Interferon Therapy Research Articles

Research progress on the effect of hepatitis B virus DNA integration on antiviral therapy

Hepatitis B virus (HBV) DNA integration occurs during the reverse transcription process of HBV replication, which develops in the early stages of HBV infection and accompanies the entire disease course. The integration of HBV DNA is detrimental to the attainment of clinical cure goals and also raises the risk of developing liver cancer. Theoretically, nucleos(t)ide analogs can reduce the synthesis of new double-stranded linear DNA, but there is no clearance function for hepatocytes that have already integrated HBV. Therefore, patients with serum HBV DNA-negative conversions still have the risk of developing liver cancer. As an immunomodulatory drug, interferon can not only inhibit viral replication but also inhibit or even eliminate existing clonally amplified hepatocytes carrying integrated HBV DNA fragments. However, there are currently few studies on the effects of nucleos(t)ide analogues and interferon therapy on HBV DNA integration. Thus, large-scale clinical studies are urgently needed for further clarification.

Burden, Outcome, and Comorbidities of Extrahepatic Manifestations in Hepatitis B Virus Infections.

Hepatitis B virus (HBV) infections affect approximately 296 million people around the world, and the prevalence of any past or present HBV infection during the years 2015-2018 was as high as 4.3%. Acute HBV infection often presents with nonspecific symptoms and is usually self-limited, but 5% of patients can have persistent infections leading to chronic HBV infection and the risk of turning into chronic HBV infection is significantly higher in babies with vertical transmission (95%). Patients with chronic HBV infection are usually asymptomatic, but 15 to 40% of chronic HBV carriers develop cirrhosis and/or hepatocellular carcinoma. In addition to liver-related disorders, HBV is also associated with several extrahepatic complications, including glomerulonephritis, cryoglobulinemia, neurologic disorders, psychological manifestations, polyarthritis, and dermatologic disorders. Making the diagnosis of HBV can be challenging since patients with chronic infections can remain symptom-free for decades before developing cirrhosis or hepatocellular carcinoma, and patients with acute HBV infection may have only mild, nonspecific symptoms. Therefore, understanding how this virus causes extrahepatic complications can help clinicians consider this possibility in patients with diverse symptom presentations. The pathophysiology of these extrahepatic disorders likely involves immune-related tissue injury following immune complex formation and inflammatory cascades. In some cases, direct viral infection of extrahepatic tissue may cause a clinical syndrome. Currently, the American Association for the Study of Liver Diseases recommends treatment of chronic HBV infections with interferon therapy and/or nucleos(t)ide analogs, and this treatment has been reported to improve some extrahepatic disorders in some patients with chronic HBV infection. These extrahepatic complications have a significant role in disease outcomes and increase medical costs, morbidity, and mortality. Therefore, understanding the frequency and pathogenesis of these extrahepatic complications provides important information for both specialists and nonspecialists and may help clinicians identify patients at an earlier stage of their infection.

Intravesical Interferon Therapy vs Hyaluronic Acid for Pain Among Female Individuals With Interstitial Cystitis

Interstitial cystitis (IC) is a debilitating condition. Although viral infection is a potential etiological cause, few studies have detected the effect of antiviral treatment. To determine the efficacy and safety of intravesical interferon instillation compared with hyaluronic acid in female patients with IC. This double-masked, randomized phase 2/3 clinical trial with parallel group design was implemented from October 2022 to April 2023 and had a 6-month follow-up period. The study was conducted at a single center. Eligible participants were female patients aged 18 to 70 years with a diagnosis of IC for more than 6 months. The last visit took place in October 2023. Data were analyzed between October and November 2023. Patients were randomized 1:1 to receive either intravesical instillation of interferon or hyaluronic acid. The primary end point was change in visual analog scale pain score. Secondary end points included changes in voiding frequency, functional bladder capacity, symptom index, and global response assessment. Adverse events were closely monitored. Among the 52 patients, the mean (SD) age was 50.0 (14.1) years and they were randomized to either the interferon group (26 [50%]) or hyaluronic acid (26 [50%]). The visual analog pain score showed the interferon group decreased more significantly than hyaluronic acid (-1.3; 95% CI, -2.3 to -0.3; P = .02) at month 6, with 20 patients (77%) exhibiting a 30% or higher reduction in pain compared with baseline. Secondary end points of voiding frequency, functional bladder capacity, and nocturia episodes showed no significant difference between 2 therapies. However, interferon showed a significantly higher reduction in the Interstitial Cystitis Symptom Index (-3.0; 95% CI, -5.3 to -0.7; P = .01) and the Problem Index (-2.5; 95% CI, -4.5 to -0.4; P = .02) at month 6, with 22 patients (85%) presenting as moderately or markedly improved. The frequencies of adverse events were similar between 2 groups. Only 1 patient discontinued hyaluronic acid because of poor effectiveness. In this randomized clinical trial, female patients with IC could benefit from intravesical interferon therapy, without serious adverse events. These results offered hope for antiviral approaches in IC, but larger-scale, multicenter trials and long-term follow-up should be considered. ClinicalTrials.gov Identifier: NCT05912946.

Relationship between Phenotypic Changes of Dendritic Cell Subsets and the Onset of Plateau Phase during Intermittent Interferon Therapy in Patients with CHB*

ObjectiveThis study aimed to evaluate whether the onset of the plateau phase of slow hepatitis B surface antigen decline in patients with chronic hepatitis B treated with intermittent interferon therapy is related to the frequency of dendritic cell subsets and expression of the costimulatory molecules CD40, CD80, CD83, and CD86. MethodThis was a cross-sectional study in which patients were divided into a natural history group (namely NH group), a long-term oral nucleoside analogs treatment group (namely NA group), and a plateau-arriving group (namely P group). The percentage of plasmacytoid dendritic cell and myeloid dendritic cell subsets in peripheral blood lymphocytes and monocytes and the mean fluorescence intensity of their surface costimulatory molecules were detected using a flow cytometer. ResultsIn total, 143 patients were enrolled (NH group, n = 49; NA group, n = 47; P group, n = 47). The results demonstrated that CD141/CD1c double negative myeloid dendritic cell (DNmDC)/lymphocytes and monocytes (%) in P group (0.041 [0.024, 0.069]) was significantly lower than that in NH group (0.270 [0.135, 0.407]) and NA group (0.273 [0.150, 0.443]), and CD86 mean fluorescence intensity of DNmDCs in P group (1832.0 [1484.0, 2793.0]) was significantly lower than that in NH group (4316.0 [2958.0, 5169.0]) and NA group (3299.0 [2534.0, 4371.0]), Adjusted P all < 0.001. ConclusionReduced DNmDCs and impaired maturation may be associated with the onset of the plateau phase during intermittent interferon therapy in patients with chronic hepatitis B.

Predictive Value of Baseline Serum Marker Levels for the Effect of Interferon Therapy in Patients With Chronic Hepatitis B

To study the changes in the serum markers in chronic hepatitis B patients who have had previous treatment with long-acting interferon therapy of nucleoside and those who have not and to assess the value of the serum markers for clinical prognosis evaluation. The clinical data of 411 cases of chronic hepatitis B were collected. All cases were given the additional treatment of long-acting interferon between October 2019 to April 2022. The cases were divided into two groups, a previously treated group consisting of patients who had been treated with nucleoside and nucleotide analogues (NAs) for more than 6 months after they became infected with hepatitis B virus (HBV) for over 6 months and an initial treatment group, or treatment naïve group, consisting of patients who had HBV infection for over 6 months and received no treatment or patients who have stopped NAs therapy for more than 6 months. The serum marker levels of the previously treated group and the initial treatment group, i.e., the previously treatment-naïve patients, were compared, and the receiver operating characteristics (ROC) curve was used to evaluate the value of the baseline levels of hepatitis B surface antigen (HBsAg) and HBV pregenomic RNA (pgRNA) for predicting the rate of cured cases in the two groups. There was no significant difference in the rate of cured cases between the previously treated group and the initial treatment group. The baseline HBV DNA, HBsAg, and hepatitis B e antigen (HBeAg) levels of the cured cases in both groups were significantly lower than those in the uncured cases (P<0.0001). After 48 weeks of treatment, the serum HBsAb levels (mIU/mL) of the cured cases in both the previously treated and initial treatment groups were significantly higher than those of the uncured cases in the two groups (previously treated group: 78.97±22.57 vs. 0.99±0.38, P<0.0001; initial treatment group: 235.50±175.00 vs. 1.32±0.88, P<0.0001). The serum HBsAb levels (mIU/mL) of the cured cases in the initial treatment groups were significantly higher than that of cured cases in the previously treated group (235.50±175.00 vs. 78.97±22.57, P<0.0001). Within 0 to 60 weeks of treatment, HBV pgRNA levels of cured cases in both groups were significantly lower than those of the the uncured cases in both groups (P<0.0001). Multivariate logistic regression and ROC curve analysis showed that baseline serum HBsAg was the influencing factor and predictor of interferon efficacy in both the previously treated cases and the initial treatment cases, with the area under the curve (AUC) being 0.80 (95% confidence interval [CI]: 0.7423-0.8615, P<0.0001) and 0.74 (95% CI: 0.6283-0.8604, P=0.0079), respectively, and the optimal cut-off values being 244.60 IU/mL and 934.40 IU/mL, respectively. However, the baseline serum HBV pgRNA level of under 1340.00 copies/mL in the initial treatment cases led to better sensitivity and better specificity in efficacy prediction, with the AUC of the baseline HBV pgRNA being 0.9649 (95% CI: 0.9042-1.0000, P<0.0001). Among the previously treated cases and the initial treatment cases, patients who achieve clinical cure have lower levels of HBV DNA, HBsAg, and HBeAg at baseline, lower level of HBV pgRNA over the course of their treatment, and higher level of HBsAb at week 48. Baseline HBsAg levels can be used to effectively predict the clinical cure outcomes in previously treated cases and initial treatment cases. Baseline HBV pgRNA levels also exhibit a high predictive value for treatment outcomes in initial treatment cases.

Elucidating the association between direct-acting antivirals and Parkinson's disease in patients with hepatitis C virus infection

BackgroundSome epidemiological studies have found an increased association between Parkinson's disease (PD) and chronic hepatitis C virus (HCV) infection. Although a few studies have also found a decreased risk of PD with interferon-α therapy, the effect of direct-acting antivirals (DAAs) on Parkinson's disease remains unclear. The current study seeks to assess and elucidate the association between DAAs and PD in patients newly diagnosed with chronic HCV infection. MethodsWe conducted a retrospective cohort study of patients ≥18 years diagnosed with HCV using MarketScan Commercial and Medicare Supplemental database (2012–2019). Follow-up started with the initiation of DAA (or randomly assigned date for the non-DAA group) and ended at occurrence of PD, disenrollment, or end of the study period. A multivariable Cox proportional hazards model was used to estimate hazard ratios (HR) and 95% confidence intervals. ResultsWe identified 48,356 patients diagnosed with HCV. The mean follow-up time of the cohort was 1.31 years. The incidence rate of PD was 53 per 100,000 person-years for the DAA group and 48 per 100,000 person-years for the non-DAA group. The adjusted HR was 1.24 (95% CI = 0.56–2.73). Results were consistent across sensitivity and subgroup analyses. ConclusionThis study did not find an association between DAAs and PD among patients with HCV infection.

Efficacy of differentiated targeted interferon and immunomodulatory therapy focused on pathological immunophenotypes in patients with atypical chronic active herpesvirus infections

Objective: In a prospective cohort study to evaluate the clinical and immunological efficacy of differentiated targeted interferon and immunomodulatory therapies focused on identified pathological immunophenotropes and associated clinical manifestations in immunocompromised patients suffering from atypical chronic active herpes viral infections (ACA-HVI).Materials and methods: 335 patients suffering from mixed-AHA-HVI were examined. The study complex included: methods for detecting herpesviruses: serodiagnosis, PCR-RV; immunological methods: a research of subpopulation of blood lymphocytes (method of a flow cytometry), determination of the spontaneous and induced products of IFNα and IFNγ, levels of serum cytokines and immunoglobulins (IL-1β, IL-6, IL-17, TNFα and IFNα and IFNγ, Ig A, M, G) by ELISA. The study was approved by the ethics board and informed consent was obtained from all patients.Results: Integral formulas of disorders in the antiviral immune defense system were created, which made it possible to isolate 3 pathological immunophenotypes (PIF): PIF1: NG↓+ind.IFNα/IFNγ↓+CTL↓+EKK↓+IgM↑+hypecytokinemiya (IL-1β↑+IL-6↑+TNFα↑); PIF2: NG↓+ ind. IFNα/IFNγ↓ + EKK↓+ IgG↓+hypercytokinemiya (IL-1β↑+IL-6↑+TNFα↑) and PIF3: NG↓+ind.IFNα/IFNγ↓+hypercytokinemiya (IL-1β↑+IL- 6↑+TNFα↑). Taking into account the identified disorders, a program of targeted interferon and immunomodulatory therapy was developed for each PIF: local and systemic IFN therapy + hexapeptide was developed for PIF1; for PIF2- local and systemic IFN therapy + glucosaminimuramyldipeptide; for PIF3-local and systemic IFN therapy.Conclusions: High clinical efficacy was demonstrated in 100% of patients with three groups of ACA-HVI. Immunological effectiveness of targeted interferon and immunomodulatory therapy programs: 89.5% for PIF1; for PIF2-57.6% and for PIF3- 37.5% of cases.

New Genetic Markers of Skin T-Cell Lymphoma Treatment.

Cutaneous T-cell lymphomas (CTCL) can be described as chronic skin inflammation lesions with the content of malignant T cells and they are considered to be T-cell-mediated skin diseases. CD147 is recognized as a 58-kDa cell surface glycoprotein of the immunoglobulin superfamily; it can induce the synthesis of MMPs (matrix metalloproteinases) on the surface of tumor cells where it was originally identified. It can also function in adjacent tumor fibroblasts using CD147-CD147 interactions. The polymorphism rs8259 T/A is situated in the untranslated region (3'UTR) of the CD147 gene. HLA DRB1*1501 takes part in the process of presentation and recognition of different antigens to T cells. It can be expressed by antigen-presenting cells-macrophages, dendritic cells, and B cells. The aim of the study is to test genotype-phenotype associations of both polymorphisms including therapy in a large cohort of CTCL patients. A final total of 104 CTCL patients were enrolled in the study. For the first remission at the clinic department, they were treated by means of local skin-directed therapy, phototherapy, and systemic therapy. Genomic DNA was isolated from peripheral blood leukocytes. A standard technique using proteinase K was applied. The polymorphisms rs8259 T/A (CD147 gene) and rs3135388 (HLA DRB1*1501) were detected through standard PCR-restriction fragment length polymorphism methods. The severity of the disease (patients with parapsoriasis, stages IA and IB, vs patients with stages IIB, IIIA, and IIIB) was associated with the CD147 genotype: the AA variant was 3.38 times more frequent in more severe cases, which reflects the decision on systemic therapy (p = 0.02, specificity 0.965). The AA genotype in the CD147 polymorphism was 12 times more frequent in patients who underwent systemic therapy of CTCL compared to those not treated with this therapy (p = 0.009, specificity 0.976). The same genotype was also associated with radiotherapy-it was observed 14 times more frequently in patients treated with radiotherapy (p = 0.009, specificity 0.959). In patients treated with interferon α therapy, the AA genotype was observed to be 5.85 times more frequent compared to the patients not treated with interferon therapy (p = 0.03, specificity 0.963). The HLA DRB1*1501 polymorphism was associated with local skin-directed therapy of CTCL. The CC genotype of the polymorphism was observed to be 3.57 times more frequent in patients treated with local therapy (p = 0.008, specificity 0.948). When both polymorphisms had been calculated together, even better results were obtained: the AACC double genotype was 11 times more frequent in patients with severe CTCL (p = 0.009, specificity 0.977). The TACT double genotype was associated with local skin-directed therapy (0.09 times lower frequency, p = 0.007, sensitivity 0.982). The AACC genotype was 8.9 times more frequent in patients treated by means of systemic therapy (p = 0.02, specificity 0.976) and as many as 18.8 times more frequent in patients treated with radiotherapy (p = 0.005, specificity 0.969). Thus, the AACC double genotype of CD147 and DRB1*1501 polymorphisms seems to be a clinically highly specific marker of severity, systemic therapy and radiotherapy of patients with T-cell lymphoma. Although genotyping results were not known during the treatment decision and could not modify it, the clinical decision on severity and therapy reflected some aspects of the genetic background of this complicated T-cell-associated disease very well.

Frequency of Type 2 Diabetes Mellitus among Patients with Hepatitis C Virus Infection

Background: Hepatitis C virus (HCV) infection and type 2 diabetes mellitus (T2DM) have established themselves as significant global health concerns, with a notable co-prevalence that suggests a potential pathophysiological connection. The increasing incidence of T2DM, particularly in developing countries, alongside the significant burden of HCV, poses challenges for healthcare systems and necessitates deeper understanding of their interrelation. Objective: This study aimed to ascertain the frequency of T2DM among patients with HCV infection and to investigate the potential association between HCV reactivity and the incidence of T2DM. Methods: A cross-sectional analysis was conducted at a molecular pathology laboratory in Lahore, Pakistan. Patients aged 18-60 years without cirrhosis or pre-existing T2DM were consecutively enrolled over a six-month period. Exclusion criteria included liver cancer, interferon therapy, end-stage renal disease, other viral hepatitides, and pregnancy. Data were collected via questionnaires after informed consent, with serum and hemoglobin A1c (HbA1c) levels measured. HCV reactivity was confirmed via real-time polymerase chain reaction (RT-PCR), and the frequency of T2DM was assessed by HbA1c criteria. Statistical analysis involved univariate analysis using SPSS version 25.0. Results: Among the 300 HCV-reactive patients, the frequency of T2DM was found to be 49.33% (148 patients). The mean age of participants was 42.71 ± 6.808 years, with 53.0% males and 47.0% females. Urban and rural participants were nearly equally represented. A significant association was noted between HCV reactivity and T2DM (p=0.001), while no significant relationship was found with gender, residence, marital status, or family history of T2DM. Conclusion: The study highlights a substantial frequency of T2DM in HCV-reactive patients and a significant association between HCV infection and the development of T2DM. Regular HbA1c monitoring in HCV-reactive patients is recommended for the early identification and management of T2DM.

A 28-year-old male patient with asymptomatic and multi-drug-resistant HBV infection: a case report

Chronic hepatitis B virus (HBV) infection poses a significant global health challenge, impacting millions of individuals and elevating the risk of morbidity and mortality. Antiviral therapies are the primary treatment for chronic HBV infection, but treatment resistance can occur, leading to poor clinical outcomes and an increased risk of liver complications. This case report presents the clinical trajectory of a 28-year-old male diagnosed with asymptomatic HBV infection in 2016 under the auspices of the Hepatitis Control Program, Government of Azad Jammu and Kashmir, Pakistan. Over 6 years, persistent HBsAg, HBV, and HBeAg were observed, with absent acute markers and co-infections. Initial HBV DNA viral load was 1 × 104 copies/mL in 2016, escalating despite entecavir and pegylated interferons therapy, indicating multi-drug resistance. Tenofovir therapy initially reduced viral load but later exacerbated it, reaching 1.86 × 106 copies/mL in 2022. Liver function abnormalities and lipid profile irregularities persisted. Urine examination consistently showed abnormalities. Pending HBV DNA sequencing results may offer insights into treatment resistance. This case underscores the need for an adaptive approach in managing chronic HBV infections within public health programs. Continuous monitoring, integration of virological and biochemical data, and a tailored treatment strategy are essential for optimizing outcomes in similar cases, stressing the importance of refining therapeutic approaches against chronic HBV infection.

Natural Product-derived Phytochemicals as Potential Inhibitors of Angiotensin Converting Enzyme 2 (ACE2): Promising Drug Candidates for COVID-19

Abstract: COVID-19 was deemed a global pandemic by the World Health Organization in February 2020. The prevalence of viral diseases worldwide has increased the importance of receiving immediate medical attention. There is currently no specific medication or vaccine under consideration to treat coronavirus infection. For reducing or preventing COVID-19 infections, a number of alternative therapies are anticipated, including the use of synthetic drugs, vaccines, interferon therapy etc. Due to the serious side effects of the utilized drug therapies, it is crucial to comprehend the pathogenesis of the coronavirus and explore safe and efficient treatment. : Considering the contribution of plants and herbs in the management of viruses like HIV, Herpes Simplex, MERS-CoV, and influenza, they can be further utilised for COVID-19 treatment. According to reports, SARS-CoV2 infects host cells through Angiotensin-converting enzyme 2 receptors, causing pneumonia linked to COVID-19 as well as acute myocardial injury and long-term cardiovascular damage. A cure for SARS-CoV2 may lie in understanding the receptor, its targets, and the mechanism of viral replication. This review article highlights several plants that have the potential to inhibit ACE2, including Punica granatum, Citrus aurantium, Allium sativum, Piper longum, Curcuma longa, and Coriandrum sativum as well as their extracts and phytoconstituents, such as flavonoids, alkaloids, anthraquinone glycosides, phenolic acids, and others. This review will provide opportunities for researchers to explore the possibility of developing promising dosage forms that will increase the bioavailability and in vivo effectiveness of the lead candidates.

Effect of interferon therapy on quality of life in patients with chronic hepatitis B

Interferon therapy is the most effective treatment for achieving clinical cure in chronic hepatitis B (CHB) patients. However, the treatment outcomes of interferon therapy are uncertain, multiple side effects can occur during treatment, and the treatment is expensive. Although these characteristics may affect patients’ quality of life, research examining this topic is limited. We used a cross-sectional design to examine 100 CHB patients receiving interferon, 100 receiving nucleoside/nucleotide analogues, and 87 receiving non-antiviral treatment. Characteristic information, the Hepatitis B Quality of Life Instrument, Connor Davidson Resilience Scale, and Work Productivity and Activity Impairment Questionnaire were used to collect information. We found that quality of life in the interferon treatment group was higher than that in the non-antiviral treatment and nucleoside/nucleotide analogue treatment groups (p < 0.05). The factors influencing quality of life were resilience, presenteeism, hair loss, and antiviral treatment (p < 0.05). Although interferon therapy has some potential side effects, the results suggested that it did not negatively affect quality of life. Overall, interferon therapy did not have a major impact on CHB patients’ daily lives and work.

Interferons as Neoadjuvant Chemotherapy for Giant Cell Tumor: A Hospital-Based Prospective Pilot Study

Abstract Introduction Neoadjuvant chemotherapy is now considered an effective way to treat Campanacci grade 2 and 3 giant cell tumors (GCTs). Assessment of these drugs is essential clinically, radiologically, and pathologically. This study analyzes the early results of angiogenesis inhibitors (interferons) in the aggressive GCT of bone. Methodology A prospective pilot study was conducted from January 2021 to July 2022 including eight biopsy-proven GCT patients subjected to interferon therapy. Radiological assessment was done with changes on plain radiograph, computerized tomography scan, and magnetic resonance imaging. Histopathological examination was done by changes in the biopsy and resected segment. Results Out of the eight patients included in the study, 26% (n = 3) were males and 62% (n = 5) were females, with mean age of the patients being 24.6 ± 8.48 years (range: 22–38). There was significant reduction of the size of swelling (p-value: 0.049), significant reduction in Visual Analog Scale score (p-value: 0.011), significant decrease in swelling size on radiograph (p-value: 0.012), significant marginal sclerosis (p-value: 0.001), significant neocortex formation on radiographs (p-value: 0.001), significant result in and osteoid formation (p-value: 0.001) on histology. Whereas Campanacci grade on plain radiographs, number of viable cells, and number of viable stromal cell were not statistically different in comparison with pretherapy and posttherapy status. Conclusion Interferon therapy in a GCT has potential beneficiary effect in terms of clinical, radiological, and pathological outcomes. It might prove to be an effective alternative to standard neoadjuvant chemotherapy in the management of aggressive GCT of bones. Level of Evidence III.

Evaluation of combination of ALA-PDT and interferon for cervical low-grade squamous intraepithelial lesion (LSIL)

BackgroundCervical LSIL is a precancerous disease which requires regular follow-up. High risk patients need active interventions. Interferon and topical PDT have been used in the treatment of cervical LSIL. The aim of this study was to evaluate the combination use of topical PDT and interferon in the treatment of cervical LSIL. Materials and methodsA prospective study was carried out involving 159 women with cervical LSIL and high risk human papillomaviruses (hr-HPV) infection. Patients were divided into three groups. Group 1-receiving interferon suppository only, Group 2-receiving 19 mg/cm2 ALA plus post PDT interferon, and Group 3-receiving 38 mg/cm2 ALA plus post PDT interferon. The primary endpoint was pathological regression. The secondary endpoints were the HPV negative conversion rate and the adverse effects of treatment. ResultsAt 6–12 months after PDT, for Group 1, the effective rate, CR rate and HPV negative conversion rate was 48.3 %, 43.3 % and 24.0 %, respectively. For Group 2, the effective rate, CR rate and HPV negative conversion rate were 89.3 %, 71.4 %, and 72.4 %, respectively. For Group 3, the effective rate, CR rate and HPV negative conversion rate were 91.5 %, 66.1 %, and 64.4 %, respectively, significantly higher than those of interferon only group. Two ALA dose group study showed similar efficacy. No patient experienced serious adverse effects. ConclusionsALA-PDT combined with interferon therapy was feasible and tolerable. Two ALA dose groups showed similar outcomes in treating cervical LSIL.

Levels of circulating cytokines in children with multiple sclerosis with different effectiveness of interferon therapy

Multiple sclerosis (MS) is a chronic, demyelinating disease that leads to disability. Understanding the etiology of MS contributes to the development of pathogenetic methods of treatment, and the search for informative biomarkers of the effectiveness of treatment will allow the patient to adjust therapy in time. The aim of this work was to determine informative cytokines and cytokine profiles to predict the effectiveness of IFN-β1a therapy in children with MS.Materials and methods. 66 children with MS aged 16 [14.2–17.5] years who are on INFß-1a therapy were examined: group 1 — patients with exacerbation of MS (with active foci of demyelination by MRI), n = 34; group 2 — patients in remission of MS (without active foci), n = 32. The content of cytokines in the blood serum of patients was assessed using the multiplex panel Human Th17 Magnetic Bead Panel.Results: There was a significant increase in cytokine concentrations in patients with exacerbation of MS compared with children in remission: IL5, IL6, IL9, IL12p70, IL17E/IL25, IL21, IL28A, GM-CSF, TNFß. Threshold values for IL9 (AUC = 0,785), IL6 (AUC = 0,750), TNFß (0,740), IL28A (AUC = 0,744) were obtained above which it is possible to predict an exacerbation of MS in patients: IL9 — 3.9 pg/ml (Sn — 70.6, Sp — 71.9), IL6 — 4.0 pg/ml (Sn — 70.6, Sp — 68.8), TNFß — 6.6 pg/ml (Sn — 70.6, Sp — 71.9), IL28A — 243.0 pg/ml (Sn — 70.6, Sp — 71.9). Cytokine profiles associated with T-lymphocytes and their functions were evaluated using z-score.Conclusions. For the first time, an increase in cytokine levels was demonstrated in children with active foci of demyelination compared to patients in remission of MS. An increase in proinflammatory cytokines and cytokine profiles associated with Th1 and Th17, as well as with Th2 and Th22 has been shown. The use of threshold values for IL9, IL6, TNFβ, IL28A will help predict the development of exacerbation in patients with MS.

Interferon therapy improves survival in patients with hepatitis B virus-related hepatocellular carcinoma after curative surgery: a meta-analysis.

A novel study found interferon enhanced antitumor activity of anti-PD-1-based immunotherapy and played a crucial role in improving efficacy on HCC, but the opposite results about the efficacy of interferon on HBV-related HCC were obtained from previous clinical studies and meta-analyses. Thus, this meta-analysis aimed to re-evaluate whether interferon could improve survival and reduce recurrence of patients with HBV-related HCC after curative surgery. MEDLINE/PubMed, Cochrane Library, EMBASE, Web of Science and CNKI were searched for eligible studies from inception to November 2022 and a meta-analysis was done. 10 trials with a total of 2062 subjects were screened.Interferon significantly improved 1-, 2-, 3- and 5-year OS and 1-, 2- and 3-year DFS, and reduced 2-, 3- and 5-year recurrence rates of patients with HBV-related HCC after curative surgery. However, interferon did not improve 8-year OS and 5-year DFS, did not reduce 1-year recurrence rate. Interferon may significantly reduce recurrence and improve DFS of patients with HBV-related HCC after curative surgery, and finally improve the OS. However, the efficacy advantage may gradually weaken as time goes on. The clinical application of interferon combined with NAs recommended in this meta-analysis is needed to be further studied.

Interferons in the treatment of myeloproliferative neoplasms.

Interferons are cytokines with immunomodulatory properties and disease-modifying effects that have been used to treat myeloproliferative neoplasms (MPNs) for more than 35 years. The initial use of interferons was limited due to difficulties with administration and a significant toxicity profile. Many of these shortcomings were addressed by covalently binding polyethylene glycol to the interferon structure, which increases the stability, prolongs activity, and reduces immunogenicity of the molecule. In the current therapeutic landscape, pegylated interferons are recommended for use in the treatment of polycythemia vera, essential thrombocythemia, and primary myelofibrosis. We review recent efficacy, molecular response, and safety data for the two available pegylated interferons, peginterferon alfa-2a (Pegasys) and ropeginterferon alfa-2b-njft (BESREMi). The practical management of interferon-based therapies is discussed, along with our opinions on whether to and how to switch from hydroxyurea to one of these therapies. Key topics and questions related to use of interferons, such as their safety and tolerability, the significance of variant allele frequency, advantages of early treatment, and what the future of interferon therapy may look like, will be examined. Pegylated interferons represent an important therapeutic option for patients with MPNs; however, more research is still required to further refine interferon therapy.

Long-Term Survival and Cancer Risk in the Hepatitis C Virus-Infected Patients After Antiviral Treatment: A Nationwide Cohort Study.

Background: Exposure to the Hepatitis C virus (HCV) has been identified as one of the most critical risk factors for Hepatocellular carcinoma (HCC). Interferons and direct-acting antivirals (DAAs) have been used to treat HCV infection with high rates (95%) of prolonged virological response, a suitable safety profile, and good compliance rates. Methods: We obtained information from Taiwan's Health and Welfare Data Science Center. (HWDSC). In this observational cohort research, patients with HCV who received a diagnosis in Taiwan between 2011 and 2018 were included. Results: 78,300 untreated HCV patients were paired for age, sex, and index date with 39,150 HCV patients who received interferon or DAAs treatment. Compared to the control group, the Interferon or DAAs treatment sample has fewer low-income individuals and more hospitalization requirements. The percentage of kidney illness was reduced in the therapy group compared to the control group, but the treatment group had a greater comorbidity rate of gastric ulcers. Interferon or DAA therapy for HCV-infected patients can substantially lower mortality. All cancer diagnoses after HCV infection with interferon treatment aHR 95% CI = 0.809 (0.774-0.846), Sofosbuvir-based DAA aHR 95% CI = 1.009 (0.737-1.381) and Sofosbuvir free DAA aHR 95% CI = 0.944 (0.584-1.526) showing cancer-protective effects in the INF-treated cohort but not DAA. Conclusion: Following antiviral therapy, women appear to have a more substantial preventive impact than men against pancreatic, colorectal, and lung cancer. Interferon or DAAs treatment effect was more significant in the cirrhotic group.

A Case of Chronic Hepatitis B in which HBs Antigen Seroclearance was Induced by Pegpegylated-interferonα-2a after Hepatocellular Carcinoma Treatment with Nucleos(t)ide Analogues: A Five-year Follow-up.

We herein report a 40-year-old Japanese man with chronic hepatitis B genotype C (viral load 6.7 LC/mL) who developed hepatocellular carcinoma (HCC) despite achieving undetectable hepatitis B virus (HBV) DNA levels with nucleos (t) ide analog (NA) treatment (entecavir). Notably, his hepatitis B surface antigen (HBsAg) level remained elevated at 388.4 IU/mL. Given the continued risk of carcinogenesis associated with HBsAg positivity, we initiated pegylated interferon (PEG-IFN) therapy one month after HCC surgery. Following three periods of PEG-IFN treatment, HBsAg seroclearance (HBsAg-negative state) was achieved.

Electron Microscopic Studying the Impact of Ozone on Chronic Hepatitis C Patients as Antifibrotic

We aimed to evaluate the histopathological and ultrastructural changes detected by light and electron microscopy, induced in patients having chronic hepatitis C receiving ozone/oxygen gas treatment. Twenty six patients with chronic hepatitis C who were at different stages of liver fibrosis, non-responders to interferon plus ribavirin therapy (n = 9), had contraindications (n = 2), or were not compliant (n = 15) were included. At baseline and 12 weeks after administering the ozone/oxygen gas mixture, liver biopsies were carried out utilizing both the major rectal insufflations and auto-hemotherapy along with clinical evaluation, kidney and liver function assessments, liver biopsies and abdominal ultrasonography. Before and 12 weeks after the treatment of ozone, quantitative PCR was performed. Two pathologists evaluated the histological activity index (HAI) using Ishak's score while working in blind settings, taking into account the degree of inflammation and the stage of fibrosis. Electron microscopy was done for all cases before and after treatment. Significant improvements in liver enzymes in hepatic fibrosis and inflammatory activity based on Ishak scoring system were detected. The mean grade of inflammation dropped from 10.3 to 8.4 and the mean stage of fibrosis dropped from 2.3 to 2.0 both with P value &lt; 0.001 and &lt; 0.05 respectively. Mean PCR values showed significant increase after 12 weeks of treatment from 17059 to 218736 with P value &lt;0.05. As regards electron microscopy findings, the ultra-structural manifestations of HCV infection were disclosed in liver specimens exposed or not to ozone treatment. Stellate cells were often encountered in unexposed samples to ozone, meanwhile they disappeared after ozone exposure. Apoptotic hepatocytes which were frequently encountered before treatment are rarely seen in specimens after treatment with ozone. Signs of cellular regeneration in the form of binucleated cells, RER enveloping mitochondria, hepatocyte progenitors insinuating between the cells at the sinusoid pole are seen after treatment. Circulating inflammatory cells in the sinusoids and infilterating the lobule were decreased after treatment. Peroxisomes were increased after exposure to ozone with longitudinal orientation of mitochondrial cristae thus increasing the antioxidative activity of hepatocytes. No single significant complication was recorded in a total of &gt;1000 settings of ozone therapy. In conclusion, ozone oxygen gas mixture is a direct anti-fibrotic and anti-inflammatory agent in treatment of chronic hepatitis C patients without improving viral PCR as evidenced by histopathology, electron microscopy and quantitative PCR.