British Columbia Hepatitis Testers Cohort Research Articles

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

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. Conclusion: 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.

Applying core theory and spatial analysis to identify hepatitis C virus infection "core areas" in 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 (~1.5million; 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.

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

BackgroundLimited 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. MethodsWe 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. FindingsOf 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). InterpretationSyndemics 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. FundingBC Centre for Disease Control and Canadian Institutes of Health Research.

Differential spatial distribution of hepatitis B virus by ethnicity in British Columbia, Canada: Expanded role of a large administrative cohort

IntroductionMost chronic hepatitis B virus (HBV) infections in Canada are diagnosed among immigrants from endemic countries and lack traditional risk factors while most acute infections are usually diagnosed in Caucasian population with co-occurring risk factors. Thus, understanding geographical distribution of HBV infection by ethnicity could inform screening and care strategies.&#x0D; Objectives and ApproachWe identified geographic clusters of HBV infection in British Columbia by ethnicity during the years 1990-2015 using the BC Hepatitis Testers Cohort (BC-HTC). The BC-HTC includes ~1.7 million individuals tested for HCV or HIV at the BC Public Health Laboratory or reported as a case of HCV, HIV, or HBV linked to healthcare administrative databases. We plotted maps of HBV diagnoses (acute and chronic) rate at the Dissemination Area level between 1990-2015 stratified by ethnicity and compared this distribution with injection drug use (IDU) distribution in BC.&#x0D; ResultsThe distribution of HBV varied considerably by ethnicity. From 1990 to 2015, a higher rate of HBV infection was found among East Asians and Caucasians followed by South Asians and other ethnicities. East Asians with highest rates were mainly concentrated in Vancouver city, Burnaby and Richmond (Metro Vancouver) while South Asians with highest rates were mostly concentrated in urban areas in Surrey and Abbotsford. Caucasians with higher rates were clustered in Downtown Eastside in Vancouver, Surrey and Abbotsford (Metro Vancouver) and urban areas in Greater Victoria (Vancouver Island), Prince George (Northern BC) and Kamloops (Interior BC). The distribution of IDU closely followed the distribution of HBV among Caucasians but did not align with other ethnic groups.&#x0D; Conclusion/ImplicationsResults highlight distinct areas of HBV infection clustering by ethnicity, which differ from areas with high IDU distribution except in Caucasians. Findings support ethnicity-based HBV screening/prevention and care services to areas with immigrants from HBV-endemic countries and integrated HBV and harm reduction services for early diagnosis and treatment in Caucasians.

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

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 46666 HCV-infected individuals, there were 12527 (26.8%) SC; 24794 (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.

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

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. 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. 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. 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. 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.

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

BackgroundUnderstanding 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 methodsThe 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.ResultsOf 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.ConclusionInjection-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.

LBP‐016: Lost to follow‐up among Ledipasvir/sofosbuvir treated patients in Canada: The BC Hepatitis Testers Cohort

LBP‐016: Lost to follow‐up among Ledipasvir/sofosbuvir treated patients in Canada: The BC Hepatitis Testers Cohort

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

BackgroundLarge 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. MethodsThe 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. ResultsSensitivity 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). ConclusionAlgorithms 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.

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

BackgroundCo-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.MethodsThe 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+.ResultsOf 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.ConclusionsThese 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.

Shift in disparities in hepatitis C treatment from interferon to DAA era: A population-based cohort study.

We evaluated the shift in the characteristics of people who received interferon-based hepatitis C virus (HCV) treatments and those who received recently introduced direct-acting antivirals (DAAs) in British Columbia (BC), Canada. The BC Hepatitis Testers Cohort includes 1.5 million individuals tested for HCV or HIV, or reported cases of hepatitis B and active tuberculosis in BC from 1990 to 2013 linked to medical visits, hospitalization, cancer, prescription drugs and mortality data. This analysis included all patients who filled at least one prescription for HCV treatment until 31 July 2015. HCV treatments were classified as older interferon-based treatments including pegylated interferon/ribavirin (PegIFN/RBV) with/without boceprevir or telaprevir, DAAs with RBV or PegIFN/RBV, and newer interferon-free DAAs. Of 11886 people treated for HCV between 2000 and 2015, 1164 (9.8%) received interferon-free DAAs (ledipasvir/sofosbuvir: n=1075; 92.4%), while 452 (3.8%) received a combination of DAAs and RBV or PegIFN/RBV. Compared to those receiving interferon-based treatment, people with HIV co-infection (adjusted odds ratio [aOR]: 2.96, 95% CI: 2.31-3.81), cirrhosis (aOR: 1.77, 95% CI: 1.45-2.15), decompensated cirrhosis (aOR: 1.72, 95% CI: 1.31-2.28), diabetes (aOR: 1.30, 95% CI: 1.10-1.54), a history of injection drug use (aOR: 1.34, 95% CI: 1.09-1.65) and opioid substitution therapy (aOR: 1.30, 95% CI: 1.01-1.67) were more likely to receive interferon-free DAAs. Socio-economically marginalized individuals were significantly less likely (most deprived vs most privileged: aOR: 0.71, 95% CI: 0.58-0.87) to receive DAAs. In conclusion, there is a shift in prescription of new HCV treatments to previously excluded groups (eg HIV-co-infected), although gaps remain for the socio-economically marginalized populations.

Incidence, risk factors, and prevention of hepatitis C reinfection: a population-based cohort study

People remain at risk of reinfection with hepatitis C virus (HCV), even after clearance of the primary infection. We identified factors associated with HCV reinfection risk in a large population-based cohort study in British Columbia, Canada, and examined the association of opioid substitution therapy and mental health counselling with reinfection. We obtained data from the British Columbia Hepatitis Testers Cohort, which includes all individuals tested for HCV or HIV at the British Columbia Centre for Disease Control Public Health Laboratory during 1990-2013 (when data were available). We defined cases of HCV reinfection as individuals with a positive HCV PCR test after either spontaneous clearance (two consecutive negative HCV PCR tests spaced ≥28 days apart without treatment) or a sustained virological response (SVR; two consecutive negative HCV PCR tests spaced ≥28 days apart 12 weeks after completing interferon-based treatment). We calculated incidence rates of HCV reinfection (per 100 person-years of follow-up) and corresponding 95% CIs assuming a Poisson distribution, and used a multivariable Cox proportional hazards model to examine reinfection risk factors (age, birth cohort, sex, year of HCV diagnosis, HCV clearance type, HIV co-infection, number of mental health counselling visits, levels of material and social deprivation, and alcohol and injection drug use), and the association of opioid substitution therapy and mental health counselling with HCV reinfection among people who inject drugs (PWID). 5915 individuals with HCV were included in this study after clearance (3690 after spontaneous clearance and 2225 after SVR). 452 (8%) patients developed reinfection; 402 (11%) after spontaneous clearance and 50 (2%) who had achieved SVR. Individuals were followed up for a median of 5·4 years (IQR 2·9-8·7), and the median time to reinfection was 3·0 years (1·5-5·4). The overall incidence rate of reinfection was 1·27 (95% CI 1·15-1·39) per 100 person-years of follow-up over a total of 35 672 person-years, with significantly higher rates in the spontaneous clearance group (1·59, 1·44-1·76) than in the SVR group (0·48, 0·36-0·63). With the adjusted Cox proportional hazards model, we noted higher reinfection risks in the spontaneous clearance group (adjusted hazard ratio [HR] 2·71, 95% CI 2·00-3·68), individuals co-infected with HIV (2·25, 1·78-2·85), and PWID (1·53, 1·21-1·92) than with other reinfection risk factors. Among the 1604 PWID with a current history of injection drug use, opioid substitution therapy was significantly associated with a lower risk of reinfection (adjusted HR 0·73, 95% CI 0·54-0·98), as was engagement with mental health counselling services (0·71, 0·54-0·92). The incidence of HCV reinfection was higher among HIV co-infected individuals, those who spontaneously cleared HCV infection, and PWID. HCV treatment complemented with opioid substitution therapy and mental health counselling could reduce HCV reinfection risk among PWID. These findings support policies of post-clearance follow-up of PWID, and provision of harm-reduction services to minimise HCV reinfection and transmission. The British Columbia Centre for Disease Control and the Canadian Institutes of Health Research.

Role of primary T-cell immunodeficiency and hepatitis B coinfection on spontaneous clearance of hepatitis C: The BC Hepatitis Testers Cohort.

T-cell host immune response against hepatitis C virus (HCV) has been suggested to play an important role in determining HCV infection outcome. However, data from human studies are not available. This study examined the effect of primary T-cell deficiency along with other factors on the spontaneous clearance of HCV in a large population-based cohort in British Columbia, Canada. The BC Hepatitis Testers Cohort includes all individuals tested for HCV in BC in 1990-2013 linked with data on their medical visits, hospitalizations and prescription drugs. HCV-positive individuals with at least one valid HCV PCR test on/after HCV diagnosis (n=46783) were included in this study. To examine factors associated with the spontaneous clearance of HCV, multivariable logistic regression was fitted on the full sample, and Cox proportional hazards model on the HCV seroconverters. Spontaneous clearance was observed in 25.1% (n=11737) of those tested for HCV. After adjusting for potential confounders, the odds of spontaneous clearance of HCV was lower in people with primary T-cell immunodeficiency (adjusted odds ratio [aOR]: 0.55, 95% CI: 0.32-0.94), and higher in females (aOR: 1.61, 95% CI: 1.54-1.68) and in those coinfected with HBV (aOR: 2.31, 95% CI: 1.93-2.77). Similar results were observed in HCV seroconverters except HBV coinfection was not significant. In conclusion, primary T-cell immunodeficiency is associated with a lower spontaneous clearance of HCV while female sex and coinfection with HBV are associated with a higher spontaneous clearance.

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

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. 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. 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. 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. 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.

The Population Level Cascade of Care for Hepatitis C in British Columbia, Canada: The BC Hepatitis Testers Cohort (BC-HTC)

BackgroundPopulation-level monitoring of hepatitis C virus (HCV) infected people across the cascade of care identifies gaps in access and engagement in care and treatment. We characterized a population-level cascade of care for HCV in British Columbia (BC), Canada and identified factors associated with leakage at each stage. MethodsThe BC Hepatitis Testers Cohort (BC-HTC) includes 1.5million individuals tested for HCV, HIV, reported cases of hepatitis B, and active tuberculosis in BC from 1990 to 2013 linked to medical visits, hospitalizations, cancers, prescription drugs and mortality data. We defined six HCV cascade of care stages: 1) estimated population prevalence; 2) HCV diagnosed; 3) HCV RNA tested; 4) genotyped; 5) initiated treatment; and 6) achieved sustained virologic response (SVR). ResultsWe estimated that 73,203 people were HCV antibody positive in BC in 2012 (undiagnosed: 18,301, 25%; diagnosed: 54,902, 75%). Of these, 56%(40,656) had HCV RNA testing; 34%(26,300) were genotyped; 12%( 8532 ) had received interferon-based therapy and 7%(5197) had SVR. Males, older birth cohorts, and HBV coinfected were less likely to undergo HCV RNA testing. Among those with chronic HCV infection, 32% had received liver-related care. Retention in liver care was more likely in those with HIV, cirrhosis, and drug/alcohol use and less likely in males and HBV coinfected. ConclusionsAlthough there are gaps in HCV RNA testing and genotyping after HCV diagnosis, the major gap in the cascade of care was low treatment initiation. People with comorbidities progressed through the cascade of testing and care but few received treatment.

Twin epidemics of new and prevalent hepatitis C infections in Canada: BC Hepatitis Testers Cohort.

BackgroundWe characterized the twin epidemics of new and prevalent hepatitis C virus (HCV) infections in British Columbia, Canada to inform prevention, care and treatment programs.MethodsThe BC Hepatitis Testers Cohort (BC-HTC) includes individuals tested for HCV, HIV or reported as a case of HBV, HCV, HIV or active TB between 1990–2013 linked with data on their medical visits, hospitalizations, cancers, prescription drugs and mortality. Prevalent infection was defined as being anti-HCV positive at first test. Those with a negative test followed by a positive test were considered seroconverters or new infections.ResultsOf 1,132,855 individuals tested for HCV, 64,634 (5.8 %) were positive and an additional 3092 cases tested positive elsewhere for a total of 67,726. Of 55,781 HCV positive individuals alive at the end of 2013, 7064 were seroconverters while 48,717 had prevalent infection at diagnosis. The HCV positivity rate (11.2 %) was highest in birth cohort 1945–1964 which declined over time. New infections were more likely to be male, 15–34 years of age (born 1965-1984), HIV- or HBV-coinfected, socioeconomically disadvantaged, have problematic drug and alcohol use and a mental health illness. The profile was similar for individuals with prevalent infection, except for lower odds of HBV-coinfection, major mental health diagnoses and birth cohort >1975.ConclusionsThe HCV positivity rate is highest in birth cohort 1945–1964 which represents most prevalent infections. New infections occur in younger birth cohorts who are commonly coinfected with HIV and/or HBV, socioeconomically marginalized, and living with mental illness and addictions.Electronic supplementary materialThe online version of this article (doi:10.1186/s12879-016-1683-z) contains supplementary material, which is available to authorized users.

Can the Renin-Angiostensin System (RAS) Be Modulated to Attenuate Fibrosis in Chronic Hepatitis C (CHC) Viral Infection?

Population-level monitoring of hepatitis C virus (HCV) infected people across the cascade of care identifies gaps in access and engagement in care and treatment. We characterized a population-level cascade of care for HCV in British Columbia (BC), Canada and identified factors associated with leakage at each stage.The BC Hepatitis Testers Cohort (BC-HTC) includes 1.5 million individuals tested for HCV, HIV, reported cases of hepatitis B, and active tuberculosis in BC from 1990 to 2013 linked to medical visits, hospitalizations, cancers, prescription drugs and mortality data. We defined six HCV cascade of care stages: 1) estimated population prevalence; 2) HCV diagnosed; 3) HCV RNA tested; 4) genotyped; 5) initiated treatment; and 6) achieved sustained virologic response (SVR).We estimated that 73,203 people were HCV antibody positive in BC in 2012 (undiagnosed: 18,301, 25%; diagnosed: 54,902, 75%). Of these, 56%(40,656) had HCV RNA testing; 34%(26,300) were genotyped; 12%( 8532 ) had received interferon-based therapy and 7%(5197) had SVR. Males, older birth cohorts, and HBV coinfected were less likely to undergo HCV RNA testing. Among those with chronic HCV infection, 32% had received liver-related care. Retention in liver care was more likely in those with HIV, cirrhosis, and drug/alcohol use and less likely in males and HBV coinfected.Although there are gaps in HCV RNA testing and genotyping after HCV diagnosis, the major gap in the cascade of care was low treatment initiation. People with comorbidities progressed through the cascade of testing and care but few received treatment.