Traumatic Encephalocele in a 16-Year-Old Male: A Rare Phenomenon.

The term "encephalocele" refers to the herniation of brain tissue caused by a cranial bone defect. It could be congenital, traumatic, neoplastic, or arise spontaneously. The possibility of traumatic fronto-ethmoidal encephalocele should be considered in patients who have experienced trauma. We report a case of a 16-year-old male with a recent history of a bike accident presented with sudden unilateral rhinorrhea. Non-contrast computed tomography (NCCT) brain was done, which showed findings of left fronto-ethmoidal encephalocele. The patient was managed with single-staged surgery without any complications.

Severe acute hepatitis of unknown etiology in a large cohort of children.

BACKGROUND: We evaluated the proportion, clinical features, and outcomes of previously healthy children presenting to a large Canadian quaternary pediatric center with severe acute hepatitis of unknown etiology. METHODS: All patients with serum alanine aminotransferase (ALT) > 500 U/L or aspartate aminotransferase (AST) > 500 U/L between June 1, 2018, and May 31, 2022, at The Hospital for Sick Children, were identified. Subjects with only AST > 500 U/L were excluded. Clinical characteristics, investigations, and outcomes for patients without clear etiology for ALT > 500 U/L (severe acute hepatitis of unknown etiology) for our study period and from October 1 to May 31 of each year 2018-2021 were reviewed. RESULTS: Of 977 patients with ALT/AST> 500 U/L, 720 had only ALT > 500 U/L. We excluded age below 6 months (n = 99) or above 16 years (n = 66), known pre-existing liver conditions (n = 66), and ALT > 500 U/L in already admitted patients (n = 151). Among the remaining 338 children with ALT > 500 U/L at presentation, an etiology was identified in 303 subjects. 33 (9.8%) children [median age 6.1 y (range 0.5-15.5); 61% male] were confirmed as severe acute hepatitis of unknown etiology. Twenty patients (60.6%) were tested for blood adenovirus by PCR, and 1 (5%) was positive (serotype B7). Liver tissue specimens from 18 patients revealed no evidence of viral inclusions or adenovirus. Twelve (36.3%) presented with pediatric acute liver failure, with 8 (24.2%) requiring liver transplantation. There were no deaths. Hepatitis-associated aplastic anemia occurred in 5 (15%) patients. CONCLUSIONS: Of children presenting with severe acute hepatitis to a quaternary children's hospital over a 48-month period, 9.8% had unknown etiology with no change over time. Liver transplantation remains an important treatment strategy for those presenting with pediatric acute liver failure phenotype. The frequency of cases associated with human adenovirus infection was noncontributory.

Province-to-province variability in hepatitis C testing, care, and treatment across Canada.

Background: Few countries have implemented the necessary policy changes to reduce the number of steps in the cascade of care to achieve hepatitis C virus (HCV) elimination, including Canada. The aim of this study was to describe and compare legislation, scope of practice, and policy as it relates to the provision of HCV care in each province. Methods: We reviewed grey literature and regulatory and legislative documents which affect various aspects of the HCV cascade of care. Findings were verified by content experts. Results: HCV RNA reflex testing ensures those that are antibody positive get an HCV RNA test; however only 80% of provinces have reflex test. Point-of-care antibody testing can be offered in most community non-health care settings, yet many types of health care providers are unable to do this independently. Following a positive test, it may not be feasible to complete venipuncture; however only a single province processes HCV RNA dried blood spot cards. In many provinces, training and verification are required for novice prescribers, and in some provinces prescribing continues to be restricted to specialists. Only a single province has task-shifted treatment to a non-physician non-nurse practitioner model, where pharmacists can prescribe treatment. Finally, 80% of provinces require authorization forms, and 30% require proof of investigations for treatment. Conclusions: No single province is optimizing the use of diagnostic tools and task shifting and decreasing paperwork to expedite treatment initiation. Collaboration between provinces is needed to streamline practice, update policy, and promote equity in HCV diagnosis, care, and treatment.

Increasing linkage to hepatitis C care following trauma-informed rehabilitation: An education and quality improvement project among women.

INTRODUCTION: The on-going substance use crisis has led to unprecedented rates of hepatitis C virus (HCV) in Canada, with increasing positivity among women who use drugs (WWUD). Despite efforts to reduce barriers to HCV testing and treatment, follow-up remains a major issue. METHODS: In this quality improvement project (QIP), we partnered with a short-stay trauma-informed residential drug treatment facility specifically for WWUD, to provide an engaging peer-led HCV education session, followed by low-barrier nurse and peer-led testing and treatment. We sought to evaluate these interventions, as well as determine what factors could improve engagement after women leave. RESULTS: The session was attended by 217 participants, 130 completed the survey and 153 opted into testing. Survey results indicated that participants were highly motivated to access general care as well as HCV testing and treatment. The most frequently reported barriers to testing and treatment were a previous negative test and being asymptomatic, respectively. Follow-up facilitators included a non-judgmental provider (88%), monetary incentives (67%), follow-up phone calls (77%), e-mails (66%) and text messages (58%). Of those who were RNA positive, 5 of 13 initiated treatment on-site. By using the results of the QIP in real-time, 6 of 13 were started after leaving the centre (one pending and one lost to follow-up). DISCUSSION AND CONCLUSIONS: The implementation of co-localised peer-led testing and treatment for HCV, along with persistent follow-up efforts, led to increases in linkage to care and treatment. Co-localisation of testing and care with substance-use services, especially if residential, is a viable, low-barrier strategy for increasing linkage to care among WWUD.

Accessing hepatitis C direct acting antivirals among people living with hepatitis C: a qualitative study.

BACKGROUND: Hepatitis C is curable with direct-acting antivirals (DAAs). However, treatment uptake remains low among marginalized populations such as people who inject drugs. We sought to understand challenges to treatment uptake with DAAs among people living with hepatitis C and compare treatment experiences between people who do and do not inject prescription and/or unregulated drugs. METHODS: We conducted a qualitative study using focus groups with 23 adults aged 18 years and over who completed DAA treatment or were about to begin such treatment at the time of the study. Participants were recruited from hepatitis C treatment clinics across Toronto, Ontario. We drew upon stigma theory to interpret participants' accounts. RESULTS: Following analysis and interpretation, we generated five theoretically-informed themes characterizing the experiences of individuals accessing DAAs: "being 'worthy' of the cure", "spatially enacted stigma", "countering social and structural vulnerability: the importance of peers", "identity disruption and contagion: attaining a 'social cure'" and "challenging stigma with population-based screening". Overall, our findings suggest that structural stigma generated and reproduced through healthcare encounters limits access to DAAs among people who inject drugs. Peer-based programs and population-based screening were proposed by participants as mechanisms for countering stigma within health care settings and 'normalizing' hepatitis C among the general population. CONCLUSIONS: Despite the availability of curative therapies, access to such treatment for people who inject drugs is limited by stigma enacted in and structured within healthcare encounters. Developing novel, low-threshold delivery programs that remove power differentials and attend to the social and structural determinants of health and reinfection are needed to facilitate further scale up of DAAs and support the goal of eradicating hepatitis C as a public health threat.

Association between virtual primary care and emergency department use during the first year of the COVID-19 pandemic in Ontario, Canada.

BACKGROUND: Uptake of virtual care increased substantially during the first year of the COVID-19 pandemic. The aim of this study was to evaluate whether a shift from in-person to virtual visits by primary care physicians was associated with increased use of emergency departments among their enrolled patients. METHODS: We conducted an observational study of monthly virtual visits and emergency department visits from Apr. 1, 2020, to Mar. 31, 2021, using administrative data from Ontario, Canada. We used multivariable regression analysis to estimate the association between the proportion of a physician's visits that were delivered virtually and the number of emergency department visits among their enrolled patients. RESULTS: The proportion of virtual visits was higher among female, younger and urban physicians, and the number of emergency department visits was lower among patients of female and urban physicians. In an unadjusted analysis, a 1% increase in a physician's proportion of virtual visits was found to be associated with 11.0 (95% confidence interval [CI] 10.1-11.8) fewer emergency department visits per 1000 rostered patients. After controlling for covariates, we observed no statistically significant change in emergency department visits per 1% increase in the proportion of virtual visits (0.2, 95% CI -0.5 to 0.9). INTERPRETATION: We did not find evidence that patients substituted emergency department visits in the context of decreased availability of in-person care with their family physician during the first year of the COVID-19 pandemic. Future research should focus on the long-term impact of virtual care on access and quality of patient care.

Cost-effectiveness modelling of birth and infant dose vaccination against hepatitis B virus in Ontario from 2020 to 2050.

BACKGROUND: The World Health Organization recommends universal birth dose vaccination for hepatitis B virus (HBV), yet only 3 provinces and territories in Canada provide birth dose vaccination, and Canadian-born children in Ontario are acquiring HBV before adolescent vaccination. We sought to determine whether birth and/or infant HBV vaccination is cost-effective. METHODS: We used a dynamic HBV model that incorporates population by year, disease stage, sex and the influence of immigration to quantify the disease and economic burden of chronic HBV infection in Ontario from 2020 to 2050. We compared 4 vaccination scenarios, which included a birth dose vaccine and variations of the 2 subsequent doses (either alone or as a part of the hexavalent vaccine) and a hexavalent-only strategy in infancy with the current adolescent vaccination strategy. Our costing estimates were based on values from 2020. RESULTS: All 4 infant vaccination approaches prevented an additional 550-560 acute and 160 chronic pediatric HBV infections from 2020 to 2050 compared with adolescent vaccination. Whereas birth dose could be cost-effective, incorporating vaccination into a hexavalent vaccine was cost saving. By 2050, the hexavalent approach led to $428 000 in cost savings per disability-adjusted life years averted. INTERPRETATION: At the current prevalence in Ontario, a switch to birth dose or infant dose will be cost-effective or even cost saving. Introducing any form of infant HBV immunization in Ontario will prevent acute and chronic pediatric HBV infections.

Leveraging COVID-19 vaccination to promote hepatitis C screening.

Health care initiatives, such as hepatitis C virus (HCV) screening, have been greatly overshadowed by the corona virus disease 2019 (COVID-19) pandemic. However, COVID-19 vaccination programs also provide an opportunity to engage with a high volume of people in a health care setting. We collaborated with a large COVID vaccination center to offer HCV point-of-care testing followed by dried blood spot collection for HCV RNA. Additionally, this opportunity was used to evaluate the practical significance of a 5-minute version of the OraQuick HCV antibody test in lieu of the standard 20-minute test. We tested 2317 individuals; 31 were HCV antibody positive and six were RNA positive of which four were treated and reached sustained virological response. Over a third of those surveyed said they would not have participated had the test required 20 minutes. Conclusion : Colocalizing HCV testing and linkage to care at a COVID vaccination clinic was found to be highly feasible; furthermore, a shortened antibody test greatly improves the acceptance of testing.

A collaborative approach to hepatitis C testing in two First Nations communities of northwest Ontario.

Background: Two remote First Nations communities each collaborated with an urban-based liver clinic to organize wide-spread testing, followed by linkage to care for hepatitis C virus (HCV). Method: Involvement of community members was central to planning and conduct of the programs. Samples were obtained using dry blood spot cards (DBS). A week-long pilot study in Community 1 investigated the effectiveness of the program, using DBS. Community 2, being larger, more remote, and known to be endemic for HCV was more challenging. Three-week-long testing drives plus a stand-alone testing day were used to collect samples over 5 months. Public Health Agency (PHAC)'s National Laboratory for HIV Reference Services (NLHRS) received and tested the DBS samples for HCV and other blood-borne infections. Outcomes were measured by number of people tested, the quality of the tests, and community members' satisfaction with the program and retained knowledge about HCV, based on interviews. Results: In Community 1, 226 people were tested for HCV over 4 days. 85% agreed to human immunodeficiency virus (HIV) testing as well. In Community 2, 484 people, one-half of the adult population, were tested. Surveys of participants showed food was the most significant draw, and Facebook the most effective way to inform people of the events. Interviews with staff and participants showed a high level of satisfaction. Conclusion: The results suggest this is an effective approach to testing for HCV in unusually challenging settings. Lessons from the program include the power of community involvement; and the effectiveness of a highly targeted health initiative when developed through collaboration.

Birth cohort hepatitis C antibody prevalence in real-world screening settings in Ontario.

Background: Widespread screening and treatment of hepatitis C virus (HCV) is required to decrease late-stage liver disease and liver cancer. Clinical practice guidelines and Canadian Task Force on Preventative Health Care recommendations differ on the value of one-time birth cohort (1945-75) HCV screening in Canada. To assess the utility of this approach, we conducted a real-world analysis of HCV antibody (Ab) prevalence among birth cohort individuals seen in different clinical contexts. Methods: Cross-sectional study of individuals born between 1945 and 1975 who completed HCV Ab testing at multiple participating centres in Ontario, Canada between January 2016 and December 2020. Differences in prevalence were compared by year of birth, gender, and setting. Results: Among 16,672 birth cohort individuals tested, HCV Ab prevalence was 3.2%. Prevalence was higher among younger individuals which increased from 0.9% among those born between 1945 and 1956 to 4.6% among those born between 1966 and 1975. Prevalence was higher among males (4.4%) compared with females (2.0%) and differed by test site. In primary care, the prevalence was 0.5%, whereas the prevalence was highest among those tested at drug treatment centres (28.7%) and through community outreach (14.0%). Conclusions: HCV Ab prevalence remains high in the 1945-1975 birth cohort. These data highlight the need to re-evaluate existing Canadian Preventative Task Force recommendations, to consider incorporating one-time birth cohort and/or other population-based approaches to HCV screening into the clinical workflow as a preventative health measure, and to increase training among community providers to screen for and treat HCV.

The impact of the first, second and third waves of covid-19 on hepatitis B and C testing in Ontario, Canada.

The COVID-19 pandemic interrupted routine healthcare services. Hepatitis B virus (HBV) and hepatitis C virus (HCV) infections are often asymptomatic, and therefore, screening and on/post-treatment monitoring are required. Our aim was to determine the effect of the first, second and third waves of the pandemic on HBV and HCV testing in Ontario, Canada. We extracted data from Public Health Ontario for HBV and HCV specimens from 1 January 2019 to 31 May 2021. Testing volumes were evaluated and stratified by age, sex and region. Changes in testing volumes were analysed by per cent and absolute change. Testing volumes decreased in April 2020 with the first wave of the pandemic and recovered to 72%-75% of prepandemic volumes by the end of the first wave. HBsAg testing decreased by 33%, 18% and 15%, and HBV DNA testing decreased by 37%, 27% and 20%, in each consecutive wave. Anti-HCV testing decreased by 35%, 21% and 19%, and HCV RNA testing decreased by 44%, 30% and 36% in each consecutive wave. These trends were consistent by age, region and sex. Prenatal HBV testing volumes were stable. In conclusion, significant decreases in HBV and HCV testing occurred during the first three waves of the pandemic and have not recovered. In addition to direct consequences on viral hepatitis elimination efforts, these data provide insight into the impacts of the pandemic on chronic disease screening and management. Strategies to make up for missed testing will be critical to avoid additional consequences of COVID-19 long after the pandemic has resolved.

Educational interventions to improve hepatitis C testing or treatment in South Asian communities: A systematic review.

BACKGROUND: Hepatitis C (HCV) places a disproportionately higher burden on the South Asian community in comparison to the general population, despite the availability of effective antiviral therapies. This study seeks to characterize the effectiveness of health promotion initiatives aimed at South Asians to improve HCV prevention, education, screening, and treatment adherence. METHODS: A systematic review (PROSPERO: CRD42021253796) was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. Ovid MEDLINE, CINAHL Plus, Web of Science, ERIC, Ovid Embase, Cochrane Library, and PsycINFO were searched from inception to 15 April 2022 for original studies that reported on any health promotion initiative directed at improving HCV outcomes in the South Asian community. Risk of bias was assessed via a quality score. RESULTS: A total of 15 studies (6 uncontrolled interventional, 3 before-after interventional, 3 randomized controlled, 2 prospective cohort, and 1 historically controlled interventional study designs) involving 69,958 participants were included. The most studied interventions were formal HCV teaching (n = 12), community outreach (n = 6), and coupling screening/testing with existing programs (n = 3). Ninety-two percent (14/15) of interventions were concluded to be successful, and 71% (10/14) of those were concluded to be feasible and/or cost-effective. CONCLUSIONS: Interventions that aim to improve HCV education and accessibility to screening/treatment can substantially reduce barriers to care in South Asian communities. Further research, of higher quality RCT evidence, is needed to study the long-term reduction in HCV prevalence from these proposed interventions, and their associated feasibility profiles.

Development and Evaluation of Active Case Detection Methods to Support Visceral Leishmaniasis Elimination in India.

As India moves toward the elimination of visceral leishmaniasis (VL) as a public health problem, comprehensive timely case detection has become increasingly important, in order to reduce the period of infectivity and control outbreaks. During the 2000s, localized research studies suggested that a large percentage of VL cases were never reported in government data. However, assessments conducted from 2013 to 2015 indicated that 85% or more of confirmed cases were eventually captured and reported in surveillance data, albeit with significant delays before diagnosis. Based on methods developed during these assessments, the CARE India team evolved new strategies for active case detection (ACD), applicable at large scale while being sufficiently effective in reducing time to diagnosis. Active case searches are triggered by the report of a confirmed VL case, and comprise two major search mechanisms: 1) case identification based on the index case's knowledge of other known VL cases and searches in nearby houses (snowballing); and 2) sustained contact over time with a range of private providers, both formal and informal. Simultaneously, house-to-house searches were conducted in 142 villages of 47 blocks during this period. We analyzed data from 5030 VL patients reported in Bihar from January 2018 through July 2019. Of these 3033 were detected passively and 1997 via ACD (15 (0.8%) via house-to-house and 1982 (99.2%) by light touch ACD methods). We constructed multinomial logistic regression models comparing time intervals to diagnosis (30-59, 60-89 and ≥90 days with <30 days as the referent). ACD and younger age were associated with shorter time to diagnosis, while male sex and HIV infection were associated with longer illness durations. The advantage of ACD over PCD was more marked for longer illness durations: the adjusted odds ratios for having illness durations of 30-59, 60-89 and >=90 days compared to the referent of <30 days for ACD vs PCD were 0.88, 0.56 and 0.42 respectively. These ACD strategies not only reduce time to diagnosis, and thus risk of transmission, but also ensure that there is a double check on the proportion of cases actually getting captured. Such a process can supplement passive case detection efforts that must go on, possibly perpetually, even after elimination as a public health problem is achieved.

From direct engagement to technical support: a programmatic evolution to improve large community health worker programs in Bihar, India.

INTRODUCTION: In 2011, through a multipartner Integrated Family Health Initiative (IFHI), CARE started supporting maternal and neonatal health (MNH) improvement goals in 8 of 38 districts in Bihar, India. The programme included a frontline health worker (FHW) component offering health advice through household visits and benefited from CARE's direct engagement during IFHI, which then evolved into statewide Technical Support Unit (TSU) to the Government of Bihar in 2014. METHODS: Using eight rounds of state-representative household surveys with mothers of infants aged 0-2 months (N=73 093) linked with two facility assessments conducted during 2012-2017, we assessed changes in FHW visit coverage, intensity and quality between IFHI and TSU phases. Using logistic regression models, we ascertained associations between FHW outputs and three MNH core practices: ≥3 antenatal care check-ups (ANC3+), institutional delivery and early breastfeeding initiation. RESULTS: Women's receipt of 1+ FHW visits declined from 60.2% (IFHI phase) to 46.3% (TSU phase) in the eight IFHI districts, being below 40% statewide during the TSU phase. Despite a parallel decline in FHW visit quality measured as the number of health advice received, all three outcomes improved during the TSU versus IFHI phase in IFHI districts. We found significant positive associations between all three outcomes and receipt of 1+ FHW visits and programme phase (TSU vs IFHI) in the eight IFHI districts. During the TSU phase, receipt of 2+ FHW visits in the third trimester increased the odds of women receiving ANC3+ (adjusted OR (aOR)=1.21; 95% CI: 1.13 to 1.31), delivering in a facility (aOR=1.64; 95% CI: 1.51 to 1.77) and initiating breast feeding early (aOR=1.18; 95% CI: 1.05 to 1.18). Independent of the number and timing of FHW visits, we also found positive associations between women reporting higher than lower quality of FHW interactions and receiving outcome-specific advice and all three MNH outcomes. CONCLUSION: Implementation of large community-based interventions under the technical support model should be continuously and strategically evaluated and adapted.

Family medicine-directed hepatitis C care and barriers to treatment: a mixed-methods study.

BACKGROUND: Antivirals for the treatment of hepatitis C virus (HCV) infection are effective, but many patients remain untreated and treatment is not yet routine in primary care. We evaluated the characteristics of patients who engaged in HCV treatment, and clinician perspectives on the barriers and facilitators to treatment. METHODS: Our mixed-method, parallel-design study was conducted at a multisite primary care centre in downtown Toronto. In a retrospective chart review, we searched records from 2011 to 2017 to collect quantitative data, including HCV infection status and HCV treatment status. To contextualize the data, we conducted in-depth interviews with select physicians between Aug. 1 and Nov. 1, 2017, and analyzed the transcripts using content analysis. RESULTS: Of the 40 381 charts reviewed, 727 patients (1.8%, 95% confidence interval [CI] 1.7%-1.9%) were infected with HCV, and 542 (74.6%) had HCV infection requiring treatment. Of those, 255 patients (47.0%) had engaged in treatment. Patients who had engaged in treatment were more likely to be male (odds ratio [OR] 1.63, 95% CI 1.10-2.42), older (OR 1.04 per year increase in age, 95% CI 1.02-1.05) and housed (OR 2.2, 95% CI 1.36-3.75), and they were more likely not to have engaged in injection drug use (OR 1.87, 95% CI 1.33-2.63). Based on interviews with 8 physicians, treatment barriers included a lack of knowledge about HCV treatment, concerns that patients would not adhere to medications and challenges related to medication access. Facilitators of treatment included access to specialist consultation, pharmacist support and primary care treatment guidelines. Common themes that emerged in both quantitative and qualitative components were the roles of unstable housing and intravenous drug use as barriers to engaging in and completing treatment. INTERPRETATION: Our study captured provider-identified barriers to HCV care and the key factors related to retention in HCV care, including gender, age, housing status and experience with drug use. Successful primary-care-led HCV treatment programs may incorporate specialist and pharmacy support and focus on younger, female, underhoused populations and people who use drugs.

Characterizing risk behaviour and reinfection rates for successful programs to engage core transmitters in HCV elimination (C-RESPECT).

BACKGROUND: Development of robust treatment programs among core transmitters (CT) of hepatitis C virus (HCV) are needed, including strategies to address reinfection risk. The aim of this study was to describe the effectiveness of direct-acting antiviral (DAA) treatment in CT versus non-CT populations and assess reinfection rates after successful treatment. METHODS: Characterizing Risk Behaviour and Reinfection Rates for Successful Programs to Engage Core Transmitters in HCV Elimination (C-RESPECT) was a prospective, observational study of HCV-infected Canadian adult patients (genotypes 1, 3, and 4) treated with DAAs between 2017 and 2020. RESULTS: The full analysis set included 429 participants (259 CT, 170 non-CT). Key differences were observed in baseline profiles: CT participants were younger (mean 42.3 [SD 11.2] y versus 55.0 [SD 11.1] y, respectively) and reported higher rates of social assistance (35.7% versus 14.8%), smoking (83.7% versus 52.4%), low socioeconomic status (yearly income <$15,000: 69.6% versus 43.9%), illicit drug use (83.7% versus 34.3%), and previous incarcerations (62.7% versus 36.9%). DAA treatment adherence was similar; 93 .5% versus 98.3% of CT versus non-CT participants completed the assigned treatment duration. Cure rates (sustained virologic response) were comparable, ranging from 94.9% to 98.1%. All reinfections were among CT participants, with a rate of 13.8/100 person-years (95% CI 9.2-20.8) with mean time to reinfection of 24.6 (SD 0.6) months. CONCLUSIONS: CT and non-CT participants respond equally well to DAA treatment; however, with some reinfections among CT participants. Innovative multidisciplinary programs must be developed to mitigate this risk in this key population.

Spontaneous Clearance After Relapse Following Direct-Acting Antiviral Treatment for Chronic HCV Infection.

BACKGROUND & AIMS: Direct-acting antivirals (DAAs) cure most cases of chronic hepatitis C virus (HCV) infection. However, a small percentage of patients relapse with reappearance of viremia after a full course of therapy. Although most who relapse require retreatment, some patients spontaneously clear HCV without additional therapy. We studied patients who relapsed with detectable HCV RNA after a full course of DAA therapy and then spontaneously cleared the HCV infection without retreatment. METHODS: We performed a case-control study of patients who spontaneously cleared chronic HCV infection following a documented relapse after DAA therapy at the Toronto Centre for Liver Disease, from January 2014 through December 2017. We collected clinical information at baseline, 12 weeks after treatment, and 6 months after relapse and compared data among spontaneous clearers, patients with persistent relapse, and patients who achieved a sustained virologic response to therapy 12 weeks after treatment (SVR12). The strength and breadth of interferon gamma cytokine secretion by HCV-specific T cells from peripheral blood were quantified using the ELISPOT assay. RESULTS: Of the 1032 individuals with chronic HCV infection who were treated with DAAs, 93 patients had a documented relapse. Of these patients, 12 patients (13%) spontaneously cleared HCV within 6 months after the documented relapse without additional therapy. The spontaneous clearers had low levels of HCV RNA (<4 log IU/mL in 11 of 12) and normal levels of alanine aminotransferase at the time of relapse, much like patients with an SVR12. There was no significant difference between the spontaneous clearance group and the SVR12 group in magnitude and breadth of HCV-specific T cell responses. CONCLUSIONS: In a case-control study of patients who spontaneously cleared chronic HCV infection following a relapse after DAA therapy, we found that it is important to confirm viremia prior to retreatment after the relapse-particularly for individuals with low levels of HCV RNA and normal or near-normal levels of alanine aminotransferase after treatment.

Reducing Read Time of Point-of-Care Test Does Not Affect Detection of Hepatitis C Virus and Reduces Need for Reflex RNA.

BACKGROUND & AIMS: Global elimination of hepatitis C virus (HCV) will require increases in diagnosis. Point of care (POC) tests that detect antibodies against HCV can be useful for testing large and difficult to reach populations. The most accurate POC test requires a 20 min read time to identify antibody-positive samples. We investigated whether viremic patients could be identified using a shorter read time, to increase efficiency and reduce the need for reflex tests (a follow-up test for HCV RNA on the same specimen to confirm viremia). METHODS: Patients with past or current HCV infections provided samples at 2 clinics in Canada for evaluation by the OraQuick HCV Rapid antibody POC test. A community HCV-screening program in Madrid, Spain (real-world cohort) invited people to be tested for HCV with the same OraQuick test. Patients provided samples of whole blood, via finger prick. Fingerprick samples were tested immediately after collection. In the clinic cohort, photographs of the developing test were taken at 15 second intervals, and blinded readers recorded the time to positivity. In the real-world cohort, readers recorded the OraQuick result at 5 minutes, and each minute after, up to 10 minutes, and then again at 20 minutes; viremia was then evaluated using a POC HCV RNA test (GeneXpert HCV Viral Load Assay). Sera from viremic and non-viremic clinic patients were used to quantify antibody titers to investigate the relationship between the time of band appearance and antibody concentration. Fisher's exact test and exact logistic regression were used to determine factors associated with a positive result at 5 minutes. RESULTS: Blood from all viremic patients produced a positive result in the antibody POC test by 5 min. Median time to a positive result for 171 viremic patients was 2.6 min (range, 1.8-4.6 min), vs 4.1 min (range, 2.3-14.4 min) for 108 patients with resolved infection (P < .001). The 5-min threshold identified all viremic cases among 176 HCV antibody-positive patients in the real-world cohort, confirmed by testing for HCV RNA. In the pooled cohorts, antibody positivity at 5 min identified viremic patients with 100% sensitivity (95% CI, 98.4%-100%); the negative predictive value was 100% (95% CI, 94.9%-100%). The positive predictive value at 5 min was 62.0% (95% CI, 56.7%-67.0%) and therefore insufficient alone to detect viremia; an HCV RNA test would still be necessary to confirm active infection. CONCLUSIONS: The wait time for the OraQuick HCV Rapid antibody POC blood test can be reduced from 20 min to 5 min and continue to reliably identify patients with HCV infection. Shortening the test time could increase high-throughput screening, reduce loss to follow up, and reduce the need for reflex HCV RNA testing.

Prenatal hepatitis B screening, and hepatitis B burden among children, in Ontario: a descriptive study.

BACKGROUND: Ontario is 1 of 5 provinces that immunize adolescents for hepatitis B virus (HBV), despite the World Health Organization recommendation for universal birth dose vaccination. One rationale for not vaccinating at birth is that universal prenatal screening and related interventions prevent vertical transmission. The aims of our study were to evaluate the uptake and epidemiology of prenatal HBV screening, and to determine the number of children in Ontario with a diagnosis of HBV before adolescent vaccination. METHODS: We extracted data from ICES, Public Health Ontario and Better Outcomes & Registry Network (BORN) Ontario databases. We assessed prenatal screening uptake and prevalence of prenatal hepatitis B surface antigen (HBsAg) from 2012 to 2016, as well as subsequent hepatitis B e-antigen (HBeAg) and HBV DNA testing and percent positivity. We used age and region to subcategorize the results. In a separate unlinked analysis, we evaluated the number of children positive for HBV aged 0-11 years who were born in Ontario from 2003 to 2013. RESULTS: From 2012 to 2016, 93% of pregnant women were screened for HBV, with an HBsAg prevalence of 0.6%. Prevalence of HBsAg increased with age, peaking at older than 45 years at 3%. North Toronto had the highest overall prevalence of 1.5%, whereas northern Ontario had the lowest. Of women who were HBsAg positive, HBeAg and HBV DNA tests were subsequently ordered in 13% and 38%, respectively. Of children born in Ontario between 2003 and 2013, 139 of 23 759 tested positive for HBV. INTERPRETATION: Prenatal HBV screening is not universal and subsequent evaluation is poor, limiting optimal intervention and possibly contributing to some Ontario-born children being given a diagnosis of HBV before age 12 years. These findings underscore the limitations of the province's adolescent vaccination strategy.