Abstract

Background/AimsLiver biopsy represents the gold standard for damage evaluation, but noninvasive serum markers that mirror liver fibrosis progression are actual goals both in adults and especially in children. The aim was to determine specific serum markers that correlate with liver fibrosis progression during chronic HCV infection.MethodsLiver biopsies and concomitant serum samples from 22 pediatric and 22 adult HCV patients were analyzed. Histological parameters were evaluated. On serum TGF-ß1, tissue inhibitor of matrix metalloprotein inhibitor-1 (TIMP-1), hyaluronic acid (HA) and aminoterminal peptide of procollagen type III (PIIINP) were tested.ResultsSignificant fibrosis (F≥2) and advanced fibrosis (F≥3) represented 64% and 20%, respectively in children; while 54% F≥2 and 23% F≥3 in adults. Hyaluronic acid (p = 0.011) and PIIINP (p = 0.016) were related to worse fibrosis stages only in adults, along with TIMP-1 (p = 0.039) just in children; but TGF-ß1 was associated with mild fibrosis (p = 0.022) in adults. The AUROC of TIMP-1 in children to discriminate advanced fibrosis was 0.800 (95%IC 0.598–0.932). In adults, the best AUROCs were that of HA, PIIINP and TGF-ß1 [0.929 (IC95% 0.736–0.994), 0.894 (IC95% 0.689–0.984) and 0.835 (IC95% 0.617–0.957)], respectively. In children, according to the cut off (165.7 ng/mL) value for TIMP-1, biopsies could have been avoided in 72% (18/25). Considering the cut off for HA (109.7 ng/mL), PIIINP (9.1 µg/L), and TGF-ß1 (10,848.3 pg/mL), biopsies could have been avoided in 87% (19/22) of adult patients by using HA and 73% (16/22) using PIIINP or TGF-ß1.ConclusionsIn adults given the diagnostic accuracy of HA, PIIINP, TGF-ß1, their combination may provide a potential useful tool to assess liver fibrosis. This first pediatric study suggests that TIMP-1 is clinically useful for predicting liver fibrosis in HCV patients.

Highlights

  • Hepatitis related to HCV is a progressive disease that may result in chronic active hepatitis, cirrhosis, and hepatocellular carcinoma [1,2,3]

  • Liver disease seems to be milder in children than in adults; the natural history of chronic HCV infection acquired in infancy and childhood remains poorly characterized and the long-term outcome of the disease is still a matter of debate [4,5]

  • The purpose of our study was to evaluate the presence of a profibrogenic cytokine (TGF-ß1) and matrix deposition markers [hyaluronic acid (HA), type III procollagen amino-terminal peptide (PIIINP) and tissue inhibitor of matrix metalloprotein inhibitor-1 (TIMP-1)] that correlate with liver injury during chronic hepatitis C virus infection, in a cohort of pediatric and adult patients

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Summary

Introduction

Hepatitis related to HCV is a progressive disease that may result in chronic active hepatitis, cirrhosis, and hepatocellular carcinoma [1,2,3]. It represents a global health problem since there is no vaccine currently available and liver failure due to chronic hepatitis C (CHC) is one of the most common reasons for liver transplants. Liver biopsy represents the gold standard for evaluating presence, type and stage of liver fibrosis and for characterizing necroinflammation; it remains a costly and invasive procedure with inherent risks. Developing noninvasive tests that can accurately predict initial disease stage and progression over time represents a high priority and growing medical need [9,10]

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