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.
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.
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.
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.
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.
Abstract
Background
Microelimination of hepatitis C virus (HCV) among people living with human immunodeficiency virus (HIV) may be feasible in Australia, given unrestricted access to direct-acting ...antiviral (DAA) therapy from 2016. Our aim was to evaluate progress towards elimination goals within HIV/HCV-coinfected adults in Australia following universal DAA access.
Methods
The CEASE prospective cohort study enrolled adults with HIV/HCV, irrespective of viremic status, from 14 primary and tertiary clinics in Australia. Annual and cumulative HCV treatment uptake, outcome, and HCV RNA prevalence were evaluated, with follow-up through May 2018 (median follow-up, 2.63 years). Factors associated with DAA uptake were analyzed.
Results
Between July 2014 and March 2017, 402 participants who were HIV/HCV antibody positive were enrolled (95% male 80% gay and bisexual men,, 13% cirrhosis, 80% history of injecting drug use 39% currently injecting). Following universal DAA access, annual HCV treatment uptake in those eligible increased from 7% and 11% per year in 2014 and 2015, respectively, to 80% in 2016. By 2018, cumulative HCV treatment uptake in those ever eligible for treatment was 91% (336/371). HCV viremic prevalence declined from 82% (95% CI, 78–86%) in 2014 to 8% (95% CI, 6–12%) in 2018. Reinfection was reported in only 5 participants for a reinfection incidence of 0.81 per 100 person-years (95% CI, 0.34–1.94).
Conclusions
High uptake and effectiveness of unrestricted DAA therapy in Australia have permitted rapid treatment scale-up, with a dramatic reduction in HCV infection burden and low reinfection rate among people living with HIV, suggesting that microelimination is feasible.
Clinical Trials Registration
NCT02102451.
Linkage to care and unrestricted access to direct-acting antiviral therapy have facilitated rapid hepatitis C virus (HCV) treatment scale-up among people living with human immunodeficiency virus in Australia, reducing HCV viremic prevalence, and highlighting the potential population-level impact of HCV treatment-as-prevention.
Abstract
Micro-elimination of hepatitis C virus (HCV) infection through rapid uptake of government-funded direct-acting antiviral therapy within an Australian prison setting is demonstrated. During a ...22-month period, 119 patients initiated treatment for chronic HCV infection, with HCV in-prison viremic prevalence declining from 12% to 1%.
We evaluated the effect of direct-acting antiviral (DAA)-induced sustained virologic response (SVR) on all-cause, liver- and drug-related mortality in a population-based cohort in British Columbia, ...Canada.
We used data from the British Columbia Hepatitis Testers Cohort, which includes people tested for 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 to balance the baseline profile of treated and untreated individuals and performed multivariable proportional hazard modelling to assess the effect of DAAs on mortality.
Our cohort comprised 10,851 people treated with DAAs (SVR 10,426 96%, no-SVR: 425) and 10,851 matched untreated individuals. Median follow-up time was 2.2 years (IQR 1.3–3.6; maximum 6.2). The all-cause mortality rate was 19.5/1,000 person-years (PY) among the SVR group (deaths = 552), 86.5/1,000 PY among the no-SVR group (deaths = 96), and 99.2/1,000 PY among the untreated group (deaths = 2,133). 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- (adjusted 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.
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 who inject drugs.
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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•Chronic HCV is associated with a higher risk of mortality.•SVR from DAAs was associated with a significant reduction in the risk of all-cause, liver- and drug-related mortality.•Older age and cirrhosis were associated with higher risk of liver-related mortality.•Younger age, injection drug use, and problematic alcohol use were associated with higher risk of drug-related mortality.
We investigated the impacts of the COVID-19 pandemic on hepatitis C (HCV) treatment initiation, including by birth cohort and injection drug use status, in British Columbia (BC), Canada. Using ...population data from the BC COVID-19 Cohort, we conducted interrupted time series analyses, estimating changes in HCV treatment initiation following the introduction of pandemic-related policies in March 2020. The study included a pre-policy period (April 2018 to March 2020) and three follow-up periods (April to December 2020, January to December 2021, and January to December 2022). The level of HCV treatment initiation decreased by 26% in April 2020 (rate ratio 0.74, 95% confidence interval CI 0.60 to 0.91). Overall, no statistically significant difference in HCV treatment initiation occurred over the 2020 and 2021 post-policy periods, and an increase of 34.4% (95% CI 0.6 to 75.8) occurred in 2022 (equating to 321 additional people initiating treatment), relative to expectation. Decreases in HCV treatment initiation occurred in 2020 for people born between 1965 and 1974 (25.5%) and people who inject drugs (24.5%), relative to expectation. In summary, the pandemic was associated with short-term disruptions in HCV treatment initiation in BC, which were greater for people born 1965 to 1974 and people who inject drugs.
To evaluate immune responses to COVID-19 vaccines in adults aged 50 years and older, spike protein (S)-specific antibody concentration, avidity, and function (via angiotensin-converting enzyme 2 ...(ACE2) inhibition surrogate neutralization and antibody dependent cellular phagocytosis (ADCP)), as well as S-specific T cells were quantified via activation induced marker (AIM) assay in response to two-dose series. Eighty-four adults were vaccinated with either: mRNA/mRNA (mRNA-1273 and/or BNT162b2); ChAdOx1-S/mRNA; or ChAdOx1-S/ChAdOx1-S. Anti-S IgG concentrations, ADCP scores and ACE2 inhibiting antibody concentrations were highest at one-month post-second dose and declined by four-months post-second dose for all groups. mRNA/mRNA and ChAdOx1-S/mRNA schedules had significantly higher antibody responses than ChAdOx1-S/ChAdOx1-S. CD8
T-cell responses one-month post-second dose were associated with increased ACE2 surrogate neutralization. Antibody avidity (total relative avidity index) did not change between one-month and four-months post-second dose and did not significantly differ between groups by four-months post-second dose. In determining COVID-19 correlates of protection, a measure that considers both antibody concentration and avidity should be considered.
Abstract
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 Hepatitis Testers Cohort was used for this study, which includes all people tested for or diagnosed with HCV in British Columbia, 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
In total, 13 803 PWUD with chronic HCV were included in this study. Among those currently on OAT at the end of the study period, 47% (2704/5770) had started HCV treatment, whereas 22% (1778/8033) of those not currently on OAT had 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% confidence interval {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.
In this retrospective longitudinal cohort study among 13 803 people who use drugs who were confirmed to have chronic hepatitis C virus (HCV) infection in British Columbia, Canada; current opioid agonist therapy was associated with higher likelihood of HCV treatment initiation.
The true severity of infection due to COVID-19 is under-represented because it is based on only those who are tested. Although nucleic acid amplifications tests (NAAT) are the gold standard for ...COVID-19 diagnostic testing, serological assays provide better population-level SARS-CoV-2 prevalence estimates. Implementing large sero-surveys present several logistical challenges within Canada due its unique geography including rural and remote communities. Dried blood spot (DBS) sampling is a practical solution but comparative performance data on SARS-CoV-2 serological tests using DBS is currently lacking. Here we present test performance data from a well-characterized SARS-CoV-2 DBS panel sent to laboratories across Canada representing 10 commercial and 2 in-house developed tests for SARS-CoV-2 antibodies. Three commercial assays identified all positive and negative DBS correctly corresponding to a sensitivity, specificity, positive predictive value, and negative predictive value of 100% (95% CI = 72.2, 100). Two in-house assays also performed equally well. In contrast, several commercial assays could not achieve a sensitivity greater than 40% or a negative predictive value greater than 60%. Our findings represent the foundation for future validation studies on DBS specimens that will play a central role in strengthening Canada's public health policy in response to COVID-19.
Abstract We assessed the impact of the COVID‐19 pandemic on hepatocellular carcinoma (HCC) surveillance among individuals with HCV diagnosed with cirrhosis in British Columbia (BC), Canada. We used ...data from the British Columbia Hepatitis Testers Cohort (BC‐HTC), including all individuals in the province tested for or diagnosed with HCV from 1 January 1990 to 31 December 2015, to assess HCC surveillance. To analyse the impact of the pandemic on HCC surveillance, we used pre‐policy (January 2018 to February 2020) and post‐policy (March to December 2020) periods. We conducted interrupted time series (ITS) analysis using a segmented linear regression model and included first‐order autocorrelation terms. From January 2018 to December 2020, 6546 HCC screenings were performed among 3429 individuals with HCV and cirrhosis. The ITS model showed an immediate decrease in HCC screenings in March and April 2020, with an overall level change of −71 screenings 95% confidence interval (CI): −105.9, −18.9. We observed a significant decrease in HCC surveillance among study participants, regardless of HCV treatment status and age group, with the sharpest decrease among untreated HCV patients. A recovery of HCC surveillance followed this decline, reflected in an increasing trend of 7.8 screenings (95% CI: 0.6, 13.5) per month during the post‐policy period. There was no level or trend change in the number of individuals diagnosed with HCC. We observed a sharp decline in HCC surveillance among people living with HCV and cirrhosis in BC following the COVID‐19 pandemic control measures. HCC screening returned to pre‐pandemic levels by mid‐2020.
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