Publications by authors named "Amanda Yu"

48 Publications

The impact of current opioid agonist therapy on hepatitis C virus treatment initiation among people who use drugs from in the DAA era: A population-based study.

Clin Infect Dis 2021 Jun 14. Epub 2021 Jun 14.

British Columbia Centre for Disease Control, Vancouver, BC, Canada.

Background: Evidence that opioid agonist therapy (OAT) is associated with increased odds of hepatitis C virus (HCV) treatment initiation among people who use drugs (PWUD) is emerging. The objective of this study was to determine the association between current OAT and HCV treatment initiation among PWUD in a population-level linked administrative dataset.

Methods: The British Columbia (BC) Hepatitis Testers Cohort was used for this study, which includes all people tested for or diagnosed with HCV in BC, linked to medical visits, hospitalizations, laboratory, prescription drug, and mortality data from 1992 until 2019. PWUD with injecting drug use or opioid use disorder and chronic HCV infection were identified for inclusion in this study. HCV treatment initiation was the main outcome, and subdistribution proportional hazards modeling was used to assess the relationship with current OAT.

Results: 13,803 PWUD with chronic HCV were included in this study. Among those currently on OAT at the end of the study period, 47% (2,704/5,770) had started HCV treatment, whereas 22% (1778/8033) of those not currently on OAT has started HCV treatment .. Among PWUD with chronic HCV infection, current OAT was associated with higher likelihood of HCV treatment initiation in time to event analysis (adjusted hazard ratio 1.84 [95%CI, 1.50, 2.26]).

Conclusions: Current OAT was associated with a higher likelihood of HCV treatment initiation. However, many PWUD with HCV currently receiving OAT have yet to receive HCV treatment. Enhanced integration between substance use care and HCV treatment is needed to improve the overall health of PWUD.
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http://dx.doi.org/10.1093/cid/ciab546DOI Listing
June 2021

Impact of HCV infection and ethnicity on incident type 2 diabetes: findings from a large population-based cohort in British Columbia.

BMJ Open Diabetes Res Care 2021 06;9(1)

School of Population and Public Health, The University of British Columbia, Vancouver, British Columbia, Canada

Introduction: Increasing evidence indicates that chronic hepatitis C virus (HCV) infection is associated with higher risk of diabetes. Previous studies showed ethnic disparities in the disease burden of diabetes, with increased risk in Asian population. We described the incidence of type 2 diabetes related to HCV infection and assessed the concurrent impact of HCV infection and ethnicity on the risk of diabetes.

Research Design And Methods: In British Columbia Hepatitis Testers Cohort, individuals were followed from HCV diagnosis to the earliest of (1) incident type 2 diabetes, (2) death or (3) end of the study (December 31, 2015). Study population included 847 021 people. Diabetes incidence rates in people with and without HCV were computed. Propensity scores (PS) analysis was used to assess the impact of HCV infection on newly acquired diabetes. PS-matched dataset included 117 184 people. We used Fine and Gray multivariable subdistributional hazards models to assess the effect of HCV and ethnicity on diabetes while adjusting for confounders and competing risks.

Results: Diabetes incidence rates were higher among people with HCV infection than those without. The highest diabetes incidence rate was in South Asians with HCV (14.7/1000 person-years, 95% CI 12.87 to 16.78). Compared with Others, South Asians with and without HCV and East Asians with HCV had a greater risk of diabetes. In the multivariable stratified analysis, HCV infection was associated with increased diabetes risk in all subgroups: East Asians, adjusted HR (aHR) 3.07 (95% CI 2.43 to 3.88); South Asians, aHR 2.62 (95% CI 2.10 to 3.26); and Others, aHR 2.28 (95% CI 2.15 to 2.42).

Conclusions: In a large population-based linked administrative health data, HCV infection was associated with higher diabetes risk, with a greater relative impact in East Asians. South Asians had the highest risk of diabetes. These findings highlight the need for care and screening for HCV-related chronic diseases such as type 2 diabetes among people affected by HCV.
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http://dx.doi.org/10.1136/bmjdrc-2021-002145DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8186745PMC
June 2021

Impact of direct-acting antivirals for HCV on mortality in a large population-based cohort study.

J Hepatol 2021 Jun 4. Epub 2021 Jun 4.

British Columbia Centre for Disease Control, Vancouver, BC, Canada; Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC, Canada.

Background: We evaluated the effect of sustained virologic response(SVR) from direct acting antiviral(DAA) treatments on all-cause, liver- and drug-related mortality in a population-based cohort in British Columbia(BC), Canada.

Methods: We used data from the BC Hepatitis Testers Cohort, which includes people tested for hepatitis C virus(HCV) since 1990, linked with data on medical visits, hospitalizations, prescription drugs and mortality. We followed people who received DAAs and people who did not receive any HCV treatment to death or December 31, 2019. We used inverse probability of treatment weighting(IPTW) to balance the baseline profile of treated and untreated individuals and performed multivariable proportional hazard modeling to assess effect of DAAs on mortality.

Findings: There were 10,855 people treated with DAAs (SVR: 10,426 [96%], no-SVR: 425) and 10,855 untreated individuals. Median follow-up time was 2.2 years (interquartile range: 1.3-3.6; maximum: 6.2). The all-cause mortality rate was 19.5/1000 person-years (PY) among the SVR group(deaths=552), 86.5/1000 PY among the no-SVR group (deaths=96), and 99.2/1000 PY among the untreated group (deaths=2133). In the multivariable model, SVR was associated with significant reduction in all-cause(adjusted hazard ratio[aHR]:0.19, 95%CI:0.17-0.21), liver-(subdistribution HR[asHR]:0.22, 95%CI: 0.18-0.27) and drug-related mortality(asHR: 0.26, 95%CI:0.21-0.32) compared to no-treatment. Older age and cirrhosis were associated with higher risk of liver-related mortality while younger age, injection drug use(IDU), problematic alcohol use and HIV/HBV co-infections were associated with a higher risk of drug-related mortality.

Conclusions: DAA treatment is associated with a substantial reduction in all-cause, liver- and drug-related mortality. The association of IDU and related syndemic factors with a higher risk of drug-related mortality calls for an integrated social support, addiction, and HCV care approach among people with IDU.

Lay Summary: We assessed the effect of treatment of hepatitis C virus infection with direct acting antiviral drugs on deaths from all causes, liver disease and drug use. We found that treatment with direct acting antiviral drugs is associated with substantial lowering in risk of death from all causes, liver disease and drug use among people with hepatitis C virus infection.
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http://dx.doi.org/10.1016/j.jhep.2021.05.028DOI Listing
June 2021

Cohort profile: development and characteristics of a retrospective cohort of individuals dispensed prescription opioids for non-cancer pain in British Columbia, Canada.

BMJ Open 2021 04 13;11(4):e043586. Epub 2021 Apr 13.

BC Centre for Disease Control, Vancouver, British Columbia, Canada.

Purpose: Prescription opioids (POs) are widely prescribed for chronic non-cancer pain but are associated with several risks and limited long-term benefit. Large, linked data sources are needed to monitor their harmful effects. We developed and characterised a retrospective cohort of people dispensed POs.

Participants: We used a large linked administrative database to create the Opioid Prescribing Evaluation and Research Activities cohort of individuals dispensed POs for non-cancer pain in British Columbia (BC), Canada (1996-2015). We created definitions to categorise episodes of PO use based on a review of the literature (acute, episodic, chronic), developed an algorithm for inferring clinical indication and assessed patterns of PO use across a range of characteristics.

Findings To Date: The current cohort includes 1.1 million individuals and 3.4 million PO episodes (estimated to capture 40%-50% of PO use in BC). The majority of episodes were acute (81%), with most prescribed for dental or surgical pain. Chronic use made up 3% of episodes but 88% of morphine equivalents (MEQ). Across the acute to episodic to chronic episode gradient, there was an increasing prevalence of higher potency POs (hydromorphone, oxycodone, fentanyl, morphine), long-acting formulations and chronic pain related indications (eg, back, neck, joint pain). Average daily dose (MEQ) was similar for acute/episodic but higher for chronic episodes. Approximately 7% of the cohort had a chronic episode and chronic pain was the characteristic most strongly associated with chronic PO use. Individuals initiating a chronic episode were also more likely to have higher social/material deprivation and previous experience with a mental health condition or a problem related to alcohol or opioid use. Overall, these findings suggest our episode definitions have face validity and also provide insight into characteristics of people initiating chronic PO therapy.

Future Plans: The cohort will be refreshed every 2 years. Future analyses will explore the association between POs and adverse outcomes.
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http://dx.doi.org/10.1136/bmjopen-2020-043586DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8051385PMC
April 2021

Differences in risk factors for hepatitis B, hepatitis C, and human immunodeficiency virus infection by ethnicity: A large population-based cohort study in British Columbia, Canada.

Int J Infect Dis 2021 May 23;106:246-253. Epub 2021 Mar 23.

British Columbia Centre for Disease Control, Vancouver, British Columbia, Canada; School of Population and Public Health, University of British Columbia, Vancouver, British Columbia, Canada.

Objectives: Addressing the needs of ethnic minorities will be key to finding undiagnosed individuals living with hepatitis B (HBV), hepatitis C (HCV), or human immunodeficiency virus (HIV). To inform screening initiatives in British Columbia (BC), Canada, the factors associated with HBV and/or HCV and/or HIV infection among different ethnic groups within a large population-based cohort were assessed.

Methods: Persons diagnosed with HBV, HCV, or HIV in BC between 1990 and 2015 were grouped as East Asian, South Asian, Other Visible Minority (African, Central Asian, Latin American, Pacific Islander, West Asian, unknown ethnicity), and Not a Visible Minority, using a validated name-recognition software. Factors associated with infection within each ethnic group were assessed with multivariable multinomial logistic regression models.

Results: Participants included 202 521 East Asians, 126 070 South Asians, 65 210 Other Visible Minorities, and 1 291 561 people who were Not a Visible Minority, 14.4%, 3.3%, 4.5%, and 6.3% of whom had HBV and/or HCV and/or HIV infections, respectively. Injection drug use was most prevalent among infection-positive people who were Not a Visible Minority (22.1%), and was strongly associated with HCV monoinfection, HBV/HCV coinfection, and HCV/HIV coinfection, but not with HBV monoinfection among visible ethnic minorities. Extreme material deprivation and social deprivation were more prevalent than injection drug use or problematic alcohol use among visible ethnic minorities.

Conclusions: Risk factor distributions varied among persons diagnosed with HBV and/or HCV and/or HIV of differing ethnic backgrounds, with lower substance use prevalence among visible minority populations. This highlights the need for tailored approaches to infection screening among different ethnic groups.
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http://dx.doi.org/10.1016/j.ijid.2021.03.061DOI Listing
May 2021

Elevated risk of colorectal, liver, and pancreatic cancers among HCV, HBV and/or HIV (co)infected individuals in a population based cohort in Canada.

Ther Adv Med Oncol 2021 11;13:1758835921992987. Epub 2021 Feb 11.

BC Centre for Disease Control, Vancouver, Canada.

Introduction: Studies of the impact of hepatitis C virus (HCV), hepatitis B virus (HBV) and HIV mono and co-infections on the risk of cancer, particularly extra-hepatic cancer, have been limited and inconsistent in their findings.

Methods: In the British Columbia Hepatitis Testers Cohort, we assessed the risk of colorectal, liver, and pancreatic cancers in association with HCV, HBV and HIV infection status. Using Fine and Gray adjusted proportional subdistribution hazards models, we assessed the impact of infection status on each cancer, accounting for competing mortality risk. Cancer occurrence was ascertained from the BC Cancer Registry.

Results: Among 658,697 individuals tested for the occurrence of all three infections, 1407 colorectal, 1294 liver, and 489 pancreatic cancers were identified. Compared to uninfected individuals, the risk of colorectal cancer was significantly elevated among those with HCV (Hazard ration [HR] 2.99; 95% confidence interval [CI] 2.55-3.51), HBV (HR 2.47; 95% CI 1.85-3.28), and HIV mono-infection (HR 2.30; 95% CI 1.47-3.59), and HCV/HIV co-infection. The risk of liver cancer was significantly elevated among HCV and HBV mono-infected and all co-infected individuals. The risk of pancreatic cancer was significantly elevated among individuals with HCV (HR 2.79; 95% CI 2.01-3.70) and HIV mono-infection (HR 2.82; 95% CI 1.39-5.71), and HCV/HBV co-infection.

Discussion/conclusion: Compared to uninfected individuals, the risk of colorectal, pancreatic and liver cancers was elevated among those with HCV, HBV and/or HIV infection. These findings highlight the need for targeted cancer prevention and diligent clinical monitoring for hepatic and extrahepatic cancers in infected populations.
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http://dx.doi.org/10.1177/1758835921992987DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7887683PMC
February 2021

Prenatal hepatitis C screening, diagnoses, and follow-up testing in British Columbia, 2008-2019.

PLoS One 2020 31;15(12):e0244575. Epub 2020 Dec 31.

British Columbia Centre for Disease Control, Vancouver, British Columbia, Canada.

Objective: Current guidelines in British Columbia recommend prenatal screening for hepatitis C antibodies (anti-HCV) if risk factors are present. We aimed to estimate frequency of prenatal anti-HCV testing, new diagnoses, repeated and follow-up testing among BC women.

Methods: BC Centre for Disease Control Public Health Laboratory data estimated the number of BC women (assigned female at birth or unknown sex) aged 13-49 who received routine prenatal serological screening (HIV, hepatitis B, syphilis and rubella) from 2008-2019. Anti-HCV tests ordered the same day as routine prenatal screens were considered prenatal anti-HCV tests. Assessment of follow-up was based on HCV RNA and/or genotype testing within one year of new prenatal anti-HCV diagnoses.

Results: In 2019, 55,202 routine prenatal screens were carried out for 50,392 BC women. Prenatal anti-HCV tests increased significantly, from 19.6% (9,704/49,515) in 2008 to 54.6% (27,516/50,392) in 2019 (p<0.001). New prenatal anti-HCV diagnoses (HCV positive diagnoses at first test or seroconversions) declined from 14.3% in 2008 to 10.1% in 2019. The proportion of women with new prenatal anti-HCV diagnoses that were a result of a first HCV test declined from 0.3% (29/9,701) in 2008 to 0.03% (8/27,500) in 2019. For women known to be anti-HCV positive at the time of prenatal screening, the proportion who had a prenatal anti-HCV test increased from 35.6% in 2008 to 50.8% in 2019.

Conclusion: Prenatal anti-HCV testing increased substantially over the study period. However, new HCV diagnoses remained relatively stable, suggesting that a considerable proportion of BC women with low or no risk are being screened as part of prenatal care. The vast majority of women with new HCV diagnoses receive appropriate follow-up HCV RNA and genotype testing, which may indicate interest in HCV treatment. These findings contribute to the discussion around potential for prenatal anti-HCV screening in an effort to eliminate HCV.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0244575PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7775094PMC
March 2021

HCV reinfection rates after cure or spontaneous clearance among HIV-infected and uninfected men who have sex with men.

Liver Int 2021 03 22;41(3):482-493. Epub 2020 Dec 22.

British Columbia Centre for Disease Control, Vancouver, British Columbia, Canada.

Background & Aims: Hepatitis C virus (HCV) reinfection among high-risk groups threatens HCV elimination goals. We assessed HCV reinfection rates among men who have sex with men (MSM) in British Columbia (BC), Canada.

Methods: We used data from the BC Hepatitis Testers Cohort, which includes nearly 1.7 million individuals tested for HCV or HIV in BC. MSM who had either achieved sustained virologic response (SVR) after successful HCV treatment, or spontaneous clearance (SC) and had ≥1 subsequent HCV RNA measurement, were followed from the date of SVR or SC until the earliest of reinfection, death, or last HCV RNA measurement. Predictors of reinfection were identified by Cox proportional modelling. The earliest study start date was 6 November 1997 and latest end date was 13 April 2018.

Results: Of 1349 HCV-positive MSM who met the inclusion criteria, 493 had SC while 856 achieved SVR. 349 (25.65%) had HIV coinfection. We identified 98 reinfections during 5203 person-years (PYs) yielding a reinfection rate of 1.88/100PYs. The reinfection rate among SC (2.74/100PYs) was more than twice that of those with SVR (1.03/100 PYs). Problematic alcohol use (aHR 1.73, 95% CI 1.003-2.92), injection drug use (aHR 2.60, 95% CI 1.57-4.29) and HIV coinfection (aHR 2.04, 95% CI 1.29-3.23) were associated with increased risk of HCV reinfection. Mental health counselling history (aHR 0.24, 95% CI 0.13-0.46) was associated with reduced HCV reinfection risk.

Conclusions: There is the need to engage MSM in harm reduction and prevention services following treatment to reduce reinfection risk.
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http://dx.doi.org/10.1111/liv.14762DOI Listing
March 2021

Drug-related deaths in a population-level cohort of people living with and without hepatitis C virus in British Columbia, Canada.

Int J Drug Policy 2020 Oct 19;86:102989. Epub 2020 Oct 19.

British Columbia Centre for Disease Control, 655 West 12(th) Avenue, Vancouver, British Columbia, Canada, V5Z 4R4; School of Population and Public Health, University of British Columbia, 2206 E Mall, Vancouver, British Columbia, Canada, V6T 1Z3.

Background: The majority of new HCV infections in Canada occur in people who inject drugs. Thus, while curative direct antiviral agents (DAAs) herald a promising new era in hepatitis C virus (HCV) treatment, improving the lives and wellbeing of people living with HCV (PLHCV) must be considered in the context of reducing overdose-related harms and with a syndemic lens. We measure drug-related deaths (DRDs) among HCV-negative people and PLHCV in British Columbia (BC), Canada, and the impact of potent contaminants like fentanyl on deaths.

Methods: We identified DRDs among PLHCV and HCV-negative individuals from 2010 to 2018 in the BC Hepatitis Testers Cohort, a population-based dataset of ~1.7 million British Columbians comprising comprehensive administrative and clinical data. We estimated annual standardized liver- and drug-related mortality rates per 100,000 person-years (PY) and described the contribution of specific drugs, including fentanyl and its analogues, implicated in DRDs over time.

Results: DRDs constituted 20.1% of deaths among PLHCV and 4.7% of deaths among HCV-negative individuals; a 4.3-fold (95% confidence interval: 4.0-4.5) difference. Drug-related mortality overtook liver-related mortality for PLHCV in 2015 and HCV-negative individuals in 2016 and rose from 241.7 to 436.5 per 100,000 PY from 2010 to 2018 amongPLHCV and from 20.0 to 57.1 per 100,000 PY for HCV-negative individuals over the same period. The proportion of deaths attributable to drugs among PLHCV and HCV-negative individuals increased from 15.1% to 26.1% and 3.1% to 8.0%, in 2010 and 2018, respectively. The proportion of DRDs attributed solely to synthetic opioids such as fentanyl averaged across both groups increased from 2.1% in 2010 to 69.6% in 2017.

Conclusion: Steep drug-related mortality increases among PLHCV and HCV-negative individuals over the last decade highlight the urgent need to address overdose-related drivers and harms in these populations using an integrated care approach.
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http://dx.doi.org/10.1016/j.drugpo.2020.102989DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7569420PMC
October 2020

Concurrent Hepatitis C and B Virus and Human Immunodeficiency Virus Infections Are Associated With Higher Mortality Risk Illustrating the Impact of Syndemics on Health Outcomes.

Open Forum Infect Dis 2020 Sep 13;7(9):ofaa347. Epub 2020 Aug 13.

British Columbia Centre for Disease Control, Vancouver, British Columbia, Canada.

Background: Hepatitis C virus (HCV), hepatitis B virus (HBV), and human immunodeficiency virus (HIV) infections are associated with significant mortality globally and in North America. However, data on impact of concurrent multiple infections on mortality risk are limited. We evaluated the effect of HCV, HBV, and HIV infections and coinfections and associated factors on all-cause mortality in British Columbia (BC), Canada.

Methods: The BC Hepatitis Testers Cohort includes ~1.7 million individuals tested for HCV or HIV, or reported as a case of HCV, HIV, or HBV from 1990 to 2015, linked to administrative databases. We followed people with HCV, HBV, or HIV monoinfection, coinfections, and triple infections from their negative status to date of death or December 31, 2016. Extended Cox proportional hazards regression was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for factors associated with all-cause mortality.

Results: Of 658 704 individuals tested for HCV, HBV, and HIV, there were 33 804 (5.13%) deaths. In multivariable Cox regression analysis, individuals with HCV/HBV/HIV (HR, 8.9; 95% CI, 8.2-9.7) infections had the highest risk of mortality followed by HCV/HIV (HR, 4.8; 95% CI, 4.4-5.1), HBV/HIV (HR, 4.1; 95% CI, 3.5-4.8), HCV/HBV (HR, 3.9; 95% CI, 3.7-4.2), HCV (HR, 2.6; 95% CI, 2.6-2.7), HBV (HR, 2.2; 95% CI, 2.0-2.3), and HIV (HR, 1.6; 95% CI, 1.5-1.7). Additional factors associated with mortality included injection drug use, problematic alcohol use, material deprivation, diabetes, chronic kidney disease, heart failure, and hypertension.

Conclusions: Concurrent multiple infections are associated with high mortality risk. Substance use, comorbidities, and material disadvantage were significantly associated with mortality independent of coinfection. Preventive interventions, including harm reduction combined with coinfection treatments, can significantly reduce mortality.
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http://dx.doi.org/10.1093/ofid/ofaa347DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7489531PMC
September 2020

Effects of Brazilian green propolis extract on planktonic cells and biofilms of multidrug-resistant strains of and .

Biofouling 2020 08 21;36(7):834-845. Epub 2020 Sep 21.

Department of Biosciences and Oral Diagnosis, Institute of Science and Technology, São Paulo State University (UNESP), São José dos Campos, SP, Brazil.

Propolis could represent an alternative therapeutic agent for targeting multidrug-resistant bacteria due to its antimicrobial potential. The effect of Brazilian green propolis (BGP) aqueous extract (AqExt) was evaluated on eight multidrug-resistant clinical strains of and , as well as on one reference strain for each bacterial species. The minimum bactericidal concentration (MBC) was determined and optimal concentrations were further evaluated in comparison with 0.12% chlorhexidine. The natural extract was chemically characterized by HPLC-DAD analysis. The MBC values ranged between 3.12 and 27.5 mg ml. Analysis of bacterial metabolic activity after treatment for 5 min with BGP-AqExt revealed a strong antimicrobial potential, similar to chlorhexidine. The extract comprised several active compounds including quercetin, gallic acid, caffeic and -coumaric acid, drupani, galangin, and artepillin C. Altogether, the findings suggest that BGP-AqExt is fast and effective against multidrug-resistant strains of and in planktonic cultures and biofilms.
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http://dx.doi.org/10.1080/08927014.2020.1823972DOI Listing
August 2020

Evaluation of a Lay First Responder Program in Sierra Leone as a Scalable Model for Prehospital Trauma Care.

Injury 2020 Nov 3;51(11):2565-2573. Epub 2020 Sep 3.

Michigan Center for Global Surgery, Ann Arbor, Michigan, 1500 E Medical Center Dr, Ann Arbor, MI, United States; University of Michigan Health System, Department of Surgery, 1500 E Medical Center Dr, Ann Arbor, MI, United States.

Introduction: Few countries in Sub-Saharan Africa have robust emergency medical services (EMS). The World Health Organization (WHO) recommends scaling-up lay first responder programs as the first step toward formal EMS development.

Materials And Methods: We trained and equipped 4,529 lay first responders (LFRs) between June-December 2019 in Bombali District, Sierra Leone, with a 5-hour hands-on, contextually-adapted prehospital trauma course to cover 535,000 people. Instructors trained 1,029 LFRs and 50 local trainers in a training-of-trainers (TOT) model, who then trained an additional 3,500 LFRs. A validated, 23-question pre-/post-test measured knowledge improvement, while six- and nine-month follow-up tests measured knowledge retention. Incident reports tracked patient encounters to assess longitudinal impact.

Results: Median pre-/post-test scores improved by 43.5 percentage points (34.8% vs. 78.3%, p<0.0001). Knowledge retention was assessed at six months, with median score dropping to 60.9%, while at nine months, median score dropped to 43.5%. Lay first responders participating in courses led by TOT trainers had a pre-/post-test median score improvement of 30.4 percentage points (21.7% vs. 52.2%, p<0.0001). LFRs treated 1,850 patients over six months, most frequently utilizing hemorrhage control skills in 61.2% of encounters (1,133/1,850). The plurality of patients were young adult males (36.8%) and 48.7% of encounters were motorcycle injury-related.

Conclusion: A 5-hour first responder course targeting laypeople demonstrates significant emergency care knowledge improvement and retention. By training networks of transportation providers, lay first responder programs represent a robust and scalable prehospital emergency care alternative for low-resource settings.
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http://dx.doi.org/10.1016/j.injury.2020.09.001DOI Listing
November 2020

Syndemic profiles of people living with hepatitis C virus using population-level latent class analysis to optimize health services.

Int J Infect Dis 2020 Nov 15;100:27-33. Epub 2020 Aug 15.

School of Population and Public Health, University of British Columbia, Vancouver, BC, Canada; BC Centre for Disease Control, Vancouver, BC, Canada; Centre for Health Evaluation and Outcome Sciences, Vancouver, BC, Canada. Electronic address:

Background: Hepatitis C (HCV) affects diverse populations such as people who inject drugs (PWID), 'baby boomers,' gay/bisexual men who have sex with men (gbMSM), and people from HCV endemic regions. Assessing HCV syndemics (i.e.relationships with mental health/chronic diseases) among subpopulations using Latent Class Analysis (LCA) may facilitate targeted program planning.

Methods: The BC Hepatitis Testers Cohort(BC-HTC) includes all HCV cases identified in BC between 1990 and 2015, integrated with medical administrative data. LCA grouped all BC-HTC HCV diagnosed people(n = 73,665) by socio-demographic/clinical indicators previously determined to be relevant for HCV outcomes. The final model was chosen based on fit statistics, epidemiological meaningfulness, and posterior probability. Classes were named by most defining characteristics.

Results: The six-class model was the best fit and had the following names and characteristics: 'Younger PWID'(n =11,563): recent IDU (67%), people born >1974 (48%), mental illness (62%), material deprivation (59%). 'Older PWID'(n =15,266): past IDU (78%), HIV (17%), HBV (17%) coinfections, alcohol misuse(68%). 'Other Middle-Aged People'(n = 9019): gbMSM (26%), material privilege (31%), people born between 1965-1974 (47%). 'People of Asian backgrounds' (n = 4718): East/South Asians (92%), no alcohol misuse (97%) or mental illness (93%), people born <1945 (26%), social privilege (66%). 'Rural baby boomers' (n = 20,401): rural dwellers (32%), baby boomers (79%), heterosexuals (99%), no HIV (100%). 'Urban socially deprived baby boomers' (n = 12,698): urban dwellers (99%), no IDU (100%), liver disease (22%), social deprivation (94%).

Conclusions: Differences between classes suggest variability in patients' service needs. Further analysis of health service utilization patterns may inform optimal service layout.
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http://dx.doi.org/10.1016/j.ijid.2020.08.035DOI Listing
November 2020

The impact of SVR from direct-acting antiviral- and interferon-based treatments for HCV on hepatocellular carcinoma risk.

J Viral Hepat 2020 08 17;27(8):781-793. Epub 2020 Apr 17.

British Columbia Centre for Disease Control, Vancouver, BC, Canada.

We evaluated the effect of sustained virologic response (SVR) from direct-acting antiviral (DAA)- and interferon-based treatments on hepatocellular carcinoma (HCC) risk in a large population-based cohort in Canada. We used data from the BC Hepatitis Testers Cohort, which includes ~1.3 million individuals tested for HCV since 1990, linked with healthcare administrative and registry datasets. Patients were followed from the end of HCV treatment to HCC, death or 31 December 2016. We assessed HCC risk among those who did and did not achieve SVR by treatment type using proportional hazard models. Of 12 776 eligible individuals, 3905 received DAAs while 8871 received interferon-based treatments, followed for a median of 1.0 [range: 0.6-2.7] and 7.9 [range: 4.4-17.1] years, respectively. A total of 3613 and 6575 achieved SVR with DAAs- and interferon-based treatments, respectively. Among DAAs-treated patients, HCC incidence rate was 6.9 (95%CI: 4.7-10.1)/1000 person yr (PY) in SVR group (HCC cases: 26) and 38.2 (95%CI: 20.6-71.0) in the no-SVR group (HCC cases: 10, P < .001). Among interferon-treated individuals, HCC incidence rate was 1.8 (95%CI: 1.5-2.2) in the SVR (HCC cases: 99) and 13.9 (95%CI: 12.3-15.8) in the no-SVR group (HCC cases: 239, P < .001). Compared with no-SVR from interferon, SVR from DAA- and interferon-based treatments resulted in significant reduction in HCC risk (adjusted subdistribution hazard ratio (adjSHR) DAA = 0.30, 95%CI: 0.19-0.48 and adjSHR interferon = 0.2, 95%CI: 0.16-0.26). Among those with SVR, treatment with DAAs compared to interferon was not associated with HCC risk (adjSHR = 0.93, 95%CI: 0.51-1.71). In conclusion, similar to interferon era, DAA-related SVR is associated with 70% reduction in HCC risk.
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http://dx.doi.org/10.1111/jvh.13295DOI Listing
August 2020

Real-world Effectiveness of Sofosbuvir/Velpatasvir for Treatment of Chronic Hepatitis C in British Columbia, Canada: A Population-Based Cohort Study.

Open Forum Infect Dis 2020 Mar 29;7(3):ofaa055. Epub 2020 Feb 29.

British Columbia Centre for Disease Control, Vancouver, British Columbia, Canada.

Background: Clinical trials show high efficacy of sofosbuvir/velpatasvir (SOF/VEL), but there are limited data from "real-world" settings. We aimed to evaluate SOF/VEL effectiveness for all hepatitis C virus (HCV) genotypes (GTs) in British Columbia (BC), Canada.

Methods: We used the BC Hepatitis Testers Cohort, which includes all HCV cases in the province (1990-2015) linked to administrative databases, including prescriptions to end of 2018. We measured sustained virologic response (SVR; negative RNA ≥10 weeks after treatment end) and identified characteristics associated with non-SVR. Conservatively, we excluded individuals with no assessment for SVR if their last RNA test after treatment initiation was negative (but included if positive).

Results: Of 2821 eligible participants, most were infected with GT1 (1076, 38.1%) or GT3 (1072, 38.0%), and a minority (278, 9.9%) were treated with RBV. SVR was 94.6% (2670/2821) overall and 94.5% (1017/1076) for GT1, 96.4% (512/531) for GT2, and 93.7% (1004/1072) for GT3. When disaggregated by GT, treatment regimen, and cirrhosis/treatment experience, SVR was lowest (30/40, 75.0%) among treatment-experienced GT3 individuals treated with RBV. Characteristics associated with non-SVR in multivariable analysis included younger age, RBV addition, and being a person with HIV (PWH) or who injects/injected drugs (PWID). When treatment regimen (±RBV) was removed from multivariable model, treatment experience was associated with non-SVR for GT3. Of 151 non-SVR individuals, 56.3% were nonvirological failures (treatment incomplete/no assessment for SVR) and 43.7% were virological failures (nonresponse/relapse). A disproportionately high percentage of non-SVR among PWID was due to nonvirological failure.

Conclusions: SOF/VEL was highly effective in this "real-world" population-based cohort. Additional support is required for PWID/PWH to reach SVR.
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http://dx.doi.org/10.1093/ofid/ofaa055DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7052750PMC
March 2020

Loss to follow-up: A significant barrier in the treatment cascade with direct-acting therapies.

J Viral Hepat 2020 03 2;27(3):243-260. Epub 2019 Dec 2.

BC Centre for Disease Control, Vancouver, BC, Canada.

Effectiveness of direct-acting antiviral (DAA) therapies could be influenced by patient characteristics such as comorbid conditions, which could lead to premature treatment discontinuation and/or irregular medical follow-ups. Here, we evaluate loss to follow-up and treatment effectiveness of sofosbuvir/ledipasvir ± ribavirin (SOF/LDV ± RBV), ombitasvir/paritaprevir/ritonavir + dasabuvir ± ribavirin (OBV/PTV/r + DSV ± RBV) for hepatitis C virus (HCV) genotype 1 (GT1) and sofosbuvir + ribavirin (SOF + RBV) for genotype 3 (GT3) in British Columbia Canada: The British Columbia Hepatitis Testers Cohort includes data on individuals tested for HCV since 1992, integrated with medical visit, hospitalization and prescription drug data. HCV-positive individuals who initiated DAA regimens, irrespective of treatment completion, for GT1 and GT3 until 31 December, 2017 were included. Factors associated with sustained virological response (SVR) and loss to follow-up were assessed by using multivariable logistic regression models. In total 4477 individuals initiated DAAs. The most common prescribed DAA was SOF/LDV ± RBV with SVR of 95%. The highest SVR of 99.5% was observed among OBV/PTV/r + DSV-treated patients. Overall, 453 (10.1%) individuals were lost to follow-up. Higher loss to follow-up was observed among GT1 patients treated with OBV (17.8%) and GT3 patients (15.7%). The loss to follow-up rate was significantly higher among individuals aged <60 years, those with a history of injection drug use (IDU), on opioid substitution therapy and with cirrhosis. Our findings indicate that loss to follow-up exceeds viral failure in HCV DAA therapy and its rate varies significantly by genotype and treatment regimen. Depending on the aetiology of lost to follow-up, personalized case management for those with medical complications and supporting services among IDU are needed to achieve the full benefits of effective treatments.
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http://dx.doi.org/10.1111/jvh.13228DOI Listing
March 2020

Reply to: "Pitfalls in measuring temporal trends for late diagnosis of viral hepatitis".

J Hepatol 2019 12 23;71(6):1256-1258. Epub 2019 Oct 23.

British Columbia Centre for Disease Control, Vancouver, BC, Canada; School of Population and Public Health, University of British Columbia, Vancouver, BC, Canada. Electronic address:

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http://dx.doi.org/10.1016/j.jhep.2019.09.015DOI Listing
December 2019

The population level care cascade for hepatitis C in British Columbia, Canada as of 2018: Impact of direct acting antivirals.

Liver Int 2019 12 20;39(12):2261-2272. Epub 2019 Sep 20.

British Columbia Centre for Disease Control (BCCDC), Vancouver, BC, Canada.

Background: Population-level monitoring of hepatitis C virus (HCV) infected people across cascades of care identifies gaps in access and engagement in care and treatment. We characterized the population-level care cascade for HCV in British Columbia (BC), Canada before and after introduction of Direct Acting Antiviral (DAA) treatment.

Methods: BC Hepatitis Testers Cohort (BC-HTC) includes 1.7 million individuals tested for HCV, HIV, reported cases of hepatitis B, and active tuberculosis in BC from 1990 to 2018 linked to medical visits, hospitalizations, cancers, prescription drugs and mortality data. We defined six HCV care cascade stages: (a) antibody diagnosed; (b) RNA tested; (c) RNA positive; (d) genotyped; (e) initiated treatment; and (f) achieved sustained virologic response (SVR).

Results: We estimated 61 127 people were HCV antibody positive in BC in 2018 (undiagnosed: 7686, 13%; diagnosed: 53 441, 87%). Of those diagnosed, 83% (44 507) had HCV RNA testing, and of those RNA positive, 90% (28 716) were genotyped. Of those genotyped, 61% (17 441) received therapy, with 90% (15 672) reaching SVR. Individuals from older birth cohorts had lower progression to HCV RNA testing. While people who currently inject drugs had the highest proportional progression to RNA testing, this group had the lowest proportional treatment uptake.

Conclusions: Although gaps in HCV RNA and genotype testing after antibody diagnosis exist, the largest gap in the care cascade is treatment initiation, despite introduction of DAA treatment and removal of treatment eligibility restrictions. Further interventions are required to ensure testing and treatment is equitably accessible in BC.
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http://dx.doi.org/10.1111/liv.14227DOI Listing
December 2019

Sustained virological response from interferon-based hepatitis C regimens is associated with reduced risk of extrahepatic manifestations.

J Hepatol 2019 12 6;71(6):1116-1125. Epub 2019 Aug 6.

British Columbia Centre for Disease Control, Vancouver, British Columbia, Canada; School of Population and Public Health, University of British Columbia, Vancouver, British Columbia, Canada. Electronic address:

Background & Aims: HCV infection is associated with several extrahepatic manifestations (EHMs). We evaluated the impact of sustained virological response (SVR) on the risk of 7 EHMs that contribute to the burden of extrahepatic disease: type 2 diabetes mellitus, chronic kidney disease or end-stage renal disease, stroke, ischemic heart disease, major adverse cardiac events, mood and anxiety disorders, and rheumatoid arthritis.

Methods: A longitudinal cohort study was conducted using data from the British Columbia Hepatitis Testers Cohort, which included ~1.3 million individuals screened for HCV. We identified all HCV-infected individuals who were treated with interferon-based therapies between 1999 and 2014. SVR was defined as a negative HCV RNA test ≥24 weeks post-treatment or after end-of-treatment, if unavailable. We computed adjusted subdistribution hazard ratios (asHR) for the effect of SVR on each EHM using competing risk proportional hazard models. Subgroup analyses by birth cohort, sex, injection drug exposure and genotype were also performed.

Results: Overall, 10,264 HCV-infected individuals were treated with interferon, of whom 6,023 (59%) achieved SVR. Compared to those that failed treatment, EHM risk was significantly reduced among patients with SVR for type 2 diabetes mellitus (asHR 0.65; 95%CI 0.55-0.77), chronic kidney disease or end-stage renal disease (asHR 0.53; 95% CI 0.43-0.65), ischemic or hemorrhagic stroke (asHR 0.73; 95%CI 0.49-1.09), and mood and anxiety disorders (asHR 0.82; 95%CI 0.71-0.95), but not for ischemic heart disease (asHR 1.23; 95%CI 1.03-1.47), major adverse cardiac events (asHR 0.93; 95%CI 0.79-1.11) or rheumatoid arthritis (asHR 1.09; 95% CI 0.73-1.64).

Conclusions: SVR was associated with a reduction in the risk of several EHMs. Increased uptake of antiviral therapy may reduce the growing burden of EHMs in this population.

Lay Summary: We estimated the rates of chronic comorbidities other than liver disease between those who were cured and those who failed treatment for hepatitis C virus (HCV) infection. Our findings showed that the rates of these non-liver diseases were largely reduced for those who were cured with interferon-based treatments. Early HCV treatments could provide many benefits in the prevention of various HCV complications beyond liver disease.
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http://dx.doi.org/10.1016/j.jhep.2019.07.021DOI Listing
December 2019

What is killing people with hepatitis C virus infection? Analysis of a population-based cohort in Canada.

Int J Drug Policy 2019 10 20;72:114-122. Epub 2019 Jun 20.

Clinical Prevention Services, British Columbia Centre for Disease Control, Vancouver, BC, Canada; School of Population and Public Health, Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada.

Background: Persons with hepatitis C virus (HCV) infection are at risk of mortality from both chronic liver disease and HCV acquisition risk activities. We compared causes of death among HCV positive and negative individuals to characterize contributions of acquisition risks and viral sequelae.

Methods: The British Columbia (BC) Hepatitis Testers Cohort (BC-HTC) includes all individuals tested for HCV or reported as a HCV case since 1992, linked to health administrative data. ICD-10 codes were used to classify deaths as: 1) liver-related (LR); 2) HCV acquisition risk-related (AR); and 3) other causes. Mortality proportions and trends were assessed among HCV positive and negative individuals overall and by birth cohort (born <1945, 1945-64 and ≥1965).

Results: As of December 31, 2018, of 1,300,204 HCV-tested individuals, 20,049 (27.5%) HCV positive and 132,999 (10.2%) HCV negative individuals had died (median age at death: 56.4 vs. 74.5 years, respectively). HCV positive individuals were more likely than negatives to die from both AR (24.7%/4.2%) and LR (23.4%/6.2%) causes. Deaths among older HCV positive individuals were more likely to be LR while younger individuals were more likely AR: 1) birth cohort <1945 (25.3%/2.7%); 2) 1945-64 (26.5%/23.7%) and ≥1965 (7.7%/59.9%). Among HCV positives, LR mortality increased from 1992 to 2014, then declined sharply, coinciding with the introduction and uptake of direct-acting antiviral drugs. AR mortality increased from 1992 to 2000, declined slowly until 2013, then rapidly increased, coinciding with the recent surge in opioid overdose deaths.

Conclusions: Curative HCV treatments reduce LR mortality, but typically will not impact AR mortality. This will need to be addressed if the World Health Organization 2030 HCV mortality reduction goals are to be achieved.
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http://dx.doi.org/10.1016/j.drugpo.2019.06.003DOI Listing
October 2019

Effectiveness of Ledipasvir/Sofosbuvir and Sofosbuvir/Velpatasvir in People Who Inject Drugs and/or Those in Opioid Agonist Therapy.

Hepatol Commun 2019 Apr 10;3(4):478-492. Epub 2019 Jan 10.

British Columbia Centre for Disease Control Vancouver Canada.

We evaluated the effectiveness of ledipasvir/sofosbuvir (LDV/SOF) in treating hepatitis C virus (HCV) genotype 1 and SOF/velpatasvir (SOF/VEL) for all genotypes among people who inject drugs (PWID) and those not injecting drugs and who were on or off opioid agonist therapy (OAT). Study participants comprised a population-based cohort in British Columbia, Canada. The British Columbia Hepatitis Testers Cohort includes data on individuals tested for HCV from 1990 to 2016 that are integrated with medical visits, hospitalization, and prescription drug data. We classified study participants as off OAT/recent injection drug use (off-OAT/RIDU), off OAT/past IDU (off-OAT/PIDU), off OAT/no IDU (off-OAT/NIDU), on OAT/IDU (on-OAT/IDU), and on OAT/no IDU (on-OAT/NIDU). We assessed sustained virologic response (SVR) 10 weeks after HCV treatment among study groups treated with LDV/SOF or SOF/VEL until January 13, 2018. Analysis included 5,283 eligible participants: 390 off-OAT/RIDU, 598 off-OAT/PIDU, 3,515 off-OAT/NIDU, 609 on-OAT/IDU, and 171 on-OAT/NIDU. The majority were male patients (64%-74%) and aged ≥50 years (58%-85%). The SVRs for off-OAT/RIDU, off-OAT/PIDU, off-OAT/NIDU, on-OAT/IDU, and on-OAT/NIDU were 91% (355/390), 95% (570/598), 96% (3,360/3,515), 93% (567/609), and 95% (163/171), respectively. Among those with no SVR, 14 individuals died while on treatment or before SVR assessment, including 4 from illicit drug overdose. In the overall multivariable model, off-OAT/RIDU, on-OAT/IDU, male sex, cirrhosis, treatment duration <8 weeks, treatment duration 8 weeks, and treatment with SOF/VEL were associated with not achieving SVR. In this large real-world cohort, PWID and/or those on OAT achieved high SVRs, although slightly lower than people not injecting drugs. This finding also highlights the need for additional measures to prevent loss to follow-up and overdose-related deaths among PWID.
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http://dx.doi.org/10.1002/hep4.1307DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6442698PMC
April 2019

Applying core theory and spatial analysis to identify hepatitis C virus infection "core areas" in British Columbia, Canada.

J Viral Hepat 2019 03 11;26(3):373-383. Epub 2018 Dec 11.

School of Population and Public Health, University of British Columbia, Vancouver, British Columbia, Canada.

"Core areas" of transmission for bacterial sexually transmitted infections have been identified. However, it is unclear whether core areas apply to viral infections, such as hepatitis C virus (HCV). We used geographic mapping and spatial analysis to identify distinct core areas of HCV infection in British Columbia (BC) using the BC Hepatitis Testers Cohort (BC-HTC), 1990-2013. The BC-HTC includes all BC residents tested for HCV (~1.5 million; 1990-2013). Core HCV infection areas were identified spatially and temporally for five time periods (1990-1993, 1994-1998, 1999-2003, 2004-2008 and 2009-2013) through thematic mapping, Kernel Density Estimation, Hotspot analysis and cluster analysis at the Census dissemination area level in ArcGIS and SatScan. HCV infection core areas were consistently identified. HCV core areas expanded from the downtown of major cities in different regions of BC (Metro Vancouver, Vancouver Island, and Northern BC; 1990-1998), to smaller cities in Metro Vancouver and Interior BC (2000 onwards). Statistically significant clusters, or hotspots, were also observed for downtown Vancouver, Northern BC (Prince George) and Vancouver Island from 1990 to 2008 with expansion to other urban areas in Metro Vancouver from 1990-2013. Statistically significant clusters persisted after adjustment for injection drug use, number of HCV tests, age, sex, material and social deprivation. Persistence of areas with high HCV diagnoses rates in Vancouver and Prince George supports the theory of core areas of HCV transmission. Identification of core areas can inform prevention, care and treatment programme interventions and evaluate their impact over time.
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http://dx.doi.org/10.1111/jvh.13043DOI Listing
March 2019

Effect of opioid-substitution therapy and mental health counseling on HIV risk among hepatitis C-infected individuals.

Clin Epidemiol 2018 31;10:1127-1145. Epub 2018 Aug 31.

School of Population and Public Health, University of British Columbia, Vancouver, BC,

Background: Understanding differences in HIV incidence among people living with hepatitis C virus (HCV) can help inform strategies to prevent HIV infection. We estimated the time to HIV diagnosis among HCV-positive individuals and evaluated factors that could affect HIV-infection risk in this population.

Patients And Methods: The British Columbia Hepatitis Testers Cohort includes all BC residents (~1.5 million: about a third of all residents) tested for HCV and HIV from 1990 to 2013 and is linked to administrative health care and mortality data. All HCV-positive and HIV-negative individuals were followed to measure time to HIV acquisition (positive test) and identify factors associated with HIV acquisition. Adjusted HRs (aHRs) were estimated using Cox proportional-hazard regression.

Results: Of 36,077 HCV-positive individuals, 2,169 (6%) acquired HIV over 266,883 years of follow-up (overall incidence of 8.1 per 1,000 person years). Overall median (IQR) time to HIV infection was 3.87 (6.06) years. In Cox regression, injection-drug use (aHR 1.47, 95% CI 1.33-1.63), HBV infection (aHR 1.34, 95% CI 1.16-1.55), and being a man who has sex with men (aHR 2.78, 95% CI 2.14-3.61) were associated with higher risk of HIV infection. Opioid-substitution therapy (OST) (aHR 0.59, 95% CI 0.52-0.67) and mental health counseling (aHR 0.48, 95% CI 0.43-0.53) were associated with lower risk of HIV infection.

Conclusion: Injection-drug use, HBV coinfection, and being a man who has sex with men were associated with increased HIV risk and engagement in OST and mental health counseling were associated with reduced HIV risk among HCV-positive individuals. Improving access to OST and mental health services could prevent transmission of HIV and other blood-borne infections, especially in settings where access is limited.
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http://dx.doi.org/10.2147/CLEP.S173449DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6124790PMC
August 2018

Hepatitis C virus reinfection after successful treatment with direct-acting antiviral therapy in a large population-based cohort.

J Hepatol 2018 Nov 22;69(5):1007-1014. Epub 2018 Aug 22.

British Columbia Centre for Disease Control, Vancouver, BC, Canada; School of Population and Public Health, University of British Columbia, Vancouver, BC, Canada. Electronic address:

Background & Aims: Direct-acting antiviral therapies (DAA) are an important tool for hepatitis C virus (HCV) elimination. However, reinfection among people who inject drugs (PWID) may hamper elimination targets. Therefore, we estimated HCV reinfection rates among DAA-treated individuals, including PWID.

Methods: We analyzed data from the British Columbia Hepatitis Testers Cohort which included ∼1.7 million individuals screened for HCV in British Columbia, Canada. We followed HCV-infected individuals treated with DAAs who achieved a sustained virologic response (SVR) and had ≥1 subsequent HCV RNA measurement to April 22nd, 2018. Reinfection was defined as a positive RNA measurement after SVR. PWID were identified using a validated algorithm and classified based on recent (<3 years) or former (≥3 years before SVR) use. Crude reinfection rates per 100 person-years (PYs) were calculated. Poisson regression was used to model adjusted incidence rate ratios (IRRs) and 95% CIs.

Results: Of 4,114 individuals who met the inclusion criteria, most were male (n = 2,692, 65%), born before 1965 (n = 3,411, 83%) and were either recent (n = 875, 21%) or former PWID (n = 1,793, 44%). Opioid-agonist therapy (OAT) was received by 19% of PWID. We identified 40 reinfections during 2,767 PYs. Reinfection rates were higher among recent (3.1/100 PYs; IRR 6.7; 95% CI 1.9-23.5) and former PWID (1.4/100 PYs; IRR 3.7; 95% CI 1.1-12.9) than non-PWID (0.3/100 PYs). Among recent PWID, reinfection rates were higher among individuals born after 1975 (10.2/100 PYs) and those co-infected with HIV (5.7/100 PYs). Only one PWID receiving daily OAT developed reinfection.

Conclusions: Population-level reinfection rates remain elevated after DAA therapy among PWID because of ongoing exposure risk. Engagement of PWID in harm-reduction and support services is needed to prevent reinfections.

Lay Summary: Direct-acting antivirals are an effective tool for the treatment of hepatitis C virus, enabling the elimination of the virus. However, some patients who have been successfully treated with direct-acting antivirals are at risk of reinfection. Our findings showed that the risk of reinfection was highest among people with recent injection drug use. Among people who inject drugs, daily use of opioid-agonist therapy was associated with a lower risk of reinfection.
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http://dx.doi.org/10.1016/j.jhep.2018.07.025DOI Listing
November 2018

Estimating the impact of early hepatitis C virus clearance on hepatocellular carcinoma risk.

J Viral Hepat 2018 12 28;25(12):1481-1492. Epub 2018 Aug 28.

British Columbia Centre for Disease Control, Vancouver, British Columbia, Canada.

Although achieving sustained virological response (SVR) through antiviral therapy could reduce the risk of hepatocellular carcinoma (HCC) attributable to hepatitis C virus (HCV) infection, the impact of early viral clearance on HCC is not well defined. In this study, we compared the risk of HCC among individuals who spontaneously cleared HCV (SC), the referent population, with the risk in untreated chronic HCV (UCHC), those achieved SVR, and those who failed interferon-based treatment (TF). The BC Hepatitis Testers Cohort (BC-HTC) includes individuals tested for HCV between 1990-2013, integrated with medical visits, hospitalizations, cancers, prescription drugs and mortality data. This analysis included all HCV-positive patients with at least one valid HCV RNA by PCR on or after HCV diagnosis. Of 46 666 HCV-infected individuals, there were 12 527 (26.8%) SC; 24 794 (53.1%) UCHC; 5355 (11.5%) SVR and 3990 (8.5%) TF. HCC incidence was lowest (0.3/1000 person-years (PY)) in the SC group and highest in the TF group (7.7/1000 PY). In a multivariable model, compared to SC, TF had the highest HCC risk (hazard ratio (HR):14.52, 95% confidence interval (CI): 9.83-21.47), followed by UCHC (HR: 5.85; 95% CI: 4.07-8.41). Earlier treatment-based viral clearance similar to SC could decrease HCC incidence by 69.4% (95% CI: 57.5-78.0), 30% (95% CI: 10.8-45.1) and 77.5% (95% CI: 69.4-83.5) among UCHC, SVR and TF patients, respectively. In conclusion, using SC as a real-world comparator group, it showed that substantial reduction in HCC risk could be achieved with earlier treatment initiation. These analyses should be replicated in patients who have been treated with direct acting antiviral therapies.
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http://dx.doi.org/10.1111/jvh.12977DOI Listing
December 2018

Differing profiles of people diagnosed with acute and chronic hepatitis B virus infection in British Columbia, Canada.

World J Gastroenterol 2018 Mar;24(11):1216-1227

British Columbia Centre for Disease Control, Vancouver BC V5Z4R4, Canada.

Aim: To describe the characteristics of people diagnosed with acute and chronic hepatitis B virus (HBV) infection in British Columbia (BC).

Methods: We used data from the BC Hepatitis Testers Cohort (BC-HTC), which includes all individuals tested for hepatitis C virus (HCV) or human immunodeficiency virus (HIV) or those diagnosed with HBV or active tuberculosis in BC since 1990. These data were integrated with prescription drug, medical visit, hospitalization and mortality data. HBV cases were classified as acute or chronic according to provincial guidelines. We compared characteristics of individuals by HBV infection group (acute, chronic and negative). Factors associated with acute or chronic HBV infection were assessed with multinomial logistic regression models in comparison to the HBV negative group.

Results: 46498 of the 1058056 eligible BC-HTC participants were diagnosed with HBV infection. 4.3% of HBV positive individuals were diagnosed with acute HBV infections while 95.7% had chronic infections. Problematic alcohol use, injection drug use, and HIV or HCV co-infection were more common among individuals diagnosed with acute HBV compared to those with chronic infections and HBV negative individuals. In multivariable multinomial logistic regression models, we observed significant associations between acute or chronic HBV diagnosis and being male, age at HBV diagnosis or birth cohort, South and East Asian ethnicity, HCV or HIV infection, and injection drug use. The odds of acute HBV decreased with increasing age among people who inject drugs, while the opposite was true for chronic HBV. Persons with acute HBV were predominantly White (78%) while those with chronic HBV were mostly East Asian (60%). Relative to Whites, East Asians had 12 times greater odds of being diagnosed with chronic HBV infection. These odds increased with increasing socioeconomic deprivation.

Conclusion: Differences in the profiles of people diagnosed with acute and chronic HBV infection necessitate differentiated screening, prevention, care and treatment programs.
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http://dx.doi.org/10.3748/wjg.v24.i11.1216DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5859224PMC
March 2018

Identifying injection drug use and estimating population size of people who inject drugs using healthcare administrative datasets.

Int J Drug Policy 2018 05 23;55:31-39. Epub 2018 Feb 23.

British Columbia Centre for Disease Control, Vancouver, BC, Canada; Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC, Canada.

Background: Large linked healthcare administrative datasets could be used to monitor programs providing prevention and treatment services to people who inject drugs (PWID). However, diagnostic codes in administrative datasets do not differentiate non-injection from injection drug use (IDU). We validated algorithms based on diagnostic codes and prescription records representing IDU in administrative datasets against interview-based IDU data.

Methods: The British Columbia Hepatitis Testers Cohort (BC-HTC) includes ∼1.7 million individuals tested for HCV/HIV or reported HBV/HCV/HIV/tuberculosis cases in BC from 1990 to 2015, linked to administrative datasets including physician visit, hospitalization and prescription drug records. IDU, assessed through interviews as part of enhanced surveillance at the time of HIV or HCV/HBV diagnosis from a subset of cases included in the BC-HTC (n = 6559), was used as the gold standard. ICD-9/ICD-10 codes for IDU and injecting-related infections (IRI) were grouped with records of opioid substitution therapy (OST) into multiple IDU algorithms in administrative datasets. We assessed the performance of IDU algorithms through calculation of sensitivity, specificity, positive predictive, and negative predictive values.

Results: Sensitivity was highest (90-94%), and specificity was lowest (42-73%) for algorithms based either on IDU or IRI and drug misuse codes. Algorithms requiring both drug misuse and IRI had lower sensitivity (57-60%) and higher specificity (90-92%). An optimal sensitivity and specificity combination was found with two medical visits or a single hospitalization for injectable drugs with (83%/82%) and without OST (78%/83%), respectively. Based on algorithms that included two medical visits, a single hospitalization or OST records, there were 41,358 (1.2% of 11-65 years individuals in BC) recent PWID in BC based on health encounters during 3- year period (2013-2015).

Conclusion: Algorithms for identifying PWID using diagnostic codes in linked administrative data could be used for tracking the progress of programing aimed at PWID. With population-based datasets, this tool can be used to inform much needed estimates of PWID population size.
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http://dx.doi.org/10.1016/j.drugpo.2018.02.001DOI Listing
May 2018

A syndemic approach to assess the effect of substance use and social disparities on the evolution of HIV/HCV infections in British Columbia.

PLoS One 2017 22;12(8):e0183609. Epub 2017 Aug 22.

School of Population and Public Health, University of British Columbia, Vancouver, British Columbia, Canada.

Background: Co-occurrence of social conditions and infections may affect HIV/HCV disease risk and progression. We examined the changes in relationship of these social conditions and infections on HIV and hepatitis C virus (HCV) infections over time in British Columbia during 1990-2013.

Methods: The BC Hepatitis Testers Cohort (BC-HTC) includes ~1.5 million individuals tested for HIV or HCV, or reported as a case of HCV, HIV, HBV, or tuberculosis linked to administrative healthcare databases. We classified HCV and HIV infection status into five combinations: HIV-/HCV-, HIV+monoinfected, HIV-/HCV+seroconverters, HIV-/HCV+prevalent, and HIV+/HCV+.

Results: Of 1.37 million eligible individuals, 4.1% were HIV-/HCV+prevalent, 0.5% HIV+monoinfected, 0.3% HIV+/HCV+ co-infected and 0.5% HIV-/HCV+seroconverters. Overall, HIV+monoinfected individuals lived in urban areas (92%), had low injection drug use (IDU) (4%), problematic alcohol use (4%) and were materially more privileged than other groups. HIV+/HCV+ co-infected and HIV-/HCV+seroconverters were materially most deprived (37%, 32%), had higher IDU (28%, 49%), problematic alcohol use (14%, 17%) and major mental illnesses (12%, 21%). IDU, opioid substitution therapy, and material deprivation increased in HIV-/HCV+seroconverters over time. In multivariable multinomial regression models, over time, the odds of IDU declined among HIV-/HCV+prevalent and HIV+monoinfected individuals but not in HIV-/HCV+seroconverters. Declines in odds of problematic alcohol use were observed in HIV-/HCV+seroconverters and coinfected individuals over time.

Conclusions: These results highlight need for designing prevention, care and support services for HIV and HCV infected populations based on the evolving syndemics of infections and social conditions which vary across groups.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0183609PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5568727PMC
October 2017

Late hepatitis B and C diagnosis in relation to disease decompensation and hepatocellular carcinoma development.

J Hepatol 2017 11 4;67(5):909-917. Epub 2017 Jul 4.

BC Centre for Disease Control, 655 West 12th Avenue, Vancouver, British Columbia V5Z 4R4, Canada; University of British Columbia, 2329 West Mall, Vancouver, British Columbia V6T 1Z4, Canada. Electronic address:

Background & Aims: We measured the timing of hepatitis B virus (HBV) and hepatitis C virus (HCV) diagnoses relative to the detection of decompensated cirrhosis (DC) and hepatocellular carcinoma (HCC) as an indicator of late hepatitis diagnosis.

Methods: HBV and HCV diagnoses were defined relative to the diagnosis of DC or HCC such that HBV/HCV diagnoses within two years prior, at the time of or after HCC or DC diagnosis were considered late. We performed multivariable logistic regression to assess factors associated with late HBV/HCV diagnoses among those with DC or HCC.

Results: From 1990 to 2012, 778/32,664 HBV cases (2.4%) and 3,925/57,866 HCV cases (6.8%) developed DC while 628/32,644 HBV cases (1.9%) and 902/57,866 HCV cases (1.6%) developed HCC. Among HBV and HCV cases with DC, 49% and 40% respectively were late diagnoses, as were 46% and 31% of HBV and HCV cases with HCC, respectively. HBV late diagnosis declined from 100% in 1992 to 11% and 26% in 2011, while HCV late diagnosis declined from 100% in 1992 to 16% and 14% in 2011 for DC and HCC respectively. In multivariable modelling, late HBV diagnosis was associated with mental illness and a fewer number of physician visits in the five years prior to HBV diagnosis. Late HCV diagnosis was also associated with fewer physician visits, while those with illicit drug use were less likely to be diagnosed late.

Conclusions: The proportion of late diagnoses has declined over time. People with better engagement with the healthcare system and with risk activities were diagnosed earlier. Lay summary: Late diagnosis of HBV and HCV represents a missed opportunity to reduce the risk of serious liver disease. Our results identify successes in earlier diagnosis over time using risk-based testing as well as groups that are being missed for screening such as those who do not see a physician regularly and those with serious mental illness.
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http://dx.doi.org/10.1016/j.jhep.2017.06.025DOI Listing
November 2017

Long-term effect of sustained virological response on hepatocellular carcinoma in patients with hepatitis C in Canada.

J Hepatol 2017 03 4;66(3):504-513. Epub 2016 Nov 4.

British Columbia Centre for Disease Control, Vancouver, BC, Canada; Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC, Canada.

Background & Aims: Evidence is limited on hepatocellular carcinoma (HCC) risk after sustained virological response (SVR) to interferon-based treatment of hepatitis C virus (HCV) infection. We evaluated the effect of SVR on the risk of HCC and estimated its incidence in post-SVR HCV patients from a large population-based Canadian cohort.

Methods: The British Columbia Hepatitis Testers Cohort includes individuals tested for HCV between 1990-2013 linked with data on their medical visits, hospitalizations, cancers, prescription drugs and mortality. Patients receiving interferon-based HCV treatments were followed from the end of treatment to HCC diagnosis, death or December 31, 2012. We examined HCC risk among those who did and did not achieve SVR using multivariable proportional hazard models with the Fine and Gray modification for competing risks.

Results: Of 8147 individuals who received HCV treatment and were eligible for analysis, 4663 (57%) achieved SVR and 3484 (43%) did not. Each group was followed for a median of 5.6years (range: 0.5-12.9) for an HCC incidence rate of 1.1/1000 person-years (PY) among the SVR and 7.2/1000 PY among the no SVR group. The HCC incidence rate was higher among those with cirrhosis (SVR: 6.4, no SVR: 21.0/1000 PY). In the multivariable model, SVR was associated with a lower HCC risk (subdistribution hazard ratio [SHR]=0.20, 95% CI: 0.13-0.3), while cirrhosis (SHR=2.61, 95% CI: 1.68-4.04), age ⩾50years, being male and genotype 3 infection were associated with a higher HCC risk. Among those who achieved SVR, cirrhosis, age ⩾50years and being male were associated with a higher HCC risk.

Conclusion: SVR after interferon-based treatment substantially reduces but does not eliminate HCC risk, which is markedly higher among those with cirrhosis and age ⩾50years at treatment initiation. Treatment of patients at an advanced fibrosis stage with new highly effective drugs will warrant continued surveillance for HCC post-SVR.

Lay Summary: We assessed the effect of successful hepatitis C treatment with older interferon-based treatment on the occurrence of liver cancer (hepatocellular carcinoma) and found that successful treatment prevents liver cancer. However, more people with cirrhosis and older age continued to develop liver cancer after successful treatment. Thus, treatment with new drugs among those with cirrhosis will require continued monitoring for liver cancer.
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http://dx.doi.org/10.1016/j.jhep.2016.10.028DOI Listing
March 2017