Virus Reactivation In Patients Research Articles

Letter to editor: Effect of pre-transplant viral therapy on post-transplant hepatitis B virus reactivation in patients with hepatitis B-related hepatocellular carcinoma

Letter to editor: Effect of pre-transplant viral therapy on post-transplant hepatitis B virus reactivation in patients with hepatitis B-related hepatocellular carcinoma

Hepatitis B virus reactivation in patients treated with monoclonal antibodies.

Hepatitis B virus (HBV) reactivation poses a significant clinical challenge, especially in patients undergoing immunosuppressive therapies, including monoclonal antibody treatments. This manuscript briefly explores the complex relationship between monoclonal antibody therapy and HBV reactivation, drawing upon current literature and clinical case studies. It delves into the mechanisms underlying this phenomenon, highlighting the importance of risk assessment, monitoring, and prophylactic measures for patients at risk. The manuscript aims to enhance the understanding of HBV reactivation in the context of monoclonal antibody therapy, ultimately facilitating informed clinical decision-making and improved patient care. This paper will also briefly review the definition of HBV activation, assess the risks of reactivation, especially in patients treated with monoclonal antibodies, and consider management for patients with regard to screening, prophylaxis, and treatment. A better understanding of patients at risk can help clinicians provide optimum management to ensure successful patient outcomes and prevent morbidity.

The frequency of hepatitis B virus reactivation in patients receiving anti-TNF treatment: a single center, retrospective study

Objective : The equilibrium between the host immune response counter the hepatitis B virus (HBV) and the amount of viral replication is a crucial factor in the pathogenesis of HBV-associated liver disease. Tumor necrosis factor-alpha (TNF-α) is an considerable proinflammatory and immune regulatory cytokine in the pathogenesis of various inflammatory and autoimmune conditions. There is no consensus on using antiviral prophylaxis treatments in cases who have been exposed to hepatitis B but have not become chronically ill, and are thus planned to receive anti-TNF-α treatment.The aim of this study is to determine the frequency of reactivation after anti-TNF treatment in cases with isolated anti-HBc total positivity who have been exposed to hepatitis B virus. Matarail and Methods: Serological HBV infection markers (HBsAg, anti-HBc IgG and anti-HBs) of 1467 adult cases who received anti-TNF therapy for the indications of various rheumatological diseases in the rheumatology and physical therapy clinics between the years 2010-2021 were retrospectively screened using the hospital’s electronic information system. Results: 140 rheumatologic disease cases who took a TNF-α inhibitor (infliximab, adalimumab, etanercept, golimumab, certolizumab) treatment were included in this study. Before the cases were started on TNF-α treatment, all cases were anti-HBc total positive, 110 were anti-HBs positive, 30 were anti-HBs negative, and 4 were HbsAg positive and HBV-DNA negative. The median pre-treatment anti-HBc total and anti-HBs values of the cases were 5.6 IU/L and 79.29 IU/L, respectively. No HBV reactivation was observed in any of the 140 cases after a median follow-up duration of 71.5 (min. 8, max. 185) months. Conclusion: In conclusion, HBV reactivation was not detected in any of the anti-HBc positive cases included in this study, which suggest that anti-HBc positive cases can be followed up with close follow-up without starting them on anti-TNF therapies and antiviral prophylaxis.

Risk of Hepatitis B Virus Reactivation in Patients with Resolved Infection on Therapy with Corticosteroids and Conventional Synthesis Immunosuppressants for Kidney Disease: A Single-Center Analysis of 258 Patients.

The risk of hepatitis B virus reactivation in patients with a previously resolved hepatitis B virus infection on therapy with corticosteroids and conventional synthesis immunosuppressants for kidney disease has not been well described. We performed a retrospective study on the risk of hepatitis B virus reactivation in patients with a previously resolved hepatitis B virus infection on therapy with corticosteroids and conventional synthesis immunosuppressants for kidney disease between January 2012 and December 2021 in the Department of Nephrology at Ruijin Hospital. A total of 258 patients with a previously resolved hepatitis B virus infection [all treated with high-dose corticosteroids, of whom 192 were receiving corticosteroids combined with conventional synthesis immunosuppressant therapy, including cyclophosphamide (155), cyclosporine A (14), mycophenolate mofetil (14), and tacrolimus (9)] were enrolled. During a mean follow-up time of 21.66 months (range 9-70 months), hepatitis B virus reactivation was not observed in these patients. Among patients with a previously resolved hepatitis B virus infection on therapy with corticosteroids and conventional synthesis immunosuppressants for kidney disease, hepatitis B virus reactivation was not common and severe, suggesting that universal prophylaxis may not be justified or cost-effective in this clinical setting.

Prevention and management of hepatitis B virus reactivation in patients with hematological malignancies in the targeted therapy era.

Hepatitis due to hepatitis B virus (HBV) reactivation can be serious and potentially fatal, but is preventable. HBV reactivation is most commonly reported in patients receiving chemotherapy, especially rituximab-containing therapy for hematological malignancies and those receiving stem cell transplantation. Patients with inactive and even resolved HBV infection still have persistence of HBV genomes in the liver. The expression of these silent genomes is controlled by the immune system. Suppression or ablation of immune cells, most importantly B cells, may lead to reactivation of seemingly resolved HBV infection. Thus, all patients with hematological malignancies receiving anticancer therapy should be screened for active or resolved HBV infection by blood tests for hepatitis B surface antigen (HBsAg) and antibody to hepatitis B core antigen. Patients found to be positive for HBsAg should be given prophylactic antiviral therapy. For patients with resolved HBV infection, there are two approaches. The first is pre-emptive therapy guided by serial HBV DNA monitoring, and treatment with antiviral therapy as soon as HBV DNA becomes detectable. The second approach is prophylactic antiviral therapy, particularly for patients receiving high-risk therapy, especially anti-CD20 monoclonal antibody or hematopoietic stem cell transplantation. Entecavir and tenofovir are the preferred antiviral choices. Many new effective therapies for hematological malignancies have been introduced in the past decade, for example, chimeric antigen receptor (CAR)-T cell therapy, novel monoclonal antibodies, bispecific antibody drug conjugates, and small molecule inhibitors, which may be associated with HBV reactivation. Although there is limited evidence to guide the optimal preventive measures, we recommend antiviral prophylaxis in HBsAg-positive patients receiving novel treatments, including Bruton's tyrosine kinase inhibitors, B-cell lymphoma 2 inhibitors, and CAR-T cell therapy. Further studies are needed to determine the risk of HBV reactivation with these agents and the best prophylactic strategy.

Hepatitis B Virus Reactivation in Patients Receiving Bruton Tyrosine Kinase Inhibitors.

Bruton tyrosine kinase (BTK) inhibitors are used to treat B-cell hematologic malignancies. Ibrutinib has been associated with hepatitis B virus (HBV) reactivation. We sought to identify patients with hematologic malignancies who developed HBV reactivation after receiving first-generation (ibrutinib) or second-generation (acalabrutinib and zanubrutinib) BTK inhibitors. We retrospectively studied all consecutive patients with hematologic malignancies with past HBV infection (HBV surface antigen [HBsAg] negative and hepatitis B core antibody [anti-HBc] positive) or chronic HBV infection (HBsAg positive and anti-HBc positive) treated with BTK inhibitors at our institution from November 1, 2015, through November 1, 2022. Of 82 patients initially identified, 53 were excluded (11 because of false-positive anti-HBc results, and 42 because they were receiving anti-HBV prophylaxis owing to recent receipt of anti-CD20 monoclonal antibodies). The 29 remaining patients were further analyzed and 3 (10%; 2/28 with past and 1/1 with chronic HBV infection) were found to have HBV reactivation. One patient received ibrutinib, and 2 received acalabrutinib. All developed HBV-associated hepatitis requiring anti-HBV therapy and survived. One patient continued receiving acalarutinib. Among the patients with past HBV infection, 13 received ibrutinib and 1 (8%) had HBV reactivation; 14 received acalabrutinib and 1 (7%) had HBV reactivation (P=1.0). HBV reactivation risk is intermediate in patients with past HBV infection who receive BTK inhibitors. For patients with past HBV infection who received BTK inhibitors, data are insufficient to recommend universal anti-HBV prophylaxis, but monitoring for HBV reactivation is warranted.

Low incidence of hepatitis B virus reactivation in patients with hematological malignancies receiving novel anticancer drugs: A report from a high epidemic area and literature review.

More and more novel anticancer drugs have been approved for patients with hematological malignancies in recent years, but HBV reactivation (HBV-R) data in this population is very scarce. This study aimed to evaluated HBV-R risk in patients with hematological malignancies receiving novel anticancer drugs. HBV markers and serum HBV DNA levels of patients with hematological malignancies receiving novel anticancer drugs in a tertiary cancer hospital were retrospectively collected. HBV-R risk in the whole cohort and subgroups was described. The relevant literature was reviewed to make a pooled analysis. Of 845 patients receiving novel anticancer drugs, 258 (30.5%) were considered at risk for HBV-R. The median duration of exposure to novel drugs was 5.6 (0.1-67.6) months. The incidence of HBV-R was 2.1% in patients with past HBV infection without prophylactic antiviral treatment (PAT) and 1.2% in all patients at risk of HBV-R. In a pooled analysis of 11 studies with 464 patients, the incidence of HBV-R was 2.4% (95% CI: 1.3-4.2) in all at-risk patients receiving novel anticancer drugs and 0.6% (95% CI: 0.03-3.5) in patients with anticancer drugs plus PAT. The incidence of death due to HBV-R was 0.4% (95% CI: 0.1-1.6) in all at-risk patients and 18.2% (95% CI: 3.2-47.7) in patients with HBV-R. Most episodes of HBV-R are preventable, and most cases with HBV-R are manageable. We recommend that novel anticancer drugs should not be intentionally avoided when treating cancer patients with HBV infection.

WED-196 - Risk factors for viral reactivation in patients with overt or occult HepatitisB Virus infection receiving immunosuppressive treatments: a systematic review and meta-analysis

WED-196 - Risk factors for viral reactivation in patients with overt or occult HepatitisB Virus infection receiving immunosuppressive treatments: a systematic review and meta-analysis

Risk factors for viral reactivation in patients with overt or occult Hepatitis B Virus infection receiving immunosuppressive treatments: A systematic review and meta-analysis with decision curve analysis

Risk factors for viral reactivation in patients with overt or occult Hepatitis B Virus infection receiving immunosuppressive treatments: A systematic review and meta-analysis with decision curve analysis

Antiviral Prophylaxis With Tenofovir for Patients With History of Hepatitis B Receiving Oncology Drug Treatment


 One randomized control trial and 2 retrospective cohort studies found no significant differences between tenofovir and entecavir in the prophylaxis of hepatitis B virus reactivation in patients who were hepatitis B surface antigen positive and/or hepatitis B core antibody positive receiving chemotherapy or immunosuppressive therapy. There were no significant differences between these 2 drugs regarding renal function and other side effects.
 One randomized controlled trial found no patients in the tenofovir prophylaxis group had HBV reactivation compared to 10.7% in the observational group. However, the difference did not reach the level of statistical significance, probably owing to a small sample size. There were no significant differences between groups in terms of renal function, liver function, and other side effects.
 All 8 included guidelines strongly recommend the use of tenofovir or entecavir as antiviral prophylaxis in all patients with high risk of hepatitis B virus reactivation (hepatitis B surface antigen positive and/or hepatitis B core antibody positive) during chemotherapy or immunosuppressive therapy.

Evaluation of hepatitis serology and frequency of viral reactivation in patients with inflammatory arthritis receiving biologic agents: a multicenter observational study.

To evaluate of hepatitis serology and reactivation frequency in patients with rheumatic disease receiving biologic agents. Our study included patients with inflammatory rheumatic diseases from 23 centers, who were followed up with biological therapy. Demographic and clinical characteristics of the patients, duration of drug use and hepatitis serology and the state of viral reactivation were analyzed. A total of 4060 patients, 2095 being males, were included in our study. Of the patients, 2463 had Ankylosing Spondylitis (AS), 1154 had Rheumatoid Arthritis (RA), 325 had Psoriatic Arthritis (PsA), and 118 had other inflammatory rheumatic diseases. When the viral serology of the patients was evaluated, 79 patients (2%) who were identified as HBs Ag positive, 486 (12%) patients who were HBs Ag negative and anti-HBc IgG positive and 20 patients (0.5%) who were anti-HCV positive. When evaluated on a disease-by-disease basis, the rate of HBsAg was found to be 2.5% in RA, 2% in AS and 0.9% in PsA. Viral reactivation was detected in 13 patients while receiving biologic agents. HBs Ag was positive in nine patients with reactivation and negative in four patients. Anti-HBc IgG, however, was positive. Six of these patients had AS, four had RA, and three had PsA. The development of hepatitis reactivation in 11.4% of HBs Ag positive patients and 0.82% of anti-HBc IgG positive patients due to the use of biologic agents is an important problem for this group of patients. Antiviral prophylaxis is recommended to be started especially in patients who are HBs Ag positive and who are using biologic agents due to viral reactivation. Therefore, it is important to carry out hepatitis screenings before biologic agent treatment and to carefully evaluate the vaccination and prophylaxis requirements.

Hepatitis B virus reactivation in patients undergoing immune checkpoint inhibition: systematic review with meta-analysis.

Immune checkpoint inhibitors (ICIs) have been explored as first-line treatment in various types of previously untreatable malignancies, while limited evidence is available on the management of hepatitis B virus (HBV) in patients undergoing immunotherapy. We systematically reviewed data concerning challenges of hepatic adverse events including HBV reactivation and hepatitis in patients with chronic HBV infection undergoing immunotherapy. A systematic search was conducted in Medline, web of science, Embase and Cochrane library up to May 31, 2022. Studies reporting the safety profile of ICIs in patients with HBV infection were eligible. Meta-analyses were conducted to generate odds ratios (ORs) with 95% confidence intervals (CIs). A total of 13 studies including 2561 patients were included for meta-analysis. The overall incidence rates of HBV reactivation in patients with chronic HBV infection and past HBV infection were 1.0% (95% CI 0-3%) and 0% (95% CI 0-0%), respectively. Among patients with chronic HBV infection, the incidence rates of HBV reactivation were 1.0% (95% CI 0-2%) and 10.0% (95% CI 4-18%) for patients with and without antiviral prophylaxis, respectively. Patients with chronic HBV infection were at a higher risk of HBV reactivation compared with those with past HBV infection [OR = 8.69, 95% CI (2.16-34.99)]. Antiviral prophylaxis significantly reduced the risk of HBV reactivation [OR = 0.12, 95% CI (0.02-0.67)] and HBV-associated hepatitis [OR = 0.05, 95% CI (0.01-0.28)] in patients with chronic HBV infection. Prophylactic antiviral therapy should be administered to patients with chronic HBV infection undergoing anticancer immunotherapy. Patients with past HBV infection are at lower risk of HBV reactivation compared with those with chronic HBV infection, they could be initiated with antiviral prophylaxis or monitored with the intent of on-demand antiviral therapy.

Hepatitis Virus Reactivation in Patients with Psoriasis Treated with Secukinumab in a Real-World Setting of Hepatitis B or Hepatitis C Infection.

Background and ObjectiveBiologics for psoriasis, especially anti-tumor necrosis factor-α therapies, may reactivate hepatitis B virus (HBV) or hepatitis C virus (HCV) infections, as well in inactive carriers or patients with occult infection. However, some biologics, including anti-interleukin-17 therapies such as secukinumab, seem to be less likely to cause hepatitis reactivation. This study assessed the safety of secukinumab treatment in patients with psoriasis with HBV or HBC infection.MethodsThis was a retrospective cohort study of patients with moderate-to-severe psoriasis treated with secukinumab at seven Italian centers. Patients serologically positive for one or more of the following viral hepatitis markers were included: HCV antibody (± HCV-RNA positivity) and/or hepatitis B surface antigen, and/or HBV core antibody and/or HBV surface antibody (± HBV-DNA positivity). Patients received secukinumab 300 mg subcutaneously at week 0/1/2/3/4 then every 4 weeks; prophylactic therapy before starting secukinumab was prescribed where indicated. The primary study endpoint was the reactivation of hepatitis viral infection, defined as conversion to HBV-DNA or HCV-RNA positivity, with or without elevation of transaminases.ResultsSixty patients (17 with concomitant psoriatic arthritis) were included. Thirteen subjects were hepatitis B surface antigen positive, 19 were HBV core antibody positive, and 30 were positive for the HCV antibody; however, all were HCV-RNA negative. After 53.5 ± 37.5 weeks of secukinumab therapy, hepatitis reactivation occurred in only one patient, who had a reactivation of both hepatitis B and hepatitis C. This patient had not undergone hepatitis B prophylaxis or hepatitis C treatment before secukinumab.ConclusionsThese real-world data support the safety of secukinumab in patients with positive markers of HBV or HCV infection, when administered together with dedicated prophylaxis.

Reactivation rates of hepatitis B or C or HIV in patients with psoriasis using biological therapies: a systematic review and meta-analysis.

Some biological therapies for psoriasis can cause the reactivation of viral infections. Although recent studies suggest no increased rate of reactivation with biological therapies, some life-threatening cases have been reported. Therefore, this meta-analysis examined the rate of virus reactivation in patients with psoriasis with biological therapies and concurrent hepatitis B virus (HBV), hepatitis C virus (HCV), or human immunodeficiency virus (HIV) infection. PubMed, Embase, and the Cochrane Library were searched for available papers from inception to December 2021. The outcome was the number of patients with virus reactivation after using biological therapies. The random-effect model was used in all analyses. Fourteen reports (1033 patients) were included. The pooled overall rate of virus reactivation was 0.04 (95%CI 0.01-0.09; I2 = 67.7%, P < 0.001). The pooled rates of HBV, HCV, and HIV reactivation were 0.04 (95%CI 0.00-0.10; I2 = 79.9%, P < 0.001), 0.07 (95%CI 0.02-0.14; I2 = 23.7%, P = 0.24), and 0.12 (95%CI 0.00-0.40), respectively. The pooled rates of HBV and HCV reactivation were 0.10 (95%CI 0.03-0.19) and 0.08 (95%CI 0.03-0.15) in Asia, but 0.00 (95%CI 0.00-0.01) and 0.04 (95%CI 0.00-0.21) in Europe. The publication type also influenced the results. The use of biological therapy in patients with psoriasis and HBV, HCV, or HIV infection might be associated with the rate of viral reactivation, but this meta-analysis had limitations, and the evidence might be weak. Nevertheless, it might suggest that at least a consultation with an infection specialist might be warranted in patients with psoriasis in whom biological therapies are considered.

Effect of an Electronic Alert System on Hepatitis B Virus Reactivation in Patients Receiving Immunosuppressive Drug Therapy.

Hepatitis B virus (HBV) reactivation (HBVr) can occur in patients receiving immunosuppressive drug therapies, causing significant morbidity and mortality. Although the guidelines for HBVr have been proposed by several academic societies, some providers do not follow them, resulting in HBVr and death. As HBV-DNA levels increase before liver enzyme levels do, we previously constructed an electronic alert system that recommends the measurement of HBV-DNA. Here, we investigated whether this alert system improves the HBV-DNA measurement rate and elicits responses according to guidelines. A total of 5329 patients were divided into two groups, before and after the introduction of the alert system, and the HBV-DNA measurement rates in both groups were compared. Because of the introduction of the alert system, the HBV-DNA measurement rate among HBsAg-negative patients with anti-HBs and/or anti-HBc before immunosuppressive drug therapy improved significantly. The HBV-DNA monitoring rate within 3 months also improved significantly (p = 0.0034) in HBV-remission phase patients. HBVr was detected immediately, and the affected patients were treated with nucleotide analogs before severe hepatitis onset. The introduction of the alert system for HBVr improved the HBV-DNA measurement rates in patients receiving immunosuppressive drug therapy, leading to the rapid treatment of patients with HBVr.

Herpes simplex virus reactivation in patients with COVID-19 and acute respiratory distress syndrome: a prospective cohort study

Background There is a paucity of data about the occurrence and risk factors of herpes simplex virus (HSV) reactivation among patients with severe COVID-19 presenting with acute respiratory distress syndrome (ARDS). Methods We performed a nested case-control study among a cohort of SARS-CoV-2 infected patients with ARDS. Between March and April 2020, all consecutive mechanically ventilated patients ≥18 years old with a positive PCR for SARS-CoV-2 on mucocutaneous samples were included in the study. We collected data on demographics, medical history, laboratory variables, administration of antivirals and other agents, respiratory and organ support procedures, microbiological results, and management of ARDS with prone positioning and the use of steroids. Univariate and multivariable Cox regression models were performed in order to identify predictors of HSV reactivation. Results Eighty-three patients with laboratory-confirmed SARS-CoV-2 infection were admitted to the ICU for mechanical ventilation. 18/83 (21.7%) patients developed mucocutaneous herpes simplex virus reactivation after a median of 17 days (IQR, 14–20). Prone positioning was the only independent risk factor for HSV reactivation (adj. hazard ratios, 1.60; 95% CI, 1.11–2.30; P = 0.009). All patients with mucocutaneous HSV reactivation were treated with antivirals. The outcome in terms of ventilator-associated pneumonia, catheter-related bloodstream infections, and in-hospital mortality was similar for patients with and without HSV reactivation. Conclusions HSV reactivation is frequent in COVID-19 patients with ARDS, especially if prolonged invasive mechanical ventilation with prone positioning is needed. Prompt testing for HSV and initiation of antiviral therapy should be performed in case of mucocutaneous lesions in this population.

Pityriasis rosea, pityriasis rosea-like eruptions, and herpes zoster in the setting of COVID-19 and COVID-19 vaccination.

Pityriasis rosea (PR), PR–like eruptions (PR-LE), and herpes zoster have been frequently reported during the COVID-19 pandemic and following COVID-19 vaccination. PR is a self-limiting exanthematous disease and herpes zoster is a treatable condition; therefore, their occurrence does not require discontinuation of the vaccination schedule. PR-LE is a hypersensitivity reaction and is, therefore, less predictable in its course. In the case of a booster dose, the clinical manifestation may not recur, may be different from PR-LE, or may present with systemic symptoms; however, in the case of PR-LE, the possibility of mild and predominantly cutaneous adverse events should not discourage all eligible candidates from receiving and completing the COVID-19 vaccination program, as such adverse reactions represent a small risk considering the possible severe and fatal outcome of COVID-19. We emphasize the relevance of looking for any viral reactivation in patients infected with SARS-CoV-2 who have skin eruptions. The search for viral reactivations could be useful not only for distinguishing between PR and PR-LE but also because viral reactivations may contribute to a patient's systemic inflammation and influence the course of the disease.

Risk for HepatitisB Virus Reactivation in Patients with Psoriasis Treated with Biological Agents: A Systematic Review and Meta-Analysis.

IntroductionNotwithstanding their numerous advantages, biological treatments have many limitations when treating patients with psoriasis (PsO) and hepatitis B (HB). Clinicians need to pay careful attention to the issue of hepatitis B virus (HBV) reactivation.MethodsIn accordance with the PRISMA guidelines, we systematically searched Pubmed, Scopus, Embase, Cochrane Library, and Web of Science databases for observational studies on the topic of HBV reactivation among patients with PsO and HB treated with biologics. The random-effects model was used to pool the reactivation rate by the Freeman–Tukey double arcsine transformation method. We selected Fisher’s exact test to compare multiple rates. To determine the sources of heterogeneity, sensitivity analysis and meta-regression were performed.ResultsTen studies with a total of 238 subjects that met the inclusion criteria were included. The pooled reactivation rate was 1.8% [95% confidence interval (CI) 0.0–5.6%] in patients with PsO and HB. Among them, the viral reactivation rates of HBsAg-positive and HBsAg-negative patients were 4.1% (95% CI 0.0–17.9%) and 0.2% (95% CI 0.0–2.8%). The difference between HBsAg-positive and HBsAg-negative patients was statistically significant (p = 0.002). The viral reactivation rate of individuals who needed antiviral prophylaxis but did not receive it was 26.6% (95% CI 5.8–53.5%), while it decreased to 0.0% (95% CI 0.0–6.6%) after accepting antiviral treatment. The two-sided Fisher’s test exact values between different durations of biological therapy showed no statistical significance (p = 0.104).ConclusionsWithout antiviral prophylaxis, HBsAg-positive patients with psoriasis are at high risk of virus reactivation when treated with biological agents. Early and sufficient antiviral prophylaxis will effectively reduce the risk of HBV reactivation and serious complications in HBsAg-positive patients. Prolonging the duration of biological treatment will not increase the risk of reactivation.Supplementary InformationThe online version contains supplementary material available at 10.1007/s13555-022-00682-5.

The Clinical, Pathological, and Prognostic Value of High PD-1 Expression and the Presence of Epstein-Barr Virus Reactivation in Patients with Laryngeal Cancer.

Simple SummaryOur immune reaction depends on some ‘immune checkpoints’, such as PD-1, PD-L1 and CTLA4, that maintain homeostasis and define new pathways in the fight against carcinogenesis. Viral infections, including EBV (Epstein-Barr Virus) are one of the risk factors for laryngeal cancer. The aim of our study was to evaluate the level of PD-1 receptor in blood, tumor and lymph node samples collected from 45 laryngeal cancer patients and 20 healthy volunteers from control group. We detected the presence of EBV molecules in cancer samples and show the relationship between tumor progression and the level of PD-1 receptor. We confirmed, that EBV infection may affect the PD-1/PD-L1 pathway and develop the laryngeal cancer. What is important, the level of PD-1 on CD4+ T cells in lymph nodes increased the risk of death, so it can be an important prognostic factor (marker) for laryngeal cancer patients’ treatment and their prognosis.Due to the development of molecular diagnostic techniques, the latest research in the diagnosis of cancer diseases, including laryngeal cancer, has been focused on the occurrence of specific types of molecular patterns, including markers expressed on cells of the immune system (e.g., PD-1, PD-L1, and CTLA-4), which may be directly or indirectly involved in the development of neoplastic diseases. Laryngeal cancer is one of the diseases that is diagnosed more often in men than in women, and many factors are involved in its development, including environmental and lifestyle factors, viral infections (e.g., HPV, HHV-1, and EBV), and disorders of the immune system. In this study, we determined the level of PD-1 receptor expression on T and B lymphocytes and their relationships based on the classification of the grade and TNM scale, in turn based on blood, tumor, and lymph node samples from patients diagnosed with laryngeal cancer. In addition, we determined the presence of EBV genetic material in the tested biological materials as well as the degree of cancer advancement and its correlation with the level of PD-1 receptor expression. The results suggested that the level of PD-1 expression on T and B lymphocytes was significantly higher in the tumor samples as compared to the lymph node samples, and their comparison with the immunophenotype results from the blood samples provided statistically significant data on changes in the incidence of individual subpopulations of T and B lymphocytes and the level of PD-1 receptor expression. The analysis of the individual parameters of the TNM scale also showed significant changes between the PD-1 expression and the tested biological material in individual subgroups of the scale. We also found that the expression of PD-1 on the CD4+ T cells from the lymph node samples caused an almost 1.5-fold increase in the risk of death. In the analyses of the presence of EBV, the highest concentration was recorded in the tumor samples, then for the lymph node samples, and followed by the blood samples. Furthermore, we showed that the presence of EBV genetic material was positively correlated with the level of PD-1 expression in the tested biological materials.

Prevalence of herpes zoster virus reactivation in patients diagnosed with Bell's palsy.

Herpes zoster virus can cause inflammatory neuropathy of the facial nerve. However, studies evaluating the prevalence of this agent in peripheral facial palsy are heterogeneous regarding sample group selection, laboratory analysis method and variables studied. In addition, there are a lack of epidemiological data in the Brazilian population on this serological phenomenon in peripheral facial palsy. This study estimated herpes zoster reactivation prevalence in serological samples through chemiluminescence immunoassay for quantitative determination of specific antibodies directed against the virus. This cross-sectional study sought to determine the prevalence of viral reactivation by herpes zoster in subjects with idiopathic peripheral facial palsy through analysis of serological samples over a year. Forty-seven patients (32 females and 15 males) participated. Severe paralysis was more common in older patients (p = 0.017). Facial pain (p = 0.02) and vertigo (p = 0.001) were related to a worse evolution of facial palsy. The rate of serological reactivation of the virus was 12.76 per cent. The rate of serological reactivation of herpes virus in idiopathic peripheral facial palsy in our population is similar to foreign literature data, suggesting similar aetiological mechanisms in the genesis of this morbidity.