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      Coffee Consumption and Risk of Biliary Tract Cancers and Liver Cancer: A Dose–Response Meta-Analysis of Prospective Cohort Studies

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          Abstract

          Background: A meta-analysis was conducted to summarize the evidence from prospective cohort and case-control studies regarding the association between coffee intake and biliary tract cancer (BTC) and liver cancer risk. Methods: Eligible studies were identified by searches of PubMed and EMBASE databases from the earliest available online indexing year to March 2017. The dose–response relationship was assessed by a restricted cubic spline model and multivariate random-effect meta-regression. A stratified and subgroup analysis by smoking status and hepatitis was performed to identify potential confounding factors. Results: We identified five studies on BTC risk and 13 on liver cancer risk eligible for meta-analysis. A linear dose–response meta-analysis did not show a significant association between coffee consumption and BTC risk. However, there was evidence of inverse correlation between coffee consumption and liver cancer risk. The association was consistent throughout the various potential confounding factors explored including smoking status, hepatitis, etc. Increasing coffee consumption by one cup per day was associated with a 15% reduction in liver cancer risk (RR 0.85; 95% CI 0.82 to 0.88). Conclusions: The findings suggest that increased coffee consumption is associated with decreased risk of liver cancer, but not BTC.

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          Chlorogenic acid reduces liver inflammation and fibrosis through inhibition of toll-like receptor 4 signaling pathway.

          Chlorogenic acid (CGA) is a type of polyphenol with anti-inflammatory, antioxidant activities. Our previous studies showed CGA could efficiently inhibit carbon tetrachloride (CCl(4))-induced liver fibrosis in rats. However, the specific underlying mechanism remains unclear. The aim of this study is to investigate the effects of CGA on liver inflammation and fibrosis induced by CCl(4) and whether they are related to inhibition of toll-like receptor 4 (TLR4) signaling pathway. Male Sprague-Dawley (SD) rats were administrated CCl(4) together with or without CGA for 8 weeks. Histopathological and biochemical analyses were carried out. The mRNA and protein expression levels of proinflammatory and profibrotic mediators were detected by RT-PCR and Western blot, respectively. The levels of serum proinflammatory cytokines were detected by ELISA. CGA significantly attenuated CCl(4)-induced liver damage and symptoms of liver fibrosis, accompanied by reduced serum transaminase levels, collagen I and α-smooth muscle actin (α-SMA) expression. As compared with the CCl(4)-treated group, the expression levels of TLR4, myeloid differentiation factor 88 (MyD88), inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) were reduced in the treatment group of CCl(4) and CGA, whereas bone morphogenetic protein and activin membrane-bound inhibitor (Bambi) expression was increased. CGA also suppressed CCl(4) induced nuclear factor-κB (NF-κB) activation. Moreover, the hepatic mRNA expression and serum levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interleukin-1β (IL-1β) were significantly increased in CCl(4)-treated rats and attenuated by co-treatment with CGA. Our data indicate that CGA can efficiently inhibit CCl(4)-induced liver fibrosis in rats and the protective effect may be due to the inhibition of TLR4/MyD88/NF-κB signaling pathway. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.
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            Coffee reduces liver damage in a rat model of steatohepatitis: the underlying mechanisms and the role of polyphenols and melanoidins.

            Epidemiological data associate coffee consumption with a lower prevalence of chronic liver disease and a reduced risk of elevated liver enzyme levels (γ glutamyl transpeptidase and alanine aminotransferase), advanced liver disease and its complications, and hepatocellular carcinoma. Knowledge of the mechanisms underlying these effects and the coffee components responsible for these properties is still lacking. In this study, 1.5 mL/day of decaffeinated coffee or its polyphenols or melanoidins (corresponding to approximately 2 cups of filtered coffee or 6 cups of espresso coffee for a 70-kg person) were added for 8 weeks to the drinking water of rats who were being fed a high-fat, high-calorie solid diet (HFD) for the previous 4 weeks. At week 12, HFD + water rats showed a clinical picture typical of advanced nonalcoholic steatohepatitis compared with control rats (normal diet + water). In comparison, HFD + coffee rats showed: (1) reduced hepatic fat and collagen, as well as reduced serum alanine aminotransferase and triglycerides; (2) a two-fold reduced/oxidized glutathione ratio in both serum and liver; (3) reduced serum malondialdehyde (lipid peroxidation) and increased ferric reducing antioxidant power (reducing activity); (4) reduced expression of tumor necrosis factor α (TNF-α), tissue transglutaminase, and transforming growth factor β and increased expression of adiponectin receptor and peroxisome proliferator-activated receptor α in liver tissue; and (5) reduced hepatic concentrations of proinflammatory TNF-α and interferon-γ and increased anti-inflammatory interleukin-4 and interleukin-10. Our data demonstrate that coffee consumption protects the liver from damage caused by a high-fat diet. This effect was mediated by a reduction in hepatic fat accumulation (through increased fatty acid β-oxidation); systemic and liver oxidative stress (through the glutathione system); liver inflammation (through modulation of genes); and expression and concentrations of proteins and cytokines related to inflammation.
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              Caffeic acid prevents acetaminophen-induced liver injury by activating the Keap1-Nrf2 antioxidative defense system.

              Acute liver failure induced by acetaminophen (APAP) overdose is the main cause of drug-induced liver injury (DILI). Caffeic acid (CA) is a phenolic compound from many natural products. This study aims to investigate the protective mechanism of CA in APAP-induced liver injury. The results of serum alanine/aspartate aminotransferases (ALT/AST), liver myeloperoxidase (MPO) activity, liver glutathione (GSH) and reactive oxygen species (ROS) levels demonstrated the protection of CA against APAP-induced liver injury. Liver histological observation provided further evidences of CA-induced protection. CA was found to reverse the APAP-induced decreased cell viability in human normal liver L-02 cells and HepG2 cells. CA also reduced the increased cellular ROS level induced by APAP in hepatocytes. The results of luciferase assay and Western-blot analysis showed that CA increased the transcriptional activation of nuclear factor erythroid 2-related factor 2 (Nrf2) in the presence of APAP. Nrf2 siRNA reduced the protection of CA against APAP-induced hepatotoxicity. CA also reversed the APAP-induced decreased mRNA and protein expression of heme oxygenase 1 (HO-1) and
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                Author and article information

                Journal
                Nutrients
                Nutrients
                nutrients
                Nutrients
                MDPI
                2072-6643
                28 August 2017
                September 2017
                : 9
                : 9
                : 950
                Affiliations
                [1 ]Department of Medical and Surgical Sciences and Advanced Technologies “G.F. Ingrassia”, University of Catania, 95124 Catania, Italy; marranz@ 123456unict.it
                [2 ]Department of Epidemiology and Population Studies, Jagiellonian University Medical College, 31-008 Krakow, Poland; agnieszka.micek@ 123456uj.edu.pl
                [3 ]Division of Gastroenterology, Ospedale di Acireale, Azienda Sanitaria Provinciale di Catania, 95024 Catania, Italy; federicosalomone@ 123456rocketmail.com
                [4 ]Department of Food and Drugs, University of Parma, 43121 Parma, Italy; daniele.delrio@ 123456unipr.it
                [5 ]NNEdPro Global Centre for Nutrition and Health (Affiliated with: Cambridge University Health Partners and the British Dietetic Association), St John’s Innovation Centre, Cambridge CB4 0WS, UK; sumantra.ray@ 123456mrc-ewl-hnr.cam.ac.uk
                [6 ]Medical Research Council (MRC) Human Nutrition Research Unit, Cambridge CB1 9NL, UK
                Author notes
                [* ]Correspondence: justyna.godos@ 123456student.uj.edu.pl ; Tel.: +39-095-378-2180
                Author information
                https://orcid.org/0000-0002-5809-5706
                https://orcid.org/0000-0001-5264-2935
                https://orcid.org/0000-0001-5394-1259
                Article
                nutrients-09-00950
                10.3390/nu9090950
                5622710
                28846640
                ce874c1d-0430-4063-8de1-7d1558d15f0b
                © 2017 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 20 July 2017
                : 24 August 2017
                Categories
                Article

                Nutrition & Dietetics
                coffee,caffeine,gallbladder cancer,biliary tract cancer,liver cancer,hepatitis,meta-analysis,dose–response

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