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)
Summary Chronic allograft nephropathy characterized by interstitial fibrosis and tubular atrophy is a major cause of renal transplant failure. Acoustic radiation force impulse (ARFI) quantification is a promising noninvasive method for assessing tissue stiffness. We evaluated if the method could reveal renal transplant fibrosis. In a prospective study, 30 adult renal transplant recipients were included. ARFI quantification, given as shear wave velocity (SWV), of the renal cortex was performed by two observers. SWV was compared to grade of fibrosis (0–3) in biopsies. The median SWV was 2.8 m/s (range: 1.6–3.6), 2.6 m/s (range: 1.8–3.5) and 2.5 m/s (range: 1.6–3) for grade 0 (n = 12), 1 (n = 10) and grades 2/3 (n = 8) fibrosis respectively. SWV did not differ significantly in transplants without and with fibrosis (grade 0 vs. grade 1, P = 0.53 and grade 0 vs. grades 2/3, P = 0.11). The mean intraobserver coefficient of variation was 22% for observer 1 and 24% for observer 2. Interobserver agreement, expressed as intraclass correlation coefficient was 0.31 (95% CI: −0.03 to 0.60). This study does not support the use of ARFI quantification to assess low‐grade fibrosis in renal transplants. ARFI quantification in its present stage of development has also high intra‐ and interobserver variation in renal transplants.
• Acoustic radiation force impulses (ARFI) can quantify tissue elasticity during ultrasound examinations. • Elasticity estimated by ARFI in kidney transplants depends on applied transducer force. • ARFI quantification cannot detect renal allograft fibrosis. • ARFI elasticity estimates may in general vary with applied transducer force.
Adrenal cortical carcinoma is a rare and highly malignant tumor. This retrospective study includes 99 patients (57 males and 42 females) reported to The Cancer Registry of Norway during the 15 year period from 1970 to 1984. The age adjusted incidence was 1.5 per million per year. Eighty-one patients were diagnosed with adrenal cortical carcinoma when still alive. In 18 cases the diagnosis was first made at autopsy. Median age at diagnosis was 54 years (range 2-88 years) with a slight male predominance. Information about initial symptoms was available in 67 patients, of whom 26 patients (18 females and 8 males) presented with clinically functioning tumors, the Cushing syndrome and virilization being most frequently encountered. Only 28 (35%) of 81 patients diagnosed when still alive had tumors confined to the adrenals. Half of the patients had distant metastases, with lungs and liver being the most frequent sites. Sixty-one patients underwent surgery; 51 patients had a radical or debulking operation and 10 patients had laparotomy with tumor biopsy. After a complete follow-up for at least 6 years (range 6-21 years), only 9 patients were still alive. Early stage (Stage I and II) and curative resection had a significant impact on the outcome of this disease. To improve prognosis, early diagnosis and radical surgery, if feasible, are needed.
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