Hepatitis delta virus (HDV) infection causes chronic hepatitis D (CHD), the most severe form of chronic viral hepatitis with a high risk of progression to advanced liver disease. Off-label pegylated interferon alpha was the primary treatment option in Europe prior to the introduction of bulevirtide, a first-in-class HDV entry inhibitor. This review aimed to describe practical learnings around the management of CHD and strategies for supporting patients since bulevirtide 2 mg became the first approved treatment option in Europe. Since bulevirtide's approval, there has been an increased urgency to connect patients to care and real-world evidence has accumulated, underscoring the importance of reflex testing, increased awareness of HDV among doctors, and harmonization of universal screening guidelines in Europe to facilitate care for patients early in the disease course. Discussions with patients have shifted from preparing for disease progression to living with a long-term, daily treatment regimen, and clinical experience provides insight into best practices for navigating these conversations; it is critical for doctors to set evidence-based treatment expectations and provide ongoing guidance and support to patients. Real-world evidence demonstrates high treatment adherence and persistence; these studies and clinical trial data also indicate that long-term bulevirtide monotherapy is safe and effective, even in patients with compensated cirrhosis, may improve liver fibrosis measurements, and potentially reduce the risk of liver-related events and decompensation, which are important motivators for patients. Future research is needed to establish the safety and effectiveness of bulevirtide in certain special populations and determine the optimal treatment duration.

Hepatitis C virus (HCV) infection remains a major global health burden, and no vaccine preventing chronic infection is available. The envelope glycoproteins, E1 and E2, form a complex essential for viral entry; however, the mechanisms governing E1/E2 assembly and stability remain incompletely defined. Here, we investigated the role of the E1/E2 transmembrane (TM) regions in HCV infectivity using chimeras of JFH1-based recombinants with isolate-specific Core-NS2 sequences in which the C-terminal TM domains of E1 (TME1), E2 (TME2), or both (TME1E2) from the H77 isolate (genotype 1a) replaced those of isolates representing genotypes 1-6. We further introduced the TM domains of S52 (genotype 3a) or J6 (genotype 2a) into H77 and included reciprocal swaps between J6 and S52. Most TM-swap chimeras displayed impaired infectivity; however, serial passaging led to partial recovery associated with adaptive mutations in E1/E2 mapping not only to the C-terminal TM regions but also to the E1 stem and the internal E1 TM region (iTME1). Extending the TME1 swap to include upstream α-helical segments improved infectivity in selected chimeras, whereas inclusion of iTME1 abolished infectivity. These findings support functional interactions between membrane-associated regions of E1/E2 and their ectodomains and highlight their relevance for E1/E2-based HCV vaccine design.

Hepatocellular carcinoma (HCC) is the most frequent type of primary liver cancer and one of the leading causes of cancer-related mortality globally, with its incidence increasingly driven not only by viral hepatitis and alcohol-related etiologies but also by metabolic dysfunction-associated steatotic liver disease. Dietary intake can modify gut microbial activity and the production of microbial metabolites, which in turn may regulate hepatic immune signaling and metabolic pathways along the gut-liver axis. Microbiota-derived metabolites have emerged as important immunometabolic mediators linking dietary factors to hepatic immune responses and metabolic reprogramming. These metabolites, which have been shown to influence hepatic immune cell function and inflammatory signaling, include short-chain fatty acids, secondary bile acids, and tryptophan-derived indoles. Changes in the production and composition of these metabolites have been associated with immune dysregulation, chronic inflammation, and metabolic reprogramming that promote hepatocellular carcinoma development. This review highlights how diet-microbiota interactions reshape hepatic immunometabolism and discusses their potential translational relevance for prevention and therapeutic strategies in hepatocellular carcinoma.

Background: Systematic infectious screening is recommended before initiation of biologic therapies in chronic inflammatory rheumatic diseases (CIRDs), yet the clinical impact of this strategy in low-prevalence settings remains insufficiently characterized. This study aimed to evaluate the proportion of abnormal findings and their impact on treatment management. Methods: We conducted a retrospective single-center study including adult patients with CIRDs who underwent systematic pre-biologic infectious screening between January 2019 and June 2025. Screening included HIV, hepatitis B virus (HBV), hepatitis C virus (HCV), interferon-γ release assay (IGRA), and chest radiography. The primary outcome was the proportion of abnormal results and their impact on biologic initiation. Results: A total of 418 patients was included (mean age 48.2 ± 14.6 years; 69.1% female). No active HIV, HBV, or HCV infections were detected. Past HBV infection markers were identified in 2.6% of patients, and anti-HCV antibodies in 0.7%, all without detectable viremia. None of these findings required modification of biologic therapy. IGRA positivity was observed in 4.3% of patients and indeterminate results were seen in 3.1%. Preventive antituberculous therapy was initiated in most newly identified IGRA-positive cases, leading to delayed biologic initiation in several patients. Chest radiography yielded limited additional diagnostic value. Conclusions: In this population, systematic pre-biologic infectious screening identified few clinically actionable viral infections, whereas latent tuberculosis screening represented the main determinant of therapeutic modification. These findings support continued emphasis on tuberculosis risk assessment and warrant further prospective studies to evaluate optimized and potentially targeted screening strategies incorporating cost-effectiveness analyses.

Background/Objective: Long-term tenofovir disoproxil fumarate (TDF) therapy is associated with progressive bone mineral density loss in patients with chronic hepatitis B (CHB), yet existing fracture risk algorithms, such as FRAX, were not designed for this population. We aimed to develop and internally validate a clinical nomogram for identifying TDF-associated osteoporosis using penalized regression on demographic, virological, and biochemical predictors. Methods: In this single-center retrospective cohort study, 237 adult CHB patients receiving TDF for at least 12 months underwent dual-energy X-ray absorptiometry (DXA). Osteoporosis was defined as a T-score of -2.5 or lower at the lumbar spine or femoral neck. Thirteen candidate predictors were evaluated using LASSO regression with 10-fold cross-validation; selected variables were entered into an unpenalized multivariable logistic regression model; internal validation employed bootstrap resampling with 200 replications to derive optimism-corrected estimates of discrimination and calibration. The clinical utility was assessed using decision curve analysis (DCA). Results: Osteoporosis prevalence was 15.2% (n = 36). LASSO selected three predictors: prior fragility fracture (OR 11.45, 95% CI 4.82-27.15), the Charlson Comorbidity Index (OR 1.45 per unit, 95% CI 1.15-1.85), and alkaline phosphatase. The model demonstrated strong discrimination (apparent C-index 0.860; optimism-corrected 0.845) with excellent calibration (slope 0.94, intercept 0.02; Brier score 0.095). At a 0.15 probability threshold, sensitivity was 86.0%, specificity 78.0%, and negative predictive value 97.0%. DCA confirmed superior net clinical benefit over default strategies across the 0.10-0.30 threshold range; a pre-specified sensitivity analysis excluding fracture history retained meaningful discrimination (corrected C-index 0.791). Conclusions: This nomogram offers a clinically actionable, disease-specific tool for stratifying osteoporosis risk in TDF-treated CHB patients, particularly well suited for safely deferring DXA imaging in low-risk individuals. External validation in multicenter and ethnically diverse cohorts is required before widespread implementation.