Medicine and Health Sciences
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)
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.
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.
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).
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.
Bonkovsky, Herbert L., "Serum Fibrosis Markers are Associated With Liver Disease Progression in Non-responder Patients With Chronic Hepatitis C" (2010). UCHC Articles - Research. 193.