Anti-fibrotic treatments for chronic liver diseases: The present and the future

Odagiri, Naoshi; Matsubara, Tsutomu; Sato-Matsubara, Misako; Fujii, Hideki; Enomoto, Masaru; Kawada, Norifumi

doi:10.3350/cmh.2020.0187

Cited by 25 publications

(19 citation statements)

References 135 publications

(153 reference statements)

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“…In this regard, results from clinical trials substantiated the efficacy of prolonged antivirals treatment in the resolution of liver fibrosis [43,44]. Current understanding on key strategies for antifibrotic therapies lie with protection from liver cell death, modulation of immune response, modulation of HSC activation, and inhibition of collagen deposition/scar evolution [45–47]. Focusing on HSCs, induction of apoptosis/senescence and reversion of activated HSCs are the main strategies [19].…”

Section: Discussionmentioning

confidence: 99%

Stanniocalcin 1 is a serum biomarker and potential therapeutic target for HBV‐associated liver fibrosis

Chan

Hon

et al. 2022

The Journal of Pathology

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Stanniocalcin 1 (STC1), a secreted protein, is upregulated in human cancers including hepatocellular carcinoma (HCC). While most HCCs develop from chronic liver disease, which involves progressive parenchymal injury and fibrosis, the role of STC1 in this preneoplastic stage remains poorly understood. In this study we investigated the clinical relevance and functional significance of secreted STC1 in liver fibrosis. To this end, the STC1 level was determined in the serum samples of chronic hepatitis B patients and correlated with the degree of liver fibrosis. Diagnostic performance of STC1 was analysed by area under the receiver operating characteristic curve (AUROC), sensitivity, specificity, positive predictive value, and negative predictive value. The results were compared with other well-characterised serum biomarkers for liver fibrosis: Aspartate transaminase to Platelet Ratio Index (APRI) and Fibrosis-4 (FIB-4). The functional role of STC1 was interrogated by in vitro experiments using cell line models. Expression of fibrogenic markers was quantified by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blotting. Our results showed that the serum STC1 level in chronic hepatitis B patients was positively correlated with the degree of liver fibrosis and showed a stepwise increase in accordance with the severity of fibrosis. The AUROCs for detecting significant fibrosis (>9.0 kPa) and cirrhosis (>12.0 kPa) was 0.911 and 0.880, respectively. STC1 demonstrated a superior specificity and positive predictive value when compared to APRI and FIB-4. Consistent with this, STC1 was elevated in the liver tissues and sera of CCl 4 -treated mice showing marked liver fibrosis. In vitro, STC1 was secreted by the human hepatic stellate cell line LX2. Human recombinant STC1 (rhSTC1) induced expression of fibrogenic markers in LX2 cells. The profibrogenic phenotype conferred by rhSTC1 or TGF-β1 in LX2 cells could be attenuated using anti-STC1 antibody. Taken together, STC1 is a specific serum biomarker for HBV-associated liver fibrosis. STC1 functionally promotes liver fibrogenesis and is a potential actionable target.

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Section: Discussionmentioning

confidence: 99%

Stanniocalcin 1 is a serum biomarker and potential therapeutic target for HBV‐associated liver fibrosis

Chan

Hon

et al. 2022

The Journal of Pathology

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“…Liver fibrosis is also the damage and inflammation in the liver caused by various pathogenic factors, resulting in extensive hyperplasia and deposition of fibrotic tissue, which is the common pathological basis of various chronic liver diseases. Hepatocyte cell death can trigger capillarization of liver sinusoidal endothelial cells, stimulation of immune cells (including macrophages and Kupffer cells), and activation of HSCs, leading to the progression of liver fibrosis ( Odagiri et al, 2021 ). Furthermore, activated HSCs are the key effectors of fibrogenesis through increased deposition of fibrillar ECM and by releasing cytokines, chemokines, and other mediators, together with inflammatory cells, establishing a pro-fibrogenic environment that negatively affects the regeneration of the liver parenchyma ( Friedman and Pinzani, 2022 ).…”

Section: Discussionmentioning

confidence: 99%

Treatment of Liver Fibrosis: A 20-Year Bibliometric and Knowledge-Map Analysis

2022

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Objectives: To analyze the research hotspots, evolution, and trends of the treatment of liver fibrosis in the recent 20 years, bibliometric and knowledge-map analysis were used.Methods: Publications associated with the treatment of liver fibrosis were retrieved from the Web of Science Core Collection on 16 April 2022. CiteSpace 5.8.R3 and VOSviewer 1.6.18 were calculated to perform bibliometric and knowledge-map analysis.Results: A total of 72,686 authors from 200 institutions in 134 countries/regions published 15,237 studies in different academic journals. United States was the most productive country, and Shanghai Jiao Tong University was the most published institution. Trauner Michael had the most published articles, whereas Scott L. Friedman was the most frequently co-cited author. Moreover, there was frequent inter-institution cooperation between countries in the years 2015 and after, but the before years showed rare inter-institution cooperation. The journal HEPATOLOGY was both the most published publication and the most frequently co-cited one in this field. Screened keywords, such as virus infection, inflammation, oxidative stress, activation of hepatic stellate cell (HSC), and hepatocellular apoptosis, could be both therapeutic targets and pathological mechanisms in terms of liver fibrosis. Furthermore, long-term suppression of hepatitis B virus replication and the activation of HSC were the latest hotspots and topics related to the treatment of liver fibrosis. Besides, the treatments of nonalcoholic fatty liver disease and nonalcoholic steatohepatitis were also involved in the treatment of liver fibrosis, which were both emerging topics and rapidly developing hot fields.Conclusion: This bibliometric analysis conducted a full overview of the treatment of liver fibrosis, which provided important clues and ideas for scholars focusing on this field. Not only that, the field is still in a stage of rapid development and will continue to be a research hotspot in the future.

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“…It is being investigated in several fibrotic disorders including Primary Biliary Cholangitis (PBC), NASH, Idiopathic Pulmonary Fibrosis (IPF), Diabetic Kidney Disease (DKD), Systemic Sclerosis (SSc), as well as in Head and Neck cancer. Aoyama et al, reported that GKT137831 showed significant improvement of liver fibrosis by suppressing ROS production, via NADPH inhibition, and fibrotic gene expression in mice induced by carbon tetrachloride (CCL4) and duct ligation [ 79 , 80 ]. In a phase 2 clinical trial for patients with PBC (NCT03226067), GKT137831 showed significant effects on serological cholestasis parameters [ 78 , 79 , 81 ].…”

Section: Innovative Approaches To Target Macrophagesmentioning

confidence: 99%

The Role of Macrophages in Liver Fibrosis: New Therapeutic Opportunities

Binatti

Gerussi

Barisani

et al. 2022

IJMS

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Chronic inflammation is the hallmark of fibrotic disorders and is characterized by the activation of immune cells in the damaged tissues. Macrophages have emerged as central players in the fibrotic process since they initiate, sustain and amplify the inflammatory reaction. As regards the liver, distinct populations of phagocytic cells, like Kupffer cells and monocyte-derived macrophages, are indisputably key cells implicated in the pathogenesis of several chronic liver diseases. In this review, we summarize the current knowledge on the origin, role and functions of macrophages in fibrotic conditions, with a specific focus on liver fibrosis; then, we discuss some innovative therapeutic strategies targeting macrophages in fibrotic liver diseases.

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Anti-fibrotic treatments for chronic liver diseases: The present and the future

Cited by 25 publications

References 135 publications

Stanniocalcin 1 is a serum biomarker and potential therapeutic target for HBV‐associated liver fibrosis

Stanniocalcin 1 is a serum biomarker and potential therapeutic target for HBV‐associated liver fibrosis

Treatment of Liver Fibrosis: A 20-Year Bibliometric and Knowledge-Map Analysis

The Role of Macrophages in Liver Fibrosis: New Therapeutic Opportunities

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