Low-level residual viremia can be present in chronic hepatitis B (CHB) patients on nucleos(t)ide analogues (NUCs). Due to the detection limits of current HBV DNA assays, the association between residual viremia and HBV-related HCC has not been well studied. This study included NUC-treated HBV-related HCC patients with unquantifiable serum HBV DNA by the conventional Cobas-Taqman assay (< 20 IU/mL) at HCC diagnosis. The HCC patients were matched in a 1:1 ratio with NUC-treated non-HCC controls. Serum samples at the time of HCC diagnosis, 1 year before, and 2 years before diagnosis were retrospectively retrieved and tested for residual viremia by a validated high-sensitivity droplet digital polymerase chain reaction assay (lower limit of detection 1.6 IU/mL). Among 208 patients (104 HCC vs. 104 controls; mean age 63.1, 80.8% male, 54.3% cirrhosis), residual viremia within 2 years was observed in 82.7% of HCC patients and 49.0% of controls (p < 0.001), and was independently associated with HCC occurrence (OR 7.243, 95% CI 1.862-28.170, p = 0.004). In HCC patients, residual viremia was associated with histological microvascular invasion (44.4% vs. 9.1% in patients without residual viremia, p = 0.033) and lower probability of presenting with Barcelona Clinic Liver Cancer stage 0 HCC (OR 0.281, 95% CI 0.094-0.838, p = 0.023). After median follow-up for 7.2 years, residual viremia within 2 years before HCC diagnosis was independently associated with liver-related mortality (HR 4.472, 95% CI 1.212-16.504, p = 0.025). Residual viremia in NUC-treated CHB patients is associated with a higher risk of HCC development, more advanced tumour staging and poorer outcomes. High-sensitivity HBV DNA assays may be utilized for monitoring in NUC treatment.

Directly acting antivirals (DAAs) revolutionised hepatitis C virus (HCV) treatment, offering higher cure rates. We aimed to quantify life expectancy (LE) differences between treated and untreated individuals diagnosed with HCV and assess the contributions of age and causes of death to these differences. We used routine HCV surveillance data linked with UK mortality records. Individuals contributed person-time from age 15 or the earliest HCV diagnosis, whichever was later, and were classified as treated six months post-treatment initiation. The study was divided into two periods: 2015-2018 (Period 1), representing early DAA roll-out targeting advanced liver disease, and 2019-2022 (Period 2). We used non-parametric survival analysis methods and mortality decomposition methods to estimate LE differences, and age- and cause-specific contributions to LE differences. A total of 92,920 individuals contributed 322,570 untreated and 200,581 treated person-years of observation, and 13,294 deaths to the analyses. In Period 1, there was an 8.5-year LE advantage at age 15 for treated females (95% CI: 5.4-11.5) and 8.9 years for treated males (95% CI: 5.6-12.2). In Period 2, this declined to 6.7 (95% CI: 3.3-10.2) and 5.3 (95% CI: 3.0-7.6), respectively. The narrowing gap was driven by rising deaths from suicide, alcohol, and drug misuse in the treated population and corresponding declines in the untreated population. Treated individuals with HCV had consistently higher LE, though the advantage decreased over time. We hypothesise that the early prioritisation of individuals with cirrhosis resulted in a relatively healthier untreated population (i.e., fewer cirrhotic cases) in the later period.

Hepatitis C virus (HCV) infection disproportionately impacts people who inject drugs (PWID). Understanding the prevalence and correlates of current and lifetime HCV infection is necessary to inform prevention, testing and treatment efforts among PWID to reduce HCV burden and achieve HCV elimination targets in this population From June 2021-December 2023, 751 PWID were recruited from syringe service harm reduction programs (SSP) and by referral from communities around New York State (NYS). Participants completed web-based surveys on risk factors and social determinants of health and were tested for HCV antibody and RNA to assess their current and lifetime HCV status (never infected, previously infected, or currently infected). Controlling for recruitment site as a fixed effect, a multivariate mixed logistic regression model was built to assess factors significantly associated with HCV status. Among PWID, 58% had a lifetime history of infection, and 29% were currently infected (50% among those with a lifetime history of infection). Daily/almost-daily injection, opioid injection, homelessness, and experience of abscess (all past-year) were significantly associated with current infection, as was younger age. Past-year SSP utilization was associated with a lifetime history of infection. PWID are a priority population to achieve HCV elimination in NYS. Our findings show that HCV burden is high among PWID utilizing SSPs. Expanding access to HCV care and treatment in harm reduction service settings while also providing services to address social determinants of health may be an effective strategy to progress towards reducing the burden of HCV among PWID.

Current uptake of chronic hepatitis B (CHB) treatment and care in Australia is well below target levels, leading to an ongoing burden of preventable liver disease and cancer. Understanding individual-level trajectories of care engagement and variation by sociodemographic factors is essential to guide efforts to improve access to and retention in care. This study analysed records of hepatitis B viral load (VL) testing and antiviral treatment provided through Australia's national health insurance system, which were linked to migration, death, and sociodemographic data from various government datasets. Treatment and VL testing by population group were assessed, and uptake was calculated using modelled estimates of the number living with CHB. VL testing frequency and treatment adherence based on scripts dispensed were also assessed. Of the estimated 219,800 people living with CHB in Australia in 2023, 118,334 (53.8%) received either VL testing or treatment during 2014-2023. Estimated uptake of VL testing and treatment uptake were lower among Aboriginal and Torres Strait Islander people and also varied by region of birth. Of the 81,360 who received any VL testing, only 17,352 (21.3%) received it regularly, while 31,715 (39.0%) had evidence of prior monitoring but no VL testing since 2019. The majority of those who initiated treatment continued therapy and received supply sufficient for adherence. This study shows that substantial gaps exist in CHB care in Australia, particularly in continued monitoring among those not on treatment. Disparities in uptake are evident by priority population. Re-engaging those lost to follow-up should be prioritised.

The risk of hepatocellular carcinoma (HCC) between chronic hepatitis B (CHB) patients in the untreated immune tolerant (U-IT) vs. treated immune active (T-IA) phases is not clear, and most data are in Asian populations. We aim to evaluate long-term risks of cirrhosis, HCC, and overall mortality between U-IT vs. T-IA CHB patients among a national cohort of U.S. Veterans. We conducted a propensity score weighted analysis of Veterans with CHB who met criteria for U-IT or T-IA from 1/1/2010 to 12/31/2021 (with follow-up through 12/31/2024). Incidence of cirrhosis, HCC, or death were compared between U-IT and T-IA groups. A total of 591 U-IT and 555 T-IA CHB patients were identified (mean age 56.4-57.5 years, 45%-50% non-Hispanic white, 37%-40% African American, 9%-10% Asian, 25%-29% concurrent diabetes, 35%-39% with FIB-4 > 3.25). Over a median follow up of 6.4 years (IQR 3.0-10.4), incidence of HCC was significantly lower in U-IT patients vs. T-IA patients (0.28 vs. 0.54 per 100 person-years; HR 0.52, 95% CI 0.32-0.83, p = 0.007). However, the risk of cirrhosis or all-cause mortality was similar between both T-IA and U-IT CHB patients. Among a predominantly non-Asian cohort of adults with CHB, we observed that HCC risk was lower in U-IT patients compared to T-IA patients. While this contrasts with some studies in Asian countries, these data do emphasize the importance of prioritizing and ensuring timely therapy for CHB patients in the IA phase. However, routine treatment in IT patients remains controversial and more data are needed to better understand long-term outcomes.

To achieve hepatitis B virus (HBV) elimination in Australia, a shift from hospital to community-based care is needed. This study aimed to describe the prevalence of chronic HBV and uptake of the cascade of care in primary care patients. This prospective cohort study was conducted in 76 urban and regional primary care clinics across Victoria, Australia between 1/7/2020 and 30/6/2023. Anonymised socio-demographic, clinical and laboratory data from general practice (GP) clinics' electronic medical records (EMR) were extracted. Descriptive analysis of the cohort of clinic clients with HBV was performed. A total of 346,927 individuals attended appointments across the study period. Of these, 25,212 had records indicating HBV-related testing. 491 (0.14%) individuals had evidence of current HBV infection defined as HBV surface antigen (HBsAg) positive and/or HBV DNA positive. 469 attended the clinics during the study period, among whom 239 (51%) were female. In the GP EMR, only 59 (13%) had evidence of at least one HBV DNA test and at least one ALT test ordered. Fourteen patients (3%) had record of being reviewed for HBV management by the clinic nurse or GP and 78 (17%) reviewed by a viral hepatitis specialist. Ninety-two (20%) were on treatment for HBV. Of people receiving treatment, 23 (25%) had a record of linkage to specialist care. Our data show that significant gaps in the cascade of care remain for people with chronic HBV in primary care settings, with a low proportion of patients having evidence of participating in all stages of the HBV cascade of care.

Daily subcutaneous bulevirtide (BLV) 2 mg has been approved as first-line treatment for chronic hepatitis D (CHD), but long-term real-world adherence data are limited. We assessed adherence rates during BLV therapy and their impact on treatment response. HERACLIS_BLV_D study (NCT05928000) included adult CHD patients initiating BLV 2 mg/day and followed in routine clinical practice. Virological response (VR) was defined as HDV RNA < 57.5 IU/mL or decline > 2 log10 and biochemical response (BR) as normal ALT (≤ 40 IU/L). Adherence was evaluated through the national prescription system based on executed monthly BLV prescriptions. Treatment discontinuation was defined as no executed BLV prescription for > 3 months at the end of follow-up. Seventy-six patients were included. VR/BR rates were 73%/71% at 12 and 93%/74% at 24 months. Thirteen (17%) patients discontinued BLV (none due to adverse events); 6%-7% per year. Mean adherence among treated patients was 98% ± 6% in 1st year declining to 93% ± 13% in 2nd and 91% ± 17% in 3rd year (p ≤ 0.010). No baseline characteristic was associated with poor (< 90%) or good (≥ 90%) adherence to BLV therapy. Patients with poor vs. good adherence had lower VR rates (1st year: 33% vs. 77%, p = 0.038; 2nd year: 60% vs. 97%, p = 0.030). In conclusion, in clinical practice, < 10% of CHD patients discontinue BLV therapy annually. Adherence is excellent in the first year and remains > 90% until the third year although gradually declines. Poor (< 90%) adherence cannot be predicted but adversely affects the VR rates emphasizing the need for strategies to support long-term treatment retention.

The current two-step model for HCV diagnosis risks losing people from care; a one-step diagnostic approach could improve retention. We investigated whether shortening the read time of an HCV antibody test from 20-min to 1 or 5-min could accurately predict HCV RNA viremia in-lieu of a standard RNA test. 1110 people in Yangon had a HCV Ab using Bioline HCV RDT. Results were recorded at 1-min intervals until 20-min, with HCV RNA testing of reactive results at 20-min. 884 participants returned both antibody and RNA results; 838 were Ab reactive at 1-min, 875 were reactive at 5-min and 728 were RNA positive. Sensitivity was 98.6% and 100% for 1 and 5-min read-times, and specificity was 23.1% and 5.8% for 1 and 5-min respectively. Our results suggest that reading the Bioline at 5 min has potential to identify patients with HCV infection ahead of reflexive RNA testing. Trial Registration: ClinicalTrials.gov:NCT03939013.

We evaluated cardiac extracellular volume (ECV) fraction, a sign of inflammation and fibrosis, in 10 individuals with chronic Hepatitis C virus (HCV) infection prior to treatment using cardiac magnetic resonance (CMR) at 3 T. Compared to age-matched, healthy volunteers, HCV-infected individuals had significantly increased ECV fraction (0.30 ± 0.03 vs. 0.26 ± 0.03, p = 0.0036) regardless of myocardial damage markers, hypertension as a comorbidity, smoking pack-years or fibrosis stage. Our results show that untreated hepatitis C is associated with the development of extrahepatic manifestations even before the onset of liver fibrosis, highlighting that early HCV treatment is prudent to reduce all-cause morbidity.

People who use drugs (PWUD) have a disproportionately elevated risk of hepatitis C virus (HCV). Appropriate screening and treatment may be limited, especially in rural environments experiencing healthcare shortages. In order to develop targeted intervention strategies for rural PWUD, we investigated individual and network-level correlates of HCV positivity. Survey data were collected from PWUD from the Illinois region of the Federal Delta Regional Authority (DRA). The primary outcome of interest was HCV positivity by self-report. We explored associations between HCV positivity and individual demographic, drug use, and service utilisation characteristics as well as degree of connectedness within social networks. Three hundred and two participants were included in analyses. At the individual level, HCV positivity was associated with injection drug use, overdose history, and prior receipt of substance use treatment. Two hundred and one participants had at least one connection to a peer via referral chains, most of which contained a mix of HCV-negative and positive individuals. Of note, isolated individuals had comparable rates of HCV positivity compared to their socially connected peers. Degree of connectedness was not associated with HCV positivity. This study highlights the heterogeneity, both with respect to HCV positivity and other characteristics, among networks of rural PWUD. Given that most participants were connected to others, HCV interventions led by peer champions may facilitate improved access to critical services for risk mitigation.

The epidemiological landscape of paired hepatitis B virus (HBV)/hepatitis delta virus (HDV) genotype (GT) among patients with HDV in the US remains unknown. HBV/HDV genotypes were assessed in two independent US cohorts: Cohort 1 included 5222 HBV-positive patients from Quest Diagnostics, including 114 anti-HDV+ patients; Cohort 2 included 178 anti-HDV+ samples from highly phenotyped patients managed at the National Institutes of Health (NIH). HBV/HDV sequencing and genotyping were analysed using phylogenetic analyses. In the overall cohort, HBV and HDV genotypes were determined for 197 (67%) and 139 (48%) patients, respectively, with HDV GT1 and GT5 and paired HBV/HDV genotypes D/1 and A/1 being the most prevalent. The most frequent HBV genotypes were GTD (40%) and GTA (35%), and the most frequent HDV genotypes were GT1 (84%) and GT5 (13%). Among 111 paired HBV/HDV genotypes, D/1 (50%) and A/1 (26%) were most common. In Cohort 2, 77 (79%) patients with HDV GT1 were foreign-born, most commonly Mongolian-born (47/77, 61%), while 21% (20/77) were US-born. Among patients with HDV GT5, GT6, or GT7, 93% (14/15) were of African origin. Overall, these findings provide the first comprehensive US analysis of HBV/HDV paired genotypes among patients with HDV and indicate that HBV genotype distributions differ between HBV/HDV coinfection and HBV monoinfection.

People who have been detained have a higher prevalence of hepatitis B virus (HBV) than the general population, yet testing uptake remains limited. Improving testing uptake in high-risk settings is essential to the World Health Organization 2030 elimination target. This systematic review examines interventions aimed at increasing hepatitis B testing uptake in prison. MEDLINE, EMBASE, CENTRAL and CINAHL were searched from January 2000 to April 2025. Quantitative interventional studies were included. Quality appraisal was conducted using the JBI critical appraisal tool. A random effects meta-analysis with Freeman-Tukey transformation estimated testing uptake. Subgroup analysis explored heterogeneity by sex, geographical region and the screening approach. Sixteen papers (15 studies) were included. Eleven were post-interventional quasi-experimental studies. Nine were conducted in Europe. The pooled testing uptake was 64% (95% CI 46%-80%; I[2] = 98%). Opt-in interventions were associated with a higher testing uptake (77%, 95% CI 59%-91%), in comparison to opt-out testing uptake (33%, 95% CI 17%-52%; p < 0.001), although opt-in screening had enhanced characteristics such as counselling, peer education and culturally tailored approaches. HBV prevalence amongst institutions ranged between 0% and 11.4%. Only one study reports costs. Opt-in programmes were associated with a higher testing uptake in comparison to opt-out programmes, which may reflect the underlying programme characteristics rather than the screening approach alone. Evidence on cost-effectiveness is limited. Most studies were heterogeneous and conducted in high-income countries. Further robust studies are needed to evaluate enhanced screening approaches to determine the most effective and scalable screening programme.

Fatigue in chronic viral hepatitis may be associated with decreased health-related quality of life and other patient-reported outcomes (PROs). We evaluated the relationship between fatigue and PROs in patients with chronic hepatitis B (CHB) and chronic hepatitis C (CHC). Patients with CHB and CHC enrolled in the Global Liver Registry completed PRO instruments: FACIT-F, CLDQ (for CHB), CLDQ-HCV (for CHC), and WPAI:SHP. Fatigue was defined as FACIT-F Fatigue Scale (FS) score < 30 (scale range: 0-52). Among 2888 patients from 14 countries, 1561 had CHB (mean age 47 ± 13 years; 60% male; 13% advanced fibrosis; 13% depression; 17% fatigue) and 1327 had CHC (50 ± 13 years; 47% male; 21% advanced fibrosis; 18% depression; 28% fatigue). CHB-fatigue was associated with younger age, female, obesity, anxiety, depression (all p < 0.01) and worse PRO scores: CLDQ (scale 1-7): 4.1 ± 0.9 vs. 5.8 ± 0.9; FACIT score (range 0-108): 67.6 ± 14.5 vs. 87.7 ± 13.7; work productivity impairment (range 0-1): 0.33 ± 0.29 vs. 0.11 ± 0.22 (all p < 0.0001). Multivariable analysis confirmed the association of fatigue with lower PRO scores, impairment up to -23% (p < 0.01). CHC-fatigue was associated with female sex, obesity, type 2 diabetes, anxiety, depression (all p < 0.05) and worse PRO scores: CLDQ-HCV: 3.8 ± 1.0 vs. 5.5 ± 1.0; FACIT: 61.8 ± 14.1 vs. 85.6 ± 14.5; work productivity impairment: 0.49 ± 0.32 vs. 0.17 ± 0.25 (all p < 0.0001). In multivariable models, fatigue remained associated with reduced PRO scores, impairment up to -33% (p < 0.01). Almost one in five patients with chronic viral hepatitis report significant fatigue, which is associated with substantial PRO and work productivity impairment. Routine assessment for and management of fatigue in CHC or CHB care is essential.

Hepatitis B surface antigen (HBsAg) loss is associated with improved clinical outcomes in patients with chronic hepatitis B virus (HBV) infection based on studies predominantly in Asian populations. We assessed real-world associations between HBsAg loss and long-term clinical outcomes in a diverse US population with chronic HBV infection. This retrospective cohort study (January 2012-December 2019) used Optum electronic health records data from patients with chronic HBV infection, identified via diagnosis codes or laboratory assessments. Patients with advanced liver disease and hepatitis C, hepatitis D or HIV co-infection at baseline were excluded. Associations between HBsAg loss, as a proxy of functional cure, and clinical outcomes were assessed using doubly robust inverse probability of treatment-weighted Cox proportional hazards models. In total, 15,760 patients with chronic HBV infection were included; 5.6% were receiving stable antiviral treatment. Overall, 4.2% (n = 667) experienced HBsAg loss across the study period. HBsAg loss was associated with an 89% and 62% reduced risk of hepatocellular carcinoma (HCC; adjusted hazard ratio [aHR]: 0.11, 95% CI: 0.01-0.76) and all-cause mortality (ACM; aHR: 0.38, 95% CI: 0.20-0.74), respectively. Risks of compensated cirrhosis (aHR: 0.84, 95% CI: 0.52-1.35) and decompensated liver disease (aHR: 0.74, 95% CI: 0.37-1.48) were lower after HBsAg loss, but did not reach significance. In this large, diverse population of patients with chronic HBV infection without advanced liver disease, HBsAg loss was associated with reduced risks of HCC and ACM compared with those without HBsAg loss.

Ongoing monitoring of hepatitis C virus (HCV) and HIV incidence among people who inject drugs (PWID) is important for epidemic control and assessing progress towards disease elimination. We estimated trends in HIV and HCV infection incidence in a community-based cohort of PWID in Montreal, Canada. Data from March 2011 to March 2025 were drawn from the HEPCO study of PWID aged ≥ 18 years and living in Montreal. Participants with at least two visits were included in analyses. We used a random point approach to estimate the date of each infection event, imputing each date 1000 times, and Rubin's rules to pool incidence rates and 95% CIs across imputations. A total of 743 participants contributed to HCV analyses, with 152 infection events and incidence of 6.47 per 100 person-years (p-y) (95% CI 6.46-6.49). Incidence peaked in 2013 and declined to 2019 before increasing again post-pandemic. There were 61 primary HCV infection events (incidence: 6.15 per 100 p-y; 95% CI 4.79-7.90) and 91 reinfection events (incidence: 6.71 per 100 p-y; 95% CI 6.69-6.73). A total of 836 participants contributed to HIV analysis, with only eight infections over 3089.89 p-y (incidence: 0.26 per 100 p-y; 95% CI 0.13-0.52). Declining HCV incidence among PWID in Montreal may have reversed, but limited data collection during the years 2020-2021 complicates interpretation. HIV incidence was persistently low. HCV incidence remains above World Health Organization elimination targets, highlighting the need for sustained investment in prevention and linkage to care for PWID.