Non-alcoholic fatty liver disease (NAFLD) is the most prevalent chronic liver disease, affecting one third of the Western population. The hallmark of the disease is excessive storage of fat in the ...liver. Most commonly, it is caused by metabolic syndrome (or one of its components). Even though the development of NAFLD has multiple effects on the human organism resulting in systemic chronic low-grade inflammation, this review is focused on NAFLD as a risk factor for the onset, progression, and outcomes of infectious diseases. The correlation between NAFLD and infections is still unclear. Multiple factors (obesity, chronic inflammation, altered immune system function, insulin resistance, altered intestinal microbiota, etc.) have been proposed to play a role in the development and progression of infections in people with NAFLD, although the exact mechanism and the interplay of mentioned factors is still mostly hypothesized. In this article we review only the selection of well-researched topics on NAFLD and infectious diseases (bacterial pneumonia, COVID,
, urinary tract infections,
, bacteremia, hepatitis B, hepatitis C, HIV, and periodontitis).
Alveolar echinococcosis is a parasitic disease caused by the tapeworm larval stage of Echinococcus multilocularis. This zoonotic disease has not been known to occur in Croatia. We report a confirmed ...case of human alveolar echinococcosis in a patient in Croatia who had never visited a known E. multilocularis-endemic area.
Clostridioides difficile
infection (CDI) is the leading cause of healthcare-associated diarrhea while nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease. The ...aim of this study was to determine whether NAFLD increases susceptibility to CDI. A retrospective cohort study included patients ≥ 65 years, treated with antimicrobial therapy ≥ 24 h, and hospitalized ≥ 72 h in a 36-month period. Three-hundred fourteen patients were included; 83 with NAFLD and 231 controls. Except for diabetes mellitus (37.35% vs. 25.11%,
p
= 0.0462) and obesity (18.07% vs. 8.23%,
p
= 0.0218) that were more frequent in NAFLD group, there were no differences in other comorbidities, hospital admissions, antibiotic therapy within 3 months, prescription, and duration of antibiotic therapy. Fourteen (16.9%) patients with NAFLD and 17 (7.4%) in control group developed in-hospital CDI (
p
= 0.0156). The Charlson Age-Comorbidity Index > 6 (OR 4.34, 95%CI 1.39–13.57), hospital admission within 3 months (OR 7.14, 95%CI 2.33–21.83), serum albumins < 28 g/L (OR 3.15, 95%CI 1.04–9.53), NAFLD (OR 3.27, 95%CI 1.04–10.35), eGFR < 40 (OR 4.89, 95%CI 1.61–14.88), treatment with piperacillin/tazobactam (OR 4.86, 95%CI 1.59–14.83), and carbapenems (OR 3.99, 95%CI 1.28–12.40) were independently associated with CDI. Our study identified NAFLD as an independent predictor of CDI.
Non-alcoholic fatty liver disease (NAFLD), the leading cause of chronic liver disease in Western countries, has been identified as a possible risk factor for COVID-19 severity. However, the ...immunological mechanisms by which NAFLD exacerbates COVID-19 remain unknown. Transforming growth factor-beta 1 (TGF-β1) has an important immunomodulatory and pro-fibrotic role, which has already been described in NAFLD. However, the role of TGF-β1 in COVID-19 remains unclear, and could also be the pathophysiology link between these two conditions. The aim of this case-control study was to analyze the expression of TGF-β1 in COVID-19 patients depending on the presence of NAFLD and COVID-19 severity. Serum TGF-β1 concentrations were measured in 60 hospitalized COVID-19 patients (30 with NAFLD). NAFLD was associated with higher serum TGF-β1 concentrations that increased with disease severity. Admission TGF-β1 concentrations showed good discriminative accuracy in predicting the development of critical disease and COVID-19 complications (need for advanced respiratory support, ICU admission, time to recovery, development of nosocomial infections and mortality). In conclusion, TGF-β1 could be an efficient biomarker for predicting COVID-19 severity and adverse outcomes in patients with NAFLD.
Semaphorins are a diverse family of immunoregulators recently recognized to play a major role in various phases of immune responses. Their role in chronic viral hepatitis C (CHC) and contribution to ...the progression of liver disease is unknown. The aim of this study was to analyse the association of secreted semaphorins with the severity of liver disease in patients with CHC. Serum concentrations of semaphorins were measured in 114 treatment-naive CHC patients and 36 healthy controls. Serum concentrations of SEMA3A, SEMA3C, SEMA5A, SEMA6B and SEMA6D were significantly increased in patients with CHC compared to controls. While serum concentrations of SEMA3C and SEMA6D significantly increased with fibrosis stage in both HCV-g1 and HCV-g3 infections, the concentration of SEMA5A inversely correlated with fibrosis stage in both HCV genotypes. ROC analysis showed that serum concentrations of SEMA3C (>4.0ng/mL, AUC 0.88) and SEMA6D (>4.5, AUC 0.82) had higher AUC than widely used APRI (AUC 0.71) and FIB-4 (AUC 0.74) scores. Serum concentrations of SEMA3C and SEMA6D significantly decreased after DAA and PEG IFN-α/ribavirin therapy, while the serum concentration of SEMA5A significantly increased after DAAs therapy. Immunohistochemistry confirmed the expression of SEMA3C and SEMA5A in hepatocytes, endothelial cells and lymphocytes of cirrhotic livers from CHC patients but not in controls. In conclusion, we provide the first evidence that SEMA3C, SEMA5A and SEMA6D can be considered as markers of liver injury in CHC.
In this study, we evaluated the effect of hepatitis C virus eradication using direct-acting antivirals (DAA) on the serum cytokine and growth factor profiles of chronic hepatitis C patients (CHC). ...Serum concentrations of 12 cytokines and 13 growth factors were measured in 56 patients with CHC before, during the DAA treatment and after sustained virological response using bead-based flow cytometry. Cytokine and growth factor levels were also measured in 15 healthy individuals. The majority of the selected cytokines and growth factors exhibited similar concentrations before, during and after successful DAA treatment, the exceptions being IL-10, EGF, HGF and VEGF. Significantly lower concentrations of IL-10, IL-13, IL-4, IL-4, IL-9, TNF- α and higher levels of Ang-2, HGF and SCF were observed in patients with CHC before and after DAA treatment compared with healthy individuals. Patients with severe fibrosis stages exhibited higher levels of Ang-2 and lower levels of EGF, PDGF-AA and VEGF. Furthermore, IL-4, IL-5 and SCF were characterized as potential biomarkers of DAA treatment using random forest. Additionally, logistic regression characterized EGF as a potential biomarker of severe CHC. Our results suggest inhibition of pro-inflammatory processes and promotion of liver regeneration in CHC patients during DAA treatment.
Background/Objectives: Various biological response modifiers play important roles in the immunopathogenesis of chronic hepatitis C (CHC). While serum levels of cytokines and growth factors change ...with the disease severity and treatment responses, the impact of concomitant liver steatosis on systemic inflammatory response is largely unknown. The aim of this study was to analyze the characteristics and kinetics of serum profiles of interleukins and growth factors in CHC patients with steatotic liver disease (SLD). Methods: Serum concentrations of 12 cytokines (IL-5, IL-13, IL-2, IL-6, IL-9, IL-10, IFN-γ, TNF-α, IL-17A, IL-17F, IL-4 and IL-22) and 6 growth factors (Angiopoietin-2, EGF, EPO, HGF, SCF, VEGF) were analyzed in 56 CHC patients at four time points (baseline, week 4, week 8 and SVR12) with bead-based flow cytometry assay. Results: At baseline, patients with SLD had significantly lower IL-9, IL-10, IL-13 and IL-22 and higher serum concentrations of EGF, VEGF and ANG. In a subgroup of patients with advanced liver fibrosis, SLD was linked with lower serum concentrations of IL-4, IL-5, IL-9, IL-10, IL-13 and IL-22 and higher concentrations of HGH and VEGF. Distinct cytokine kinetics during DAA treatment was observed, and SLD was identified as the main source of variation for IL-5, IL-9, IL-10, IL-13, IL-17A, IL-22, EGF, VEGF and ANG. Patients with SLD at SVR12 had significantly higher VEGF and HGF serum concentrations. Conclusions: SLD is associated with distinct cytokine and growth factor profiles and kinetics during CHC treatment, which might be associated with disease severity and the capacity for liver regeneration and contribute to fibrosis persistence.
: While it has been shown that steatotic liver disease (SLD) is associated with systemic changes in immune response, the impact of SLD on sepsis outcomes has not yet been established. The aim of this ...study was to investigate the association between SLD and sepsis severity and outcomes.
: A prospective observational study included consecutively hospitalized adult patients with community-acquired sepsis during a 16-month period.
: Of the 378 included patients (49.5% male, median age of 69, IQR 57-78 years), 174 (46%) were diagnosed with SLD. Patients with SLD were older and more frequently fulfilled the criteria for metabolic syndrome. There were no differences in the source and etiology of sepsis between the groups. Patients with SLD exhibited a higher incidence of acute kidney injury (29.3% vs. 17.6%), the need for renal replacement therapy (16.1% vs. 8.8%), and more frequent use of invasive mechanical ventilation (29.3% vs. 18.1%). In-hospital mortality was significantly higher in the SLD group (18.39% vs. 9.8%). The multivariable analysis indicated that SLD was associated with mortality (HR 2.82, 95% CI 1.40-5.71) irrespective of the other elements within metabolic syndrome.
: SLD might be associated with higher sepsis in-hospital mortality, and more frequent development of acute kidney and respiratory insufficiency requiring more critical care support.
: The aim of this study was to analyze the expression of genes on transcriptomic levels involved in inflammatory immune responses and the development of fibrosis in patients with chronic hepatitis C.
...: Expression patterns of 84 selected genes were analyzed with real-time quantitative RT PCR arrays in the peripheral blood of treatment-naive patients with chronic hepatitis C and healthy controls. The panel included pro- and anti-fibrotic genes, genes coding for extracellular matrix (EMC) structural constituents and remodeling enzymes, cell adhesion molecules, inflammatory cytokines, chemokines and growth factors, signal transduction members of the transforming growth factor- beta (TGF-ß) superfamily, transcription factors, and genes involved in epithelial to mesenchymal transition.
: The expression of SMAD-6 coding for a signal transduction TGF-beta superfamily member as well as MMP-8 coding for an ECM protein were significantly increased in CHC patients compared with controls.
: Chronic hepatitis C was also characterized by a significant downregulation of a set of genes including CAV-1, CTGF, TIMP-3, MMP-1, ITGA-1, LOX, ITGA-2, PLG and CEBPB encoding various biological response modifiers and transcription factors. Our results suggest that chronic hepatitis C is associated with distinct patterns of gene expression modulation in pathways associated with the regulation of immune responses and development of fibrosis.
Semaphorins have recently been recognized as crucial modulators of immune responses. In the pathogenesis of COVID-19, the activation of immune responses is the key factor in the development of severe ...disease. This study aimed to determine the association of serum semaphorin concentrations with COVID-19 severity and outcomes. Serum semaphorin concentrations (SEMA3A, -3C, -3F, -4D, -7A) were measured in 80 hospitalized adult patients with COVID-19 (moderate (n = 24), severe (n = 32), critical, (n = 24)) and 40 healthy controls. While SEMA3C, SEMA3F and SEMA7A serum concentrations were significantly higher in patients with COVID-19, SEMA3A was significantly lower. Furthermore, SEMA3A and SEMA3C decreased with COVID-19 severity, while SEMA3F and SEMA7A increased. SEMA4D showed no correlation with disease severity. Serum semaphorin levels show better predictive values than CRP, IL-6 and LDH for differentiating critical from moderate/severe COVID-19. SEMA3F and SEMA7A serum concentrations were associated with the time to recovery, requirement of invasive mechanical ventilation, development of pulmonary thrombosis and nosocomial infections, as well as with in-hospital mortality. In conclusion, we provide the first evidence that SEMA3A, SEMA3C, SEMA3F and SEMA7A can be considered as new biomarkers of COVID-19 severity.
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