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The relation between interferon-gamma (IFN-γ) levels and the severity of liver diseases through fibrosis, cirrhosis, and hepatocellular carcinoma (HCC) has not been fully clarified. Thus, we aimed to characterize IFN-γ levels in liver-diseased patients. IFN-γ levels were determined by Western-blot and ELISA in sera from 30 healthy individuals, 53 patients with non-significant fibrosis (F0-F1), 47 with moderate/severe fibrosis (F2-F3), 44 cirrhotic patients (F4), and 50 with HCC. Enhanced levels of IFN-γ were associated with the progression of liver disease. The differences were statistically significant (P < 0.0001) when patients with F2-F3, F4, or HCC were compared with F0-F1 or healthy controls. The increase in IFN-γ was associated with HCC (OR = 0.98, 95% CI 0.97-0.99, P = 0.002). There was no statistically significant association between IFN-γ levels and HCV-RNA (IU/ml) (r = 0.1, P = 0.43) or HCV-NS4 (µg/mL) (r = 0.1, P = 0.17). There was significant (P < 0.0001) association between IFN-γ levels and the fibrosis stages and activity, albumin, platelet count, total bilirubin, and international normalized ratio (INR). In conclusion, elevated concentrations of IFN-γ represent a characteristic feature of liver disease severity regardless of underlying disease. Significant correlations with indices of hepatic dysfunction suggest that enhanced IFN-γ levels represent a consequence of liver dysfunction rather than of inflammatory disease.

Chronic hepatitis C (CHC) leads eventually to liver fibrosis, advanced hepatic disease and related deaths. Therefore, it is very important to assess clinical risk factors associated with rapid CHC and hepatic fibrosis progression. Former studies reported diabetes mellitus synergistic interactions with other host factors to fibrosis progression. Here, we aimed to evaluate the association between elevated blood glucose levels and CHC progression according to METAVIR system in patients chronically infected with HCV-genotype 4 and to evaluate the correlation between elevated glucose levels and liver- and viral-related biochemical parameters. A total of 160 patients with CHC (80 with liver fibrosis and 80 with cirrhosis) and 40 healthy volunteers, negative for HCV, were included. Our results revealed that cirrhotic patients had high (P =.0001) fasting (169.1 ± 50.2 mg/dL), postprandial (208 (123–320) mg/dL), and random (176.8 ± 51 mg/dL) glucose levels compared to patients with liver fibrosis (105.0 ± 32, 120 (105-135), and 113.5 ± 35 mg/dL, respectively). Mean serum fasting, postprandial and random glucose levels were significantly (P =.0001) increased with an increase in fibrosis stages, F1< F2< F3< F4. Blood glucose levels were also significantly (P <.05) correlated with liver disease related biological parameters and HCV-Ab titer. In conclusion, our results highlighted the fibrogenic impact of elevated glucose levels on CHC patients. [ABSTRACT FROM AUTHOR]

The current study aimed to investigate the diagnostic value of glycated albumin (GA), glycated hemoglobin (HbA1c), and a number of routine biomarkers as noninvasive indicators of liver fibrosis in patients with chronic hepatitis C (CHC). One hundred patients with CHC were subjected to full medical history and examination, in addition to ultrasound‐guided liver biopsy and histopathological examination for assessment of liver fibrosis stage. GA and HbA1c values, GA/HbA1c ratio, liver function tests, complete blood count, and alpha fetoprotein (AFP) were determined. A novel noninvasive index, dubbed Fibrosis Prediction Score (FPS), was selected for predicting significant liver fibrosis based on total bilirubin, glycated albumin, platelet count, age, and AFP. A validation study for FPS was applied on archival data which include 66 diabetics' patients. The FPS had area under the curve (AUC) of 0.92 for classification of patients with significant fibrosis with 81% sensitivity and 95% specificity. The AUCs of FPS in predicting advanced fibrosis and cirrhosis were 0.86 and 0.82, respectively. Comparison of AST‐to‐platelet ratio index (APRI) and FIB‐4 with FPS indicated increased sensitivity and specificity of FPS over APRI and FIB4 in both significant and advanced fibrosis. FPS has a good sensitivity and specificity for prediction of significant and advanced liver fibrosis in patients with CHC. Highlights: Progression of hepatitis C virus infection to chronicity is one of the most pressing health problems.Accurate assessment of liver fibrosis is important to make therapeutic decisions, determine prognosis and to follow‐up disease progression.Accurate, reproducible and easily applied methods are required for evaluation of hepatic fibrosis.Fibrosis Prediction Score (FPS), based on five simple variables including AFP, age, glycated albumin, total bilirubin and platelet count, demonstrated better diagnostic power for detection significant and advanced liver fibrosis. [ABSTRACT FROM AUTHOR]

Aim: The epithelial membrane antigen (EMA) could detect small deposits of liver malignant cells. However, no information exists regarding the use of EMA in patients with chronic hepatitis C (CHC). Therefore, we attempted to evaluate the diagnostic performance of EMA to distinguish patients with different liver fibrosis stages. Methods: Epithelial membrane antigen was identified in sera of 154 CHC patients using Western blot and enzyme linked immunosorbent assay (ELISA). Multivariate discriminant analysis (MDA) and receiver operating characteristic (ROC) curve analyses were used to create a predictive model including EMA in addition to a panel of routine blood markers. A combination algorithm was developed and validated prospectively in 170 CHC additional patients. Results: Epithelial membrane antigen at 130 kDa was identified, purified and quantified in sera of CHC patients using ELISA. Based on these encouraging results, we purified and developed a direct ELISA for the quantitation of EMA in sera of CHC. MDA selected a score for the prediction of significant liver fibrosis patients based on measurements of EMA, aspartate aminotransferase to platelet ratio index and albumin. Areas under the ROC curves (AUC) of the score for the three biomarkers were 0.82 for patients with liver fibrosis (F1-F4), 0.86 for significant liver fibrosis (F2-F4), 0.87 for advanced liver fibrosis (F3-F4) and 0.86 for liver cirrhosis (F4). The results of the validation study demonstrated that (74%) of patients could have avoided liver biopsy. Conclusion: This score was validated for the prediction of liver fibrosis stages and may minimize the need for liver biopsy. [ABSTRACT FROM AUTHOR]

Abstract: Background: This study aimed to develop and evaluate a predictive score named Fibrosis Routine Test (FRT) for liver fibrosis staging and to compare FRT with APRI, Lok, GUCI, FI, FibroQ, FCI, FIB-4 and 4RLB scores in large numbers of untreated HCV-monoinfected patients. Methods: Large numbers of estimation (N=2045) and validation patients (N=3212) were included in this study. Stepwise linear discriminant analysis and area under receiver-operating characteristic curves (AUCs) were used to create a predictive score comprising age, AFP, APRI and albumin. Results: In the estimation study, FRT produced AUCs 0.84, 0.85 and 0.86 for significant (F2–F4), advanced fibrosis (F3–F4) and cirrhosis (F4), respectively. FRT >4 was 83% specific and 73% sensitive for F2–F4, FRT >5 was 83% specific and 71% sensitive for F3–F4 and FRT >5.5 was 81% specific and 73% sensitive for F4. In the validation study, FRT produced AUCs 0.81, 0.89 and 0.95 for F2–F4, F3–F4 and F4, respectively. The above eight scores demonstrated lower AUCs than FRT. Conclusion: While liver biopsy is invasive, costly and associated with complications, Fibrosis Routine Test (FRT) is a non-invasive, inexpensive, simple and may reduce the need of liver biopsy. [Copyright &y& Elsevier]