Factors associated with hepatitis C testing, treatment, and current hepatitis C infection among men and women who inject drugs: The ETHOS engage study.

BACKGROUND: Evaluating gender-specific trends in hepatitis C virus (HCV) treatment uptake among men and women who inject drugs is crucial for ensuring equitable progress towards HCV elimination. This study aimed to quantify differences in testing, treatment, and current HCV infection between men and women who inject drugs. METHOD: ETHOS Engage is an observational cohort study of people who inject drugs attending drug treatment clinics and needle and syringe programs in Australia recruited from May 2018-September 2019 (wave 1) and November 2019-April 2021 (wave 2). Participants completed a questionnaire including self-reported HCV testing and treatment history and underwent point-of-care HCV RNA testing (Xpert® HCV Viral Load Fingerstick). Logistic regression was used to compare the factors associated with self-reported HCV testing and treatment and current HCV infection for men and women who inject drugs. RESULTS: Among 2,395 participants enrolled in ETHOS Engage, 66% (n = 1,591) were men, 33% (n = 786) women, and <1% (n = 18) did not identify as a man or woman. HCV testing history and current infection were similar among men and women. Among men or women ever eligible for HCV treatment (ever chronic HCV) (n = 1,242), women were less likely to report a history of HCV treatment compared to men (227/352, 64% vs. 631/890, 71%; p = 0.03). Among women, those aged <45 were less likely to report HCV testing (aOR: 0.57, 95%CI: 0.36, 0.90), treatment (aOR: 0.47, 95%CI: 0.29, 0.77), and more likely to have HCV infection (aOR: 1.48, 95%CI: 1.00, 2.20) CONCLUSION: Among women, those of childbearing age (<45) were less likely to report testing and treatment and were more likely to have current HCV infection. Women <45 years old should be a priority population for HCV care. Services that interface with these women should be optimised to enhance HCV testing and treatment.

Corrigendum to "Trends in decompensated cirrhosis and hepatocellular carcinoma among people with a hepatitis B notification in New South Wales" [JHEP Reports 4 (2022)].

[This corrects the article DOI: 10.1016/j.jhepr.2022.100552.].

TRPA1 as a promising target in ischemia/reperfusion: A comprehensive review.

Ischemic disorders, including myocardial infarction, cerebral ischemia, and peripheral vascular impairment, are the main common reasons for debilitating diseases and death in Western cultures. Ischemia occurs when blood circulation is reduced in tissues. Reperfusion, although commanded to return oxygen to ischemic tissues, generates paradoxical tissue responses. The responses include generating reactive oxygen species (ROS), stimulating inflammatory responses in ischemic organs, endoplasmic reticulum stress, and the expansion of postischemic capillary no-reflow, which intensifies organ damage. Multiple pathologic processes contribute to ischemia/reperfusion; therefore, targeting different pathologic processes may yield an effective therapeutic approach. Transient Receptor Potential A1 (TRPA1) belongs to the TRP family of ion channels, detects a broad range of chemicals, and promotes the transduction of noxious stimuli, e.g., methylglyoxal, ROS, and acrolein effects are attributed to the channel's sensitivity to intracellular calcium elevation or phosphoinositol phosphate modulation. Hypoxia and ischemia are associated with oxidative stress, which activates the TRPA1 channel. This review describes the role of TRPA1 and its related mechanisms that contribute to ischemia/reperfusion. Relevant articles were searched from PubMed, Scopus, Web of Sciences, and Google Scholar electronic databases, up to the end of August 2023. Based on the evidence presented here, TRPA1 may have protective or deteriorative functions during the ischemia/reperfusion process. Its function depends on the activation level, the ischemic region, the extent of lesions, and the duration of ischemia.

Alnustone: A review of its sources, pharmacology, and pharmacokinetics .

Alnustone (4(E)-,6(E)-1,7-Diphenyl-hepta-4,6-dien-3-one) is a non-phenolic natural diarylheptanoid, which was first isolated and identified from the male flower of Alnus pendula (Betulaceae). It can also be isolated from Curcuma xanthorrhiza Roxb (Zingiberaceae) rhizomes and Alpinia katsumadai Hayata (Zingiberaceae) seeds. It was first synthesized through a five-step process from ß-phenyl propionyl chloride. In later years, new methods for synthesizing Alnustone were designed and performed with different yields. Due to the various therapeutic effects exhibited by alnustone like other diarylheptanoids, its biological activities such as antioxidant, antibacterial, and anti-inflammatory properties have been the subject of many studies. This article has reviewed different aspects of this valuable natural compound, including its natural and synthetic sources, therapeutic effects, and pharmacokinetics as a potential future therapeutic agent.

Lipid-lowering drugs and cancer: an updated perspective.

Statins and non-statin medications used for the management of dyslipidemia have been shown to possess antitumor properties. Since the use of these drugs has steadily increased over the past decades, more knowledge is required about their relationship with cancer. Lipid-lowering agents are heterogeneous compounds; therefore, it remains to be revealed whether anticancer potential is a class effect or related to them all. Here, we reviewed the literature on the influence of lipid-lowering medications on various types of cancer during development or metastasis. We also elaborated on the underlying mechanisms associated with the anticancer effects of antihyperlipidemic agents by linking the reported in vivo and in vitro studies.

Temporal change in aetiology and clinical characteristics of hepatocellular carcinoma in a large cohort of patients in New South Wales, Australia.

BACKGROUND: Viral hepatitis, alcohol-related liver disease (ARLD) and nonalcoholic fatty liver disease (NAFLD) are the main risk factors for hepatocellular carcinoma (HCC) in many countries. In Australia, given the access to hepatitis C virus (HCV) direct-acting antiviral (DAA) therapy since 2016, a temporal change in HCC aetiology was hypothesized. This study evaluated the temporal change in the aetiology and characteristics of HCC in New South Wales (NSW). METHODS: Patients diagnosed with HCC, admitted to three public hospitals in NSW between 2008 and 2021, were included in the analyses. We assessed the annual frequency of each HCC aetiology and the distribution of HCC characteristics in participants. RESULTS: Among 1370 patients, the most common HCC etiologies were HCV (n = 483, 35%), ARLD (n = 452, 33%), NAFLD (n = 347, 25%) and hepatitis B virus (n = 301, 22%). The proportion of HCV-related HCC was the highest in 2011-2016 (41%) and significantly declined to 30% in 2017-2021 (odds ratio [OR], 0.53 [95% confidence interval (CI), 0.35-0.79]; P = 0.002). The proportion of HCC diagnosed at an early stage (Barcelona Clinic Liver Cancer stage O/A) increased from 41% in 2008-2009 to 56% in 2020-2021 (OR per annum, 1.05 [95% CI, 1.02-1.08]; P = 0.002), and the proportion of patients receiving potentially curative HCC management increased from 29% in 2008-2009 to 41% in 2020-2021 (OR per annum, 1.06 [95% CI, 1.03-1.10]; P < 0.001). CONCLUSION: The contribution of HCV to HCC burden has been decreasing in the DAA era, suggesting the role of HCV elimination in decreasing HCC risk. Increasing frequency of less advanced HCC at diagnosis over time suggests improved HCC surveillance.

Krüppel-like Factor 5 Plays an Important Role in the Pathogenesis of Chronic Pancreatitis.

Chronic pancreatitis results in the formation of pancreatic intraepithelial neoplasia (PanIN) and poses a risk of developing pancreatic cancer. Our previous study demonstrated that Krüppel-like factor 5 (KLF5) is necessary for forming acinar-to-ductal metaplasia (ADM) in acute pancreatitis. Here, we investigated the role of KLF5 in response to chronic injury in the pancreas. Human tissues originating from chronic pancreatitis patients showed increased levels of epithelial KLF5. An inducible genetic model combining the deletion of Klf5 and the activation of KrasG12D mutant expression in pancreatic acinar cells together with chemically induced chronic pancreatitis was used. The chronic injury resulted in increased levels of KLF5 in both control and KrasG12D mutant mice. Furthermore, it led to numerous ADM and PanIN lesions and extensive fibrosis in the KRAS mutant mice. In contrast, pancreata with Klf5 loss (with or without KrasG12D) failed to develop ADM, PanIN, or significant fibrosis. Furthermore, the deletion of Klf5 reduced the expression level of cytokines and fibrotic components such as Il1b, Il6, Tnf, Tgfb1, Timp1, and Mmp9. Notably, using ChIP-PCR, we showed that KLF5 binds directly to the promoters of Il1b, Il6, and Tgfb1 genes. In summary, the inactivation of Klf5 inhibits ADM and PanIN formation and the development of pancreatic fibrosis.

Cascade of care among people with hepatitis B in New South Wales, Australia.

Hepatitis B virus (HBV) care cascade characterisation is important for monitoring HBV elimination progress. This study evaluated care cascade and factors associated with HBV DNA testing and treatment in New South Wales, Australia. HBV care cascade were determined through linkage of HBV notifications (1993-2017) to Medicare and pharmaceutical benefits schemes (2010-2018). Timely HBV DNA testing was within 4 weeks of HBV notification. Multivariate Cox proportional hazards regression evaluated factors associated with HBV DNA testing and treatment. Among 15,202 people with HBV notification, 10,479 (69%) were tested for HBV DNA. A total of 3179 (21%) initiated HBV treatment. HBV DNA testing was more likely among age ≥45 years (adjusted hazard ratio [aHR] 1.07, 95% CI: 1.02, 1.12), hepatocellular carcinoma (HCC) (aHR 1.23, 95% CI: 1.01, 1.50), coinfection (aHR 1.61, 95% CI: 1.23, 2.09), later notification (2014-2017) (aHR 1.21, 95% CI: 1.16, 1.26) and less likely among females (aHR 0.95, 95% CI: 0.91, 0.99), history of alcohol use disorder (AUD) (aHR 0.77, 95% CI: 0.66, 0.89), HCV coinfection (aHR .62, 95% CI: 0.55, 0.70) and Indigenous peoples (aHR 0.84, 95% CI: 0.71, 0.98). HBV treatment was associated with age ≥45 years (aHR 1.35, 95% CI: 1.24, 1.48), decompensated cirrhosis (aHR 2.07, 95% CI: 1.62, 2.65), HCC (aHR 2.96, 95% CI: 2.35, 3.74), HIV coinfection (aHR 4.27, 95% CI: 3.43, 5.31) and later notification (2014-2017) (aHR 1.37, 95% CI: 1.26, 1.47). HBV treatment was less likely among females (aHR 0.68, 95% CI: 0.63, 0.73) and Indigenous peoples (aHR 0.58, 95% CI: 0.42, 0.80). HBV DNA testing and treatment coverage have increased, but remain sub-optimal among some key populations.

Factors associated with hepatitis C treatment uptake among females of childbearing age in New South Wales, Australia: A population-based study.

INTRODUCTION: Females of childbearing age with hepatitis C virus (HCV) face increased marginalisation with intersecting, sex-specific barriers to direct acting antiviral (DAA) therapy. We assessed the factors associated with uptake of DAA therapy among females of childbearing age, including those with evidence of recent drug dependence. METHODS: HCV notifications in New South Wales, Australia (1995-2017) were linked to opioid agonist therapy (OAT), hospitalisations, incarcerations, perinatal, HIV notifications, deaths and prescription databases. Recent drug dependence was defined as hospitalisation due to injectable drugs or receipt of OAT occurring in the DAA era (2016-2018). Logistic regression was used to analyse factors associated with DAA uptake among females of childbearing age (18-44), including those with recent drug dependence. RESULTS: Among 57,467 people with evidence of chronic HCV in the DAA era (2016-2018), 20,161 (35%) were female, including 33% (n = 6563/20,161) of childbearing age (18-44). Among all females of childbearing age (n = 6563) and those with evidence of recent drug dependence (n = 2278/6563, 35%), DAA uptake was lower among those who had given birth in the DAA era (vs. no birth record, all females of childbearing age; aOR: 0.74, 95% CI 0.61, 0.89; those with recent drug dependence; aOR 0.69, 95% CI 0.51, 0.93) and Aboriginal and Torres Strait Islander peoples (all females of childbearing age; aOR 0.81, 95% CI 0.71, 0.93; those with recent drug dependence aOR 0.75, 95% CI 0.62, 0.90). CONCLUSION: Females of childbearing age should be considered a key population for DAA therapy. Enhancing antenatal and postnatal HCV care may be critical in the pursuit towards elimination.

Liver-related mortality among people with hepatitis B and C: Evaluation of definitions based on linked healthcare administrative datasets.

Routinely collected and linked healthcare administrative datasets could be used to monitor mortality among people with hepatitis B (HBV) and C (HCV). This study aimed to evaluate the concordance in records of liver-related mortality among people with an HBV or HCV notification, between data on hospitalization for end-stage liver disease (ESLD) and death certificates. In New South Wales, Australia, HBV and HCV notifications (1993-2017) were linked to hospital admissions (2001-2018), all-cause mortality (1993-2018) and cause-specific mortality (1993-2016) datasets. Hospitalization for ESLD was defined as a first-time hospital admission due to decompensated cirrhosis (DC) or hepatocellular carcinoma (HCC). Consistency of liver death definition of mortality following hospitalization for ESLD was compared with two death certificate-based definitions of liver deaths coded among primary and secondary cause-specific mortality data, including ESLD-related (deaths due to DC and HCC) and all-liver deaths (ESLD-related and other liver-related causes). Of 63,292 and 107,430 individuals with an HBV and HCV notification, there were 4478 (2.6%) post-ESLD hospitalization deaths, 5572 (3.3%) death certificate liver disease deaths and 2910 (1.7%) death certificate ESLD deaths. Between 2001 and 2016, among HBV post-ESLD hospitalization deaths (n = 891), 63% (562) had death certificate ESLD recorded, and 83% (741) had death certificate liver disease recorded. Between 2001 and 2016, among HCV post-ESLD hospitalization deaths (n = 3587), 58% (2082) had death certificate ESLD recorded, and 87% (3135) had death certificate liver disease recorded. At least one-third of death certificates with DC and HCC as cause of death had no mention of HBV, HCV or viral hepatitis. Our study identified limitations in estimating and tracking HBV and HCV liver disease mortality using death certificate-based data only. The optimum data for this purpose is either ESLD hospitalisations with vital status information or a combination of these with cause-specific death certificate data.

Hepatitis C care cascade before and during the direct-acting antiviral eras in New South Wales, Australia: A population-based linkage study.

The hepatitis C virus (HCV) care cascade characterization is important for monitoring progress towards HCV elimination. This study evaluated HCV care cascade and factors associated with treatment during pre-DAA (2011-2012 and 2013-2015) and DAA (2016-2018) eras in New South Wales (NSW), Australia. We conducted a cohort study of people with an HCV notification (1993 to 2017) through end 2018, linked to administrative datasets, including HCV treatment and non-hospital services. Those aged <18 years, died within first 6 months of study period or notification, and who had successful HCV treatment in period before were excluded. Sex-specific spontaneous viral clearance was incorporated to estimate treatment-eligible population. The study population in each period were cumulative and brought forward from one period to the next. Among 115,667 people with HCV notification, 87,063 fulfilled eligibility criteria. During 2011 to 2012, 2013 to 2015, and 2016 to 2018, cumulative HCV notifications were 71,677, 77,969, and 80,017; 52,016, 56,793, and 57,467 were eligible for treatment; 29%, 48%, and 64% confirmed HCV RNA positive; and 0.6%, 5%, and 38% initiated HCV treatment, respectively. Birth cohort 1945 to 1964 (vs. ≥1965), males, non-Aboriginal ethnicity, regional/rural area of residence, and HCV/HIV co-infection were associated with higher treatment uptake. Incarceration and drug dependence were associated with higher treatment uptake during the DAA era. In Australia, many marginalized populations including those incarcerated and those with drug dependence have equitable treatment uptake in the DAA era. Targeted strategies are required to enhance treatment uptake for females and Aboriginal populations.

Dscam1 overexpression impairs the function of the gut nervous system in Drosophila.

BACKGROUND: Down syndrome (DS) patients have a 100-fold increase in the risk of Hirschsprung syndrome of the colon and rectum (HSCR), a lack of enteric neurons in the colon. The leading DS candidate gene is trisomy of the Down syndrome cell adhesion molecule (DSCAM). RESULTS: We find that Dscam1 protein is expressed in the Drosophila enteric/stomatogastric nervous system (SNS). Axonal Dscam1 phenotypes can be rescued equally by diverse isoforms. Overexpression of Dscam1 resulted in frontal and hindgut nerve overgrowth. Expression of dominant negative Dscam1-ΔC led to a truncated frontal nerve and increased branching of the hindgut nerve. Larval locomotion is influenced by feeding state, and we found that the average speed of larvae with Dscam1 SNS expression was reduced, whereas overexpression of Dscam1-ΔC significantly increased the speed. Dscam1 overexpression reduced the efficiency of food clearance from the larval gut. CONCLUSION: Our work demonstrates that overexpression of Dscam1 can perturb gut function in a model system.

Awareness of hepatitis C virus infection status among people who inject drugs in a setting of universal direct-acting antiviral therapy: The ETHOS Engage study.

BACKGROUND: Awareness of hepatitis C virus (HCV) infection status among people who inject drugs (PWID) can empower people with diagnosis, enable treatment uptake, and facilitate elimination. We aimed to evaluate awareness of HCV infection status among a large national cohort of PWID in an era of unrestricted HCV treatment. METHODS: ETHOS Engage is an observational cohort study of PWID attending drug treatment clinics and needle and syringe programs in Australia. Participants completed a questionnaire containing self-reported HCV data (including infection status: never tested, tested/unknown, no current HCV infection [HCV RNA not detectable], current HCV infection [HCV RNA detectable]) and underwent point-of-care HCV RNA testing (Xpert® HCV Viral Load Fingerstick). Awareness was defined as concordant self-reported HCV status and test result. Awareness was assessed among all participants, those with current HCV infection, and participants who reported a lifetime history of HCV treatment. Logistic regression was used to assess factors associated with awareness in these three populations. RESULTS: Among 2,305 PWID, 65% (n=1,506) were aware of their HCV infection status (self-reported HCV status matched HCV point-of-care result). Awareness of infection status was higher among those who were not currently infected (70%, n=1,281/1,818) compared to those with current HCV infection (46%, n=225/487). After adjusting, those with current HCV infection were less likely to be aware of infection status (aOR: 0.40, 95%CI: 0.30, 0.45). Among those who reported a lifetime history of HCV treatment, 71% (n=592/829) were aware of their HCV infection status. CONCLUSION: Among a large cohort of PWID in Australia, awareness of HCV infection status is sub-optimal, with particularly concerning levels among those with active infection. Increased and simplified testing, post-test counselling, and post-treatment monitoring is warranted.

In Silico analysis of the sequence and structure of plant microRNAs packaged in extracellular vesicles.

Small RNA (sRNA)-mediated RNA interference (RNAi) is a conserved eukaryotic cellular process associated with immune defense and pathogen virulence. The cross-kingdom transfer of noncoding regulatory sRNAs between host and pathogen can be mediated via lipid, membrane-bound extracellular vesicles (EVs). Several studies have reported in mammalian and plant systems there is selective packaging of sRNAs into EVs. In mammals, sequence patterns and structural motifs are implicated in signaling pathways related to EV cargo sorting. However, in the emerging plant EV field, there is a lack of knowledge of the mechanisms involved in selecting sRNAs for EV transport. In this study, we accessed publicly available databases where the sRNA content of plant EVs has been characterized from control plants and those released in response to fungal pathogen infection. An in-depth analysis revealed 158 sRNAs are EV packaged, with ∼60 % sharing a sequence motif and 98.1 % forming a secondary hairpin stem-loop structure. Many of the predicted plant targets for the EV sRNAs were associated with biological pathways involved in metabolism and regulation processes. Overall, our in silico analysis of sRNAs packaged in plant EVs highlight that a computational approach can offer valuable insights into the cross-kingdom EV transport of sRNAs.

Trends in decompensated cirrhosis and hepatocellular carcinoma among people with a hepatitis B notification in New South Wales.

Background & Aims: Population-level trends and factors associated with HBV-related decompensated cirrhosis (DC), hepatocellular carcinoma (HCC), and liver-related mortality are crucial to evaluate the impacts of therapeutic interventions. Methods: Trends in HBV-DC and -HCC diagnoses and liver-related mortality in New South Wales, Australia, were determined through linkage of HBV notifications (1993-2017) to hospital admissions (2001-2018), mortality (1993-2018), and cancer registry (1994-2014) databases. Late HBV notification was defined as notification at or within 2 years of a DC or HCC diagnosis. Cox proportional-hazards regression and multivariable logistic regression analyses were performed to evaluate associated factors. Results: Among 60,660 people with a HBV notification, 1,276 (2.0%) DC and 1,087 (1.8%) HCC diagnoses, and 1,219 (2.0%) liver-related deaths were documented. Since the early 2000s, the number of DC and HCC diagnoses increased; however, age-standardised incidence decreased from 2.64 and 1.95 in 2003 to 1.14 and 1.09 per 1,000 person-years in 2017, respectively. Similarly, age-standardised liver mortality decreased from 2.60 in 2003 to 1.14 per 1,000 person-years in 2017. Among people with DC and HCC diagnoses, late HBV notification declined from 41% and 40% between 2001-2009 to 29% and 25% in 2010-2018, respectively. Predictors of DC diagnosis included older age (birth <1944, adjusted hazard ratio [aHR] 2.06, 95% CI 1.57-2.69), alcohol use disorder (aHR 4.82, 95% CI 3.96-5.87) and HCV co-infection (aHR 1.88, 95% CI 1.53-2.31). Predictors of HCC diagnosis included older age (birth <1944, aHR 3.94, 95% CI 2.91-5.32) and male sex (aHR 3.79, 95% CI 3.05-4.71). Conclusion: In an era of improved antiviral therapies, the risk of HBV-related liver morbidity and mortality has declined. HCV co-infection and alcohol use disorder are key modifiable risk factors associated with the burden of HBV. Lay summary: Rising hepatitis B-related morbidity and mortality is a major public health concern. However, the development of highly effective medicines against hepatitis B virus (HBV) has brought renewed optimism for its elimination by 2030. This study shows a steady decline in HBV-related liver morbidity and mortality in New South Wales, Australia. Moreover, late hepatitis notification has also declined, allowing individuals with HBV to have access to timely antiviral treatment. Despite this, hepatitis C co-infection and alcohol use disorder are key modifiable risk factors associated with HBV disease burden. To attain the desired benefits from highly effective antiviral treatment, managing comorbidities, including hepatitis C and high alcohol use, must improve among individuals with hepatitis B.

Timely Hepatitis C RNA Testing and Treatment in the Era of Direct-Acting Antiviral Therapy among People with Hepatitis C in New South Wales, Australia.

This study aimed to identify the factors associated with timely (within four weeks) HCV RNA testing and timely (within six months) DAA initiation following HCV notification in the DAA era. We conducted a cohort study of people with an HCV notification in NSW, Australia. Notifications of positive HCV serology were linked to administrative datasets. Weights were applied to account for spontaneous clearance. Logistic regression analyses were performed. Among 5582 people with an HCV notification during 2016-2017, 3867 (69%) were tested for HCV RNA, including 2770 (50%) who received timely testing. Among an estimated 3925 people with chronic HCV infection, 2372 (60%) initiated DAA therapy, including 1370 (35%) who received timely treatment. Factors associated with timely HCV RNA testing included age (≥30 years), female sex, non-Aboriginal ethnicity, country of birth being Australia, and no history of drug dependence. Factors associated with timely treatment were age (≥30 years), male sex, non-Aboriginal ethnicity, country of birth being Australia, no history of drug dependence, and HCV/HIV co-infection. In the DAA era, 50% of people with an HCV notification did not receive timely HCV RNA testing. Most people with an HCV infection received therapy; however, DAA initiation was delayed among many.

A Testing Campaign Intervention Consisting of Peer-Facilitated Engagement, Point-of-Care HCV RNA Testing, and Linkage to Nursing Support to Enhance Hepatitis C Treatment Uptake among People Who Inject Drugs: The ETHOS Engage Study.

This study evaluated HCV treatment initiation among people who inject drugs (PWID) following an intervention of campaign days involving peer connection, point-of-care HCV RNA testing, and linkage to nursing support. ETHOS Engage is an observational cohort study of PWID attending 25 drug treatment clinics and needle and syringe programs in Australia (May 2018-September 2019). Point-of-care results were provided to the nurse, facilitating confirmatory testing and treatment. The study aimed to evaluate treatment uptake and factors associated with treatment at 24 months post-enrolment. There were 317 people with current HCV infection and eligible for treatment (median age 43, 65% male, 15% homeless, 69% receiving opioid agonist treatment, 70% injected in last month). Overall, 15% (47/317), 27% (85/317), 38% (120/317), and 49% (155/317) of people with current HCV infection had initiated treatment at 3-, 6-, 12-, and 24-months following testing, respectively. Homelessness (adjusted hazard ratio (aHR): 0.40; 95% confidence interval: 0.23, 0.71) and incarceration in the past 12 months (vs. never, aHR:0.46; 0.28, 0.76) were associated with decreased treatment initiation in the 24 months post-enrolment. This testing campaign intervention facilitated HCV treatment uptake among PWID. Further interventions are needed to achieve HCV elimination among people experiencing homelessness or incarceration.

Prevalence and factors associated with hospitalisation for bacterial skin infections among people who inject drugs: The ETHOS Engage Study.

BACKGROUND: Injecting-related skin and soft tissue infections (SSTIs) are a preventable cause of inpatient hospitalisation among people who inject drugs (PWID). This study aimed to determine the prevalence of hospitalisation for SSTIs among PWID, and identify similarities and differences in factors associated with hospitalisation for SSTIs versus non-bacterial harms related to injecting drug use. METHODS: We performed cross-sectional analyses of baseline data from an observational cohort study of PWID attending drug treatment clinics and needle and syringe programs in Australia. Logistic regression models were used to identify factors associated with self-reported hospitalisation for (1) SSTIs (abscess and/or cellulitis), and (2) non-bacterial harms related to injecting drug use (e.g., non-fatal overdose; hereafter referred to as non-bacterial harms), both together and separately. RESULTS: 1851 participants who injected drugs in the previous six months were enrolled (67% male; 85% injected in the past month; 42% receiving opioid agonist treatment [OAT]). In the previous year, 40% (n = 737) had been hospitalised for drug-related causes: 20% (n = 377) and 29% (n = 528) of participants were admitted to hospital for an SSTI and non-bacterial harm, respectively. Participants who were female (adjusted odds ratio [aOR]: 1.53, 95% CI: 1.19-1.97) or homeless (aOR: 1.59, 95% CI: 1.16-2.19) were more likely to be hospitalised for an SSTI, but not a non-bacterial harm. Both types of hospitalisation were more likely among people recently released from prison. CONCLUSIONS: Hospitalisation for SSTIs is common among PWID. Community-based interventions to prevent SSTIs and subsequent hospitalisation among PWID will require targeting of at-risk groups, including women, people experiencing homelessness, and incarcerated people upon prison release.

Declining prevalence of current HCV infection and increased treatment uptake among people who inject drugs: The ETHOS Engage study.

BACKGROUND: Evaluating trends in HCV treatment and prevalence is crucial for monitoring elimination. We evaluated the change in current infection and treatment among people who inject drugs (PWID) between 2018-2019 and 2019-2021. METHODS: ETHOS Engage is an observational cohort study of PWID attending drug treatment clinics and needle and syringe programs in Australia. Participant enrolment occurred over two periods, Wave 1 (May 2018-September 2019, 25 sites) and Wave 2 (November 2019-June 2021, 21 sites), with baseline questionnaire completion and point-of-care HCV RNA testing (Xpert® HCV Viral Load Fingerstick). Logistic regression was used to identify factors associated with current HCV infection and historic HCV treatment. RESULTS: 2,395 individuals were enrolled across the two recruitment waves (66% male, median age 43, 72% current opioid agonist therapy, and 65% injecting in the previous month). HCV prevalence decreased from 24% to 17% between 2018-2019 and 2019-2021, respectively (p=0.003). HCV treatment increased from 66% to 74% between 2018-2019 and 2019-2021, respectively (p<0.001). After adjusting, there was a reduction in current HCV infection in 2019-2021 (adjusted odds ratio [aOR] 0.62; 95% CI, 0.50, 0.77) compared to 2018-2019. Other factors associated with current infection included homelessness (aOR, 1.70; 1.26, 2.30), incarceration (vs. never; historic: aOR 1.69; 95%CI 1.31, 2.19; recent: aOR 1.85; 95%CI, 1.35, 2.54), and recently injecting drugs (vs. >12 months ago; previous month

Willingness of people who inject drugs to participate in a randomised controlled trial involving financial incentives to initiate hepatitis C treatment.

BACKGROUND: Evidence regarding the acceptability of contingency management is limited. We investigated the willingness of people who inject drugs to participate in a randomised controlled trial (RCT) involving financial incentives to initiate HCV treatment. METHODS: ETHOS Engage is an observational cohort study of people with a history of injecting drug use who either injected in the past six months or receive opioid agonist therapy (OAT) in Australia. We assessed willingness to participate in a RCT with financial incentives and factors associated with preference for entire incentive ($60) at first clinic visit versus delayed incentive with logistic regression. RESULTS: 93% (593/635) of eligible participants agreed to participate in an RCT with financial incentives of which 24% were Aboriginal or Torres Strait Islander, 84% had completed secondary school, and 59% injected drugs in the prior month. Willingness to participate in an RCT increased by amount offered: unspecified (72%), $20 (75%), $60 (80%), and $100 (85%). The preferred incentive distribution method over three clinical visits was entire incentive at first clinical visit (32%). Among those with a preferred distribution method (n = 369), factors associated with entire incentive at first clinic visit were being Aboriginal or Torres Strait Islander (aOR 1.75; 95% CI 1.05-2.94), completion of secondary school (aOR 0.46; 95% CI 0.26-0.83) and mainly injected heroin in month prior (aOR 1.82; 95% CI 1.03-3.20). CONCLUSION: Most participants were willing to participate in an RCT involving financial incentives to initiate treatment but differed regarding distribution. Study findings inform implementation of incentives in clinical practice.