Congenital dyserythropoietic anaemia type-I (CDA-I) is a rare autosomal recessive disease characterised by ineffective erythropoiesis, haemolysis and non-haematological developmental abnormalities. Its treatment is multifactorial, including the management of anaemia, iron overload and prevention of osteoporosis. The only treatment specific to CDA-I is subcutaneous interferon alpha (IFNα) 2A. This study presents the first summary of all published cases of CDA-I patients (n = 33) treated with IFNα and categorises their outcome. We also present new unpublished cases (n = 7). Overall, we find that IFNα administration causes a statistically significant mean increase in haemoglobin of 30.7 g/L (p < 0.001). However, we note that previous studies do not assess the impact of IFNα therapy on providing symptomatic benefit to patients with CDA-I, or the weight of side effects on their quality of life. We collaborate directly with patients through the organisation Congenital Anaemia Network to establish patient preferences regarding IFNα treatment. We propose a classification framework for the use of IFNα in CDA-I that includes patient-reported outcome measures in addition to grading response according to changes in Hb levels. We believe that the use of this framework will aid standardisation in measuring response to therapy, improve clinical practice and assist in future research.

Melanocytic Tumors of Uncertain Malignant Potential (MELTUMPs) remain among the most challenging entities in dermatopathology due to overlapping morphologic features and marked inter-observer variability. This comprehensive review critically assesses the diagnostic and potential prognostic significance of combining p16 and methylthioadenosine phosphorylase (MTAP) immunohistochemistry (IHC) as a practical surrogate for genomic alterations involving the 9p21 (CDKN2A/MTAP) locus. We analyzed the molecular underpinnings of the CDKN2A/MTAP axis and systematically reviewed existing literature to define an integrated IHC strategy for ambiguous melanocytic lesions. The combined use of p16, a sensitive marker of CDKN2A inactivation, and MTAP, a highly specific marker for homozygous 9p21 deletion, was assessed for its diagnostic complementarity and potential clinical utility. p16 IHC demonstrates high sensitivity but limited specificity due to heterogeneous staining in borderline lesions. In contrast, MTAP loss exhibits near-absolute specificity for CDKN2A/MTAP co-deletion, albeit with lower sensitivity. Concordant loss of both markers strongly supports melanoma or high-risk melanocytoma, while MTAP retention may predict responsiveness to adjuvant interferon therapy. Combined p16/MTAP IHC provides a synergistic, biologically grounded approach that refines diagnostic accuracy in MELTUMPs. This dual-marker algorithm promotes a shift from purely morphology-based evaluation toward a reproducible, molecularly informed classification, improving both diagnostic confidence and patient management.

Polycythemia vera (PV) and essential thrombocythemia (ET) are associated with a well-recognized increased risk of thrombotic events, bleeding, and all-cause mortality, but the frequency of these outcomes during treatment has rarely been assessed in large cohorts. In this nationwide, population-based study, we analyzed 2604 PV and 3141 ET patients using multiple Swedish health care registers, covering 43 612 patient-years. Rates of arterial and venous events, major bleeding, and all-cause mortality (ACM) were evaluated across therapies. Unexpectedly, 42.3% of low-risk PV patients and 29.7% of very low/low-risk ET patients received hydroxyurea (HU) during follow-up. High-risk PV patients treated with interferon (IFN) exhibited the lowest arterial event rate (2.21 per 100 patient-years). In high-risk ET, patients with IFN therapy experienced the lowest arterial and venous event rates (1.55 and 0.44 per 100 patient-years). Advanced age and leukocytosis at diagnosis independently predicted thrombosis, bleeding, and ACM in both PV and ET. Multivariable analysis showed that HU and IFN were associated with reduced ACM risk; HU also conferred protection against thromboembolism and major bleeding. This study highlights risk factors associated with complications during treatment in a real-world context and reinforces the role of HU and IFN as first-line therapies in PV and ET.

The cost-effectiveness of increasing hepatitis Delta testing for individuals co-infected with HBV and HIV in the Netherlands.

Association of PD-1+ B cells and IgG+ plasma cells with clinical cure of hepatitis B following interferon therapy.

Hepatitis B virus (HBV) infection remains a major cause of hepatocellular carcinoma (HCC). It is estimated that 254 million people are chronically infected with HBV, with 1.1 million deaths projected in 2025. Functional cure, defined as sustained loss of hepatitis B surface antigen (HBsAg), is important for the prevention of HCC. While nucleos(t)ide analogs maintain viral suppression in over 95% of patients, HBsAg clearance is achieved in only 2%-11%. The functional cure rate with interferon therapy is highly variable in different populations, ranging from 2% to over 40%. Consequently, functional cure remains the primary focus of novel therapeutic development. Here, we analyze the virological and immunological barriers to functional cure and summarize current therapeutic methods. Among these, novel RNA-interference-based therapeutics reduce HBsAg to below 10% of baseline in most patients. However, monotherapy with these agents results in HBsAg loss in fewer than 10% of cases. However, sequential interferon or immunomodulatory agents raise the HBsAg loss to 15%-30%. To achieve the &gt; 50% cure rate likely required for the World Health Organization’s 2030 elimination goals, we analyze promising strategies focused on multi-target combination approaches and precision-medicine frameworks.

Background and aimsHBsAg seroclearance is a key indicator of functional cure in chronic HBV. We evaluated the efficacy of pegylated interferon-α (Peg-IFN-α) in HBeAg-negative patients and its association with T-cell subsets.MethodsWe retrospectively analyzed 618 patients, 34 of whom underwent longitudinal immune profiling.ResultsAmong 618 patients, a total of 214 cases (34.6%) achieved HBsAg clearance, namely 214 cases in group R and 404 cases in group NR. The R group was younger, had longer treatment, and had lower baseline HBsAg levels compared to the NR group. In 34 HBeAg-negative patients with chronic HBV infection, we studied the distribution of CD4 + and CD8 + T cells at different stages of differentiation. After 24 weeks of interferon therapy, responders exhibited increased CD4 + TCM and stable CD8 + TCM levels, along with decreased CD8 + TEMRA and Th2 cells. In contrast, non-responders showed reductions in TCM, elevated TEMRA, and Th2 cells. Responders exhibited a marked decline in PD-1 + CD8 + and CD160 + CD8 + T cells (at 0.97 and 0.95 times the baseline), whereas non-responders showed relative increases (at 1.74 and 1.55 times the baseline).ConclusionPeg-IFN-α may promote HBsAg clearance in selected HBeAg-negative patients with low antigen burden and partially reversible T-cell exhaustion.Supplementary InformationThe online version contains supplementary material available at 10.1186/s12879-025-12042-7.

Background. The etiology of acute respiratory viral infections is quite diverse, including influenza virus, respiratory syncytial virus, adenovirus, seasonal coronaviruses, bocavirus, rhino- and metavirus, and parainfluenza virus. The frequency of mixed infections is quite high: according to various sources, viral coinfection accounts for approximately 30%, bacterial coinfection up to 20%, and fungal coinfection up to 8%. The development of coinfections significantly complicates the course of the infection, increasing the risk of death. Severe illness and death are more common with influenza, COVID-19, adenovirus, and respiratory syncytial virus infections. According to current clinical guidelines, treatment of patients with acute respiratory viral infections should be aimed not only at achieving a full and lasting recovery but also at preventing potential complications. Therapeutic tactics for acute respiratory viral infections, as a rule, include etiotropic, pathogenetic and symptomatic treatment; the use of agents with indirect antiviral and immunomodulatory effects may also be recommended. Results. This review article focuses on the prevention of acute respiratory viral infections, influenza, and COVID-19 in outpatient practice, with a focus on high-risk patients. It examines the mechanisms of complication development in the most vulnerable populations, including pregnant women and the elderly, as well as the characteristics of their immune response. The potential of interferon therapy as a preventive measure is discussed. Particular attention is paid to the use of recombinant interferon alpha-2b in various pharmacological forms, its antiviral and immunomodulatory effects, as well as its clinical efficacy and safety in outpatient practice. The importance of a comprehensive strategy combining vaccination, non-specific protective measures, and the use of interferon-containing drugs for the effective protection and treatment of high-risk patients is emphasized. Conclusion. The data presented in the article indicate that interferon alfa-2b with antioxidants is appropriate for use in high-risk patients to reduce the incidence and severity of respiratory viral infections, as well as to prevent complications and adverse outcomes.

Background: Pre-fibrotic myelofibrosis (pre-PMF) is a rare subentity of myeloproliferative neoplasm (MPN) with limited overall survival and the potential for progression toward overt, symptomatic myelofibrosis or blastic transformation. To date, a consensus on the treatment of pre-PMF, especially in asymptomatic cases, has yet to be reached. Interferon therapy has been employed as an effective treatment for MPN for many decades, due to its immunomodulatory properties and disease-modifying effects. Methods: The objective of this monocentric study was to evaluate hematological, molecular, and clinical responses, as well as the overall outcome, to pegylated interferon (peginterferon) in pre-PMF cases harboring a JAK2 or CALR mutation. Results: In a cohort of 55 consecutive patients with a median follow-up period of 3.89 (1.63; 6.10) years, a high rate of complete hematological response (81%) was documented after 24 months. Deep molecular responses with a >50% reduction in allele burden were documented in 54.6% of the JAK2-mutated and 7.7% of CALR-mutated patients, respectively (p = 0.023). Concerning fibrosis, at least the stabilization of disease was achieved in 73% of evaluable patients. Furthermore, only one case of blastic transformation was observed, along with three cases of thromboembolic events in the JAK2-mutated cohort. Conclusions: The study confirms the substantial efficacy of interferon in pre-PMF patients with rapid hematological normalization in most patients. Molecular responses were striking, but largely confined to JAK2-mutated patients. To our knowledge, this is the largest retrospective cohort of strictly WHO-defined pre-PMF patients treated with interferon and observed for a reasonable duration of time.

Successful Interferon-α Therapy for a Huge Lesion Including Eye and Eyelids.

Interferon-based optimal antiviral strategies in underage patients with chronic hepatitis B: A propensity score-weighted cohort study.

Background. Chronic hepatitis C (CHC) remains a significant health issue that requires effective treatment approaches. The incidence of CHC in Russia amounted to 34.86 per 100 thousand population in 2024, more than half of the patients having HCV genotype 1. Objective. To evaluate the effectiveness of the direct-acting antiviral drug grazoprevir + elbasvir in patients with HCV genotype 1. Material and methods. The study involved 93 patients with HCV genotype 1, confirmed by ELISA and PCR, aged 18 to 77 years who were treated in the Day patient facility of the Kirov Infectious Diseases Clinical Hospital in 2024. All patients received combination therapy with grazoprevir 100 mg + elbasvir 50 mg for 8 and 12 weeks. Results. The age of patients with CHC was 60 years (47; 65). 5.4% of patients underwent pegylated interferon and ribavirin therapy. The viral load was 1.3×106 (1.6×105; 1.4×106) IU/mL. After the therapy, all patients showed a biochemical response. Liver enzymes decreased significantly: ALT 40 (21.8; 70.5) – 16 (12.6; 22) U/L, AST 37 (26.8; 61.3) – 20 (17.2; 27.4) U/L. Other parameters were within normal ranges. Conclusion. A sustained virological response was obtained in 99% of cases after antiviral therapy in patients with HCV genotype 1, regardless of the liver fibrosis stage and compensated liver cirrhosis.

Interferon-α is emerging as the preferential cytoreductive therapy for polycythemia vera (PV) and essential thrombocythemia (ET) due to improved long-term outcomes over alternatives such as hydroxyurea. Historically, interferon-α therapy has been marked by high rates of adverse events and subsequently poor adherence. Long-acting formulations of interferon-α, i.e., ropeginterferon-α-2b (ropeg), improve tolerability. However, nearly half of ropeg-treated patients experience fatigue, arthralgias, or myalgias and 10-20% discontinue treatment or cannot tolerate maximal ropeg doses, due to adverse events. Herein, we report our retrospective experience of adjunct metformin therapy in 11 PV and ET patients who were intolerant of ropeg. Metformin improved ropeg-related fatigue and/or myalgias in 10 of 11 patients. A complete hematologic response (CHR) was maintained in all 6 patients who had already achieved this prior to starting metformin, and a deepened hematologic response was observed in 3 of 4 patients after the addition of metformin. These encouraging results merit further evaluation in a randomized clinical study. Further, additional investigations are needed to elucidate the mechanism of interferon-α-mediated fatigue and myalgias and the mechanism of putative beneficial interaction between interferon-α and metformin.

BackgroundAdjuvant therapies are now considered standard care for high-risk melanoma patients. It is urgent to identify reliable biomarkers to select patients at high risk of relapse, who will derive more benefit from adjuvant therapy.MethodsTargeted next-generation sequencing using a 437 cancer-related gene panel was performed on primary tumor samples from 55 patients in stage I-III melanoma and postsurgical plasma samples from 46 patients. Association analysis of clinico-genomic characteristics with disease-free survival was conducted.ResultsThe median DFS was 39.2 months (rangement: 1.4–49.7 months). Patients receiving anti-PD-1 adjuvant therapy had a longer DFS than those receiving adjuvant interferon therapy (mDFS, NA vs. 21.3 months, HR 0.36 [95% CI: 0.13–1.03], P = 0.047). No significant correlation of DFS with driver mutations in BRAF, NRAS and KIT was observed. Chromosomal instability score (CIS) was identified as an independent predictive factor of DFS following adjustment for clinical and genetic factors (HR 4.06 [95% CI: 1.28–12.89], P = 0.017), with an inferior DFS observed in patients with high CIS compared with the CIS-low patients (mDFS, 14.3 vs. 49.7 months, HR 3.90 [95%CI: 1.40–11.00], P = 0.005). In addition, patients with a maxVAF > 1% in the postsurgical ctDNA had a worse DFS compared with those with a maxVAF ≤1% (mDFS, 11.0 vs. 49.7 months, HR 3.70 [95% CI: 1.20–11.00], P = 0.012). Finally, CIS and postsurgical ctDNA status were considered as independent factors for recurrence risk in stage I-III melanoma.ConclusionIdentification of clinical and genetic biomarkers for recurrence risk prediction in resected melanoma may aid in clinical decision-making for early disease monitoring and optimal design of therapeutic strategies.Supplementary InformationThe online version contains supplementary material available at 10.1186/s12885-025-15093-w.

PurposeTo identify early predictive factors for hepatitis B surface antigen (HBsAg) clearance at week 48 following pegylated interferon (Peg-IFN) therapy in inactive HBsAg carriers (IHC), and to develop an early machine learning-based model to assist clinical decision-making.MethodsThis retrospective analysis was based on a multicenter, prospective cohort and included 777 IHC patients who received at least 48 weeks of Peg-IFN therapy. Least Absolute Shrinkage and Selection Operator (LASSO) regression and the Boruta algorithm were applied to select predictive variables. Nine machine learning models—including logistic regression (LR), decision tree (DT), and random forest (RF)—were constructed and evaluated using 10-fold cross-validation. An external validation cohort (n = 167) from three medical centers in Beijing was used for model validation. SHapley Additive exPlanations (SHAP) values were used to interpret variable contributions.ResultsThe overall HBsAg clearance rate at week 48 was 29.9% (232/777). Key predictors included baseline HBsAg level, HBsAg decline > 1 log IU/mL at week 12, and the ratio of alanine aminotransferase (ALT) to HBsAg at week 12. The RF model demonstrated the best performance with an area under the curve (AUC) of 0.829 (95% CI: 0.784–0.874) and specificity of 0.774 in the training set, and an AUC of 0.838 (95% CI: 0.759–0.917) with specificity of 0.968 in the external validation set. SHAP analysis showed that baseline HBsAg had the highest predictive importance.ConclusionsThe RF-based model accurately predicts HBsAg clearance in IHC patients undergoing Peg-IFN therapy and offers a promising tool for early identification of candidates for individualized treatment strategies.Supplementary InformationThe online version contains supplementary material available at 10.1186/s12985-025-03012-1.

Background: Chronic hepatitis B (CHB) patients with high hepatitis B surface antigen [hepatitis B surface antigen (HBsAg), &gt; 1500 IU/mL] during nucleos(t)ide analogs (NAs) treatment are considered a "non-optimal population" with poor responses. Sequential pegylated interferon (PEG-IFN) therapy can reduce HBsAg levels, but individual responses vary. Objectives: The present study aimed to explore factors influencing HBsAg response in this population. Methods: This retrospective, single-center study included 85 CHB patients who had received NAs for at least one year, had HBsAg levels &gt; 1500 IU/mL, and were HBV DNA-negative. Patients were divided into two groups: The study group (n = 35) received PEG-IFN sequentially combined with NAs, while the control group (n = 50) continued on NAs monotherapy. The HBsAg decline rates at weeks 12, 24, and 48 were compared between the two groups. A generalized estimating equation (GEE) model was used to analyze factors associated with HBsAg reduction. Results: The median HBsAg decline rates at weeks 12, 24, and 48 in the study group were 43.92%, 63.68%, and 84.55%, respectively, significantly greater than those in the control group (2.86%, 5.95%, and 11.02%, respectively; all P &lt; 0.001). At week 48, the clinical response rate was 22.86% in the study group versus 0% in the control group (P &lt; 0.001). The GEE analysis showed that treatment group, time, and their interaction significantly influenced HBsAg dynamics (all P &lt; 0.05). The odds ratio for HBsAg reduction in the study group was 2.673 (95% CI: 1.815 - 3.937). Conclusions: Sequential PEG-IFN combined with NAs significantly improves HBsAg reduction and clinical response rates in CHB patients with high baseline HBsAg, with efficacy increasing over time, supporting its role in optimizing treatment for this population.

Interferon therapy achieves potent reduction in JAK2 allele burden in patients with myeloproliferative neoplasms: A real-world analysis

High-frequency monitoring of clonal dynamics in MPN using saliva and peripheral blood during interferon therapy

Modern oncology needs to develop and implement antineoplastic agents that provide sustained remission without serious side effects. Immunotherapy and targeted therapy agents that activate innate immunity may address this issue. The stimulator of interferon genes (STING), an intracellular protein, mediates the synthesis of type I interferons, which have antiviral, antitumor, and antiproliferative properties. The multifaceted effects of interferons may be beneficial in cancer therapy. However, potential side effects of systemic interferon therapy underlie the need for the methods of stimulating them locally in the tumor nodule by targeting the STING pathway. STING is directly activated by the cyclic dinucleotide cGAMP. It is synthesized by the cyclic GMP-AMP synthase (cGAS) from adenosine triphosphate and guanosine triphosphate. However, cGAMP cannot be used as a therapeutic agent because it is unstable and only persists in the cell for a short period of time before being hydrolyzed. Therefore, researchers all over the world are working to synthesize new activators of the STING pathway. In cancer therapy, using STING activators as part of an immunoconjugate for targeted delivery to the tumor nodule is considered more effective. A monoclonal antibody against a tumor-specific antigen is the second component of the immunoconjugate. Given the high risk of tumor cell resistance to cytostatic drugs commonly used in current clinical practice, an immunoconjugate with a STING activator may provide advantages over existing therapies. Several immunoconjugates have already been tested in preclinical studies and are considered promising for drug development. However, further research is needed to study the properties of new compounds and improve their efficacy and tolerability. The search was performed in PubMed, eLIBRARY.RU, Google Scholar, NCBI ClinicalTrials, and PubChem and included publications from June to August 2025. The following search terms were used: STING protein, cGAS protein, cGAS-STING pathway, IFN-β, interferon-based treatment, type I IFN induction, antibody-drug conjugate, STING activation, STING agonist, and HER2-targeted therapies.

Background: Subacute sclerosing panencephalitis (SSPE) is a rare condition notorious for causing a chronic, progressive encephalitis that affects children and young adults, resulting from persistent infection with an immune-resistant measles virus. Methods: Descriptive study of a case of an eleven-year-old child who had a rapid and fulminant course of illness, suggesting a rare phenotype of “Fulminant SSPE”. This was confirmed with an electroencephalogram (EEG) and measles antibodies in the cerebrospinal fluid (CSF). Results: The clinical deterioration and electrophysiological features with imaging provided evidence of a grave entity. Our patient had a downhill course despite starting on intrathecal interferon therapy. The child succumbed to the illness very rapidly, and autopsy revealed predominant inflammation and minimal gliosis. Conclusion: Awareness of this rare entity, fulminant SSPE, is of paramount importance to recognise it early (as the presentation may be atypical), prognosticate about the illness, and initiate available immunomodulatory therapy