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

We aimed to determine the biomarker performance of the proteolytic enzymes cathepsin B (Cat B) and plasma kallikrein (PKa) and transforming growth factor (TGF)-ß 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-ß (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-ß (p < 0.0001) and active TGF-ß (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-ß 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.

Restoring Inflammatory Mediator Balance after Sofosbuvir-Induced Viral Clearance in Patients with Chronic Hepatitis C.

This study aimed at analyzing circulating levels of inflammatory and profibrogenic cytokines in patients with hepatitis C virus (HCV) chronic infection undergoing therapy with direct-acting antiviral agents (DAA) and correlating these immune biomarkers with liver disease status. We studied 88 Brazilian monoinfected chronic hepatitis C patients receiving interferon- (IFN-) free sofosbuvir-based regimens for 12 or 24 weeks, followed-up before therapy initiation and three months after the end of treatment. Liver disease was determined by transient elastography, in addition to APRI and FIB-4 indexes. Analysis of 30 immune mediators was carried out by multiplex or enzymatic immunoassays. Sustained virological response rate was 98.9%. Serum levels of cytokines were increased in HCV-infected patients when compared to control group. CCL-2, CCL-3, CCL-4, CXCL-8, CXCL-10, IL-1ß, IL-15, IFN-γ, IL-4, IL-10, TGF-ß, FGFb, and PAI-1 decreased significantly after antiviral therapy, reaching values similar to noninfected controls. TGF-ß and suPAR levels were associated with fibrosis/cirrhosis. Also, we observed amelioration in hepatic parameters after DAA treatment. Together, our results suggest that viral control induced by IFN-free DAA therapy restores inflammatory mediators in association with improvement in liver function.

Exploring lipid and apolipoprotein levels in chronic hepatitis C patients according to their response to antiviral treatment.

BACKGROUND: Hepatitis C virus is known to be highly dependent of lipid metabolism to infect new cells and replicate. AIMS: To investigate lipid and apolipoprotein profile in chronic HCV patients according to treatment response. METHODS: Patients recruited from the Hepatitis Treatment Center at Niteroi (Brazil) who received interferon (IFN)-based therapies were separated into two groups, those who achieved sustained virological response (SVR) or not (non-SVR). Another group of patients treated with IFN-free direct-acting antiviral (DAA) therapies was followed from before starting the treatment until one year after therapy. Triglycerides, total cholesterol and fractions were determined by colorimetric and/or electrophoresis techniques. Lecithin cholesterol acyltransferase (LCAT) activity and serum levels of apolipoproteins A1, A2, B, C2, C3 and E were assessed by enzymatic and multiplex assays, respectively. RESULTS: We studied 114 patients, and SVR was reached in 28 (39.4%) patients treated with IFN-therapy and in all (100%) patients who received DAA. Non-SVR patients (n = 43) presented altered liver parameters post-treatment. Levels of total cholesterol, LDL-C, VLDL-C and triglycerides were significant higher in SVR group. In contrast, LCAT activity and HDL-C levels were elevated in non-SVR patients. Only apolipoproteins B, C2 and C3 levels were increased in SVR group. The follow-up of SVR-DAA patients (n = 43) revealed a significant and progressive increase in serum levels of total cholesterol, LDL-C, VLDL-C and triglycerides. CONCLUSIONS: After a successful treatment, chronic hepatitis C patients experienced a reestablishment of lipid metabolism. Our results suggest that the monitoring of serum lipids could be a practical and routine laboratory tool to be applied during the treatment follow-up.