BACKGROUND:Hepatitis A virus (HAV) infection is infrequently diagnosed in Canada, and little data are available regarding its epidemiology. Transmitted fecal-orally, HAV is an ideal candidate for wastewater-based surveillance (WBS). We set out to characterize HAV using WBS in a low-prevalence setting. METHODS:This observational study was conducted in the province of Alberta, Canada. Weekly composite wastewater samples were collected from eight municipalities (populations 7909-1,306,784), and eight neighbourhoods within Calgary, the largest city. HAV genomic material was quantified using RT-qPCR targeted on VP1 and sequenced at the VP1/2A junction. HAV case data from Alberta's Public Health Laboratory and population demographics from census data were correlated with wastewater HAV burden. RESULTS:Between July and December 2023, low levels of HAV were detected in wastewater from 50% of the municipalities and 50% of urban neighbourhoods (with 15.4% and 8.3% of samples testing positive, respectively). Wastewater HAV levels correlated with clinical HAV prevalence in larger communities. For genotyped clinical cases, wastewater with a matching VP1/2A sequence within a two-week period was observed for 8/9 episodes (median 6.42 days). Wastewater-measured HAV associated with population size, population density, and immigration from HAV endemic areas. CONCLUSION:HAV was detectable in wastewater of both municipalities and neighbourhoods within a low prevalence setting. Wastewater HAV was associated with population metrics and socioeconomic factors, including immigration. WBS data correlated strongly with clinical disease revealing a minimal burden of undiagnosed infections. This demonstrates the feasibility of HAV WBS and its potential as a public health tool in non-endemic settings.

BACKGROUND:Waitlist volumes for hepatology referrals in Calgary, Alberta, have increased with population growth and rising chronic liver disease [alcohol-related, metabolic dysfunction-associated steatotic liver disease, hepatitis B virus (HBV) infection, and cirrhosis complications]. Prolonged waits threaten timely surveillance, diagnosis, and treatment. We conducted a QI (quality improvement) project in the Calgary Liver Unit at the University of Calgary Medical Clinic (UCMC), a tertiary clinic using a central access and triage (CAT) system serving ~2 million residents. METHODS:Our aim was to cut the median wait for routine referrals from 78.4 to 39 weeks (50%) between October 2023 and August 2025. Six Plan-Do-Study-Act cycles targeted referral coding (ICD-10 groupings), a dedicated HBV clinic, clearer triage acuity criteria, standardized waitlist management, redirecting benign liver neoplasms to primary care with guidance, and recruiting 2 additional hepatologists to expand capacity. The primary outcome was median routine wait time; secondary outcomes included urgent and emergent wait times and total waitlist size. Net waitlist accrual (accepted referrals minus new patients seen per month) tracked the flow. Data from CAT and scheduling systems were analyzed using statistical process control (SPC) charts. RESULTS:By August 2025, the median routine wait fell to 8.4 weeks, the urgent wait fell from 28.3 to 6.6 weeks, and the emergent wait remained near the 2-week target (2.4 to ~2.7 weeks). The waitlist decreased from 1426 to 158 patients, and net accrual shifted from persistently positive to sustained negative values, reflecting backlog reduction. Routine-wait SPC charts showed special-cause variation and a sustained performance shift after key interventions. CONCLUSION:This multi-component, data-driven strategy within a CAT model improved access for routine referrals while protecting timely care for higher-acuity patients and may translate to other subspecialty clinics facing similar constraints.

BACKGROUND & AIMS:Chronic hepatitis B (CHB) remains a leading cause of cirrhosis and hepatocellular carcinoma (HCC) worldwide, yet treatment uptake is suboptimal even in high-resource settings. This pan-Canadian study aimed to quantify treatment gaps within the Canadian Hepatitis B Network (CanHepB) Registry, compare characteristics of treatment-eligible but untreated patients to those receiving therapy, and assess patient and specialist perspectives on barriers to treatment. METHODS:A cross-sectional, retrospective analysis of 1983 adults with CHB followed in 18 Canadian hepatitis B specialty clinics between January 2018 and November 2024. Treatment eligibility was determined using the 2018 Canadian Association for the Study of the Liver guidelines. An anonymous survey captured patient-reported barriers and perspectives (n = 191), while a separate survey evaluated specialist perceptions (n = 54). RESULTS:Among 881 untreated patients, 46.4% (n = 409) were treatment eligible. Compared with the treatment group (n = 1087), the treatment-eligible but untreated patients were younger (median 47.3 vs. 54.5 years), more frequently female (54.2% vs. 39.7%), and more likely to be of Black/African/Caribbean origin (18.2% vs. 9.7%). They had a lower prevalence of cirrhosis (2.4% vs. 20.3%), HCC (0.7% vs. 9.3%), and hypertension (17.1% vs. 22.9%), but a higher prevalence of steatotic liver disease (36.4% vs. 24.6%) and dyslipidemia (14.7% vs. 10.8%). Among untreated respondents, concerns included side effects, the need for long-term therapy, and lack of curative options. Conversely, specialists identified cost as the primary barrier and side effects as the least concerning. CONCLUSION:This nationwide study reveals a significant treatment gap in CHB care, driven by demographic disparities and a mismatch between patient concerns and clinician perceptions.

Chronic hepatitis B (CHB) and hepatitis D virus (HDV) coinfection are major causes of cirrhosis and hepatocellular carcinoma. The geographic distribution of CHB and alignment of anti-HDV testing with CHB burden remain poorly defined. We aimed to examine if anti-HDV testing and seropositivity align with areas of highest CHB burden. Adults with CHB (2014-2022) were identified using a validated serologic algorithm in the provincial laboratory database capturing HBV/HDV serology. Cases were geolocated to Aggregate Dissemination Areas (ADAs), linked to Alberta Health Services zones and rural-urban continuum levels. Age- and sex-standardized CHB prevalence was calculated per ADA using the 2016 Canadian Census. Descriptive mapping, global spatial autocorrelation and local hotspot analysis were used to assess spatial clustering. Among 8317 persons with CHB, the provincial age- and sex-standardized prevalence was 1.70 per 1000 population (95% CI, 1.66-1.74). Prevalence ranged from 2.15 per 1000 in metropolitan areas to 0.40 per 1000 in remote regions and was higher in Calgary than Edmonton (2.53 vs. 1.73 per 1000). Overall, 17.5% of CHB patients were tested for anti-HDV, and 4.1% of those tested were anti-HDV positive. CHB prevalence hotspots were concentrated in metropolitan ADAs, whereas hotspots of anti-HDV testing and positivity showed only partial overlap with these high-burden areas. CHB burden in Alberta is geographically clustered, particularly within specific neighbourhoods of metropolitan cities, whereas anti-HDV testing remains infrequent and only partially aligned with high-burden areas. Reflex or systematic anti-HDV testing, paired with geographically informed outreach, may improve case detection.

Bangladeshi immigrants in Canada face elevated chronic liver disease risk, yet awareness and hepatitis screening remain low. In a bilingual survey of 966 Bangladeshi adults in Calgary, only 23% reported prior testing and overall liver health knowledge was low. Lack of physician recommendation was the primary barrier. Higher liver health knowledge was strongly associated with screening uptake. Findings suggest screening remains largely provider-initiated and highlight the need for culturally responsive liver health literacy interventions.

Abstract Background: Chronic hepatitis B (CHB) imposes adverse health outcomes but may also cause psychosocial and quality-of-life (QOL) challenges. Hepatitis B surface antigen (HBsAg) loss, whether spontaneous or due to treatment (ie, a functional cure), is associated with improved clinical outcomes, but the impact of HBsAg clearance on patient-reported outcome measures (PROMs) is poorly understood. Methods: Two surveys (hepatitis B self-stigma and hepatitis B–related QOL [HBQOL]) were administered to adults with a history of CHB with documented HBsAg clearance from six Canadian hepatology clinics. Results: Eighty-four participants were enrolled (median age: 60 years; 53.6% male). Nearly three quarters (72.6%) of patients reported never feeling self-stigma. HBQOL scores improved across all six domains ( p < 0.001 for each), with the largest relative gains in psychological well-being (60% reduction), transmission concerns (55%), and stigma (53%). Conclusions: HBsAg loss was associated with significant improvements in patient-reported stigma and QOL. These findings highlight the importance of incorporating PROMs into hepatitis B virus clinical care to better capture treatment experiences.

BACKGROUND:Treatment with bepirovirsen, an antisense oligonucleotide targeting hepatitis B virus (HBV) transcripts, has the potential to result in a functional cure, defined by at least 24 weeks of a sustained HBV DNA level below the lower limit of quantification (LLOQ) and hepatitis B surface antigen (HBsAg) loss after fixed-duration therapy. METHODS:In two replicate, double-blind trials (B-Well 1 and B-Well 2), we randomly assigned adults with noncirrhotic chronic HBV infection in a 2:1 ratio to receive subcutaneous bepirovirsen (at a weekly dose of 300 mg) or placebo for 24 weeks. All the patients were receiving stable nucleoside or nucleotide analogue (NA) therapy and had an HBsAg level of more than 100 to 3000 IU per milliliter. Eligible patients discontinued NA therapy at 48 weeks. The primary outcome was a functional cure at week 72. RESULTS:The percentage of patients with a functional cure at week 72 was significantly higher with bepirovirsen than with placebo both in the B-Well 1 trial (in 127 of 650 patients [20%] vs. none of 328 patients) and in the B-Well 2 trial (in 106 of 570 patients [19%] vs. none of 286 patients). In a pooled analysis at 72 weeks, adverse events were reported in 91% of the patients in the bepirovirsen groups and in 73% of those in the placebo groups; serious adverse events were reported in 7% and 4% of the patients, respectively. During the treatment period, adverse events of grade 3 or higher were reported in 16% of the patients who received bepirovirsen and in 3% of those who received placebo; increases in the alanine aminotransferase level were the most common grade 3 adverse events with bepirovirsen (in 6% of the patients). CONCLUSIONS:In two phase 3 trials involving patients with chronic HBV infection, a functional cure after the discontinuation of NA therapy was reported in significantly more patients treated with bepirovirsen than in those who received placebo. (Funded by GSK; ClinicalTrials.gov numbers, NCT05630807 and NCT05630820.).

Background & Aims: Bepirovirsen, an antisense oligonucleotide, induces sustained reductions in hepatitis B surface antiger (HBsAg) and HBV DNA to below the lower limit of quantification (

L'infection chronique par le virus de l'hépatite B (VHB) pose d'importants problèmes de santé publique au Canada, en particulier chez les nouveaux arrivants provenant de régions à forte prévalence du VHB. Conformément à l'objectif de l'Organisation mondiale de la Santé d’éliminer le VHB d'ici 2030, cette mise à jour 2025 des lignes directrices, élaborée conjointement par l'Association canadienne pour l’étude du foie (ACEF) et l'Association pour la microbiologie médicale et l'infectiologie (AMMI) Canada, présente des recommandations pour le dépistage universel du VHB chez l'adulte, la vaccination, les analyses de laboratoire et le traitement. Ces lignes directrices mettent l'emphase sur les soins centrés sur le patient, le diagnostic précoce et les indications de traitement antiviral élargies, notamment pour les personnes en phase indéterminée ou « zone grise » et les populations spéciales comme les femmes enceintes, les enfants et les personnes co-infectées par le VIH, le VHC ou le VHD. Elles recommandent notamment le test réflexe du VHD et l'utilisation de routine de l'AgHBs quantitatif pour appuyer les décisions de prise en charge. Ces recommandations sont fondées sur des données probantes s'appuyant sur le consensus des experts, la littérature récente et les standards internationaux, dans le but d'améliorer les issues cliniques, de réduire la stigmatisation et d'informer les futures politiques et priorités de recherche.

BACKGROUND AND AIMS:Immunosuppression can cause hepatitis B virus (HBV) reactivation, leading to severe outcomes in patients with "resolved" HBV infection. This multicenter, randomized, placebo-controlled trial assessed the efficacy of preemptive antiviral therapy in HBsAg-negative, anti-HBc-positive patients receiving rituximab-based chemotherapy for non-Hodgkin lymphoma (NHL). METHODS:Patients were randomized 1:1 to tenofovir alafenamide (TAF)/placebo across 3 phases: chemotherapy plus TAF/placebo (phase 1), TAF/placebo post-chemotherapy (phase 2), and follow-up after therapy cessation (phase 3). The primary endpoint was HBsAg reverse seroconversion. HBsAg and ALT were monitored every 3-12 weeks, depending on treatment phase, and HBV DNA was measured post hoc. ClinicalTrials.gov (NCT02186574). RESULTS:Among 42 patients (median age 65.2 years, 52.4% male, 52.4% aggressive lymphoma, 73.8% anti-HBs positive), 20 received TAF and 22 received a placebo. Median ALT was 20.0 U/L (IQR: 15.0-28.0) at baseline. Median follow-up was 69.4 weeks (IQR: 63.7-166), with 6.1 weeks (IQR: 4.7-8.3) between visits. During follow-up, 2 patients in the TAF arm, but none receiving placebo, experienced HBsAg reverse seroconversions: occurring in phase 3 at 62.3 weeks from baseline, and in phase 1 at 20.0 weeks from baseline. Neither patient experienced ALT >2× ULN. HBV DNA >1000 IU/mL was observed in 8 instances among 6 patients, 3 in each arm, with no associated hepatitis. Low-level DNA (<1000 IU/mL) was not indicative of reverse seroconversion, DNA increases, or ALT elevations. CONCLUSIONS:The use of preemptive TAF therapy did not reduce the risk of HBsAg reverse seroconversion; however, the findings should be interpreted with caution as the study was underpowered due to slow enrolment leading to early termination. Low-level HBV DNA elevations were not associated with HBV reactivation. Thus, close HBsAg and ALT monitoring are adequate in HBsAg-negative patients undergoing rituximab-based chemotherapy.

Globally, an estimated 254 million people are living with chronic hepatitis B virus (HBV) infection, yet only 10.5% have been diagnosed, underscoring the urgent need to expand testing to meet the World Health Organization’s HBV elimination targets by 2030. Many HBV diagnostic tests remain expensive and inaccessible in resource-limited settings. In this study, we demonstrate how individually sourced, commercially available reagents can be used to develop cost-effective in-house assays for total DNA isolation, HBV viral load quantification by (q)PCR, and qHBsAg and qHBeAg measurement using sandwich ELISA. These assays were validated using known HBV-positive and HBV-negative plasma samples (genotypes A–F) and HepAD38 cells treated with tenofovir disoproxil fumarate (TDF). DNA isolation using a commercial column-based kit was compared to a high-throughput, column-free method, allowing for HBV quantification from 50 µL of plasma with lower limits of detection (LLOD) of 1.8 × 103 and 1.8 × 104 HBV DNA copies IU/mL, respectively. Both commercial and in-house DNA isolation methods yielded comparable half-maximal effective concentration (EC50) values in TDF-treated HepAD38 cells. Additionally, in-house sandwich ELISA assays were developed for quantitative HBsAg and HBeAg detection, with LLOD values of 0.78 IU/mL and 0.38 PEI U/mL (Paul Ehrlich Institute), respectively. The in-house reagents for DNA isolation, molecular testing, and serological detection of HBV were estimated to be at least 10 times more cost-effective than commercially available kits, highlighting their potential for broader application in resource-limited regions.

Chronic hepatitis B virus (HBV) infection poses significant public health challenges in Canada, particularly among newcomers from regions with high HBV prevalence. In alignment with the World Health Organization's goal of HBV elimination by 2030, this 2025 guidelines update-developed jointly by the Canadian Association for the Study of the Liver (CASL) and the Association of Medical Microbiology and Infectious Disease (AMMI) Canada-presents recommendations for universal adult HBV screening, vaccination, laboratory assessment, and treatment. These guidelines emphasize patient-centred care, early diagnosis, and expanded antiviral treatment, including for individuals in the indeterminate or grey zone and special populations such as pregnant individuals, children, and those coinfected with HIV, hepatitis C, or hepatitis D. Notably, the guidelines recommend reflex HDV testing and routine use of quantitative HBsAg to support management decisions. These evidence-based recommendations are informed by expert consensus, recent literature, and international standards, with the aim of improving outcomes, reducing stigma, and informing future policy and research priorities.

Abstract Background Hepatitis A virus (HAV) incident infection in Canada is rarely diagnosed (i.e. incidence of 3.6-10 cases/100,000 persons) (PMID: 18159360). Infections generally relate to imported contaminated food-products, or travelers returning from endemic countries. Due to its fecal-oral spread, possible underdiagnosis, and often-cryptic presentation, HAV is an ideal candidate for wastewater (WW)-based surveillance, a tool increasingly utilized to monitor infectious diseases globally.Figure 1.Longitudinal monitoring of HAV RNA wastewater abundance across eight Alberta municipalities over a 4-month period. Methods 24-hour composite WW was collected weekly from eight geographically disparate, and socioeconomically diverse municipal WW treatment plants in Alberta from August to December 2023. After short-term cold storage, WW was centrifuged, and RNA from the raw pellet was extracted using Qiagen’s RNeasy PowerFecal pro. HAV levels were quantified by RT-qPCR of the vp1 gene. 2021 Canadian census data was used to define population demographics for each participating site. Results HAV was detected in 18/117 (15.4%) WW samples and 5/8 (62.5%) municipalities over the 4-month period (Figure 1). RNA abundance in HAV positive WW samples was a median of 3.4 copies/mL (IQR 0.44 - 6.97). Larger population size (p=0.007), and greater density (p=0.001) were associated with increased likelihood of HAV WW detection, whereas social and economic demographics of populations within sewershed catchments did not associate with likelihood of HAV detection (Table 1). Conclusion HAV RNA is rarely detected in the wastewater of Alberta. Detection was more frequently observed in larger municipalities, which is consistent with non-endemic, imported disease. WW surveillance can potentially be adapted to monitor HAV in the context of outbreaks to reduce secondary transmission, and safeguard public health. Disclosures Mark Swain, MD MSc, Abbott: Advisor/Consultant|Advanz: Advisor/Consultant|Gilead, BMS, CymaBay, Intercept, Genfit, Pfizer, Novartis, Astra Zeneca, GSK, Celgene, Novo Nordisk, Axcella Health Inc., Merck, Galectin Therapeutics: Grant/Research Support|GSK: Advisor/Consultant|Ipsen: Advisor/Consultant|Novo Nordisk: Advisor/Consultant Carla Coffin, MD MSc, Altimmune: Grant/Research Support|Gilead: Grant/Research Support|GSK: Grant/Research Support|Janssen: Grant/Research Support Steven J. Drews, PhD FCCM D(ABMM), Abbott: Grant/Research Support|Danaher: Honoraria|Roche: Advisor/Consultant|Roche: Grant/Research Support