Cathepsin B and Plasma Kallikrein Are Reliable Biomarkers to Discriminate Clinically Significant Hepatic Fibrosis in Patients with Chronic Hepatitis-C Infection

• Published in: Microorganisms (Basel) Vol. 10; no. 9; p. 1769
• Main Authors: Zanelatto, Alexia de Cassia Oliveira, Lacerda, Gilmar de Souza, Accardo, Camila de Melo, Rosário, Natalia Fonseca do, Silva, Andréa Alice da, Motta, Guacyara, Tersariol, Ivarne Luis Dos Santos, Xavier, Analucia Rampazzo
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 01-09-2022; MDPI
• Subjects: Biological markers; Biomarkers; Biopsy; Blood & organ donations; Blood platelets; Cathepsin B; Cathepsins; chronic hepatitis C; Chronic infection; Clinical significance; Diagnosis; Enzymes; Fibrosis; Genotype & phenotype; Growth factors; HCV; Health aspects; hepatic fibrosis; Hepatitis; Hepatitis C; Infections; Inflammation; Kallikrein; Laboratories; Liver cancer; Liver diseases; Metabolism; Plasma; Plasma kallikrein; Protein kinase A; Proteolysis; Proteolytic enzymes; Serum levels; TGF-β; Transforming growth factor-b; Viral infections; Brazil; United States > US; TGF-β; HCV; plasma kallikrein; hepatic fibrosis; cathepsin B; chronic hepatitis C
• DOI: 10.3390/microorganisms10091769
• EISSN: 2076-2607

We aimed to determine the biomarker performance of the proteolytic enzymes cathepsin B (Cat B) and plasma kallikrein (PKa) and transforming growth factor (TGF)-β to detect hepatic fibrosis (HF) in chronic hepatitis C (CHC) patients. We studied 53 CHC patients and 71 healthy controls (HCs). Hepatic-disease stage was determined by liver biopsies, aminotransferase:platelet ratio index (APRI) and Fibrosis (FIB)4. Hepatic inflammation and HF in CHC patients were stratified using the METAVIR scoring system. Cat-B and PKa activities were monitored fluorometrically. Serum levels of TGF-β (total and its active form) were determined using ELISA-like fluorometric methods. Increased serum levels of Cat B and PKa were found (p < 0.0001) in CHC patients with clinically significant HF and hepatic inflammation compared with HCs. Levels of total TGF-β (p < 0.0001) and active TGF-β (p < 0.001) were increased in CHC patients compared with HCs. Cat-B levels correlated strongly with PKa levels (r = 0.903, p < 0.0001) in CHC patients but did not correlate in HCs. Levels of Cat B, PKa and active TGF-β increased with the METAVIR stage of HF. Based on analyses of receiver operating characteristic (ROC) curves, Cat B and PKa showed high diagnostic accuracy (area under ROC = 0.99 ± 0.02 and 0.991 ± 0.007, respectively) for distinguishing HF in CHC patients from HCs. Taken together, Cat B and PKa could be used as circulating biomarkers to detect HF in HCV-infected patients.