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Journal of Family Medicine and Primary... May 2024The Coronavirus disease 2019 (COVID-19) pandemic has been the biggest threat to humankind during the last 3 years. It has caused the loss of more than 6.9 million...
INTRODUCTION
The Coronavirus disease 2019 (COVID-19) pandemic has been the biggest threat to humankind during the last 3 years. It has caused the loss of more than 6.9 million precious lives across the world. The only method by which the massacre could be stopped was by mass vaccination or mass immunization. The patients suffering from autoimmune rheumatic disorders (AIRDs) and treated with immunosuppressants were the high-priority candidates for vaccination. However, the data regarding the efficacy of COVID-19 vaccines in this group of patients are very less. Hence, this study was planned to study the immunogenicity of Covishield in patients with AIRDs attending the rheumatology OPD at DMCH, Ludhiana.
MATERIALS AND METHODS
It was a prospective cohort study and was planned by the Department of Biochemistry and Department of Clinical Immunology and Rheumatology at Dayanand Medical College and Hospital, Ludhiana. Fifty patients with AIRDs attending the DMCH rheumatology OPD and 52 age and sex-matched healthy controls who had received two doses of Covishield vaccine were included in this study. Patients having any other immunosuppressive conditions like uncontrolled diabetes, hepatitis, malignancy or HIV were excluded. Patients who had suffered from previous laboratory-confirmed COVID-19 infection (by RT-PCR) were also excluded. Blood samples were collected following all aseptic precautions from patients and controls on the 28 day after administration of a second dose of Covishield vaccine and total antibodies to the severe acute respiratory syndrome coronavirus 2 spike (S) protein receptor binding domain was measured using Elecsys Anti-SARS-CoV-2 S kit from Roche.
RESULTS
It was observed that no significant difference was there in antibody titre between cases and controls (6213 ± 4418 vs. 8331 ± 7979, = 0.1022). It was also observed that no statistically significant difference in antibody titre in cases without prednisolone and those taking treatment with prednisolone was found ( = 0.7058). A similar observation was found in terms of methotrexate also ( = 0.457). No significant difference in antibody titres was there when compared with controls (for prednisolone, = 0.169, for methotrexate, = 0.078). We found that only the patients receiving mycophenolate mofetil showed a statistically significant decrease in antibody titre in comparison to healthy controls ( = 0.03). Our study showed no statistically significant difference in antibody titres between patients suffering from different AIRDs.
CONCLUSION
Our study supplements the fact that patients with AIRDs in India can receive Covishield as the primary vaccine against COVID-19 without concerns regarding decreased immunogenicity or increased adverse effects.
PubMed: 38948615
DOI: 10.4103/jfmpc.jfmpc_1021_23 -
World Journal of Hepatology Jun 2024Delving into the immunological crossroads of liver diseases, this editorial explores the dynamic interplay between hepatitis C virus (HCV) and autoimmune hepatitis...
Delving into the immunological crossroads of liver diseases, this editorial explores the dynamic interplay between hepatitis C virus (HCV) and autoimmune hepatitis (AIH). While HCV primarily manifests as a viral infection impacting the liver, previous studies unveil a captivating connection between HCV and the emergence of AIH. The dance of the immune system in response to HCV appears to set the stage for an intriguing phenomenon-an aberrant autoimmune response leading to the onset of AIH. Evidence suggests a heightened presence of autoimmune markers in individuals with chronic HCV infection, hinting at a potential overlap between viral and autoimmune liver diseases. Navigating the intricate terrain of viral replication, immune response dynamics, and genetic predisposition, this editorial adds a layer of complexity to our understanding of the relationship between HCV and AIH. In this immunological crossroads, we aim to unearth insights into the complex interplay, using a compelling case where AIH and primary sclerosing cholangitis overlapped following HCV treatment with direct-acting antivirals as background.
PubMed: 38948443
DOI: 10.4254/wjh.v16.i6.867 -
Cureus May 2024Rodenticides are easily available in the market and suicidal attempts by ingesting such poisonous products are commonly reported in rural India. We aimed to analyze...
Rodenticides are easily available in the market and suicidal attempts by ingesting such poisonous products are commonly reported in rural India. We aimed to analyze predictive factors, biological markers, and treatment outcomes among patients who ingested rodenticides (yellow phosphorus) with the brand name, Rattol. Here, we present three such cases who were admitted to a tertiary care hospital. We recorded socio-demographic characteristics, probable predictive factors, and serial charting biological markers. Conventional treatment was given to these cases. All cases were young women (age range: 17-30 years) from rural areas, two were married and one was unmarried. The approximate quantity of ingestion was 20, 10, and 5 grams, respectively. The time lag between the ingestion and sought first health care was 6 hours, 18 hours, and 1 hour, respectively. Major symptoms were vomiting, abdominal pain, and headache. Biological markers, including total bilirubin, alanine aminotransferase, aspartate aminotransferase, creatinine, prothrombin time, international normalized ratio, and model for end-stage liver disease (MELD) score were statistically significant. Two women had toxic hepatitis and acute liver failure and one did not have any organ damage. All of them were recovered within 17 days of mean hospital stay. A lethal dosage of rodenticides and delayed presentation to the hospital can prompt acute liver failure and severe ailment. Creating awareness, promoting mental health and suicide prevention, and framing proper guidelines for treatment will reduce morbidity and mortality.
PubMed: 38947661
DOI: 10.7759/cureus.61416 -
Frontiers in Immunology 2024Follicular helper T cells are essential for helping in the maturation of B cells and the production of neutralizing antibodies (NAbs) during primary viral infections....
INTRODUCTION
Follicular helper T cells are essential for helping in the maturation of B cells and the production of neutralizing antibodies (NAbs) during primary viral infections. However, their role during recall responses is unclear. Here, we used hepatitis C virus (HCV) reinfection in humans as a model to study the recall collaborative interaction between circulating CD4 T follicular helper cells (cTfh) and memory B cells (MBCs) leading to the generation of NAbs.
METHODS
We evaluated this interaction longitudinally in subjects who have spontaneously resolved primary HCV infection during a subsequent reinfection episode that resulted in either another spontaneous resolution (SR/SR, = 14) or chronic infection (SR/CI, = 8).
RESULTS
Both groups exhibited virus-specific memory T cells that expanded upon reinfection. However, early expansion of activated cTfh (CD4CXCR5PD-1ICOSFoxP3) occurred in SR/SR only. The frequency of activated cTfh negatively correlated with time post-infection. Concomitantly, NAbs and HCV-specific MBCs (CD19CD27IgME2-Tet) peaked during the early acute phase in SR/SR but not in SR/CI. Finally, the frequency of the activated cTfh1 (CXCR3CCR6) subset correlated with the neutralization breadth and potency of NAbs.
CONCLUSION
These results underscore a key role for early activation of cTfh1 cells in helping antigen-specific B cells to produce NAbs that mediate the clearance of HCV reinfection.
PubMed: 38947319
DOI: 10.3389/fimmu.2024.1403769 -
Bioscience Trends Jun 2024Liver transplantation (LT) has been an established treatment for end-staged liver disease for acute, chronic, metabolic diseases and liver cancer. Advanced surgical...
Liver transplantation (LT) has been an established treatment for end-staged liver disease for acute, chronic, metabolic diseases and liver cancer. Advanced surgical techniques, refined indications and contraindications for LT, improvements of donor selection, prognostic scorings system and immunosuppressive regimens have contributed to the improved outcomes of liver transplantation. The etiologies of cirrhosis have been shifting from viral hepatitis to metabolic associated fatty liver disease. New indications include peripheral or mass forming bile duct cancer, metastases from bowel cancers or neuroendocrine tumors. Resection and partial liver segments 2-3 transplantation with delayed total hepatectomy has been performed to the limited cases, which was the explored technique of auxiliary partial orthotopic LT. Minimally invasive donor hepatectomy (laparoscopic or robotic) has been increasingly done. In this review are described the recent pressing topics in LT.
PubMed: 38945855
DOI: 10.5582/bst.2024.01176 -
Chinese Medical Journal Jun 2024Hepatic inflammatory cell accumulation and the subsequent systematic inflammation drive acute-on-chronic liver failure (ACLF) development. Previous studies showed that...
BACKGROUND
Hepatic inflammatory cell accumulation and the subsequent systematic inflammation drive acute-on-chronic liver failure (ACLF) development. Previous studies showed that the vagus nerve exerts anti-inflammatory activity in many inflammatory diseases. Here, we aimed to identify the key molecule mediating the inflammatory process in ACLF and reveal the neuroimmune communication arising from the vagus nerve and immunological disorders of ACLF.
METHODS
Proteomic analysis was performed and validated in ACLF model mice or patients, and intervention animal experiments were conducted using neutralizing antibodies. PNU-282987 (acetylcholine receptor agonist) and vagotomy were applied for perturbing vagus nerve activity. Single-cell RNA sequencing (scRNA-seq), flow cytometry, immunohistochemical and immunofluorescence staining, and CRISPR/Cas9 technology were used for in vivo or in vitro mechanistic studies.
RESULTS
The unbiased proteomics identified C-X-C motif chemokine ligand 9 (CXCL9) as the greatest differential protein in the livers of mice with ACLF and its relation to the systematic inflammation and mortality were confirmed in patients with ACLF. Interventions on CXCL9 and its receptor C-X-C chemokine receptor 3 (CXCR3) improved liver injury and decreased mortality of ACLF mice, which were related to the suppressing of hepatic immune cells' accumulation and activation. Vagus nerve stimulation attenuated while vagotomy aggravated the expression of CXCL9 and the severity of ACLF. Blocking CXCL9 and CXCR3 ameliorated liver inflammation and increased ACLF-associated mortality in ACLF mice with vagotomy. scRNA-seq revealed that hepatic macrophages served as the major source of CXCL9 in ACLF and were validated by immunofluorescence staining and flow cytometry analysis. Notably, the expression of CXCL9 in macrophages was modulated by vagus nerve-mediated cholinergic signaling.
CONCLUSIONS
Our novel findings highlighted that the neuroimmune communication of the vagus nerve-macrophage-CXCL9 axis contributed to ACLF development. These results provided evidence for neuromodulation as a promising approach for preventing and treating ACLF.
PubMed: 38945689
DOI: 10.1097/CM9.0000000000003104 -
Mymensingh Medical Journal : MMJ Jul 2024Major causes of acute insult in Hepatitis B virus related acute on chronic liver failure in the Asian region are reactivation of Hepatitis B virus and super infection... (Randomized Controlled Trial)
Randomized Controlled Trial Comparative Study
Major causes of acute insult in Hepatitis B virus related acute on chronic liver failure in the Asian region are reactivation of Hepatitis B virus and super infection with hepatitis A and E virus (ACLF). Anti viral therapy should be started as soon as possible in the ACLF patients at presentation while waiting for confirmation by HBV DNA level. This randomized controlled trial was carried out at the Department of Hepatology, BSMMU, Bangladesh from September 2019 to august 2020 with Hepatitis B virus related ACLF patient. This trial was conducted among twenty seven HBV acute on chronic liver failure patient to compare Child Turcotte pugh (CTP) score, Model for end stage liver disease (MELD) score, Asia Pacific Association for study of Liver (APASL) ACLF Research consortium (AARC) score, survival of the patients and HBV DNA level at 3 months with antiviral therapy between tenofovir alafenamide (25mg) and entecavir (0.5mg) group. CTP score, MELD score and AARC score were significantly (p<0.05) decline from baseline to all subsequent follow-up at 1st (at 7 days), 2nd (at 14 days), 3rd (at 30 days) and 4th (at 90 days) in each group but non significant (p>0.05) difference occurred between two group. All twenty seven patients had detectable HBV DNA level at pre-treatment and all survived patients became undectable at 4th, 90 days follow-up. Total 10 patients (37.07%) were survived at 90 days follow-up, out of them seven patients (70.0%) were in tenofovir alafenamide group and three patients (30.0%) were in entecavir group which was statistically significant (p<0.05) in between two group. Hepatic encephalopathy and hepatorenal syndrome were most common causes of death in both groups. Both drugs tenofovir alafenamide and entecavir significantly improves liver functions but the former one is superior regarding survival.
Topics: Humans; Tenofovir; Guanine; Antiviral Agents; Male; Acute-On-Chronic Liver Failure; Female; Adult; Middle Aged; Treatment Outcome; Alanine; Hepatitis B; Hepatitis B virus
PubMed: 38944709
DOI: No ID Found -
Clinics and Research in Hepatology and... Jun 2024The majority of indeterminate pediatric acute liver failure (PALF) cases are secondary to immune dysregulation, labeled activated T-cell hepatitis (TCHep). We aimed to...
BACKGROUND AND AIMS
The majority of indeterminate pediatric acute liver failure (PALF) cases are secondary to immune dysregulation, labeled activated T-cell hepatitis (TCHep). We aimed to describe a cohort of children with acute severe hepatitis and PALF and define how clinical immune labs may help identify the TCHep group.
METHODS
Retrospective review of children with acute hepatitis and PALF between March 2020 and August 2022. Patients were classified as known diagnosis, indeterminate hepatitis (IND-Hep), or TCHep (defined by liver biopsy with predominant CD8 T-cell inflammation or development of aplastic anemia).
RESULTS
124 patients were identified: 83 with known diagnoses, 16 with TCHep, and 25 with IND-Hep. Patients with TCHep had significantly increased median total bilirubin levels (7.5 mg/dL (IQR 6.8-8.9) vs 1.5 mg/dL (IQR 1.0-3.6), p < 0.0001), soluble interleukin-2 receptor levels (4512 IU/mL (IQR 4073-5771) vs 2997 IU/mL (IQR 1957-3237), p = 0.02), and percent of CD8+ T-cells expressing perforin (14.5 % (IQR 8.0-20.0) vs 1.0 % (IQR 0.8-1.0), p = 0.004) and granzyme (37.5 % (IQR 15.8-54.8) vs 4.0 % (IQR 2.5-5.5), p = 0.004) compared to IND-Hep patients. Clinical flow cytometry showed that TCHep patients had significantly increased percent CD8+ T cells (29.0 % (IQR 24.5-33.5) vs 23.6 % (IQR 19.8-25.8), p = 0.04) and HLA-DR+ (16.0 % (IQR 14.5-24.5) vs 2.7 (1.8-5.3), p < 0.001) compared to IND-Hep patients indicative of increase in CD8+ T cells that are activated.
CONCLUSIONS
Peripheral blood clinical immune studies demonstrate increased markers of CD8 T-cell activation, proliferation, and cytotoxic function for TCHep patients. These readily available immune function labs can be used to help distinguish patients with TCHep from those with other causes. This provides a non-invasive tool for early detection of potential TCHep before progression to liver failure.
PubMed: 38936769
DOI: 10.1016/j.clinre.2024.102407 -
European Journal of Pharmacology Jun 2024The interleukin-1 receptor-associated kinase (IRAK) family is a group of serine-threonine kinases that regulates various cellular processes via toll-like receptor... (Review)
Review
The interleukin-1 receptor-associated kinase (IRAK) family is a group of serine-threonine kinases that regulates various cellular processes via toll-like receptor (TLR)/interleukin-1 receptor (IL1R)-mediated signaling. The IRAK family comprises four members, including IRAK1, IRAK2, IRAK3, and IRAK4, which play an important role in the expression of various inflammatory genes, thereby contributing to the inflammatory response. IRAKs are key proteins in chronic and acute liver diseases, and recent evidence has implicated IRAK family proteins (IRAK1, IRAK3, and IRAK4) in the progression of liver-related disorders, including alcoholic liver disease, non-alcoholic steatohepatitis, hepatitis virus infection, acute liver failure, liver ischemia-reperfusion injury, and hepatocellular carcinoma. In this article, we provide a comprehensive review of the role of IRAK family proteins and their associated inflammatory signaling pathways in the pathogenesis of liver diseases. The purpose of this study is to explore whether IRAK family proteins can serve as the main target for the treatment of liver related diseases.
PubMed: 38936453
DOI: 10.1016/j.ejphar.2024.176773 -
PloS One 2024Hepatitis B virus (HBV) infection is a global public health issue. We offer a comprehensive analysis of the dynamics of HBV, which can be successfully controlled with...
Hepatitis B virus (HBV) infection is a global public health issue. We offer a comprehensive analysis of the dynamics of HBV, which can be successfully controlled with vaccine and treatment. Hepatitis B virus (HBV) causes a significantly more severe and protracted disease compared to hepatitis A. While it initially presents as an acute disease, in approximately 5 to 10% of cases, it can develop into a chronic disease that causes permanent damage to the liver. The hepatitis B virus can remain active outside the body for at least seven days. If the virus penetrates an individual's body without immunization, it may still result in infection. Upon exposure to HBV, the symptoms often last for a duration ranging from 10 days to 6 months. In this study, we developed a new model for Hepatitis B Virus (HBV) that includes asymptomatic carriers, vaccination, and treatment classes to gain a comprehensive knowledge of HBV dynamics. The basic reproduction number [Formula: see text] is calculated to identify future recurrence. The local and global stabilities of the proposed model are evaluated for values of [Formula: see text] that are both below and above 1. The Lyapunov function is employed to ensure the global stability of the HBV model. Further, the existence and uniqueness of the proposed model are demonstrated. To look at the solution of the proposed model graphically, we used a useful numerical strategy, such as the non-standard finite difference method, to obtain more thorough numerical findings for the parameters that have a significant impact on disease elimination. In addition, the study of treatment class in the population, we may assess the effectiveness of alternative medicines to treat infected populations can be determined. Numerical simulations and graphical representations are employed to illustrate the implications of our theoretical conclusions.
Topics: Humans; Hepatitis B; Hepatitis B virus; Computer Simulation; Epidemics; Hepatitis B Vaccines; Basic Reproduction Number; Vaccination
PubMed: 38935766
DOI: 10.1371/journal.pone.0304375