Signs and related mechanisms of ethanol hepatotoxicity

Current Drug Abuse Reviews

Volumn 8, Issue 2, 2015, Pages 86-103

  Dinisoliveira, Ricardo Jorge ^b   Magalhães, Teresa ^b   Queirós, Odília ^a   Proença, Jorge Brandão ^a   Moreira, Roxana ^a   Bastos, Maria de Lourdes ^b   Carvalho, Félix ^b  

^a UNIVERSITY INSTITUTE OF HEALTH SCIENCES IUCS   (Portugal)

^b UNIVERSITY OF PORTO   (Portugal)

Author keywords

Alcohol; Ascites; Caput medusae; Cirrhosis; Dilated congestive cardiomyopathy; Ecchymoses; Esophageal varices; Ethanol; Gynecomastia; Hemochromatosis; Hemorrhoids; Hepatotoxicity; Jaundice; Nutritional deficiency; Petechiae; Splenomegaly; Steatosis; Testicular atrophy; Xanthelasma

Indexed keywords

ACRODERMATITIS; ALCOHOL ABUSE; ARTICLE; ASCITES; CONGESTIVE CARDIOMYOPATHY; ECCHYMOSIS; ESOPHAGUS VARICES; GYNECOMASTIA; HEMOCHROMATOSIS; HEMORRHOID; HUMAN; JAUNDICE; LIVER CIRRHOSIS; LIVER TOXICITY; MALNUTRITION; NUTRITIONAL DEFICIENCY; PETECHIA; PRIORITY JOURNAL; SKIN DISEASE; SPLENOMEGALY; STEATOSIS; TESTIS ATROPHY; XANTHELASMA; ALCOHOL LIVER DISEASE; ALCOHOLISM; COMPLICATION; HEALTH; PATHOPHYSIOLOGY;

ALCOHOL;

ALCOHOLISM; ETHANOL; GLOBAL HEALTH; HUMANS; LIVER DISEASES, ALCOHOLIC;

EID: 84945418591     PISSN: 18744737     EISSN: 18744745     Source Type: Journal    
DOI: 10.2174/1874473708666150916113352     Document Type: Article

References (217)

1. Dinis-Oliveira RJ, Magalhaes T, Moreira R, et al. Clinical and forensic signs related to ethanol abuse: a mechanistic approach. Toxicol Mech Methods 2014; 24: 81-110.
2. Beier JI, McClain CJ. Mechanisms and cell signaling in alcoholic liver disease. Biol Chem 2010; 391: 1249-64.
3. World Health Organization. Global status report on alcohol and health. Switzerland: World Health Organization 2014.
4. Kumar V, Abbas AK, Aster JC. Robbins basic pathology. Philadelphia: Elsevier Saunders 2012.
5. Klaassen CD. Casarett & Doull's Toxicology: The Basic Science of Poisons. New York: McGraw-Hill 2013.
6. Orman ES, Odena G, Bataller R. Alcoholic liver disease: Pathogenesis, management, and novel targets for therapy. J Gastroenterol Hepatol 2013; 28: 77-84.
7. Altamirano J, Bataller R. Alcoholic liver disease: pathogenesis and new targets for therapy. Nat Rev Gastroenterol Hepatol 2011; 8: 491-501.
8. Lucey MR, Mathurin P, Morgan TR. Alcoholic hepatitis. N Engl J Med 2009; 360: 2758-69.
9. Dominguez M, Rincon D, Abraldes JG, Miquel R, et al. A new scoring system for prognostic stratification of patients with alcoholic hepatitis. Am J Gastroenterol 2008; 103: 2747-56.
10. Rahimi RS, Rockey DC. End-stage liver disease complications. Curr Opin Gastroenterol 2013; 29: 257-63.
11. Wang DQ, Portincasa P, Neuschwander-Tetri BA. Steatosis in the liver. Compr Physiol 2013; 3: 1493-532.
12. Baraona E, Lieber CS. Effects of ethanol on lipid metabolism. J Lipid Res 1979; 20: 289-315.
13. Salaspuro MP, Shaw S, Jayatilleke E, Ross WA, Lieber CS. Attenuation of the ethanol-induced hepatic redox change after chronic alcohol-consumption in baboons - metabolic consequences invivo and invitro. Hepatol 1981; 1: 33-8.
14. Zhou J, Febbraio M, Wada T, et al. Hepatic fatty acid transporter Cd36 is a common target of LXR, PXR, and PPARgamma in promoting steatosis. Gastroenterol 2008; 134: 556-67.
15. Hoek JB, Cahill A, Pastorino JG. Alcohol and mitochondria: a dysfunctional relationship. Gastroenterol 2002; 122: 2049-63.
16. Sozio MS, Liangpunsakul S, Crabb D. The Role of Lipid Metabolism in the Pathogenesis of Alcoholic and Nonalcoholic Hepatic Steatosis. Seminars Liver Disease 2010; 30: 378-90.
17. You M, Fischer M, Deeg MA, Crabb DW. Ethanol induces fatty acid synthesis pathways by activation of sterol regulatory elementbinding protein (SREBP). J Biol Chem 2002; 277: 29342-7.
18. Yu S, Rao S, Reddy JK. Peroxisome proliferator-activated receptors, fatty acid oxidation, steatohepatitis and hepatocarcinogenesis. Curr Mol Med 2003; 3: 561-72.
19. Wagner M, Zollner G, Trauner M. Nuclear Receptors in Liver Disease. Hepatol 2011; 53: 1023-34.
20. Viollet B, Guigas B, Leclerc J, et al. AMP-activated protein kinase in the regulation of hepatic energy metabolism: from physiology to therapeutic perspectives. Acta Physiologica 2009; 196: 81-98.
21. Li Y, Xu SQ, Mihaylova MM, et al. AMPK Phosphorylates and Inhibits SREBP Activity to Attenuate Hepatic Steatosis and Atherosclerosis in Diet-Induced Insulin-Resistant Mice. Cell Metabolism 2011; 13: 376-88.
22. Berman JE, Lamkin BC. Hepatic disease and the skin. Dermatologic Clinics 1989; 7: 435-48.
23. Katz SK, Gordon KB, Roenigk HH. The cutaneous manifestations of gastrointestinal disease. Primary Care - Clinics in Office Practice 1996; 23: 455-76.
24. Smith KE, Fenske NA. Cutaneous manifestations of alcohol abuse. J Am Acad Dermatol 2000; 43: 1-16; quiz 16-18.
25. Sticova E, Jirsa M. New insights in bilirubin metabolism and their clinical implications. World J Gastroenterol 2013; 19: 6398-407.
26. Gossard AA, Talwalkar JA. Cholestatic Liver Disease. Medical Clinics North America 2014; 98: 73-85.
27. Vidal D, Altes J, Smandia JA. Yellow skin discoloration induced by quinacrine in a patient with cutaneous lupus erythematosus. Actas Dermosifiliogr 2013; 104: 89-90.
28. Schuppan D, Afdhal NH. Liver cirrhosis. Lancet 2008; 371: 838- 851.
29. Pinzani M, Rosselli M, Zuckermann M. Liver cirrhosis. Best Practice Res Clin Gastroenterol 2011; 25: 281-90.
30. Hernandez-Gea V, Friedman SL. Pathogenesis of liver fibrosis. Annu Rev Pathol 2011; 6: 425-56.
31. Sanyal AJ, Bosch J, Blei A, Arroyo V. Portal hypertension and its complications. Gastroenterol 2008; 134: 1715-28.
32. Wells RG. The portal fibroblast: not just a poor man's stellate cell. Gastroenterol 2014; 147: 41-7.
33. Puche JE, Saiman Y, Friedman SL. Hepatic stellate cells and liver fibrosis. Compr Physiol 2013; 3: 1473-92.
34. Fujii H, Kawada N. Fibrogenesis in alcoholic liver disease. World J Gastroenterol 2014; 20: 8048-54.
35. Rosmorduc O, Wendum D, Corpechot C, et al. Hepatocellular hypoxia-induced vascular endothelial growth factor expression and angiogenesis in experimental biliary cirrhosis. Am J Pathol 1999; 155: 1065-73.
36. DeLeve LD. Hepatic microvasculature in liver injury. Seminars in Liver Disease 2007; 27: 390-400.
37. Wang JH, Batey RG, George J. Role of ethanol in the regulation of hepatic stellate cell function. World J Gastroenterol 2006; 12: 6926-32.
38. Moreno M, Bataller R. Cytokines and renin-angiotensin system signaling in hepatic fibrosis. Clin Liver Dis 2008; 12: 825-52, ix.
39. Arthur MJ, Iredale JP, Mann DA. Tissue inhibitors of metalloproteinases: role in liver fibrosis and alcoholic liver disease. Alcohol Clin Exp Res 1999; 23: 940-3.
40. Kluwe J, Pradere JP, Gwak GY, et al. Modulation of hepatic fibrosis by c-Jun-N-terminal kinase inhibition. Gastroenterol 2010; 138: 347-59.
41. Mello T, Ceni E, Surrenti C, Galli A. Alcohol induced hepatic fibrosis: role of acetaldehyde. Mol Aspects Med 2008; 29: 17-21.
42. Niemela O. Distribution of ethanol-induced protein adducts in vivo: relationship to tissue injury. Free Radic Biol Med 2001; 31: 1533- 1538.
43. Chen A. Acetaldehyde stimulates the activation of latent transforming growth factor-beta1 and induces expression of the type II receptor of the cytokine in rat cultured hepatic stellate cells. Biochem J 2002; 368: 683-693.
44. Jeong WI, Park O, Gao B. Abrogation of the antifibrotic effects of natural killer cells/interferon-gamma contributes to alcohol acceleration of liver fibrosis. Gastroenterol 2008; 134: 248-58.
45. Radaeva S, Sun R, Jaruga B, Nguyen VT, Tian Z, Gao B. Natural killer cells ameliorate liver fibrosis by killing activated stellate cells in NKG2D-dependent and tumor necrosis factor-related apoptosisinducing ligand-dependent manners. Gastroenterology 2006; 130: 435-52.
46. Muhanna N, Abu Tair L, Doron S, et al. Amelioration of hepatic fibrosis by NK cell activation. Gut 2011; 60: 90-8.
47. Jeong WI, Park O, Radaeva S, Gao B. STAT1 inhibits liver fibrosis in mice by inhibiting stellate cell proliferation and stimulating NK cell cytotoxicity. Hepatology 2006; 44: 1441-51.
48. Cales P, Zabotto B, Meskens C, et al. Gastroesophageal endoscopic features in cirrhosis. Observer variability, interassociations, and relationship to hepatic dysfunction. Gastroenterol 1990; 98: 156- 62.
49. Kravetz D. Gastrointestinal bleeding: Secondary prophylaxis for variceal bleeding. Nat Rev Gastroenterol Hepatol 2010; 7: 10-11.
50. Dettmeyer RB, Verhoff MA, Schütz HF. Forensic Medicine - Fundamentals and Perspectives. Berlin: Springer Berlin Heidelberg 2014.
51. Sarkany I. The skin-liver connection. Clin Exp Dermatol 1988; 13: 151-9.
52. Georgiades CS. Etymology of selected medical terms used in radiology: the mythologic connection. AJR Am J Roentgenol 2002; 178: 1101-7.
53. Yang PM, Chen DS. Images in clinical medicine. Caput medusae. N Engl J Med 2005; 353: e19.
54. Kumar V, Sharma V. Medical image. Cruveilhier-Baumgarten syndrome with caput medusae. N Z Med J 2011; 124: 89-90.
55. Gines P, Quintero E, Arroyo V, et al. Compensated cirrhosis: natural history and prognostic factors. Hepatol 1987; 7: 122-8.
56. Reshamwala PA. Management of Ascites. Crit Care Nursing Clin North Am 2010; 22: 309-14.
57. Cardoso C, Cremers I, Oliveira AP. Spontaneous bacterial peritonitis caused by Listeria monocytogenes: a case report and literature review. Ann Hepatol 2012; 11: 955-7.
58. Alonso JC. Pleural effusion in liver disease. Semin Respir Crit Care Med 2010; 31: 698-705.
59. Garcia N Jr, Mihas AA. Hepatic hydrothorax: pathophysiology, diagnosis, and management. J Clin Gastroenterol 2004; 38: 52-8.
60. Desmet VJ, Roskams T. Cirrhosis reversal: a duel between dogma and myth. J Hepatol 2004; 40: 860-7.
61. Hernández-Guerra M, García-Pagán JC, Bosch J. Increased Hepatic Resistance: A New Target in the Pharmacologic Therapy of Portal Hypertension. J Clin Gastroenterol 2005; 39: S131-7.
62. Gines P, Cardenas A, Arroyo V, Rodes J. Management of cirrhosis and ascites. N Engl J Med 2004; 350: 1646-54.
63. Arroyo V, Gines P. Mechanism of sodium retention and ascites formation in cirrhosis. J Hepatol 1993; 17 Suppl 2: S24-8.
64. Granese J, Valaulikar G, Khan M, Hardy Iii H. Ruptured umbilical hernia in a case of alcoholic cirrhosis with massive ascites. American Surgeon 2002; 68: 733-4.
65. Dokmak S, Aussilhou B, Belghiti J. Umbilical hernias and cirrhose. J Visceral Surgery 2012; 149: e32-e39.
66. Long WD, Hayden GE. Man With Rushing Fluid From His Umbilicus. Ann Em Medicin 2013; 62: 431-439.
67. Ferreira AO, Marinho RT, Ramalho F, Velosa J. Ascitic eruption in an umbilical hernia in cirrhosis. BMJ Case Rep 2013; 2013: doi: 10.1136/bcr-2012-007741.
68. Mucino-Bermejo J, Carrillo-Esper R, Uribe M, Mendez-Sanchez N. Coagulation abnormalities in the cirrhotic patient. Ann Hepatol 2013; 12: 713-24.
69. Caldwell SH, Hoffman M, Lisman T, et al. Coagulation disorders and hemostasis in liver disease: pathophysiology and critical assessment of current management. Hepatol 2006; 44: 1039-46.
70. Ng VL. Liver disease, coagulation testing, and hemostasis. Clin Lab Med 2009; 29: 265-82.
71. Monroe DM, Hoffman M. The coagulation cascade in cirrhosis. Clin Liver Dis 2009; 13: 1-9.
72. Goulis J, Chau TN, Jordan S, et al. Thrombopoietin concentrations are low in patients with cirrhosis and thrombocytopenia and are restored after orthotopic liver transplantation. Gut 1999; 44: 754-8.
73. Hugenholtz GG, Porte RJ, Lisman T. The platelet and platelet function testing in liver disease. Clin Liver Dis 2009; 13: 11-20.
74. Kostovic K, Lipozencic J. Skin diseases in alcoholics. Acta Dermatovenerol Croat 2004; 12: 181-90.
75. Amitrano L, Guardascione MA, Brancaccio V, Iannaccone L, Ames PR, Balzano A. Portal and mesenteric venous thrombosis in cirrhotic patients. Gastroenterol 2002; 123: 1409-10.
76. Amitrano L, Guardascione MA, Brancaccio V, Balzano A. Coagulation disorders in liver disease. Semin Liver Dis 2002; 22: 83-96.
77. Iwakiri Y. Pathophysiology of Portal Hypertension. Clinics in Liver Disease 2014; 18: 281-91.
78. Romero M, Palmer SL, Kahn JA, et al. Imaging appearance in acute liver failure: correlation with clinical and pathology findings. Dig Dis Sci 2014; 59: 1987-95.
79. Iwakiri Y. Pathophysiology of portal hypertension. Clin Liver Dis 2014; 18: 281-91.
80. Ulvik RJ. The liver in haemochromatosis. J Trace Elem Med Biol 2014.
81. Darshan D, Frazer DM, Anderson GJ. Molecular basis of ironloading disorders. Expert Rev Mol Med 2010; 12: e36.
82. Feder JN, Gnirke A, Thomas W, et al. A novel MHC class I-like gene is mutated in patients with hereditary haemochromatosis. Nat Genet 1996; 13: 399-408.
83. Bardou-Jacquet E, Ben Ali Z, Beaumont-Epinette M-P, Loreal O, Jouanolle A-M, Brissot P. Non-HFE hemochromatosis: Pathophysiological and diagnostic aspects. Clinics and Research in Hepatol Gastroenterology 2014; 38: 143-54.
84. Bloom PD, Gordeuk VR, MacPhail AP. HLA-linked hemochromatosis and other forms of iron overload. Dermatol Clin 1995; 13: 57-63.
85. Tavill AS, Sharma BK, Bacon BR. Iron and the liver: genetic hemochromatosis and other hepatic iron overload disorders. Prog Liver Dis 1990; 9: 281-305.
86. Waalen J, Nordestgaard BG, Beutler E. The penetrance of hereditary hemochromatosis. Best Pract Res Clin Haematol 2005; 18: 203-20.
87. Chapman RW, Morgan MY, Laulicht M, Hoffbrand AV, Sherlock S. Hepatic iron stores and markers of iron overload in alcoholics and patients with idiopathic hemochromatosis. Dig Dis Sci 1982; 27: 909-16.
88. Irving MG, Halliday JW, Powell LW. Association between alcoholism and increased hepatic iron stores. Alcohol Clin Exp Res 1988; 12: 7-13.
89. Adams PC, Agnew S. Alcoholism in hereditary hemochromatosis revisited: prevalence and clinical consequences among homozygous siblings. Hepatol 1996; 23: 724-7.
90. Hourihane DO, Weir DG. Suppression of erythropoiesis by alcohol. Br Med J 1970; 1: 86-9.
91. Duane P, Raja KB, Simpson RJ, Peters TJ. Intestinal iron absorption in chronic alcoholics. Alcohol Alcohol 1992; 27: 539- 44.
92. Harrison-Findik DD. Role of alcohol in the regulation of iron metabolism. World J Gastroenterol 2007; 13: 4925-30.
93. Moirand R, Kerdavid F, Loreal O, et al. Regulation of ferritin expression by alcohol in a human hepatoblastoma cell line and in rat hepatocyte cultures. J Hepatol 1995; 23: 431-9.
94. Bridle K, Cheung TK, Murphy T, et al. Hepcidin is down-regulated in alcoholic liver injury: implications for the pathogenesis of alcoholic liver disease. Alcohol Clin Exp Res 2006; 30: 106-12.
95. Harrison-Findik DD, Schafer D, Klein E, et al. Alcohol metabolism-mediated oxidative stress down-regulates hepcidin transcription and leads to increased duodenal iron transporter expression. J Biol Chem 2006; 281: 22974-82.
96. Fletcher LM, Powell LW. Hemochromatosis and alcoholic liver disease. Alcohol 2003; 30: 131-6.
97. Fletcher LM, Dixon JL, Purdie DM, Powell LW, Crawford DHG. Excess alcohol greatly increases the prevalence of cirrhosis in hereditary hemochromatosis. Gastroenterol 2002; 122: 281-9.
98. McCord JM. Iron, free radicals, and oxidative injury. Semin Hematol 1998; 35: 5-12.
99. Feierman DE, Winston GW, Cederbaum AI. Ethanol oxidation by hydroxyl radicals: role of iron chelates, superoxide, and hydrogen peroxide. Alcohol Clin Exp Res 1985; 9: 95-102.
100. Bergman R. The pathogenesis and clinical significance of xanthelasma palpebrarum. J Am Acad Dermatol 1994; 30: 236-42.
101. Kim J, Kim YJ, Lim H, Lee SI. Bilateral circular xanthelasma palpebrarum. Arch Plast Surg 2012; 39: 435-7.
102. Jain A, Goyal P, Nigam PK, Gurbaksh H, Sharma RC. Xanthelasma Palpebrarum-clinical and biochemical profile in a tertiary care hospital of Delhi. Indian J Clin Biochem 2007; 22: 151-3.
103. Gandelman G, Aronow WS, Weiss MB. Resolving hyperlipidemia after liver transplantation in a patient with primary sclerosing cholangitis. Am J Ther 2006; 13: 171-4.
104. Assy N, Kaita K, Mymin D, Levy C, Rosser B, Minuk G. Fatty infiltration of liver in hyperlipidemic patients. Dig Dis Sci 2000; 45: 1929-34.
105. Otto AI, Horvath I, Feldmann J. Multiple firm, painless erythematous papules with a yellowish hue. Arch Dermatol 2005; 141: 1595-600.
106. Allocca M, Crosignani A, Gritti A, et al. Hypercholesterolaemia is not associated with early atherosclerotic lesions in primary biliary cirrhosis. Gut 2006; 55: 1795-800.
107. Dickson ER, Fleming CR, Ludwig J. Primary biliary cirrhosis. Prog Liver Dis 1979; 6: 487-502.
108. Estruch R, Sacanella E, Fernandez-Sola J, Nicolás JM. Nutritional Status in Alcoholics. In: Preedy VR, Watson RR, editors. Comprehensive Handbook of Alcohol Related Pathology. London: Elsevier 2005, pp. 361-75.
109. Ruocco V, Psilogenis M, Lo Schiavo A, Wolf R. Dermatological manifestations of alcoholic cirrhosis. Clin Dermatol 1999; 17: 463- 8.
110. Gloria L, Cravo M, Camilo ME, et al. Nutritional deficiencies in chronic alcoholics: relation to dietary intake and alcohol consumption. Am J Gastroenterol 1997; 92: 485-9.
111. Morgan MY, Levine JA. Alcohol and nutrition. Proc Nutr Soc 1988; 47: 85-98.
112. Cook CC, Walden RJ, Graham BR, Gillham C, Davies S, Prichard BN. Trace element and vitamin deficiency in alcoholic and control subjects. Alcohol Alcohol 1991; 26: 541-8.
113. Lieber CS. Herman Award Lecture, 1993: a personal perspective on alcohol, nutrition, and the liver. Am J Clin Nutr 1993; 58: 430- 42.
114. Delahoussaye AR, Jorizzo JL. Cutaneous manifestations of nutritional disorders. Dermatol Clin 1989; 7: 559-70.
115. Sanchez MR. Alcohol, social behavior disorders, and their cutaneous manifestations. Clin Dermatol 1999; 17: 479-89.
116. Nicolas JM, Fernandez-Sola J, Fatjo F, et al. Increased circulating leptin levels in chronic alcoholism. Alcohol Clin Exp Res 2001; 25: 83-8.
117. Addolorato G, Montalto M, Capristo E, et al. Influence of alcohol on gastrointestinal motility: lactulose breath hydrogen testing in orocecal transit time in chronic alcoholics, social drinkers and teetotaler subjects. Hepatogastroenterol 1997; 44: 1076-81.
118. Ragunatha S, Kumar VJ, Murugesh SB. A clinical study of 125 patients with phrynoderma. Indian J Dermatol 2011; 56: 389-92.
119. Sharma A, Aggarwal S, Sharma V. Bitot's Spots: Look at the Gut. Int J Prev Med 2014; 5: 1058-9.
120. Barbul A, Purtill WA. Nutrition in wound healing. Clin Dermatol 1994; 12: 133-40.
121. Goez HR, Scott O, Hasal S. Fetal exposure to alcohol, developmental brain anomaly, and vitamin a deficiency: a case report. J Child Neurol 2011; 26: 231-4.
122. Martin PR, Singleton CK, Hiller-Sturmhofel S. The role of thiamine deficiency in alcoholic brain disease. Alcohol Res Health 2003; 27: 134-42.
123. Sechi G, Serra A. Wernicke's encephalopathy: new clinical settings and recent advances in diagnosis and management. Lancet Neurol 2007; 6: 442-55.
124. Miller SJ. Nutritional deficiency and the skin. J Am Acad Dermatol 1989; 21: 1-30.
125. Sheetal A, Hiremath VK, Patil AG, Sajjansetty S, Kumar SR. Malnutrition and its oral outcome - a review. J Clin Diagn Res 2013; 7: 178-80.
126. Harper C, Fornes P, Duyckaerts C, Lecomte D, Hauw JJ. An international perspective on the prevalence of the Wernicke- Korsakoff syndrome. Metab Brain Dis 1995; 10: 17-24.
127. Gascon-Bayarri J, Campdelacreu J, Garcia-Carreira MC, et al. Wernicke's encephalopathy in non-alcoholic patients: a series of 8 cases. Neurologia 2011; 26: 540-7.
128. Spivak JL, Jackson DL. Pellagra: an analysis of 18 patients and a review of the literature. Johns Hopkins Med J 1977; 140: 295-309.
129. Filgueiras Fde M, Stolarczuk Dde A, Gripp AC, Succi IC. Benign symmetrical lipomatosis and pellagra associated with alcoholism. An Bras Dermatol 2011; 86: 1189-92.
130. Oldham MA, Ivkovic A. Pellagrous encephalopathy presenting as alcohol withdrawal delirium: a case series and literature review. Addict Sci Clin Pract 2012; 7: 12.
131. Nogueira A, Duarte AF, Magina S, Azevedo F. Pellagra associated with esophageal carcinoma and alcoholism. Dermatol Online J 2009; 15: 8.
132. Rosmaninho A, Sanches M, Fernandes IC, Pinto-Almeida T, Vilaca S, Oliveira A, Selores M. Letter: Pellagra as the initial presentation of Crohn disease. Dermatol Online J 2012; 18: 12.
133. Lopez M, Olivares JM, Berrios GE. Pellagra encephalopathy in the context of alcoholism: review and case report. Alcohol Alcohol 2014; 49: 38-41.
134. Badawy AA. Pellagra and alcoholism: a biochemical perspective. Alcohol Alcohol 2014; 49: 238-50.
135. Karthikeyan K, Thappa DM. Pellagra and skin. Int J Dermatol 2002; 41: 476-81.
136. Williams AC, Ramsden DB. Pellagra: A clue as to why energy failure causes diseases? Med Hypotheses 2007; 69: 618-28.
137. Hendricks WM. Pellagra and pellagralike dermatoses: etiology, differential diagnosis, dermatopathology, and treatment. Semin Dermatol 1991; 10: 282-92.
138. Halsted CH. B-Vitamin dependent methionine metabolism and alcoholic liver disease. Clin Chem Lab Med 2013; 51: 457-65.
139. Medici V, Halsted CH. Folate, alcohol, and liver disease. Mol Nutr Food Res 2013; 57: 596-606.
140. Pontes HA, Neto NC, Ferreira KB, et al. Oral manifestations of vitamin B12 deficiency: a case report. J Can Dent Assoc 2009; 75: 533-7.
141. Savage D, Lindenbaum J. Anemia in alcoholics. Medicine (Baltimore) 1986; 65: 322-38.
142. Halsted CH, Medici V. Vitamin-dependent methionine metabolism and alcoholic liver disease. Adv Nutr 2011; 2: 421-7.
143. Cylwik B, Chrostek L. [Disturbances of folic acid and homocysteine metabolism in alcohol abuse]. Pol Merkur Lekarski 2011; 30: 295-9.
144. Olmedo JM, Yiannias JA, Windgassen EB, Gornet MK. Scurvy: a disease almost forgotten. Int J Dermatol 2006; 45: 909-13.
145. Maltos AL, Portari GV, Saldanha JC, Bernardes Junior AG, Pardi GR, da Cunha DF. Scurvy in an alcoholic malnourished cirrhotic man with spontaneous bacterial peritonitis. Clinics (Sao Paulo) 2012; 67: 405-7.
146. Robinson S, Roth J, Blanchard S. Light-headedness and a petechial rash. J Fam Pract 2013; 62: 203-5.
147. Leung FW, Guze PA. Adult scurvy. Ann Emerg Med 1981; 10: 652-5.
148. Crandon JH, Lennihan RJr., Mikal S, Reif AE. Ascorbic acid economy in surgical patients. Ann N Y Acad Sci 1961; 92: 246-67.
149. Reuler JB, Broudy VC, Cooney TG. Adult scurvy. JAMA 1985; 253: 805-7.
150. Velandia B, Centor RM, McConnell V, Shah M. Scurvy is still present in developed countries. J Gen Intern Med 2008; 23: 1281-4.
151. Wijnia JW, Wielders JP, Lips P, van de Wiel A, Mulder CL, Nieuwenhuis KG. Is vitamin D deficiency a confounder in alcoholic skeletal muscle myopathy? Alcohol Clin Exp Res 2013; 37 Suppl 1: E209-215.
152. Hewitt SM, Winter RJ. Rhabdomyolysis following acute alcohol intoxication. J Accid Emerg Med 1995; 12: 143-44.
153. Diamond I, Messing RO. Neurologic effects of alcoholism. West J Med 1994; 161: 279-87.
154. Preedy VR, Ohlendieck K, Adachi J, et al. The importance of alcohol-induced muscle disease. J Muscle Res Cell Motil 2003; 24: 55-63.
155. Slavin G, Martin F, Ward P, Levi J, Peters T. Chronic alcohol excess is associated with selective but reversible injury to type 2B muscle fibres. J Clin Pathol 1983; 36: 772-7.
156. Preedy VR, Peters TJ. Alcohol and muscle disease. J R Soc Med 1994; 87: 188-90.
157. Trepo E, Ouziel R, Pradat P, et al. Marked 25-hydroxyvitamin D deficiency is associated with poor prognosis in patients with alcoholic liver disease. J Hepatol 2013; 59: 344-50.
158. Puri AS, Poddar U, Ghoshal UC, Khan EM, Saraswat VA. Rapid reversal of manifestations of acquired zinc deficiency in alcoholic cirrhosis with diet therapy. Trop Gastroenterol 1995; 16: 119-22.
159. Vallee BL, Wacker WE, Bartholomay AF, Hoch FL. Zinc metabolism in hepatic dysfunction. II. Correlation of metabolic patterns with biochemical findings. N Engl J Med 1957; 257: 1055- 65.
160. Maverakis E, Fung MA, Lynch PJ, et al. Acrodermatitis enteropathica and an overview of zinc metabolism. J Am Acad Dermatol 2007; 56: 116-24.
161. Kostler E, Porst H, Wollina U. Cutaneous manifestations of metabolic diseases: uncommon presentations. Clin Dermatol 2005; 23: 457-64.
162. McClain CJ, Antonow DR, Cohen DA, Shedlofsky SI. Zinc metabolism in alcoholic liver disease. Alcohol Clin Exp Res 1986; 10: 582-9.
163. Wang LC, Busbey S. Images in clinical medicine. Acquired acrodermatitis enteropathica. N Engl J Med 2005; 352: 1121.
164. Chaudhry AA, Warthan MM, Pariser RJ, Hood AF. Acquired acrodermatitis enteropathica secondary to alcoholism. Cutis 2008; 82: 60-2.
165. Krause W. Drug-inducing gynaecomastia - a critical review. Andrologia 2012; 44: 621-6.
166. Calzada L, Torres-Calleja J, Martinez JM, Pedron N. Measurement of androgen and estrogen receptors in breast tissue from subjects with anabolic steroid-dependent gynecomastia. Life Sci 2001; 69: 1465-9.
167. Gimenez-Roqueplo AP, Dupuy M, Delalande O, Visot A, Jedynak CP, Peillon F, Derome PJ. [Prolactin microadenoma in men. Study of 14 cases]. Ann Med Interne (Paris) 1992; 143: 94-7.
168. Burra P. Liver abnormalities and endocrine diseases. Best Practice Res Clin Gastroenterol 2013; 27: 553-63.
169. Van Thiel DH, Gavaler JS, Eagon PK, Chiao YB, Cobb CF, Lester R. Alcohol and sexual function. Pharmacol Biochem Behav 1980; 13: 125-9.
170. Deepinder F, Braunstein GD. Drug-induced gynecomastia: an evidence-based review. Expert Opin Drug Saf 2012; 11: 779-95.
171. Boyden TW, Pamenter RW. Effects of ethanol on the male hypothalamic-pituitary-gonadal axis. Endocr Rev 1983; 4: 389-95.
172. Van Thiel DH, Cobb CF, Herman GB, Perez HA, Estes L, Gavaler JS. An examination of various mechanisms for ethanol-induced testicular injury: studies utilizing the isolated perfused rat testes. Endocrinology 1981; 109: 2009-15.
173. Karagiannis A, Harsoulis F. Gonadal dysfunction in systemic diseases. Eur J Endocrinol 2005; 152: 501-13.
174. Gavaler JS. Alcoholic beverages as a source of estrogens. Alcohol Health Res World 1998; 22: 220-27.
175. Rosenblum E, Gavaler JS, Van Thiel DH. Lipid peroxidation: a mechanism for ethanol-associated testicular injury in rats. Endocrinol 1985; 116: 311-8.
176. Zhu Q, Van Thiel DH, Gavaler JS. Effects of ethanol on rat Sertoli cell function: studies in vitro and in vivo. Alcohol Clin Exp Res 1997; 21: 1409-17.
177. Farghali H, Williams DS, Simplaceanu E, Ho C, Van Thiel DH. An evaluation of the integrity of the blood-testis barrier by magnetic resonance imaging. Magn Reson Med 1991; 22: 81-7.
178. Guzzo-Merello G, Cobo-Marcos M, Gallego-Delgado M, Garcia- Pavia P. Alcoholic cardiomyopathy. World J Cardiol 2014; 6: 771- 81.
179. Roerecke M, Rehm J. The cardioprotective association of average alcohol consumption and ischaemic heart disease: a systematic review and meta-analysis. Addiction 2012; 107: 1246-60.
180. Kloner RA, Rezkalla SH. To drink or not to drink? That is the question. Circulation 2007; 116: 1306-17.
181. Vaideeswar P, Chaudhari C, Rane S, Gondhalekar J, Dandekar S. Cardiac pathology in chronic alcoholics: a preliminary study. J Postgrad Med 2014; 60: 372-6.
182. Fauchier L, Babuty D, Poret P, et al. Comparison of long-term outcome of alcoholic and idiopathic dilated cardiomyopathy. Eur Heart J 2000; 21: 306-14.
183. McKenna CJ, Codd MB, McCann HA, Sugrue DD. Alcohol consumption and idiopathic dilated cardiomyopathy: a case control study. Am Heart J 1998; 135: 833-7.
184. Fernandez-Sola J, Nicolas JM, Oriola J, et al. Angiotensinconverting enzyme gene polymorphism is associated with vulnerability to alcoholic cardiomyopathy. Ann Intern Med 2002; 137: 321-6.
185. Piano MR. Alcoholic cardiomyopathy: incidence, clinical characteristics, and pathophysiology. Chest 2002; 121: 1638-50.
186. Guzzo-Merello G, Segovia J, Dominguez F, et al. Natural History and Prognostic Factors in Alcoholic Cardiomyopathy. JACC: Heart Failure 2015; 3: 78-86.
187. Lee HS, Lee SA, Shin HS, et al. A case of cardiac beriberi: a forgotten but memorable disease. Korean Circ J 2013; 43: 569-72.
188. Wooley JA. Characteristics of thiamin and its relevance to the management of heart failure. Nutr Clin Pract 2008; 23: 487-93.
189. Sutherland DJ, Jaussi AW, Gubler CJ. The effects of thiamine deprivation, and oxythiamine- and pyrithiamine-treatment on cardiac function and metabolism in the rat. J Nutr Sci Vitaminol (Tokyo) 1974; 20: 35-54.
190. Smithline HA. Thiamine for the treatment of acute decompensated heart failure. Am J Emerg Med 2007; 25: 124-6.
191. Urbano-Marquez A, Estruch R, Navarro-Lopez F, Grau JM, Mont L, Rubin E. The effects of alcoholism on skeletal and cardiac muscle. N Engl J Med 1989; 320: 409-15.
192. Dinis-Oliveira RJ, Carvalho F, Moreira R, et al. Clinical and forensic signs related to chemical burns: A mechanistic approach. Burns 2014; 41: 658-79.
193. Dinis-Oliveira RJ, Caldas I, Carvalho F, Magalhaes T. Bruxism after 3,4-methylenedioxymethamphetamine (ecstasy) abuse. Clin Toxicol (Phila) 2010; 48: 863-864.
194. Dinis-Oliveira RJ, Carvalho F, Duarte JA, Proenca JB, Santos A, Magalhaes T. Clinical and forensic signs related to cocaine abuse. Curr Drug Abuse Rev 2012; 5: 64-83.
195. Dinis-Oliveira RJ, Carvalho F, Duarte JA, et al. Collection of biological samples in forensic toxicology. Toxicol Mech Methods 2010; 20: 363-414.
196. Dinis-Oliveira RJ, Carvalho F, Magalhaes T, Santos A. Postmortem changes in carbon monoxide poisoning. Clin Toxicol (Phila) 2010; 48: 762-3.
197. Dinis-Oliveira RJ, Carvalho F, Moreira R, et al. Clinical and forensic signs related to opioids abuse. Curr Drug Abuse Rev 2012; 5: 273-90.
198. Dinis-Oliveira RJ, Magalhaes T, Carvalho F, Santos A. A cocaine body packer case report: clinical and forensic aspects. Clin Toxicol (Phila) 2009; 47: 590-1.
199. Dinis-Oliveira RJ, Santos A, Magalhaes T. "Foam Cone" exuding from the mouth and nostrils following heroin overdose. Toxicol Mech Methods 2012; 22: 159-60.
200. Humpath.com. Hepatocytic steatosis. Human pathology. http://www.humpath.com/spip.php?article404 2015.
201. Homoeopathic cure. Jaundice Serum Bilirubin level 44.7. http://raviclinic.com/gallery/jaundice-case-serum-bilirubin-44-7/. Balrampur, U.P. India homoeopathic cure 2015.
202. Angemi N. Mortui vivos docent. http://iheartautopsy.com/wpcontent/ uploads/2012/05/DSC_0001.jpg. Philadelphia 2012.
203. PathoPic. Rupture of esophageal varices. Basel. http://alf3.urz.unibas.ch/pathopic/e/getpic-fra.cfm?id=1207: PathoPic 2015.
204. Kim S, Keum B, Kim E, Jeen Y, Chun H. Hepatobiliary and pancreatic: Caput medusae. J Gastroenterol Hepatol 2014; 29: 1952.
205. Alvarez-Martinez P, Granero-Castro P, Fernandez-Vega I, Renilla- Gonzalez A, Rodrigo-Saez L, Varela-Calvo M. Giant hepatocellular carcinoma. Rev Esp Enferm Dig 2012; 104: 264-5.
206. Wilairatana P, Tangpukdee N, Jittaseree L. Cruveilhier- Baumgarten syndrome in a cirrhotic patient taking alcohol with Boesenbergia pundurata. Southeast Asian J Trop Med Public Health 2010; 41: 1267-70.
207. Geßlein M, Vierzigmann T. Aszites: Bitteres Ende einer Alkoholikerkarriere. MMW - Fortschritte der Medizin 2005; 40: 61.
208. Goldberg C. Ascitis. http://meded.ucsd.edu/clinicalimg/abdomen_ ascites5.htm. San Diego: University of California 2005.
209. DocCheck Medical Services. Peritoneal puncture. http://pictures.do ccheck.com/com/photo/18189-peritoneal-puncture. 2013.
210. Angemi N. Mortui vivos docent. http://iheartautopsy.com/wpcontent/ uploads/2012/05/DSC_0065.jpg. Philadelphia 2012.
211. Pandhi D, Gupta P, Singal A, Tondon A, Sharma S, Madhu SV. Xanthelasma palpebrarum: a marker of premature atherosclerosis (risk of atherosclerosis in xanthelasma). Postgrad Med J 2012; 88: 198-204.
212. Tulsyan SH, Chaudhary S, Mishra D. A school survey of dermatological disorders and associated socio-economic factors in Lucknow; a region of north India. Egyptian Dermatol Online J 2012; 8: 4.
213. Tasman W, Jaeger EA. Duane's Ophthalmology on DVD-ROM, 2013 Edition. Philadelphia: Lippincott Williams & Wilkins 2013.
214. Stoopler ET, Nadeau C, Sollecito TP. How do I manage a patient with angular cheilitis? J Can Dent Assoc 2013; 79: d68.
215. Library D. Angular cheilitis. https://www.dermquest.com/image library/large/025293HB.JPG?wm=true. Galderma S.A. 2003.
216. Kim ST, Kang JS, Baek JW, et al. Acrodermatitis enteropathica with anorexia nervosa. J Dermatol 2010; 37: 726-9.
217. Prahlow J, Byard R. Natural Deaths. In: Prahlow J, Byard R, editors. Atlas of Forensic Pathology: Humana Press 2012, pp. 243- 341.