Evaluation of Liver Fibrosis by Serum Hyalornic Acid Measurement in β-Thalassemic Children Infected With Hepatitis C Virus Before and After Direct-Acting Antiviral Therapy

The thalassemias are a heterogeneous group of genetic heritable disorders of hemoglobin (Hb) synthesis, considered as the most common monogenic disorder in the world, affecting men and women equally and poses a severe health and economic burden to patients and families at risk (Mohammad and Al-Doski, 2012). Thalassemia is a major health problem in Egypt since it estimated out of 1.5 million live births, 1000 children with thalassemia are born annually (Youssef et al., 2012).

Thalassemics can develop liver fibrosis because of iron liver overload and hepatitis virus C (HCV) infection. Multicenter cross-sectional studies have reported that the development and the severity of liver fibrosis are strongly related to the extent of liver iron overload and to the presence of chronic HCV infection (Di Marco et al., 2008). HCV infection is the main risk factor for liver fibrosis in transfusion-dependent thalassemics. Excess liver iron is now clearly recognized as a cofactor for the development of advanced fibrosis in patients with HCV infection (Elalfy et al., 2013). Although, hepatic fibrogenesis has long been thought to be an irreversible process, it is now evident that it is a dynamic process with significant potential for reversal; unlike cirrhosis, which is irreversible. Identification of liver fibrosis at an early stage would be of great significance (Manning DS and Afdhal NH, 2008, Xu et al., 2003) Liver biopsy is an essential method for assessing fibrosis and it continues to have an important role in the diagnosis, prognosis, and management of patients with elevated results of iron studies and abnormal liver function test results. Therefore, liver biopsy is currently considered the gold standard for assessing hepatic fibrosis (Di Marco et al., 2008). However, it is an invasive and painful procedure, with rare but potential life threatening complications, limiting its acceptance and repetition in usually asymptomatic patients. In addition, the accuracy of liver biopsy in assessing fibrosis may be questioned because of sampling error and interobserver variability, which may lead to under or overstaging of fibrosis or cirrhosis (Foucher et al., 2006).

Thus there is a need to develop and validate non-invasive tests that can accurately reflect the full spectrum of hepatic fibrosis, cirrhosis, and its severity in liver diseases (Foucher et al., 2006). Serum markers and imaging methods are increasingly in vogue non-invasive alternatives to liver biopsy and the development of safe, inexpensive, and reliable non-invasive fibrosis measurement tools remains a research priority in clinical hepatology (Rockey DC 2006).

Hyaluronic acid (HA) is a high molecular weight glycosaminoglycan which is an essential component of extracellular matrix in almost every tissue in the body (Papastamataki, 2010). In the liver, HA is mostly synthesized by the hepatic stellate cells and removed via sinusoidal cell adhesion molecules (Halfon, 2005). This mechanism is impeded in fibrosis, leading to a rise in serum levels of HA. Therefore, serum HA is considered a marker that appears early before pathological changes occur (Zheng, 2003). Serum HA levels have been shown to correlate with histological stages of liver fibrosis in hepatitis C virus patients. Therefore, HA has a good diagnostic accuracy as a noninvasive assessment of fibrosis and cirrhosis (Parise et al, 2006).

Children with chronic hepatitis C (CHC) in are at risk for major complications, including cirrhosis, hepatocellular carcinoma, and death. The combined pegylated interferon-α and ribavirin (PEG-IFN/ribavirin) remains the standard therapy for CHC in children until 2016 (Aziz S, 2014, Suzuki et al. 2016, Yang et al 2017). The approved PEG-IFN/ribavirin therapy for children aged 3 and older is often held from use until adulthood because of its extensive list of potential side effects and high likelihood of causing adverse symptoms. In children and adolescents with HCV, treatment and reduction of the spread of HCV before adulthood is important, as there can be transmission to other individuals via sexual activity and infected females can later vertically transmit the infection during pregnancy, the latter representing a common source of transmission for children (Yang et al 2017).