Exploring the Link Between Platelet Numbers and Vascular Homeostasis Across Early and Late Stages of Fibrosis in Hepatitis C.

BACKGROUND: Thrombocytopenia is a hallmark of advanced liver disease. Platelets, growth factors (GFs), and vascular integrity are closely linked factors in disease pathogenesis, and their relationship, particularly in early disease stages, is not entirely understood. The aim was to compare circulating platelets, growth factors, and vascular injury markers (VIMs) in hepatitis C-infected (HCV) patients with early fibrosis and cirrhosis. METHODS: Retrospective evaluation of serum GFs and VIMs by ELISA were evaluated from twenty-six HCV patients. Analytes from an earlier time-point were correlated with MELD at a later time-point. RESULTS: Platelets and GFs decreased, and VIMs increased with fibrosis. Platelets correlated positively with PDGF-AA, PDGF-BB, TGFB1, EGF, and P-selectin, and negatively with ICAM-3 and VCAM-1. P-selectin showed no correlations with VIMs but positively correlated with PDGF-AA, PDGF-BB, TGFB1, and EGF. Soluble VCAM-1 and ICAM-3 were linked to increasing fibrosis, liver enzymes, and synthetic dysfunction. Higher VCAM-1 and ICAM-3 and lower P-selectin at an earlier time-point were linked to higher MELD score at a later time-point. CONCLUSION: In chronic HCV, progressive decline in platelets and growth factors with fibrosis and their associations suggest that platelets are an important source of circulating GFs and influence GF decline with fibrosis. Enhanced markers of vascular injury in patients with early fibrosis suggest an earlier onset of endothelial dysfunction preceding cirrhosis. Associations of VIMs with platelets suggest a critical link between platelets and vascular homeostasis. Circulating markers of vascular injury may not only have prognostic importance but emphasize the role of vascular dysfunction in liver disease pathogenesis (NCT00001971).

Bacterial Translocation and Host Immune Activation in Chronic Hepatitis C Infection.

Hepatitis C virus (HCV) infects 71 million individuals, and barriers to treatment remain. Bacterial translocation is a complication of chronic HCV infection, and this study evaluated circulating microbial components including lipopolysaccharide, peptidoglycan, and ß-D-glucan in addition to their pattern recognition receptors and degree of hepatic macrophage uptake. The findings suggest that regulation of serum peptidoglycan and ß-D-glucan differs from that of lipopolysaccharide. Additionally, macrophage activation in the liver may be better reflected by the degree of macrophage uptake than by circulating levels of microbial markers. These findings allow for a greater understanding of bacterial translocation and host immune activation during HCV infection.

Antimicrobial Residues in Chicken and Fish, Chittagong, Bangladesh.

A cross-sectional observation and an intervention study were conducted in Chittagong, Bangladesh in 2015 to assess the status of antimicrobial residues in chicken and fish. The samples were tested for selected antimicrobials (amoxicillin, ciprofloxacin, oxytetracycline and enrofloxacin) using thin-layer chromatography (TLC). The TLC-based overall prevalence of residues was 87.9% in chicken (N = 182) and 56.9% in fish (N = 153). The prevalences in chicken in June (N = 91) and in October (N = 91), respectively, were 91.2% and 83.5% (amoxicillin), 1.1% and 1.1% (enrofloxacin), 1.1% and 0% (ciprofloxacin), and 0% and 6.6% (oxytetracycline). In fish, the prevalence in September (N = 74) and in October (N = 79) was 52.7% and 44.3% (amoxicillin) and 1.4% and 27.8% (oxytetracycline), respectively. The mean concentration of amoxicillin residue was evaluated by ultra-high-performance liquid chromatography to be 508.4 mg/kg (chicken) and 515.4 mg/kg (fish). The random effect model identified market (Chawkbazar vs. Boalkhali: OR 5.7; Steelmill bazar vs. Boalkhali: OR 5.6) as significant factors for amoxicillin residue in chicken. Amoxicillin concentration was significantly reduced in chicken of Kazirhat (ß= - 1.3) and Chawkbazar (ß= - 1.1) and increased in October (ß= 0.77) based on a generalized linear model (GLM). Climbing perch fish had significantly more risk of having amoxicillin residue than that of Bombay duck (OR = 0.05). All samples were treated by washing, boiling and cooking with spices, and then, TLC-based screening of amoxicillin residues was done. A subset of each treated group was evaluated by UHPLC. Treatment reduced amoxicillin residue levels significantly.

Factors associated with the platelet count in patients with chronic hepatitis C.

BACKGROUND: There are many potential causes of thrombocytopenia in patients with chronic hepatitis C (CHC). AIMS: We sought to determine the association between thrombopoietin (TPO) level, immature platelet fraction (IPF), immunoglobulin G (IgG) level, spleen size, and the platelet count in CHC. METHODS: We studied a consecutive sample of patients enrolled in an observational study at a referral-based research center, excluding subjects based on eligibility criteria. TPO, glycocalicin, and von Willebrand Factor (vWF) levels were determined using stored sera. Hepatic fibrosis was assessed via transient elastography (TE) when available, and clinical laboratory values and radiologic data were obtained from the medical record. We performed analyses of the relationships between independent variables and the platelet count. RESULTS: On univariate analysis, the following variables were significantly associated with the platelet count: age, alanine aminotransferase (ALT), direct bilirubin, total bilirubin, IPF, international normalized ratio (INR), spleen size, vWF, glycocalicin, fibrosis stage on liver biopsy, and TE (P-values all <0.05). A multivariable model determined that imputed TE score, TPO, IPF, and spleen size were independently associated with the platelet count (P-values all<0.05). CONCLUSIONS: The platelet count in CHC is significantly associated with fibrosis, TPO level, IPF, and spleen size. Our findings challenge the proposed mechanism of decreased TPO levels or decreased bone marrow production of platelets as a cause of thrombocytopenia in CHC. Future studies focusing on the effects of fibrosis and splenomegaly on platelets may shed more light on the pathophysiology of thrombocytopenia in patients with CHC.