Inflammatory Biomarkers and Liver Histopathology in Non-Uremic and Uremic Chronic Hepatitis C Patients (original) (raw)
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The Turkish journal of gastroenterology : the official journal of Turkish Society of Gastroenterology, 2018
The hepatitis C virus (HCV) infection is important cause of chronic hepatitis. Liver biopsy is considered the gold standard for assessment of fibrosis but this procedure is an invasive procedure. We aimed to evaluate the diagnostic efficiency of non-invasive serum biomarkers, separately and in combinations, on liver fibrosis in treatment-naive chronic hepatitis C (CHC) patients. Two hundred and sixteen treatment-naive CHC patients were enrolled from 32 locations across Turkey in this open-labelled, non-interventional prospective observational study. FibroTest®, aspartate aminotransferase-to-platelet ratio index(APRI), aspartate aminotransferase and alanine aminotransferase ratio (AAR), fibrosis index based on four factors (FIB-4), Age-platelet(AP) index and Forns index were measured and compared with Metavir scores got from liver biopsies. Data from 182 patients with baseline liver biopsy were suitable for analysis. One hundred and twenty patients (65.9%) had F0-F1 fibrosis and 62 p...
Inflammation Research, 2012
Objective This work investigated the profile of inflammation biomarkers in patients with chronic hepatitis C and its association with liver fibrosis, hepatic necroinflammatory activity, viral genotypes and cryoglobulinemia. Subjects and methods Seventy-eight untreated patients were studied. Biomarker levels were determined by immunoassays, cryoglobulinemia by cryoprecipitation and liver histopathology investigated using METAVIR scores. Results Decreased levels of a 1-acid glycoprotein (AGP), C3 and haptoglobin (Hp) were observed in the patients (P \ 0.0001). Increased a 1-antitrypsin (P \ 0.01) and ferritin (P \ 0.0001) levels were found in this group, but C-reactive protein (CRP) and C4 levels were unaltered. Alanine aminotransferase inversely correlated with Hp (P \ 0.01) and AGP (P = 0.01), whereas it was directly correlated with ferritin (P \ 0.05) and AGP (P \ 0.0001). The levels of CRP, C3 and C4 were lower in the patients with hepatic necroinflammatory activity (P \ 0.05). Patients with advanced fibrosis had low levels of Hp and AGP (P \ 0.05 and P \ 0.01, respectively). Neither infection with different viral genotypes nor cryoglobulinemia caused an alteration in biomarker levels. Conclusion Chronic hepatitis C virus infection alters the levels of some biomarkers, which are mainly observed in patients with liver fibrosis and hepatic necroinflammatory activity.
Annals of gastroenterology : quarterly publication of the Hellenic Society of Gastroenterology
The aim of this study was to compare noninvasive biomarkers, FibroTest and ActiTest in predicting fibrosis stage and inflammation grade in chronic hepatitis C (CHC) patients with liver biopsy (LB). In 107 patients with CHC, levels of six serum biomarkers (alanine aminotransferase, γ-glutamyl transpeptidase, total bilirubin, haptoglobin, apolipoprotein, α-2 macroglobulin) were determined at the time of LB. LB was evaluated by Metavir score for fibrosis and inflammation. Voluntary blood donors (n=106) were taken as controls for the study. Fibrosis estimated by Fibrotest was significantly higher in patients compared to control group. The observed area under the receiver operating characteristic curve (AUROC) for advanced fibrosis (F3, F4) adjusted according to the observed difference between advanced and non-advanced fibrosis prevalence (DANA) was 0.80 (0.69-0.88) and the AUROC for cirrhosis (F4) was 0.94 (0.86-0.98). ActiTest AUROC for moderate to severe activity (A2A3) was 0.72 (0.61...
ABSTRACT Background: Studies on the characteristics CD4+ and CD8+ in hepatitis C and their correlation with the severity of the disease have been rarely conducted. This study was aimed to obtain the mean difference between CD4+ and CD8+ count in liver to evaluate their correlation with fibrosis and necroinflammatory grades in chronic hepatitis C. Method: A cross-sectional study was conducted between March and July 2010 with 30 liver biopsies obtained from patients with non-B and non-HIV chronic hepatitis C who visited the Outpatient Clinic of Hepatology Unit at Cipto Mangunkusumo Hospital in January 2008–February 2010. Fibrosis and necroinflammatory grades were determined using METAVIR methods on liver biopsies. The mean values of CD4+ and CD8+ in portal tracts and hepatic lobules in liver biopsy specimens were evaluated. Statistical analysis was performed by using independent T-test and Spearman test. Results: There was a difference in mean CD4+ counts between portal tracts and the...
Journal of Viral Hepatitis, 2002
Our aims were to measure the kinetics of serum tumour necrosis alpha (TNF-alpha) and transforming growth factor beta (TGF-beta) levels as markers of progression of disease in nontreated chronic hepatitis C virus (HCV)-infected patients with minimal or no fibrosis and minimal histology activity index (HAI) scores. Our study group consisted of 56 patients diagnosed with minimal (1) or no fibrosis (0) and minimal HAI (0-1) on their first biopsy as defined by Knodell and METAVIR scores. We compared their initial (entry of study) cytokine levels with a group of 103 HCV controls with minimal (0-1) to mild fibrosis (0-3) and mild HAI (5.5). Serum TNF-alpha and TGF-beta levels were measured by enzyme-linked-immunosorbent-assay. A significant difference was seen in TNF-alpha levels at baseline in the study group vs. controls. Regardless of their HAI, there was a correlation between TGF-beta and degree of fibrosis. As shown by their biopsies, during the 3 years (from entry to follow up), many of the patients that initially had minimal fibrosis progressed to higher degree of fibrosis. This progression is paralleled by an increase in TGF-beta levels when comparing initial and follow-up levels. In conclusion, serum TNF-alpha reflects the progression of inflammation as seen in liver biopsies and TGF-beta reflects the degree of fibrosis in HCV patients.
Histological factors that predict the liver fibrosis in patients with chronic hepatitis C
Romanian journal of morphology and embryology = Revue roumaine de morphologie et embryologie, 2016
In chronic hepatitis, pathologies reveal a prominent inflammatory infiltrate portal consisting mostly of lymphocytes and plasma cells invading the portal spaces, although one can also identify macrophages, neutrophils or eosinophils. In all the forms of chronic hepatitis, fibrosis starts in the portal area, namely periportally, subsequently extends towards the lobules to the central veins, causing septa, followed by fibrosis. We studied 52 patients with chronic hepatitis C, who underwent a hematological, biochemical, virological and histopathological investigation. We found that the severity degree of the portal inflammation was in direct relation to the hepatitis activity index (HAI) and to the degree of fibrosis. The portal inflammation is dependent to the degree of fibrosis. The degree of inflammation significantly changes the distribution of cases with different degrees of fibrosis (chi-square p=0.00011 <0.001). Periportal inflammation, periportal necrosis and focal necrosis ...
Gut, 2010
Objectives The aim of this study was to explore the association of serum fibrosis marker levels with the risk of clinical and histological disease progression in a large cohort of patients with chronic hepatitis C (CHC). Methods 462 prior non-responders to peginterferon and ribavirin enrolled in the randomised phase of the Hepatitis C Antiviral Long-term Treatment against Cirrhosis (HALT-C) Trial had baseline and annual serum samples tested for hyaluronic acid (HA), N-terminal peptide of procollagen type 3, tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) and YKL-40. All patients underwent a pretreatment liver biopsy and follow-up biopsies at years 2 and 4. Histological progression was defined as a 2pointincreaseinIshakfibrosisscoreinpatientswithoutcirrhosis.Clinicaloutcomesincludeddevelopmentofdecompensation,hepatocellularcancer,deathoranincreaseintheCTP(ChildeTurcotteePugh)scoreto2 point increase in Ishak fibrosis score in patients without cirrhosis. Clinical outcomes included development of decompensation, hepatocellular cancer, death or an increase in the CTP (ChildeTurcotteePugh) score to 2pointincreaseinIshakfibrosisscoreinpatientswithoutcirrhosis.Clinicaloutcomesincludeddevelopmentofdecompensation,hepatocellularcancer,deathoranincreaseintheCTP(ChildeTurcotteePugh)scoreto7. Results Mean patient age was 49.5 years and 39% had histological cirrhosis at entry. Baseline HA, YKL-40 and TIMP-1 levels combined with other laboratory parameters were all significantly associated with clinical outcomes in the 69 (15%) patients with disease progression (p<0.0001). The best multivariate model to predict clinical outcomes included baseline bilirubin, albumin, international normalised ratio (INR) and YKL-40 levels. All of the baseline serum fibrosis marker levels were also significantly associated with histological fibrosis progression that developed in 70 (33%) of the 209 patients with cirrhosis (p <0.0001). However, baseline HA and platelet counts were best at predicting histological progression (area under the curve (AUC)¼0.663). Conclusion Pretreatment serum fibrosis marker levels are significantly increased in patients with CHC at risk of clinical and histological disease progression. If validated in additional cohorts, measurement of these markers could help identify patients with CHC who would benefit from more frequent and intensive monitoring. Trial Registration Number NCT00006164.
Use of Serum Levels of Proinflammatory Cytokine IL-1α in Chronic Hepatitis C
Collegium Antropologicum, 2015
Immunoregulatory cytokines infl uence the persistence of hepatitis C virus chronic infection and the extent of liver damage. Interleukin-1 plays an important role in the infl ammatory process. Some studies have demonstrated that IL-1 production was impaired in patients with chronic infections of hepatitis C virus, implying that IL-1 may play a role in viral clearance. In this study, along with routine laboratory tests, has been performed the analysis of serum levels of proinfl ammatory cytokine IL-1a in order of better understanding and monitoring of chronic hepatitis C. The aim of study was to analyze the usefulness of laboratory tests, which are routinely used in the assessment of liver disease with specifi ed immunological parameters, in patients with chronic hepatitis C. Total of 60 subjects were divided into two groups: HCV-PCR positive and negative group. The control group of 30 healthy participans was included. Apart from standard laboratory tests, the analysis included serum levels of cytokine IL-1 a. IL-1a had the highest mean concentration in group of viral hepatitis C, with PCR positive test (5.73 pg / mL), and then in of chronic viral hepatitis C, PCR negative test (5.39 pg / mL). ANOVA test proves that IL-1a in the healthy group was different from other groups as follows: in relation to HCV-RNA-PCR positive patients statistical signifi cance level was p<0.001 (F=32 755); in relation to HCV-RNA-PCR negative was also statistically signifi cant at p <0.001 (F=182 361); Cytokine IL-1 was statistically analyzed separately and compared by group 1 and 2 using Student t-test for independent samples. Statistical signifi cance was observed at p=0.026. IL-1 a was positively correlated with the duration of the illness (p<0.01) and with serum ALT activity (p<0.01) and serum AST activity (p<0.01). Using multivariate analysis model »Factor Analysis«, was made signifi cant stratifi cation predictive parameters in relation to the cytokine IL-1a, stratifi ed signifi cance is indicated as follows: 1. Age, 2. history of receiving transfusions, 3. ALT, 4. AST, 5. MELD score (negative), 6. Child-Pugh score (negative). IL-1a was signifi cantly elevated in infl ammatory conditions of pronounced activity (PCR positive hepatitis). IL-1a may have important role as marker of both infl ammation and hepatic injury, particularly in the course of hepatitis C. Results suggest that infl ammatory and immune parameters, analyzed together can signifi cantly contribute to the understanding and predicting of chronic liver damage.
Saudi medical journal, 2017
To validate the diagnostic performance of Hepa-Index in predicting different stages of hepatic fibrosis in Egyptian patients with chronic hepatitis C (CHC). Methods: Hundred treatment naïve chronic hepatitis C Egyptian patients were prospectively enrolled between June 2014 and January 2015. They were subjected to: platelet count, alpha-2-macroglobulin (α2-MG), total bilirubin, gamma glutamyl transpeptidase (GGT), total cholesterol, liver biopsy and histopathological staging of hepatic fibrosis according to METAVIR scoring system. Hepa-Index was calculated according to the formula: Hepa-Index=exp (-0.021 x platelet +1.65 x α2-MG+0.2 x total bilirubin + 0.026 x GGT -1.215 x total cholesterol) / (1+exp (-0.021 x platelet + 1.65 x α2-MG + 0.2 x total bilirubin +0.026 x GGT -1.215 x total cholesterol). Results: Hepa-Index correlates positively with the stage of hepatic fibrosis. Cut off values of Hepa-Index were: 0.2 for predicting significant hepatic fibrosis (≥F2 METAVIR), 0.3 for sev...