RESUMO
Background: The expression of CD64 on neutrophils (nCD64), measured using flow cytometry, has been proposed as a biomarker for bloodstream infections (BSI). However, data regarding its use in the setting of liver cirrhosis are lacking. Methods: We compared nCD64 levels in 15 cirrhotic patients with BSI to those in 19 controls, including outpatients with stable decompensated cirrhosis without infection. Additionally, we compared nCD64 with C-reactive protein (CRP) and procalcitonin (PCT) in infected hospitalized cirrhotic patients. Results: Cirrhotic patients with infection had higher levels of nCD64 compared to controls (6.0 [5.4-7.1] vs. 2.0 [1.5-2.2]; p<0.001). Among infected patients, a correlation between nCD64 (AUC=0.934 [0.875-0.982 95% CI]), CRP (AUC=0.972 [0.942-0.993 95% CI]), and PCT (AUC=0.859 [0.739-0.953 95% CI]) was observed. However, in our sample of cirrhotic individuals, nCD64 values were not significantly different between patients with worse prognosis and those with positive outcomes (p=0.448), and its expression was not influenced by Gram stain. Conclusions: In our cohort, nCD64 appears to be a promising new biomarker for BSI. Additional prospective studies are needed to confirm its role and limitations in conjunction with other biomarkers and rapid microbiology in the diagnostic multidisciplinary pathway for septic cirrhotic patients.
RESUMO
To explore the relationship between innate immunity and hepatitis C Virus (HCV) in determining the risk of cirrhosis (CIR), hepatocellular carcinoma (HCC), mixed cryoglobulinemia syndrome (MCS) and non-Hodgkin lymphoma (NHL), we investigated the impact of the toll-like receptor-2 (TLR2) and interleukin-28B (IL28B) genetic variants. TLR2 -174 del variant was associated with TLR2 expression and with specific downstream molecules that drive the expression of different interleukins; rs12979860 Il28B was important in response to interferon-treatment and in spontaneous clearance of HCV. The risk for liver and lymphoproliferative diseases in HCV progression was clarified by stratifying 862 HCV-positive patients into groups based on liver (CIR, HCC) and lymphoproliferative HCV-related diseases (MCS, NHL) and compared with chronic HCV (CHC) infection. Analysis of TLR2-IL28B haplotypes showed an association of wild type haplotype with the lymphoproliferative diseases (OR 1.77, p = 0.029) and a slight increase in HCV viral load (HR 1.38, p = 0.054). Wild type haplotype (TLR2 ins/ins- IL28B C/C) was also found associated with older age in patients with an hepatic diseases (in CIR and in HCC p = 0.038 and p = 0.020, respectively) supporting an effect of innate immunity in the liver disease progression. TLR2 and IL28B polymorphisms in combination showed a role in the control of HCV viral load and different HCV disease progression.