Publications by authors named "Naveed Z Janjua"

83 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

Opportunities to enhance linkage to hepatitis C care among hospitalised people with recent drug dependence in New South Wales, Australia: A population-based linkage study.

Clin Infect Dis 2021 Jun 9. Epub 2021 Jun 9.

The Kirby Institute, UNSW Sydney, Sydney, Australia.

Background: People who inject drugs are at greater risk of hepatitis C virus (HCV) infection and hospitalisation, yet admissions are not utilised for HCV treatment initiation. We aimed to assess the extent to which people with HCV notification, including those with evidence of recent drug dependence, are hospitalised while eligible for direct-acting antiviral (DAA) therapy, and treatment uptake according to hospitalisation in the DAA era.

Methods: We conducted a longitudinal, population-based cohort study of people living with HCV in the DAA era (March 2016-December 2018) through analysis of linked databases in New South Wales, Australia. Kaplan Meier estimates were used to report HCV treatment uptake by frequency, length, and cause-specific hospitalisation.

Results: Among 57,467 people, 14,938 (26%) had evidence of recent drug dependence, 50% (n=7,506) of whom were hospitalised while DAA eligible. Incidence of selected cause-specific hospitalisation was highest for mental health-related (15.84 per 100 person-years [PY]), drug-related (15.20 per 100PY), and injection-related infectious disease (9.15 per 100PY) hospitalisations, and lowest for alcohol use disorder (4.58 per 100PY) and liver-related (3.13 per 100PY). 65% (n=4,898) of those hospitalised had been admitted >2 times and 46% (n=3,437) were hospitalised >7 days. By the end of 2018, DAA therapy was lowest for those hospitalised >2 times, for >7 days, and those whose first admission was for injection-related infectious disease, mental health disorders, and drug-related complications.

Conclusions: Among people who have evidence of recent drug dependence, frequent hospitalisation-particularly mental health, drug, and alcohol admissions-presents an opportunity for engagement in HCV care.
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http://dx.doi.org/10.1093/cid/ciab526DOI Listing
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

How much leeway is there to relax COVID-19 control measures?

Epidemics 2021 06 18;35:100453. Epub 2021 Mar 18.

Department of Mathematics, Simon Fraser University, Burnaby, BC, Canada; Department of Mathematics, Imperial College London, London, UK. Electronic address:

Following successful non-pharmaceutical interventions (NPI) aiming to control COVID-19, many jurisdictions reopened their economies and borders. As little immunity had developed in most populations, re-establishing higher contact carried substantial risks, and therefore many locations began to see resurgence in COVID-19 cases. We present a Bayesian method to estimate the leeway to reopen, or alternatively the strength of change required to re-establish COVID-19 control, in a range of jurisdictions experiencing different COVID-19 epidemics. We estimated the timing and strength of initial control measures such as widespread distancing and compared the leeway jurisdictions had to reopen immediately after NPI measures to later estimates of leeway. Finally, we quantified risks associated with reopening and the likely burden of new cases due to introductions from other jurisdictions. We found widely varying leeway to reopen. After initial NPI measures took effect, some jurisdictions had substantial leeway (e.g., Japan, New Zealand, Germany) with > 0.99 probability that contact rates were below 80% of the threshold for epidemic growth. Others had little leeway (e.g., the United Kingdom, Washington State) and some had none (e.g., Sweden, California). For most such regions, increases in contact rate of 1.5-2 fold would have had high (> 0.7) probability of exceeding past peak sizes. Most jurisdictions experienced June-August trajectories consistent with our projections of contact rate increases of 1-2-fold. Under such relaxation scenarios for some regions, we projected up to ∼100 additional cases if just one case were imported per week over six weeks, even between jurisdictions with comparable COVID-19 risk. We provide an R package covidseir to enable jurisdictions to estimate leeway and forecast cases under different future contact patterns. Estimates of leeway can establish a quantitative basis for decisions about reopening. We recommend a cautious approach to reopening economies and borders, coupled with strong monitoring for changes in transmission.
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http://dx.doi.org/10.1016/j.epidem.2021.100453DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7970422PMC
June 2021

Social vulnerability in persons with chronic hepatitis C virus infection is associated with a higher risk of prescription opioid use.

Sci Rep 2021 Mar 15;11(1):5883. Epub 2021 Mar 15.

Weill Cornell Medical College, New York, NY, USA.

Prescription opioid use (POU) is often a precursor to opioid use disorder (OUD) and subsequent consequences. Persons with chronic hepatitis C virus infection (CHC) may be at a higher risk of POU due to a higher comorbidity burden and social vulnerability factors. We sought to determine the burden of POU and associated risk factors among persons with CHC in the context of social vulnerability. We identified CHC persons and propensity-score matched HCV- controls in the electronically retrieved Cohort of HCV-Infected Veterans and determined the frequency of acute, episodic long-term and chronic long-term POU and the prevalence of social vulnerability factors among persons with POU. We used logistic regression analysis to determine factors associated with POU. Among 160,856 CHC and 160,856 propensity-score matched HCV-controls, acute POU was recorded in 38.4% and 38.0% (P = 0.01) respectively. Episodic long-term POU was recorded in 3.9% in each group (P = 0.5), while chronic long-term POU was recorded in 28.4% and 19.2% (P < 0.0001). CHC was associated with a higher risk of chronic long-term POU (OR 1.66, 95%CI 1.63, 1.69), but not with acute or episodic long-term POU. Black race, female sex and homelessness were associated with a higher risk of chronic long-term POU. Presence of ≥ 1 factor was associated with a higher risk of all POU patterns. Persons with CHC have more social vulnerability factors and a higher risk of chronic long-term POU. Presence of ≥ 1 social vulnerability factor is associated with a higher risk of POU. Downstream consequences of POU need further study.
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http://dx.doi.org/10.1038/s41598-021-85283-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7961056PMC
March 2021

Hepatitis C Virus Prevalence, Screening, and Treatment Among People Who Are Incarcerated in Canada: Leaving No One Behind in the Direct-Acting Antiviral Era.

Clin Liver Dis (Hoboken) 2021 Feb 28;17(2):75-80. Epub 2021 Feb 28.

Department of Medicine Division of Infectious Diseases and Chronic Viral Illness Service McGill University Montreal QC Canada.

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http://dx.doi.org/10.1002/cld.1023DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7916434PMC
February 2021

Viral hepatitis C cascade of care: A population-level comparison of immigrant and long-term residents.

Liver Int 2021 08 19;41(8):1775-1788. Epub 2021 Apr 19.

Dalla Lana School of Public Health, University of Toronto, Toronto, ON, Canada.

Background & Aims: Viral hepatitis C represents a major global burden, particularly among immigrant-receiving countries such as Canada, where knowledge of disparities in hepatitis C virus among immigrant groups for micro-elimination efforts is lacking. We quantify the hepatitis C cascades of care among immigrants and long-term residents prior to the introduction of direct-acting antiviral medications.

Methods: Using laboratory and health administrative records, we described the hepatitis C virus cascades of care in terms of diagnosis, engagement with care, treatment initiation, and clearance in Ontario, Canada (1997-2014). We stratified the cascade by immigrant and long-term resident groups and identify drivers at each stage using multivariable Poisson regression.

Results: We included 940 245 individuals in the study with an estimated hepatitis C prevalence of 167 923 (1.4%) overall, 23 759 (0.7%) among all immigrants, and 6019 (1.1%) among immigrants from hepatitis C endemic countries. Overall there were 104 616 individuals with reactive antibody results, 73 861 tested for viral RNA, 52 388 with viral RNA detected, 50 805 genotyped, 13 159 on treatment and 3919 with evidence of viral clearance. Compared to long-term residents, immigrants showed increased nucleic-acid testing (aRR: 1.09 [95%CI: 1.08, 1.10]), treatment initiation (aRR: 1.46 [95%CI: 1.38, 1.54]), and higher clearance rates (aRR: 1.07 [95%CI: 1.03, 1.11]).

Conclusions: Hepatitis C virus is more prevalent among long-term residents compared to immigrants overall, however, immigrants from endemic countries are an important subgroup to consider for future screening and linkage to care initiatives. These findings are prior to the introduction of newer medications and provide a population-based benchmark for follow-up studies and evaluation of treatment programs and surveillance activities.
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http://dx.doi.org/10.1111/liv.14840DOI Listing
August 2021

The impact of public coverage of newer hepatitis C medications on utilization, adherence, and costs in British Columbia.

PLoS One 2021 1;16(3):e0247843. Epub 2021 Mar 1.

The Centre for Health Services and Policy Research, School of Population and Public Health, The University of British Columbia, Vancouver, British Columbia, Canada.

Background: Sofosbuvir and ledipasvir-sofosbuvir are both newer direct-acting antiviral agents for the treatment of hepatitis C. The high list prices for both drugs have led to concern about the budget impact for public drug coverage programs. Therefore, we studied the impact of public prescription drug coverage for both drugs on utilization, adherence, and public and private expenditure in British Columbia, Canada.

Methods: We used provincial administrative claims data from January 2014 to June 2017 for all individuals historically tested for either hepatitis C and/or human immunodeficiency virus. Using interrupted time series analysis, we examined the impact of public insurance coverage on treatment uptake, adherence (proportion of days covered), and public and private expenditures.

Results: Over our study period, 4,462 treatment initiations were eligible for analysis (1,131 sofosbuvir and 3,331 ledipasvir-sofosbuvir, which include 19 patients initiated on both treatments). We found the start of public coverage for sofosbuvir and ledipasvir-sofosbuvir increased treatment uptake by 154%. Adherence rates were consistently high and did not change with public coverage. Finally, public expenditure increased after the policy change, and crowded out some private expenditure.

Conclusion: Public coverage for high-cost drugs for hepatitis C dramatically increased use of these drugs, but did not reduce adherence. From a health policy perspective, public payers should be prepared for increased treatment uptake following the availability of public coverage. However, they should not be concerned that populations without private insurance coverage will be less adherent and not finish their treatment course.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0247843PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7920374PMC
March 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

Validating viral hepatitis B and C diagnosis codes: a retrospective analysis using Ontario's health administrative data.

Can J Public Health 2021 Jun 8;112(3):502-512. Epub 2021 Jan 8.

Dalla Lana School of Public Health, University of Toronto, Toronto, Canada.

Objective: We aimed to determine the criterion validity of using diagnosis codes for hepatitis B virus (HBV) and hepatitis C virus (HCV) to identify infections.

Methods: Using linked laboratory and administrative data in Ontario, Canada, from January 2004 to December 2014, we validated HBV/HCV diagnosis codes against laboratory-confirmed infections. Performance measures (sensitivity, specificity, and positive predictive value) were estimated via cross-validated logistic regression and we explored variations by varying time windows from 1 to 5 years before (i.e., prognostic prediction) and after (i.e., diagnostic prediction) the date of laboratory confirmation. Subgroup analyses were performed among immigrants, males, baby boomers, and females to examine the robustness of these measures.

Results: A total of 1,599,023 individuals were tested for HBV and 840,924 for HCV, with a resulting 41,714 (2.7%) and 58,563 (7.0%) infections identified, respectively. HBV/HCV diagnosis codes ± 3 years of laboratory confirmation showed high specificity (99.9% HBV; 99.8% HCV), moderate positive predictive value (70.3% HBV; 85.8% HCV), and low sensitivity (12.8% HBV; 30.8% HCV). Varying the time window resulted in limited changes to performance measures. Diagnostic models consistently outperformed prognostic models. No major differences were observed among subgroups.

Conclusion: HBV/HCV codes should not be the only source used for monitoring the population burden of these infections, due to low sensitivity and moderate positive predictive values. These results underscore the importance of ongoing laboratory and reportable disease surveillance systems for monitoring viral hepatitis in Ontario.
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http://dx.doi.org/10.17269/s41997-020-00435-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8076389PMC
June 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

Quantifying the impact of COVID-19 control measures using a Bayesian model of physical distancing.

PLoS Comput Biol 2020 12 3;16(12):e1008274. Epub 2020 Dec 3.

Department of Mathematics, Simon Fraser University, Burnaby, Canada.

Extensive non-pharmaceutical and physical distancing measures are currently the primary interventions against coronavirus disease 2019 (COVID-19) worldwide. It is therefore urgent to estimate the impact such measures are having. We introduce a Bayesian epidemiological model in which a proportion of individuals are willing and able to participate in distancing, with the timing of distancing measures informed by survey data on attitudes to distancing and COVID-19. We fit our model to reported COVID-19 cases in British Columbia (BC), Canada, and five other jurisdictions, using an observation model that accounts for both underestimation and the delay between symptom onset and reporting. We estimated the impact that physical distancing (social distancing) has had on the contact rate and examined the projected impact of relaxing distancing measures. We found that, as of April 11 2020, distancing had a strong impact in BC, consistent with declines in reported cases and in hospitalization and intensive care unit numbers; individuals practising physical distancing experienced approximately 0.22 (0.11-0.34 90% CI [credible interval]) of their normal contact rate. The threshold above which prevalence was expected to grow was 0.55. We define the "contact ratio" to be the ratio of the estimated contact rate to the threshold rate at which cases are expected to grow; we estimated this contact ratio to be 0.40 (0.19-0.60) in BC. We developed an R package 'covidseir' to make our model available, and used it to quantify the impact of distancing in five additional jurisdictions. As of May 7, 2020, we estimated that New Zealand was well below its threshold value (contact ratio of 0.22 [0.11-0.34]), New York (0.60 [0.43-0.74]), Washington (0.84 [0.79-0.90]) and Florida (0.86 [0.76-0.96]) were progressively closer to theirs yet still below, but California (1.15 [1.07-1.23]) was above its threshold overall, with cases still rising. Accordingly, we found that BC, New Zealand, and New York may have had more room to relax distancing measures than the other jurisdictions, though this would need to be done cautiously and with total case volumes in mind. Our projections indicate that intermittent distancing measures-if sufficiently strong and robustly followed-could control COVID-19 transmission. This approach provides a useful tool for jurisdictions to monitor and assess current levels of distancing relative to their threshold, which will continue to be essential through subsequent waves of this pandemic.
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http://dx.doi.org/10.1371/journal.pcbi.1008274DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7738161PMC
December 2020

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

High hepatitis C treatment uptake among people with recent drug dependence in New South Wales, Australia.

J Hepatol 2021 Feb 12;74(2):293-302. Epub 2020 Sep 12.

The Kirby Institute, UNSW Sydney, Sydney, Australia.

Background & Aims: High HCV treatment uptake among people at most risk of transmission is essential to achieve elimination. We aimed to characterise subpopulations of people with HCV based on drug dependence, to estimate direct-acting antiviral (DAA) uptake in an unrestricted treatment era, and to evaluate factors associated with treatment uptake among people with recent drug dependence.

Methods: HCV notifications in New South Wales, Australia (1995-2017) were linked to opioid agonist therapy (OAT), hospitalisations, incarcerations, HIV notifications, deaths, and prescription databases. Drug dependence was defined as hospitalisation due to injectable drugs or receipt of OAT, with indicators in 2016-2018 considered recent. Records were weighted to account for spontaneous clearance. Logistic regression was used to analyse factors associated with treatment uptake among those with recent drug dependence.

Results: 57,467 people were estimated to have chronic HCV throughout the DAA era. Treatment uptake was highest among those with recent (47%), compared to those with distant (38%), and no (33%) drug dependence. Among those with recent drug dependence, treatment was more likely among those with HIV (adjusted odds ratio [aOR] 1.71; 95% CI 1.24-2.36), recent incarceration (aOR 1.10; 95% CI 1.01-1.19), and history of alcohol use disorder (aOR 1.22; 95% CI 1.13-1.31). Treatment was less likely among women (aOR 0.78; 95% CI 0.72-0.84), patients of Indigenous ethnicity (aOR 0.75; 95% CI 0.69-0.81), foreign-born individuals (aOR 0.86; 95% CI 0.78-0.96), those with outer-metropolitan notifications (aOR 0.90; 95% CI 0.82-0.98), HBV coinfection (aOR 0.69; 95% CI 0.59-0.80), and >1 recent hospitalisation (aOR: 0.91; 95% CI 0.84-0.98).

Conclusions: These data provide evidence of high DAA uptake among people with recent drug dependence, including those who are incarcerated. Enhancing this encouraging initial uptake among high-risk populations will be essential to achieve HCV elimination.

Lay Summary: To facilitate HCV elimination, those at highest risk of infection and transmission are a treatment priority. This study shows the successes of Australia's universal provision of DAA therapy in reducing the barriers to treatment which have historically persisted among people who inject drugs. Despite higher DAA therapy uptake among those with recent drug dependence, gaps remain. Strategies which aim to reduce marginalisation and increase treatment uptake to ensure equitable HCV elimination must be advanced.
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http://dx.doi.org/10.1016/j.jhep.2020.08.038DOI Listing
February 2021

Comparing direct acting antivirals for hepatitis C using observational data - Why and how?

Pharmacol Res Perspect 2020 10;8(5):e00650

Division of Infectious Diseases and Chronic Viral Illness Service, Department of Medicine, Glen Site, McGill University Health Centre, Montreal, QC, Canada.

The World Health Organisation's goal of hepatitis C virus (HCV) elimination by 2030 will require lower drug prices. Estimates of comparative efficacy promote competition between pharmaceutical companies but direct acting antivirals have been approved for the treatment of HCV without comparative trials. We emulated a randomized trial to answer the question of whether easy to treat patients with genotype 1 HCV could be treated with sofosbuvir/ledipasvir (SOF/LDV) rather than sofosbuvir/velpatasvir (SOF/VEL). Patients without comorbidities or end stage liver disease were selected from the British Colombia Hepatitis Testers Cohort. To create a conceptual trial, we matched each patient starting SOF/VEL (a 'case') to the patient starting SOF/LDV with the closest propensity score (a 'control'). We estimated the probability of treatment failure under a Bayesian logistic model with a random effect for each case-control set and used that model to give an estimate of a risk difference for the conceptual trial. Treatment failure was recorded for 27 of 825 (3%) cases and for 29 of 602 (5%) matched controls. Estimates from our model were treatment success rates of 97% (95% credible interval, CrI, 95%-98%) for treatment with SOF/VEL, 95% (95% CrI 93%-97%) for treatment with SOF/LDV and a risk difference between treatments of 2% (95% CrI 0%-4%). This risk difference is evidence that SOF/LDV is not inferior to SOF/VEL for easy to treat patients with genotype 1 HCV. The approach is a template for comparing drugs when there are no data from comparative trials.
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http://dx.doi.org/10.1002/prp2.650DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7507378PMC
October 2020

Estimating chronic hepatitis C prevalence in British Columbia and Ontario, Canada, using population-based cohort studies.

J Viral Hepat 2020 12 14;27(12):1419-1429. Epub 2020 Sep 14.

School of Pharmacy, University of Waterloo, Kitchener, ON, Canada.

Patients identified as having chronic hepatitis C (CHC) infection can be effectively and rapidly treated using direct-acting antiviral agents. However, there remains a substantial burden of subclinical undetected infection. This study estimates the prevalence and undiagnosed proportion of CHC in British Columbia (BC) and Ontario, Canada, using a model-based approach, informed by provincial population-level health administrative data. A two-step approach was used: Step 1) Two population-based retrospective analyses of administrative health data for a cohort of British Columbians and a cohort of Ontarians with CHC were conducted to generate population-level statistics of CHC-related health events; Step 2) using a validated natural history model of hepatitis C virus (HCV) infection, the historical prevalence of CHC was back-calculated from the data collected in Step 1. Our retrospective study found that, in BC and Ontario, the number of newly diagnosed CHC cases is declining yearly while the complications of the disease are increasing yearly. BC had a 2014 CHC prevalence of 1.04% (95% CI: 0.84%-1.44%), with 33.3% (95% CI: 25.5%-42.0%) of CHC cases undiagnosed. Ontario had a 2014 CHC prevalence of 0.91% (95% CI: 0.83%-1.02%) with 36.0% (95% CI: 31.2%-38.9%) of CHC cases undiagnosed. Our study offers robust estimates based on the integration of a validated natural history model with population-level health administrative data on HCV-related events, which can provide vital evidence for policymakers to develop appropriate policies to achieve elimination targets. Our approach can also be applied to produce robust region-specific estimates in other countries.
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http://dx.doi.org/10.1111/jvh.13373DOI Listing
December 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

Association between markers of immune response at hospital admission and COVID-19 disease severity and mortality: A meta-analysis and meta-regression.

J Med Virol 2021 02 28;93(2):1078-1098. Epub 2020 Sep 28.

Cancer Control Research, BC Cancer Research Centre, Vancouver, Canada.

Background: To determine the utility of admission laboratory markers in the assessment and prognostication of coronavirus disease-2019 (COVID-19), a systematic review and meta-analysis were conducted on the association between admission laboratory values in hospitalized COVID-19 patients and subsequent disease severity and mortality.

Material And Methods: Searches were conducted in MEDLINE, Pubmed, Embase, and the WHO Global Research Database from December 1,2019 to May 1, 2020 for relevant articles. A random effects meta-analysis was used to calculate the weighted mean difference (WMD) and 95% confidence interval (95% CI) for each of 27 laboratory markers. The impact of age and sex on WMDs was estimated using meta-regression techniques for 11 markers.

Results: In total, 64 studies met the inclusion criteria. The most marked WMDs were for neutrophils (ANC) at 3.82 × 10 /L (2.76, 4.87), lymphocytes (ALC) at -0.34 × 10 /L (-0.45, -0.23), interleukin-6 (IL-6) at 32.59 pg/mL (23.99, 41.19), ferritin at 814.14 ng/mL (551.48, 1076.81), C-reactive protein (CRP) at 66.11 mg/L (52.16, 80.06), D-dimer at 5.74 mg/L (3.91, 7.58), LDH at 232.41 U/L (178.31, 286.52), and high sensitivity troponin I at 90.47 pg/mL (47.79, 133.14) when comparing fatal to nonfatal cases. Similar trends were observed comparing severe to non-severe groups. There were no statistically significant associations between age or sex and WMD for any of the markers included in the meta-regression.

Conclusion: The results highlight that hyper inflammation, blunted adaptive immune response, and intravascular coagulation play key roles in the pathogenesis of COVID-19. Markers of these processes are good candidates to identify patients for early intervention and, importantly, are likely reliable regardless of age or sex in adult patients.
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http://dx.doi.org/10.1002/jmv.26411DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7436507PMC
February 2021

Hospital Costs of Injection Drug Use in Florida.

Clin Infect Dis 2021 02;72(3):499-502

Department of Medicine, University of Miami Miller School of Medicine, Miami, Florida, USA.

People who inject drugs (PWID) experience significant injection-related infections (IRIs) at significant healthcare system cost. This study used and validated an algorithm based on the International Classification of Diseases, Tenth Revision, to estimate hospitalized PWID populations, assess the total statewide morbidity for IRIs among PWID, and calculate associated costs of care.
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http://dx.doi.org/10.1093/cid/ciaa823DOI Listing
February 2021

Assessment of Treatment Strategies to Achieve Hepatitis C Elimination in Canada Using a Validated Model.

JAMA Netw Open 2020 05 1;3(5):e204192. Epub 2020 May 1.

British Columbia Centre for Disease Control, Vancouver, Canada.

Importance: Achievement of the World Health Organization (WHO) target of eliminating hepatitis C virus (HCV) by 2030 will require an increase in key services, including harm reduction, HCV screening, and HCV treatment initiatives in member countries. These data are not available for Canada but are important for informing a national HCV elimination strategy.

Objective: To use a decision analytical model to explore the association of different treatment strategies with HCV epidemiology and HCV-associated mortality in Canada and to assess the levels of service increase needed to meet the WHO elimination targets by 2030.

Design, Setting, And Participants: Study participants in this decision analytical model included individuals with hepatitis C virus infection in Canada. Five HCV treatment scenarios (optimistic, very aggressive, aggressive, gradual decrease, and rapid decrease) were applied using a previously validated Markov-type mathematical model. The optimistic and very aggressive treatment scenarios modeled a sustained annual treatment of 10 200 persons and 14 000 persons, respectively, from 2018 to 2030. The aggressive, gradual decrease, and rapid decrease scenarios assessed decreases in treatment uptake from 14 000 persons to 10 000 persons per year, 12 000 persons to 8500 persons per year, and 12 000 persons to 4500 persons per year, respectively, between 2018 and 2030.

Main Outcomes And Measures: Hepatitis C virus prevalence and HCV-associated health outcomes were assessed for each of the 5 treatment scenarios with the goal of identifying strategies to achieve HCV elimination by 2030.

Results: An estimated mean 180 142 persons (95% CI, 122 786-196 862 persons) in Canada had chronic HCV infection at the end of 2017. The optimistic and gradual decrease scenarios estimated a decrease in HCV prevalence from 180 142 persons to 37 246 persons and 37 721 persons, respectively, by 2030. Relative to 2015, this decrease in HCV prevalence was associated with 74%, 69%, and 69% reductions in the prevalence of decompensated cirrhosis, hepatocellular carcinoma, and liver-associated mortality, respectively, leading to HCV elimination by 2030. More aggressive treatment uptake (very aggressive scenario) could result in goal achievement up to 3 years earlier than 2030, although a rapid decrease in the initiation of treatment (rapid decrease scenario) would preclude Canada from reaching the HCV elimination goal by 2030.

Conclusions And Relevance: The study findings suggest that Canada could meet the WHO goals for HCV elimination by 2030 by sustaining the current national HCV treatment rate during the next decade. This target will not be achieved if treatment uptake is allowed to decrease rapidly.
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http://dx.doi.org/10.1001/jamanetworkopen.2020.4192DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7203608PMC
May 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

Hepatitis C reinfection after successful antiviral treatment among people who inject drugs: A meta-analysis.

J Hepatol 2020 04 27;72(4):643-657. Epub 2019 Nov 27.

The Kirby Institute, UNSW Sydney, Sydney, NSW, Australia.

Background & Aims: HCV reinfection following successful treatment can compromise treatment outcomes. This systematic review assessed the rate of HCV reinfection following treatment among people with recent drug use and those receiving opioid agonist therapy (OAT).

Methods: We searched bibliographic databases and conference abstracts for studies assessing post-treatment HCV reinfection rates among people with recent drug use (injecting or non-injecting) or those receiving OAT. Meta-analysis was used to cumulate reinfection rates and meta-regression was used to explore heterogeneity across studies.

Results: Thirty-six studies were included (6,311 person-years of follow-up). The overall rate of HCV reinfection was 5.9/100 person-years (95% CI 4.1-8.5) among people with recent drug use (injecting or non-injecting), 6.2/100 person-years (95% CI 4.3-9.0) among people recently injecting drugs, and 3.8/100 person-years (95% CI 2.5-5.8) among those receiving OAT. Reinfection rates were comparable following interferon-based (5.4/100 person-years; 95% CI 3.1-9.5) and direct-acting antiviral (3.9/100 person-years; 95% CI 2.5-5.9) therapy. In stratified analysis, reinfection rates were 1.4/100 person-years (95% CI 0.8-2.6) among people receiving OAT with no recent drug use, 5.9/100 person-years (95% CI 4.0-8.6) among people receiving OAT with recent drug use, and 6.6/100 person-years (95% CI 3.4-12.7) among people with recent drug use not receiving OAT. In meta-regression analysis, longer follow-up was associated with lower reinfection rate (adjusted rate ratio [aRR] per year increase in mean/median follow-up 0.77; 95% CI 0.69-0.86). Compared with people receiving OAT with no recent drug use, those with recent drug use receiving OAT (aRR 3.50; 95% CI 1.62-7.53), and those with recent drug use not receiving OAT (aRR 3.96; 95% CI 1.82-8.59) had higher reinfection rates.

Conclusion: HCV reinfection risk following treatment was higher among people with recent drug use and lower among those receiving OAT. The lower rates of reinfection observed in studies with longer follow-up suggested higher reinfection risk early post-treatment.

Lay Summary: Our findings demonstrate that although reinfection by hepatitis C virus occurs following successful treatment in people with recent drug use, the rate of hepatitis C reinfection is lower than the rates of primary infection reported in the literature for this population - reinfection should not be used as a reason to withhold therapy from people with ongoing injecting drug use. The rate of hepatitis C reinfection was lowest among people receiving opioid agonist therapy with no recent drug use. These data illustrate that harm reduction services are required to reduce the reinfection risk, while regular post-treatment hepatitis C assessment is required for early detection and retreatment.
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http://dx.doi.org/10.1016/j.jhep.2019.11.012DOI Listing
April 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

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

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

Syndemic Characterization of HCV, HBV, and HIV Co-infections in a Large Population Based Cohort Study.

EClinicalMedicine 2018 Oct-Nov;4-5:99-108. Epub 2018 Nov 5.

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

Background: Limited data are available on HBV, HCV, and HIV co-infections and triple infection. We characterized co-occurrence of HIV, HBV, and HCV infections at the population level in British Columbia (BC) to identify patterns of predisposing factors unique to co-infection subgroups.

Methods: We analyzed data from the BC Hepatitis Testers Cohort, which includes all individuals tested for HCV or HIV in BC between 1992 and 2013, or included in provincial public health registries of HIV, HCV, HBV, and active tuberculosis. Individuals were classified as negative, mono-, and co-infection groups based on HIV, HBV, and HCV status. We evaluated associations between risk factors (injection drug use, sexual orientation etc.) and co-infection groups using multivariate multinomial logistic regression.

Findings: Of a total of 1,376,989 individuals included in the analysis, 1,276,290 were negative and 100,699 were positive for HIV, HBV, and/or HCV. Most cases (91,399, 90.8%) were mono-infected, while 3991 (4.0%) had HBV/HCV, 670 HBV/HIV (0.7%), 3459 HCV/HIV (3.4%), and 1180 HBV/HCV/HIV (1.2%) co-infection. Risk factor and demographic distribution varied across co-infection categories. MSM classification was associated with higher odds of all HIV co-infection groups, particularly HBV/HIV (OR 6.8; 95% CI: 5.6, 8.27), while injection drug use was most strongly associated with triple infection (OR 64.19; 95% CI: 55.11, 74.77) and HIV/HCV (OR 23.23; 95% CI: 21.32, 25.31).

Interpretation: Syndemics of substance use, sexual practices, mental illness, socioeconomic marginalization, and co-infections differ among population groups, highlighting avenues for optimal composition and context for health services to meet each population's unique needs.

Funding: BC Centre for Disease Control and Canadian Institutes of Health Research.
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http://dx.doi.org/10.1016/j.eclinm.2018.10.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6537523PMC
November 2018

Assessment of the Feasibility and Cost of Hepatitis C Elimination in Pakistan.

JAMA Netw Open 2019 05 3;2(5):e193613. Epub 2019 May 3.

Houston Veterans Affairs Health Services Research and Development Center of Excellence, Michael E. DeBakey Veterans Affairs Medical Center, Houston, Texas.

Importance: Chronic hepatitis C virus (HCV) infection is a global health problem. The World Health Assembly recently pledged to eliminate HCV by 2030. However, in Pakistan, a country with one of the highest prevalence rates, the feasibility and cost of HCV elimination are not known.

Objectives: To investigate whether and under what conditions HCV elimination is feasible in Pakistan and to estimate the cost of such elimination.

Design, Setting, And Participants: This decision analytical model study used a microsimulation model of the HCV epidemic in Pakistan from 2015 to 2030. Using Pakistan-specific variables, the model simulated the landscape of HCV in Pakistan and evaluated the minimum required screening and treatment rates needed to eliminate HCV in Pakistan. The study used simulated individuals chronically infected with HCV from 2015 to 2030. The analysis was performed in 2018.

Interventions: The status quo and 7 scenarios that can lead to HCV elimination in Pakistan by 2030, which were defined by different combinations of tests for screening, detection of viremia before treatment, and confirmation of treatment response.

Main Outcomes And Measures: Temporal trends in HCV infection prevalence, mortality, and disability-adjusted life-years and total cost of HCV infection care under the status quo and scenarios that can eliminate HCV by 2030.

Results: Under the status quo, from 2015 to 2030, 1.44 million people are projected to die of HCV infection; 48% of deaths would be among people younger than 50 years. To achieve HCV elimination in Pakistan, HCV testing would need to be scaled up to at least 25 million people to diagnose 900 000 persons and treatment to 700 000 people per year. Compared with the status quo, the elimination scenario would avert 323 000 liver-related deaths and 13.0 million HCV-associated disability-adjusted life-years from 2015 to 2030. The elimination scenario was associated with cost savings of $2.6 billion from 2018 to 2030 with use of a point-of-care test for population-wide antibody screening and detection of viremia and treatment response.

Conclusions And Relevance: Substantial scale-up of HCV testing and treatment may be essential to eliminate HCV infection in Pakistan, and such a strategy may be associated with cost savings in the near future. Although HCV elimination in Pakistan may be ambitious, strategic planning and strong support from the government may aid in its elimination.
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http://dx.doi.org/10.1001/jamanetworkopen.2019.3613DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6512462PMC
May 2019
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