Document Type

Article

Disciplines

Medicine and Health Sciences

Abstract

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.

Comments

Gut. Author manuscript; available in PMC 2013 August 10. Published in final edited form as: Gut. 2010 October; 59(10): 1401–1409. Published online 2010 July 30. doi: 10.1136/gut.2010.207423 PMCID: PMC3740000 NIHMSID: NIHMS487633

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