ABSTRACT
INTRODUCTION AND AIM: The correlation between interleukin-28B (IL-28B) polymorphisms and chronic hepatitis C (CHC) progression is debatable. Here, we aimed to evaluate the relation between IL-28B C/T genotypes and the development of cirrhotic liver. Extracellular matrix (ECM) proteins, FibroScan and model for end-stage liver disease (MELD) were used to substantiate the severity of liver disease. MATERIAL AND METHODS: IL-28B rs12979860, liver stiffness and ECM proteins were assessed in 272 CHC patients. RESULTS: Cirrhosis percentage increased to 10%, 52% and 96% with the increasing number of T alleles (CC, CT and TT, respectively). Also, elevated ECM proteins levels were correlated with the increasing number of T alleles. Interestingly, among cirrhotic patients, liver stiffness, MELD and ECM proteins were significantly (P < 0.0001) higher in patients with TT more than CT genotype. FibroScan, hyaluronic acid, Laminin, Collagen IV and the N-terminal pro-peptide of collagen type III have high accuracy to differentiate liver status in CC from TT genotype. Area under receiver-operating characteristic curve (95% CI) were 1.0 (1.0-1.0), 0.97 (0.96- 1.0), 0.93 (0.85-1.0), 0.98 (0.97-1.0) and 0.93 (0.91-0.97), respectively. CONCLUSION: This study suggests that IL-28B T allele affects the natural course of CHC type 4 and also suggests that carriage of the IL-28B C allele protects from unfavorable clinical outcomes in CHC as coexistence of C allele with T allele reduced cirrhosis severity.
Subject(s)
Extracellular Matrix Proteins/analysis , Hepatitis C, Chronic/genetics , Hepatitis C, Chronic/metabolism , Interleukins/genetics , Liver/chemistry , Polymorphism, Single Nucleotide , Disease Progression , Egypt , Elasticity Imaging Techniques , Genetic Predisposition to Disease , Hepatitis C, Chronic/diagnosis , Hepatitis C, Chronic/virology , Humans , Interferons , Liver/diagnostic imaging , Liver/pathology , Liver/virology , Phenotype , Prognosis , Protective Factors , Retrospective Studies , Risk Factors , Severity of Illness Index , Up-RegulationABSTRACT
Stage of liver fibrosis is critical for treatment decision and prediction of outcomes in chronic hepatitis C (CHC) patients. We evaluated the diagnostic accuracy of transient elastography (TE)-FibroScan and noninvasive serum markers tests in the assessment of liver fibrosis in CHC patients, in reference to liver biopsy. One-hundred treatment-naive CHC patients were subjected to liver biopsy, TE-FibroScan, and eight serum biomarkers tests; AST/ALT ratio (AAR), AST to platelet ratio index (APRI), age-platelet index (AP index), fibrosis quotient (FibroQ), fibrosis 4 index (FIB-4), cirrhosis discriminant score (CDS), King score, and Goteborg University Cirrhosis Index (GUCI). Receiver operating characteristic curves were constructed to compare the diagnostic accuracy of these noninvasive methods in predicting significant fibrosis in CHC patients. TE-FibroScan predicted significant fibrosis at cutoff value 8.5 kPa with area under the receiver operating characteristic (AUROC) 0.90, sensitivity 83%, specificity 91.5%, positive predictive value (PPV) 91.2%, and negative predictive value (NPV) 84.4%. Serum biomarkers tests showed that AP index and FibroQ had the highest diagnostic accuracy in predicting significant liver fibrosis at cutoff 4.5 and 2.7, AUROC was 0.8 and 0.8 with sensitivity 73.6% and 73.6%, specificity 70.2% and 68.1%, PPV 71.1% and 69.8%, and NPV 72.9% and 72.3%, respectively. Combined AP index and FibroQ had AUROC 0.83 with sensitivity 73.6%, specificity 80.9%, PPV 79.6%, and NPV 75.7% for predicting significant liver fibrosis. APRI, FIB-4, CDS, King score, and GUCI had intermediate accuracy in predicting significant liver fibrosis with AUROC 0.68, 0.78, 0.74, 0.74, and 0.67, respectively, while AAR had low accuracy in predicting significant liver fibrosis. TE-FibroScan is the most accurate noninvasive alternative to liver biopsy. AP index and FibroQ, either as individual tests or combined, have good accuracy in predicting significant liver fibrosis, and are better combined for higher specificity.
