High-abundance proteins present in blood plasma make the detection of low-abundance proteins extremely difficult by proteomics technology. Hexapeptide combinatorial ligand libraries can be used to investigate the hidden proteome in depth. Here we describe how liver disease biomarkers can be successfully discovered in blood plasma by two main steps: preparative methods that reduce the dynamic range of protein concentration, and analytic methods that allow resolution of proteins. Thus, blood plasma from hepatitis B virus infected patients were treated with ProteoMiner™ enrichment kit and analyzed by two dimensional gel electrophoresis and mass spectrometry. This approach allowed us to identify plasma gelsolin as possible candidate biomarker for hepatitis B-associated liver cirrhosis.