Non invasive fibrosis biomarkers reduce but not substitute the need for liver biopsy

Sebastiani, Giada; Alberti, Alfredo

doi:10.3748/wjg.v12.i23.3682

Cited by 237 publications

(227 citation statements)

References 114 publications

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“…These tests are already widely used in routine clinical practice in France resulting in a significant decrease in the need for liver biopsy [127]. However, it is likely that non-invasive methods will reduce but not completely abolish the need for liver biopsy [28]. The most rational way of using these tools is to make a compromise: use non-invasive methods to classify those patients in whom they perform with high accuracy, limiting liver biopsy to the subset of patients in whom precise noninvasive staging is not possible.…”

Section: Resultsmentioning

confidence: 99%

“…The performances of ''direct'' and ''indirect'' serum markers have been evaluated in chronic hepatitis C (reviewed in [12,[28][29][30]), with hyaluronate being the most extensively studied. Apart from hyaluronate [14,15,31], ''direct'' and ''indirect'' markers, when used individually, are useful for the diagnosis or the exclusion of cirrhosis, but have limited accuracy for the diagnosis of significant fibrosis [32].…”

Section: Biological Approach: Serum Fibrosis Biomarkersmentioning

confidence: 99%

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Non-invasive assessment of liver fibrosis in chronic hepatitis C

Castéra

2011

Hepatol Int

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Section: Resultsmentioning

confidence: 99%

Section: Biological Approach: Serum Fibrosis Biomarkersmentioning

confidence: 99%

Non-invasive assessment of liver fibrosis in chronic hepatitis C

Castéra

2011

Hepatol Int

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“…Bioprinting is an efficient and reproducible means of establishing key architectural relationships between cells and preserving tissue-level functions over prolonged periods of time (Nguyen et al, 2016). The 3D nature and substantial biomass of the model enable histological assessment of treated liver tissues, which remains the diagnostic gold standard for the accurate detection and staging of fibrosis (Sebastiani and Alberti, 2006). The unique compartmentalized architecture of bioprinted tissues compared to other 3D models, such as spheroids (Leite et al, 2016), facilitates the temporal assessment of progression by revealing specific patterns of collagen deposition that are analogous to patterns described in human biopsy samples.…”

Section: Discussionmentioning

confidence: 99%

“…For complex disease processes such as fibrosis that lack early and informative biomarkers, histological assessment remains the gold standard for detecting and evaluating the progression of fibrotic injury (Barker et al, 2011;Sebastiani and Alberti, 2006). In order to assess the effects of compound treatment, a subset of tissues from each treatment group were examined histologically.…”

Section: Evidence Of Collagen Deposition In Tissues Treated With Fibrmentioning

confidence: 99%

Editor’s Highlight: Modeling Compound-Induced FibrogenesisIn VitroUsing Three-Dimensional Bioprinted Human Liver Tissues

et al. 2016

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Compound-induced liver injury leading to fibrosis remains a challenge for the development of an Adverse Outcome Pathway useful for human risk assessment. Latency to detection and lack of early, systematically detectable biomarkers make it difficult to characterize the dynamic and complex intercellular interactions that occur during progressive liver injury. Here, we demonstrate the utility of bioprinted tissue constructs comprising primary hepatocytes, hepatic stellate cells, and endothelial cells to model methotrexate-and thioacetamide-induced liver injury leading to fibrosis. Repeated, low-concentration exposure to these compounds enabled the detection and differentiation of multiple modes of liver injury, including hepatocellular damage, and progressive fibrogenesis characterized by the deposition and accumulation of fibrillar collagens in patterns analogous to those described in clinical samples obtained from patients with fibrotic liver injury. Transient cytokine production and upregulation of fibrosis-associated genes ACTA2 and COL1A1 mimics hallmark features of a classic wound-healing response. A surge in proinflammatory cytokines (eg, IL-8, IL-1b) during the early culture time period is followed by concentration-and treatment-dependent alterations in immunomodulatory and chemotactic cytokines such as IL-13, IL-6, and MCP-1. These combined data provide strong proof-of-concept that 3D bioprinted liver tissues can recapitulate drug-, chemical-, and TGF-b1-induced fibrogenesis at the cellular, molecular, and histological levels and underscore the value of the model for further exploration of compound-specific fibrogenic responses. This novel system will enable a more comprehensive characterization of key attributes unique to fibrogenic agents during the onset and progression of liver injury as well as mechanistic insights, thus improving compound risk assessment.Key words: liver fibrosis in vitro; 3D bioprinted liver; compound-induced liver injury.Chronic liver injury progressing to fibrosis and liver failure can result from a wide range of insults including drug or chemical exposure, metabolic disease, alcoholism, or viral infection, and is a major health burden worldwide with 2% of all deaths attributable to liver cirrhosis Murray et al., 2012). Whereas the major precipitating factors underlying drug-and chemicalinduced fibrosis have been gleaned from animal models, the key initiating and series of adaptive events that perpetuate this response, especially in humans, are still not well understood. Regardless of etiology, progressive fibrotic liver injury is

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“…Immunoglobulin G (IgG) -Recent studies have shown that immunoglobulins exert a direct effect on hepatic fibrogenesis and that IgGs stimulate the proliferation of HSCs (Sebastiani & Alberti 2006).…”

Section: Serum Type VI Collagenmentioning

confidence: 99%