Application of Novel Organ-Specific Serum Protein Biomarker Candidates to Diagnose Hepatic Fibrosis in Hepatitis C Patients in HALT-C Trial

Investigators:

Investigators: Anna S. Lok, MD, Leroy Hood, MD

Hypotheses/Aims

Hypotheses Organ-specific proteins can be detected in the circulation and can be used to monitor disease-specific changes in the primary organ affected, namely liver for hepatic fibrosis and its progression.

Background The ISB investigators have utilized findings from highly sensitive transcriptomic analyses with massively parallel signature sequencing and next-generation high throughput sequencing and from proteomics analyses (multiple reaction monitoring (MRM); unique N-glycopeptides) to identify liver-specific protein biomarker candidates detectable in plasma.

Specific Aim 1, Pilot Phase Use panels of liver-specific protein biomarker candidates in high-throughput format with HALT-C specimens in a preliminary study to determine whether these markers can distinguish patients with cirrhosis from those with fibrosis. Liver biopsy specimens and serum specimens collected at the same time from such patients will be tested to relate protein changes in liver to homologous protein changes in serum.

Specific Aim 2 Validate serum biomarker findings from Aim 1 in a larger number of HALT-C specimens (independent of those used in Aim 1) to evaluate usefulness of this panel in identifying patients with cirrhosis and in predicting which patients will have disease progression.