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      Transjugular intrahepatic portosystemic shunt for the treatment of hepatic sinusoidal obstruction syndrome caused by pyrrolizidine alkaloids: A multicenter retrospective study

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          Abstract

          Purpose

          To assess the impact of transjugular intrahepatic portosystemic shunt (TIPS) on clinical outcomes and liver histology in patients with hepatic sinusoidal obstruction syndrome (HSOS) caused by pyrrolizidine alkaloids (PA), and compare these results with those of patients who received supportive treatment alone.

          Materials and methods

          From June 2015 to August 2022, 164 patients diagnosed with PA-HSOS in six tertiary care centers were retrospectively included in this study and divided into TIPS group (n = 69) and supportive treatment (ST) group (n = 95). The main endpoint was to determine whether TIPS placement could improve survival in PA-HSOS patients. The clinical symptoms associated with portal hypertension were also evaluated in this study. Additionally, a small TIPS-subgroup of 7 patients received liver biopsies before and after TIPS for histological analysis.

          Results

          The incidence of death was markedly lower in the TIPS group than in the ST group (log-rank p = 0.026). Multivariate Cox model revealed that group assignment (hazard ratio (HR) 5.146; 95 % confidence interval (CI) 1.587–16.687; p = 0.006), total bilirubin (HR 1.029; 95 % CI 1.020–1.038; p < 0.001), and INR (HR 13.291; 95 % CI 3.637–48.566; p < 0.001) were independent predictors for mortality. In addition, TIPS placement reduced the risk of complications associated with portal hypertension but did not increase the rate of overt hepatic encephalopathy (log-rank p = 0.731). Furthermore, six of 7 TIPS patients receiving liver biopsies improved after TIPS placement, and one patient developed fibrosis.

          Conclusions

          TIPS placement decreased the mortality and risk of complications associated with portal hypertension. Histological evaluation in a few patients showed a potential improvement by TIPS.

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          Most cited references25

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          Molecular and cellular mechanisms of liver fibrosis and its regression

          Chronic liver injury leads to liver inflammation and fibrosis, through which activated myofibroblasts in the liver secrete extracellular matrix proteins that generate the fibrous scar. The primary source of these myofibroblasts are the resident hepatic stellate cells. Clinical and experimental liver fibrosis regresses when the causative agent is removed, which is associated with the elimination of these activated myofibroblasts and resorption of the fibrous scar. Understanding the mechanisms of liver fibrosis regression could identify new therapeutic targets to treat liver fibrosis. This Review summarizes studies of the molecular mechanisms underlying the reversibility of liver fibrosis, including apoptosis and the inactivation of hepatic stellate cells, the crosstalk between the liver and the systems that orchestrate the recruitment of bone marrow-derived macrophages (and other inflammatory cells) driving fibrosis resolution, and the interactions between various cell types that lead to the intracellular signalling that induces fibrosis or its regression. We also discuss strategies to target hepatic myofibroblasts (for example, via apoptosis or inactivation) and the myeloid cells that degrade the matrix (for example, via their recruitment to fibrotic liver) to facilitate fibrosis resolution and liver regeneration.
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            Hepatic stellate cells as key target in liver fibrosis.

            Progressive liver fibrosis, induced by chronic viral and metabolic disorders, leads to more than one million deaths annually via development of cirrhosis, although no antifibrotic therapy has been approved to date. Transdifferentiation (or "activation") of hepatic stellate cells is the major cellular source of matrix protein-secreting myofibroblasts, the major driver of liver fibrogenesis. Paracrine signals from injured epithelial cells, fibrotic tissue microenvironment, immune and systemic metabolic dysregulation, enteric dysbiosis, and hepatitis viral products can directly or indirectly induce stellate cell activation. Dysregulated intracellular signaling, epigenetic changes, and cellular stress response represent candidate targets to deactivate stellate cells by inducing reversion to inactivated state, cellular senescence, apoptosis, and/or clearance by immune cells. Cell type- and target-specific pharmacological intervention to therapeutically induce the deactivation will enable more effective and less toxic precision antifibrotic therapies.
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              EASL Clinical Practice Guidelines: Vascular diseases of the liver.

              (2016)
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                Author and article information

                Contributors
                Journal
                Heliyon
                Heliyon
                Heliyon
                Elsevier
                2405-8440
                08 December 2023
                15 January 2024
                08 December 2023
                : 10
                : 1
                : e23455
                Affiliations
                [a ]Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
                [b ]Hubei Province Key Laboratory of Molecular Imaging, Wuhan, 430022, China
                [c ]Department of Vascular and Interventional Radiology, Nanfang Hospital, Southern Medical University, Guangzhou, 510000, China
                [d ]Department of Interventional Radiology, The First Affiliated Hospital of Soochow University, Suzhou, 215000, China
                [e ]Department of Interventional Radiology, The First Affiliated Hospital of Henan University of Science and Technology, Luoyang, 471000, China
                [f ]Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhejiang University, Hangzhou, 310000, China
                [g ]Department of Interventional Radiology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510000, China
                Author notes
                []Corresponding author. Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Jiefang Avenue #1277, Wuhan 430022, China. And Department of Interventional Radiology, The First Affiliated Hospital of Guangzhou Medical University, Jiangxi Avenue #151, Guangzhou, 510000, China. herr_xiong@ 123456126.com
                [1]

                These authors contributed equally to this paper.

                Article
                S2405-8440(23)10663-3 e23455
                10.1016/j.heliyon.2023.e23455
                10755310
                945f47ac-0ac6-4289-bee5-13ad6746b9ec
                © 2023 The Authors

                This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

                History
                : 12 May 2023
                : 4 December 2023
                : 4 December 2023
                Categories
                Research Article

                transjugular intrahepatic portosystemic shunt,hepatic sinusoidal obstruction syndrome,pyrrolizidine alkaloids,multicenter

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