BACKGROUND AND OBJECTIVES

Pelargonium sidoides DC. Root (PELARGO) 20 mg capsule is approved by the Philippine Food and Drug Administration (FDA) for the symptomatic treatment of common cold. In compliance with FDA, this post-authorization safety study was conducted to determine the incidence of signs and symptoms of liver injury with PELARGO intake. It also aimed to look at symptom improvement and the incidence of other adverse events.

This non-interventional post-authorization safety study enrolled 300 adult patients with common cold, pre- scribed with Pelargonium sidoides DC. 20 mg capsule three times a day for seven days during routine clinical care from May 2023 to December 2023 in Cavite, Philippines. Demographic, clinical, and physical exam data were collected at baseline. Physical exam data, signs and symptoms of liver injury, symptom improvement, and other adverse events were determined post-treatment. Descriptive statistics were computed to characterize the participants at baseline (day 0) and end-study visit (day 8).

There were 300 enrolled patients, 53% female and 60% single. The mean age was 36 years and the mean BMI was 26 kg/m2. Vital signs at baseline were mostly within normal limits and most had respiratory f indings. Two hundred ninety-eight (298) completed the study. Only a few had respiratory findings at end-study visit. There were no signs and symptoms of liver toxicity nor serious adverse events after seven days of PELARGO intake. Reported adverse effects with 2.0% to 1.3% incidence in seven days include dizziness, drowsiness, headache, and polyphagia. Others wereCONCLUSION

There is no evidence of liver toxicity after seven days of PELARGO intake for common cold among Filipino adults. The drug was well tolerated, and most patients experienced significant symptom improvement. Results should be interpreted with caution in the light of study limitations.

Hepatitis B virus (HBV)-specific CD8⁺ T cells play a central role in controlling HBV infection; however, their function is impaired during chronic HBV infection, manifesting as a state of dysfunction. Recent studies have revealed that CD8⁺ T cell dysfunction in chronic HBV infection differs from the classical exhaustion observed in other viral infections or tumors. In 2024, several pivotal studies further elucidated novel mechanisms underlying CD8⁺ T cell dysfunction in chronic HBV infection and identified new therapeutic targets, including 4-1BB and transforming growth factor-beta (TGF-β). This review, while elucidating the dysfunction of CD8⁺ T cells in chronic HBV infection and its underlying mechanisms, focuses on summarizing the key findings from these latest studies and explores their translational value and clinical significance.
Humans ; Hepatitis B, Chronic/virology* ; CD8-Positive T-Lymphocytes/immunology* ; Hepatitis B virus/physiology* ; Animals ; Transforming Growth Factor beta/immunology*

Objective To investigate the role and mechanism of RNA-Specific adenosine deaminase 3 (Adar3) in regulating macrophage polarization during Coxsackievirus B3(CVB3)-induced viral myocarditis (VM). Methods Bone marrow-derived macrophages (BMDM) from mice were cultured in vitro and induced into M1/M2 macrophages using interferon-gamma (IFN-γ)/lipopolysaccharide (LPS) or interleukin 4 (IL-4), respectively. The mRNA expression levels of Adar1, Adar2, and Adar3 in each group of cells were assessed by real-time quantitative PCR (qRT-PCR). Specific siRNAs targeting the Adar3 gene were designed, synthesized, and transiently transfected into M2 macrophages. The mRNA levels of M2 polarization-related marker genes-including arginase 1 (Arg1), chitinase 3-like molecule 3 (YM1/Chi3l3), and resistin-like molecule alpha (RELMα/FIZZ1)-were detected by qRT-PCR. RNA sequencing was performed to analyze the signaling pathways affected by Adar3. The expression levels of Wnt/β-catenin signaling pathway were further validated using qRT-PCR and Western blot. The adeno-associated virus overexpressing Adar3 was designed, synthesized, and injected into mice via tail vein. Three weeks later, a myocarditis mouse model was established. After an additional week, the phenotype and function of cardiac macrophages, as well as multiple indicators of VM (including echocardiography, body weight, histopathology and serology) were examined. Additionally, the protein levels of the Wnt/β-catenin signaling pathway were assessed. Results Compared to M0-type macrophages, the expression level of Adar3 was significantly increased in M2-type macrophages. After transfection of Adar3 siRNA, the mRNA levels of Arg1, YM1 and FIZZ1 in M2 macrophages were downregulated. RNA sequencing revealed 149 upregulated genes and 349 downregulated genes. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis and subsequent validation experiments indicated that Adar3 modulated the Wnt/β-catenin signaling pathway. In vivo experiments demonstrated that Adar3 overexpression alleviated the cardiac dysfunction of VM mice. The proportion of M1 macrophages in the heart decreased, while the proportion of M2 macrophages increased. At the same time, the Adar3 overexpression activated the Wnt/β-catenin signaling pathway. Conclusion Adar3 promotes macrophage polarization toward the M2 phenotype by activating the Wnt/β-catenin signaling pathway, thereby alleviating VM.
Animals ; Adenosine Deaminase/metabolism* ; Macrophages/immunology* ; Wnt Signaling Pathway/genetics* ; Myocarditis/immunology* ; Mice ; Coxsackievirus Infections/metabolism* ; Male ; Mice, Inbred BALB C ; Enterovirus B, Human/physiology* ; beta Catenin/genetics*

BACKGROUND

The World Health Organization (WHO) estimates that in 2015, approximately 325 million or 4.4% of the global population were living with chronic hepatitis B or hepatitis C infection. In the same year, around 1.34 million died from this disease.

This study aimed to estimate the burden of hepatitis B in the Philippines and to determine the costeffectiveness of possible interventions.

This study utilized the Center for Disease Analysis Foundation’s (CDAF’s) mathematical disease burden model of hepatitis B. Model inputs were collected using literature review, key informant interviews, expert panel interviews, and records review, and were validated through a series of round table discussions with experts.

Results show that in 2017, the prevalence of chronic hepatitis B infection in the Philippines was 9.7%, equivalent to 10 million infected individuals. Although the model projects a decreasing trend in chronic hepatitis B virus (HBV) infections, liver-related mortality and morbidity due to these viruses are expected to rise if the status quo is maintained. Results show that substantial increase in government subsidy for WHO elimination scenarios would be required to achieve cost-effective outcomes.

Hepatitis B remains a huge problem in the Philippines. The HBV modelling exercise reveal that it will be worthwhile and cost-effective to adhere to the WHO elimination targets. A substantial financial investment will be necessary to do so, specifically a significant scale up in the screening, diagnosis, treatment, and monitoring of patients with HBV. While this modelling exercise does not yield burden of disease as accurate as a prevalence survey, experts consulted in the round table discussions agreed with the modelling inputs.

BACKGROUND AND OBJECTIVE

Stigma remains a profound barrier to public health, particularly in managing diseases such as Hepatitis B, which is highly prevalent in hyperendemic regions like the Philippines. The social stigma associated with such health conditions can severely limit access to care and hinder adherence to treatment, exacerbating the overall disease burden. Despite the critical impact of stigma on health outcomes, there is a notable gap in the systematic evaluation of the tools used to measure stigma related to health conditions like Hepatitis B. This study aims to fill this gap by reviewing existing instruments for their methodologies, reliability, and validity to inform the development of a refined tool tailored to the Philippine context.

A systematic search was conducted across six databases, including PubMed, Cochrane Database of Systematic Reviews, Open Grey, DissOnline, Philippine Health Research Registry (PHRR), and Health Research and Development Information Network (HERDIN), following PRISMA guidelines. The search strategy focused on identifying quantitative and mixed-methods studies using questionnaires to measure HBV-related stigma and discrimination. Studies published between January 1, 1992, and December 31, 2023, were considered. The selection process involved screening for duplicates, reviewing titles and abstracts, and performing a full-text review based on predetermined eligibility criteria.

The initial search yielded 1,198 articles, with 24 duplicates removed. After title and abstract screening, 28 articles were considered for full-text review, resulting in 17 relevant articles in the final analysis with 15 unique instrumentations. The majority of studies employed cross-sectional designs (n=8), with a significant concentration in Asian countries (n=11), indicating a regional focus in HBV stigma research. The review identified a range of questionnaire methodologies, but most studies lacked specificity regarding the type of stigma measured. The Likert Scale was the most commonly used measurement tool, yet few studies provided cut-off values for stigma levels. Validity and reliability testing was reported in 12 articles, including pilot studies, Cronbach’s alpha, and factor analysis.

The lack of a universal methodology and specificity in existing instruments underscores the importance of developing a refined tool that can accurately capture the nuances of stigma and discrimination associated with HBV. The urgent need for standardized, reliable, and culturally sensitive questionnaires is evident, underscoring their importance in developing effective public health strategies and improving treatment outcomes for individuals living with HBV, especially in the Philippines.

OBJECTIVE: To investigate chronic hepatitis C virus (HCV) infection's effect on gestational liver function, pregnancy and delivery complications, and neonatal development. METHODS: A total of 157 HCV antibody-positive (anti-HCV[+]) and HCV RNA(+) patients (Group C) and 121 anti-HCV(+) and HCV RNA(-) patients (Group B) were included as study participants, while 142 anti-HCV(-) and HCV RNA(-) patients (Group A) were the control group. Data on biochemical indices during pregnancy, pregnancy complications, delivery-related information, and neonatal complications were also collected. RESULTS: Elevated alanine aminotransferase (ALT) rates in Group C during early, middle, and late pregnancy were 59.87%, 43.95%, and 42.04%, respectively-significantly higher than Groups B (26.45%, 15.70%, 10.74%) and A (23.94%, 19.01%, 6.34%) ( P < 0.05). Median ALT levels in Group C were significantly higher than in Groups A and B at all pregnancy stages ( P < 0.05). No significant differences were found in neonatal malformation rates across groups ( P > 0.05). However, neonatal jaundice incidence was significantly greater in Group C (75.16%) compared to Groups A (42.25%) and B (57.02%) ( χ ² = 33.552, P < 0.001). HCV RNA positivity during pregnancy was an independent risk factor for neonatal jaundice ( OR = 2.111, 95% CI 1.242-3.588, P = 0.006). CONCLUSIONS Chronic HCV infection can affect the liver function of pregnant women, but does not increase the pregnancy or delivery complication risks. HCV RNA(+) is an independent risk factor for neonatal jaundice.
Humans ; Female ; Pregnancy ; Adult ; Pregnancy Complications, Infectious/epidemiology* ; Retrospective Studies ; Pregnancy Outcome ; Infant, Newborn ; Viremia/virology* ; Hepatitis C ; Hepacivirus/physiology* ; Hepatitis C, Chronic/virology* ; Young Adult ; Alanine Transaminase/blood*

Senecavirus A (SVA) is a major viral pathogen causing disease in pigs, and effective monitoring of SVA infection is critical for disease control. In this study, we aimed to develop a reliable ELISA method for rapidly detecting neutralizing antibodies against SVA. We used HEK293F cells to express an SVA-specific porcine Fab antibody and verified the biological activity of the Fab antibody by indirect ELISA, immunofluorescence assay, virus neutralization test, and Western blotting. The Fab antibody was biotinylated and used as a competitive antibody to establish a competitive ELISA (C-ELISA) for detecting neutralizing antibodies against SVA. We then evaluated the C-ELISA in terms of sensitivity, specificity, repeatability, and result agreement rate with the VNT. The results showed that we successfully prepared an SVA-specific porcine Fab antibody, which showed high affinity for SVA. We named this antibody 1M33Fab and designated it as Bio-1M33Fab after biotin labeling. The assay conditions were optimized as follows: the coating concentration of SVA particles being 1 μg/mL, the working concentration of Bio-1M33Fab being 0.5 μg/mL, the optimal serum dilution of 1:10, and the optimal dilution of enzyme-labeled avidin being 1:30 000. At a percent inhibition (PI) of 47%, the assay demonstrated the highest sensitivity (96.88%) and specificity (100%), with no cross-reactivity observed with the positive sera of major porcine viral diseases. The intra-assay coefficient of variation ranged from 1.12% to 7.34%, while the inter-assay coefficient of variation ranged from 1.10% to 8.97%, indicating good repeatability. In the detection of 224 clinical pig serum samples, C-ELISA and VNT showed a result agreement rate of 93.75%. In conclusion, we successfully develop a C-ELISA method for detecting neutralizing antibodies against SVA by using a porcine-derived Fab antibody, which lays a foundation for the development of detection kits.
Animals ; Swine ; Antibodies, Neutralizing/immunology* ; Enzyme-Linked Immunosorbent Assay/methods* ; Immunoglobulin Fab Fragments/immunology* ; Antibodies, Viral/immunology* ; Picornaviridae/immunology* ; Humans ; HEK293 Cells ; Swine Diseases/diagnosis* ; Picornaviridae Infections/diagnosis*

Viral infections are one of the main causes of deaths and economic losses around the globe, and effective virus detection methods are essential for epidemic prevention and control. Most existing detection methods have problems such as high false negative/positive rates, slow responses, high costs, and dependence on professional equipment and personnel, which are not conducive to the rapid and accurate detection of viruses. Field effect transistor (FET) biosensors have attracted widespread attention due to their advantages of label-free detection, high sensitivity, fast responses, real-time measurement, low power consumption, and small sizes for portability. This article first briefly describes the basic situation of viruses and the structure and detection principle of FET biosensors. Subsequently, it delves into the research achievements in the application of FET biosensors in the detection of influenza viruses, hepatitis viruses, human immunodeficiency virus, and severe acute respiratory syndrome coronavirus 2. Finally, we make a comprehensive summary and reasonable outlook on the role played by FET biosensors in biomedicine.
Biosensing Techniques/instrumentation* ; Transistors, Electronic ; Humans ; SARS-CoV-2/isolation & purification* ; Viruses/isolation & purification* ; Orthomyxoviridae/isolation & purification* ; Hepatitis Viruses/isolation & purification* ; Virus Diseases/virology* ; HIV/isolation & purification* ; COVID-19/diagnosis*

Hepatitis E is the liver inflammation caused by a hepatitis E virus infection.Immunocompetent patients with acute hepatitis E can spontaneously clear the infection,whereas immunosuppressed patients may not be able to clear the hepatitis E virus infection and develop chronic hepatitis.Most patients with hepatitis E are asymptomatic and present only with mild and persistent liver function abnormalities.This article reports a case of hepatitis E in an immunocompetent adult with elevated aminotransferases as the main manifestation.Hepatic fibrosis was detected by hepatic puncture biopsy.This report aims to remind other physicians to evaluate liver fibrosis when encountering acute hepatitis E,especially in patients with chronic liver disease.
Adult ; Humans ; Acute Disease ; Hepatitis E/complications* ; Liver Cirrhosis/etiology*

A 4-year-old boy was admitted to the hospital with a 3-day history of rash and intermittent abdominal pain, during which abnormal results from routine blood tests were discovered. Initially, he presented with acute jaundice hepatitis and pancytopenia. The patient's condition progressed rapidly, with recurrent fever, worsening jaundice of the skin and sclera, and progressively worsening hepatosplenomegaly. Liver function impairment and bone marrow failure continued to deteriorate, while cytokine levels continued to rise. After excluding infections, autoimmune diseases, tumors, genetic metabolic disorders, and toxicities, the patient was diagnosed with hepatitis-associated aplastic anemia (HAAA) complicated by hemophagocytic lymphohistiocytosis (HLH). Following treatment with corticosteroids, plasma exchange, intravenous immunoglobulin, and liver protection therapy, the patient's symptoms partially alleviated. Aplastic anemia complicated by HLH is relatively uncommon, and HAAA complicated by HLH is even rarer, often presenting insidiously and severely. This paper presents a case of HAAA complicated by HLH and summarizes previously reported cases in the literature, providing references for the early diagnosis and treatment of this condition.
Humans ; Lymphohistiocytosis, Hemophagocytic/therapy* ; Male ; Anemia, Aplastic/complications* ; Child, Preschool ; Hepatitis/complications*