hepatitis-B vaccine

Elevated ALT correlates with severe liver injury, monocyte infiltration, and Pro-inflammatory immune dysregulation in chronic hepatitis B virus infection.

Huang Jian J, Xu Ning N, Liang Xiuyan X, Cai Defeng D

Hepatitis B virus (HBV) infection remains a global health burden. Although alanine aminotransferase (ALT) is a well-established marker of liver injury, its relationship with immune infiltration, monocyte activation, and inflammatory immune skewing in chronic HBV infection remains incompletely understood. This study aimed to investigate the associations of ALT with liver injury, monocyte infiltration, and hepatic immune microenvironment dysregulation. A total of 192 HBV-infected patients and 37 healthy controls were enrolled. Serum ALT, AST, HBV seromarkers, HBV-DNA, alpha-fetoprotein (AFP), and serum fibrosis markers (COLIV, HA, PIIINP, LN) were measured. Univariate and multivariate regression analyses were used to adjust for confounders including age, sex, HBV-DNA, fibrosis markers, and HBeAg status. Transcriptomic data from the GSE84044 liver biopsy cohort (n = 105) were analyzed using the xCell algorithm to evaluate hepatic immune infiltration, macrophage polarization, and immune scores. Gene set enrichment analysis (GSEA) was performed to explore monocyte chemotaxis, activation, and WNT/β-catenin signaling pathway. Chronic hepatitis B (CHB) patients showed significantly elevated ALT and AST. Higher ALT levels were strongly associated with elevated fibrosis markers and AFP, indicating more severe liver injury. Peripheral monocytes count and intrahepatic monocyte infiltration were both significantly increased in high-ALT patients. However, after multivariate adjustment, ALT was no longer independently associated with monocyte infiltration, suggesting that the association was largely attributable to overall disease severity rather than a specific ALT-related association. GSEA showed that ALT was positively correlated with monocyte chemotaxis, activation, macrophage differentiation, and WNT/β-catenin signaling pathway. Immune landscape analysis revealed a pro-inflammatory immune profile in high-ALT patients, characterized by increased M1 macrophages, CD8+ T cells, and elevated immune scores, accompanied by decreased Tregs and Th1 cells. Elevated ALT in chronic HBV infection correlates with severe liver injury and a pro-inflammatory, dysregulated hepatic immune microenvironment characterized by enhanced monocyte infiltration and M1 macrophage polarization. Transcriptomic associations reveal a statistical link between WNT/β-catenin signaling activation and hepatic immune dysregulation in HBV-related liver injury; these correlative findings provide preliminary clues for developing immunomodulatory therapeutic strategies for CHB.

Clinical spectrum and burden of extrahepatic manifestations in chronic hepatitis B: A multinational study from 2000 to 2025.

Khan Sajjad Ahmed SA, Subedi Anuj A, Marasini Anurag A, Shrestha Alisha A et al.

Chronic hepatitis B virus (HBV) infection is associated with both hepatic and extrahepatic complications. While liver-related outcomes are well characterized, the burden, demographic patterns, and survival associated with extrahepatic manifestations (EHMs) remain incompletely defined. This study aimed to evaluate the spectrum, incidence, and survival impact of EHMs in a large, geographically diverse cohort of patients with chronic HBV infection. We conducted a retrospective cohort study using the TriNetX Global Research Network, including 2,32,820 patients aged 0 to 90 years with chronic HBV infection. Demographic variables included age, sex, race, ethnicity, and geographic region. EHMs assessed comprised renal (glomerulonephritis), vasculitic (polyarteritis nodosa), musculoskeletal (arthralgia), hematologic (aplastic anemia), immunologic (cryoglobulinemia), and neurologic (polyneuropathy) conditions. Incidence proportions and incidence rates per person-day were calculated and stratified by demographic characteristics. Survival probabilities were estimated for each manifestation. The mean age of the cohort was 60 ± 14 years, and 56.9% were male. Racial distribution included Asian (34.4%), White (15.4%), Black or African American (12.1%), and unknown race (34.4%). Most patients were non-Hispanic (53.6%), with 44.1% reporting unknown ethnicity. Patients were represented across all US regions and internationally. Glomerulonephritis occurred in 1.26% of patients, with higher incidence in older adults, males, and Native Hawaiian/Other Pacific Islander and Hispanic/Latino populations. Polyarteritis nodosa was rare (0.04%) and predominated in older individuals, American Indian/Alaska Native, and Hispanic/Latino patients. Arthralgia was the most frequent EHM (13.76%), increasing with age and more common among females and Black or African American individuals. Cryoglobulinemia (0.10%) and aplastic anemia (0.12%) were uncommon. Polyneuropathy affected 3.27% of patients, with higher prevalence among older adults and males. Chronic HBV infection is associated with a wide spectrum of extrahepatic manifestations, with substantial variation by demographic factors. These findings underscore the need for comprehensive multisystem surveillance and targeted risk stratification in patients with chronic HBV infection.

Comprehensive Stability Assessment of Squalene in a Nanoemulsion Adjuvant and the SpiN-Tec Vaccine: HPLC Quantification, Stress Testing, and Stability Studies.

Gomes Isabela Pereira IP, Rivelli Graziella Gomes GG, Bagno Flávia Fonseca FF, Hojo-Souza Natália Satchiko NS et al.

Squalene-based nanoemulsions are widely used as adjuvants in vaccine formulations, but their stability can be affected by environmental factors such as pH, oxidative stress, temperature, and light. We have produced a squalene nanoemulsion (CTVad1) to support the clinical development of new vaccines. This study aimed to develop and validate an HPLC method for squalene quantification in SpiN-Tec, a recombinant protein vaccine against COVID-19. We also aimed to evaluate the stability of the CTVad1 adjuvant and SpiN-Tec under controlled storage conditions. A reversed-phase HPLC method was developed and validated, and comprehensive forced degradation studies were performed on the raw material and SpiN-Tec under acidic, basic, oxidative, thermal, and photolytic conditions to demonstrate the stability-indicating capability of the method. Physicochemical, morphological, and biological characteristics were assessed, and stability studies of both the vaccine and the CTVad1 adjuvant were performed under accelerated and long-term conditions. The HPLC method was selective, precise, accurate, linear, and robust. Squalene raw material degraded under all tested conditions, whereas formulation in nano-sized globules improved its stability, with degradation observed only under hydrogen peroxide and light exposure. CTVad1 remained stable over time, exhibiting only minor, non-critical changes within the specification limits in both accelerated and long-term stability studies, regardless of the glass packaging used (clear or amber). In addition, the SpiN-Tec vaccine maintained its physicochemical and biological integrity under all tested conditions, with all evaluated parameters remaining within the established specification ranges. Our findings demonstrate that proper formulation, packaging, and storage conditions can preserve squalene stability in nanoemulsion-based vaccines, ensuring the quality, safety, and efficacy of the SpiN-Tec vaccine and its adjuvant throughout shelf life.

Untangling the Web of Hepatitis C Risk in Rural Communities.

Sami Muhammad Mohsin MM, Amjad Muhammad Waqar MW, Latif Muhammad Bilal MB