Journal of Viral Hepatitis最新文献

The quest for a functional cure for chronic hepatitis B (CHB) remains an elusive objective. Haematopoietic stem cell transplantation (HSCT) may elicit viral clearance by immunological remodelling in recipients with positive HBsAg; however, the factors that determine its effectiveness are yet unknown. The aim of the study is to assess HSCT-induced hepatitis B surface antigen (HBsAg) seroclearance rates and identify immunological mechanisms and combination therapy strategies through meta-analysis and systematic review. In this study, nine trials (308 patients) were subjected to single-arm meta-analysis (R4.4.2 ‘meta’ package) in accordance with PRISMA/Cochrane criteria. Heterogeneity was addressed via random-effects models (I² = 87.1%). Subgroup analysis accounted for donor HBsAb/recipient HBeAg impacts. The total HBsAg clearance rate was 26% (95% CI: 14%–39%), greater than that of standard therapies. Notably, HBsAb-positive donors had significantly enhanced clearance (55% vs. 8%, p < 0.01). HBeAg-negative recipients fared better (29% vs. 2%). In patients who achieved HBsAg loss, HBsAb-positive donors and HBeAg-negative recipients are the most prevalent types (10/11). Sensitivity analyses confirmed robustness and publication bias was nonsignificant (Egger's p = 0.271). In conclusion, HSCT demonstrates the potential for functional cure in CHB, providing valuable insights into new immunological therapeutic strategies. More importantly, it serves as a powerful paradigm for identifying the immunological prerequisites for cure, informing the development of safer, targeted immunotherapies.

Chronic hepatitis B virus (CHB) infection poses a serious health threat with high morbidity and mortality, influenced significantly by both innate and adaptive immune responses. The work of innate and adaptive immune systems determines the development and prognosis of CHB. Immune checkpoints (ICs) play a crucial role in regulating the immune response by providing inhibitory or stimulatory signals when interacting with their ligands. However, the precise mechanism by which ICs affect the outcome of CHB patients remains unclear. In this study, we analysed clinical and immune data from 334 CHB patients, along with 17 healthy controls (HC). Using flow cytometry, we assessed immune cell profiles and examined the expression patterns of ICs on innate immune cells (NK/NKT) and adaptive immune cells (T cells) across different stages of CHB. Our analysis revealed distinct immune profiles and differential ICs expression among patients at various disease stages. Moreover, ICs levels were associated with immune cell functions, including cytotoxicity and antiviral cytokines production. We also found that NK and NKT cells may influence T cell function via their ICs expression. Overall, this study provides a comprehensive view of innate and adaptive immunity along with ICs variations in CHB patients, offering systematic immunological insights and suggesting ICs as a potential therapeutic target in HBV treatment.

Hepatitis A virus (HAV), traditionally a paediatric illness in endemic regions, is now exhibiting an emerging age shift in symptomatic cases. This study investigates the sero-molecular epidemiology of Hepatitis A in Puducherry and surrounding regions. Between January and November 2024, 513 acute viral hepatitis cases were evaluated for serum IgM anti-HAV. Representative samples underwent sequencing and B-cell epitope analysis. Of the 150 patients (29.23%) tested positive for HAV, children under 12 years (50%) were most affected, with an increasing trend in adult infection (31.33%), while adolescents aged 12–17 years accounted for 18.66%. All viral strains were genotype IIIA with no major B-cell epitope changes. A total of 732 asymptomatic individuals (2023–2024) were screened for IgG anti-HAV across different age strata (1–5, 6–10, 11–15, 16–20 and 21–30 years). The seroprevalence of HAV IgG varied by age: 1–5 years (58.5%), 6–10 years (52.87%), 11–15 years (44.95%), 16–20 years (56.88%) and 21–30 years (83.16%). Hepatitis A remains a significant health concern in Puducherry and its surrounding regions, with symptomatic infections occurring more frequently in children, followed by adults. However, HAV seroprevalence was higher in young adults and comparatively lower in children and adolescents.

Hepatitis B (HBV) prevalence is very high in pregnant women in the Dolpa district of Nepal, a region characterised by a remote geographic landscape and low vaccination coverage. Using mathematical modelling, we evaluated the impact of third-trimester tenofovir disoproxil fumarate (TDF) prophylaxis on HBV burden and estimated the time required to achieve HBV elimination in Dolpa. We developed a mathematical model to assess the impact of TDF prophylaxis on HBV elimination under four scenarios: baseline 50% vaccination coverage (scenario I), 50% TDF and baseline vaccination coverage (scenario II), 90% TDF plus baseline vaccination (scenario III) and 90% TDF and birth-dose plus 95% vaccination coverage (scenario IV). We estimated the impact TDF prophylaxis has on HBV-related morbidity and mortality and projected the time required for HBV elimination in the district. Our model suggests that HBV elimination is unlikely in Dolpa by 2100 under baseline interventions. The scale-up of TDF coverage to 90% with the baseline vaccination significantly reduces HBV prevalence and HBV-related mortality, making elimination possible in < 60 years. Implementing 90% TDF alongside birth-dose vaccination and 95% infant HBV vaccination coverage could accelerate HBV elimination—≤ 0.1% HBV prevalence in children younger than 5 years–achieving it by 2045. In geographically inaccessible settings, a micro-elimination approach using third-trimester TDF is an effective and equitable strategy for HBV control. This approach is likely to substantially reduce HBV burden and HBV-related mortality even before achieving elimination, while also addressing some of the challenges of immunoprophylaxis.

We assessed the characteristics and treatment outcomes of hepatitis C virus (HCV)-infected Canadian immigrants evaluated for antiviral therapy with a specific focus on time from arrival to HCV care engagement and the Direct-Acting Antiviral (DAA) era. A retrospective cohort analysis was conducted using medical records from HCV RNA positive patients assessed at The Ottawa Hospital Viral Hepatitis Program between August 1997 and March 2025. Of 2620 patients, 563 (21.5%) were immigrants. Proportions of treatment initiation, completion and SVR were comparable between immigrant and Canadian-born groups. SVR bloodwork completion was higher in the immigrant cohort (93.6% vs. 80.7%, p < 0.001). The overall median time from immigrant arrival in Canada to first HCV clinic assessment was 8 years. This delay in accessing HCV care trended downwards with each 5-year interval from 1990 to 2025 (median years = 23, 18, 12, 7, 3, 2, 1, p < 0.001). More recently immigrated patients demonstrated high proportions of DAA initiation (arrived in Canada 1990–1994: 62.3%; 1995–1999: 80.0%; 2000–2004: 92%; 2005–2009: 80.0%; 2010–2014: 90.7%; 2015–2019: 91.5%; 2020–2025: 89.3%, p < 0.001). Reduced times from immigrant arrival to specialty HCV care engagement and high DAA treatment initiation amongst more recently arrived patients suggest improved success in immigrant progression along the HCV care cascade. This reflects positive developments in Canadian HCV care over the past three decades and reinforces the importance of sustaining efforts towards national HCV elimination.