Assessment of liver fibrosis using serum markers

Serum markers of liver fibrosis include direct markers, which are components of the fibrotic process, and indirect markers, which have no role in fibrosis but are correlated with the presence of liver fibrosis. To improve diagnostic performance, direct and indirect markers have been combined with other relevant parameters (eg age, BMI) into clinically useful tests—see examples in Examples of noninvasive tests for liver fibrosis using serum markers. Some are freely available while others are proprietary.

The advantages of using serum markers are that they have a low failure rate (compared with liver stiffness tests), produce reproducible results, and in the case of nonproprietary tests, are low cost. The limitations of serum markers are that they may be influenced by factors such as extrahepatic fibrogenesis or inflammation, thrombocytopenia not related to the liver, haemolysis and Gilbert syndrome. Use of proprietary tests may be costly.

In the diagnosis of cirrhosis, serum markers of fibrosis are generally outperformed by liver stiffness measurement.

Table 1. Examples of noninvasive tests for liver fibrosis using serum markers
Test	Test components	Uses
Tests that use indirect markers [NB1]
AST to Platelet Ratio Index (APRI) [URL]	AST, platelets	stratify risk of cirrhosis
Fibrosis-4 (FIB-4) Index [URL]	age, AST, ALT, platelets	stratify risk of advanced fibrosis
NAFLD Fibrosis Score (NFS) [URL]	age, BMI, impaired fasting glucose status, AST, ALT, platelets, albumin	stratify risk of advanced fibrosis in NAFLD
Tests that use both direct and indirect markers [NB2]
Enhanced Liver Fibrosis (ELF)	hyaluronate, procollagen III N-terminal-peptide, tissue inhibitor of metalloproteinase-1	stratify risk of advanced fibrosis or cirrhosis
Hepascore	alpha-2-macroglobulin, bilirubin, GGT, hyaluronate, age, sex	stratify risk of advanced fibrosis or cirrhosis
Note: ALT = alanine aminotransferase; AST = aspartate aminotransferase; BMI = body mass index; GGT = gamma glutamyltransferase; NAFLD = nonalcoholic fatty liver disease NB1: Calculators for tests that use indirect markers are available on various websites including MD+CALC [URL], Hepatitis C Online (University of Washington) [URL] and GIHEP (Indiana University) [URL]. NB2: The tests that use both direct and indirect markers are proprietary and may be costly.