ABSTRACT
There is a need, in NAFLD management, to develop non-invasive methods to detect steatohepatitis (NASH) and to predict advanced fibrosis stages. We evaluated a tool based on optical analysis of liver magnetic resonance images (MRI) as biomarkers for NASH and fibrosis detection by investigating patients with biopsy-proven NAFLD who underwent magnetic resonance (MR) protocols using 1.5T General Electric (GE) or Philips devices. Two imaging biomarkers (NASHMRI and FibroMRI) were developed, standardised and validated using area under the receiver operating characteristic curve (AUROC) analysis. The results indicated NASHMRI diagnostic accuracy for steatohepatitis detection was 0.83 (95% CI: 0.73-0.93) and FibroMRI diagnostic accuracy for significant fibrosis determination was 0.85 (95% CI: 0.77-0.94). These findings were independent of the MR system used. We conclude that optical analysis of MRI has high potential to define non-invasive imaging biomarkers for the detection of steatohepatitis (NASHMRI) and the prediction of significant fibrosis (FibroMRI) in NAFLD patients.
Subject(s)
Biomarkers/metabolism , Fatty Liver/pathology , Liver Cirrhosis/pathology , Non-alcoholic Fatty Liver Disease/pathology , Adult , Aged , Area Under Curve , Elasticity Imaging Techniques , Fatty Liver/diagnostic imaging , Female , Humans , Keratin-18/metabolism , Liver/diagnostic imaging , Liver/pathology , Liver Cirrhosis/complications , Liver Cirrhosis/diagnostic imaging , Magnetic Resonance Imaging/standards , Male , Middle Aged , Non-alcoholic Fatty Liver Disease/complications , Non-alcoholic Fatty Liver Disease/diagnostic imaging , ROC Curve , Severity of Illness IndexABSTRACT
The current anti-hepatitis C virus (HCV) therapy, based on pegylated-interferon alpha and ribavirin, has limited success rate and is accompanied by several side effects. The aim of this study was to identify protein profiles in pretreatment liver biopsies of HCV patients correlating with the outcome of antiviral therapy. Cytosolic or membrane/organelle-enriched protein extracts from liver biopsies of eight HCV patients were analyzed by two-dimensional fluorescence difference gel electrophoresis and mass spectrometry. Overall, this analysis identified 21 proteins whose expression levels correlate with therapy response. These factors are involved in interferon-mediated antiviral activity, stress response, and energy metabolism. Moreover, we found that post-translational modifications of dihydroxyacetone kinase were also associated with therapy outcome. Differential expression of the five best performing markers (STAT1, Mx1, DD4, DAK, and PD-ECGF) was confirmed by immunoblotting assays in an independent group of HCV patients. Finally, we showed that a prediction model based on the expression levels of these markers classifies responder and nonresponder patients with an accuracy of 85.7%. These results provide evidence that the analysis of pretreatment liver protein profiles is valuable for discriminating between responder and nonresponder HCV patients, and may contribute to reduce the number of nonresponder patients exposed to therapy-associated risks.
Subject(s)
Antiviral Agents/therapeutic use , Hepatitis C, Chronic/drug therapy , Hepatitis C, Chronic/metabolism , Interferon-alpha/therapeutic use , Liver/drug effects , Liver/metabolism , Polyethylene Glycols/therapeutic use , Proteome/analysis , Area Under Curve , Biomarkers/analysis , Biopsy , Cluster Analysis , Electrophoresis, Gel, Two-Dimensional , Hepatitis C, Chronic/diagnosis , Humans , Liver/chemistry , Principal Component Analysis , Prognosis , Proteomics , Recombinant Proteins/therapeutic use , Reproducibility of Results , Retrospective Studies , Ribavirin/therapeutic use , Treatment OutcomeABSTRACT
The use of adjuvants capable of improving the deficient immune response to hepatitis B virus (HBV) vaccine in haemodialysis patients is highly needed. Among potential adjuvants, type I interferons deserve a special attention in view of their known effects promoting cellular and humoral immune responses. The aim of the present trial was to evaluate the effects of recombinant interferon-alpha2b (IFN) administered as an adjuvant of HBV vaccine in unvaccinated haemodialysis patients. A significant and early enhancing effect on the antibody response was observed in patients receiving IFN. In addition, a predominance of IgG1 anti-HBs along with a transient normalization of circulating Th1 lymphocytes was only found in patients receiving IFN who achieved an early seroprotection. However, 6 months after the last vaccine dose, no significant differences were observed in the seroprotection rate achieved in patients vaccinated with IFN compared to that in patients receiving HBV vaccine alone. Mild to moderate fever, asthenia, and arthromyalgia were the most common reactions that occurred in vaccinees given IFN. In conclusion, addition of IFN to HBV vaccine, under the conditions used in this trial, is safe and achieves an earlier and higher seroprotection rate improving Th1-dependent immune response in haemodialysis patients.
