ABSTRACTMedication nonadherence among patients with chronic hepatitis B (CHB) can lead to severe liver disease progression, including liver cirrhosis and hepatocellular carcinoma (HCC). Yet the factors that influence adherence in high‐risk groups, like Korean Americans, remain unclear. Thus, this study explored the psychosocial and clinical factors affecting medication adherence in CHB patients. A cohort of 365 Korean American patients with CHB from two clinics in Philadelphia and Los Angeles was studied. The 8‐item Morisky Medication Adherence Scale (MMAS‐8) gauged their adherence to antiviral medication. Using descriptive and multivariable logistic regression analyses, we identified factors associated with MMAS‐8 scores. Of the participants, 78% were undergoing antiviral therapy, with over two‐thirds (69%) reporting medium to high adherence levels. The multivariable logistic regression analysis revealed that age, knowledge of sequalae of CHB, perceived HBV stigma and possession of pharmacy plan were associated with medication adherence. Older participants had higher medication adherence than younger. High knowledge of sequalae of CHB and low perceived HBV stigma were associated with higher medication adherence. Having pharmacy plans was also associated with higher medication adherence to antiviral therapy. These findings highlight the critical role of person‐related factors (e.g., knowledge and stigma) and healthcare factors in medication adherence. Future research should focus on developing targeted educational interventions focusing on personal factors to improve medication adherence among Korean American patients with CHB.

ABSTRACTAlpha‐fetoprotein (AFP) level and its changes in chronic hepatitis B (CHB) may influence the risk of future hepatocellular carcinoma (HCC). This study aims to evaluate the HCC risk in CHB patients with no overt HCC but with elevated AFP level and to explore the prognostic role of longitudinal changes in AFP and liver‐related laboratory values. This multicentre cohort study included 10,639 CHB patients without a history of HCC from seven medical facilities in South Korea. Patients with a baseline serum AFP test and no HCC diagnosis on imaging within 3 months were included. Patients were categorised into high‐AFP (≥ 10 ng/mL) and normal‐AFP (< 10 ng/mL) groups. The primary outcome was the incidence of HCC within 2 years, with secondary outcomes focused on longitudinal changes in AFP and liver‐related laboratory values. Propensity score matching (PSM) and Cox proportional hazard models were used to assess HCC risk. After 1:4 PSM, 1278 high‐AFP and 3731 normal‐AFP patients were analysed. The high‐AFP group had a significantly higher 2‐year incidence of HCC (HR: 4.29; 95% CI: 3.31–5.57). AFP levels increased in patients who developed HCC in both groups (p < 0.01). Among the high‐AFP group, patients who did not develop HCC had elevated baseline alanine aminotransferase levels (p < 0.01), which decreased during follow‐up (p < 0.01) unlike those who developed HCC. In conclusion, baseline AFP elevation in CHB patients is associated with an increased risk of developing HCC within 2 years. Longitudinal monitoring of AFP and liver‐related laboratory values can help in risk stratification.

ABSTRACTUsing a systematic review and meta‐analytic approach, this study determined the durability of HBV immunity and the prevalence of anamnestic response to a booster HBV vaccine dose in individuals previously vaccinated with a 3‐dose HBV vaccine series as children or adolescents. Two researchers independently searched PubMed, Embase and Cochrane from inception to 6/1/2023 and performed data extraction. Studies that included individuals with significant comorbidities or < 5 years of follow‐up were excluded. Of 2517 potential studies, we analysed 91 eligible studies (193,359 individuals from 208 cohorts [some studies provided data for more than one cohort]). Median age at vaccination was 0 years (range: 0–20.00). After a median follow‐up of 10.15 years (range: 5–35), 63.2% (95% CI: 59.3–67.0) retained HBV immunity. HBV immunity declined by 6.62% per follow‐up year (Ptrend < 0.0001). In meta‐regression adjusting for vaccine type, follow‐up time and geographic location, age at vaccination was significantly associated with retaining HBV immunity (adjusted odds ratio [aOR] 1.12 per year, p < 0.0001). Anamnestic response rate (44 studies, 66 cohorts, 29,040 patients) was 90.34% (95% CI: 86.84–92.98), with highest rates in Europe and Asia, but only study setting (clinical versus community‐based: aOR 2.21, p = 0.034) was an independent factor. HBV immunity prevalence was about 60% after 10 years following childhood vaccination. Anamnestic response rate was about 90% and varied by study setting. Testing for immunity should be considered in individuals with high exposure risk and distant vaccination history with booster as needed.

ABSTRACTDirect‐acting antiviral (DAA) therapy is associated with a significant reduction in hepatocellular carcinoma (HCC) incidence among patients with cirrhosis, but data are conflicting about the risk of recurrence following DAA therapy. DAA‐PASS was a prospective, pragmatic, observational study designed to estimate the risk of HCC recurrence associated with DAA therapy exposure during routine clinical care. Eligible patients were DAA treatment naive with Barcelona Clinic Liver Cancer (BCLC) stage A. Patients were followed at regular intervals for up to 24 months. To provide additional data, outcomes were compared to the Italian Liver Cancer Group (ITA.LI.CA) cohort. Of 42 patients enrolled, 24 were treated with DAA therapy. Ten HCC recurrence events were observed during the study, with 5 each in DAA‐treated and DAA‐untreated patients (cumulative incidences of 23 and 37 per 100 PY, respectively). The overall crude hazard ratio (HR) for HCC recurrence associated with DAA therapy was 0.6 (95% CI, 0.2–2.2). In the ITA.LI.CA cohort, HCC recurrence was observed in 193 patients during 24 months of follow‐up, resulting in a cumulative incidence rate of 28 per 100 PY. Although limited by small sample size, this prospective study suggests DAA therapy is not associated with increased HCC recurrence risk among patients with a history of complete response to prior HCC therapy.

ABSTRACTAs the second most populated country in Africa, Ethiopia needs public health measures to control diseases that impact its population. The goal of this study is to analyse disease burdens of HBV and HCV, while also highlighting their estimated associated costs for the country. A literature review and a Delphi process reflecting input of Ethiopian experts and the National Viral Hepatitis Technical Working Group were used to complement mathematical modelling to estimate HBV and HCV disease and economic burdens. Two scenarios were created for HCV: 2023 base and WHO elimination. For HBV, three scenarios were created: 2023 base, WHO elimination and universal birth dose. Using current country costs, each scenario was also examined through an economic lens. There were an estimated 7.6 million HBV infections in 2023. To impact transmission, a universal birth dose and pregnant women screening program would allow Ethiopia to vaccinate approximately 3.9 million infants annually, with a budget of $4.68 million USD, meeting the WHO prevalence elimination target (≤ 0.1% in ≤ 5‐year‐olds) by 2043. Ethiopia had an estimated 690,000 HCV infections in 2023. To achieve HCV elimination, the country would need to expand screening and treatment to 74,000 individuals annually with a peak budget of $12 million USD per year until 2032, decreasing to less than $2 million USD in 2035. Ethiopia can begin making steps towards elimination of HBV through expansion of birth dose vaccination. However, larger investments will be needed to scale‐up treatment and diagnosis interventions for both diseases.

ABSTRACTZanzibar, a low‐resource semiautonomous region of Tanzania, has an estimated prevalence of hepatitis B virus (HBV) infections of 3.6%. To assess the feasibility of care and treatment, a 5‐year hepatitis B demonstration project was implemented in Zanzibar during January 2017–December 2021, following the 2015 WHO HBV care and treatment guidelines. Participants included adults (aged ≥ 18 years) who tested positive for HBV surface antigen and tested negative for HIV and hepatitis C antibody. Participants were examined for clinical signs of liver disease and testing was conducted at baseline to assess treatment eligibility and every 6–12 months thereafter. Tenofovir disoproxil fumarate (TDF) was provided at no cost to treatment‐eligible participants. Clinical and laboratory data were analysed to assess improvement in proximal disease outcomes. Among 596 participants enrolled, the median age was 32 years (IQR 26–39) and 365 (61%) were male. Of those enrolled, 268 (45%) returned for ≥ 1 follow‐up visit, with a median of 511 days of follow‐up. Overall, 58 patients initiated treatment: 15 met treatment criteria based on liver cirrhosis alone; 13 by APRI > 1.5; among those with HBV DNA results, six met criteria based on HBV DNA levels and ALT activity; 24 met ≥ 2 criteria. Significant decreases in ALT activities, APRI scores and HBV DNA levels were observed among those treated. This hepatitis B care and treatment programme was demonstrated to be feasible in a low‐resource setting. Despite challenges, testing and linkage to care is critical to decrease the global burden of hepatitis B.

ABSTRACTHepatitis D (HDV) is a severe infection with well‐recognised clinical ramifications that remains relatively neglected and underdiagnosed; consequently, the epidemiology of HDV is poorly characterised, both in the United States and globally. In 2022, a pilot project involving eight healthcare institutions was undertaken to ascertain the prevalence of HDV in healthcare institutions with an HBV seropositivity of at least 1%, describe the characteristics of patients testing positive for HDV, and evaluate diagnostic and laboratory processes of HDV screening. From August 2022 to April 2024, a total of 106,693 patients were tested for HBsAg, of whom 65,341 (61.2%) were female and 40,863 (38.3%) were male, with a mean age of 47 years. The overall HBsAg positivity rate was 1.04% (n = 1112). Among the HBsAg+ samples, 645 (58.0%) underwent HDV Ab testing. The HDV Ab positivity rate was 0.81% (n = 9), with 2 cases of HDV RNA positivity (0.18%). The incomplete testing reflects several challenges associated with screening for both HBV and HDV. Further research is necessary to better understand the epidemiology and burden of HDV in the United States and considerations for implementation.

ABSTRACTHepatitis C virus (HCV) infection is associated with a myriad of extrahepatic manifestations (EHM), as well as the production of autoantibodies, including rheumatoid factor (RF). This study aims to elucidate whether serum levels of RF change before and after HCV eradication, and whether these changes differ according to the type of therapy used. This is a retrospective cohort study of adults with chronic HCV infection treated with interferon‐free or interferon‐based regimens. All patients had HCV viremia at baseline and documented sustained virological response (SVR) 12 or 24 weeks after completing treatment. We measured the serum levels of RF at baseline and at SVR‐12 or −24 to analyse the changes after eradication. This study enrolled 297 patients (median age, 59 years; female, 48.5%; cirrhosis, 16.8%). Among them, 78 (26.3%) were RF‐positive by qualitative serology at baseline. This number decreased to 49 (16.5%) at SVR‐12 or −24 (p < 0.001). Quantitatively, the median RF also decreased from 1.6 IU/mL (interquartile range [IQR], undetectable—15.8) to undetectable (IQR, undetectable—6.6 IU/mL) (p < 0.001). Significant reductions were observed in both groups. The proportion with RF seropositivity decreased from 24.3% to 15.4% (p = 0.001) in patients treated with interferon‐free agents (n = 214) and from 31.3% to 19.3% (p = 0.006) in patients treated with interferon‐based regimens (n = 83), without significant difference between two groups (p = 0.40). Serum RF decreased after HCV eradication, regardless of treatment regimen. Our findings suggest that HCV eradication may attenuate HCV‐related autoimmunity.

ABSTRACTProgress in treating chronic hepatitis C virus (HCV) infection has been slow amongst people who use drugs (PWUD). This study describes the HCV treatment cascade amongst people accessing a mobile clinic offering integrated low‐threshold buprenorphine and infectious disease services in Baltimore City. From May 1, 2021, to December 31, 2022, 560 people had a rapid HCV antibody test, of whom 201 (36%) had a positive result and amongst those, 117 (58%) had an HCV RNA test performed, 81 (40%) had a documented positive RNA, 45 (22%) were prescribed medication, 42 (21%) started medication, 32 (16%) completed medication, 22 (11%) had blood work to assess for sustained virologic response and 20 (10%) had a documented cure. Challenges including housing instability, insurance barriers and lack of venous access limit progress in this cascade. Providing integrated care models to meet the needs of PWUD in the community is necessary but not sufficient to make progress in improving HCV treatment. Removal of insurance restrictions, availability of point‐of‐care HCV RNA testing, development of rapid HCV treatment guidelines and development of long‐acting injectable HCV treatment are needed to move towards a same‐day, one‐time test and treat model of care.

ABSTRACTDespite available curative treatments, global rates of hepatitis C virus (HCV) infection persist with significant burden in low‐ and middle‐income countries (LMICs). Long‐acting (LA) antiviral products are in development. This study explored the challenges and opportunities in LA‐HCV treatment across three LMICs: Egypt, Ethiopia and India. The survey focused on understanding barriers and facilitators to treatment, with emphasis on LA treatment preferences. Four‐hundred respondents completed a survey including demographics, HCV treatment history and preferences for injections, implants and microarray patches (MAPs) compared to pills. Overall, 78% of respondents were willing to receive injections, 43% were willing to receive implants and 55% were willing to receive MAPs. Marked heterogeneity in acceptability of non‐oral treatments was observed. Among respondents who had not previously received HCV treatment, 94%, 43%, and 75% were willing to receive injections, implants, or MAPs, respectively. In contrast, among those already cured by oral HCV treatment, 61%, 40% and 43% were willing to receive injections, implants or MAPs. Other characteristics associated with willingness to receive an injection included urban residence, younger age, male sex, higher education level and taking pills for any reason (all results p < 0.001). The most common concern for all LA modalities was lack of effectiveness. Prior experience with injection or implant increased willingness to receive any LA modality (p < 0.001). Coupled with a point‐of‐care HCV diagnostic test, availability of and willingness to receive HCV treatment delivered by a LA formulation could simplify and expand treatment access in LMICs and contribute towards global HCV elimination goals.

ABSTRACTModels estimate that the United States will not meet its 2030 hepatitis C virus (HCV) elimination goal. Engagement of healthcare providers including pharmacists is critical for HCV elimination efforts. We aimed to characterise the involvement of pharmacists in HCV management. The study design was a cross‐sectional survey. Investigators sent the questionnaire to pharmacy and HCV organisations' listservs and limited responses to licensed pharmacists with direct patient care. Questions assessed setting, HCV screening, prescribing, and management; and opinions, and perceived barriers and facilitators to pharmacists' HCV management. Two hundred and nine survey respondents across 45 states reported managing 24 patients/month, with 5.3 (±4.4) years' experience in HCV, and identified pharmacist‐managed HCV at their site since 2013 (±5.8 years). Most practice at academic medical centres (29%, 58/203) under collaborative practice agreements (67%, 127/189), as ambulatory care pharmacists (70%, 131/187), in primary care (50%, 65/131). Many pharmacists provide screening, linkage to care, and/or referral (81%, 157/194); 99.5% (190/191) perform treatment evaluation and selection; 98% (180/183) provide treatment education, 93% (171/183) initiate treatment, and 90% (162/180) provide on‐ and/or post‐treatment monitoring. Respondents indicated collaboration with prescribers as most helpful in their role in HCV management, whereas lack of reimbursement was a main barrier. Satisfying components include HCV cure, care and education provision; frustrations include socioeconomic factors impeding patients' follow‐up and prior authorisations/insurance barriers. Survey results show the variety of pharmacists' roles in direct HCV patient care and may be used to increase other providers' awareness of pharmacists' services and contributions to HCV elimination efforts.

ABSTRACTThis multicentre study investigated the dynamics of thrombospondin 2 (TSP2) levels during direct‐acting antiviral (DAA) therapy in hepatitis C virus (HCV) infected patients and evaluated TSP2's potential as a predictive marker for hepatocellular carcinoma (HCC). All 134 participants achieved sustained virological response at 12 weeks (SVR12) with DAA therapy, and serum TSP2 levels significantly decreased from before and after treatment (p < 0.001). During the median follow‐up period of 6.0 years, HCC after DAA therapy was observed in 16 patients (11.9%). Patients with serum TSP2 High (≥ 32 ng/mL) at SVR12 had a significantly higher cumulative occurrence of HCC than did those without (26.5% vs. 7.0%, p = 0.0033). A multivariate Cox proportional hazards model identified male gender (HR 4.84, p = 0.005), HCC history (HR 4.61, p = 0.017) and TSP2 High (HR 3.93, p = 0.009) as significant independent predictors of HCC occurrence after DAA therapy. The model had a high concordance index of 0.878. Additionally, combining TSP2 High and FIB‐4 High (≥ 3.538) at SVR12 yielded high specificity and negative predictive value (0.941 and 0.917, respectively) for predicting HCC. Kaplan–Meier analysis showed a higher HCC incidence in the TSP2 High + FIB‐4 High group (log‐rank p < 0.0001). In conclusion, TSP2 may be a promising biomarker for personalised HCC surveillance in DAA‐treated hepatitis C patients.

ABSTRACTExposure to healthcare procedures might be a source of hepatitis C virus (HCV) transmission in Georgia, one of the few countries currently on track to eliminate hepatitis C. While there has been a history of iatrogenic transmission of HCV, the risk of HCV transmission related to endoscopic procedures has not been previously assessed in Georgia. The goal of this study was to assess HCV seroconversion among individuals undergoing endoscopic procedures to estimate the relative role and incidence of HCV infection attributable to endoscopic procedures. A prospective cohort study was conducted in four endoscopy units in two cities (Tbilisi and Kutaisi) of Georgia during April–September, 2021. Recruitment of study participants was conducted using convenience sampling, and every eligible patient was approached and invited to participate in the study. Study population included adults (age ≥ 18 years) who received an endoscopic procedure (gastroscopy, colonoscopy and bronchoscopy) in inpatient or outpatient unit at the study sites. HCV antibody (anti‐HCV) testing was conducted using rapid diagnostic test (RDT) on the same day they underwent the endoscopic procedure. Patients with a non‐reactive anti‐HCV baseline test were retested after 6 months. Patients with reactive baseline tests were excluded from the study and linked to further testing and care. Participants with a reactive result on follow‐up RDTs were retested using a lab‐based anti‐HCV and HCV ribonucleic acid (RNA) test. A total of 981 HCV antibody non‐reactive participants were enrolled; 590 (64.8%) of them were reached and retested after 6 months. At retesting, two out of 590 (0.3%) individuals had a reactive anti‐HCV result on RDT and both were negative on laboratory‐based anti‐HCV and HCV RNA tests. Based on the results of this study, endoscopic procedures were not shown to contribute to HCV transmission in Georgia.

ABSTRACTA nationwide serosurvey among adults in 2021 showed a 2.7% (95% confidence interval [CI]: 2.3%–3.4%) prevalence of hepatitis B. Our analysis evaluates knowledge, attitudes and practices (KAP) for hepatitis B virus (HBV) infection among primary healthcare physicians (PHPs) in Georgia. We randomly selected 550 PHPs from medical facilities in Georgia's six largest cities. Using bivariate ordinal regression, we assessed the association of socio‐demographic factors with an ordinal knowledge score (low/middle/high). Multivariable logistic regression was performed to calculate adjusted odds ratios (aOR) and 95% CI to determine associations between HBV knowledge score and practices. Of 550 selected PHPs, 506 (92.0%) agreed to participate. Among them, 62.8% scored in the medium or high knowledge tertiles, 72.7% were confident in diagnosing HBV infection, 37.3% were confident in managing patients with hepatitis B; 47.4% reported being screened for and 26.2% reported being vaccinated against HBV infection. Compared to those with low knowledge scores, PHPs with a high score were less likely to recommend activities not supported by evidence, such as: the use of ‘hepatoprotective’ medications (aOR 0.43, 95% CI 0.25–0.73), caesarean sections (aOR 0.47, 95% CI 0.27–0.82) and withholding breastfeeding (aOR 0.57, 95% CI 0.34–0.96) to prevent HBV transmission. The majority of PHPs were confident in diagnosing HBV infection, but only one in three were confident in managing patients with hepatitis B. PHPs with higher HBV knowledge were less likely to provide inaccurate instructions to their patients. These findings will help to develop awareness and education campaigns supporting HBV elimination in Georgia.

ABSTRACTScreening for hepatitis D virus (HDV) is recommended for all individuals with hepatitis B virus (HBV) infection. Coinfected individuals experience more severe liver‐related outcomes. We determined the HDV testing and coinfection rates and all‐cause mortality among those infected with HBV. We used the US Department of Veterans Affairs (VA) healthcare system's national databases to identify individuals with HBV infection. We determined the proportion of individuals referred to gastroenterologists/hepatologists, or infectious diseases providers, and the proportion screened and tested positive for HDV. We calculated the HBV treatment rates, defined as ≥ 3 months of continuous prescription with an approved drug. Finally, we calculated all‐cause mortality stratified by HDV coinfection and HBV treatment status. Among 44,951 individuals with at least one positive HBsAg, HBeAg or HBV DNA test, 5964 (13.3%) were screened for HDV (180 [3.0%] tested positive), and 28,291 (62.9%) were referred to gastroenterology/hepatology or infectious diseases. Treatment for HBV was prescribed for 73 (40.5%) of HDV‐coinfected and 2425 (41.9%) HDV‐uninfected individuals. All‐cause mortality rate per 100 person‐years was lower among those without HDV coinfection (2.98 for untreated HBV, 2.53 for treated HBV; p < 0.001) compared with those with HDV coinfection (5.14 for untreated HBV, 3.0 for treated HBV; p = 0.02). Kaplan–Meier curves demonstrated a significantly higher mortality among HDV‐coinfected individuals who were not treated for HBV (log‐rank p < 0.0001). Screening rates for HDV among HBV‐infected individuals are suboptimal. While HDV coinfection is associated with higher all‐cause mortality, HBV treatment may confer a survival benefit.

ABSTRACTA subset of patients with chronic hepatitis C virus (HCV) infection demonstrate liver enzyme elevation (LEE) after achieving sustained virologic response (SVR). Risk factors for LEE are not well characterised. We conducted a single‐centre retrospective cohort study of adults with HCV infection in the Duke University Health System who received direct‐acting antiviral therapy and achieved SVR. We performed multivariable logistic regression to assess the relationship between potential risk factors and LEE. We used generalised linear mixed‐effects models to explore longitudinal relationships between HIV and LEE. Among 1356 patients, 556 (41.0%) had LEE after achieving SVR. Higher pretreatment alanine aminotransferase (ALT) (adjusted odds ratio [aOR] 1.08 per 10 IU/L increase; 95% confidence interval [CI] 1.05–1.11) and pretreatment cirrhosis (aOR 2.26, 95% CI 1.60–3.21) were associated with higher odds of LEE; male sex was associated with lower odds of LEE (aOR 0.28, 95% CI 0.21–0.38). There was insufficient evidence of an association between HIV and LEE (aOR 0.83, 95% CI 0.47–1.44). Pretreatment ALT, cirrhosis and female sex predicted LEE in this cohort of patients with HCV infection who achieved SVR. These findings can help to identify patients at greatest risk of post‐SVR liver injury.

ABSTRACTHepatitis C virus (HCV) elimination requires treatment access expansion, especially for underserved populations. Telehealth has the potential to improve HCV treatment access, although data are limited on its incorporation into standard clinical practice. We conducted a cross‐sectional, email survey of 598 US HCV treatment providers who had valid email addresses and (1) were located in urban areas and had written ≥ 20 prescriptions for HCV treatment to US Medicare beneficiaries in 2019–2020 or (2) were located in non‐urban areas and wrote any HCV prescriptions in 2019–2020. Through email, we notified providers of a self‐administered electronic 28‐item survey of clinical strategies and attitudes about telemedicine for HCV. We received 86 responses (14% response rate), of which 75 used telemedicine for HCV in 2022. Of those 75, 24% were gastroenterologists/hepatologists, 23% general medicine, 17% infectious diseases and 32% non‐physicians. Most (82%) referred patients to commercial laboratories, and 85% had medications delivered directly to patients. Overwhelmingly, respondents (92%) felt that telehealth increases healthcare access, and 76% reported that it promotes or is neutral for treatment completion. Factors believed to be ‘extremely’ or ‘very’ important for telehealth use included patient access to technology (86%); patients' internet access (74%); laboratory access (76%); reimbursement for video visits (74%) and audio‐only visits (66%). Non‐physician licensing and liability statutes were rated ‘extremely’ or ‘very’ important by 43% and 44%, respectively. Providers felt that telehealth increases HCV treatment access. Major limitations were technological requirements, reimbursement, and access to ancillary services. These findings support the importance of digital equity and literacy to achieve HCV elimination goals.

ABSTRACTThe WHO recommends hepatitis B birth‐dose vaccination (HepB‐BD), but it is not routinely given in most sub‐Saharan African countries. We aimed to assess the immunogenicity of HepB‐BD in addition to the existing hepatitis B vaccine (HepB3) schedule in Kinshasa, Democratic Republic of Congo among HBV‐unexposed and HBV‐exposed infants. Using an open‐label, randomised, controlled design, HBV‐unexposed infants were randomised (1:1) to receive the standard HepB3 vaccine series (group U3), or to receive HepB‐BD in addition to HepB3 (group U4). A supplemental cohort of HBV‐exposed infants (group E4) received HepB‐BD and HepB3. We compared the proportion of infants with protective antibodies against HBV (HBV surface antibody ≥ 10 mIU/mL) between groups U3 and U4 and groups U4 and E4 at 12 months of age. Between August 20 and October 9, 2019, we enrolled 281 mother/infant dyads; 88 (31.3%) returned at 12 months. Most infants had protective antibodies against HBV at 12 months: 92.9% (75.7%–98.2%) in group U3, 85.7% (67.5%–94.5%) in group U4 and 96.9% (95% CI: 81.2%–99.6%) in group E4. Trends held in estimates adjusted for loss‐to‐follow‐up (LTFU) and baseline imbalance across groups. In this first randomised trial assessing the addition of HepB‐BD to the hepatitis B vaccine schedule in SSA, we found that HBV‐unexposed infants who received the 3‐dose and 4‐dose vaccine series had similar immunogenicity against HBV at 12 months. A high proportion of infants, and notably HBV‐exposed infants, had protective antibodies. Though extrapolation of findings may be limited by LTFU, this study adds real‐world evidence regarding HepB‐BD implementation in sub‐Saharan Africa.Trial Registration: ClinicalTrials.gov identifier: NCT03897946

ABSTRACTHepatitis D virus leads to a severe form of viral hepatitis and affects nearly 5% of people living with chronic hepatitis B. Chronic infection with hepatitis D virus leads to more rapid progression to cirrhosis, hepatocellular carcinoma and ultimately liver disease‐related death compared with hepatitis B monoinfection. Health outcomes and treatment adherence can be affected by patient perception of, engagement in, and satisfaction with care. Our objective was to better understand the experiences of people with chronic hepatitis D, identify their preferred sources of information, and recognise unmet needs from their perspectives. Sixty‐seven participants from the United States and the European Union took part in monthly, online, self‐guided surveys for a minimum of 3 months with an optional extension. Participants reported feeling anxious and scared at the time of diagnosis but over time came to accept living with chronic hepatitis D. They voiced a need for access to information from trusted sources, fewer barriers to care, and shorter wait times for provider visits and test results after diagnosis. Participants experienced both physical and psychological strain living with chronic hepatitis D. Although most participants reported the ability to continue their regular activities and employment, some stated such activities were done at a reduced pace. Self‐reported overall health appeared to be closely linked with emotional support. Understanding patient perspectives, with concurrent clinician perspectives, is crucial when working toward developing solutions to fulfil unmet patient needs associated with chronic hepatitis D management and advancing health equity.

ABSTRACTHepatitis C virus (HCV) causes substantial morbidity and mortality, particularly among people who inject drugs (PWID). While elimination of HCV as a public health problem may be possible through treatment‐as‐prevention, reinfection can attenuate the impact of treatment scale‐up. There is a need to better understand the distribution and temporal trends in HCV infection risk, including among HCV‐seropositive individuals who will be eligible for treatment and at risk for subsequent reinfection. In this analysis of 840 seronegative and seropositive PWID in Baltimore, MD USA, we used random forest methods to develop a composite risk score of HCV infection from sociodemographic and behavioural risk factors. We characterised the individual heterogeneity and temporal trajectories in this composite risk score using latent class methods and compared that index with a simpler, conventional measure, injection drug use frequency. We found that 15% of the population remained at high risk of HCV infection and reinfection by the composite metric for at least 10 years from study enrolment, while others experienced transient periods of moderate and low risk. Membership in this high‐risk group was strongly associated with higher rates of HCV seroconversion and post‐treatment viraemia, as a proxy of reinfection risk. Injection frequency alone was a poor measure of risk, evidenced by the weak associations between injection frequency classes and HCV‐associated outcomes. Together, our results indicate HCV infection risk is not equally distributed among PWID nor well captured by injection frequency alone. HCV elimination programmes should consider targeted, multifaceted interventions among high‐risk individuals to reduce reinfection.

ABSTRACTHepatitis A is a vaccine‐preventable disease that typically causes mild illness. Hepatitis A outbreaks associated with person‐to‐person transmission have been widespread in the United States since 2016. We used public‐use US Multiple Cause of Death data to compare characteristics and listed comorbidities among decedents with hepatitis A‐listed deaths during non‐outbreak (2011–2015) and outbreak (2017–2021) periods and assessed the median age at death among decedents with and without hepatitis A‐listed deaths during the outbreak period. From the non‐outbreak period to the outbreak period, hepatitis A‐listed deaths more than doubled (from 369 to 801), while the hepatitis A‐listed age‐adjusted mortality rate increased 150% (p < 0.001). When compared with the non‐outbreak period, hepatitis A‐listed decedents during the outbreak period were more frequently male, aged 18–49 years, non‐Hispanic White, died in an inpatient setting, and had hepatitis A listed as their underlying cause of death. The median age at death for hepatitis A‐listed decedents was significantly younger during the outbreak period overall and among females (62 and 66 years, respectively) compared with the non‐outbreak period (64 and 72 years, respectively, p < 0.001). During the outbreak period, median age at death for hepatitis A‐listed decedents was 14 years younger than decedents without hepatitis A listed. Compared with the general US population, decedents with hepatitis A listed on the death certificate died at younger ages during 2017–2021. Efforts are needed to improve hepatitis A vaccination coverage among adults recommended for hepatitis A vaccination to prevent additional premature hepatitis A deaths.

ABSTRACTAn integral component to achieving worldwide chronic hepatitis B (CHB) elimination is addressing vertical transmission. Guidelines differ in their recommendations for breastfeeding while on tenofovir disoproxil fumarate (TDF). To conduct a systematic review of published studies analysing the concentration of tenofovir (TFV) in the breast milk of mothers receiving TDF and determining infant exposure from breastfeeding. We conducted a systematic literature search of studies evaluating infant safety from the breast milk of breastfeeding mothers receiving TDF for any indication that reported a TFV breast milk concentration. Daily infant exposure was used to calculate the relative dose of TFV in infants. Other pertinent information collected was the concentration of TFV in maternal and infant plasma, the duration of therapy of TDF and the indication for TDF. We identified 10 studies including 443 patients—266 of whom were mothers, and the remaining were infants—that reported the TFV concentration of breast milk in breastfeeding mothers receiving TDF. A total of 654 breast milk samples were included. The mean TFV concentration from all the studies that reported a median concentration of TFV was 4.8 ng/mL (95% CI [3.8, 5.8]). The mean infant exposure of TFV from breast milk was 0.56 μg/kg/day (95% CI [0.44, 0.68]). The mean relative dose was determined to be 0.01% of the weight‐based recommended infant dose. Infant plasma levels of TFV were also collected. This was undetectable in a majority of the studies that reported it. Based on the negligible infant exposure of TFV while breastfeeding, from a pharmacologic and toxicity standpoint, maternal dosing of TDF appears safe for breastfeeding infants.

ABSTRACTChronic hepatitis B virus (HBV) infection is a global issue and can lead to cirrhosis and hepatocellular carcinoma (HCC). Hepatitis B surface antigen (HBsAg) is an important marker of HBV infection and HBsAg quantification could be a useful tool in clinical practice. This systematic literature review aimed to explore the association between HBsAg titres and long‐term disease outcomes and evaluate the relationship between HBsAg titres, or changes in HBsAg titres, and clinical and treatment characteristics in patients with chronic HBV infection. Structured searches were performed in MEDLINE and Embase (January 2000 to 31 March 2023). Eighty‐two studies were included, comprising 51% retrospective cohort studies, mostly conducted in Asia (85%). HBsAg levels were shown to predict the long‐term development of cirrhosis and HCC in patients who were untreated prior to and during follow‐up; however, these data were inconclusive in mixed and treated populations. HBsAg titres were significantly associated with various virological markers including serum HBV DNA, HBcrAg, HBeAg, HBV RNA levels, intrahepatic covalently closed circular DNA (cccDNA) and intrahepatic HBsAg expression. HBsAg titres generally declined over time; this decline was more pronounced in early (HBeAg‐positive) than later disease phases (HBeAg‐negative). Higher decline in HBsAg levels was consistently associated with subsequent HBsAg seroclearance and a greater decline in total intrahepatic HBV DNA and cccDNA levels. In conclusion, this review showed that HBsAg levels and rates of decline could inform assessment, management and prediction of outcomes in chronic HBV infection. Further studies in broader, more diverse populations and treated patients are needed.

ABSTRACTIt is critical to address hepatitis C virus (HCV) in carceral settings to achieve worldwide elimination of the virus. We describe New Mexico's (NM) experience expanding HCV treatment in state prisons, supplemented with Project ECHO (ECHO; virtual mentorship through guided practice) and the NM Peer Education Program (NMPEP). We describe how using these programs may be a model for expanding treatment in prisons globally. ECHO, NM Corrections Department (NMCD) and Wexford Health Services (WHS) collaborate to treat HCV in state prisons and increase HCV knowledge among incarcerated persons using NMPEP. Each person arriving in prison is tested for HCV and those with active infection receive baseline labs, which are reviewed. Patients not meeting criteria for simplified treatment are presented to ECHO for expert guidance. Otherwise, patients are treated by WHS without consultation. NMPEP provides patient‐to‐patient education in prisons, addressing HCV myths and exploring treatment refusals. From December 2020 to June 2023, 3603 people had HCV viremia. In this study, 1685 people started treatment: 1280 were treated using the simplified algorithm and 405 were presented to ECHO. Of the 988 people who completed treatment and had sustained virologic response (SVR) labs drawn, 89.2% achieved SVR (i.e., cure). Most of the 107 people who did not achieve SVR had presumed reinfection. NMPEP trained 148 peer educators who educated 3832 peers about HCV prevention and treatment. HCV treatment in prisons can be expanded by implementing simplified treatment algorithms, use of the ECHO model for patients with advanced disease and peer education.