The Enhanced Liver Fibrosis test and FibroTest identified advanced liver fibrosis in patients with a history of excessive alcohol consumption with high diagnostic accuracy, according to recently published data.
“Alcoholic liver disease has higher mortality than liver disease of any other etiology and while abstinence improves survival, this effect is most pronounced in early stages,” Maja Thiele, PhD, from the Odense University Hospital of Southern Denmark, and colleagues wrote. “Consequently, there is an urgent need to strengthen detection of advanced fibrosis in primary care and improve community methods for screening people at high risk, as this will allow for timely alcohol rehabilitation and future antifibrotic therapies.”
The Enhanced Liver Fibrosis (ELF) test is a commercially available algorithm with a model that combines hyaluronic acid, the N-terminal pro-peptide of collagen type III and tissue inhibitor of metalloproteinase-1. The recommended cut-off value for ELF is 10.5.
To validate ELF as a diagnostic tool for advanced alcoholic liver fibrosis, the researchers enrolled 289 patients with a history of excessive alcohol use (>24 g/day for women and >36 g/day for men), including 128 patients from primary care and 161 patients from secondary care.
According to liver biopsy, eight primary care patients and 58 secondary care patients had advanced fibrosis. Twenty-eight percent of patients enrolled had steatohepatitis.
ELF diagnosed advanced fibrosis with excellent discriminatory accuracy and performed equally well in patients from primary care (AUROC = 0.89; 95% CI, 0.75-1) as those from secondary care (AUROC = 0.9; 95% CI, 0.85-0.95). ELF slightly overestimated the probably of advanced fibrosis in patients recruited from primary care, but the predictions fit the observed probabilities of advanced fibrosis better than other noninvasive markers.
The ELF cut-off value of 10.5 correctly diagnosed advanced fibrosis in 79% of patients and the absence of advanced fibrosis in 91%. The 10.5 cut-off ruled out advanced fibrosis with a negative predictive value of 98%, but could not affirm diagnosis of advanced fibrosis as the positive predictive value was 60%.
FibroTest performed better in intention-to-diagnose (AUROC = 0.94; 95% CI, 0.89-0.99) and per-protocol analyses (AUROC = 0.94; 95% CI, 0.89-0.99) among patients from primary care than intention-to-diagnose (AUROC = 0.83; 95% CI, 0.76-0.89) or per-protocol analyses in those from secondary care (AUROC = 0.86; 95% CI, 0.8-0.92). The recommended 0.58 cut-off ruled out advanced fibrosis in primary care patients with a negative predictive value of 97%.
ELF outperformed the aspartate aminotransferase-to-platelet-ratio index (APRI), age-platelet index (AP index), Fibrosis-4 index (FIB-4), Forns index, AST:ALT ratio and gamma-glutamyltransferase-to-platelet ratio (GPR). ELF did not outperform FibroTest and there was no added diagnostic value from combining ELF with FibroTest or a routine serum index.
Transient elastography and 2D-shear wave elastography diagnosed advanced fibrosis with higher accuracy than ELF and FibroTest in per-protocol analysis, but not in intention-to-diagnose analyses. Combined transient elastography and ELF did not increase diagnostic accuracy compared with transient elastography.
“The Enhanced Liver Fibrosis test and FibroTest are highly accurate serum markers to assess patients with a prior or current alcohol overuse for advanced fibrosis. While ultrasound elastography has higher diagnostic accuracy if a reliable measurement can be obtained, serum markers may be more accessible to primary and secondary care.” – by Talitha Bennett
Disclosure: The authors report relevant financial disclosures.