Enhanced liver fibrosis score predicts transplant‐free survival in primary sclerosing cholangitis

Abstract

There is a need to determine biomarkers reflecting disease activity and prognosis in primary sclerosing cholangitis (PSC). We evaluated the prognostic utility of the enhanced liver fibrosis (ELF) score in Norwegian PSC patients. Serum samples were available from 305 well-characterized large-duct PSC patients, 96 ulcerative colitis patients, and 100 healthy controls. The PSC patients constituted a derivation panel (recruited 1992-2006 [n 5 167]; median age 41 years, 74% male) and a validation panel (recruited 2008-2012 [n 5 138]; median age 40 years, 78% male). We used commercial kits to analyze serum levels of hyaluronic acid, tissue inhibitor of metalloproteinases-1, and propeptide of type III procollagen and calculated ELF scores by the previously published algorithm. Results were also validated by analysis of ELF tests using the ADVIA Centaur XP system and its commercially available reagents. We found that PSC patients stratified by ELF score tertiles exhibited significantly different transplant-free survival in both panels (P < 0.001), with higher scores associated with shorter survival, which was confirmed in the validation panel stratified by ELF test tertiles (P 5 0.003). The ELF test distinguished between mild and severe disease defined by clinical outcome (transplantation or death) with an area under the curve of 0.81 (95% confidence interval [CI] 0.73-0.87) and optimal cutoff of 10.6 (sensitivity 70.2%, specificity 79.1%). In multivariate Cox regression analysis in both panels, ELF score (hazard ratio 5 1.9, 95% CI 1.4-2.5, and 1.5, 95% CI 1.1-2.1, respectively) was associated with transplant-free survival independently of the Mayo risk score (hazard ratio 5 1.3, 95% CI 1.1-1.6, and 1.6, 95% CI 1.2-2.1, respectively). The ELF test correlated with ultrasound elastography in separate assessments. Conclusion: The ELF score is a potent prognostic marker in PSC, independent of the Mayo risk score. (HEPATOLOGY 2015;62:188-197)

Enhanced liver fibrosis test predicts transplant‐free survival in primary sclerosing cholangitis, a multi‐centre study

“…Although the difference between these three groups was statistically significant, when comparing the Kaplan-Meier curves of the present study with the original results, a diminished ability to distinguish mild from moderate disease was suggested. [17] This may in part be due to the use of thresholds proposed by the manufacturer, that were not originally developed to differentiate mild, moderate and severe disease in a biliary disease with a porto-portal fibrosis pattern like PSC. However, the manufacturer's optimal cut-off to discriminate between patients with and without severe fibrosis (9.8) was similar to the optimal cut-off value to discriminate between patients that do and do not reach an endpoint as estimated by the Youden's index in our study population (9.85), therefore this seems to be a robust cut-off level to identify high-risk patients.…”

“…[12][13][14][15][16] Recently, the prognostic value of the ELF test in PSC was assessed in a large single center study from Norway including two independent PSC cohorts. [17] It was demonstrated that ELF test consistently predicted liver transplant-free survival in PSC patients independently of other risk factors or risk scores. [17] In the present study, we aimed to validate the prognostic value of the ELF test in a large, multicenter PSC cohort.…”

“…[17] It was demonstrated that ELF test consistently predicted liver transplant-free survival in PSC patients independently of other risk factors or risk scores. [17] In the present study, we aimed to validate the prognostic value of the ELF test in a large, multicenter PSC cohort. Rates of transplant-free survival were estimated for three groups of fibrosis severity: mild, moderate and severe fibrosis defined as ELF test level <7.7, ≥7.7 to <9.8, and ≥9.8, respectively, as recommended by the manufacturer; crude risk was compared using log-rank test.…”

Biomarkers of intestinal fibrosis – one step towards clinical trials for stricturing inflammatory bowel disease

“…Additionally, ELF test was identified as a prognostic marker in a cohort of patients with primary sclerosing cholangitis, most of whom were affected by IBD. 26 Laminin, which is a component of basement membrane, is higher in the serum of Crohn's disease patients than in controls and it is associated with disease activity but not with the stricturing behaviour. 27 Fibronectin, a high-molecular weight ECM glycoprotein, is increased in the plasma of patients with stricturing Crohn's disease.…”

Advances in the diagnosis and treatment of liver fibrosis

“…[94] ELF score can be used to assess transplant-free survival of the patients with primary sclerosing cholangitis, [95] HCV/HIV co-infected women [96] and the prognosis if patients with different chronic liver diseases.…”