Nonalcoholic steatohepatitis (NASH) is a chronic
liver disease that can lead to
cirrhosis, liver transplant, and even
hepatocellular carcinoma. While liver biopsy remains the reference standard for disease diagnosis, analytical and clinical development of non-invasive soluble
biomarkers of NASH are of great importance to advance the field. To this end, we performed analytical and clinical validation on a series of pro-inflammatory
cytokines and
chemokines implicated hepatic
inflammation;
IL-6, CRP, TNFα, MCP-1, MIP-1β, eotaxin,
VCAM-1.
Biomarker assays were validated for accuracy and precision. Clinical performance was evaluated in a random sample of 52 patients with biopsy-proven
NAFLD/NASH. Patients were categorized into three groups according to their
fibrosis stage; advanced (F3-F4), mild (F1-2) and no (F0)
fibrosis. Serum
IL-6 was increased in patients with advanced
fibrosis (2.71 pg/mL; 1.26 pg/mL; 1.39 pg/mL p<0.01) compared to patients with mild or no
fibrosis respectively. While, there was no significant difference noted in CRP, TNFα, MCP-1, MIP-1β, eotaxin among the three groups,
VCAM-1 levels were increased by 55% (p<0.01) and 40% (p<0.05) in the advanced cohort compared to the mild and no
fibrosis groups respectively.
VCAM-1 also displayed good clinical performance as a
biomarker of advanced
fibrosis with an area under the receiver operating curve of 0.87. The
VCAM-1 assay demonstrated robust accuracy and precision, and
VCAM-1 outperformed
IL-6, CRP, TNFα, and the
chemokines MCP-1, MIP-1β, and eotaxin as a
biomarker of advanced
fibrosis in NASH. Addition of
biomarkers such as
IL-6 and
VCAM-1 to panels may yield increased sensitivity and specificity for staging of NASH.