The Role of Serum Biomarkers in Predicting Fibrosis Progression in Pediatric and Adult Hepatitis C Virus Chronic Infection

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.

Serum hyaluronan levels increase with the total number of osteoarthritic joints and are strongly associated with the presence of knee and finger osteoarthritis

“…On the other hand, it is considered that serum biomarkers are affected by other systemic factors, such as medical problems associated with aging, circadian rhythm, food intake and vigorous activities [15] because data are obtained from blood samples. In this study, to analyse the relationship between a serum biomarker and OA, major diseases were excluded, such as liver failure, renal failure, rheumatoid arthritis and presence of malignant tumours [22][23][24]. Also, the timing of blood sampling was standardised to the early morning to diminish the effect of physical activity, food intake or circadian rhythms.…”

Performance of diagnostic biomarkers in predicting liver fibrosis among hepatitis C virus-infected Egyptian children

“…Recently, biochemical parameters were found to be good indicators of liver fibrosis, especially in children (Valva et al 2011). Serum markers of liver fibrosis are divided into two categories: direct markers, which reflect ECM turnover, and indirect markers, which reflect alterations in hepatic function, but not ECM metabolism (Grigorescu 2006).…”

Extracellular Matrix Condition in Case of Hcvassociated Liver Fibrosis

“…В настоящее время одним из ведущих меха-низмов развития фиброза печени считают на-рушение равновесия в системе ММP/ТIМP, следствием которого является дисбаланс между синтезом и разрушением компонентов межкле-точного матрикса [9,16,18,22]. Исследование отдельных представите-лей семейства внеклеточных протеиназ и их тканевых ингибиторов в сыворотке крови HCV-инфицированных пациентов обнаружило изменения изучаемых показателей относитель-но контрольной группы здоровых лиц.…”

“…Современные данные отечественной и за-рубежной литературы свидетельствуют, что фи-брогенез в печени -это универсальный пато-физиологический процесс, характеризующийся нарушением равновесия между продукцией и де-градацией компонентов экстрацеллюлярного матрикса [1,18,22]. Данный дисбаланс способ-ствует чрезмерному синтезу внеклеточных про-теинов, их накоплению и отложению в печени, а, следовательно, перестройке архитектоники орга-на-мишени с формированием в конечном итоге цирроза печени [12,14,15].…”