CURRENT CONCEPTS IN MINIMAL HEPATIC ENCEPHALOPATHY
Abstract
Minimal hepatic encephalopathy (MHE) defines the presence of neurocognitive impairments in patients with cirrhosis or portal-systemic shunting that show a normal neurologic and psychiatric status on clinical examination. Although ammonia has the central role in MHE pathogenesis, factors such as infection, oxidative stress, manganese or intestinal bacterial overgrowth contribute to the development of the neurocognitive deficits associated with this disease. Many methods have proven useful in identifying MHE but because of the major drawbacks (standardization requirements, high price, sophisticated equipment, and limited access) a gold-standard test is still missing. Although beneficial, the treatment of MHE is not routinely recommended and should be taken into consideration in patients at risk for accidents and in those with cognitive complaints or decline in work performance.
References
1. Vilstrup et al. Hepatic encephalopathy in chronic liver disease: 2014 Practice Guideline by the American Association for the Study of Liver Diseases and the European Association for the Study of the Liver. Hepatol 2014; 60(2): 715-735.
2. Prakash R, Mullen DK. Mechanisms, diagnosis and management of hepatic encephalopathy. Nat Rev Gastroenterol Hepatol 2010; 7(9): 515-525.
3. Ferenci P, Lockwood A, Mullen K, Tarter R, Weissenborn K, Blei AT. Hepatic encephalopathy - definition, nomenclature, diagnosis, and quantification: final report of the working party at the 11th World Congresses of Gastroenterology, Vienna, 1998. Hepatol 2002; 35: 716-721.
4. Bajaj JS, Wade JB, Sanyal AJ. Spectrum of neurocognitive impairment in cirrhosis: Implications for the assessment of hepatic encephalopathy. Hepatol 2009; 50: 2014-2021.
5. Rivera Ramos JF, Rodríguez Leal C. Review of the final report of the 1998 Working Party on defini-tion, nomenclature and diagnosis of hepatic encephalopathy. Ann Hepatol 2011; 10 Suppl 2: S36-S39.
6. Haliga R, Didita A, Anton C, Sorodoc L. Updates in the pathogenesis and diagnosis of hepatic en-cephalopathy. Rev Med Chir Soc Med Nat Iasi 2014; 118(3): 601-607.
7. Cichoż-Lach A, Michalak A. Current pathogenetic aspects of hepatic encephalopathy and noncirrhotic hyperammonemic encephalopathy. World J Gastroenterol 2013; 19(1): 26-34.
8. Patel D, McPhail MJ, Cobbold JF, Taylor-Robinson SD. Hepatic encephalopathy. Br J Hosp Med 2012; 73: 79-85.
9. Olde Damink SW, Jalan R, Dejong CH. Interorgan ammonia trafficking in liver disease. Metab Brain Dis 2009; 24:169-181.
10. Häussinger D, Schliess F. Pathogenetic mechanisms of hepatic encephalopathy. Gut 2008; 57: 1156-1165.
11. Tanigami H, Rebel A, Martin LJ, Chen TY, Brusilow SW, Traystman RJ, Koehler RC. Effect of glutamine synthetase inhibition on astrocyte swelling and altered astroglial protein expression during hyperammonemia in rats. Neurosci 2005; 131: 437-449.
12. Butterworth RF. Hepatic encephalopathy. Alcohol Res Health 2003; 27: 240-246.
13. Haussinger, D. Low grade cerebral edema and the pathogenesis of hepatic encephalopathy in cirrhosis. Hepatol 2006; 43: 1187-1190.
14. Cordoba J, Sanpedro F, Alonso J, Rovira A. 1H magnetic resonance in the study of hepatic encepha-lopathy in humans. Metab Brain Dis 2002; 17: 415-429.
15. Shawcross, D. L. et al. Low myo-inositol and highglutamine levels in brain are associated with neu-ropsychological deterioration after induced hyperammonemia. Am J Physiol Gastrointest Liver Physiol 2004; 287(3): G503-G509.
16. Butterworth RF Pathophysiology of hepatic encephalopathy: The concept of synergism. Hepatol Res 2008; 38: Suppl 1: S116-121
17. Norenberg MD, Jayakumar AR, Rama Rao KV, et al. New concepts in the mechanism of ammonia-induced astrocyte swelling. Metab Brain Dis 2007; 22: 219-234.
18. Knudsen GM, Schmidt J, Almdal T, Paulson OB, Vilstrup H. Passage of amino acids and glucose across the blood-brain barrier in patients with hepatic encephalopathy. Hepatol 1993; 17(6): 987-992.
19. Skowrońska M, Albrecht J. Alterations of blood brain barrier function in hyperammonemia: an over-view. Neurotox Res 2012; 21(2): 236-244.
20. Shawcross D, Jalan R. The pathophysiologic basis of hepatic encephalopathy: central role for ammonia and inflammation. Cell Mol Life Sci 2005; 62: 2295-2304.
21. Williams R. Bacterial flora and pathogenesis in hepatic encephalopathy. Aliment Pharmacol Ther 2007; 25(Suppl 1): 17-22.
22. Bajaj JS Ridlon JM, Hylemon PB, Thacker LR, Heuman DM, Smith S, Sikaroodi M, Gillevet PM. Linkage of gut microbiome with cognition in hepatic encephalopathy. Am J Physiol Gastrointest Liver Physiol 2012; 302(1): G168-G175.
23. Sturgeon JP, Shawcross DL. Recent insights into the pathogenesis of hepatic encephalopathy and treatments. Expert Rev Gastroenterol Hepatol 2014; 8(1): 83-100.
24. Alvarez VM, Rama Rao KV, Brahmbhatt M, Norenberg MD. Interaction between cytokines and ammonia in the mitochondrial permeability transition in cultured astrocytes. J Neurosci Res 2011; 89(12): 2028-2040.
25. Rama Rao KV, Jayakumar AR, Tong X, Alvarez VM, Norenberg MD. Marked potentiation of cell swelling by cytokines in ammonia-sensitized cultured astrocytes. J Neuroinflamm 2010; 7: 66-70.
26. Jain L, Sharma BC, Srivastava S, Puri SK, Sharma P, Sarin S. Serum endotoxin, inflammatory media-tors, and magnetic resonance spectroscopy before and after treatment in patients with minimal hepatic encephalopathy. J Gastroenterol Hepatol 2013; 28(7): 1187-1193.
27. Schliess F, Gorg B, Haussinger D. Pathogenetic interplay between osmotic and oxidative stress: the hepatic encephalopathy paradigm. Biol Chem 2006; 387: 1363-1370.
28. Murthy CR, Rama Rao KV, Bai G, Norenberg MD. Ammonia-induced production of free radicals in primary cultures of rat astrocytes. J Neurosci Res 2001; 66: 282-298.
29. Reinehr R. et al. Hypoosmotic swelling and ammonia increase oxidative stress by NADPH oxidase in cultured astrocytes and vital brain slices. Glia 2007; 55: 758-771.
30. Albrecht J, Norenberg MD. Glutamine: a Trojan horse in ammonia neurotoxicity. Hepatol 2006; 44: 788-794.
31. Spahr L et al. Increased blood manganese in cirrhotic patients: relationship to pallidal magnetic reso-nance signal hyperintensity and neurological symptoms. Hepatol 1996; 24(5): 1116-1120.
32. Krieger D et al. Manganese and chronic hepatic encephalopathy. Lancet 1995; 346: 270-274.
33. Rose C et al. Manganese deposition in basal ganglia structures results from both portal-systemic shunting and liver dysfunction. Gastroenterol 1999; 117: 640-644.
34. Ahboucha S, Butterworth RF. The neurosteroid system: implication in the pathophysiology of hepatic encephalopathy. Neurochem Int 2008; 52: 575-587.
35. Cagnin A, Taylor-Robinson SD, Forton DM, Banati RB In vivo imaging of cerebral “peripheral benzodiazepine binding sites” in patients with hepatic encephalopathy. Gut 2006; 55: 547-553.
36. Jones EA, Mullen KD. Theories of the pathogenesis of hepatic encephalopathy. Clin Liver Dis 2012; 16: 7-26.
37. Jones EA. Ammonia, the GABA neurotransmitter system, and hepatic encephalopathy. Metab Brain Dis. 2002; 17: 275-281.
38. Liu Q et al. Synbiotic modulation of gut flora: effect on minimal hepatic encephalopathy in patients with cirrhosis. Hepatol 2004; 39(5): 1441-1449.
39. Rose C et al. Role of small intestinal bacterial overgrowth and delayed gastrointestinal transit time in cirrhotic patients with minimal hepatic encephalopathy. J Hepatol 2010; 53(5): 849-855.
40. Groeneweg M, Quero JC, De Bruijn I, et al. Subclinical hepatic encephalopathy impairs daily func-tioning. Hepatol 1998; 28: 45-49.
41. Kappus MR, Bajaj JS. Covert hepatic encephalopathy: not as minimal as you might think. Clin Gas-troenterol Hepatol 2012; 10(11): 1208-1219.
42. Prasad S, Dhiman RK, Duseja A, Chawla Y, Sharma A, Agarwal R. Lactulose improves cognitive functions and health-related quality of life in cirrhotic patients with minimal hepatic encephalopathy. Hepatol 2007; 45: 549-559.
43. Samanta J., Dhiman R.K., Khatri A., Thumburu K.K. Correlation between degree and quality of sleep disturbance and the level of neuropsychiatric impairment in patients with liver cirrhosis. Metab Brain Dis 2013; 28(2): 249-259.
44. Bersagliere A., Raduazzo I.D., Nardi M., Schiff S. Induced hyperammonemia may compromise the ability to generate restful sleep in patients with cirrhosis. Hepatol 2012; 55(3): 869-878.
45. Weissenborn K, Heidenreich S, Giewekemeyer K, Ruckert N, Hecker H. Memory function in early hepatic encephalopathy. J Hepatol 2003; 39: 320-325.
46. Bajaj JS. Minimal hepatic encephalopathy matters in daily life. World J Gastroenterol 2008; 14(23): 3609-3615.
47. Bajaj JS et al. Cognitive dysfunction is associated with poor socioeconomic status in patients with cirrhosis: an international multicenter study. Clin Gastroenterol Hepatol 2013; 11(11):1511-1516.
48. Bajaj JS et al. The multi-dimensional burden of cirrhosis and hepatic encephalopathy on patients and caregivers. Am J Gastroenterol 2011; 106: 1646-1653.
49. Hartmann IJ et al. The prognostic significance of subclinical hepatic encephalopathy. Am J Gastroen-terol 2000; 95: 2029-2034.
50. Prakash RK, Brown TA, Mullen KD.Minimal hepatic encephalopathy and driving: is the genie out of the bottle? Am J Gastroenterol 2011; 106(8):1415-1416.
51. Amodio P, Montagnese S, Merkel C. Attention: Minimal hepatic encephalopathy and road accidents. Hepatol 2012; 55(4): 985-987.
52. Wein C, Koch H, Popp B, Oehler G, Schauder P. Minimal hepatic encephalopathy impairs fitness to drive. Hepatol 2004; 39(3): 739-745.
53. Amodio P et al. Clinical features and survival of cirrhotic patients with subclinical cognitive alterations detected by the number connection test and computerized psychometric tests. Hepatol 1999; 29: 1662-1667.
54. Dhiman RK et al.. Diagnosis and prognostic significance of minimal hepatic encephalopathy in patients with cirrhosis of liver. Dig Dis Sci 2010; 55: 2381-2390.
55. Simon -Talero M., Ventura M, Cordoba J. Minimal hepatic encephalopathy. In: Gines P,Forns X, Fernandez J, Crespo G, Rodes J, Arroyo V Therapy in Liver Diseases 2013; Barcelona: Elsevier Doyma. 20: 151-157.
56. Dhiman RK, Chawla YK. Minimal hepatic encephalopathy. Indian J Gastroenterol 2009; 28: 5-16.
57. Randolph C et al. International Society for Hepatic Encephalopathy and Nitrogen Metabolism (ISHEN). Neuropsychological assessment of hepatic encephalopathy: ISHEN practice guidelines. Liver Int 2009; 29(5): 629-635.
58. Bajaj JS. Expanding the Spectrum of Hepatic Encephalothy. In: Di Biseglie AM, Martin P. AASLD The liver meeting - Postgraduate Course 2013. Washington: American Association for the Study of Liver Disease: 169-175.
59. Als Nielsen B,Gluud LL,Gluud C. Non absorabable disaccharides for hepatic encephalopathy: sys-tematic review of randomized trials. BMJ 2004; 328: 1046.
60. Liu Q et al. Lactulose improves cognitive functions and health-related quality of life in patients with cirrhosis who have minimal hepatic encephalopathy. Hepatol 2007; 45: 549-559.
61. Sidhu SS et al. Rifaximin improves psychometric performance and health-related quality of life in patients with minimal hepatic encephalopathy (the RIME trial). Am J Gastroenterol 2011; 106: 307-316.
62. Irimia R, Trifan A. Efficacy of rifaximin versus lactulose for reducing the recurrence of overt hepatic encephalopathy and hopitalizations in cirrhosis. Rev Med Chir Soc Med Nat Iasi 2012; 116(4):1021-1027.
63. Mittal VV et al. An randomized controled trial comparing lactulose, probiotics and L-ornithine L-aspartate in treatment of minimal hepatic encephalopathy. Eur J Gastroenterol Hepatol 2011; 23: 725-732.
64. Bajaj JS et al. Probiotic yogurt for the treatment of minimal hepatic encephalopathy. Am J Gastroenterol 2008; 103: 1707-1715.
65. Shukla S. et al. Meta-analysis: the effects of gut flora modulation using prebiotics, probiotics and synbiotics on minimal hepatic encephalopathy. Aliment Pharmacol Ther 2011; 33: 662-671.
2. Prakash R, Mullen DK. Mechanisms, diagnosis and management of hepatic encephalopathy. Nat Rev Gastroenterol Hepatol 2010; 7(9): 515-525.
3. Ferenci P, Lockwood A, Mullen K, Tarter R, Weissenborn K, Blei AT. Hepatic encephalopathy - definition, nomenclature, diagnosis, and quantification: final report of the working party at the 11th World Congresses of Gastroenterology, Vienna, 1998. Hepatol 2002; 35: 716-721.
4. Bajaj JS, Wade JB, Sanyal AJ. Spectrum of neurocognitive impairment in cirrhosis: Implications for the assessment of hepatic encephalopathy. Hepatol 2009; 50: 2014-2021.
5. Rivera Ramos JF, Rodríguez Leal C. Review of the final report of the 1998 Working Party on defini-tion, nomenclature and diagnosis of hepatic encephalopathy. Ann Hepatol 2011; 10 Suppl 2: S36-S39.
6. Haliga R, Didita A, Anton C, Sorodoc L. Updates in the pathogenesis and diagnosis of hepatic en-cephalopathy. Rev Med Chir Soc Med Nat Iasi 2014; 118(3): 601-607.
7. Cichoż-Lach A, Michalak A. Current pathogenetic aspects of hepatic encephalopathy and noncirrhotic hyperammonemic encephalopathy. World J Gastroenterol 2013; 19(1): 26-34.
8. Patel D, McPhail MJ, Cobbold JF, Taylor-Robinson SD. Hepatic encephalopathy. Br J Hosp Med 2012; 73: 79-85.
9. Olde Damink SW, Jalan R, Dejong CH. Interorgan ammonia trafficking in liver disease. Metab Brain Dis 2009; 24:169-181.
10. Häussinger D, Schliess F. Pathogenetic mechanisms of hepatic encephalopathy. Gut 2008; 57: 1156-1165.
11. Tanigami H, Rebel A, Martin LJ, Chen TY, Brusilow SW, Traystman RJ, Koehler RC. Effect of glutamine synthetase inhibition on astrocyte swelling and altered astroglial protein expression during hyperammonemia in rats. Neurosci 2005; 131: 437-449.
12. Butterworth RF. Hepatic encephalopathy. Alcohol Res Health 2003; 27: 240-246.
13. Haussinger, D. Low grade cerebral edema and the pathogenesis of hepatic encephalopathy in cirrhosis. Hepatol 2006; 43: 1187-1190.
14. Cordoba J, Sanpedro F, Alonso J, Rovira A. 1H magnetic resonance in the study of hepatic encepha-lopathy in humans. Metab Brain Dis 2002; 17: 415-429.
15. Shawcross, D. L. et al. Low myo-inositol and highglutamine levels in brain are associated with neu-ropsychological deterioration after induced hyperammonemia. Am J Physiol Gastrointest Liver Physiol 2004; 287(3): G503-G509.
16. Butterworth RF Pathophysiology of hepatic encephalopathy: The concept of synergism. Hepatol Res 2008; 38: Suppl 1: S116-121
17. Norenberg MD, Jayakumar AR, Rama Rao KV, et al. New concepts in the mechanism of ammonia-induced astrocyte swelling. Metab Brain Dis 2007; 22: 219-234.
18. Knudsen GM, Schmidt J, Almdal T, Paulson OB, Vilstrup H. Passage of amino acids and glucose across the blood-brain barrier in patients with hepatic encephalopathy. Hepatol 1993; 17(6): 987-992.
19. Skowrońska M, Albrecht J. Alterations of blood brain barrier function in hyperammonemia: an over-view. Neurotox Res 2012; 21(2): 236-244.
20. Shawcross D, Jalan R. The pathophysiologic basis of hepatic encephalopathy: central role for ammonia and inflammation. Cell Mol Life Sci 2005; 62: 2295-2304.
21. Williams R. Bacterial flora and pathogenesis in hepatic encephalopathy. Aliment Pharmacol Ther 2007; 25(Suppl 1): 17-22.
22. Bajaj JS Ridlon JM, Hylemon PB, Thacker LR, Heuman DM, Smith S, Sikaroodi M, Gillevet PM. Linkage of gut microbiome with cognition in hepatic encephalopathy. Am J Physiol Gastrointest Liver Physiol 2012; 302(1): G168-G175.
23. Sturgeon JP, Shawcross DL. Recent insights into the pathogenesis of hepatic encephalopathy and treatments. Expert Rev Gastroenterol Hepatol 2014; 8(1): 83-100.
24. Alvarez VM, Rama Rao KV, Brahmbhatt M, Norenberg MD. Interaction between cytokines and ammonia in the mitochondrial permeability transition in cultured astrocytes. J Neurosci Res 2011; 89(12): 2028-2040.
25. Rama Rao KV, Jayakumar AR, Tong X, Alvarez VM, Norenberg MD. Marked potentiation of cell swelling by cytokines in ammonia-sensitized cultured astrocytes. J Neuroinflamm 2010; 7: 66-70.
26. Jain L, Sharma BC, Srivastava S, Puri SK, Sharma P, Sarin S. Serum endotoxin, inflammatory media-tors, and magnetic resonance spectroscopy before and after treatment in patients with minimal hepatic encephalopathy. J Gastroenterol Hepatol 2013; 28(7): 1187-1193.
27. Schliess F, Gorg B, Haussinger D. Pathogenetic interplay between osmotic and oxidative stress: the hepatic encephalopathy paradigm. Biol Chem 2006; 387: 1363-1370.
28. Murthy CR, Rama Rao KV, Bai G, Norenberg MD. Ammonia-induced production of free radicals in primary cultures of rat astrocytes. J Neurosci Res 2001; 66: 282-298.
29. Reinehr R. et al. Hypoosmotic swelling and ammonia increase oxidative stress by NADPH oxidase in cultured astrocytes and vital brain slices. Glia 2007; 55: 758-771.
30. Albrecht J, Norenberg MD. Glutamine: a Trojan horse in ammonia neurotoxicity. Hepatol 2006; 44: 788-794.
31. Spahr L et al. Increased blood manganese in cirrhotic patients: relationship to pallidal magnetic reso-nance signal hyperintensity and neurological symptoms. Hepatol 1996; 24(5): 1116-1120.
32. Krieger D et al. Manganese and chronic hepatic encephalopathy. Lancet 1995; 346: 270-274.
33. Rose C et al. Manganese deposition in basal ganglia structures results from both portal-systemic shunting and liver dysfunction. Gastroenterol 1999; 117: 640-644.
34. Ahboucha S, Butterworth RF. The neurosteroid system: implication in the pathophysiology of hepatic encephalopathy. Neurochem Int 2008; 52: 575-587.
35. Cagnin A, Taylor-Robinson SD, Forton DM, Banati RB In vivo imaging of cerebral “peripheral benzodiazepine binding sites” in patients with hepatic encephalopathy. Gut 2006; 55: 547-553.
36. Jones EA, Mullen KD. Theories of the pathogenesis of hepatic encephalopathy. Clin Liver Dis 2012; 16: 7-26.
37. Jones EA. Ammonia, the GABA neurotransmitter system, and hepatic encephalopathy. Metab Brain Dis. 2002; 17: 275-281.
38. Liu Q et al. Synbiotic modulation of gut flora: effect on minimal hepatic encephalopathy in patients with cirrhosis. Hepatol 2004; 39(5): 1441-1449.
39. Rose C et al. Role of small intestinal bacterial overgrowth and delayed gastrointestinal transit time in cirrhotic patients with minimal hepatic encephalopathy. J Hepatol 2010; 53(5): 849-855.
40. Groeneweg M, Quero JC, De Bruijn I, et al. Subclinical hepatic encephalopathy impairs daily func-tioning. Hepatol 1998; 28: 45-49.
41. Kappus MR, Bajaj JS. Covert hepatic encephalopathy: not as minimal as you might think. Clin Gas-troenterol Hepatol 2012; 10(11): 1208-1219.
42. Prasad S, Dhiman RK, Duseja A, Chawla Y, Sharma A, Agarwal R. Lactulose improves cognitive functions and health-related quality of life in cirrhotic patients with minimal hepatic encephalopathy. Hepatol 2007; 45: 549-559.
43. Samanta J., Dhiman R.K., Khatri A., Thumburu K.K. Correlation between degree and quality of sleep disturbance and the level of neuropsychiatric impairment in patients with liver cirrhosis. Metab Brain Dis 2013; 28(2): 249-259.
44. Bersagliere A., Raduazzo I.D., Nardi M., Schiff S. Induced hyperammonemia may compromise the ability to generate restful sleep in patients with cirrhosis. Hepatol 2012; 55(3): 869-878.
45. Weissenborn K, Heidenreich S, Giewekemeyer K, Ruckert N, Hecker H. Memory function in early hepatic encephalopathy. J Hepatol 2003; 39: 320-325.
46. Bajaj JS. Minimal hepatic encephalopathy matters in daily life. World J Gastroenterol 2008; 14(23): 3609-3615.
47. Bajaj JS et al. Cognitive dysfunction is associated with poor socioeconomic status in patients with cirrhosis: an international multicenter study. Clin Gastroenterol Hepatol 2013; 11(11):1511-1516.
48. Bajaj JS et al. The multi-dimensional burden of cirrhosis and hepatic encephalopathy on patients and caregivers. Am J Gastroenterol 2011; 106: 1646-1653.
49. Hartmann IJ et al. The prognostic significance of subclinical hepatic encephalopathy. Am J Gastroen-terol 2000; 95: 2029-2034.
50. Prakash RK, Brown TA, Mullen KD.Minimal hepatic encephalopathy and driving: is the genie out of the bottle? Am J Gastroenterol 2011; 106(8):1415-1416.
51. Amodio P, Montagnese S, Merkel C. Attention: Minimal hepatic encephalopathy and road accidents. Hepatol 2012; 55(4): 985-987.
52. Wein C, Koch H, Popp B, Oehler G, Schauder P. Minimal hepatic encephalopathy impairs fitness to drive. Hepatol 2004; 39(3): 739-745.
53. Amodio P et al. Clinical features and survival of cirrhotic patients with subclinical cognitive alterations detected by the number connection test and computerized psychometric tests. Hepatol 1999; 29: 1662-1667.
54. Dhiman RK et al.. Diagnosis and prognostic significance of minimal hepatic encephalopathy in patients with cirrhosis of liver. Dig Dis Sci 2010; 55: 2381-2390.
55. Simon -Talero M., Ventura M, Cordoba J. Minimal hepatic encephalopathy. In: Gines P,Forns X, Fernandez J, Crespo G, Rodes J, Arroyo V Therapy in Liver Diseases 2013; Barcelona: Elsevier Doyma. 20: 151-157.
56. Dhiman RK, Chawla YK. Minimal hepatic encephalopathy. Indian J Gastroenterol 2009; 28: 5-16.
57. Randolph C et al. International Society for Hepatic Encephalopathy and Nitrogen Metabolism (ISHEN). Neuropsychological assessment of hepatic encephalopathy: ISHEN practice guidelines. Liver Int 2009; 29(5): 629-635.
58. Bajaj JS. Expanding the Spectrum of Hepatic Encephalothy. In: Di Biseglie AM, Martin P. AASLD The liver meeting - Postgraduate Course 2013. Washington: American Association for the Study of Liver Disease: 169-175.
59. Als Nielsen B,Gluud LL,Gluud C. Non absorabable disaccharides for hepatic encephalopathy: sys-tematic review of randomized trials. BMJ 2004; 328: 1046.
60. Liu Q et al. Lactulose improves cognitive functions and health-related quality of life in patients with cirrhosis who have minimal hepatic encephalopathy. Hepatol 2007; 45: 549-559.
61. Sidhu SS et al. Rifaximin improves psychometric performance and health-related quality of life in patients with minimal hepatic encephalopathy (the RIME trial). Am J Gastroenterol 2011; 106: 307-316.
62. Irimia R, Trifan A. Efficacy of rifaximin versus lactulose for reducing the recurrence of overt hepatic encephalopathy and hopitalizations in cirrhosis. Rev Med Chir Soc Med Nat Iasi 2012; 116(4):1021-1027.
63. Mittal VV et al. An randomized controled trial comparing lactulose, probiotics and L-ornithine L-aspartate in treatment of minimal hepatic encephalopathy. Eur J Gastroenterol Hepatol 2011; 23: 725-732.
64. Bajaj JS et al. Probiotic yogurt for the treatment of minimal hepatic encephalopathy. Am J Gastroenterol 2008; 103: 1707-1715.
65. Shukla S. et al. Meta-analysis: the effects of gut flora modulation using prebiotics, probiotics and synbiotics on minimal hepatic encephalopathy. Aliment Pharmacol Ther 2011; 33: 662-671.
Additional Files
Published
2015-03-31
Issue
Section
INTERNAL MEDICINE - PEDIATRICS
License
COPYRIGHT
Once an article is accepted for publication, MSJ requests a transfer of copyrights for published articles.
COPYRIGHT TRANSFER FORM FOR
REVISTA MEDICO-CHIRURGICALĂ A SOCIETĂȚII DE MEDICI ȘI NATURALIȘTI DIN IAȘI /
THE MEDICAL-SURGICAL JOURNAL OF THE SOCIETY OF PHYSICIANS AND NATURALISTS FROM IASI
We, the undersigned authors of the manuscript entitled
_____________________________________________________________________________________
_____________________________________________________________________________________
warrant that this manuscript, which is submitted for publication in the REVISTA MEDICO-CHIRURGICALĂ, has not been published and it is not under consideration for publication in another journal.
- we give the consent for publication in the REVISTA MEDICO-CHIRURGICALĂ, in printed and electronic format and we transfer unconditioned and complete the copyright of this manuscript to the REVISTA MEDICO-CHIRURGICALĂ, in the event of its acceptance.
- the manuscript does not break the intellectual property rights of any other person.
- we have read the submitted version of the manuscript and we are fully responsible for the content.
Names and signatures of authors / copyright owners (the following sequence is the authorship of the article):
- ______________________________/_________________________
- ______________________________/_________________________
- ______________________________/_________________________
N.B. All the authors must sign this form
