An appraisal of the histopathological assessment of liver fibrosis

Academic Department of Histopathology, Royal Free and University College Medical School, London, UK.
Gut (Impact Factor: 14.66). 05/2006; 55(4):569-78. DOI: 10.1136/gut.2005.084475
Source: PubMed


One of the most important aspects of the histopathological assessment of liver biopsies in the setting of chronic liver disease is determination of the degree of fibrosis and architectural change. Most of the work in this regard has been concerned with chronic viral hepatitis. This article attempts to assess critically our current and historical biopsy practice, from subjective fibrosis scoring systems to biopsy sample size; and the appropriate use of the data that scoring systems generate in the research and clinical setting. An understanding of the limitations of each of the components of the fibrosis assessment process can help to devise appropriate protocols to ensure that the information obtained is optimised, and its degree of reliability appreciated. It is only from this starting point that recently promulgated antifibrotic medications and "non-invasive" liver fibrosis assessment techniques can be evaluated properly.

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    • "First identified in 1980s, the cause of the disease is still unknown [14]. Recent studies have suggested that progression to NASH may increase mortality risk [15], while fibrosis severity is a critical diagnostic tool for chronic liver disease [16] [17] and indicative of long-term liver complications and enhanced mortality risk [18] [19]. The molecular mechanisms driving NAFLD progression to NASH have remained elusive, though NAFLD patients presenting with any degree of systemic inflammation and any degree of fibrosis are thought to be at highest risk for NASH [15]. "
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    ABSTRACT: Nonalcoholic fatty liver disease (NAFLD) prevalence is increasing worldwide, with the affected US population estimated near 30%. Diet is a recognized risk factor in the NAFLD spectrum, which includes nonalcoholic steatohepatitis (NASH) and fibrosis. Low hepatic copper (Cu) was recently linked to clinical NAFLD/NASH severity. Simple sugar consumption including sucrose and fructose is implicated in NAFLD, while consumption of these macronutrients also decreases liver Cu levels. Though dietary sugar and low Cu are implicated in NAFLD, transcript-level responses that connect diet and pathology are not established. We have developed a mature rat model of NAFLD induced by dietary Cu deficiency, human-relevant high sucrose intake (30% w/w) or both factors in combination. Compared to the control diet with adequate Cu and 10% (w/w) sucrose, rats fed either high-sucrose or low-Cu diet had increased hepatic expression of genes involved in inflammation and fibrogenesis, including hepatic stellate cell activation, while the combination of diet factors also increased ATP citrate lyase and fatty acid synthase gene transcription (fold change >2, P<0.02). Low dietary Cu decreased hepatic and serum Cu (P≤0.05), promoted lipid peroxidation and induced NAFLD-like histopathology, while the combined factors also induced fasting hepatic insulin resistance and liver damage. Neither low Cu nor 30% sucrose in the diet led to enhanced weight gain. Taken together, transcript profiles, histological and biochemical data indicate that low Cu and high sucrose promote hepatic gene expression and physiological responses associated with NAFLD and NASH, even in the absence of obesity or severe steatosis. Copyright © 2015. Published by Elsevier Inc.
    The Journal of nutritional biochemistry 05/2015; 134(10). DOI:10.1016/j.jnutbio.2015.04.009 · 3.79 Impact Factor
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    • "A preliminary analysis of the method indicated that it achieves quantitative agreement with MRE in the assessment of severe fibrosis. In a larger test with DECT images collected from a cohort consisting of 12 patients the proposed algorithm yielded measures of fibrosis severity with statistically significant agreement with the Ishak fibrosis score [35] [36], which was assumed to be the gold standard. This result was observed across the full range of disease severities, and a longitudinal study showed that the method is highly repeatable. "
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    ABSTRACT: Assessing the severity of liver fibrosis has direct clinical implications for patient diagnosis and treatment. Liver biopsy, typically considered the gold standard, has limited clinical utility due to its invasiveness. Therefore, several imaging-based techniques for staging liver fibrosis have emerged, such as magnetic resonance elastography (MRE) and ultrasound elastography (USE), but they face challenges that include limited availability, high cost, poor patient compliance, low repeatability, and inaccuracy. Computed tomography (CT) can address many of these limitations, but is still hampered by inaccuracy in the presence of confounding factors, such as liver fat. Dual-energy CT (DECT), with its ability to discriminate between different tissue types, may offer a viable alternative to these methods. By combining the "multi-material decomposition" (MMD) algorithm with a biologically driven hypothesis we developed a method for assessing liver fibrosis from DECT images. On a twelve-patient cohort the method produced quantitative maps showing the spatial distribution of liver fibrosis, as well as a fibrosis score for each patient with statistically significant correlation with the severity of fibrosis across a wide range of disease severities. A preliminary comparison of the proposed algorithm against MRE showed good agreement between the two methods. Finally, the application of the algorithm to longitudinal DECT scans of the cohort produced highly repeatable results. We conclude that our algorithm can successfully stratify patients with liver fibrosis and can serve to supplement and augment current clinical practice and the role of DECT imaging in staging liver fibrosis.
    IEEE Transactions on Medical Imaging 08/2014; 34(3). DOI:10.1109/TMI.2014.2353044 · 3.39 Impact Factor
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    • "It has the capability of providing histopathological information on various morphological parameters that have been clinically validated for their pathophysiological relevance, but are not obtainable with non-invasive techniques [7] [8] such as liver stiffness measurements [9] and biochemical markers [10]. Currently, liver biopsy-based assessment remains the standard reference for monitoring therapeutic responses in both clinical research trials and actual practice [4] [11]. However, conventional histological staging of fibrosis in liver biopsy is semiquantitative and highly subjective to sampling error and observer variations, as it basically relies on a global assessment of architectural distortion and associated fibrosis. "
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    ABSTRACT: Background & Aims There is increasing need for accurate assessment of liver fibrosis/cirrhosis. We aimed to develop qFibrosis, a fully-automated assessment method combining quantification of histopathological architectural features, to address unmet needs in core biopsy evaluation of fibrosis in chronic hepatitis B (CHB) patients. Methods qFibrosis was established as a combined index based on 87 parameters of architectural features. Images acquired from 25 Thioacetamide-treated rat samples and 162 CHB core biopsies were used to train and test qFibrosis and to demonstrate its reproducibility. qFibrosis scoring was analyzed employing Metavir and Ishak fibrosis staging as standard references, and collagen proportionate area (CPA) measurement for comparison. Results qFibrosis faithfully and reliably recapitulates Metavir fibrosis scores, as it can identify differences between all stages in both animal samples (p < 0.001) and human biopsies (p < 0.05). It is robust to sampling size, allowing for discrimination of different stages in samples of different sizes (area under the curve (AUC): 0.93 - 0.99 for animal samples: 1 mm2 - 16 mm2; AUC: 0.84 - 0.97 for biopsies: 10 mm - 44 mm in length). qFibrosis can significantly predict staging underestimation in suboptimal biopsies (< 15 mm) and under- and over-scoring by different pathologists (p < 0.001). qFibrosis can also differentiate between Ishak stages 5 and 6 (AUC: 0.73, p = 0.008), suggesting the possibility of monitoring intra-stage cirrhosis changes. Best of all, qFibrosis demonstrates superior performance to CPA on all counts. Conclusions qFibrosis can improve fibrosis scoring accuracy and throughput, thus allowing for reproducible and reliable analysis of efficacies of anti-fibrotic therapies in clinical research and practice.
    Journal of Hepatology 08/2014; 61(2). DOI:10.1016/j.jhep.2014.02.015 · 11.34 Impact Factor
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