A systematic review and meta-analysis of the use of oral zinc in the treatment of hepatic encephalopathy

Nutrition Journal

Misael Uribe²  Nahum Méndez-Sanchez²  Francisco A Villegas-López²  Tonatiuh Barrientos-Gutiérrez¹  Asunción Cesar-Arce²  Norberto C Chavez-Tapia² 

[1] Center for Integrative Approaches to Health Disparities, University of Michigan, Ann Arbor, USA;Obesity and Digestive Diseases Unit, Medica Sur Clinic & Foundation, Mexico City, Mexico

关键词: Evidence-based medicine;    Liver cirrhosis;    Therapy;   

Others  :  806642
DOI  :  10.1186/1475-2891-12-74

 received in 2012-10-29, accepted in 2013-06-04,  发布年份 2013

【 摘 要 】

Background and aim

Because low serum zinc levels precipitate hepatic encephalopathy, zinc supplementation is considered a potential therapeutic option. The aim of this study was to assess the effects of oral zinc supplementation in the treatment of hepatic encephalopathy.

Methods

For this systematic review and meta-analysis, data sources included electronic databases (CENTRAL, MEDLINE, EMBASE) and manual searching. Randomized clinical trials of adult patients diagnosed with liver cirrhosis and hepatic encephalopathy were included. The types of interventions considered were any oral zinc supplementation versus no intervention, placebo, or other interventions for the management of hepatic encephalopathy. The data were analyzed by calculating the RR for each trial and expressing the uncertainty as 95% CI. Continuous data were analyzed by calculating the standard mean differences (SMD) between groups within each trial and their 95% CI. Statistical heterogeneity was defined as a P-value > 0.10 (χ²) or I² > 25%.

Results

Four trials with a total of 233 patients were included. Oral zinc supplementation was associated with a significant improvement in performance on the number connection test (SMD –0.62; 95% CI –1.12 to –0.11) reported in three trials (n = 189), but not with encephalopathy recurrence reduction (RR 0.64; 95% CI 0.26 to 1.59) reported in two trials (n = 169). Other clinically significant outcomes (mortality, liver related morbidity, quality of life) were not reported.

Conclusion

Oral zinc supplementation improved performance on the number connection test, but no evidence about other clinical or biochemical outcomes was available.

【 授权许可】

   
2013 Chavez-Tapia et al.; licensee BioMed Central Ltd.

【 图 表 】

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【 参考文献 】

• [1]Takuma Y, Nouso K, Makino Y, Hayashi M, Takahashi H: Clinical trial: oral zinc in hepatic encephalopathy. Alimen Pharmacol Therap 2010, 32:1080-1090.
• [2]Schliess F, Gorg B, Haussinger D: RNA oxidation and zinc in hepatic encephalopathy and hyperammonemia. Metab Brain Dis 2009, 24:119-134.
• [3]Kobashi-Margain RA, Gavilanes-Espinar JG, Gutierrez-Grobe Y, Gutierrez-Jimenez AA, Chavez-Tapia N, Ponciano-Rodriguez G, Uribe M, Mendez Sanchez N: Albumin dialysis with molecular adsorbent recirculating system (MARS) for the treatment of hepatic encephalopathy in liver failure. Ann Hepatol 2011, 10(Suppl 2):S70-S76.
• [4]Sharma P, Sharma BC: Lactulose for minimal hepatic encephalopathy in patients with extrahepatic portal vein obstruction. Saudi J Gastroenterol J Saudi Gastroenterol Assoc 2012, 18:168-172.
• [5]Haussinger D, Schliess F: Pathogenetic mechanisms of hepatic encephalopathy. Gut 2008, 57:1156-1165.
• [6]Brusilow SW, Traystman R: Hepatic encephalopathy. N Engl J Med 1986, 314:786-787. author reply 787
• [7]Marchesini G, Fabbri A, Bianchi G, Brizi M, Zoli M: Zinc supplementation and amino acid-nitrogen metabolism in patients with advanced cirrhosis. Hepatology 1996, 23:1084-1092.
• [8]Tuerk MJ, Fazel N: Zinc deficiency. Cur Opin Gastroenterol 2009, 25:136-143.
• [9]Poo JL, Rosas-Romero R, Rodriguez F, Silencio JL, Munoz R, Bourges H, Uribe M: Serum zinc concentrations in two cohorts of 153 healthy subjects and 100 cirrhotic patients from Mexico City. Digest Dis 1995, 13:136-142.
• [10]Reding P, Duchateau J, Bataille C: Oral zinc supplementation improves hepatic encephalopathy. Results of a randomised controlled trial. Lancet 1984, 2:493-495.
• [11]Bresci G, Parisi G, Banti S: Management of hepatic encephalopathy with oral zinc supplementation: a long-term treatment. Eur J Med 1993, 2:414-416.
• [12]Takeda A: Zinc homeostasis and functions of zinc in the brain. Biomet Int J Role Metal Ions Biol Biochem Med 2001, 14:343-351.
• [13]Cochrane Handbook for Systematic Reviews of Interventions Version 5.0.2. http://www.cochrane-handbook.org webcite
• [14]Centre TNC: Review Manager (RevMan). 50th edition. Copenhagen: The Cochrane Collaboration; 2010.
• [15]Egger M, Davey Smith G, Schneider M, Minder C: Bias in meta-analysis detected by a simple, graphical test. BMJ 1997, 315:629-634.
• [16]Hayashi M, Ikezawa K, Ono A, Okabayashi S, Hayashi Y, Shimizu S, Mizuno T, Maeda K, Akasaka T, Naito M, et al.: Evaluation of the effects of combination therapy with branched-chain amino acid and zinc supplements on nitrogen metabolism in liver cirrhosis. Hepatol Res J Japan Soc Hepatol 2007, 37:615-619.
• [17]Binesh N, Huda A, Thomas MA, Wyckoff N, Bugbee M, Han S, Rasgon N, Davanzo P, Sayre J, Guze B, et al.: Hepatic encephalopathy: a neurochemical, neuroanatomical, and neuropsychological study. J App Clin Med Physics/Am Coll Med Physics 2006, 7:86-96.
• [18]Butterworth RF: Neurotransmitter dysfunction in hepatic encephalopathy: new approaches and new findings. Metab Brain Dis 2001, 16:55-65.
• [19]Norenberg MD: Astrocytic-ammonia interactions in hepatic encephalopathy. Sem Liver Dis 1996, 16:245-253.
• [20]Haussinger D, Laubenberger J, Vom Dahl S, Ernst T, Bayer S, Langer M, Gerok W, Hennig J: Proton magnetic resonance spectroscopy studies on human brain myo-inositol in hypo-osmolarity and hepatic encephalopathy. Gastroenterol 1994, 107:1475-1480.
• [21]Haussinger D: Low grade cerebral edema and the pathogenesis of hepatic encephalopathy in cirrhosis. Hepatology 2006, 43:1187-1190.
• [22]Morgan MY: Cerebral magnetic resonance imaging in patients with chronic liver disease. Metab Brain Dis 1998, 13:273-290.
• [23]Ross BD, Jacobson S, Villamil F, Korula J, Kreis R, Ernst T, Shonk T, Moats RA: Subclinical hepatic encephalopathy: proton MR spectroscopic abnormalities. Radiology 1994, 193:457-463.
• [24]Aschner M: The functional significance of brain metallothioneins. FASEB J 1996, 10:1129-1136.
• [25]Kruczek C, Gorg B, Keitel V, Pirev E, Kroncke KD, Schliess F, Haussinger D: Hypoosmotic swelling affects zinc homeostasis in cultured rat astrocytes. Glia 2009, 57:79-92.