Provided herein are methods of detecting and staging liver fibrosis in an individual with liver disease. Also provided are methods of detecting necroinflammatory activity. Invention methods utilize four serum markers, age, and gender to determine an end value. The end value is compared to a cut-off value, in order to identify significant fibrosis (METAVIR stages F2 to F4), or an absence of advanced fibrosis (stages F3 and F4) or cirrhosis (stage F4). In particular aspects, progression or treatment of liver fibrosis can be monitored by invention methods. The end value is also used to distinguish between no to mild necroinflammatory activity (METAVIR grade A0 to A1) and moderate to severe necroinflammatory activity (grade A2 to A3).