Current Status of Non-invasive Alternatives to Liver Biopsy to Assess Hepatic Fibrosis

• The extent of hepatic fibrosis in patients with chronic liver disease is associated with the risk of hepatic morbidity and mortality via the development of portal hypertension and liver cancer. • Ideal features of a non-invasive test of hepatic fibrosis include simplicity, reproducibility, accuracy, association with disease severity, improvement with therapy, association with clinical outcomes in untreated patients, and widespread availability and cost. • Liver elastography using ultrasound and magnetic resonance based modalities offers great promise in providing accurate and reliable information in patients with moderate to severe hepatic fibrosis as well as potentially clinically useful prognostic information. • Panels of routine laboratory tests such as APRI and FIB-4 are simple and widely available indices to estimate the likelihood of advanced fibrosis but they are not liver disease specific, have limited discrimination for milder degrees of fibrosis and their prognostic utility is not well established. • Serum fibrosis marker panels consisting of PIIINP, hyaluronic acid, and TIMP-1 more directly reflect hepatic fibrogenesis and matrix turnover but have largely been tested in patients with viral hepatitis. Additional testing in prospective cohorts and patients with alcoholic liver disease and NAFLD are needed for further validation and refinement. • Liver specific physiologic tests based upon hepatic enzyme activity (methacetin breath test), kupfer cell mass (liver-spleen scan ratio), intra-hepatic shunting (cholate shunt), proteomics, and genomics may also provide important information but require further development.