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      Causes of Thickening of Carotid Intima-Media Thickness in Patients With Alcoholic Liver Disease : A Prospective Observational Study

      research-article
      , MSc, , MSc, , MSc, , MSc, , BSc, , BSc, , BSc, , MSc, , BSc, , BSc
      Medicine
      Wolters Kluwer Health

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          Abstract

          Several studies have reported the relationship between alcoholic liver disease (ALD) and carotid intima-media thickness (CIMT). Few studies, however, have investigated the causes of CIMT thickening in patients with ALD. The authors explored the causes of CIMT thickening in patients with ALD.

          The authors enrolled 152 patients who were stratified into groups: nonthickening CIMT with ALD (group A); thickening CIMT with ALD (group B); nonthickening CIMT without ALD (group C); and thickening CIMT without ALD (group D).

          The CIMT was significantly different between patients with and without ALD (χ 2 = 3.875, P = 0.049). The patients in groups A, B, and C were significantly younger than group D ( P = 0.001, 0.036, and 0.001, respectively). The body mass indexes (BMI) in groups A and B were significantly higher than in group C ( P = 0.000 and 0.007, respectively). The blood glucose levels in groups B and D were significantly higher than in group C ( P = 0.016 and 0.018, respectively). The blood uric acid levels in group B were significantly higher than in groups A, C, and D ( P = 0.009, 0.000, and 0.003, respectively). The blood uric acid in group A was significantly higher than in group C ( P = 0.002). The serum total cholesterol (TC) levels of patients in group B were significantly higher than in groups A and C ( P = 0.027 and 0.000, respectively) and the serum TC level in group A was significantly higher than in group C ( P = 0.048). The serum triglyceride (TG) levels in groups A and B were significantly higher than in group C ( P = 0.027 and 0.000, respectively). The serum of very low-density lipoprotein (VLDL) levels in group B were significantly higher than in group C ( P = 0.000). Although a comparison of the low-density lipoprotein (LDL) and high-density lipoprotein (HDL) serum levels among the 4 groups indicated no changes. The serum LDL levels in group B were significantly higher than in group A ( P = 0.008). No significant differences were observed among the groups with respect to serum homocysteine, C-reactive protein (CRP), interleukin-6 (IL-6), malondialdehyde (MDA), superoxide dismutase (SOD), soluble OX40 ligand (sOX40L), or heat shock protein (HSP) 60 or 70.

          Alcoholic liver disease may result in CIMT thickening. Carotid intima-media thickness is associated with age and metabolic factors in patients with ALD. In addition, ALD might promote the premature occurrence of CIMT thickening. The thickening of carotid artery intima thickness, however, is not associated with cytokine profiles, oxidative balance, or immune responses in patients with ALD.

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          Most cited references32

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          Heat shock proteins in cancer: diagnostic, prognostic, predictive, and treatment implications.

          Heat shock proteins (Hsps) are overexpressed in a wide range of human cancers and are implicated in tumor cell proliferation, differentiation, invasion, metastasis, death, and recognition by the immune system. We review the current status of the role of Hsp expression in cancer with special emphasis on the clinical setting. Although Hsp levels are not informative at the diagnostic level, they are useful biomarkers for carcinogenesis in some tissues and signal the degree of differentiation and the aggressiveness of some cancers. In addition, the circulating levels of Hsp and anti-Hsp antibodies in cancer patients may be useful in tumor diagnosis. Furthermore, several Hsp are implicated with the prognosis of specific cancers, most notably Hsp27, whose expression is associated with poor prognosis in gastric, liver, and prostate carcinoma, and osteosarcomas, and Hsp70, which is correlated with poor prognosis in breast, endometrial, uterine cervical, and bladder carcinomas. Increased Hsp expression may also predict the response to some anticancer treatments. For example, Hsp27 and Hsp70 are implicated in resistance to chemotherapy in breast cancer, Hsp27 predicts a poor response to chemotherapy in leukemia patients, whereas Hsp70 expression predicts a better response to chemotherapy in osteosarcomas. Implication of Hsp in tumor progression and response to therapy has led to its successful targeting in therapy by 2 main strategies, including: (1) pharmacological modification of Hsp expression or molecular chaperone activity and (2) use of Hsps in anticancer vaccines, exploiting their ability to act as immunological adjuvants. In conclusion, the present times are of importance for the field of Hsps in cancer, with great contributions to both basic and clinical cancer research.
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            Alcohol, oxidative stress and free radical damage.

            The involvement of free radical mechanisms in the pathogenesis of alcoholic liver disease (ALD) is demonstrated by the detection of lipid peroxidation markers in the liver and the serum of patients with alcoholism, as well as by experiments in alcohol-feed rodents that show a relationship between alcohol-induced oxidative stress and the development of liver pathology. Ethanol-induced oxidative stress is the result of the combined impairment of antioxidant defences and the production of reactive oxygen species by the mitochondrial electron transport chain, the alcohol-inducible cytochrome P450 (CYP) 2E1 and activated phagocytes. Furthermore, hydroxyethyl free radicals (HER) are also generated during ethanol metabolism by CYP2E1. The mechanisms by which oxidative stress contributes to alcohol toxicity are still not completely understood. The available evidence indicates that, by favouring mitochondrial permeability transition, oxidative stress promotes hepatocyte necrosis and/or apoptosis and is implicated in the alcohol-induced sensitization of hepatocytes to the pro-apoptotic action of TNF-alpha. Moreover, oxidative mechanisms can contribute to liver fibrosis, by triggering the release of pro-fibrotic cytokines and collagen gene expression in hepatic stellate cells. Finally, the reactions of HER and lipid peroxidation products with hepatic proteins stimulate both humoral and cellular immune reactions and favour the breaking of self-tolerance during ALD. Thus, immune responses might represent the mechanism by which alcohol-induced oxidative stress contributes to the perpetuation of chronic hepatic inflammation. Together these observations provide a rationale for the possible clinical application of antioxidants in the therapy for ALD.
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              Nonalcoholic fatty liver disease is associated with carotid atherosclerosis: a case-control study.

              Nonalcoholic fatty liver disease (NAFLD) frequently coexists with obesity, diabetes, and dyslipidemia. We examined whether NAFLD was associated with atherosclerosis, as measured by ultrasound in the carotid arteries. Carotid atherosclerosis and cardiovascular risk factors were assessed in 40 patients with an ultrasound diagnosis of primary NAFLD and 40 matched population controls. The metabolic syndrome and all its individual traits, including elevated C-reactive protein, were significantly (P<0.005) more frequent in NAFLD patients than in control subjects. Patients with NAFLD showed more carotid atherosclerosis than controls, with mean intima-media thickness (IMT) of 0.70+/-0.20 mm and 0.54+/-0.13 mm (P<0.0001) and plaque prevalence of 50% and 25% (P=0.021), respectively. By multivariate analysis, older age (odds ratio [OR], 2.5 per 10 years; 95% CI, 1.4 to 4.4; P=0.002), the presence of NAFLD (OR, 8.4; 95% CI, 2.49 to 29.4; P=0.001), and elevated serum ferritin (OR, 3.1; 95% CI, 1.2 to 7.9; P=0.016) were independent predictors of an increased IMT. Patients with NAFLD show a cluster of risk factors of the metabolic syndrome and advanced carotid atherosclerosis. NAFLD appears to be a feature of the metabolic syndrome, and its detection on abdominal ultrasound should alert to the existence of an increased cardiovascular risk.
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                Author and article information

                Journal
                Medicine (Baltimore)
                Medicine (Baltimore)
                MEDI
                Medicine
                Wolters Kluwer Health
                0025-7974
                1536-5964
                July 2015
                17 July 2015
                : 94
                : 28
                : e1087
                Affiliations
                Department of Gastroenterology, Taishan Hospital; Taishan Medical College, Taian, Shandong, China.
                Author notes
                Correspondence: Baoge QU, MSc, Department of Gastroenterology, Taishan Hospital, Shandong Province, No. 3 Tianwaicun Street, Taian 271000, China (e-mail: qubaoge@ 123456sina.com ).
                Article
                01087
                10.1097/MD.0000000000001087
                4617078
                26181540
                c47f556f-6b4a-4c73-86a8-cc92fae9fbd9
                Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.

                This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as the author is credited and the new creations are licensed under the identical terms. http://creativecommons.org/licenses/by-nc-sa/4.0

                History
                : 8 March 2015
                : 4 June 2015
                : 8 June 2015
                Categories
                3400
                Research Article
                Observational Study
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