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Background and aims: Direct‐acting antiviral (DAA) treatment has an established positive effect on liver outcomes in people with hepatitis C infection; however, there is insufficient evidence regarding its effects on the 'extra‐hepatic' outcomes of drug‐related hospitalization and mortality (DRM) among people who inject drugs (PWID). We investigated associations between these outcomes and DAA treatment by comparing post‐treatment to baseline periods using a within‐subjects design to minimize selection bias concerns with cohort or case–control designs. Design: This was a self‐controlled case‐series study. Setting Scotland, 1 January 2015–30 November 2020. Participants: The study population of non‐cirrhotic, DAA‐treated PWID was identified using a data set linking Scotland's hepatitis C diagnosis, HCV clinical databases, national inpatient/day‐case hospital records and the national deaths register. Three principal outcomes (drug overdose admission, non‐viral injecting related admission and drug‐related mortality) were defined using ICD codes. Measurements Self‐controlled case‐series methodology was used to estimate the relative incidence (RI) of each outcome associated with time on treatment and up to six 90‐day exposure risk periods thereafter. Findings A total of 6050 PWID were treated with DAAs in the sampling time‐frame. Compared with the baseline period, there was a significantly lowered risk of a drug overdose hospital admission in the second to fifth exposure risk periods only [relative incidence (RI) = 0.86, 95% confidence interval (CI) = 0.80–0.99; 0.89, 95% CI = 0.80–0.99; 0.86, 95% CI = 0.77–0.96; 0.88, 95% CI = 0.78–0.99, respectively]. For non‐viral injecting‐related admission, there was a reduced risk in the first, third and fourth exposure risk periods (RI = 0.76, 95% CI = 0.64–0.90; 0.75, 95% CI = 0.62–0.90; 0.79, 95% CI = 0.66–0.96, respectively). There was no evidence for reduced DRM risk in any period following treatment end. Conclusions: Among people who inject drugs in Scotland, direct‐acting antiviral treatment appears to be associated with a small, non‐durable reduction in the risk of drug‐related hospital admission, but not drug‐related mortality. Direct‐acting antiviral therapy, despite high effectiveness against liver disease, does not appear to offer a panacea for reducing other drug‐related health harms. [ABSTRACT FROM AUTHOR]

Background and Aims: Chronic infection with the hepatitis C virus (HCV) has a detrimental impact on health‐related quality of life (QoL). Scale‐up of HCV direct‐acting antiviral (DAA) therapy among people who inject drugs (PWID) is underway in several countries since the introduction of interferon‐free regimens. This study aimed to assess the impact of DAA treatment success on QoL for PWID. Design: Cross‐sectional study using two rounds of the Needle Exchange Surveillance Initiative, a national anonymous bio‐behavioural survey and a longitudinal study involving PWID who underwent DAA therapy. Setting: The setting for the cross‐sectional study was Scotland (2017–2018, 2019–2020). The setting for the longitudinal study was the Tayside region of Scotland (2019–2021). Participants: In the cross‐sectional study PWID were recruited from services providing injecting equipment (n = 4009). In the longitudinal study, participants were PWID on DAA therapy (n = 83). Measurements In the cross‐sectional study, the association between QoL (measured using the EQ‐5D‐5L quality of life instrument) and HCV diagnosis and treatment was assessed using multilevel linear regression. In the longitudinal study, QoL was compared at four timepoints using multilevel regression, from treatment commencement until 12 months following commencement. Findings In the cross‐sectional study, 41% (n = 1618) were ever chronically HCV infected, of whom 78% (n = 1262) were aware of their status and of whom 64% (n = 704) had undergone DAA therapy. There was no evidence for a marked QoL improvement associated with viral clearance among those treated for HCV (B = 0.03; 95% CI, −0.03 to 0.09). In the longitudinal study, improved QoL was observed at the sustained virologic response test timepoint (B = 0.18; 95% CI, 0.10–0.27), but this was not maintained at 12 months following start of treatment (B = 0.02; 95% CI, −0.05 to 0.10). Conclusions: Successful direct‐acting antiviral therapy for hepatitis C infection may not lead to a durable improvement in quality of life among people who inject drugs, although there may be a transient improvement around the time of sustained virologic response. Economic models of the impact of scaling‐up treatment may need to include more conservative quality of life benefits over and above reductions in mortality, disease progression and transmission of infection. [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]

Interferon‐free DAA therapies have recently been licensed for patients infected with hepatitis C virus (HCV) who have decompensated cirrhosis (DC). Our aim was to describe factors associated with uptake of IFN‐free DAAs in DC patients and to compare mortality risk and hospital admission rates between pre‐DAA and DAA eras. This observational study used record‐linkage between Scotland's HCV Clinical Database and national inpatient hospitalization and mortality registers. For the DAA uptake analysis, the study population (n = 297) was restricted to patients alive on 1 November 2014, and Cox regression was used to estimate uptake associated with various covariates. For the Cox regression of mortality comparing pre‐DAA and DAA eras, the study population (n = 624) comprised those diagnosed with DC in 2005–2018; follow‐up was censored at two years. DAA uptake was 63% overall and was significantly higher for treatment‐experienced patients (adjusted hazard ratio (aHR) = 1.64, 95% CI:1.14–2.34), genotype 1 vs. other genotypes (aHR = 1.55. 95% CI:1.15–2.10) and lower for persons diagnosed with DC pre‐2014 (0.47, 95% CI:0.33–0.68) and in Greater Glasgow (0.64, 95% CI:0.47–0.88). The intention‐to‐treat SVR rate was 89% (95% CI:83–93%). All‐cause and liver‐related mortality risk were significantly reduced among patients diagnosed with DC in the DAA era (November 2014–December 2018) compared with the pre‐DAA era (2005–October 2014) (aHRs of 0.68, 95% CI:0.49–0.93; 0.69, 95% CI:0.50–0.95, respectively); in contrast, hospital admission rates were higher in the DAA era (aRR = 1.14, 95% CI:1.04–1.26). The majority of HCV‐infected DC patients engaged with specialist services can be treated with IFN‐free DAAs. Improved survival among patients diagnosed with DC in the DAA era supports the beneficial impact of IFN‐free therapies among those with advanced liver disease. [ABSTRACT FROM AUTHOR]

Following positive serology, the gold standard confirmatory test of hepatitis C virus (HCV) infection is detection of HCV RNA by PCR. We assessed the utility of HCV core antigen testing to identify active infection among those positive for anti‐HCV antibodies, when introduced to routine testing. We identified serum samples that were tested at a single laboratory in Scotland from June 2011to December 2017. Serum samples testing positive for HCV antibodies (HCV Ab positive) followed by reflex HCV core antigen (Ag) testing during the study period were identified. Those patients for whom a PCR test was requested on the baseline sample were also identified. For this group, the sensitivity and specificity of HCV Ag as a diagnostic tool were assessed using HCV PCR as gold standard. In our cohort of 744 patients, we demonstrated a sensitivity of 82.1% (95% CI 77.1%‐86.2%) and a specificity of 99.8% (95% CI 98.6%‐100%). Genotype 3 was associated with increased odds of a false‐negative result (OR = 3.59, 95% CI: 1.32‐9.71), and reduced odds of a false negative were associated with older age (odds ratio (OR)=0.92, 95% CI: 0.88‐0.97 per year) and viral load (OR = 0.10, 95% CI: 0.05‐0.21 per log10 IU/ml). While the implementation of HCV core antigen testing for diagnosis could lead to significant cost savings in national screening programmes, our data suggest that a significant proportion of HCV‐infected individuals may be missed. These findings have implications for HCV diagnosis and determination of viral clearance after treatment, particularly in low‐ and middle‐income regions, where genotype 3 is prevalent. [ABSTRACT FROM AUTHOR]

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. [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]

Abstract: 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. [ABSTRACT FROM AUTHOR]

Accurate detection of incident hepatitis C virus (HCV) infection is required to target and evaluate public health interventions, but acute infection is largely asymptomatic and difficult to detect using traditional methods. Our aim was to evaluate a previously developed HCV avidity assay to distinguish acute from chronic HCV infection. Plasma samples collected from recent seroconversion subjects in two large Australian cohorts were tested using the avidity assay, and the avidity index (AI) was calculated. Demographic and clinical characteristics of patients with low/high AI were compared via logistic regression. Sensitivity and specificity of the assay for recent infection and the mean duration of recent infection (MDRI) were estimated stratified by HCV genotype. Avidity was assessed in 567 samples (from 215 participants), including 304 with viraemia (defined as ≥250 IU/mL). An inverse relationship between AI and infection duration was found in viraemic samples only. The adjusted odds of a low AI (<30%) decreased with infection duration (odds ratio [OR] per week of 0.93; 95% CI:0.89-0.97), and were lower for G1 compared with G3 samples (OR = 0.14; 95% CI:0.05-0.39). Defining recent infection as <26 weeks, sensitivity (at AI cut-off of 20%) was estimated at 48% (95% CI:39-56%), 36% (95% CI:20-52%), and 65% (95% CI:54-75%) and MDRI was 116, 83, and 152 days for all genotypes, G1, and G3, respectively. Specificity (≥52 weeks infection duration, all genotypes) was 96% (95% CI:90-98%). HCV avidity testing has utility for detecting recent HCV infection in patients, and for assessing progress in reaching incidence targets for eliminating transmission, but variation in assay performance across genotype should be recognized. [ABSTRACT FROM AUTHOR]

Background: The prevalence of hepatitis C virus (HCV) infection in Malaysia has been estimated at 2.5% of the adult population. Our objective, satisfying one of the directives of the WHO Framework for Global Action on Viral Hepatitis, was to forecast the HCV disease burden in Malaysia using modelling methods. Methods: An age-structured multi-state Markov model was developed to simulate the natural history of HCV infection. We tested three historical incidence scenarios that would give rise to the estimated prevalence in 2009, and calculated the incidence of cirrhosis, end-stage liver disease, and death, and disability-adjusted life-years (DALYs) under each scenario, to the year 2039. In the baseline scenario, current antiviral treatment levels were extended from 2014 to the end of the simulation period. To estimate the disease burden averted under current sustained virological response rates and treatment levels, the baseline scenario was compared to a counterfactual scenario in which no past or future treatment is assumed. Results: In the baseline scenario, the projected disease burden for the year 2039 is 94,900 DALYs/year (95% credible interval (CrI): 77,100 to 124,500), with 2,002 (95% CrI: 1340 to 3040) and 540 (95% CrI: 251 to 1,030) individuals predicted to develop decompensated cirrhosis and hepatocellular carcinoma, respectively, in that year. Although current treatment practice is estimated to avert a cumulative total of 2,200 deaths from DC or HCC, a cumulative total of 63,900 HCV-related deaths is projected by 2039. Conclusions: The HCV-related disease burden is already high and is forecast to rise steeply over the coming decades under current levels of antiviral treatment. Increased governmental resources to improve HCV screening and treatment rates and to reduce transmission are essential to address the high projected HCV disease burden in Malaysia. [ABSTRACT FROM AUTHOR]

Background & Aims The global burden associated with hepatitis C virus (HCV) infection has prompted a scale-up of antiviral therapy. Hitherto, no data exist on the impact of scaling-up, on the characteristics of treated populations, or on sustained viral response (SVR) rates. We assessed the country-wide scale-up of antiviral therapy in Scotland, a country which nationally monitors uptake of and response to HCV treatment. Methods Data for patients, initiated on combined pegylated interferon and ribavirin therapy at 13 specialist HCV clinics in 2001–2010, were extracted from the Scottish HCV Clinical Database (n = 3895). Patient characteristics included age, genotype, PWID (people who inject drugs) status, prison referral, and diagnosed cirrhosis. Temporal trends in covariates and adjusted effects on a SVR were examined via mixed-effects regression. Results The number of patients starting treatment increased from 237 in 2001–2002 to 1560 in 2009–2010, with an increasing trend in SVR from 44% to 57% over this period. For a given clinic, between 2001/2 and 2010 there was a decrease in the odds of those treated being diagnosed with cirrhosis (odds ratio [OR] = 0.84 per year), and increasing temporal trends for those treated being PWID (OR = 1.08) and prison referrals (OR = 1.06). Adjusting for covariates, the proportion of a given clinic’s patients achieving SVR was positively associated with the percentage of PWID (OR = 1.01 per percent increase; 95% confidence interval [CI]: 1.00–1.02) and genotype 2/3 (OR = 1.03; 95% CI: 1.02–1.04). Conclusions Despite changes in patient characteristics, a country-wide scale-up of antiviral therapy did not compromise SVR rates. Results are highly relevant to countries planning on scaling-up treatment, given the forthcoming availability of new interferon-free therapies. [ABSTRACT FROM AUTHOR]

Background Collecting adequate information on key epidemiological indicators is a prerequisite to informing a public health response to reduce the impact of hepatitis C virus (HCV) infection in Malaysia. Our goal was to overcome the acute data shortage typical of low/middle income countries using statistical modelling to estimate the national HCV prevalence and the distribution over transmission pathways as of the end of 2009. Methods Multi-parameter evidence synthesis methods were applied to combine all available relevant data sources - both direct and indirect - that inform the epidemiological parameters of interest. Results An estimated 454,000 (95% credible interval [CrI]: 392,000 to 535,000) HCV antibody-positive individuals were living in Malaysia in 2009; this represents 2.5% (95% CrI: 2.2- 3.0%) of the population aged 15-64 years. Among males of Malay ethnicity, for 77% (95% CrI: 69-85%) the route of probable transmission was active or a previous history of injecting drugs. The corresponding proportions were smaller for male Chinese and Indian/other ethnic groups (40% and 71%, respectively). Females of all ethnicities represented 1% (95% CrI: 0.6 to 1.4%) of all HCV infections, 92% (95% CrI: 88 to 95%) of which were attributable to non-drug injecting routes of transmission. Conclusions The prevalent number of persons living with HCV infection in Malaysia is estimated to be very high. Low/middle income countries often lack a comprehensive evidence base; however, evidence synthesis methods can assist in filling the data gaps required for the development of effective policy to address the future public health and economic burden due to HCV. [ABSTRACT FROM AUTHOR]

Background & Aims: Chronic hepatitis C virus (HCV) infection can significantly reduce health-related quality of life (QoL), but it is not clear if reduction is associated with the infection or with being aware of one’s infection status. Understanding the impact of a HCV diagnosis on QoL is essential to inform decision-making regarding screening/testing and treatment. Methods: Using a cross-sectional design, we assessed QoL in 2898 people who inject drugs (PWID), surveyed in Scotland during 2010 using EQ-5D. Multifactorial regression compared self-reported QoL between PWID who were (i) chronically HCV-infected and aware of their infected status, (ii) chronically HCV-infected but unaware, and (iii) not chronically infected. Results: Median time since onset of injecting was 10years; not chronically infected PWID were younger and had shorter injecting careers than chronically infected PWID. Median EQ-5D was highest for the not chronically infected and the chronic/unaware groups (0.73) compared with the chronic/aware group (0.66). After adjustment for demographic and behavioural co-factors, QoL was significantly reduced in chronic/aware compared with chronic/unaware PWID (adjusted B =−0.09, p =0.005); there was no evidence for a difference in QoL between not chronically infected and chronic/unaware PWID (adjusted B =−0.03, p =0.13). Conclusions: Awareness of one’s chronic HCV status was associated with reduced health-related QoL, but there was no evidence for further reduction attributable to chronic infection itself after adjusting for important covariate differences. [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]

Abstract: Background: The rate of hepatitis C (HCV) related liver disease progression is known to be strongly associated with alcohol consumption, yet there are very few data on alcohol use in injecting drug users (IDUs), who represent 90% of Scotland''s HCV-diagnosed population. To investigate the extent of alcohol use in IDUs, we used hospitalisation with an alcohol-related diagnosis as an indicator for problematic consumption levels, and compared admission rates pre- and post-HCV diagnosis. Methods: Data for 41,062 current/former IDUs attending drug treatment/support services in Scotland from April 1995 to March 2006 were linked to the national hospital discharge database to retrieve alcohol-related episodes, and to the national HCV Diagnosis database to determine HCV-diagnosed status. Relative risks were estimated using Cox proportional hazards regression for recurrent events. Results: The proportion of IDUs with ≥1 alcohol-related admission following first attendance at drug services was greater among those diagnosed with HCV by the end of follow-up (16%) compared with those who were not (6%). For the 9145 IDUs who had been diagnosed with HCV by 31 March 2006, there was a 1.5-fold increased relative risk of an alcohol-related admission >30 days post-HCV diagnosis (95% CI: 1.2–1.7) compared with >30 days pre-HCV diagnosis, adjusted for sex, age, and deprivation. Conclusions: IDUs diagnosed with HCV infection have an increased risk of subsequent hospital admission for an alcohol-related cause. Because of the synergistic effect of HCV infection and excessive alcohol intake on the development of cirrhosis, it is imperative that alcohol intake is addressed in the management of chronic HCV infection in this population. [Copyright &y& Elsevier]

Infection with the hepatitis C virus (HCV) is known to increase the risk of death from severe liver disease and, because HCV status is strongly associated with a history of injecting drug use, the effect of a key disease progression cofactor, infection with human immunodeficiency virus (HIV), is of interest. We examined all-cause, liver-related and drug-related mortality and excess risk of death from these causes in a large cohort of HCV-monoinfected and HIV-coinfected persons in Scotland. The study population consisted of 20,163 persons confirmed to be infected with hepatitis C through laboratory testing in Scotland between 1991 and 2005. Records with sufficient identifiers were linked to the General Register Office for Scotland death register to retrieve associated mortality data, and were further linked to a national database of HIV-positive individuals to determine coinfection status. A total of 1715 HCV monoinfected and 305 HIV coinfected persons died of any cause during the follow-up period (mean of 5.4 and 6.4 years, respectively). Significant excess mortality was observed in both HCV monoinfected and HIV coinfected populations from liver-related underlying causes (standardised mortality ratios of 25, 95% CI=23-27; and 37, 95% CI=26-52 for the two groups, respectively) and drug-related causes (25, 95% CI=23-27; 39, 95% CI=28-53. The risk of death from hepatocellular carcinoma, alcoholic or non-alcoholic liver disease, or from a drug-related cause, was greatly increased compared with the general Scottish population, with the highest standardised mortality ratio observed for hepatocellular carcinoma in the monoinfected group (70, 95% CI=57-85). This study has revealed considerable excess mortality from liver- and drug-related causes in the Scottish HCV-diagnosed population; these data are crucial to inform on the clinical management, and projected future public health burden, of HCV infection. [ABSTRACT FROM AUTHOR]

Background & Aims Previous studies have reported a high frequency of hepatocellular carcinoma (HCC) occurrence in patients with advanced liver disease, after receipt of interferon (IFN)-free therapy for hepatitis C virus (HCV) infection. Our objective was to verify and account for this phenomenon using data from the Scottish HCV clinical database. Methods We identified HCC-naïve individuals with liver cirrhosis receiving a course of antiviral therapy in Scotland from 1997–2016 resulting in a sustained virologic response. Patients were followed-up from their treatment start date to the earliest of: date of death, date of HCC occurrence, or 31 January 2017. We used Cox regression to compare the risk of HCC occurrence according to treatment regimen after adjusting for relevant co-factors (including: demographic factors; baseline liver disease stage; comorbidities/health behaviours, virology, and previous treatment experience). HCC occurrence was ascertained through both the HCV clinical database and medical chart review. For our main analysis, treatment regimen was defined as IFN-free vs. IFN-containing. Results A total of 857 patients met the study criteria, of whom 31.7% received an IFN-free regimen. Individuals receiving IFN-free therapy were more likely to be: older; of white ethnicity, Child-Turcotte-Pugh B/C vs. Child-Turcotte-Pugh A; thrombocytopenic; non-genotype 3; and treatment experienced. HCC occurrence was observed in 46 individuals during follow-up. In univariate analysis, IFN-free therapy was associated with a significantly increased risk of HCC (HR: 2.48; p  = 0.021). However, after multivariate adjustment for baseline factors, no significant risk attributable to IFN-free therapy persisted (aHR: 1.15, p  = 0.744). Conclusion These findings suggest that the higher incidence of HCC following sustained virologic response with IFN-free therapy relates to baseline risk factors/patient selection, and not the use of IFN-free therapy per se . Lay summary We examined the risk of liver cancer in 857 patients with cirrhosis in Scotland who received hepatitis C antiviral therapy and achieved a cure. We compared the risk of first-time liver cancer in patients treated with the newest interferon-free regimens, to patients treated with interferon. After accounting for the different characteristics of these two treatment groups, we found no evidence that interferon-free therapy is associated with a higher risk of liver cancer. [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]