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      The therapeutic effect of silymarin in the treatment of nonalcoholic fatty disease : A meta-analysis (PRISMA) of randomized control trials

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          Abstract

          Supplemental Digital Content is available in the text

          Abstract

          Background:

          Silymarin (SIL) is an active extraction of the silybum marianum, milk thistle, which is an ancient medicinal plant for treatment of various liver diseases for centuries. This study is to assess the therapeutic effect of SIL in the treatment of nonalcoholic fatty liver disease through meta-analysis.

          Methods:

          Published randomized controlled trials (RCTs) were included from electronic databases (PubMed, Embase, Cochrane library, Web of Science, and so forth). Cochrane handbook was applied to evaluate the methodological quality. All statistical analyses were directed by Revman 5.3 software, and statistical significance was defined as P < .05.

          Results:

          Eight RCTs involved 587 patients were included in this study. The results showed that SIL reduced the AST and ALT levels more significantly than the control group (AST UI/L: MD = −6.57; 95% CI, −10.03 to −3.12; P = .0002; ALT UI/L: MD = −9.16; 95% CI, −16.24 to −2.08; P = .01). Compared with other interventions, there were significant differences decreasing AST and ALT levels when SIL was used alone (AST UI/L: MD = −5.44; 95% CI, −8.80 to −2.08; P = .002; ALT UI/L: MD = −5.08; 95% CI, −7.85 to −2.32; P = .0003).

          Conclusion:

          SIL has positive efficacy to reduce transaminases levels in NAFLD patients. SIL can be an encouraging and considerable phytotherapy for NAFLD patients.

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          Most cited references30

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          Alternative M2 activation of Kupffer cells by PPARdelta ameliorates obesity-induced insulin resistance.

          Macrophage infiltration and activation in metabolic tissues underlie obesity-induced insulin resistance and type 2 diabetes. While inflammatory activation of resident hepatic macrophages potentiates insulin resistance, the functions of alternatively activated Kupffer cells in metabolic disease remain unknown. Here we show that in response to the Th2 cytokine interleukin-4 (IL-4), peroxisome proliferator-activated receptor delta (PPARdelta) directs expression of the alternative phenotype in Kupffer cells and adipose tissue macrophages of lean mice. However, adoptive transfer of PPARdelta(-/-) (Ppard(-/-)) bone marrow into wild-type mice diminishes alternative activation of hepatic macrophages, causing hepatic dysfunction and systemic insulin resistance. Suppression of hepatic oxidative metabolism is recapitulated by treatment of primary hepatocytes with conditioned medium from PPARdelta(-/-) macrophages, indicating direct involvement of Kupffer cells in liver lipid metabolism. Taken together, these data suggest an unexpected beneficial role for alternatively activated Kupffer cells in metabolic syndrome and type 2 diabetes.
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            Hepatocellular carcinomas in patients with metabolic syndrome often develop without significant liver fibrosis: a pathological analysis.

            Metabolic syndrome (MS) is a newly identified risk factor in chronic liver disease (CLD) and hepatocellular carcinoma (HCC). The aim of this study was to analyze the pathological characteristics of HCC and nontumoral liver in patients with MS as the only risk factor for liver disease in comparison with those that developed in the course of other CLDs in order to provide further insight into the physiopathology of HCC associated with MS. HCC patients with features of MS as the only risk factor for liver diseases (MS group, n = 31) were compared to HCC patients with overt causes of CLD (CLD group, n = 81) or without causes of CLD (cryptogenic group, n = 16) who underwent surgical resection during the same period of time. Among the patients of the MS group, there were 30 males and 1 female. In comparison with the patients with HCC of the CLD group, the patients with MS were older (mean age: 67+/- 7 versus 59 +/- 14 years, P < 0.01), and the background liver was significantly more often free of significant fibrosis (F0-F2: 65% in the MS group versus 26% in the CLD group, P < 0.001). In addition, HCCs associated with MS were more often well differentiated (65% versus 28%, P < 0.001). Five HCCs, all from the MS group, developed on a preexisting liver cell adenoma, with three of them showing typical histological features of telangiectatic adenoma. This study shows that HCCs in patients with features of MS as the only risk factor for liver disease have distinct morphological characteristics and mainly occur in the absence of significant fibrosis in the background liver. In addition, some of them arise through malignant transformation of a preexisting liver cell adenoma.
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              Metformin reverses fatty liver disease in obese, leptin-deficient mice.

              There is no known treatment for fatty liver, a ubiquitous cause of chronic liver disease. However, because it is associated with hyperinsulinemia and insulin-resistance, insulin-sensitizing agents might be beneficial. To evaluate this possibility, insulin-resistant ob/ob mice with fatty livers were treated with metformin, an agent that improves hepatic insulin-resistance. Metformin improved fatty liver disease, reversing hepatomegaly, steatosis and aminotransferase abnormalities. The therapeutic mechanism likely involves inhibited hepatic expression of tumor necrosis factor (TNF) alpha and TNF-inducible factors that promote hepatic lipid accumulation and ATP depletion. These findings suggest a mechanism of action for metformin and identify novel therapeutic targets in insulin-resistant states.
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                Author and article information

                Journal
                Medicine (Baltimore)
                Medicine (Baltimore)
                MEDI
                Medicine
                Wolters Kluwer Health
                0025-7974
                1536-5964
                December 2017
                08 December 2017
                : 96
                : 49
                : e9061
                Affiliations
                [a ]Department of Neurosurgery, The First Hospital of Jilin University
                [b ]Clinical College, Jilin University
                [c ]Hepatopancreatobiliary Medicine Department, The First Hospital of Jilin University, Changchun
                [d ]Basic Medical College, Qiqihar Medical University, Qiqihar
                [e ]Department of Radiology, The First Hospital of Jilin University, Changchun, China.
                Author notes
                []Correspondence: Huimao Zhang, The First Hospital of Jilin University, Changchun, Jilin, China (e-mail: huimaozhang_jdyy@ 123456126.com ).
                Article
                MD-D-17-04904 09061
                10.1097/MD.0000000000009061
                5728929
                29245314
                60c82d59-3172-4451-9508-156d2eb06f17
                Copyright © 2017 the Author(s). Published by Wolters Kluwer Health, Inc.

                This is an open access article distributed under the Creative Commons Attribution License 4.0 (CCBY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. http://creativecommons.org/licenses/by/4.0

                History
                : 7 August 2017
                : 17 October 2017
                : 11 November 2017
                Categories
                4500
                Research Article
                Systematic Review and Meta-Analysis
                Custom metadata
                TRUE

                combination therapy,monotherapy,nonalcoholic fatty liver disease,pharmacological therapy,silymarin

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