Minimal hepatic encephalopathy: Consensus statement of a working party of the Indian National Association for Study of the Liver

Journal of Gastroenterology and Hepatology (Australia)

Volumn 25, Issue 6, 2010, Pages 1029-1041

  Dhiman, Radha K ^a   Saraswat, Vivek A ^b   Sharma, Barjesh K ^c   Sarin, Shiv K ^d   Chawla, Yogesh K ^a   Butterworth, Roger ^l   Duseja, Ajay ^a   Aggarwal, Rakesh ^b   Amarapurkar, Deepak ^g   Sharma, Praveen ^d   Madan, Kaushal ^d   Shah, Samir ^h   Seth, Avnish K ^e   Gupta, Rakesh K ^b   Koshy, Abraham ⁱ   Rai, Ramesh R ^j   Dilawari, Jang B ^m   Mishra, Sri Prakash ^k   Acharya, Subrat K ^f  

^a POSTGRADUATE INSTITUTE OF MEDICAL EDUCATION AND RESEARCH   (India)

^b SANJAY GANDHI POSTGRADUATE INSTITUTE OF MEDICAL SCIENCES   (India)

^c G B PANT HOSPITAL   (India)

^d INSTITUTE OF LIVER AND BILIARY SCIENCES   (India)

^e ARMY HOSPITAL RESEARCH AND REFERRAL   (India)

^f ALL INDIA INSTITUTE OF MEDICAL SCIENCES   (India)

^g BOMBAY HOSPITAL   (India)

^h JASLOK HOSPITAL AND RESEARCH CENTRE   (India)

ⁱ Department of Hepatology Lakeshore Hospital ^*  (India)

^j Sawai Mann Singh Medical College and Hospital   (India)

^k UNIVERSITY OF ALLAHABAD   (India)

^l UNIVERSITY OF MONTREAL   (Canada)

^m INVERCLYDE ROYAL HOSPITAL   (United Kingdom)

more..

Author keywords

Critical clicker frequency; Health related quality of life; Hepatic encephalopathy; Lactulose; Minimal hepatic encephalopathy; Psychometric hepatic encephalopathy score; Psychometry

Indexed keywords

AMMONIA; ANTIBIOTIC AGENT; LACTITOL; LACTULOSE; ORNITHINE ASPARTATE; PLACEBO; PREBIOTIC AGENT; PROBIOTIC AGENT; SUCROSE; SYNBIOTIC AGENT; YOGHURT; ANTIINFECTIVE AGENT; GASTROINTESTINAL AGENT;

CLINICAL FEATURE; CLINICAL PRACTICE; CLINICAL TRIAL; COGNITIVE DEFECT; HEALTH CARE COST; HEPATIC ENCEPHALOPATHY; HUMAN; INDIA; INFLAMMATION; INTESTINE FLORA; LIVER CIRRHOSIS; MOTOR DYSFUNCTION; NEUROPHYSIOLOGY; NUCLEAR MAGNETIC RESONANCE IMAGING; NUCLEAR MAGNETIC RESONANCE SPECTROSCOPY; PRACTICE GUIDELINE; PREVALENCE; PRIORITY JOURNAL; QUALITY OF LIFE; REVIEW; ALGORITHM; COMPLICATION; CONSENSUS DEVELOPMENT; DISEASE COURSE; MEDICAL SOCIETY; TREATMENT OUTCOME; ARTICLE; CRITICAL FLICKER FUSION; ECONOMIC ASPECT; INDIAN; MINIMAL HEPATIC ENCEPHALOPATHY; NEUROPSYCHOLOGICAL TEST; PATHOGENESIS;

ALGORITHMS; ANTI-BACTERIAL AGENTS; CONSENSUS DEVELOPMENT CONFERENCES AS TOPIC; DISEASE PROGRESSION; GASTROINTESTINAL AGENTS; HEPATIC ENCEPHALOPATHY; HUMANS; LIVER CIRRHOSIS; PRACTICE GUIDELINES AS TOPIC; PREVALENCE; PROBIOTICS; QUALITY OF LIFE; SOCIETIES, MEDICAL; TREATMENT OUTCOME;

EID: 77952992962     PISSN: 08159319     EISSN: 14401746     Source Type: Journal    
DOI: 10.1111/j.1440-1746.2010.06318.x     Document Type: Review

References (98)

1. Poordad FF. Review article: the burden of hepatic encephalopathy. Aliment. Pharmacol. Ther. 2007 25 (Suppl 1 3 9.
2. 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. Hepatology 2002 35 : 716 721.
3. Prasad S, Dhiman RK, Duseja A, Chawla YK, Sharma A, Agarwal R. Lactulose improves cognitive functions and health-related quality of life in patients with cirrhosis who have minimal hepatic encephalopathy. Hepatology 2007 45 : 549 559.
4. Das A, Dhiman RK, Saraswat VA, Verma M, Naik SR. Prevalence and natural history of subclinical hepatic encephalopathy in cirrhosis. J. Gastroenterol. Hepatol. 2001 16 : 531 535.
5. Centre for evidence-based medicine. Levels of evidence. 2001. Cited 2 March 2008. Available from URL: http://www.cebm.net/index.aspx?o=1047.
6. Mullen KD. Review of the final report of the 1998 Working Party on definition, nomenclature and diagnosis of hepatic encephalopathy. Aliment. Pharmacol. Ther. 2007 25 (Suppl 1 11 6.
7. Sarin SK, Nundy S. Subclinical encephalopathy after portosystemic shunts in patients with non-cirrhotic portal fibrosis. Liver. 1985 5 : 142 146.
8. Mínguez B, García-Pagán JC, Bosch J et al. Noncirrhotic portal vein thrombosis exhibits neuropsychological and MR changes consistent with minimal hepatic encephalopathy. Hepatology 2006 43 : 707 714.
9. Sharma P, Sharma BC, Puri V, Sarin SK. Minimal hepatic encephalopathy in patients with extrahepatic portal vein obstruction. Am. J. Gastroenterol. 2008 103 : 1406 1412.
10. Sharma P, Sharma BC, Puri V, Sarin SK. Natural history of minimal hepatic encephalopathy in patients with extrahepatic portal vein obstruction. Am. J. Gastroenterol. 2009 104 : 885 890.
11. Sharma P, Sharma BC, Tyagi P, Kumar M, Sarin SK. Neuropsychological impairment in severe acute viral hepatitis is due to minimal hepatic encephalopathy. Liver. Int. 2009 29 : 260 264.
12. Gitlin N, Lewis DC, Hinkley L. The diagnosis and prevalence of subclinical hepatic encephalopathy in apparently healthy, ambulant, non-shunted patients with cirrhosis. J. Hepatol. 1986 3 : 75 82.
13. Quero JC, Hartman IJ, Meulstee J, Hop WC, Schalm SW. The diagnosis of subclinical hepatic encephalopathy in patients with cirrhosis using neuropsychological tests and automated electroencephalogram analysis. Hepatology 1996 24 : 556 560.
14. Goeneweg M, Moerland W, Quero JC. Screening of subclinical hepatic encephalopathy. J. Hepatology 2000 32 : 748 753.
15. Romero-Gomez M, Boza F, Garcia-Valdecasas MS, García E, Aguilar-Reina J. Subclinical hepatic encephalopathy predicts the development of overt hepatic encephalopathy. Am. J. Gastroenterol. 2001 96 : 2718 2723.
16. Hartmann IJ, Groeneweg M, Quero JC et al. The prognostic significance of subclinical hepatic encephalopathy. Am. J. Gastroenterol. 2000 95 : 2029 2034.
17. Saxena N, Bhatia M, Joshi YK, Garg PK, Dwivedi SN, Tandon RK. Electrophysiological and neuropsychological tests for the diagnosis of subclinical hepatic encephalopathy and prediction of overt encephalopathy. Liver. 2002 22 : 190 197.
18. Li YY, Nie YQ, Sha WH, Zeng Z, Yang FY. Prevalence of subclinical hepatic encephalopathy in cirrhotic patients in China. World. J. Gastroenterol. 2004 15 (1 2397 2401.
19. Sharma P, Sharma BC, Puri V, Sarin SK. Critical flicker frequency: diagnostic tool for minimal hepatic encephalopathy. J. Hepatol. 2007 47 : 67 73.
20. Romero-Gómez M, Córdoba J, Jover R et al. Value of the critical flicker frequency in patients with minimal hepatic encephalopathy. Hepatology 2007 45 : 879 885.
21. Bajaj JS, Saeian K, Verber MD, Hischke D, Hoffmann RG, Franco J. Inhibitory control test is a simple method to diagnose minimal hepatic encephalopathy and predict development of overt hepatic encephalopathy. Am. J. Gastroenterol. 2007 102 : 754 760.
22. Dhiman RK, Kurmi R, Thumburu KK et al. Diagnosis and prognostic significance of minimal hepatic encephalopathy in patients with cirrhosis of liver. Dig. Dis. Sci. 2010 55 In press).
23. Groeneweg M, Quero JC, De Bruijn I et al. Subclinical hepatic encephalopathy impairs daily functioning. Hepatology 1998 28 : 45 9.
24. Schomerus H, Hamster W. Quality of life in cirrhotics with minimal hepatic encephalopathy. Metab. Brain. Dis. 2001 16 : 37 41.
25. Schomerus H, Hamster W, Blunck H, Reinhard U, Mayer K, Dolle W. Latent portasystemic encephalopathy. I. Nature of cerebral functional defects and their effect on fitness to drive. Dig. Dis. Sci. 1981 26 : 622 630.
26. Watanabe A, Tuchida T, Yata Y, Kuwabara Y. Evaluation of neuropsychological function in patients with liver cirrhosis with special reference to their driving ability. Metab. Brain. Dis. 1995 10 : 239 248.
27. Srivastava A, Mehta R, Rothke SP, Rademaker AW, Blei AT. Fitness to drive in patients with cirrhosis and portal-systemic shunting: a pilot study evaluating driving performance. J. Hepatol. 1994 21 : 1023 1028.
28. Wein C, Koch H, Popp B, Oehler G, Schauder P. Minimal hepatic encephalopathy impairs fitness to drive. Hepatology 2004 39 : 739 745. (Pubitemid 38337653)
29. Marotolli RA, Cooney LM, Wagner S, Doucette J, Tinetti ME. Predictors of automobile crashes and moving violations among elderly drivers. Ann. Intern. Med. 1994 121 : 842 846.
30. Bajaj JS, Hafeezullah M, Hoffmann RG, Saeian K. Minimal hepatic encephalopathy: a vehicle for accidents and traffic violations. Am. J. Gastroenterol. 2007 102 : 1903 1909.
31. Bajaj JS, Ananthakrishnan AN, McGinley EL, Hoffmann RG, Brasel KJ. Deleterious effect of cirrhosis on outcomes after motor vehicle crashes using the nationwide inpatient sample. Am. J. Gastroenterol. 2008 103 : 1674 1681.
32. Bajaj JS, Saeian K, Schubert CM et al. Minimal hepatic encephalopathy is associated with motor vehicle crashes: the reality beyond the driving test. Hepatology 2009 50 : 1175 1183.
33. Bajaj JS, Hafeezullah M, Hoffmann RG et al. Navigation skill impairment: Another dimension of the driving difficulties in minimal hepatic encephalopathy. Hepatology 2008 47 : 596 604.
34. Folstein M, Folstein SE, McHugh PR. "Mini-Mental State" a practical method for grading the cognitive state of patients for the clinician. J. Psych. Res. 1975 12 : 189 198.
35. Dhiman RK, Chawla YK. Minimal hepatic encephalopathy. Indian. J. Gastroenterol. 2009 28 : 5 16.
36. Weissenborn K, Ennen JC, Schomerus H, Ruckert N, Hecker H. Neuropsychological characterization of hepatic encephalopathy. J. Hepatol. 2001 34 : 768 773.
37. Weissenborn K. PHES: one label, different goods?! J. Hepatol. 2008 49 : 308 312.
38. Dhiman RK, Saraswat VA, Verma M, Naik SR. Figure connection test: A modified number connection test for the objective assessment of mental state in illiterates. J. Gastroenterol. Hepatol. 1995 10 : 14 23.
39. Weissenborn K, Scholz M, Hinrichs H, Wiltfang J, Schmidt FW, Kunkel H. Neurophysiological assessment of early hepatic encephalopathy. Electroencephalogr. Clin. Neurophysiol. 1990 75 : 289 295.
40. Amodio P, Quero JC, Del Piccolo F, Gatta A, Schalm SW. Diagnostic tools for the detection of subclinical hepatic encephalopathy: comparison of standard and computerized psychometric tests with spectral-EEG. Metab. Brain. Dis. 1996 11 : 315 327.
41. Amodio P, Del Piccolo F, Pettenò E et al. Prevalence and prognostic value of quantified electroencephalogram (EEG) alterations in cirrhotic patients. J. Hepatol. 2001 35 : 37 45.
42. Amodio P, Valenti P, Del Piccolo F et al. P300 latency for the diagnosis of minimal hepatic encephalopathy: evidence that spectral EEG analysis and psychometric tests are enough. Dig. Liver. Dis. 2005 37 : 861 868.
43. Amodio P, Gatta A. Neurophysiological investigation of hepatic encephalopathy. Metab. Brain. Dis. 2005 20 : 369 379.
44. Kullmann F, Hollerbach S, Holstege A, Scholmerich J. Subclinical hepatic encephalopathy: the diagnostic value of evoked potentials. J. Hepatol. 1995 22 : 101 110.
45. Saxena N, Bhatia M, Joshi YK et al. Auditory P300 event-related potentials and number connection test for evaluation of subclinical hepatic encephalopathy in patients with cirrhosis of the liver: a follow-up study. J. Gastroenterol. Hepatol. 2001 16 : 322 327.
46. Kircheis G, Wettstein M, Timmermann L et al. Critical flicker frequency for quantification of low-grade hepatic encephalopathy. Hepatology 2002 35 : 357 366.
47. Bajaj JS, Hafeezullah M, Franco J et al. Inhibitory control test for the diagnosis of minimal hepatic encephalopathy. Gastroenterology 2008 135 : 1591 1600.
48. Inoue E, Hori S, Narumi Y et al. Portal-systemic encephalopathy: presence of basal ganglia lesions with high signal intensity on MR images. Radiology 1991 179 : 551 555.
49. Zeneroli ML, Cioni G, Crisi G, Vezzelli C, Ventura E. Globus pallidus alterations and brain atrophy in liver cirrhosis patients with encephalopathy: an MR imaging study. Magn. Reson. Imaging. 1991 9 : 295 302.
50. Spahr L, Butterworth RF, Fontaine S et al. Increased blood manganese in cirrhotic patients: relationship to pallidal magnetic resonance signal hyperintensity and neurological symptoms. Hepatology 1996 24 : 1116 1120.
51. Binesh N, Huda A, Bugbee M et al. Adding another spectral dimension to 1H magnetic resonance spectroscopy of hepatic encephalopathy. J. Magn. Reson. Imaging. 2005 21 : 398 405.
52. Weissenborn K, Ehrenheim C, Hori A, Kubicka S, Manns MP. Pallidal lesions in patients with liver cirrhosis: clinical and MRI evaluation. Metab. Brain. Dis. 1995 10 : 219 231.
53. Rose C, Butterworth RF, Zayed J et al. Manganese deposition in basal ganglia structures results from both portal-systemic shunting and liver dysfunction. Gastroenterology 1999 117 : 640 644.
54. Yadav SK, Srivastava A, Srivastava A et al. Encephalopathy assessment in children with extra-hepatic portal vein obstruction with MR, psychometry and critical flicker frequency. J. Hepatol. 2010 216 : 683 691.
55. Naegele T, Grodd W, Viebahn R et al. MR imaging and (1)H spectroscopy of brain metabolites in hepatic encephalopathy: time-course of renormalization after liver transplantation. Radiology 2000 52 : 348 354.
56. Weissenborn K, Ahl B, Fischer-Wasels D et al. Correlations between magnetic resonance spectroscopy alterations and cerebral ammonia and glucose metabolism in cirrhotic patients with and without hepatic encephalopathy. Gut. 2007 56 : 1736 1742.
57. Schaefer PW, Grant PE, Gonzalez RG. Diffusion-weighted MR imaging of the brain. Radiology 2000 217 : 331 345.
58. Lodi R, Tonon C, Stracciari A et al. Diffusion MRI shows increased water apparent diffusion coefficient in the brains of cirrhotics. Neurology 2004 62 : 762 766.
59. Kale RA, Gupta RK, Saraswat VA et al. Demonstration of interstitial cerebral edema with diffusion tensor MR imaging in type C hepatic encephalopathy. Hepatology 2006 43 : 698 706.
60. Cordoba J, Cabrera J, Lataif L, Pener P, Zee P, Blei AT. High prevalence of sleep disturbances in cirrhosis. Hepatology 1998 27 : 339 345.
61. Weissenborn K, Heidenreich S, Giewekemeyer K, Ruckert N, Hecker H. Memory function in early hepatic encephalopathy. J. Hepatol. 2003 39 : 320 325.
62. Dhiman RK, Sawhney MS, Chawla YK, Das G, Ram S, Dilawari JB. Efficacy of lactulose in cirrhotic patients with subclinical hepatic encephalopathy. Dig. Dis. Sci. 2000 45 : 1549 1552.
63. Bajaj JS, Saeian K, Christensen KM et al. Probiotic yogurt for the treatment of minimal hepatic encephalopathy. Am. J. Gastroenterol. 2008 103 : 1707 1715.
64. Sharma P, Sharma BC, Puri V, Sarin SK. An open-label randomized controlled trial of lactulose and probiotics in the treatment of minimal hepatic encephalopathy. Eur. J. Gastroenterol. Hepatol. 2008 20 : 506 511.
65. Liu Q, Duon ZP, Ha DK et al. Synbiotic modulation of gut flora: effect on minimal hepatic encephalopathy in patients with cirrhosis. Heptology 2004 39 : 1441 1449.
66. Malaguarnera M, Greco F, Barone G, Gargante MP, Malaguarnera M, Toscano MA. Bifidobacterium longum with fructo-oligosaccharide (FOS) treatment in minimal hepatic encephalopathy: a randomized, double-blind, placebo-controlled study. Dig. Dis. Sci. 2007 52 : 3259 3265.
67. Mittal VV, Sharma P, Sharma BC, Sarin S. Treatment of minimal hepatic encephalopathy: A randomised controlled trial comparing lactulose, probiotics and l-ornithine l-aspartate with placebo. Hepatology 2009 50 (Suppl 471A.
68. Sharma BC, Sharma P, Agrawal A, Sarin SK. Secondary prophylaxis of hepatic encephalopathy: an open-label randomized controlled trial of lactulose versus placebo. Gastroenterology 2009 137 : 885 891.
69. Takano T, Tian GF, Peng W et al. Astrocyte-mediated control of cerebral blood flow. Nat. Neurosci. 2006 9 : 260 270.
70. Lockwood AH, McDonald JM, Reiman RE et al. The dynamics of ammonia metabolism in man. Effects of liver disease and hyperammonemia. J. Clin. Invest. 1979 63 : 449 460.
71. Felipo V, Butterworth RF. Neurobiology of ammonia. Prog. Neurobiol. 2002 67 : 259 279.
72. Ahboucha S, Butterworth RF. The neurosteroid system: implication in the pathophysiology of hepatic encephalopathy. Neurochem. Int. 2008 52 : 575 587.
73. Butterworth RF. Pathogenesis of hepatic encephalopathy: new insights from neuroimaging and molecular studies. J. Hepatol. 2003 39 : 278 285.
74. Rama Rao KV, Chen M, Simard JM, Norenberg MD. Increased aquaporin-4 expression in ammonia-treated cultured astrocytes. Neuroreport 2003 14 : 2379 2382.
75. Lozeva V, Montgomery JA, Rochelau B, Tuomisto L, Huet P-M, Butterworth RF. Selective alterations of central serotoninergic and histaminergic function following graded portal-systemic shunts: implications for the pathogenesis of post-TIPS encephalopathy. Hepatology 2001 34 : 185A.#45.
76. Coy DL, Mehta R, Zee P, Salchli F, Turek FW, Blei AT. Portal-systemic shunting and the disruption of circadian locomotor activity in the rat. Gastroenterology 1992 103 : 222 228.
77. Fan P, Lavoie J, Le NLO, Szerb JC, Butterworth RF. Neurochemical and electrophysiological studies on the inhibitory effect of ammonium ions on synaptic transmission in slices of rat hippocampus: evidence for a postsynaptic action. Neuroscience 1990 37 : 327 334.
78. Bergeron M, Swain MS, Reader TA, Grondin L, Butterworth RF. Effect of ammonia on brain serotonin metabolism in relation to function in the portacaval shunted rat. J. Neurochem. 1990 55 : 222 229.
79. De Waele JP, Audet RM, Leong DK, Butterworth RF. Portacaval anastomosis induces in region-selective alterations of the endogenous opioid system in the rat brain. Hepatology 1996 24 : 895 901.
80. Lozeva V, Tuomisto L, Sola D, Plumed C, Hippelainen M, Butterworth RF. Increased density of brain histamine H1 receptors in rats with portacaval anastomosis and in cirrhotic patients with chronic hepatic encephalopathy. Hepatology 2001 33 : 1370 1376.
81. Lockwood AH, Yap EW, Wong WH. Cerebral ammonia metabolism in patients with severe liver disease and minimal hepatic encephalopathy. J. Cereb. Blood. Flow. Metab. 1991 11 : 337 341.
82. Cordoba J, Alonso J, Rovira A et al. The development of low-grade cerebral edema in cirrhosis is supported by the evolution of (1)H-magnetic resonance abnormalities after liver transplantation. J. Hepatol. 2001 35 : 598 604.
83. Balata S, Damink SW, Ferguson K et al. Induced hyperammonemia alters neuropsychology, brain MR spectroscopy and magnetization transfer in cirrhosis. Hepatology 2003 37 : 931 939.
84. Shawcross DL, Balata S, Olde Damink SW et al. Low myo-inositol and high glutamine levels in brain are associated with neuropsychological deterioration after induced hyperammonemia. Am. J. Physiol. Gastrointest. Liver. Physiol. 2004 287 : G503 G509.
85. Shawcross DL, Davies NA, Williams R, Jalan R. Systemic inflammatory response exacerbates the neuropsychological effects of induced hyperammonemia in cirrhosis. J. Hepatol. 2004 40 : 247 254.
86. Shawcorss DL, Wright G, Olde Damink SWM, Jalan R. Role of ammonia and inflammation in minimal hepatic encephalopathy. Metab. Brain. Dis. 2007 22 : 125 138.
87. Zhao HY, Wang HJ, Zhi LU, Zhen XU. Intestinal microflora in patients with liver cirrhosis. Chin. J. Dig. 2004 5 : 64 7.
88. Amodio P, Piccolo FD, Marchetti P et al. Clinical features and survival of cirrhotic patients with subclinical cognitive alterations detected by the number connection test and computerized psychometric tests. Hepatology 1999 29 : 1662 1667.
89. Hartmann IJC, Groeneweg M, Quero JC et al. The prognostic significance of subclinical hepatic encephalopathy. Am. J. Gastroenterol. 2000 95 : 2029 2034.
90. Romero-Gomez M, Grande L, Camacho I, Benitez S, Irles JA, Castro M. Altered response to oral glutamine challenge as prognostic factor for overt episodes in patients with minimal hepatic encephalopathy. J. Hepatol. 2002 37 : 781 787.
91. McClain CJ, Potter TJ, Kromhort JP, Zieve L. The effect of lactulose on psychomotor performance tests in alcoholic cirrhotics without overt hepatic encephalopathy. J. Clin. Gastroenterol. 1981 6 : 325 329.
92. Morgan MY, Alonso M, Stanger LC. Lactilol and lactulose for treatment of subclinical HE in cirrhotic patients. J. Hepatol. 1989 8 : 208 217.
93. Watanabe A, Sakai T, Sato S et al. Clinical efficacy of lactulose in cirrhotic patients with and without subclinical hepatic encephalopathy. Hepatology 1997 26 : 1410 1414.
94. Horsmans Y, Solbreux PM, Daenens C, Desager JP, Geubel AP. Lactulose improves psychometric testing in cirrhotic patients with subclinical encephalopathy. Aliment. Pharmacol. Ther. 1997 11 : 165 170.
95. Nie YQ, Zeng Z, Li YY, Sha WH, Ping L, Dai SJ. [Long-term efficacy of lactulose in patients with subclinical hepatic encephalopathy]. Zhonghua. Nei. Ke. Za. Zhi. 2003 42: 4 261-263.
96. In Chinese G, Severijnen R, Timmerman H. Effect of antibiotics, prebiotics and probiotics in treatment for hepatic encephalopathy. Med. Hypotheses. 2005 64 : 64 8.
97. Bouhnik Y, Attar A, Joly FA et al. Lactulose ingestion increases faecal bifidobacterial counts: a randomised double-blind study in healthy humans. Eur. J. Clin. Nutr. 2004 58 : 462 466.
98. Solga SF. Probiotics can treat hepatic encephalopathy. Medical. Hypotheses. 2003 61 : 307 313.