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

Nutrition Journal - Tập 12 - Trang 1-6 - 2013
Norberto C Chavez-Tapia1, Asunción Cesar-Arce1, Tonatiuh Barrientos-Gutiérrez2,3, Francisco A Villegas-López1, Nahum Méndez-Sanchez1, Misael Uribe1
1Obesity and Digestive Diseases Unit, Medica Sur Clinic & Foundation, Mexico City, Mexico
2National Institute of Public Health, Mexico City, Mexico
3Center for Integrative Approaches to Health Disparities, University of Michigan, Ann Arbor, USA

Tóm tắt

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. 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 (χ 2) or I 2 > 25%. 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. Oral zinc supplementation improved performance on the number connection test, but no evidence about other clinical or biochemical outcomes was available.

Tài liệu tham khảo

Takuma Y, Nouso K, Makino Y, Hayashi M, Takahashi H: Clinical trial: oral zinc in hepatic encephalopathy. Alimen Pharmacol Therap. 2010, 32: 1080-1090. 10.1111/j.1365-2036.2010.04448.x. Schliess F, Gorg B, Haussinger D: RNA oxidation and zinc in hepatic encephalopathy and hyperammonemia. Metab Brain Dis. 2009, 24: 119-134. 10.1007/s11011-008-9125-2. 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. 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. 10.4103/1319-3767.96448. Haussinger D, Schliess F: Pathogenetic mechanisms of hepatic encephalopathy. Gut. 2008, 57: 1156-1165. 10.1136/gut.2007.122176. Brusilow SW, Traystman R: Hepatic encephalopathy. N Engl J Med. 1986, 314: 786-787. author reply 787 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. 10.1002/hep.510230523. Tuerk MJ, Fazel N: Zinc deficiency. Cur Opin Gastroenterol. 2009, 25: 136-143. 10.1097/MOG.0b013e328321b395. 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. 10.1159/000171495. Reding P, Duchateau J, Bataille C: Oral zinc supplementation improves hepatic encephalopathy. Results of a randomised controlled trial. Lancet. 1984, 2: 493-495. 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. Takeda A: Zinc homeostasis and functions of zinc in the brain. Biomet Int J Role Metal Ions Biol Biochem Med. 2001, 14: 343-351. 10.1023/A:1012982123386. Cochrane Handbook for Systematic Reviews of Interventions Version 5.0.2. http://www.cochrane-handbook.org, Centre TNC: Review Manager (RevMan). 2010, Copenhagen: The Cochrane Collaboration, 50 Egger M, Davey Smith G, Schneider M, Minder C: Bias in meta-analysis detected by a simple, graphical test. BMJ. 1997, 315: 629-634. 10.1136/bmj.315.7109.629. 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. 10.1111/j.1872-034X.2007.00095.x. 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. 10.1120/jacmp.2027.25374. Butterworth RF: Neurotransmitter dysfunction in hepatic encephalopathy: new approaches and new findings. Metab Brain Dis. 2001, 16: 55-65. 10.1023/A:1011614528751. Norenberg MD: Astrocytic-ammonia interactions in hepatic encephalopathy. Sem Liver Dis. 1996, 16: 245-253. 10.1055/s-2007-1007237. 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. Haussinger D: Low grade cerebral edema and the pathogenesis of hepatic encephalopathy in cirrhosis. Hepatology. 2006, 43: 1187-1190. 10.1002/hep.21235. Morgan MY: Cerebral magnetic resonance imaging in patients with chronic liver disease. Metab Brain Dis. 1998, 13: 273-290. 10.1023/A:1020680624084. 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. Aschner M: The functional significance of brain metallothioneins. FASEB J. 1996, 10: 1129-1136. 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. 10.1002/glia.20737.