Abstract
BackgroundLiver biopsy represents the gold standard for evaluating damage and progression in patients with chronic hepatitis C (CHC); however, developing noninvasive tests that can predict liver injury represents a growing medical need. Considering that hepatocyte apoptosis plays a role in CHC pathogenesis; the aim of our study was to evaluate the presence of different apoptosis markers that correlate with liver injury in a cohort of pediatric and adult patients with CHC.MethodsLiver biopsies and concomitant serum samples from 22 pediatric and 22 adult patients with CHC were analyzed. Histological parameters were evaluated. In serum samples soluble Fas (sFas), caspase activity and caspase-generated neoepitope of the CK-18 proteolytic fragment (M30) were measured.ResultssFas was associated with fibrosis severity in pediatric (significant fibrosis p = 0.03, advanced fibrosis p = 0.01) and adult patients (advanced fibrosis p = 0.02). M30 levels were elevated in pediatric patients with severe steatosis (p = 0.01) while in adults no relation with any histological variable was observed. Caspase activity levels were higher in pediatric samples with significant fibrosis (p = 0.03) and they were associated with hepatitis severity (p = 0.04) in adult patients. The diagnostic accuracy evaluation demonstrated only a good performance for sFas to evaluate advanced fibrosis both in children (AUROC: 0.812) and adults (AUROC: 0.800) as well as for M30 to determine steatosis severity in children (AUROC: 0.833).ConclusionsSerum sFas could be considered a possible marker of advanced fibrosis both in pediatric and adult patient with CHC as well as M30 might be a good predictor of steatosis severity in children.
Highlights
Hepatitis related to Hepatitis C virus (HCV) is a progressive disease that may result in chronic active hepatitis, cirrhosis, and hepatocellular carcinoma
Considering that 1) apoptosis plays a major role in the tissue development and homeostasis and in pathological processes [16]; 2) it has been demonstrated that hepatocyte apoptosis plays a role in liver pathogenesis of chronic hepatitis C (CHC); as well as it may be associated with liver fibrogenesis [17,18,19,20]; the aim of our study was to evaluate the presence of different apoptosis markers which correlate with liver injury in a cohort of pediatric and adult patients with CHC infection
According to available data and their importance in the pathogenesis, three components of the apoptosis process were selected for evaluation: 1) soluble Fas (sFas), since it has been proposed that apoptosis triggered by Fas/FasL is a major cause of hepatocyte damage together with the observed high Fas/FasL expression levels which correlate with liver injury during CHC [31,32,33,34,35]; 2) caspase activity, since it has been reported that caspases are activated in HCV infected patient hepatocytes and are responsible for most of the morphological changes of the apoptotic cells [36]; and 3) M30, since CK18 is the major intermediate filament of hepatocytes which is, in turn, a caspase substrate whose cleavage contribute to cellular collapse during apoptosis
Summary
Hepatitis related to Hepatitis C virus (HCV) is a progressive disease that may result in chronic active hepatitis, cirrhosis, and hepatocellular carcinoma. It is estimated that over 200 million people are infected worldwide, while 80% develop a chronic form [1] It represents a global health problem since there is no vaccine available, the response to current standard of care therapy is limited and liver failure related to chronic hepatitis C (CHC) virus infection is one of the most common reasons for liver transplants [2]. Liver biopsy represents the gold standard for evaluating presence, type and stage of liver fibrosis and for characterizing necroinflammation; it remains an expensive and invasive procedure with inherent risks. Liver biopsy represents the gold standard for evaluating damage and progression in patients with chronic hepatitis C (CHC); developing noninvasive tests that can predict liver injury represents a growing medical need. Considering that hepatocyte apoptosis plays a role in CHC pathogenesis; the aim of our study was to evaluate the presence of different apoptosis markers that correlate with liver injury in a cohort of pediatric and adult patients with CHC
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