Correlation of FIBROSpect II with histologic and morphometric evaluation of liver fibrosis in chronic hepatitis C
ABSTRACT Accurate disease staging in chronic hepatitis C (CHC) infection helps guide treatment and may provide prognostic information. Liver biopsies are invasive, costly, and associated with morbidity. We hypothesized that a noninvasive test of liver fibrosis can accurately stage liver fibrosis. We prospectively evaluated the FIBROSpect II (FSII) biomarker panel versus pathology assessment and a quantitative measure of fibrosis.
Liver biopsy specimens and serum were obtained from 252 CHC patients, including 50 posttransplant, from 3 tertiary centers. Biopsy specimens were scored centrally and independently at each site, along with central quantification of fibrosis by digitized morphometry. Serum tests were performed blinded to clinical or histologic evaluation.
The mean biopsy specimen length was 1.95 +/- 0.87 cm; prevalence of stage F2 through F4 fibrosis was 77%. Agreement between central and site readings for individual stages was modest (k = 0.674), with concordant readings in 106 of 248 (43%) biopsy specimens. The area under the receiver operating characteristic curve for FSII and morphometry for stages F2 through F4 for concordant biopsy specimens were 0.823 and 0.728, respectively. Sensitivity and specificity for FSII were 83.5% and 66.7%, respectively, with an accuracy of 80.2%. The aspartate aminotransferase to platelet ratio index sensitivity and specificity for predicting F2 through F4 were 30.4% and 100%, respectively, the indeterminate rate was 40.4%, and the accuracy rate was 48.4%. The accuracy of FSII in concordant biopsy specimens in the posttransplant cohort was 73%.
Serum biomarkers can differentiate mild from moderate-to-severe fibrosis. This prospective study validates the performance characteristics of FSII in CHC patients and a posttransplant cohort. Assessing the diagnostic utility of biomarkers is limited by variability in methods to quantify fibrosis and poor interobserver agreement for histologic staging.
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ABSTRACT: Noninvasive or minimally invasive alternatives are proposed as substitutes for liver biopsy and include clinical indices, cross-sectional imaging, serum biomarkers, liver stiffness measurement, and portal pressure measurement. Most alternatives to liver biopsy assess one aspect of liver disease and translate this into a numeric score. Overlap between categories may limit applications. Liver biopsy provides information about numerous variables: tissue architectural changes; necroinflammatory injury; fibrotic stage; alterations of parenchyma and bile duct epithelium; accumulation of fat, copper, and iron; and molecular and genetic changes. Liver biopsy may identify multiple disease etiologies. A single numeric score cannot be a substitute for complete histologic assessment. However, within defined clinical contexts, noninvasive assessment is an attractive alternative for many patients given the ease, avoidance of risk from invasive procedures, and validated contribution to clinical management. Serum biomarkers and liver stiffness assessment may become indispensable in longitudinal studies and to document outcome of treatments. The accuracy of the more reliable techniques is typically around 80%. Neither liver biopsy nor any single alternative option represents an absolute assessment of liver disease. Biopsy and alternatives are not mutually exclusive options. Liver biopsy and the noninvasive alternatives require a clear understanding of significance and limitations of each investigation. This places a responsibility on the clinician to consider fully the results of any of the investigative options used within the diagnostic and prognostic context of each individual patient, and to choose critically the most appropriate investigations for the patient's needs.Clinical gastroenterology and hepatology: the official clinical practice journal of the American Gastroenterological Association 06/2008; 6(5):491-6. DOI:10.1016/j.cgh.2008.02.023 · 6.53 Impact Factor
- Gastroenterology and Hepatology 08/2008; 4(8):539-41.
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ABSTRACT: This review summarizes the methodological aspects of the interpretation of non-invasive biomarkers in liver fibrosis. A scoring system has been updated to better compare the quality of fibrosis biomarkers. Several methodological issues are related to the classical methodology using biopsy, as this is considered the gold standard. However, from evidence-based data, it appears that the methodology needs to change to prevent flawed conclusions among key opinion leaders as well as in obsolete guidelines. As waiting for the perfect biomarker for the diagnosis of advanced fibrosis to come along is probably a waste of time, in the meantime, methods can be improved. The main proposals for improving the methodology are, to take into account the spectrum bias, to assess accuracy between adjacent stages, to compare biomarkers in the same patient, to assess the cause of failure among discordant cases and to use specific statistical methods adapted for imperfect gold standards.Gastroentérologie Clinique et Biologique 09/2008; 32(6 Suppl 1):8-21. DOI:10.1016/S0399-8320(08)73990-3 · 1.14 Impact Factor