Optimal ALT threshold for the automated diagnosis of MASLD: A population-based study using iLFT.

INTRODUCTION AND OBJECTIVES: Early diagnosis of metabolic dysfunction-associated steatotic liver disease (MASLD), especially with advanced fibrosis, is crucial due to the increased risk of complications and mortality. Serum alanine aminotransferase (ALT) is commonly used; however, many patients have normal ranges (<55 U/L) who may remain undetected. We investigated the clinical implications of a lower ALT cut-off (>30 U/L) using intelligent liver function testing (iLFT) to identify MASLD patients with and without advanced fibrosis in primary care. MATERIALS AND METHODS: All patients entering the iLFT diagnostic pathway had liver aetiological screening investigations if ALT >30 U/L. In those with MASLD the proportions with and without advanced fibrosis at different ALT thresholds: 31-41 U/L, 42-54 U/L and ≥55 U/L were compared. RESULTS: 16,373 patients underwent iLFT between March 2016 to April 2022. 762 (5 %) patients had MASLD with abnormal fibrosis scores, while 908 (6 %) had MASLD with normal fibrosis scores. 428 (56 %) patients were assessed in liver clinics, where 169 (39 %) had evidence of fibrosis. Of these, 22 (13 %) had ALT 31-41 U/L, 31 (18 %) had ALT 42-54 U/L and 116 (69 %) had ALT ≥55 U/L. 145 (86 %) patients had advanced fibrosis or cirrhosis, where 20 (14 %) had ALT 31-41 U/L, 28 (19 %) had ALT 42-54 U/L and 97 (67 %) had ALT ≥55 U/L. CONCLUSIONS: 33 % of MASLD patients with advanced fibrosis or cirrhosis had ALT 31-54 U/L, who would have been missed using the conventional ALT range. This suggests that lowering the ALT cut-off improves diagnosis of MASLD with advanced fibrosis in primary care.

Characterizing the risk interplay between alcohol intake and body mass index on cirrhosis morbidity.

BACKGROUND AND AIMS: It is thought that alcohol intake and body mass index (BMI) interact supra-additively to modulate the risk of cirrhosis, but evidence for this phenomenon is limited. We investigated the interrelationship between alcohol and BMI on the incidence of cirrhosis morbidity for participants of the United Kingdom Biobank (UKB) study. APPROACH AND RESULTS: The primary outcome was the cumulative incidence of cirrhosis morbidity, defined as a first-time hospital admission for cirrhosis (with noncirrhosis mortality incorporated as a competing risk). All UKB participants without a previous hospital admission for cirrhosis were included in the analysis. We determined the ratio of the 10-year cumulative incidence in harmful drinkers versus safe drinkers according to BMI. We also calculated the excess cumulative incidence at 10 years for individuals with obesity and/or harmful alcohol compared to safe drinkers with a healthy BMI of 20-25.0 kg/m2 . A total of 489,285 UK Biobank participants were included, with mean of 10.7 person-years' follow-up. A total of 2070 participants developed the primary outcome, equating to a crude cumulative incidence of 0.36% at 10 years (95% CI:0.34-0.38). The 10-year cumulative incidence was 8.6 times higher for harmful (1.38%) versus safe drinkers (0.16%) if BMI was healthy. Conversely, it was only 3.6 times higher for obese participants (1.99% vs. 0.56%). Excess cumulative incidence was 1.22% (95% CI:0.89-1.55) for harmful drinkers with a healthy BMI, 0.40% (95% CI:0.34-0.46) for obese individuals drinking at safe levels, and 1.83% (95% CI:1.46-2.20) for obese harmful drinkers (all compared to safe drinkers with a healthy BMI). CONCLUSIONS: Alcohol intake and obesity are independent risk factors for cirrhosis morbidity, but they do not interact supra-additively to modulate the cumulative incidence of this outcome.

Laying the foundations for hepatitis C elimination: evaluating the development and contribution of community care pathways to diagnostic efforts.

BACKGROUND: Hepatitis C Virus (HCV) is a public health threat which contributes substantially to the global burden of liver disease. There is much debate about effective approaches to scaling up diagnosis of HCV among risk groups. Tayside, a region in the East of Scotland, developed low-threshold community pathways for HCV to lay the foundations of an elimination strategy. In this retrospective study, we sought to: quantify the contribution of community pathways to increasing HCV diagnosis; understand if shifting diagnosis to community settings led to a higher proportion of individuals tested for HCV being actively infected; and describe functional characteristics of the care pathways. METHODS: Descriptive statistics were used to for analysis of routinely-collected HCV testing data from 1999 to 2017, and a review of the development of the care pathways was undertaken. Community-based testing was offered through general practices (GP); nurse outreach clinics; prisons; drug treatment services; needle and syringe provision (NSP) sites; community pharmacies; and mosques. RESULTS: Anti-HCV screening was undertaken on 109,430 samples, of which 5176 (4.7%) were reactive. Of all samples, 77,885 (71.2%) were taken in secondary care; 25,044 (22.9%) in GPs; 2970 (2.7%) in prisons; 2415 (2.2%) in drug services; 753 (0.7%) in NSPs; 193 (0.2%) pharmacies; and 170 (0.1%) in mosques. The highest prevalence of HCV infection among those tested was in NSP sites (26%), prisons (14%), and drug treatment centres (12%). CONCLUSIONS: Decentralised care pathways, particularly in harm reduction and other drug service settings, were key to increasing diagnosis of HCV in the region, but primary and secondary care remain central to elimination efforts.

A Global Systematic Review of Hepatitis C Elimination Efforts through Micro-Elimination.

Microelimination targets specific subpopulations and/or geographic settings for hepatitis C virus (HCV) elimination. This review reports on global HCV microelimination literature published from 2013 to 2020. Data were extracted from publications to report a score based on the four key components defining microelimination. Sustained virologic response (SVR) and treatment initiation proportions were calculated for each manuscript and grouped means of these estimates were compared depending on microelimination score and care setting. A total of 83% of the studies were from high-income settings and mainly included people who use drugs or those incarcerated. Among manuscripts, 18 had "low" microelimination scores, 11 had "high" scores, and the differences in mean proportion who initiated treatment and achieved SVR between low and high score groups were statistically significant. Microelimination can be a useful complementary strategy for driving engagement in HCV treatment and cure. Our analysis suggests that adhering to more of the core microelimination components can improve outcomes. This study is registered with Prospero, registration identification: CRD42020175211.

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

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

Comparing Predicted Probability of Hepatocellular Carcinoma in Patients With Cirrhosis With the General Population: An Opportunity to Improve Risk Communication?

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.

Randomized clinical trial: Direct-acting antivirals as treatment for hepatitis C in people who inject drugs: Delivered in needle and syringe programs via directly observed therapy versus fortnightly collection.

Hepatitis C virus (HCV) treatment in people who inject drugs (PWID) is delivered within settings frequented by PWID, such as needle and syringe programs (NSP). The optimal direct-acting antiviral (DAA) dispensing regimen among NSP clients is unknown. This study compared cures (Sustained virologic response 12 weeks post-treatment, [SVR12 ]) across three dispensing schedules to establish non-inferiority of fortnightly dispensing versus directly observed therapy. The ADVANCE HCV study was a randomized, unblinded trial, recruiting PWID attending NSP in Tayside, Scotland, between January 2018 and November 2019. HCV-positive participants were randomized to receive DAAs via directly observed therapy, fortnightly provision or fortnightly provision with psychological intervention. A modified intention to treat analysis was used to identify differences in cures between the three treatment regimes. The study was registered with clinicaltrials.gov; NCT03236506. A total of 110 participants completed the study. 33 participants received directly observed therapy, with 90.91% SVR12 ; 37 received fortnightly provision, with 86.49% SVR12 and 40 received fortnightly provision and psychological intervention at treatment initiation, with 92.50% SVR12 . Analysis showed no significant difference in SVR12 (p = 0.67). This study did not demonstrate a statistically significant difference in cure rate between groups. This provides evidence of the non-inferiority of fortnightly dispensing of direct-acting antivirals (DAAs) compared to directly observed therapy among PWID. It suggests that tight control of adherence through directly observed therapy dispensing of DAAs among this population offers no therapeutic advantage. Therefore, less restrictive dispensing patterns can be used, tailored to patient convenience.

Gamma-Glutamyl Transferase (γ-GT) - an old dog with new tricks?

Gamma-Glutamyl Transferase (γGT) is a key transferase involved in the transpeptidation of functional gamma-glutamyl groups to various receptor moieties. It performs important roles in antioxidant defence mechanisms, particularly glutathione recycling, xenobiotic metabolism, but analogously may also have a pro-oxidant role. γGT is very sensitive for the diagnosis of liver injury, although it has poor specificity for particular aetiologies. It has been used to reflect temporal changes as a form of monitoring depending on aetiology. Given its cellular role in antioxidant function, it has been investigated as a surrogate biomarker of oxidative stress. It has also been found to be a predictor of mortality across a spectra of non-hepatic disease pathologies, from metabolic and cardiovascular risk to chronic kidney disease and neoplasia. Similarly, it also remains of interest to the insurance industry given an apparent ability to predict mortality, in addition to a historical interest from law enforcement as a marker of chronic alcohol ingestion. Here, we review some of the unique characteristics of this important enzyme, previously considered as a mere specific marker of liver dysfunction, but now with clear extra-hepatic implications and novel applications and utility.

Declining incidence of hepatitis C related hepatocellular carcinoma in the era of interferon-free therapies: A population-based cohort study.

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.

Cohort study: Apparent redundancy of fibrosis assessment in young persons with HCV; development of realistic approaches to break the paradigm.

INTRODUCTION AND OBJECTIVES: Hepatitis C Virus (HCV) is a blood-borne, hepatotropic RNA virus causing both acute and chronic infection. Chronic HCV infection predisposes individuals to liver fibrosis, cirrhosis and hepatocellular carcinoma. Staging of fibrosis prior to treatment to determine either treatment choice or required follow up, is standard practice. However, this often acts as a barrier to treatment initiation. We sought to validate the hypothesis that those individuals; mono-infected with HCV, ≤35 years of age; with no additional hepatic insult were unlikely to have significant fibrosis. METHODS: We performed a retrospective analysis of a Hepatitis C Virus database; with collation of relevant basic demographics including age, sex and baseline Transient Elastography measurements pre-treatment. Additionally, we compared the reliability of biochemical fibrosis scores with corresponding transient elastography scores. RESULTS: Our results support the hypothesis that those individuals with chronic HCV ≤35 years old, with no additional risk for fibrogenesis did not have significant liver fibrosis within our cohort. CONCLUSION: Patients ≤35 years old likely do not necessitate fibrosis assessment prior to Direct Acting Antiviral (DAA) treatment in the absence of other significant risk factors for fibrosis. Given the emerging evidence that DAA treatment results in a significant decrease in all-cause mortality and hepatocellular carcinoma development, treatment of those with chronic HCV represents a global priority.

Drug network identification predicts injecting risk behavior among people who inject drugs on hepatitis C virus treatment in Tayside, Scotland.

The risk of Hepatitis C Virus (HCV) acquisition among People Who Inject Drugs (PWID) remains high when injecting risk behavior within networks endures. Several psychosocial factors influence such behavior. Following a drive within Tayside, a geographic region in Scotland, to achieve World Health Organization HCV elimination targets, addressing HCV re-infection risk as a barrier to elimination is critically important. This cross-sectional study seeks to address this barrier to elimination by investigating associations between group identification (one's subjective sense of belonging and connectedness to a social group coupled with a sense of shared goals, beliefs and values with the other members of the group) and injecting risk behavior among PWID on HCV treatment at needle and syringe provision sites in Tayside. Participants completed psychosocial questionnaires between treatment weeks zero and three of treatment. Correlation analyses were undertaken, and significant factors included in multiple linear regression models for injecting risk behavior. Injecting frequency, drug network identification, and family identification, were correlated with injecting risk behavior, and drug network identification had a positive predictive on injecting risk behavior. Identification with a social group, conventionally associated with improved health, may pose health risks in specific contexts. Healthcare providers should consider stratifying individuals with higher group identification with PWID networks for enhanced harm reduction engagement to mitigate transmissible infection risk among PWID. Additionally, psychological interventions to strengthen group identification with networks which impact positively on health behavior should be explored.

Genome-Wide Association Study for Alcohol-Related Cirrhosis Identifies Risk Loci in MARC1 and HNRNPUL1.

BACKGROUND AND AIMS: Little is known about genetic factors that affect development of alcohol-related cirrhosis. We performed a genome-wide association study (GWAS) of samples from the United Kingdom Biobank (UKB) to identify polymorphisms associated with risk of alcohol-related liver disease. METHODS: We performed a GWAS of 35,839 participants in the UKB with high intake of alcohol against markers of hepatic fibrosis (FIB-4, APRI, and Forns index scores) and hepatocellular injury (levels of aminotransferases). Loci identified in the discovery analysis were tested for their association with alcohol-related cirrhosis in 3 separate European cohorts (phase 1 validation cohort; n=2545). Variants associated with alcohol-related cirrhosis in the validation at a false discovery rate of less than 20% were then directly genotyped in 2 additional European validation cohorts (phase 2 validation, n=2068). RESULTS: In the GWAS of the discovery cohort, we identified 50 independent risk loci with genome-wide significance (P < 5 × 10-8). Nine of these loci were significantly associated with alcohol-related cirrhosis in the phase 1 validation cohort; 6 of these 9 loci were significantly associated with alcohol-related cirrhosis in phase 2 validation cohort, at a false discovery rate below 5%. The loci included variants in the mitochondrial amidoxime reducing component 1 gene (MARC1) and the heterogeneous nuclear ribonucleoprotein U like 1 gene (HNRNPUL1). After we adjusted for age, sex, body mass index, and type-2 diabetes in the phase 2 validation cohort, the minor A allele of MARC1:rs2642438 was associated with reduced risk of alcohol-related cirrhosis (adjusted odds ratio, 0.76; P=.0027); conversely, the minor C allele of HNRNPUL1:rs15052 was associated with an increased risk of alcohol-related cirrhosis (adjusted odds ratio, 1.30; P=.020). CONCLUSIONS: In a GWAS of samples from the UKB, we identified and validated (in 5 European cohorts) single-nucleotide polymorphisms that affect risk of alcohol-related cirrhosis in opposite directions: the minor A allele in MARC1:rs2642438 decreases risk, whereas the minor C allele in HNRNPUL1:rs15052 increases risk.

High Sustained Virologic Response Rates of Glecaprevir/Pibrentasvir in Patients With Dosing Interruption or Suboptimal Adherence.

INTRODUCTION: Pangenotypic, all-oral direct-acting antivirals, such as glecaprevir/pibrentasvir (G/P), are recommended for treatment of hepatitis C virus (HCV) infection. Concerns exist about the impact on efficacy in patients with suboptimal adherence, particularly with shorter treatment durations. These post hoc analyses evaluated adherence (based on pill count) in patients prescribed 8- or 12-week G/P, the impact of nonadherence on sustained virologic response at post-treatment week 12 (SVR12), factors associated with nonadherence, and efficacy in patients interrupting G/P treatment. METHODS: Data were pooled from 10 phase 3 clinical trials of treatment-naive patients with HCV genotype 1-6 without cirrhosis/with compensated cirrhosis (treatment adherence analysis) and 13 phase 3 clinical trials of all patients with HCV (interruption analysis). RESULTS: Among 2,149 patients included, overall mean adherence was 99.4%. Over the treatment duration, adherence decreased (weeks 0-4: 100%; weeks 5-8: 98.3%; and weeks 9-12: 97.1%) and the percentage of patients with ≥80% or ≥90% adherence declined. SVR12 rate in the intention-to-treat (ITT) population was 97.7% (modified ITT SVR12 99.3%) and remained high in nonadherent patients in the modified ITT population (<90%: 94.4%-100%; <80%: 83.3%-100%). Psychiatric disorders were associated with <80% adherence, and shorter treatment duration was associated with ≥80% adherence. Among 2,902 patients in the interruption analysis, 33 (1.1%) had a G/P treatment interruption of ≥1 day, with an SVR12 rate of 93.9% (31/33). No virologic failures occurred. DISCUSSION: These findings support the impact of treatment duration on adherence rates and further reinforce the concept of "treatment forgiveness" with direct-acting antivirals.

Evaluating and communicating hepatitis C cascades of care data in Tayside, Scotland: A journey towards elimination.

Chronic hepatitis C virus (HCV) is one of the leading causes of liver cirrhosis and hepatocellular carcinoma. The WHO 2030 Elimination Goals require each country to evaluate their response to their epidemics. This can be achieved by visualization of cascades of care, depicting how infected cases move through disease control stages. However, methods of displaying data are debated and lack practical application. This project proposes a new way of codifying and displaying HCV data using Tayside as a case study. 1464 cases of active HCV infections in Tayside from 2015 to 2019 were analysed from NHS Tayside's HCV Database. Variables were evaluated to create a systematic coding framework that was then used to code each patient's diagnosis, treatment and cure status each year from 2015 to 2019. Graphical representation of the data in the form of a stacked clustered bar chart demonstrates general trends and conversion rates. For example, Tayside has seen an increase in diagnosis-to-cure rates from 18% to 49% (2015-2019). This method also demonstrates the portion of newly and previously diagnosed people accessing treatment, those with unsuccessful or incomplete treatments, completed treatments with unconfirmed cure, and the number of deaths and relocations. In conclusion, this project proposes a novel way of displaying cascades of care data that relays yearly snapshots of an epidemic, cumulative progression over time, nuanced information of each stage and progression towards elimination targets. This method can be meaningfully used to improve local service planning, knowledge exchange across health systems and reporting to bodies like the WHO.

Hepatitis C reinfection by treatment pathway among people who inject drugs in Tayside, Scotland.

The efficacy of direct-acting antivirals (DAA) provides an excellent opportunity to scale up HCV diagnosis and treatment, achieving the WHO target of HCV elimination by 2030. However, HCV reinfection among people who inject drugs (PWID) remains a concern and may impede elimination efforts. We assessed reinfection rates among PWID across six specialized treatment pathways, following DAA-based and interferon-based therapies in Tayside, Scotland. Data were collected retrospectively for every treatment episode that resulted in a sustained viral response (SVR) after undergoing treatment. Reinfection rates were calculated for each treatment pathway: hospital outpatient clinic; community pharmacy; drug treatment outreach; prison clinic; nurse-led outreach clinic; and injection equipment provision site. Reinfection is defined as a positive RNA test result after SVR. Incidences of reinfection are expressed in 100 person-years (PYs). In total, 916 treatment episodes met selection criteria. Of these, 100 reinfections were identified, generating an overall reinfection rate of 5.27 per 100 PYs (95%CI: 4.36-6.38). The hospital outpatient clinic had the lowest reinfection incidence (1.81 per 100 PYs, 95%CI: 1.11-2.93), with the injection equipment provision site treatment pathway having the highest reinfection incidence (19.89 per 100 PYs, 95%CI: 14.91-26.54). The incidence of reinfection among those treated with interferon-based therapies and those treated with DAA-based therapies was 4.93 per 100 PYs (95%CI: 3.97-6.11) and 7.17 per 100 PYs (95%CI: 4.75-10.82), respectively. Specialized treatment pathways in Tayside yield varying reinfection incidence rates, with different subpopulations of patients at varying risk of reinfection post-SVR. Results suggest that resources should be targeted at the injection equipment provision site pathway in order to reduce the incidence of reinfection and achieve elimination targets. The study found comparable rates of reinfection following interferon-based and DAA-based therapies, providing support for widening access to treatment services.

Uptake of interferon-free DAA therapy among HCV-infected decompensated cirrhosis patients and evidence for decreased mortality.

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.

Disconnect between psychiatric and addiction services: a review of patients' attendances at Alcohol Tobacco and Other Drug Services after a psychiatric admission.

OBJECTIVE: To investigate the rate of attendance at Alcohol Tobacco and Other Drug Services (ATODS) for patients discharged from an acute mental health unit with a primary/secondary diagnosis of substance use disorder (SUD); and describe factors, demographics, diagnoses and service provision that relate to their attendance. METHOD: All inpatients between 1 November 2016 and 31 October 2017 with a diagnosis of SUD were compared for their attendance at ATODS within 30 days of discharge. Other measures included their admission data (e.g. demographics, diagnosis), and indices of their illness severity. RESULTS: Of 1295 admissions for a total of 900 patients, 32.4% of patients had an SUD diagnosis. Only 10.3% of these patients attended ATODS. There were no significant differences by gender, age, indigenous status, illness severity or dual diagnosis intervention during their inpatient stay on attendance. Relative to the SUD-only group, individuals with any psychiatric comorbidity were three-four times less likely to attend ATODS. CONCLUSION: Despite the ongoing emphasis on dual diagnosis treatment, the rate of engagement with ATODS remains low. Further review is needed to determine whether enhanced information sharing or case management models may improve attendance rates.

Subtyping Hyperchloremia among Hospitalized Patients by Machine Learning Consensus Clustering.

Background and Objectives: Despite the association between hyperchloremia and adverse outcomes, mortality risks among patients with hyperchloremia have not consistently been observed among all studies with different patient populations with hyperchloremia. The objective of this study was to characterize hyperchloremic patients at hospital admission into clusters using an unsupervised machine learning approach and to evaluate the mortality risk among these distinct clusters. Materials and Methods: We performed consensus cluster analysis based on demographic information, principal diagnoses, comorbidities, and laboratory data among 11,394 hospitalized adult patients with admission serum chloride of >108 mEq/L. We calculated the standardized mean difference of each variable to identify each cluster's key features. We assessed the association of each hyperchloremia cluster with hospital and one-year mortality. Results: There were three distinct clusters of patients with admission hyperchloremia: 3237 (28%), 4059 (36%), and 4098 (36%) patients in clusters 1 through 3, respectively. Cluster 1 was characterized by higher serum chloride but lower serum sodium, bicarbonate, hemoglobin, and albumin. Cluster 2 was characterized by younger age, lower comorbidity score, lower serum chloride, and higher estimated glomerular filtration (eGFR), hemoglobin, and albumin. Cluster 3 was characterized by older age, higher comorbidity score, higher serum sodium, potassium, and lower eGFR. Compared with cluster 2, odds ratios for hospital mortality were 3.60 (95% CI 2.33-5.56) for cluster 1, and 4.83 (95% CI 3.21-7.28) for cluster 3, whereas hazard ratios for one-year mortality were 4.49 (95% CI 3.53-5.70) for cluster 1 and 6.96 (95% CI 5.56-8.72) for cluster 3. Conclusions: Our cluster analysis identified three clinically distinct phenotypes with differing mortality risks in hospitalized patients with admission hyperchloremia.

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

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

Simplification of Care for Chronic Hepatitis C Virus Infection.

In 2016, the World Health Organization (WHO) set a target for eliminating viral hepatitis as a major public health threat by 2030. However, while today's highly effective and well-tolerated pangenotypic direct-acting antiviral regimens have maximized simplification of hepatitis C virus (HCV) treatment, there remain a plethora of barriers to HCV screening, diagnosis, and linkage to care. As of 2017, only 19% of the estimated 71 million individuals living with chronic HCV worldwide were diagnosed and in 2015 to 2016, only 21% of diagnosed individuals had accessed treatment. Simplification and decentralization of the HCV care cascade would bolster patient engagement and support the considerable scale-up needed to achieve WHO targets. Recent developments in HCV screening and diagnosis, together with reduced pretreatment assessment and on-treatment monitoring requirements, can further streamline the care continuum, ensuring patients are linked to care quickly and earlier in the disease course, and minimize clinic visits.