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Cureus Jun 2024Wilson's disease (WD) is an autosomal recessive disorder that impairs copper metabolism. Copper accumulates in vital organs such as the brain, liver, and kidneys. The...
Wilson's disease (WD) is an autosomal recessive disorder that impairs copper metabolism. Copper accumulates in vital organs such as the brain, liver, and kidneys. The disease typically starts with copper accumulation in the liver and can initially present as acute hepatitis and hepatomegaly. Hemolytic anemia is a typically uncommon complication of WD. We present the case of a healthy 18-year-old female who presented with hemolytic anemia and quickly decompensated to fulminant hepatic failure requiring a liver transplant due to previously undiagnosed WD. This case recognizes the importance of early diagnosis as treatment can be lifesaving.
PubMed: 38912076
DOI: 10.7759/cureus.62966 -
Cureus May 2024Legionnaires' disease is an atypical pneumonia caused by species are found in freshwater sources and are transmitted through inhalation of contaminated aerosols....
Legionnaires' disease is an atypical pneumonia caused by species are found in freshwater sources and are transmitted through inhalation of contaminated aerosols. Patients commonly present with fever, chills, and cough. However, in immunosuppressed patients or severe cases, the disease can lead to multiorgan failure. In recent years, the incidence of Legionnaires' disease has drastically increased and unfortunately is commonly underdiagnosed. Gold-standard diagnosis is made through sputum cultures; however, urine antigen remains the most common test used for diagnosis. Goal-directed care includes antibiotics and supportive care. This case highlights a rare and unique presentation of Legionnaires' disease presenting with an elevated 2:1 aspartate aminotransferase to alanine transaminase pattern, typically seen with alcoholic hepatitis.
PubMed: 38910759
DOI: 10.7759/cureus.60856 -
Journal of Nanobiotechnology Jun 2024Patients who suffer from sepsis typically experience acute lung injury (ALI). Extracellular vesicles (EVs) contain miRNAs, which are potentially involved in ALI....
Patients who suffer from sepsis typically experience acute lung injury (ALI). Extracellular vesicles (EVs) contain miRNAs, which are potentially involved in ALI. However, strategies to screen more effective EV-miRNAs as therapeutic targets are yet to be elucidated. In this study, functional EV-miRNAs were identified based on multiomics analysis of single-cell RNA sequencing of targeted organs and serum EV (sEV) miRNA profiles in patients with sepsis. The proportions of neutrophils and macrophages were increased significantly in the lungs of mice receiving sEVs from patients with sepsis compared with healthy controls. Macrophages released more EVs than neutrophils. MiR-125a-5p delivery by sEVs to lung macrophages inhibited Tnfaip3, while miR-221-3p delivery to lung neutrophils inhibited Fos. Macrophage membrane nanoparticles (MM NPs) loaded with an miR-125a-5p inhibitor or miR-221-3p mimic attenuated the response to lipopolysaccharide (LPS)-induced ALI. Transcriptome profiling revealed that EVs derived from LPS-stimulated bone marrow-derived macrophages (BMDMs) induced oxidative stress in neutrophils. Blocking toll-like receptor, CXCR2, or TNFα signaling in neutrophils attenuated the oxidative stress induced by LPS-stimulated BMDM-EVs. This study presents a novel method to screen functional EV-miRNAs and highlights the pivotal role of macrophage-derived EVs in ALI. MM NPs, as delivery systems of key sEV-miRNA mimics or inhibitors, alleviated cellular responses observed in sepsis-induced ALI. This strategy can be used to reduce septic organ damage, particularly lung damage, by targeting EVs.
Topics: Animals; Acute Lung Injury; Sepsis; Extracellular Vesicles; MicroRNAs; Mice; Nanoparticles; Macrophages; Mice, Inbred C57BL; Humans; Male; Lipopolysaccharides; Neutrophils; Oxidative Stress; Lung; Biomimetic Materials; Multiomics
PubMed: 38910259
DOI: 10.1186/s12951-024-02597-z -
Journal of Hepatology Jun 2024Chronic liver disease (CLD) leads to hepatocellular injury that triggers a pro-inflammatory state in several parenchymal and non-parenchymal hepatic cell types... (Review)
Review
Chronic liver disease (CLD) leads to hepatocellular injury that triggers a pro-inflammatory state in several parenchymal and non-parenchymal hepatic cell types ultimately resulting in liver fibrosis, cirrhosis, portal hypertension (PH) and liver failure. Thus, an improved understanding of the inflammasomes - as key molecular drivers of liver injury - supports the development of novel diagnostic or prognostic biomarkers and effective therapeutics. In liver disease, innate immune cells respond to hepatic noxes by activating cell-intrinsic inflammasomes via toll-like receptors (TLRs) and nuclear factor kappa-B (NF-κB) and release of pro-inflammatory cytokines (such as IL-1β, IL-18, TNF-α and IL-6). Subsequently, cells of the adaptive immune system are recruited to fuel hepatic inflammation, and liver parenchymal cells may undergo programmed cell-death mediated by gasdermin D, termed pyroptosis. With liver disease progression, there is a shift towards a type 2 inflammatory response, which promotes tissue repair but also fibrogenesis. Inflammasome activation may also occur at extrahepatic sites, such as the white adipose tissue in metabolic dysfunction-associated steatohepatitis (MASH). In end-stage liver disease, flares of inflammation (e.g., in severe alcohol-related hepatitis) that spark on a dysfunctional immune system, contribute to inflammasome-mediated liver injury and potentially result in organ dysfunctions/failures, as seen in acute-on-chronic liver failure (ACLF). This review provides an overview on current concepts regarding inflammasome activation in liver disease progression and related biomarkers and therapeutic approaches that are being developed for patients with liver disease.
PubMed: 38908436
DOI: 10.1016/j.jhep.2024.06.016 -
Biomedicine & Pharmacotherapy =... Jun 2024Hepatocyte transplantation is an effective treatment for end-stage liver disease. However, due to the limited supply of human hepatocytes, porcine hepatocytes have...
Hepatocyte transplantation is an effective treatment for end-stage liver disease. However, due to the limited supply of human hepatocytes, porcine hepatocytes have garnered attention as a potential alternative source. Nonetheless, traditional primary porcine hepatocytes exhibit certain limitations in function maintenance and in vitro proliferation. This study has discovered that by using histone deacetylase inhibitors (HDACi), primary porcine hepatocytes can be successfully reprogrammed into liver progenitor cells with high proliferative potential. This method enables porcine hepatocytes to proliferate over an extended period in vitro and exhibit increased susceptibility in lentivirus-mediated gene modification. These liver progenitor cells can readily differentiate into mature hepatocytes and, upon microencapsulation transplantation into mice with acute liver failure, significantly improve the survival rate. This research provides new possibilities for the application of porcine hepatocytes in the treatment of end-stage liver disease.
PubMed: 38908204
DOI: 10.1016/j.biopha.2024.116973 -
Medicina 2024Autoimmune hepatitis (AIH) is a rare, chronic, inflammatory, and necrotic liver disease characterized by the presence of autoantibodies. Its etiology is unknown. It... (Review)
Review
Autoimmune hepatitis (AIH) is a rare, chronic, inflammatory, and necrotic liver disease characterized by the presence of autoantibodies. Its etiology is unknown. It affects 1 in 200 000 people annually in the US and occurs predominantly in women. Its presentation varies from asymptomatic forms to cirrhosis and acute liver failure and its diagnosis is based on the measurement of autoantibodies, such as antinuclear autoantibodies (ANA), anti-smooth muscle antibodies (ASMA) and anti-liver and kidney microsomal antibodies (anti-LKM). 1). 10% of HAIs do not present antibodies, being called seronegative HAI, requiring a liver biopsy for diagnosis. To date the evidence remains limited and different societies have issued suggestions and recommendations. For this reason, we believe it is relevant to carry out a bibliographic review on the subject, capturing in this document the important information for the understanding and management of this pathology.
Topics: Humans; Hepatitis, Autoimmune; Autoantibodies; Female; Biopsy; Male
PubMed: 38907968
DOI: No ID Found -
Infection, Genetics and Evolution :... Jun 2024Human adenovirus type 41 (HAdV-F41) usually causes pediatrics gastroenteritis. However, it was reported to be associated with the outbreaks of severe acute hepatitis of...
Human adenovirus type 41 (HAdV-F41) usually causes pediatrics gastroenteritis. However, it was reported to be associated with the outbreaks of severe acute hepatitis of unknown aetiology (SAHUA) in pediatrics during COVID-19 pandemic. In this study, we investigated the prevalence of enteric HAdV-F41 in 37,920 paediatric gastroenteritis cases from 2017 to 2022 in Guangzhou, China. All children presented were tested negative for SARS-CoV-2 during the "zero-COVID" period. The main clinical symptom of the children was diarrhea (96.5%). No fatalities nor liver abnormal symptoms was found. In 2021, one year since the pandemic of COVID-19, the prevalence of HAdV-F41 abruptly increased from 3.71% to 8.64% (P < 0.001). All of HAdV-F41 circulating worldwide were classified into eight different subtypes (G1-G8) based on the phylogenetic clustering permutation of the four capsid genes of HAdV-F41. G3 was the predominant subtype (56.2%; 77/137). CRV5 isolates from SAHUA cases belong to this subtype, in which N312D and H335D mutations in the short fiber knob were identified in both Guangzhou and CRV5 isolates, presumably changing the virus tropism by directly interacting with the heparin sulfate (HS) receptor. Additionally, a novel recombinant G6 subtype, which is unique and only circulating in China was first identified in this study. This is the first study highlighting the prevalence of HAdV-F41 in paediatric cases of gastroenteritis during COVID-19 pandemic in China. The clinical and viral evolution finding of HAdV-F41 provide insight into the clinical characteristics of children with HAdV-F41 infections as well as the uncertain role of HAdV-F41 in the cause of SAHUA.
PubMed: 38906518
DOI: 10.1016/j.meegid.2024.105619 -
BMC Public Health Jun 2024The economic crisis that began in 2008 has severely affected Southern (Greece, Italy, Portugal, Spain) Western European (SWE) countries of Western Europe (WE) and may...
BACKGROUND
The economic crisis that began in 2008 has severely affected Southern (Greece, Italy, Portugal, Spain) Western European (SWE) countries of Western Europe (WE) and may have affected ongoing efforts to eliminate viral hepatitis. This study was conducted to investigate the impact of the economic crisis on the burden of HBV and HCV disease.
METHODS
Global Burden of Diseases 2019 data were used to analyse the rates of epidemiological metrics of HBV and HCV acute and chronic infections in SWE and WE. Time series modelling was performed to quantify the impact of healthcare expenditure on the time trend of HBV and HCV disease burden in 2000-2019.
RESULTS
Declining trends in incidence and prevalence rates of acute HBV (aHBV) and chronic HBV were observed in SWE and WE, with the pace of decline being slower in the post-austerity period (2010-2019) and mortality due to HBV stabilised in SWE. Acute HCV (aHCV) metrics and chronic HCV incidence and mortality showed a stable trend in SWE and WE, whereas the prevalence of chronic HCV showed an oscillating trend, decreasing in WE in 2010-2019 (p < 0.001). Liver cancer due to both hepatitis infections showed a stagnant burden over time. An inverse association was observed between health expenditure and metrics of both acute and chronic HBV and HCV.
CONCLUSIONS
Epidemiological metrics for HBV and HCV showed a slower pace of decline in the post-austerity period with better improvement for HBV, a stabilisation of mortality and a stagnant burden for liver cancer due to both hepatitis infections. The economic crisis of 2008 had a negative impact on the burden of hepatitis B and C. Elimination of HBV and HCV by 2030 will be a major challenge in the SWE countries.
Topics: Humans; Europe; Economic Recession; Hepatitis B; Cost of Illness; Incidence; Hepatitis C; Prevalence; Health Expenditures; Female; Male; Hepatitis C, Chronic; Global Burden of Disease; Hepatitis B, Chronic
PubMed: 38902642
DOI: 10.1186/s12889-024-18912-0 -
Pathology, Research and Practice Jun 2024The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), presents diverse clinical manifestations and...
INTRODUCTION
The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), presents diverse clinical manifestations and multi-organ involvement. This study aimed to evaluate the extra-pulmonary histopathological patterns underpinning COVID-19-induced lesions in cardiac, hepatic, renal, brainstem, and splenic tissues.
MATERIALS AND METHODS
The research involved conventional forensic autopsies conducted between April 2020 and April 2021 on individuals with confirmed SARS-CoV-2 infection in Cluj-Napoca, Romania. Tissues were processed and stained for histological examination. Differences in patients with and without diffuse alveolar damage (DAD) were evaluated.
RESULTS
In our study of 79 COVID-19 autopsies conducted on unvaccinated patients besides lung involvement, the patients had histological changes in at least two out of five (brain, heart, liver, kidney, and spleen) organs. Notable findings include hepatitis observed in 46.8 % of cases, 21.5 % with lobular hepatitis, and 41.8 % with liver steatosis. Additionally, 69.6 % exhibited acute tubular necrosis, and 55.7 % had varying degrees of splenic lymphocyte depletion. Almost 41 % of cases had pericardial effusion, 36.7 % myocarditis, 24.1 % myocardial infarction, and 12.7 % of cases had encephalitis. Acute tubular necrosis (78.6 %) was the most frequent histopathological finding observed in patients with DAD. Myocarditis was described in 45.9 % of the patients without DAD.
DISCUSSION
The autopsy findings in our cohort of COVID-19 victims align with international scientific literature. Distinguishing viral-induced myocarditis, encephalitis, hepatitis, or systemic inflammatory syndrome remains challenging.
CONCLUSION
Post-mortem analysis identified lesions associated with SARS-CoV-2 in multiple organs, highlighting the systemic nature of the virus and emphasizing the need for continued research into organ-specific damage and long-term sequelae of COVID-19.
PubMed: 38901140
DOI: 10.1016/j.prp.2024.155373 -
World Journal of Clinical Cases Jun 2024High-dose vitamin C treatment (HVCT) can reduce the adverse effect of chemotherapy and enhance the effect of antitumor therapy, which has been considered one of the...
BACKGROUND
High-dose vitamin C treatment (HVCT) can reduce the adverse effect of chemotherapy and enhance the effect of antitumor therapy, which has been considered one of the safest alternative treatments. However, the severity of its adverse effects may have been underestimated. The most serious adverse effect is hemolysis, which may result in acute kidney injury or death. Although glucose-6-phosphate dehydrogenase (G6PD) deficiency is considered to be the main cause, the probability and pathological mechanism are not completely understood, leading to a lack of effective and standardized treatment methods.
CASE SUMMARY
Two patients with colorectal cancer developed hemolytic anemia after using 1 g/kg HVCT. In contrast to previous cases, the lowest hemoglobin level in the two cases was < 50 g/L, which was lower than previously reported. This may be because Case 1 had chronic hepatitis B for many years, which caused abnormal liver reserve function, and Case 2 had grade II bone marrow suppression. Both patients improved and were discharged after blood replacement therapy. Our cases had the most severe degree of hemolysis but the best prognosis, suggesting that our treatment may be helpful for rescue of drug-induced hemolysis. This is the first review of the literature on hemolysis caused by HVCT, and we found that all patients with G6PD deficiency developed hemolysis after HVCT.
CONCLUSION
G6PD deficiency should be considered as a contraindication to HVCT, and it is not recommended for patients with bone marrow suppression, moderate-to-severe anemia, hematopoietic abnormalities, or abnormal liver and kidney function. Early blood purification and steroid therapy may avoid acute kidney injury or death caused by HVCT-related hemolytic anemia.
PubMed: 38898838
DOI: 10.12998/wjcc.v12.i17.3168