The role of non-invasive markers in the determinationof liver fibrosis in patients with chronic hepatitis C andevaluation of their changes after therapy with directacting antiviral agents

Chronic hepatitis C virus (HCV) infection is an important factor in the development of chronic hepatitis, liver fibrosis , liver cirrhosis and hepatocellular carcinoma. The degree and extent of fibrosis, a predictor of disease progression, may help in selecting the optimal treatment as well as the optimal duration of treatment. AST-platelet ratio index (APRI) score, FIB-4 index, and ratio of aspartate aminotransferase and alanine aminotransferase activities (AST/ALT) (AAR) are used as fibrosis index. New treatment protocols using direct-acting oral antiviral agents (DAAA) in the treatment of chronic HCV have been used effectively and reliably. These advances in the diagnosis and treatment of HCV disease have significantly reduced the need for liver biopsy in clinical practice. The aims of this study is to evaluate the role of APRI, FIB-4 and AAR scores, which are non-invasive fibrosis markers, in detecting fibrosis in chronic HCV patients and the changes after DEAA treatment. Between July 2016 and September 2018, the data of 72 patients treated with DEAA for chronic HCV infection were completed retrospectively. In these patients, APRI, FIB-4 score and AAR ratio were determined and and these markers were recalculated at the end of treatment and their changes after treatment were evaluated. In addition, CTP and MELD (model of end-stage liver disease) scores were evaluated at the beginning and end of treatment in patients with liver cirrhosis. As results; the post-treatment APRI and FIB-4 scores were significantly lower than pre-treatment measurements, and AAR values after treatment were significantly higher than pre-treatment measurements. It is detected that APRI, FIB4 and AAR scores of the patients with advanced fibrosis according to Ishak fibrosis scores were also significantly increased. According to Ishak fibrosis scoring; fibrosis stage 1-2, FIB-4 score <1.45, APRI score ≤0.5, AAR score ≤1; 33.3% of patients with fibrosis stage 3-4 had FIB-4 score <1.45; FIB-4 score was> 3.25 in 81.1% of patients with fibrosis stage 5-6. There was a high degree of correlation between FIB-4 and AAR values and a moderate correlation between APRI values and Isaac fibrosis classification. In order to investigate the efficacy of non-invasive markers in showing mild fibrosis, areas under the ROC curve (AUROC) were found to be high with APRI 0.79, FIB4 0.878, and AAR 0.82. When the cut-off value for FIB4 was taken as ≤2.52, the significance of showing mild fibrosis was <0.001, sensitivity 93%, specificity 82%. It was observed that when the cut-off value of ≤0.95 for APRI and ≤0.79 for AAR were taken, it was able to distinguish between patients and intact patients. To investigate the efficacy in predicting cirrhosis and to compare with the group with fibrosis score F0-F4, the third ROC curve was plotted to show that the AUROC values were AAR 0.882, FIB4 0.952, and APRI 0.82 high. When the cut-off value for FIB-4 was taken as ≥1.34, the significance in detecting cirrhosis was found as <0.001, sensitivity 100%, specificity 60%. Non-invasive fibrosis markers such as APRI, FIB-4, and AAR in patients with chronic HCV patients correlate with fibrosis identified by biopsy and greatly reduce the need for liver biopsy in the management of HCV infection. New DAAAs are highly effective and safe in the treatment of chronic HCV. It is seen that post-treatment APRI and FIB-4 scores also improved. Proper use and interpretation of non-invasive fibrosis markers will also be important for optimizing hepatology follow-up after treatment. The effect of achieving a permanent virologic response on fibrosis regression and how to measure it by non-invasive methods remains an exciting way of further investigation.