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Previous reports have shown that IL‐6 and IFN‐⍺ induce distinct transcriptomic and morphological changes in microglia. Here, we demonstrate that IL‐6 increases tissue surveillance, migration and phagocytosis in primary murine microglia, whereas IFN‐⍺ inhibits these functions. Our results provide a crucial link between transcriptome and function. It holds the potential to serve as the foundation for future studies aimed at identifying therapeutic targets for cytokine‐mediated neuroinflammatory diseases. [ABSTRACT FROM AUTHOR]

Globally, hepatitis C virus (HCV) and coronavirus disease 2019 (COVID‐19) are the most common causes of death due to the lack of early predictive and diagnostic tools. Therefore, research for a new biomarker is crucial. Inflammatory biomarkers are critical central players in the pathogenesis of viral infections. IL‐18, produced by macrophages in early viral infections, triggers inflammatory biomarkers and interferon production, crucial for viral host defense. Finding out IL‐18 function can help understand COVID‐19 pathophysiology and predict disease prognosis. Histamine and its receptors regulate allergic lung responses, with H1 receptor inhibition potentially reducing inflammation in severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection. angiotensin‐converting enzyme 2 (ACE‐2) receptors on cholangiocytes suggest liver involvement in SARS‐CoV‐2 infection. The current study presents the potential impact of circulating acetylcholine, histamine, IL‐18, and interferon‐Alpha as diagnostic tools in HCV, COVID‐19, and dual HCV‐COVID‐19 pathogenesis. The current study was a prospective cross‐section conducted on 188 participants classified into the following four groups: Group 1 COVID‐19 (n = 47), Group 2 HCV (n = 47), and Group 3 HCV‐COVID‐19 patients (n = 47), besides the healthy control Group 4 (n = 47). The levels of acetylcholine, histamine, IL‐18, and interferon‐alpha were assayed using the ELISA method. Liver and kidney functions within all groups showed a marked alteration compared to the healthy control group. Our statistical analysis found that individuals with dual infection with HCV‐COVID‐19 had high ferritin levels compared to other biomarkers while those with COVID‐19 infection had high levels of D‐Dimer. The histamine, acetylcholine, and IL‐18 biomarkers in both COVID‐19 and dual HCV‐COVID‐19 groups have shown discriminatory power, making them potential diagnostic tests for infection. These three biomarkers showed satisfactory performance in identifying HCV infection. The IFN‐Alpha test performed well in the HCV‐COVID‐19 group and was fair in the COVID‐19 group, but it had little discriminative value in the HCV group. Moreover, our findings highlighted the pivotal role of acetylcholine, histamine, IL‐18, and interferon‐Alpha in HCV, COVID‐19, and dual HCV‐COVID‐19 infection. Circulating levels of acetylcholine, histamine, IL‐18, and interferon‐Alpha can be potential early indicators for HCV, COVID‐19, and dual HCV‐COVID‐19 infection. We acknowledge that further large multicenter experimental studies are needed to further investigate the role biomarkers play in influencing the likelihood of infection to confirm and extend our observations and to better understand and ultimately prevent or treat these diseases. [ABSTRACT FROM AUTHOR]

Chronic hepatitis delta (CHD) affects millions worldwide with many undiagnosed. It requires the presence of hepatitis B virus (HBV) for viral propagation, and those who are coinfected have a more rapid development of cirrhosis, hepatocellular carcinoma and fulminant liver failure. Treatments licensed for HBV have been ineffective in those with CHD. As an orphan disease, there is only one licensed treatment for CHD in Europe, which has relatively limited efficacy and viral control. This review focuses on current treatments, recent advances and unresolved issues in hepatitis delta management. Chronic hepatitis delta is a very serious liver disease caused by the hepatitis delta virus, which can only infect people who already have hepatitis B. Worldwide, about 15 to 20 million people are affected. The disease can lead to severe liver damage and liver cancer. Medications that work for hepatitis B do not work for hepatitis delta, and until recently, there were no specific treatments approved for it. A new drug called bulevirtide was approved in Europe in 2020, and the UK in 2023, and is showing promise in ongoing studies around the world. It offers hope for better management of the disease. However, it is a daily injection needed indefinitely. Many people do not completely clear the virus. This article discusses new treatment strategies, including combining bulevirtide with other drugs, to improve the lives of the people living with the condition. These approaches aim to either significantly reduce the virus in the liver or (ideally) get rid of it completely. Article highlights Background Chronic hepatitis delta (CHD) is the most severe form of viral hepatitis, affecting 15–20 million people globally. The disease progresses rapidly and can lead to severe liver-related morbidity and mortality, with cirrhosis, liver cancer and fulminant liver failure. Hepatitis delta virus (HDV) relies on hepatitis B virus (HBV) for propagation. Drugs effective against suppressing HBV do not work against HDV. The first ever clinical guidelines were published on hepatitis delta management by the European Association for the Study of the Liver (EASL) in 2023. The first approved drug (bulevirtide) for HDV was approved in 2020 in Europe, and 2023 in the UK. It is currently not licensed in the USA. Current treatments Treatment aims to prevent liver damage and improve life quality, ideally aiming for a finite treatment duration with complete viral suppression. Pegylated interferon-alpha (peg-IFNα) has been the standard treatment for decades (although this is used off-label) but is limited by side effects and partial efficacy. After a finite therapy duration, viral levels often rebound either shortly after or years after. Bulevirtide offers a new treatment avenue by blocking the virus's entry into hepatocytes, but it may require combination with other drugs for better effectiveness. There are no stopping criteria for this medication and many experience viral rebound if treatment is stopped. Novel HDV therapies & targets Ongoing research targets various aspects of the HDV life cycle and the immune response to develop more effective treatments. Pegylated interferon-lambda (peg-IFN-L) shows promise due to fewer side effects compared with traditional interferons. However, recent clinical trials were terminated due to liver-related complications, and therefore safety and use need to be carefully re-examined. Lonafarnib, a drug inhibiting a critical viral process, shows potential in combination therapies, though side effects and optimal dosing need further research. Nucleic acid polymers (NAPs) and emerging treatments like monoclonal antibodies and siRNA are in development, targeting the viral components and processes more directly and potentially offering new treatment modalities. Unresolved issues in hepatitis delta There is no international consensus on screening for CHD, leading to underdiagnosis and delayed treatment. Some countries are now implementing reflex testing in those with hepatitis b which will increase detection rates of delta. Diagnostic tools have until recently lacked standardization and fail to capture the full diversity of HDV, which hampers effective management. Better pangenotypic assays are essential. The optimal end points for treatment are debated, with ongoing discussions about how best to measure treatment success and the relevance of viral load and liver enzyme levels. Conclusion HDV remains a complex viral infection with a significant impact on global health and lack of effective, widely applicable treatments. Recent advances in therapy and diagnostics are promising, but a finite cure remains elusive. Future perspective Future research needs to focus on understanding the virus-host interactions and the dynamics of co-infections, to develop targeted and effective treatments. [ABSTRACT FROM AUTHOR]