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      The Prevalence and Implication of Zinc Deficiency in Patients With Chronic Liver Disease

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          Abstract

          Background

          Patients with liver cirrhosis often exhibit zinc deficiency. Although zinc is involved in many bioactivities, many aspects of clinical implications of zinc deficiency in liver cirrhosis remain unclear. We aimed to reveal the prevalence and implications of zinc deficiency in liver cirrhosis by assessing associations with parameters such as clinical symptoms and laboratory data.

          Methods

          In 235 cirrhosis patients enrolled at multiple medical institutions in 2009, we assessed how blood zinc levels were associated with their clinical symptoms, patients characteristics, and liver function test results.

          Results

          Blood zinc levels were most strongly correlated with blood albumin levels among the study parameters (r = 0.587, P < 0.0001). When blood albumin levels were ≤ 3.5 g/dL, blood zinc levels were < 70 μg/dL in 88% of patients. Additionally, significant correlations were observed with age (r = -0.253, P = 0.0014), aspartate aminotransferase levels (r = -0.254, P = 0.0020), total bilirubin levels (r = -0.222, P = 0.0053), prothrombin time (r = -0.255, P = 0.0029), branched-chain amino acid to tyrosine ratio (r = 0.357, P < 0.0001), Child-Pugh score (r = 0.469, P < 0.0001), ammonia levels (r = -0.246, P = 0.0028), and total cholesterol levels (r = 0.314, P < 0.0001). Blood zinc levels were significantly lower in patients with edema/ascites (P < 0.0001), those with hepatic encephalopathy (P = 0.0215), those receiving oral diuretics (P = 0.0045), and those receiving oral branched-chain amino acids (P < 0.0001) than in those without these conditions.

          Conclusions

          Zinc deficiency is prevalent in cirrhosis patients, whereas nitrogen metabolic disorders, particularly hypoalbuminemia, can be an indicator of zinc deficiency. Thus, cirrhosis patients exhibiting a nitrogen metabolic disorder should be examined for the presence of zinc deficiency.

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          Most cited references43

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          Diabetes increases the risk of chronic liver disease and hepatocellular carcinoma.

          An association between diabetes and chronic liver disease has been reported. However, the temporal relationship between these conditions remains unknown. We identified all patients with a hospital discharge diagnosis of diabetes between 1985 and 1990 using the computerized records of the Department of Veterans Affairs. We randomly assigned 3 patients without diabetes for every patient with diabetes. We excluded patients with concomitant liver disease. The remaining cohort was followed through 2000 for the occurrence of chronic nonalcoholic liver disease (CNLD) and hepatocellular carcinoma (HCC). Hazard rate ratios (HRR) were determined in Cox proportional hazard survival analysis. The study cohort comprised 173,643 patients with diabetes and 650,620 patients without diabetes. Most were men (98%). Patients with diabetes were older (62 vs. 54 years) than patients without diabetes. The incidence of chronic nonalcoholic liver disease was significantly higher among patients with diabetes (incidence rate: 18.13 vs. 9.55 per 10,000 person-years, respectively, P < 0.0001). Similar results were obtained for HCC (incidence rate: 2.39 vs. 0.87 per 10,000 person-years, respectively, P < 0.0001). Diabetes was associated with an HRR of 1.98 (95% CI: 1.88 to 2.09, P < 0.0001) of CNLD and an HRR of 2.16 (1.86 to 2.52, P < 0.0001) of hepatocellular carcinoma. Diabetes carried the highest risk among patients with longer than 10 years of follow-up. Among men with diabetes, the risk of CNLD and HCC is doubled. This increase in risk is independent of alcoholic liver disease, viral hepatitis, or demographic features.
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            The LIM domain: from the cytoskeleton to the nucleus.

            First described 15 years ago as a cysteine-rich sequence that was common to a small group of homeodomain transcription factors, the LIM domain is now recognized as a tandem zinc-finger structure that functions as a modular protein-binding interface. LIM domains are present in many proteins that have diverse cellular roles as regulators of gene expression, cytoarchitecture, cell adhesion, cell motility and signal transduction. An emerging theme is that LIM proteins might function as biosensors that mediate communication between the cytosolic and the nuclear compartments.
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              The biochemical basis of zinc physiology.

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                Author and article information

                Journal
                J Clin Med Res
                J Clin Med Res
                Elmer Press
                Journal of Clinical Medicine Research
                Elmer Press
                1918-3003
                1918-3011
                May 2018
                16 March 2018
                : 10
                : 5
                : 437-444
                Affiliations
                [a ]Department of Hepato-Biliary and Pancreatic Oncology, Osaka International Cancer Institute, 3-1-69 Otemae, Chuo-ku, Osaka 541-8567, Japan
                [b ]Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, 67 Asahi-cho, Kurume 830-0011, Japan
                [c ]Department of Gastroenterology, Tokai University School of Medicine, 143 Kasuya, Isehara 259-1193, Japan
                [d ]Department of Gastroenterology, JCHO Osaka Hospital, 4-2-78 Fukushima, Fukushima-ku, Osaka 553-0003, Japan
                [e ]Department of Gastroenterology, Shuuwa General Hospital, 1200 Taniharanitta, Kasugabe 344-0035, Japan
                [f ]Liver Disease Center, Kansai Medical University Medical Center, 10-15 Fumizono-cho, Moriguchi 570-8507, Japan
                [g ]Department of Gastroenterology, International University of Health and Welfare Hospital, 537-3 Iguchi, Nasushiobara 329-2763, Japan
                [h ]Department of Gastroenterology and Hepatology, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu 514-8507, Japan
                [i ]Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Shizugawa, Toon 791-0295, Japan
                [j ]Division of Gastroenterology and Hepatology, Iwate Medical University, 19-1 Uchimaru, Morioka 020-8505, Japan
                [k ]Third Department of Internal Medicine, Kyorin University School of Medicine, 6-20-2 Shinkawa, Mitaka 181-8611, Japan
                [l ]Department of Gastroenterology, Gifu University Graduate School of Medicine, 1-1 Yanagido, Gifu 501-1194, Japan
                [m ]Department of Nutritional Medicine, Osaka City University Graduate School of Human Life Science, 1-5-7 Asahimachi, Abeno-ku, Osaka 545-8586, Japan
                [n ]Deparment of Gastroenterology and Hepatology, NHO Beppu Medical Center, 1473 Ooaza Utikamada, Beppu 874-0011, Japan
                [o ]Miwa Clinic, 3-3 Nagarahigashi, Gifu 502-0082, Japan
                [p ]Department of Hepatology, Osaka City University Graduate School of Medicine, 1-5-7 Asahimachi, Abeno-ku, Osaka 545-8586, Japan
                [q ]Department of Internal Medicine, Morioka Municipal Hospital, 5-15-1 Motomiya, Morioka 020-0866, Japan
                [r ]Center of Preventive Medicine, International University of Health and Welfare Hospital, 537-3 Iguchi, Nasushiobara 329-2763, Japan
                [s ]Department of Cancer Epidemiology, Cancer Control Center, Osaka International Cancer Institute, 3-1-69 Otemae, Chuo-ku, Osaka 541-8567, Japan
                [t ]Division of Hepatobiliary and Pancreatic Disease, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya 663-8501, Japan
                [u ]Department of Nutritional Science, Morioka University, 808 Sunakomi, Takizawa 020-0694, Japan
                Author notes
                [v ]Corresponding Author: Kazuhiro Katayama, Department of Hepatobiliary and Pancreatic Oncology, Osaka International Cancer Institute, 3-1-69, Otemae, Chuo-ku, Osaka 541-8567, Japan. Email: katayama-ka@ 123456mc.pref.osaka.jp
                Article
                10.14740/jocmr3374w
                5862092
                29581807
                cd09e432-a8a4-4765-a695-2d36063aceb4
                Copyright 2018, Katayama et al.

                This article is distributed under the terms of the Creative Commons Attribution Non-Commercial 4.0 International License, which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 30 January 2018
                : 20 February 2018
                Categories
                Original Article

                Medicine
                liver cirrhosis,nitrogen metabolism,branched-chain amino acid,ammonia,albumin
                Medicine
                liver cirrhosis, nitrogen metabolism, branched-chain amino acid, ammonia, albumin

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