Serum biomarkers
Many serum biomarkers and biomarker panels have been studied for the assessment of fibrosis and diagnosis of cirrhosis. Overall, these markers are good indicators of the presence or absence of fibrosis (F0 or F>0), or the presence of cirrhosis (F4 or F<4). However, their use in distinguishing between fibrosis stages, or the rate of fibrosis progression has not been well established. Similarly, the prognostic value of many serum biomarkers has not been studied.
These biomarkers can be divided into two broad categories – direct and indirect. Indirect biomarkers reflect liver function, which may decline with the onset of cirrhosis. Direct biomarkers, on the other hand, reflect extracellular matrix turnover, and include many molecules involved in hepatic fibrogenesis.
Indirect markers
APRI
AST-Platelet Ratio Index (APRI= (AST/upper limit of normal)*100/platelet count) is a simple and easily available biomarker panel for the estimation of fibrosis. APRI values increase as fibrosis-induced portal hypertension results in a decline in platelet count.
APRI has been extensively validated in chronic hepatitis C [23723714]. In a meta-analysis of 18 studies, APRI>2 had a specificity of 94% for the diagnosis of cirrhosis (sensitivity 48%), with a pooled AUROC of 0.84 across 40 studies. APRI greater than 0.5 was found to have a sensitivity of 81% and specificity of 55% (AUROC 0.77) for the diagnosis of fibrosis (n=28 studies).
APRI has also been studied in non-alcoholic fatty liver disease (NAFLD) [23278163]. In a systematic review of 242 NAFLD patients, an APRI cutoff of 0.54 was found to have an AUROC of 0.75 (Sensitivity 77.3%, Specificity 70.9%).
The use of APRI is not as well validated in other etiologies. In a stud...
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...0.70, lower than other serum markers such as HA and Fibrospect.
ELF
The European Liver Fibrosis (ELF) score was developed in a cohort of 1021 patients with chronic liver disease [15578508]. It combined age, HA, TIMP1 and P3NP. The model predicts cirrhosis with an AUROC of 0.89 (sensitivity 90%, specificity 69%). The AUROC of ELF was particularly high in patients with ALD or NAFLD (0.87-0.94). This was validated in a further study using a modified ELF (without age), with an AUROC of 0.90 for severe fibrosis in NAFLD patients [18038452, 18992746].
The ELF score has been validated in both CHB and CHC, with AUROC values of 0.85 (CHC) and 0.86 (CHB) for severe fibrosis (>F3) [20196799, 22848675]. In patients with CHB, ELF performed as well as LSM for prediction of significant fibrosis (>F2), although LSM was superior for prediction of severe fibrosis [22848675].
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