Serum fibrosis markers are associated with liver disease progression in non-responder patients with chronic hepatitis C

Abstract

OBJECTIVES The aim of this study was to explore the association of serum fibrosis marker levels with the risk of clinical and histological disease progression in a large cohort of patients with chronic hepatitis C (CHC) DESIGN/SETTING 462 prior non-responders to peginterferon and ribavirin enrolled in the randomized phase of the Hepatitis C Antiviral Long-term Treatment against Cirrhosis (HALT-C) Trial had baseline and annual serum samples tested for hyaluronic acid (HA), n-terminal peptide of procollagen type 3, tissue inhibitor of matrix metalloproteinase-1, and YKL-40. OUTCOME MEASURES All patients underwent a pretreatment liver biopsy and follow-up biopsies at years 2 and 4. Histological progression was defined as a ≥ 2 point increase in Ishak fibrosis score in non-cirrhotic patients. Clinical outcomes included development of decompensation, hepatocellular cancer, death, or an increase in the CTP score to ≥ 7. RESULTS Mean patient age was 49.5 years and 39% had histological cirrhosis at entry. Baseline HA, YKL-40 and TIMP-1 levels combined with other laboratory parameters were all significantly associated with clinical outcomes in the 69 (15%) patients with disease progression (p< 0.0001). The best multivariate model to predict clinical outcomes included baseline bilirubin, albumin, INR, and YKL-40 levels. All of the baseline serum fibrosis marker levels were also significantly associated with histological fibrosis progression that developed in 70 (33%) of the 209 non-cirrhotic patients (p < 0.0001). However, baseline HA and platelet counts were best at predicting histological progression (AUC = 0.663). CONCLUSION Pretreatment serum fibrosis marker levels are significantly increased in CHC patients at risk of clinical and histological disease progression. If validated in additional cohorts, measurement of these markers could help identify CHC patients who would benefit from more frequent and intensive monitoring.

High prevalence of autoantibodies to C-reactive protein in patients with chronic hepatitis C infection: association with liver fibrosis and portal inflammation

“…Such candidate biomarker could not only aid in monitoring and staging of fibrosis, but also help understanding the underlying pathology driving the development of cirrhosis in viral hepatitis. Numerous serum biomarkers have been proposed to be associated with liver fibrosis with varying reliability [33]. This study, which comprises a limited number of well-characterized hepatitis C patients with longterm follow-up, was undertaken to evaluate 2 biomarkers and their potential associations with liver disease, autoimmunity, histopathology and treatment outcome.…”

Evolving therapies for liver fibrosis

“…Recent studies suggest that certain marker combinations such as the (indirect) Fibrotest (122) and the (direct) enhanced liver fibrosis (ELF) test can predict hard endpoints. Thus ELF was superior to fibrosis stage, the Child-Pugh or the Model for End-Stage Liver Disease (MELD) score, to predict hepatic decompensation or death in long-term, retrospective follow-up studies of patients with advanced chronic HCV or PBC (123)(124)(125).…”

Chitinase-Like Protein Brp-39/YKL-40 Modulates the Renal Response to Ischemic Injury and Predicts Delayed Allograft Function

“…[15][16][17] In many of these disorders, YKL-40 correlates with disease activity and its expression is believed to reflect distinct pathways in disease pathogenesis. [18][19][20] However, to date, the expression and biology of Brp-39/YKL-40 in the kidney, its roles in the pathogenesis of acute or other forms of kidney injury, and its utility as a biomarker for renal diseases have not been investigated.…”