Assessment of Serum Hydroxyproline and Osteopontin as Noninvasive Markers of Hepatic Fibrosis in Egyptian Patients with Chronic Hepatitis C Virus Infection

Abstract

Background: Hepatitis C virus (HCV) infection is a progressive disease that may result in chronic hepatitis, cirrhosis and hepatocellular carcinoma (HCC). Liver fibrosis is an essential factor that must be considered in the management of patients with HCV. Although liver biopsy represents the gold standard for evaluating the presence, type and stage of liver fibrosis, this technique remains a costly and invasive procedure. Therefore, several diagnostic methods for determining liver fibrosis, such as the detection of serum biomarkers, have been used. Objective: To evaluate the use of serum hydroxyproline (HYP) and osteopontin (OPN) as non invasive direct markers to assess the degree of hepatic fibrosis in Egyptian patients with chronic HCV infection in comparison to indirect markers such as aspartate aminotransferase platelet ratio index (APRI) and to determine the most diagnostically accurate non invasive marker of hepatic fibrosis, hoping to replace liver biopsy in the next few years. Methodology: This study was carried out on 48 patients with chronic HCV infection who had undergone liver biopsy and scored as mild fibrosis (F1), moderate fibrosis (F2), sever fibrosis (F3) and liver cirrhosis (F4) based on Metavir scoring system, and 12 age and sex matched controls. The serum levels of HYP and OPN were measured by enzyme linked immunosorbent assay (ELISA). Results: There was a highly significant increase in HYP, OPN and APRI in all patients groups in comparison to control group and their increase was significantly associated with the degree of hepatic fibrosis. Furthermore, HYP, OPN and APRI values showed highly significant increase in significant hepatic fibrosis (F2- F4) in comparison to mild fibrosis (F1), and in hepatic cirrhosis (F4) in comparison to hepatic fibrosis (F1-F3). There was a highly significant positive correlation between serum HYP level, OPN and APRI. The receiver operating characteristic (ROC) curve analysis revealed that OPN has the highest area under the curve (AUC) value for discriminating fibrosis stages, followed by HYP and lastly APRI. Conclusion: This study demonstrated that OPN was the most diagnostically accurate marker for assessing the severity of hepatic fibrosis and served as a prognostic index towards the progression of hepatic fibrosis to cirrhosis in patients with chronic HCV infection, followed by HYP and lastly APRI. These findings indicated that OPN and HYP could be used as non invasive markers of hepatic fibrosis and cirrhosis which would help to reduce the need for liver biopsy in chronic HCV infection