Correlation of FIBROSpect II with histologic and morphometric evaluation of liver fibrosis in chronic hepatitis C

Division of Gastroenterology, Duke Clinical Research Institute, Duke University Medical Center, Durham, North Carolina 27705, USA.
Clinical gastroenterology and hepatology: the official clinical practice journal of the American Gastroenterological Association (Impact Factor: 6.53). 02/2008; 6(2):242-7. DOI: 10.1016/j.cgh.2007.11.009
Source: PubMed

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.

  • [Show abstract] [Hide abstract]
    ABSTRACT: Aims Staging for liver fibrosis is recommended in the management of hepatitis C as an argument for treatment priority. Our aim was to construct a noninvasive algorithm to predict the significant liver fibrosis (SLF) using common biochemical markers and compare it with some existing models. Methods The study group included 104 consecutive cases; SLF was defined as Ishak fibrosis stage greater than 2. The patient population was assigned randomly to the training and the validation groups of 52 cases each. The training group was used to construct the algorithm from parameters with the best predictive value. Each parameter was assigned a score that was added to the noninvasive fibrosis score (NFS). The accuracy of NFS in predicting SLF was tested in the validation group and compared with APRI, FIB4, and Forns models. Results Our algorithm used age, alkaline phosphatase, ferritin, APRI, alpha 2 macroglobulin, and insulin and the NFS ranged from -4 to 5. The probability of SLF was 2.6 versus 77.1% in NFS < 0 and NFS > 0, leaving NFS = 0 in a gray zone (29.8% of cases). The area under the receiver operating curve was 0.895 and 0.886, with a specificity, sensitivity, and diagnostic accuracy of 85.1, 92.3, and 87.5% versus 77.8, 100, and 87.9% for the training and the validation group. In comparison, the area under the receiver operating curve for APRI = 0.810, FIB4 = 0.781, and Forns = 0.703 with a diagnostic accuracy of 83.9, 72.3, and 62% and gray zone cases in 46.15, 37.5, and 44.2%. Conclusion We devised an algorithm to calculate the NFS to predict SLF with good accuracy, fewer cases in the gray zone, and a straightforward clinical interpretation. NFS could be used for the initial evaluation of the treatment priority. (C) 2014 Wolters Kluwer Health broken vertical bar Lippincott Williams & Wilkins.
    European Journal of Gastroenterology & Hepatology 10/2014; 26(10):1108-1115. DOI:10.1097/MEG.0000000000000182 · 2.15 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Chronic infection with hepatitis C virus (HCV) is a leading cause of liver-related morbidity and mortality worldwide and predisposes to liver fibrosis and end-stage liver complications. Liver fibrosis is the excessive accumulation of extracellular matrix proteins, including collagen, and is considered as a wound healing response to chronic liver injury. Its staging is critical for the management and prognosis of chronic hepatitis C (CHC) patients, whose number is expected to rise over the next decades, posing a major health care challenge. This review provides a brief update on HCV epidemiology, summarizes basic mechanistic concepts of HCV-dependent liver fibrogenesis, and discusses methods for assessment of liver fibrosis that are routinely used in clinical practice. Liver biopsy was until recently considered as the gold standard to diagnose and stage liver fibrosis. However, its invasiveness and drawbacks led to the development of non-invasive methods, which include serum biomarkers, transient elastography and combination algorithms. Clinical studies with CHC patients demonstrated that non-invasive methods are in most cases accurate for diagnosis and for monitoring liver disease complications. Moreover, they have a high prognostic value and are cost-effective. Non-invasive methods for assessment of liver fibrosis are gradually being incorporated into new guidelines and are becoming standard of care, which significantly reduces the need for liver biopsy.
    World Journal of Gastroenterology 08/2014; 20(32):11033-11053. DOI:10.3748/wjg.v20.i32.11033 · 2.43 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Assessment of liver fibrosis in chronic hepatitis C virus (HCV) infection is considered a relevant part of patient care and key for decision making. Although liver biopsy has been considered the gold standard for staging liver fibrosis, it is an invasive technique and subject to sampling errors and significant intra- and inter-observer variability. Over the last decade, several noninvasive markers were proposed for liver fibrosis diagnosis in chronic HCV infection, with variable performance. Besides the clear advantage of being noninvasive, a more objective interpretation of test results may overcome the mentioned intra- and inter-observer variability of liver biopsy. In addition, these tests can theoretically offer a more accurate view of fibrogenic events occurring in the entire liver with the advantage of providing frequent fibrosis evaluation without additional risk. However, in general, these tests show low accuracy in discriminating between intermediate stages of fibrosis and may be influenced by several hepatic and extra-hepatic conditions. These methods are either serum markers (usually combined in a mathematical model) or imaging modalities that can be used separately or combined in algorithms to improve accuracy. In this review we will discuss the different noninvasive methods that are currently available for the evaluation of liver fibrosis in chronic hepatitis C, their advantages, limitations and application in clinical practice.
    World Journal of Gastroenterology 03/2014; 20(11):2854-2866. DOI:10.3748/wjg.v20.i11.2854 · 2.43 Impact Factor