Blood Of Chronic Hepatitis Research Articles

КЛИНИКО-ДИАГНОСТИЧЕСКОЕ ЗНАЧЕНИЕ ЛИПОПОЛИСАХАРИД — СВЯЗЫВАЮЩЕГО ПРОТЕИНА И РАСТВОРИМОГО КЛАСТЕРА ДИФФЕРЕНЦИРОВКИ 14 ПРИ ХРОНИЧЕСКИХ ГЕПАТИТАХ И ЦИРРОЗАХ ПЕЧЕНИ

The aim of the study was to investigate the pathogenetic and diagnostic significance of changes in the concentrations of lipopolysaccharide-binding protein (LBP) and the Soluble Cluster of Differentiation 14 (sCD14) in plasma of the blood in chronic hepatitis (CH) and liver cirrhosis (LC). Materials and methods: 54 patients with CH and 120 with LC was included in the study. Control group (CG) - 30 practically healthy donors. The concentration of LBP and sCD14 was studied in EDTA plasma by enzyme immunoassay using a commercial test - HyCult biotechnology systems (Netherlands). The study of the organs of the abdominal cavity and pulse dopplerography with color flow Doppler mapping of vessels were performed on an Ultrasound Monitor "Logic-500" (USA) with a 3.5-MHz convection sensor. Results: The mean values of LBP and sCD14 in CH and LC were significantly higher than in CG and did not differ significantly depending on the etiology of the disease. The concentration in the blood of LBP and sCD14 was influenced by the activity of CH and LC, the severity of portal hypertension and associated clinical manifestations, hepatic encephalopathy, the Child's Pugh class of severity. Reliable relationships between the studied parameters and a number of diagnostically significant ultrasound parameters of the portal blood flow (PBF) have been established. Conclusion: The study of the blood levels of LBP and sCD14 in CH and LC can be used to diagnose endotoxemia syndrome, the degree of activation of the anti-endotoxin immune response. Determination of the concentration of LBP in combination with the leading ultrasound parameters of the PBF contributes to the clarification of the degree of severity of the pathological process in the liver, allows predicting the transformation of CH to LC.

IFNL3/4 genotype is associated with altered immune cell populations in peripheral blood in chronic hepatitis C infection.

Single-nucleotide polymorphisms near the interferon lambda 3 (IFNL3) gene predict outcomes to infection and anti-viral treatment in hepatitis C virus (HCV) infection. To identify IFNL3 genotype effects on peripheral blood, we collected phenotype data on 400 patients with genotype 1 chronic hepatitis C (CHC). The IFNL3 responder genotype predicted significantly lower white blood cells (WBCs), as well as lower absolute numbers of monocytes, neutrophils and lymphocytes for both rs8099917 and rs12979860. We sought to define the WBC subsets driving this association using flow cytometry of 67 untreated CHC individuals. Genotype-associated differences were seen in the ratio of CD4CD45RO+ to CD4CD45RO− CD8CD45RO+ to CD8CD45RO−, NK CD56 dim to bright and monocyte numbers and percentages. Whole blood expression levels of IFNL3, IFNLR1 (interferon lambda receptor 1), IFNLR1-mem (a membrane-associated receptor), IFNLR1-sol (a truncated soluble receptor), MxA and T- and NK (natural killer) cell transcription factors TBX21, GATA3, RORC, FOXP3 and EOMES in two subjects were also determined. CHC patients demonstrated endogenous IFN activation with higher levels of MxA, IFNLR1, IFNLR1-mem and IFNLR1-sol, and IFNL3 genotype-associated differences in transcription factors. Taken together, these data provide evidence of an IFNL3 genotype association with differences in monocyte, T- and NK cell levels in the peripheral blood of patients with CHC. This could underpin genotype associations with spontaneous and treatment-induced HCV clearance and hepatic necroinflammation.

Frequency of FOXP3+ Regulatory T-cells in the Blood of Chronic Hepatitis C Patients with Immune Mediated Skin Manifestations; Relationship to Hepatic Condition and Viral Load.

Chronic hepatitis C (CHC) infection causes a wide range of immune mediated hepatic and extrahepatic manifestations. Cutaneous manifestations constitute a major portion of the latter group. Host immune response to the virus - particularly regulatory T lymphocytes - is important in determining the outcome of the infection and the possibility of extrahepatic manifestations. The present study aims to investigate the relationship between immune-mediated cutaneous manifestations of CHC infection and the frequency of CD4+CD25 high FOXP3+ T regulatory lymphocytes. We also investigated the relationships to viral load and hepatic conditions. A total of 58 CHC patients (30 had cutaneous manifestations and 28 did not) and 30 healthy HCV free subjects were enrolled in this study. The frequency of CD4+CD25 high FOXP3+ Treg cells was measured in the peripheral blood of all participants. Additionally, serum ALT, RNA viral load, and hepatic ultrasonographic studies were performed for all patients. Skin manifestations were dominated by small vessel vasculitis and to a lesser extent lichen planus. Treg cell frequency was significantly lower in CHC patients with skin manifestations compared to those without. Chronic hepatic insult was significantly more common among patients with skin manifestations, although serum ALT levels were significantly lower in this group. Treg frequencies did not correlate to either ALT level or viral load. HCV-associated skin lesions are associated with low frequency of Treg cells. They are not related to liver enzymes or viral load; however, they are associated with a more advanced gross liver insult.

Development of a novel IGRA assay to test T cell responsiveness to HBV antigens in whole blood of chronic Hepatitis B patients.

BackgroundInterferon gamma release assays (IGRA) have been developed to support easy and fast diagnosis of diseases like tuberculosis, and CMV in transplant patients. IGRAs focus on cellular immunity especially memory T cells and thus also allow rapid screening prior to complex flow cytometric testing. Here, we describe a novel, sensitive whole blood based cytokine release assay capable of assessing T cell responsiveness to HBV antigens in Hepatitis B patients and assessing hepatitis B vaccination status in healthy individuals.MethodsSeventy two chronic Hepatitis B patients (CHB), 8 acute hepatitis B patients (AHB) and 80 healthy controls (HC) were tested by ELISA for IFNγ- and IL2-secretion in whole blood after challenge with synthetic peptide libraries of hepatitis B core antigen (HBcAg) or hepatitis B surface antigen (HBsAg).ResultsThe developed IGRA test reliably differentiated between Hepatitis B patients, vaccinees and unvaccinated healthy controls. Treatment naïve and treated CHB patients showed a weaker IFNγ response to HBcAg (16 ± 5 and 35 ± 28 pg/ml, respectively) compared to the AHB group (82 ± 39 pg/ml), whereas HC remained unresponsive (6 ± 1 pg/ml). IL2 levels after HBcAg challenge were also higher in the AHB group compared to naive and treated CHB as well as HC (47 ± 21 vs. 12 ± 3, 15 ± 10 and 12 ± 9 pg/ml, respectively). HBsAg stimulation led to increased IFNγ and IL2 levels in the AHB group (33 ± 12 and 22 ± 12 pg/ml) and even higher levels in HC due to a high hepatitis B vaccination rate (41 ± 10 and 167 ± 58 pg/ml). Naive and treated CHB patients developed no or only weaker IFNγ or IL2 responses to HBsAg (5 ± 2 and 12 ± 7 pg/ml, for naive CHB, 12 ± 10 and 18 ± 15 pg/ml, for treated CHB). For HC, IL2 release after HBsAg stimulation depicted hepatitis B vaccination status with a diagnostic sensitivity and specificity of 85 % and 90 %.ConclusionOur novel whole blood based cytokine release assay constitutes an easy and robust tool for screening HBV specific cellular immunity as alternative to flow cytometry or ELISPOT assays.Electronic supplementary materialThe online version of this article (doi:10.1186/s12967-015-0513-1) contains supplementary material, which is available to authorized users.

P0470 : Development of a novel IGRA assay to test T cell responsiveness to HBV antigens in whole blood of chronic hepatitis B patients

P0470 : Development of a novel IGRA assay to test T cell responsiveness to HBV antigens in whole blood of chronic hepatitis B patients

Easy and robust testing of T cell responsiveness to HBV antigens in whole blood of chronic Hepatitis B patients

Easy and robust testing of T cell responsiveness to HBV antigens in whole blood of chronic Hepatitis B patients

Cytokine levels in peripheral blood of chronic hepatitis C (CHC) patients pre- and post-treatment with PEG-interferon ALFA-2B and ribavirin

Cytokine levels in peripheral blood of chronic hepatitis C (CHC) patients pre- and post-treatment with PEG-interferon ALFA-2B and ribavirin

Monokine production by peripheral whole blood in chronic hepatitis C patients treated with interferon.

Using our scoring system, we studied the production of monokines (interleukin-1 alpha, interleukin-1 beta, tumor necrosis factor-alpha, and interleukin-6) by lipopolysaccharide-stimulated peripheral whole blood in 34 patients with chronic hepatitis C during the interferon-alpha/beta therapy. It decreased in 25.7% (9/35 group A), fluctuated in 60.0% (21/35, group B), and increased in 14.3% (5/35, group C). The patients in group A were younger than those in group B (P < 0.05). The histological grade of injury was milder in group A than in group B or C. The rate of sustained response was 66.7% (6/9) in group A, 19.0% (4/21) in group B, and 40.0% (2/5) in group C(P = 0.0184, group A versus group B). In summary, monokine production by peripheral whole blood varied during interferon therapy for chronic hepatitis C patients. No significant change was noted in 60% of the patients. However, patients with decreased monokine production were younger, with a mild histological grade, and likely to respond to the interferon therapy.