that a Government-backed, coordinated and invested approach can transform services and rapidly improve the lives of thousands. Cited as "an impressive example of a national strategy" by the Global Commission on Drug Policy, the Scottish Plan has also provided fundamental insights of international relevance into the management of HCV among PWID. [ABSTRACT FROM AUTHOR]

Abstract: Background: Unsafe injecting practices put injecting drug users (IDUs) at repeat exposure to infection with the hepatitis C virus (HCV). It has not yet been determined if spontaneously clearing one''s primary infection influences the risk of reinfection; our aim was to estimate the relative risk of reinfection in IDUs who have cleared the virus. Methods: We conducted a retrospective study using a large database of HCV test results covering Greater Glasgow Health Board during 1993–2007 to calculate rates of infection and reinfection in current/former IDUs. The relative risk of (re)infection in previously infected compared with never-infected IDUs was estimated using Poisson regression, adjusting for age at study entry, sex, and calendar period of test. Results: Although the rate of reinfection in IDUs who were HCV antibody-positive, RNA-negative at baseline was lower (7/100 person-years, 95% CI: 5–9) than the rate of acute infection in IDUs who were HCV antibody-negative at baseline (10/100 person-years, 95% CI: 9–12), the risk of reinfection was not significantly different than the risk of initial infection (adjusted rate ratio=0.78, 95% CI: 0.57–1.08). Conclusion: We found only weak evidence for a reduced risk of HCV reinfection in IDUs who had cleared their previous infection. Further research among those who have cleared infection through antiviral therapy is needed to help inform decisions regarding treatment of IDUs. [Copyright &y& Elsevier]

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., Competing Interests: Competing interests: SJH reports grants from Health Protection Scotland, during the conduct of the study; personal fees from Gilead, outside the submitted work. SB reports grants, personal fees and other from Gilead; grants, personal fees and other from AbbVie; all outside the submitted work. RF reports personal fees from Gilead, outside the submitted work. KT reports grants from GenMark, grants from Cepheid, grants from Qiagen, other from SpeedX, all outside the submitted work. PCH reports personal fees from Gilead, personal fees from AbbVie, personal fees from BMS, personal fees from Jannsen, personal fees from Roche, all outside the submitted work. NK reports personal fees from Gilead, personal fees from AbbVie, all outside the submitted work. JFD reports grants and personal fees from Gilead, grants and personal fees from BMS, grants and personal fees from MSD, grants and personal fees from Janssen, grants and personal fees from Roche, grants and personal fees from AbbVie, all outside the submitted work., (© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Aims/hypothesis: Our aim was to investigate the geospatial distribution of diabetic foot ulceration (DFU), lower extremity amputation (LEA) and mortality rates in people with diabetes in small geographical areas with varying levels of multiple deprivation., Methods: We undertook a population cohort study to extract the health records of 112,231 people with diabetes from the Scottish Care Information - Diabetes Collaboration (SCI-Diabetes) database. We linked this to health records to identify death, LEA and DFU events. These events were geospatially mapped using multiple deprivation maps for the geographical area of National Health Service (NHS) Greater Glasgow and Clyde. Tests of spatial autocorrelation and association were conducted to evaluate geographical variation and patterning, and the association between prevalence-adjusted outcome rates and multiple deprivation by quintile., Results: Within our health board region, people with diabetes had crude prevalence-adjusted rates for DFU of 4.6% and for LEA of 1.3%, and an incidence rate of mortality preceded by either a DFU or LEA of 10.5 per 10,000 per year. Spatial autocorrelation identified statistically significant hot spot (high prevalence) and cold spot (low prevalence) clusters for all outcomes. Small-area maps effectively displayed near neighbour clustering across the health board geography. Disproportionately high numbers of hot spots within the most deprived quintile for DFU (p < 0.001), LEA (p < 0.001) and mortality (p < 0.001) rates were found. Conversely, a disproportionately higher number of cold spots was found within the least deprived quintile for LEA (p < 0.001)., Conclusions/interpretation: In people with diabetes, DFU, LEA and mortality rates are associated with multiple deprivation and form geographical neighbourhood clusters.

Few studies have investigated clinical outcomes among patients with cirrhosis who were treated with interferon (IFN)-free direct-acting antiviral (DAA). We aimed to quantify treatment impact on first decompensated cirrhosis hospital admission, first hepatocellular carcinoma (HCC) admission, liver-related mortality and all-cause mortality among a national cohort of cirrhotic patients. Through record linkage between Scotland's HCV Clinical Database and inpatient/day-case hospitalization and deaths records, a study population comprising chronic HCV-infected patients with compensated cirrhosis and initiated on IFN-free DAA between 1 March 2013 and 31 March 2018 was analysed. Cox regression evaluated the association of each clinical outcome with time-dependent treatment status (on treatment, responder, nonresponder or noncompliant), adjusting for patient factors including Child-Pugh class. Among the study population (n = 1073) involving 1809 years of follow-up, 75 (7.0%) died (39 from liver-related causes), 47 progressed to decompensated cirrhosis, and 28 developed HCC. Compared with nonresponders, treatment response (96% among those attending their 12 weeks post-treatment SVR test) was associated with a reduced relative risk of decompensated cirrhosis (hazard ratio [HR] = 0.14; 95% CI: 0.05-0.39), HCC (HR = 0.17; 95% CI: 0.04-0.79), liver-related death (HR = 0.13; 95% CI: 0.05-0.34) and all-cause mortality (HR = 0.30; 95% CI: 0.12-0.76). Compared with responders, noncompliant patients had an increased risk of liver-related (HR = 6.73; 95% CI: 2.99-15.1) and all-cause (HR = 5.45; 95% CI: 3.07-9.68) mortality. For HCV patients with cirrhosis, a treatment response was associated with a lower risk of severe liver complications and improved survival. Our findings suggest additional effort is warranted to address the higher mortality among the minority of cirrhotic patients who do not comply with DAA treatment or associated RNA testing., (© 2019 John Wiley & Sons Ltd.)

Introduction: Hepatitis C virus (HCV) is the second largest contributor to liver disease in the UK, with injecting drug use as the main risk factor among the estimated 200 000 people currently infected. Despite effective prevention interventions, chronic HCV prevalence remains around 40% among people who inject drugs (PWID). New direct-acting antiviral (DAA) HCV therapies combine high cure rates (>90%) and short treatment duration (8 to 12 weeks). Theoretical mathematical modelling evidence suggests HCV treatment scale-up can prevent transmission and substantially reduce HCV prevalence/incidence among PWID. Our primary aim is to generate empirical evidence on the effectiveness of HCV 'Treatment as Prevention' (TasP) in PWID., Methods and Analysis: We plan to establish a natural experiment with Tayside, Scotland, as a single intervention site where HCV care pathways are being expanded (including specialist drug treatment clinics, needle and syringe programmes (NSPs), pharmacies and prison) and HCV treatment for PWID is being rapidly scaled-up. Other sites in Scotland and England will act as potential controls. Over 2 years from 2017/2018, at least 500 PWID will be treated in Tayside, which simulation studies project will reduce chronic HCV prevalence among PWID by 62% (from 26% to 10%) and HCV incidence will fall by approximately 2/3 (from 4.2 per 100 person-years (p100py) to 1.4 p100py). Treatment response and re-infection rates will be monitored. We will conduct focus groups and interviews with service providers and patients that accept and decline treatment to identify barriers and facilitators in implementing TasP. We will conduct longitudinal interviews with up to 40 PWID to assess whether successful HCV treatment alters their perspectives on and engagement with drug treatment and recovery. Trained peer researchers will be involved in data collection and dissemination. The primary outcome - chronic HCV prevalence in PWID - is measured using information from the Needle Exchange Surveillance Initiative survey in Scotland and the Unlinked Anonymous Monitoring Programme in England, conducted at least four times before and three times during and after the intervention. We will adapt Bayesian synthetic control methods (specifically the Causal Impact Method) to generate the cumulative impact of the intervention on chronic HCV prevalence and incidence. We will use a dynamic HCV transmission and economic model to evaluate the cost-effectiveness of the HCV TasP intervention, and to estimate the contribution of the scale-up in HCV treatment to observe changes in HCV prevalence. Through the qualitative data we will systematically explore key mechanisms of TasP real world implementation from provider and patient perspectives to develop a manual for scaling up HCV treatment in other settings. We will compare qualitative accounts of drug treatment and recovery with a 'virtual cohort' of PWID linking information on HCV treatment with Scottish Drug treatment databases to test whether DAA treatment improves drug treatment outcomes., Ethics and Dissemination: Extending HCV community care pathways is covered by ethics (ERADICATE C, ISRCTN27564683, Super DOT C Trial clinicaltrials.gov: NCT02706223). Ethical approval for extra data collection from patients including health utilities and qualitative interviews has been granted (REC ref: 18/ES/0128) and ISCRCTN registration has been completed (ISRCTN72038467). Our findings will have direct National Health Service and patient relevance; informing prioritisation given to early HCV treatment for PWID. We will present findings to practitioners and policymakers, and support design of an evaluation of HCV TasP in England., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY. Published by BMJ.)

Background & Aims: To describe the burden on inpatient hospital resources over time from patients diagnosed with hepatitis C virus (HCV) infection and who have reached the decompensated stage of cirrhosis (DC), as existing estimates of hospital stay in these patients are limited., Methods: A retrospective longitudinal dataset was formed via record-linkage between the national HCV diagnosis database and inpatient/daycase hospitalisation and death registers in Scotland. The study population consisted of HCV-diagnosed patients with a first DC admission in 1996-2013, with follow-up available until 31 May 2014. We investigated and quantified the mean cumulative length of hospital stay, distributions over discharge diagnosis categories, and trends in admission rates., Results: Among our study population (n = 1543), we identified 10 179 admissions with any diagnosis post-first DC admission. Between 1996 and 2013 there was a 16-fold rise in annual total admissions (from 112 to 1791) and an 11-fold rise in hospital stay (719-8045). When restricting minimum possible follow-up to 2 years, DC patients (n = 1312) had an overall admission rate of 7.3 per person-year, and spent on average 43 days (26 days during first 6 months) in hospital; for all liver-related, liver-related other than HCC/DC, and non-liver related only admissions, this was 39, 14, and 5 days respectively., Conclusions: HCV-infected DC patients impose a considerable inpatient hospital burden, mostly from DC- and other liver-related admissions, but also from admissions associated with non-liver comorbidities. Estimates will be useful for monitoring the impact of prevention and treatment, and for computing the cost-effectiveness of new therapies., (© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background & Aims: The advent of direct-acting antivirals (DAAs) has led to ambitious targets for hepatitis C virus (HCV) elimination. However, in the context of alcohol use disorder the ability of DAAs to achieve these targets may be compromised. The aim of this study was to evaluate the contribution of alcohol use disorder to HCV-related decompensated cirrhosis in three settings., Methods: HCV notifications from British Columbia, Canada; New South Wales, Australia, and Scotland (1995-2011/2012/2013, respectively) were linked to hospital admissions (2001-2012/2013/2014, respectively). Alcohol use disorder was defined as non-liver-related hospitalisation due to alcohol use. Age-standardised decompensated cirrhosis incidence rates were plotted, associated factors were assessed using Cox regression, and alcohol use disorder-associated population attributable fractions (PAFs) were computed., Results: Among 58,487, 84,529, and 31,924 people with HCV in British Columbia, New South Wales, and Scotland, 2,689 (4.6%), 3,169 (3.7%), and 1,375 (4.3%) had a decompensated cirrhosis diagnosis, and 28%, 32%, and 50% of those with decompensated cirrhosis had an alcohol use disorder, respectively. Age-standardised decompensated cirrhosis incidence rates were considerably higher in people with alcohol use disorder in New South Wales and Scotland. Decompensated cirrhosis was independently associated with alcohol use disorder in British Columbia (aHR 1.92; 95% CI 1.76-2.10), New South Wales (aHR 3.68; 95% CI 3.38-4.00) and Scotland (aHR 3.88; 95% CI 3.42-4.40). The PAFs of decompensated cirrhosis-related to alcohol use disorder were 13%, 25%, and 40% in British Columbia, New South Wales and Scotland, respectively., Conclusions: Alcohol use disorder was a major contributor to HCV liver disease burden in all settings, more distinctly in Scotland. The extent to which alcohol use would compromise the individual and population-level benefits of DAA therapy needs to be closely monitored. Countries, where appropriate, must develop strategies combining promotion of DAA treatment uptake with management of alcohol use disorders, if World Health Organization 2030 HCV mortality reduction targets are going to be achieved., Lay Summary: The burden of liver disease has been rising among people with hepatitis C globally. The recent introduction of highly effective medicines against hepatitis C (called direct-acting antivirals or DAAs) has brought renewed optimism to the sector. DAA scale-up could eliminate hepatitis C as a public health threat in the coming decades. However, our findings show heavy alcohol use is a major risk factor for liver disease among people with hepatitis C. If continued, heavy alcohol use could compromise the benefits of new antiviral treatments at the individual- and population-level. To tackle hepatitis C as a public health threat, where needed, DAA therapy should be combined with management of heavy alcohol use., (Copyright © 2017 European Association for the Study of the Liver. All rights reserved.)

Background & Aims: Although people who inject drugs (PWID) are at greatest risk of hepatitis C (HCV), treatment uptake in this population has historically been low. Highly effective direct acting antiviral (DAA) treatments for HCV have recently become available. Our aim was to assess the awareness among PWID of these new therapies and their effectiveness., Methods: A national survey of PWID attending injecting equipment provision sites in Scotland during 2015-2016 included questions to gauge the awareness in this population of antiviral treatment and the high cure rates associated with new therapies (defined here as >80%)., Results: Among 2623 PWID, 92% had ever been tested for HCV. After excluding those ever treated for HCV (n = 226), 79% were aware of HCV treatment. Awareness was more likely among those who had ever been tested and self-reported either a positive (adjusted odds ratio: 16.04, 95%CI 10.57-24.33) or negative (3.11, 2.30-4.22) test result, compared to those who were never tested. The minority of all respondents (17%) were aware of high cure rates. This awareness was more likely among those who had ever been in HCV specialist care (9.76, 5.13-18.60) and those who had not been in specialist care but had been tested and self-reported either a positive (3.91, 2.20-7.53) or negative (2.55, 1.35-4.81) test result, compared to those who had never been tested., Conclusion: We found poor awareness of the high cure rates associated with DAAs among PWID in Scotland, despite relatively high rates of HCV testing in this population. Increased effort is needed to ensure population groups with high risk of HCV infection are fully informed of the highly effective antiviral medications now available to treat this chronic disease., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Unlabelled: Liver mortality among individuals with chronic hepatitis C (CHC) infection is common, but the relative contribution of CHC per se versus adverse health behaviors is uncertain. We explored data on spontaneous resolvers of hepatitis C virus (HCV) as a benchmark group to uncover the independent contribution of CHC on liver mortality. Using national HCV diagnosis and mortality registers from Denmark and Scotland, we calculated the liver mortality rate (LMR) for persons diagnosed with CHC infection (LMRchronic ) and spontaneously resolved infection (LMRresolved ), according to subgroups defined by age, sex, and drug use. Through these mortality rates, we determined subgroup-specific attributable fractions (AFs), defined as (LMRchronic - LMRresolved )/LMRchronic , and then calculated the total attributable fraction (TAF) as a weighted average of these AFs. Thus, the TAF represents the overall fraction (where 0.00 = not attributable at all; and 1.00 = entirely attributable) of liver mortality attributable to CHC in the diagnosed population. Our cohort comprised 7,005 and 21,729 persons diagnosed with HCV antibodies in Denmark and Scotland, respectively. Mean follow-up duration was 6.3-6.9 years. The TAF increased stepwise with age. It was lowest for death occurring at <45 years of age (0.21 in Denmark; 0.26 in Scotland), higher for death occurring at 45-59 years (0.69 in Denmark; 0.69 in Scotland), and highest for death at 60+years (0.92 in Denmark; 0.75 in Scotland). Overall, the TAF was 0.66 (95% confidence interval [CI]: 0.55-0.78) in Denmark and 0.55 (95% CI: 0.44-0.66) in Scotland., Conclusions: In Denmark and Scotland, the majority of liver death in the CHC-diagnosed population can be attributed to CHC-nevertheless, an appreciable fraction cannot, cautioning that liver mortality in this population is a compound problem that can be reduced, but not solved, through antiviral therapy alone., (© 2016 by the American Association for the Study of Liver Diseases.)

Objective: The expense of new therapies for HCV infection may force health systems to prioritise the treatment of certain patient groups over others. Our objective was to forecast the population impact of possible prioritisation strategies for the resource-rich setting of Scotland., Design: We created a dynamic Markov simulation model to reflect the HCV-infected population in Scotland. We determined trends in key outcomes (e.g., incident cases of chronic infection and severe liver morbidity (SLM)) until the year 2030, according to treatment strategies involving prioritising, either: (A) persons with moderate/advanced fibrosis or (B) persons who inject drugs (PWID)., Results: Continuing to treat the same number of patients with the same characteristics will give rise to a fall in incident infection (from 600 cases in 2015 to 440 in 2030) and a fall in SLM (from 195 cases in 2015 to 145 in 2030). Doubling treatment-uptake and prioritising PWID will reduce incident infection to negligible levels (<50 cases per year) by 2025, while SLM will stabilise (at 70-75 cases per year) in 2028. Alternatively, doubling the number of patients treated, but, instead, prioritising persons with moderate/advanced fibrosis will reduce incident infection less favourably (only to 280 cases in 2030), but SLM will stabilise by 2023 (i.e., earlier than any competing strategy)., Conclusions: Prioritising treatment uptake among PWID will substantially impact incident transmission, however, this approach foregoes the optimal impact on SLM. Conversely, targeting those with moderate/advanced fibrosis has the greatest impact on SLM but is suboptimal in terms of averting incident infection., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Background & Aims: People living with hepatitis C virus (HCV) are at increased risk of all-cause and liver-related mortality, although successful treatment has been shown to reduce this risk. The aim of this study was to provide baseline data on trends in cause-specific mortality and to establish an international surveillance system for evaluating the population level impact of HCV treatments., Methods: Population level HCV diagnosis databases from Scotland (1997-2010), Australia (New South Wales [NSW]) (1997-2006), and Canada (British Columbia [BC]) (1997-2003) were linked to corresponding death registries using record linkage. For each region, age-adjusted cause-specific mortality rates were calculated, and trends in annual age-adjusted liver-related mortality were plotted., Results: Of 105,138 individuals diagnosed with HCV (21,810 in Scotland, 58,484 in NSW, and 24,844 in BC), there were 7275 deaths (2572 in Scotland, 2655 in NSW, and 2048 in BC). Liver-related deaths accounted for 26% of deaths in Scotland, 21% in NSW, and 22% in BC. Temporal trends in age-adjusted liver related mortality were stable in Scotland (males p=0.4; females p=0.2) and NSW (males p=0.9; females p=0.9), while there was an increase in BC (males p=0.002; females p=0.04)., Conclusions: The risk of liver-related mortality after a diagnosis of HCV has remained stable or increased over time across three regions with well-established diagnosis databases, highlighting that HCV treatment programmes to-date have had minimal impact on population level HCV-related liver disease. With more effective therapies on the horizon, and greater uptake of treatment anticipated, the potential of future therapeutic strategies to reduce HCV-related mortality is considerable., (Copyright © 2014 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Unlabelled: A substantial baseline risk of liver cirrhosis exists for patients with chronic hepatitis C virus (HCV) infection. However, the extent to which this could be driven by heavy alcohol use is unclear. Therefore, our principal aim was to determine the fraction of cirrhosis attributable to heavy alcohol use among chronic HCV patients attending a liver clinic. The study population comprised chronic HCV patients who had attended one of five liver clinics in Scotland during 1996-2010 and had (1) remained in follow-up for at least 6 months, (2) acquired HCV through either injecting drugs or blood transfusion, and (3) an estimated date of acquiring infection. Predictors of cirrhosis were determined from multivariate logistic regression. Regression parameters were used to determine the fraction of cirrhosis attributable to heavy alcohol use. Among 1,620 patients, 9% were diagnosed with cirrhosis, and 34% had ever engaged in heavy alcohol use (>50 units/week for a sustained period). Significant predictors of cirrhosis were age, duration of infection, and ever heavy alcohol use. The fraction of cirrhosis attributable to ever heavy alcohol use was 36.1% (95% confidence interval [CI]: 24.4-47.4). Moreover, among patients who had ever engaged in heavy alcohol use specifically, this attributable fraction exceeded 50% (61.6%; 95% CI: 47.0-72.2)., Conclusions: A substantial proportion of patients with chronic HCV develop liver cirrhosis as a consequence of heavy alcohol use. This has not been adequately acknowledged by cost utility analyses (CUAs). As such, estimates of cost-effectiveness may be exaggerated. Thus, these data are important to guide forthcoming CUAs in terms of taking better account of the factors leading to cirrhosis among patients with chronic HCV., (Copyright © 2012 American Association for the Study of Liver Diseases.)

Unlabelled: Our objective was to address two shortfalls in the hepatitis C virus (HCV) literature: (1) Few data exist comparing post-treatment liver-related mortality/morbidity in HCV-sustained virologic response (SVR) patients to non-SVR patients and (2) no data exist examining liver-related morbidity among treatment response subgroups,particularly among noncirrhotic SVR patients, a group who in the main are discharged from care without further follow-up. A retrospective cohort of 1,215 previously naïve HCV interferon patients (treated 1996-2007)was derived using HCV clinical databases from nine Scottish clinics. Patients were followed up post-treatment for a mean of 5.3 years. (1) By Cox-regression, liver-related hospital episodes (adjusted hazard ratio [AHR]:0.22; 95% confidence interval [CI]: 0.15-0.34) and liver-related mortality [corrected] (AHR: 0.22; 95% CI: 0.09-0.58)were significantly lower in SVR patients, compared to non-SVR patients. (2) Rates of liver-related hospitalization were elevated among all treatment subgroups compared to the general population: Among noncirrhotic SVR patients, adjusted standardized morbidity ratio (SMBR) up to 5.9 (95% CI: 4.5-8.0); among all SVR patients,SMBR up to 10.5 (95% CI: 8.7-12.9); and among non-SVR patients, SMBR up to 53.2 (95% CI: 49.4-57.2).Considerable elevation was also noted among patients who have spontaneously resolved their HCV infection(a control group used to gauge the extent to which lifestyle factors, and not chronic HCV, can contribute toliver-related morbidity), SMBR up to 26.8 (95% CI: 25.3-28.3)., Conclusions: (1) Patients achieving an SVR were more than four times less likely to be hospitalized, or die for a liver-related reason, than non-SVR patients and (2) although discharged, noncirrhotic SVR patients harbor a disproportionate burden of liver-related morbidity; up to six times that of the general population. Further, alarming levels of liver-related morbidity in spontaneous resolvers is an important finding warranting further study.., (Copyright © 2011 American Association for the Study of Liver Diseases.)