Article

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

ABSTRACT

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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    • "SR and MT stainings highlight the collagenous component of liver fibrosis, whereas, according to Scheuer and Lefkowtich [1], Victoria blue or orcein staining is important to highlight the elastic fibers, usually absent in normal portal tracts. SR is the preferred staining to best quantify the liver fibrosis by recently introduced techniques, such as the computerassisted Digital Image Analysis (DIA) of liver collagen [2] [3]. Previous studies showed that the amount of liver collagen obtained with DIA is significantly correlated with semiquantitative evaluation of liver fibrosis, Hepatic Venous Pressure Gradient (HVPG), and clinical decompensation in HCVinfected post-LT patients [4] [5] suggesting a prognostic role of this tool in this setting. "
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    ABSTRACT: Background and Aim. The best staining to evaluate liver fibrosis in liver hepatitis is still a debated topic. This study aimed to compare Masson’s trichrome (MT), Sirius Red (SR), and orcein stainings in evaluating liver fibrosis in chronic HCV hepatitis (CHC) with semiquantitative and quantitative methods (Collagen Proportionate Area (CPA) by Digital Image Analysis (DIA)) and correlate them with transient elastography (TE). Methods. Liver stiffness evaluation of 111 consecutive patients with CHC was performed by TE. Semiquantitative staging by Metavir score system and CPA by DIA were assessed on liver biopsy stained with MT, SR, and orcein. Results. MT, SR, and orcein staining showed concordant results in 89.6% of cases in staging CHC, without significant difference in both semiquantitative and quantitative evaluations of fibrosis. TE values were concordant with orcein levels in 86.5% of the cases and with MT/RS in 77.5% ( P < 0.001 ). No significant correlation between the grade of necroinflammatory activity and TE values was found. Conclusion. In CHC, SR/MT and orcein stainings are almost concordant and when discordant, orcein staining is better related to TE values than MT/RS. This suggests that elastic fibers play a more important role than reticular or collagenous ones in determining stiffness values in CHC.
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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.
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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.
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