7.4 Efficient Implementation
7.4.1 Parallelism
108
CONCLUSIONS AND RECOMMENDATIONS 6.1 CONCLUSIONS:
1. Psychometric hepatic encephalopathy score is a useful tool for the diagnosis of minimal hepatic encephalopathy and can be applied both in the outpatient and inpatient situation.
2. The frequency of minimal hepatic encephalopathy in patients with liver cirrhosis without overt hepatic encephalopathy attending the Gastroenterology unit of UNTH, Ituku/Ozalla is high at 46%.
3. The presence of MHE in patients with liver cirrhosis who do not have overt hepatic encephalopathy is predicted by the presence of splenomegaly, thrombocytopaenia and hypoalbuminaemia.
4. MHE was strongly correlated with severity of liver disease as measured by the Child-Pugh grading system.
109
1. In view of the high prevalence of MHE and its negative implication, it is recommended that Physicians and Hepatologists who care for patients with liver cirrhosis should apply simple psychometric tests like PHES to diagnose MHE more easily if present.
2. Child-Pugh B/C, liver cirrhosis patients with thrombocytopenia, splenomegaly and hypoalbuminaemia should raise the clinician’s index of suspicion for MHE.
3. Gastroenterology societies, Physicians and General practitioners who care for patients with liver cirrhosis should have a high index of suspicion for MHE and use every
opportunity of clinic visit to screen at risk patients thereby improving on the awareness of this condition.
4. Further studies are needed to determine the frequency and pattern of minimal hepatic encephalopathy in patients with liver cirrhosis from other centres in Nigeria and Africa.
This will both validate the findings from this study and derive a population based normative data for psychometric tests.
5. In view of the high prevalence of MHE among patients with liver cirrhosis in this study and its known negative impact on activities requiring concentration such as driving, it may be necessary for policy makers to restrict patients with MHE from such activities.
REFERENCES
110
1. Amodio P. The liver, the brain and nitrogen metabolism. Metab Brain Dis 2009;24:1-4.
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;(3)35:716-772.
3. 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(11):11-16.
4. Ramos JF, Leal CR. Review of the final report of the 1998 working party on definition, nomenclature and diagnosis of hepatic encephalopathy. Ann of Hepatol 2011;10(2):36-39.
5. Raskin NH, Price JB, Fishman RA. Portal-systemic encephalopathy due to congenital intrahepatic shunts. N Engl J Med 1964;270:225-229.
6. Lockwood AH. "What's in a name?" Improving the care of cirrhotics. J Hepatol 2000;32:859–861.
7. Romero-Gomez M, Boza F, Garcia-Valdecasas MS, Garcia E, Aguilar-Reina J.
Subclinical hepatic encephalopathy predicts the development of overt hepatic encephalopathy. Am J of Gastroenterol 2001;96:2718–2723.
8. Ortiz M, Jacas C, Cordoba J. Minimal hepatic encephalopathy: diagnosis, clinical significance and recommendations. J Hepatol 2005;42 (1):45-53.
9. Hartmann IJ, Groeneweg M, Quero JC, Beijeman SJ, De-Man RA, Hop WC, et al. The prognostic significance of subclinical hepatic encephalopathy. Am J Gastroenterol 2000;95:2029–2034.
111
10. Groeneweg M, Quero JC, De-Bruijn I, Hartmann IJC, Essink-Bot M, Hop WCJ, et al. Subclinical hepatic encephalopathy impairs daily functioning. Hepatology 2003; 28(1):45-49.
11. Baskin-Bey ES, Stewart CA, Mitchell MM, Bida JP, Rosenthal TJ, Nyberg SL.
Preliminary report of the hepatic encephalopathy assessment driving simulator (heads) score. Ethnic and Dis 2008;18:65-67.
12. Bajaj JS, Pinkerton SD, Sanyal AJ, Heuman DM. Diagnosis and treatment of minimal hepatic encephalopathy to prevent motor vehicle accidents: A cost-effectiveness analysis. Hepatology 2012;55:1164–1171.
13. Bajaj JS, Hafeezullah M, Hoffmann RG, Saeian K. Minimal hepatic encephalopathy: a vehicle for accidents and traffic violations.Am J Gastroenterol2007;102:1903–1909.
14. Sharma P, Sharma BC, Amit A, Shiv KS. Primary prophylaxis of overt hepatic encephalopathy in patients with cirrhosis. J Gastroenterol Hepatol 2012;27(8):
1329-1335.
15. Zhan T, Stremmel W. The Diagnosis and treatment of minimal hepatic encephalopathy. Dtsch Arztebl Int2012;109(10):180–187.
16. Bajaj JS, Etemadian A, Hafeezullah M, Saeian K. Testing for minimal hepatic encephalopathy in the United States: an AASLD survey. Hepatology 2007;
45:833–834.
17. Vilstrup H, Amodio P, Bajal J, Cordoba J, Ferenci P, Mullen KD, et al. hepatic encephalopathy in chronic liver disease 2014 practice guideline by the
112
American Association for the Study of Liver Diseases and European Association for the Study of the Liver. Hepatology 2014;60(2):715-735.
18. Guillen JC, Harreri JM. Diagnostic methods in hepatic encephalopathy. Clin Chim Acta 2006;365(2):1-8.
19. Cordoba-Cardona J. Dimitroulopoulos D. Minimal hepatic encephalopathy. Ann Gastroenterol 2004;17(1):37-42.
20. Onyekwere CA, Ogbera AO, Hameed L. Chronic liver disease and hepatic encephalopathy: Clinical profile and outcomes. Nig J Clin Pract 2011;14:181-185.
21. Sunmonu TA, Adekanle O, Komolafe MA, Ndububa DA. Cognitive function in patients with liver cirrhosis without overt hepatic encephalopathy: Assessment using an automated neuropsychological test battery. Arab J Gastroenterol 2012;
13(1):4-8.
22. Adekanle O, Sunmonu TA, Komolafe MA, Ndububa DA. Cognitive functions in patients with liver cirrhosis: Assessment using community screening
interview for dementia. Ann Afr Med 2012;11(4):222-229.
23. Ekanem EE, Etuk IS, Uniga AJ. Features of childhood hepatic failure in Calabar, Nigeria. Niger Postgrad Med J 2001;8:86-89.
24. Duarte-RojoA, Estradas J, Hernandez-Ramos R, Ponce-de-Leon S, CordobaJ, Torre A. Validation of the psychometric hepatic encephalopathy score (PHES) for identifying patients with minimal hepatic encephalopathy. Dig Dis Sci 2011;56(10):3014-3023.
25. Badea MA,Prelipcean CC,Mihai C,Popa I,Drug VL. Psychometric hepatic encephalopathy score for the diagnosis of minimal hepatic encephalopathy in Romanian cirrhotic patients- partial results. Rev Med Chir Soc Med Nat Iasi.2015; 119(2):368-373.
113
26. Dhiman RK, Saraswat VA, Sharma BK, Sarin SK, Chawla YK, Butterworth R, et al. Minimal hepatic encephalopathy: Consensus statement of a working party of the Indian National Association for Study of the Liver. J Gastroenterol Hepatol 2010;25:1029–1041.
27. Bojuwoye BJ. The burden of viral hepatitis in Africa. West Afr J Med 1997;
16:198-203.
28. Ghany M, Hoofnagle JH. Approach to the patient with liver disease: in: Kasper DL, Braunwauld E, Fauci AS, Hauser SL, Longo DL, Jameson JL (eds).
Harrison’s Principles of Internal Medicine, 16th edn. New York: The McGraw-Hill 2005:1808-1813.
29. Tsega E. The Liver :in: Eldryd P, Richard G, David M, Geoffrey G (eds).
Principles of Medicine in Africa. 3rd edn. United Kingdom: Cambridge University Press 2004: 991-993.
30. Bojuwoye BJ. Chronic liver diseases in Nigeria: An overview. Dokita 1996;23:1-4.
31. Anthony PP, Ishah KG, Nayak NC, Pouslen ME , Scheuer PJ, Sorbin LH. The morphology of cirrhosis: definition, nomenclature, and classification. Bull World Health Organ 1977;55:521-40.
32. Burroughs AK, Westaby D. Liver, biliary tract and pancreatic disease: in:
Kumar P, Clark M. (eds). Clinical Medicine, 6th Edn. Philadelphia: Elsevier 2005;347-356.
33. Schuppan D, Afdhal NH. Liver cirrhosis. Lancet 2008; 371(9615): 838–851.
34. Desa HG. Cryptogenic cirrhosis: A vanishing entity. J Ass of Ind Physi 2009;57:
751-755.
114
35. AbdelSalam MH. Aetiology, complications, and preventive measures of liver cirrhosis. Sudan J Med Sci 2008;3:25-29.
36. Nwokediuko SC, Ijoma U. Seroprevalence of antibody to HDV in Nigerians with hepatitis B virus-related liver diseases. Niger J Clin Prac 2009; 12(4):439-442.
37. Nwokediuko SC, Ibegbulam O. Quantitative platelet abnormalities in patients with hepatitis B virus-related liver disease. Gastroenterol Resea 2009;2:344-349.
38. Ndububa DA, Ojo OS, Aladegbaiye AO, Adebayo RA, Adetiloye VA, Durosinmi MA. Liver cirrhosis: Child-Pugh grading of cases seen in Nigeria.
Trop Doct 2005;35:169-171.
39. Lesi OA, Kehinde MO, Anomneze EE. Chronic liver disease in Lagos: A clinicopathological study. Niger Postgrad Med J 2004;11(2):91-96.
40. Mendy ME, Welzel T, Lesi OA,Hainaut P,Hall AJ, Kuniholm MH, et al.
Hepatitis B viral load and risk for liver cirrhosis and hepatocellular carcinoma in the Gambia, West Africa. J Viral Hepat 2010;17(2):115–122.
41. Olubuyide IO. Natural history of liver cirrhosis in 116 Nigerians. East Afr Med J 1996; 73(4):233-235.
42. Ndububa DA, Ojo OS, Adetiloye VA, Adekanle O. The contribution of alcohol to chronic liver disease in patients from South-west Nigeria. Niger J Clin Pract 2010; 13(4):360-364.
43. Adekanle O,Ndububa AD,OrjiEO, IjarotimiO. Assessment of the sexual functions of males with chronic liver disease in South West Nigeria. Ann Afr Med 2014:13(2);81-86.
115
44. Achinge IG, Malu AO, Okeke EN, Agaba EI, Misauno MA. Prevalence of oesophageal varices in newly diagnosed chronic liver disease patients at the Jos university teaching hospital, Jos. Niger Med J 2011;52(2):128-132.
45. Okeke EN, Malu AO, Obafunwa JO, Nwana EJ. Aetiological significance of alcohol in liver cirrhosis on the Jos Plateau. West Afr J Med 2002;21:12-14.
46. National Center for Health Statistics. National Vital Statistics Report. Chronic liver disease/cirrhosis. Accessed January 15 2016 at:
http://www.cdc.gov/nchs/fastats/liver-disease.htm.
47. Heidelbaugh JJ, Bruderly M. Cirrhosis and chronic liver failure: Part I.
Diagnosis and evaluation. Am Fam Physician 2006; 74(5):756-762.
48. Okunola OO, Akintunde AA, Akinwusi PO. Some emerging issues in medical admission pattern in the tropics. Niger J Clin Pract 2012;15(1):51-54.
49. Iliyasu Z, Abubakar IS, Gajida AU. Magnitude and leading causes of in-hospital mortality at Aminu Kano Teaching Hospital, Kano, Northern Nigeria: A 4-year prospective analysis. Niger J Med 2010;19(4):400-406.
50. Adeniji KA, Anjorin AS. Histopathological assessment of the pattern of liver cirrhosis in a tropical population. Afr J Med Sci 2002;31:367-369.
51. Echejoh GO, Tanko MN, Manasseh AN, Silas OA, Ogala-Echejoh SE, Mandong BM. Liver cirrhosis in Jos, north-central Nigeria. Jos J of Med 2008;3(1):26-28.
52. Nwokediuko SC, Osuala PC, Uduma UV, Alaneme AK, Onwuka CC, Mesigo C. Pattern of liver disease admissions in a Nigerian tertiary hospital. Nig J Clin Pract 2013;16(3):339-342.
116
53. Child CG, Turcotte J. Surgery and portal hypertension. In: Child CG, ed. The liver and portal hypertension. Philadelphia. Saunders, 1964,50-58.
54. Pugh RNH, Murray-Lyon M, Dawson JL, Pietroni MC, Williams R.
Transection of the oesophagus for bleeding oesophageal varices. Br J Surg 1973; 60: 646-649.
55. Christensen E, Schlichting P, Fauerholdt L, Gluud C, Andersen PK, Juhl E, et al. Prognostic value of Child-Turcotte criteria in medically treated cirrhosis.
Hepatology 1984;4:430-435.
56. Angermayr B,Cejna M, Karnel F,Gschwantler M,Koenig F,Pidlich J, et al.
Child-Pugh versus MELD score in predicting survival in patients undergoing transjugular intrahepatic portosystemic shunt. Gut 2003; 52(6): 879–885.
57. Kamath PS, Wiesner RH, Malinchoc M, Kremers W, Therneau TM, Kosberg CL. A model to predict survival in patients with end-stage liver. Hepatology 2001; 33:464–470.
58. Martin AP, Bartels M, Hauss J, Fangmann J: Overview of the MELD score and the UNOS adult liver allocation system. Transplant Proc 2007, 39:3169-3174.
59. Durand F, Villa D. Assessment of Prognosis of Cirrhosis. Semin Liver Dis 2008;
28(1):110-122.
60. Prakash R, Mullen KD. Mechanism, diagnosis and management of hepatic encephalopathy. Nat Rev Gastroenterol Hepatol 2010;7:515-525.
61. Poordad FF. Review article: the burden of hepatic encephalopathy. Aliment Pharmacol Ther 2007; 25: 3–9.
117
62. Onwuchekwa AC, Asekomeh EG, Iyagba AM, Onung SO. Medical mortality in the accident and emergency unit of the University of Port Harcourt Teaching Hospital. Niger J Med 2008; 17: 184-187.
63. Philip-Ephraim EE, Eyong KI, Oparah SK, Williams UE, Udonwa N, Gyuse AN, et al. Profile of neurologic emergencies at the accident and emergency department of a tertiary hospital in South Nigeria. J Neurolog Sci 2013;34:72-80.
64. Bajaj JS, Cordoba J, Mullen KD, Amodio, P, Shawcross DL, Butterworth RF, et al. Review article: the design of clinical trials in hepatic encephalopathy – an International Society for Hepatic Encephalopathy and Nitrogen Metabolism (ISHEN) consensus statement. Aliment Pharmacol Ther 2011; 33:739-747.
65. Maric D, Klasnja B, FilipovicD, Brkic S, Ruzic M, Bugarski V. Minimal hepatic encephalopathy in patients with decompensated liver cirrhosis. Acta Clin Croat 2011;50:375-380.
66. 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(5):531-535.
67. 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.
68. 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.
118
69. Sharma P, Sharma BC, Puri V, Sarin SK. Critical flicker frequency diagnostic tool for minimal hepatic encephalopathy. J Hepatol 2007;47:67-73.
70. Romero-Gomez M, Cordoba J, Jover R, Del-Olmo JA, Ramirez M, de-Madaria E, et al. Value of the critical flicker frequency in patients with minimal hepatic encephalopathy. Hepatology 2007;45(4):879-885.
71. Wang Y,Zhang N, Chi B, Mi Y,Meng L,Liu Y, et al. Prevalence of minimal hepatic encephalopathy and quality of life evaluations in hospitalized cirrhotic patients in China World J Gastroenterol 2013;19(30):4984–4991.
72. Dhiman RK,Kurmi R,Thumburu KK,Venkataramarao SH,Agarwal R,Duseja A. Diagnosis and prognostic significance of minimal hepatic encephalopathy in patients with cirrhosis of liver. Dig Dis Sci2010;55(8):2381-2390.
73. Zeng Z, Li YY, Nie YQ. An epidemiological survey of subclinical hepatic encephalopathy. Zhonghua Gan Zang Bing Za Zhi 2003;11(11):680-682.
74. Ayouty ME, Sharabasy AE, Regal MEE, Megahed A. The diagnosis and prevalence of subclinical hepatic encephalopathy in apparently healthy children and adolescents with cirrhosis. Int J Ch Neuropsychiatry 2004;1:60-65.
75. Sharma P, Sharma BC. Predictors of minimal hepatic encephalopathy in patients with cirrhosis. Saudi J Gastroenterol 2010;16:181–187.
76. Cordoba J, Lucke R. Driving under the influence of minimal hepatic encephalopathy. Hepatology 2004;39:599–601.
77. Schomerus H, Hamster W. Quality of life in cirrhotics with minimal hepatic encephalopathy. Metab Brain Dis 2001;16:37–41.
78. Bajaj JS. Minimal hepatic encephalopathy matters in daily life. World J Gastroenterol 2008;14(23):3609–3615.
119
79. McMillin M, DeMorrow S. The Ammonia hypothesis of hepatic encephalopathy should be revisited. J Cell Sci Ther 2012;3(6):1-3.
80. Ong JP,Aggarwal A,Krieger D,Easley KA,Karafa MT,Van Lente F, et al Correlation between ammonia levels and the severity of hepatic
Encephalopathy. Am J Med2003;114(3):188-193.
81. Frederick RT. Current concepts in the Pathophysiology and management of hepatic encephalopathy. Gastroenterol Hepatol 2001;7(4):222-233.
82. Zieve L, Dolzaki WM, Zieve FJ. Synagism between mercaptans and ammonia or fatty acids in the production of coma; a possible role for mercaptans in the pathogenesis of hepatic coma. J Lab Clin Med1974;83(1):16-28.
83. Fogel WA, Andrzejewski W, Maslinski C. Neurotransmitters in hepatic encephalopathy. Acta Neurobiol Exp (Wars) 1990;50:281-294.
84. Basile AS, Jones EA. Ammonia and GABA-ergic neurotransmission:
interrelated factors in the pathogenesis of hepatic encephalopathy. Hepatology 1997; 25(6):1303-1305.
85. Jones EA, Basile AS. Does ammonia contribute to increased GABergic neurotransmission in liver failure? Metab Brain Dis 1998;13(4):321-360.
86. Dasarathy S, Mullen KD. Benzodiazepines in hepatic encephalopathy: Sleeping with the enemy. Gut 1998;42:764-765.
87. Krieger D, Krieger S, Theilmann L , Jansen O, Gass P, Lichtnecker H.
Manganese and chronic hepatic encephalopathy. Lancet 1995;346:270-274.
88. Darakhshan MS, Saida H, Moona MK, Tahir S, Darakhshan JH. Role of tryptophan in the pathogenesis of hepatic encephalopathy. J Pak Med Assoc 2008;58(2):68-70.
120
89. Hazell AS, Butterworth RF. Hepatic encephalopathy: An update of pathophysiologic mechanism. Exp Biol Med 1999;222:99-112.
90. Chetri K, Choudhuri G. Role of trace elements in hepatic encephalopathy: Zinc and manganese. Indian J.Gastroenterol 2003;22:28-30.
91. Zhao HY, Wang HJ, Zhi LU, Shu ZX. Intestinal microflora in patients with liver cirrhosis. Chin J Dig Dis. 2004;5:64–67.
92. Garcovich M, Zocco MA, Roccarina D, Ponziani FR, Gasbarrini A. Prevention and treatment of hepatic encephalopathy: Focusing on gut microbiota. World J Gastroenterol 2012;18(46):6693-6700.
93. Wright G, Jalan R. Ammonia and Inflammation in the Pathogenesis of Hepatic Encephalopathy: Pandora’s Box? Hepatology 2007;46:291-294.
94. Conn HO, Leevy CM, Vlahcevic ZR, Rodgers JB,Maddrey WC,Seeff L, et al.
Comparison of lactulose and neomycin in the treatment of chronic porto-systemic encephalopathy: A double blind controlled trial. Gastroenterol 1977;72:573–583.
95. Hassanein TI, Hilsabeck RC, Perry W. Introduction to the hepatic
encephalopathy scoring algorithm (HESA). Dig Dis Sci 2008;53(2):529-538.
96. Ortiz M, Cordoba J, Doval E, Jacas C, Pujadas F, Esteban R, et al.
Development of a clinical hepatic encephalopathy staging scale. Aliment Pharmacol Ther2007; 26(6):859-867.
97. Folstein MF, Folstein SE, McHugh PR. “Mini-mental state”. A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res 1975;12:189–198.
121
98. Onwuekwe I. Assessment of mild cognitive impairment with mini mental state examination among adults in southeast Nigeria. Ann Med Health Sci Res 2012;
2(2):99-102.
99. Atya H. Questions and guide to answers. Egypt J intern Med 2013;25:232-236.
100. Weissenborn K, Ennen JC, Schomerus H, Ru ckert N, Hecker H.
Neuropsychological characterization of hepatic encephalopathy. J Hepatol 2001;34:768–773.
101. Weissenborn K. PHES: One label, different goods? J Hepatol.
2008;49(3):308-312.
102. Seo YS, Yim SY, Jung JY, Kim CH, Kim JD, Keum B, et al. Psychometric hepatic encephalopathy score for the detection of minimal hepatic
encephalopathy in Korean patients with liver cirrhosis. J Gastroenterol Hepatol 2012;27:1695-1704.
103. Romero Gomez M, Cordoba J, Jover R, del Olmo J, Fernandez A, Flavia M, et al. Normality tables in the Spanish population for psychometric tests used in the diagnosis of minimal hepatic encephalopathy. Med Clin (Barc)
2006;127:246–249.
104. Amodio P, Campagna F, Olianas S, Iannizzi P, Mapelli D, Penzo M, et al.
Detection of minimal hepatic encephalopathy: Normalization and optimization of the Psychometric Hepatic Encephalopathy Score. A neuropsychological and quantified EEG study. J Hepatol 2008;49:346–353.
122
105. Randolph C, Tierney MC, Mohr E, Chase TN. The repeatable battery for the assessment of neuropsychological status (RBANS): Preliminary clinical validity. J Clin Exp Neuropsychol 1998;20(3):310-319.
106. Cordoba-Cordona J, Dimitroulopoulos D. Minimal hepatic encephalopathy.
Ann Gastroenterol 2004;17(1):37-42.
107. Bajaj JS, Saeian K, Verber MD, Hischke D, Hoffmann RG, FrancoJ, et al.
Inhibitory control test is a simple method to diagnose minimal hepatic
encephalopathy and predict development of overt hepatic encephalopathy. Am J Gastroenterol 2007;102(4):754–760.
108. Lockwood AH, Weissenborn K, Butterworth RF. Image of the brain in patients with liver disease. Curr Opin Neurol 1997;10(6):525-533.
109. Cordoba J, Sanpedro F, Alonso J, Rovira A. Magnetic resonance in the study of hepatic encephalopathy in humans. Metab Brain Dis 2002;17:415–429.
110. Trzepacz PT, Tarter RE, Shah A, Tringali R, Faett DG, Van Thiel DH. SPECT scan and cognitive findings in subclinical hepatic encephalopathy.J
Neuropsychiatry Clin Neurosci 1994;6:170–175.
111. National Population Commission. Official Gazette (FGP 71/52007/2,500 (OL24). Legal notice on publication of the details of the breakdown of the national and state provisional totals 2006 census. Federal Republic of Nigeria, Abuja. 2007; 94(24): B175-198.
112. Human Experimentation: code of ethics of the world medical association.Br Med J1964;2:177.
123
113. Araoye MO. Research methodology with statistics for health and social sciences. Ilorin. Nathadex Publishers, 2003:117-121.
114. Mailliard ME, Sorrel MF. Alcoholic liver disease : in: Kasper DL, Braunwauld E, Fauci AS, Hauser SL, Longo DL, Jameson JL (eds). Harrison’s Principles of Internal Medicine, 16th edn. New York: The McGraw-Hill publishers 2005:
1855-1856.
115. Sherlock S. The natural history of hepatitis B. Post Grad Med J 1987; 63(2):7-11.
116. Yuen MF, Lai CL. Natural history of chronic hepatitis B infection. J of Gastro Hepatol 2000; 15(2):20-25.
117. Croagh CMN, Lubel JS. Natural history of chronic hepatitis B: Phases in a complex relationship. World J Gastroenterol 2014;20(30):10395–10404.
118. Yanghttp://pubs.acs.org/doi/abs/10.1021/pr900593r?tokenDomain=presspac&token Access=presspac&forwardService=showFullText&journalCode=jprobs - afn1 F, Yin Y,Wanghttp://pubs.acs.org/doi/abs/10.1021/pr900593r?tokenDomain=presspac&to kenAccess=presspac&forwardService=showFullText&journalCode=jprobs - cor1 F,Zhang L,Wang Y,
Sunhttp://pubs.acs.org/doi/abs/10.1021/pr900593r?tokenDomain=presspac&tokenA ccess=presspac&forwardService=showFullText&journalCode=jprobs - cor1 S. An altered pattern of liver apolipoprotein A-I isoforms is implicated in male chronic hepatitis B progression. J Proteome Res2010;9(1):134-143.
119. Yim HJ, Lok AS. Natural history of chronic hepatitis B virus infection: What we knew in 1981 and what we know in 2005. Hepatology 2006;43(2):173-181.
124
120. Oluyinka OO,Tong HV, Tien SB,Fagbami AH, Adekanle O,Ojurongbe O, et al. Occult hepatitis B virus Infection in Nigerian blood donors and hepatitis B virus transmission risks. PLoS One 2015; 10(7): 1-13.
121. Japhet MO,Adesina OA, Donbraye E,Adewumi MO. Hepatitis B Core IgM antibody (anti-HBcIgM) among hepatitis B surface antigen (HBsAg) negative blood donors in Nigeria. Virol J 2011;8:513-515.
122. Olotu AA, Oyelese AO,Salawu L,Audu RA, Okwuraiwe AP, Aboderin AO.
Occult Hepatitis B virus infection in previously screened blood donors in Ile-Ife, Nigeria: Implications for blood transfusion and stem cell transplantation.
Virol J 2016;13:76-85.
123. Nna E, Mbamalu C, Ekejindu I. Occult hepatitis B viral infection among blood donors in South-Eastern Nigeria. Pathog Glob Health 2014;108(5):1-6.
124. Mendez-Sanchez N, Aguilar-Ramirez JR, Reyes A, Dehesa M, JuorezA, Castneda B, et al. Etiology of liver cirrhosis in Mexico. Ann of Hepatol 2004;3(1):30-33.
125. Rehm J, Taylor B, Mohapatra S, Irving H, Baliunas D, Patra J, et al. Alcohol as a risk factor for liver cirrhosis: a systematic review and meta-analysis. Drug Alcohol Rev 2010; 29(4):437-445.
126. Hall KS,Gao S,Emsley CL,Ogunniyi AO,Morgan O,Hendrie HC.
Community screening interview for dementia (CSID); performance in five disparate study sites. Int J Geriatr Psychiatry 2000;15(6):521-531.
127. Shawcross DL,Wright G,Olde Damink SW,Jalan R. Role of ammonia and inflammation in minimal hepatic encephalopathy. Metab Brain Dis 2007;
22(1):125-138.
125
128. Pantiga C, Rodrigo LR, Cuesta M, Arias JL. Cognitive deficits in patients with hepatic cirrhosis and in liver transplant recipients. J Neuropsychiatry Clin Neurosci 2003;15:84–89.
129. Carlen PL, Wilkinson DA, Wortzman G, Holgate R, Cordingley J, Lee MA,et al. Cerebral atrophy and functional deficits in alcoholics without clinically apparent liver disease.Neurology1981;31(4):377–385.
130. Hilsabeck RC, Perry W, Hassanein TI.Neuropsychological impairment in patients with chronic hepatitis C.Hepatology 2002;35(2):440–446.
131. Kramer L, Bauer E, Funk G, Hofer H, Jessner W, Steindl-Munda P, et
al.Subclinical impairment of brain function in chronic hepatitis C infection.J Hepatol2002;37(3):349–354.
132. Newton JL, Hollingsworth KG, Taylor R, El-Sharkawy AM, Khan ZU, Pearce R, et al.Cognitive impairment in primary biliary cirrhosis: Symptom impact and potential etiology.Hepatology2008;48(2):541–549.
133. Ong SC, Mak B, Aung MO, Li SC, Lim SG. Health-related quality of life in chronic hepatitis B patients. Hepatology 2008;47(4):1108-1117.
134. Kalaitzakis E, Josefsson A,Einar Bjornsson E. Type and etiology of liver cirrhosis are not related to the presence of hepatic encephalopathy or health-related quality of life: a cross-sectional study. BMC Gastroenterol 2008;8(1):46-48.
135. Hashemi F, Ashtiani AF, Mirminachi B, Sharafkhah M, Ekhlasi G, Jafari E, et al. Impact of hepatitis C virus infection on cognitive function in patients with covert hepatic encephalopathy. Hepat Mon 2015;15(7):1-6.
126
136. Savlan I, Liakina V, Valantinas J. Value of computerized inhibitory control test and blood tests in minimal hepatic encephalopathy diagnosis. Acta Med
Litu2013;20(3):109–116.
137. 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(7):622–630.
138. 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(3):239–248.
139. Wein C, Koch H, Popp B, Oehler G, Schauder P. Minimal hepatic
encephalopathy impairs fitness to drive. Hepatology 2004;39(3):739–745.
140. Gad YZ,Zaher AA,Moussa NH,El-desoky AE,Al-Adarosy HA. Screening for minimal hepatic encephalopathy in asymptomatic drivers with liver
cirrhosis. Arab J Gastroenterol 2011;12(2):58-61.