Advertisement

Diagnostic Approaches and Clinical End Points of Treatment in Alcoholic Liver Disease

  • Jaeyoun Cheong
  • Eva Stein
  • Ramon BatallerEmail author

Abstract

The clinical types of alcoholic liver disease (ALD) are quite heterogeneous, ranging from early asymptomatic forms to life-threatening conditions such as alcoholic hepatitis (AH). Diagnosis of early-stage ALD is based on the combination of clinical, laboratory, and imaging findings. In these patients, the degree of liver fibrosis can be estimated by noninvasive tools. The diagnosis of AH is mainly based on clinical and analytical grounds, but in some cases, a definitive diagnosis requires a liver biopsy. The clinical end points of therapy in patients with ALD depend on the baseline condition. In patients with early asymptomatic phenotypes (fatty liver and steatohepatitis with or without fibrosis), the end points consist of normalization of laboratory abnormalities and resolution of fibrosis. In contrast, patients with severe forms such as decompensated cirrhosis and/or AH often have severe complications leading to early mortality. Therefore, the main clinical end point in these patients is short-term survival. Other important end points are the reduction in the occurrence and severity of clinical complications (i.e., acute kidney injury and sepsis) and the improvement of tests indicative of liver failure (i.e., MELD score). In this chapter, we describe the phenotypes, natural history, and diagnostic approaches as well as the clinical end points of patients with ALD.

Keywords

Alcoholic hepatitis Clinical trials Acute kidney injury Noninvasive markers Prognostic assessment 

Abbreviations

ABIC

Age, bilirubin, international normalized ratio, and creatinine

AH

Alcoholic hepatitis

AHHS

Alcoholic hepatitis histological score

ALD

Alcoholic liver disease

ASH

Alcoholic steatohepatitis

AST

Aspartate aminotransferase

ALT

Alanine aminotransferase

AUDIT

Alcohol Use Disorder Inventory Test

CAP

Controlled attenuation parameter

CDT

Carbohydrate-deficient transferrin

CT

Computed tomography

DF

Discriminant function

GGT

γ-Glutamyl-transpeptidase

HCC

Hepatocellular carcinoma

HSC

Hepatic stellate cells

INR

International normalized ratio

MELD

Model for End-Stage Liver Disease

MARS

Molecular adsorbent recirculating system

MRI

Magnetic resonance imaging

NASH

Nonalcoholic steatohepatitis

References

  1. 1.
    Becker U, Deis A, Sorensen TI, et al. Prediction of risk of liver disease by alcohol intake, sex, and age: a prospective population study. Hepatology. 1996;23:1025–9.PubMedCrossRefGoogle Scholar
  2. 2.
    Yoon Y, Yi H. Liver cirrhosis mortality in the United States, 1970–2007. Surveillance report #88. NIAAA Homepage 2010: http://pubs.niaaa.nih.gov/publications/surveillance89/HDS07.htm
  3. 3.
    Rehm J, Mathers C, Popova S, et al. Global burden of disease and injury and economic cost attributable to alcohol use and alcohol-use disorders. Lancet. 2009;373:2223–33.PubMedCrossRefGoogle Scholar
  4. 4.
    Lieber CS. Susceptibility to alcohol-related liver injury. Alcohol Alcohol Suppl. 1994;2:315–26.PubMedGoogle Scholar
  5. 5.
    Thurman RG, Bradford BU, Iimuro Y, et al. The role of gut-derived bacterial toxins and free radicals in alcohol-induced liver injury. J Gastroenterol Hepatol. 1998;13(Suppl):S39–50.PubMedGoogle Scholar
  6. 6.
    Tsukamoto H, Lu SC. Current concepts in the pathogenesis of alcoholic liver injury. FASEB J. 2001;15:1335–49.PubMedCrossRefGoogle Scholar
  7. 7.
    Hoek JB, Cahill A, Pastorino JG. Alcohol and mitochondria: a dysfunctional relationship. Gastroenterology. 2002;122:2049–63.PubMedCentralPubMedCrossRefGoogle Scholar
  8. 8.
    Lumeng L, Crabb DW. Alcoholic liver disease. Curr Opin Gastroenterol. 2001;17:211–20.PubMedCrossRefGoogle Scholar
  9. 9.
    Arteel G, Marsano L, Mendez C, et al. Advances in alcoholic liver disease. Best Pract Res Clin Gastroenterol. 2003;17:625–47.PubMedCrossRefGoogle Scholar
  10. 10.
    Tome S, Lucey MR. Review article: current management of alcoholic liver disease. Aliment Pharmacol Ther. 2004;19:707–14.PubMedCrossRefGoogle Scholar
  11. 11.
    Helman RA, Temko MH, Nye SW, et al. Alcoholic hepatitis. Natural history and evaluation of prednisolone therapy. Ann Intern Med. 1971;74:311–21.PubMedCrossRefGoogle Scholar
  12. 12.
    Altamirano J, Bataller R. Alcoholic liver disease: pathogenesis and new targets for therapy. Nat Rev Gastroenterol Hepatol. 2011;8:491–501.PubMedCrossRefGoogle Scholar
  13. 13.
    Gao B, Bataller R. Alcoholic liver disease: pathogenesis and new therapeutic targets. Gastroenterology. 2011;141:1572–85.PubMedCentralPubMedCrossRefGoogle Scholar
  14. 14.
    Lefkowitch JH. Morphology of alcoholic liver disease. Clin Liver Dis. 2005;9:37–53.PubMedCrossRefGoogle Scholar
  15. 15.
    Elphick DA, Dube AK, McFarlane E, et al. Spectrum of liver histology in presumed decompensated alcoholic liver disease. Am J Gastroenterol. 2007;102:780–8.PubMedCrossRefGoogle Scholar
  16. 16.
    Adachi M, Brenner DA. Clinical syndromes of alcoholic liver disease. Dig Dis. 2005;23:255–63.PubMedCrossRefGoogle Scholar
  17. 17.
    Lucey MR, Mathurin P, Morgan TR. Alcoholic hepatitis. N Engl J Med. 2009;360:2758–69.PubMedCrossRefGoogle Scholar
  18. 18.
    Barrio E, Tome S, Rodriguez I, et al. Liver disease in heavy drinkers with and without alcohol withdrawal syndrome. Alcohol Clin Exp Res. 2004;28:131–6.PubMedCrossRefGoogle Scholar
  19. 19.
    O’Shea RS, Dasarathy S, McCullough AJ. Alcoholic liver disease. Hepatology. 2010;51:307–28.PubMedCrossRefGoogle Scholar
  20. 20.
    Mathurin P, Beuzin F, Louvet A, et al. Fibrosis progression occurs in a subgroup of heavy drinkers with typical histological features. Aliment Pharmacol Ther. 2007;25:1047–54.PubMedCrossRefGoogle Scholar
  21. 21.
    Hall PD. Pathological spectrum of alcoholic liver disease. Alcohol Alcohol Suppl. 1994;2:303–13.PubMedGoogle Scholar
  22. 22.
    Bataller R, Mandrekar P. Identifying molecular targets to improve immune function in alcoholic hepatitis. Gastroenterology. 2015;148(3):498–501.PubMedCentralPubMedCrossRefGoogle Scholar
  23. 23.
    Tsukamoto H, Machida K, Dynnyk A, et al. “Second hit” models of alcoholic liver disease. Semin Liver Dis. 2009;29:178–87.PubMedCentralPubMedCrossRefGoogle Scholar
  24. 24.
    Wilfred de Alwis NM, Day CP. Genetics of alcoholic liver disease and nonalcoholic fatty liver disease. Semin Liver Dis. 2007;27:44–54.PubMedCrossRefGoogle Scholar
  25. 25.
    Askgaard G, Grønbæk M, Kjær MS, et al. Alcohol drinking pattern and risk of alcoholic liver cirrhosis: a prospective cohort study. J Hepatol. 2015;62(5):1061–7. pii: S0168-8278(14)00923-4.PubMedCrossRefGoogle Scholar
  26. 26.
    Stickel F, Buch S, Lau K, et al. Genetic variation in the PNPLA3 gene is associated with alcoholic liver injury in caucasians. Hepatology. 2011;53:86–95.PubMedCrossRefGoogle Scholar
  27. 27.
    Hatton J, Burton A, Nash H, et al. Drinking patterns, dependency and life-time drinking history in alcohol-related liver disease. Addiction. 2009;104:587–92.PubMedCrossRefGoogle Scholar
  28. 28.
    Raynard B, Balian A, Fallik D, et al. Risk factors of fibrosis in alcohol-induced liver disease. Hepatology. 2002;35:635–8.PubMedCrossRefGoogle Scholar
  29. 29.
    Naveau S, Giraud V, Borotto E, et al. Excess weight risk factor for alcoholic liver disease. Hepatology. 1997;25:108–11.PubMedCrossRefGoogle Scholar
  30. 30.
    Xu JLK, Verlinsky A, Lugea A, French SW, Cooper MP, Ji C, Tsukamoto H. Synergistic steatohepatitis by moderate obesity and alcohol in mice despite increased adiponectin and p-AMPK. J Hepatol. 2011;55(3):673–82.PubMedCentralPubMedCrossRefGoogle Scholar
  31. 31.
    Gao B. Alcohol and hepatitis virus interactions in liver pathology. In: Preedy VR, Watson R, editors. Comprehensive handbook of alcohol related pathology, vol. 2. New York: Academic Press; 2005. p. 819–32.Google Scholar
  32. 32.
    Siu L, Foont J, Wands JR. Hepatitis C virus and alcohol. Semin Liver Dis. 2009;29:188–99.PubMedCentralPubMedCrossRefGoogle Scholar
  33. 33.
    Gual A, Segura L, Contel M, et al. Audit-3 and audit-4: effectiveness of two short forms of the alcohol use disorders identification test. Alcohol Alcohol. 2002;37:591–6.PubMedCrossRefGoogle Scholar
  34. 34.
    Sorbi D, Boynton J, Lindor KD. The ratio of aspartate aminotransferase to alanine aminotransferase: potential value in differentiating nonalcoholic steatohepatitis from alcoholic liver disease. Am J Gastroenterol. 1999;94:1018–22.PubMedCrossRefGoogle Scholar
  35. 35.
    Nyblom H, Berggren U, Balldin J, et al. High AST/ALT ratio may indicate advanced alcoholic liver disease rather than heavy drinking. Alcohol Alcohol. 2004;39:336–9.PubMedCrossRefGoogle Scholar
  36. 36.
    Cohen JA, Kaplan MM. The SGOT/SGPT ratio – an indicator of alcoholic liver disease. Dig Dis Sci. 1979;24:835–8.PubMedCrossRefGoogle Scholar
  37. 37.
    Bortolotti F, De Paoli G, Tagliaro F. Carbohydrate-deficient transferrin (CDT) as a marker of alcohol abuse: a critical review of the literature 2001–2005. J Chromatogr B Analyt Technol Biomed Life Sci. 2006;841:96–109.PubMedCrossRefGoogle Scholar
  38. 38.
    Hietala J, Koivisto H, Anttila P, et al. Comparison of the combined marker GGT-CDT and the conventional laboratory markers of alcohol abuse in heavy drinkers, moderate drinkers and abstainers. Alcohol Alcohol. 2006;41:528–33.PubMedCrossRefGoogle Scholar
  39. 39.
    Palmentieri B, de Sio I, La Mura V, et al. The role of bright liver echo pattern on ultrasound B-mode examination in the diagnosis of liver steatosis. Dig Liver Dis. 2006;38:485–9.PubMedCrossRefGoogle Scholar
  40. 40.
    Saverymuttu SH, Joseph AE, Maxwell JD. Ultrasound scanning in the detection of hepatic fibrosis and steatosis. Br Med J (Clin Res Ed). 1986;292:13–5.CrossRefGoogle Scholar
  41. 41.
    d’Assignies G, Ruel M, Khiat A, et al. Noninvasive quantitation of human liver steatosis using magnetic resonance and bioassay methods. Eur Radiol. 2009;19:2033–40.PubMedCrossRefGoogle Scholar
  42. 42.
    Mueller S, Seitz HK, Rausch V. Non-invasive diagnosis of alcoholic liver disease. World J Gastroenterol. 2014;20:14626–41.PubMedCentralPubMedCrossRefGoogle Scholar
  43. 43.
    Lieber CS, Weiss DG, Morgan TR, et al. Aspartate aminotransferase to platelet ratio index in patients with alcoholic liver fibrosis. Am J Gastroenterol. 2006;101:1500–8.PubMedCrossRefGoogle Scholar
  44. 44.
    Naveau S, Raynard B, Ratziu V, et al. Biomarkers for the prediction of liver fibrosis in patients with chronic alcoholic liver disease. Clin Gastroenterol Hepatol. 2005;3:167–74.PubMedCrossRefGoogle Scholar
  45. 45.
    Cales P, Oberti F, Michalak S, et al. A novel panel of blood markers to assess the degree of liver fibrosis. Hepatology. 2005;42:1373–81.PubMedCrossRefGoogle Scholar
  46. 46.
    Naveau S, Gaude G, Asnacios A, et al. Diagnostic and prognostic values of noninvasive biomarkers of fibrosis in patients with alcoholic liver disease. Hepatology. 2009;49:97–105.PubMedCrossRefGoogle Scholar
  47. 47.
    Parkes J, Roderick P, Harris S, et al. Enhanced liver fibrosis test can predict clinical outcomes in patients with chronic liver disease. Gut. 2010;59:1245–51.PubMedCrossRefGoogle Scholar
  48. 48.
    Imbert-Bismut F, Ratziu V, Pieroni L, et al. Biochemical markers of liver fibrosis in patients with hepatitis C virus infection: a prospective study. Lancet. 2001;357:1069–75.PubMedCrossRefGoogle Scholar
  49. 49.
    Thabut D, Naveau S, Charlotte F, et al. The diagnostic value of biomarkers (AshTest) for the prediction of alcoholic steato-hepatitis in patients with chronic alcoholic liver disease. J Hepatol. 2006;44:1175–85.PubMedCrossRefGoogle Scholar
  50. 50.
    Nahon P, Kettaneh A, Tengher-Barna I, et al. Assessment of liver fibrosis using transient elastography in patients with alcoholic liver disease. J Hepatol. 2008;49:1062–8.PubMedCrossRefGoogle Scholar
  51. 51.
    Nguyen-Khac E, Chatelain D, Tramier B, et al. Assessment of asymptomatic liver fibrosis in alcoholic patients using fibroscan: prospective comparison with seven non-invasive laboratory tests. Aliment Pharmacol Ther. 2008;28:1188–98.PubMedCrossRefGoogle Scholar
  52. 52.
    Mueller S, Millonig G, Sarovska L, et al. Increased liver stiffness in alcoholic liver disease: differentiating fibrosis from steatohepatitis. World J Gastroenterol. 2010;16:966–72.PubMedCentralPubMedCrossRefGoogle Scholar
  53. 53.
    Castera L, Pinzani M. Biopsy and non-invasive methods for the diagnosis of liver fibrosis: does it take two to tango? Gut. 2010;59:861–6.PubMedCrossRefGoogle Scholar
  54. 54.
    Gelsi E, Dainese R, Truchi R, et al. Effect of detoxification on liver stiffness assessed by Fibroscan(R) in alcoholic patients. Alcohol Clin Exp Res. 2011;35:566–70.PubMedCrossRefGoogle Scholar
  55. 55.
    Sasso M, Beaugrand M, de Ledinghen V, et al. Controlled attenuation parameter (CAP): a novel VCTE guided ultrasonic attenuation measurement for the evaluation of hepatic steatosis: preliminary study and validation in a cohort of patients with chronic liver disease from various causes. Ultrasound Med Biol. 2010;36:1825–35.PubMedCrossRefGoogle Scholar
  56. 56.
    Bird GL. Investigation of alcoholic liver disease. Baillieres Clin Gastroenterol. 1993;7:663–82.PubMedCrossRefGoogle Scholar
  57. 57.
    Poynard T, Ratziu V, Bedossa P. Appropriateness of liver biopsy. Can J Gastroenterol. 2000;14:543–8.PubMedGoogle Scholar
  58. 58.
    MacSween RN, Burt AD. Histologic spectrum of alcoholic liver disease. Semin Liver Dis. 1986;6:221–32.PubMedCrossRefGoogle Scholar
  59. 59.
    Denk H, Lackinger E. Cytoskeleton in liver diseases. Semin Liver Dis. 1986;6:199–211.PubMedCrossRefGoogle Scholar
  60. 60.
    Bacon BR, Farahvash MJ, Janney CG, et al. Nonalcoholic steatohepatitis: an expanded clinical entity. Gastroenterology. 1994;107:1103–9.PubMedGoogle Scholar
  61. 61.
    Yip WW, Burt AD. Alcoholic liver disease. Semin Diagn Pathol. 2006;23:149–60.PubMedCrossRefGoogle Scholar
  62. 62.
    Kryger P, Schlichting P, Dietrichson O, et al. The accuracy of the clinical diagnosis in acute hepatitis and alcoholic liver disease. Clinical versus morphological diagnosis. Scand J Gastroenterol. 1983;18:691–6.PubMedCrossRefGoogle Scholar
  63. 63.
    Mookerjee RP, Lackner C, Stauber R, et al. The role of liver biopsy in the diagnosis and prognosis of patients with acute deterioration of alcoholic cirrhosis. J Hepatol. 2011;55:1103–11.PubMedCrossRefGoogle Scholar
  64. 64.
    European Association for the Study of Liver. EASL clinical practical guidelines: management of alcoholic liver disease. J Hepatol. 2012;57:399–420.CrossRefGoogle Scholar
  65. 65.
    Qamar AA, Grace ND, Groszmann RJ, et al. Incidence, prevalence, and clinical significance of abnormal hematologic indices in compensated cirrhosis. Clin Gastroenterol Hepatol. 2009;7:689–95.PubMedCentralPubMedCrossRefGoogle Scholar
  66. 66.
    Okazaki H, Ito K, Fujita T, et al. Discrimination of alcoholic from virus-induced cirrhosis on MR imaging. AJR Am J Roentgenol. 2000;175:1677–81.PubMedCrossRefGoogle Scholar
  67. 67.
    Murray KF, Carithers Jr RL. AASLD practice guidelines: evaluation of the patient for liver transplantation. Hepatology. 2005;41:1407–32.PubMedCrossRefGoogle Scholar
  68. 68.
    Altamirano J, Miquel R, Katoonizadeh A, et al. A histologic scoring system for prognosis of patients with alcoholic hepatitis. Gastroenterology. 2014;146(5):1231–9. e1-6.PubMedCentralPubMedCrossRefGoogle Scholar
  69. 69.
    Piano MR, Schwertz DW. Alcoholic heart disease: a review. Heart Lung. 1994;23:3–17. Quiz 18–20.PubMedGoogle Scholar
  70. 70.
    Preedy VR, Adachi J, Ueno Y, et al. Alcoholic skeletal muscle myopathy: definitions, features, contribution of neuropathy, impact and diagnosis. Eur J Neurol. 2001;8:677–87.PubMedCrossRefGoogle Scholar
  71. 71.
    Gonzalez-Reimers E, Santolaria-Fernandez F, Martin-Gonzalez MC, et al. Alcoholism: a systemic proinflammatory condition. World J Gastroenterol. 2014;20:14660–71.PubMedCentralPubMedCrossRefGoogle Scholar
  72. 72.
    Steer ML, Waxman I, Freedman S. Chronic pancreatitis. N Engl J Med. 1995;332:1482–90.PubMedCrossRefGoogle Scholar
  73. 73.
    Nordstrom P, Nordstrom A, Eriksson M, et al. Risk factors in late adolescence for young-onset dementia in men: a nationwide cohort study. JAMA Intern Med. 2013;173:1612–8.PubMedCrossRefGoogle Scholar
  74. 74.
    Bates ME, Bowden SC, Barry D. Neurocognitive impairment associated with alcohol use disorders: implications for treatment. Exp Clin Psychopharmacol. 2002;10:193–212.PubMedCrossRefGoogle Scholar
  75. 75.
    Chopra K, Tiwari V. Alcoholic neuropathy: possible mechanisms and future treatment possibilities. Br J Clin Pharmacol. 2012;73:348–62.PubMedCentralPubMedCrossRefGoogle Scholar
  76. 76.
    Borowsky SA, Strome S, Lott E. Continued heavy drinking and survival in alcoholic cirrhotics. Gastroenterology. 1981;80:1405–9.PubMedGoogle Scholar
  77. 77.
    Morgan MY. The prognosis and outcome of alcoholic liver disease. Alcohol Alcohol Suppl. 1994;2:335–43.PubMedGoogle Scholar
  78. 78.
    Soyka M, Rosner S. Emerging drugs to treat alcoholism. Expert Opin Emerg Drugs. 2010;15:695–711.PubMedCrossRefGoogle Scholar
  79. 79.
    Mohanty SR, LaBrecque DR, Mitros FA, et al. Liver transplantation for disulfiram-induced fulminant hepatic failure. J Clin Gastroenterol. 2004;38:292–5.PubMedCrossRefGoogle Scholar
  80. 80.
    Mann K, Lehert P, Morgan MY. The efficacy of acamprosate in the maintenance of abstinence in alcohol-dependent individuals: results of a meta-analysis. Alcohol Clin Exp Res. 2004;28:51–63.PubMedCrossRefGoogle Scholar
  81. 81.
    Mason BJ, Lehert P. Acamprosate for alcohol dependence: a sex-specific meta-analysis based on individual patient data. Alcohol Clin Exp Res. 2012;36:497–508.PubMedCentralPubMedCrossRefGoogle Scholar
  82. 82.
    Addolorato G, Leggio L. Safety and efficacy of baclofen in the treatment of alcohol-dependent patients. Curr Pharm Des. 2010;16:2113–7.PubMedCrossRefGoogle Scholar
  83. 83.
    Yamini D, Lee SH, Avanesyan A, et al. Utilization of baclofen in maintenance of alcohol abstinence in patients with alcohol dependence and alcoholic hepatitis with or without cirrhosis. Alcohol Alcohol. 2014;49:453–6.PubMedCrossRefGoogle Scholar
  84. 84.
    Lieber CS, Weiss DG, Groszmann R, et al. II. Veterans Affairs Cooperative Study of polyenylphosphatidylcholine in alcoholic liver disease. Alcohol Clin Exp Res. 2003;27:1765–72.PubMedCrossRefGoogle Scholar
  85. 85.
    Verrill C, Markham H, Templeton A, et al. Alcohol-related cirrhosis – early abstinence is a key factor in prognosis, even in the most severe cases. Addiction. 2009;104:768–74.PubMedCrossRefGoogle Scholar
  86. 86.
    Masson S, Emmerson I, Henderson E, et al. Clinical but not histological factors predict long-term prognosis in patients with histologically advanced non-decompensated alcoholic liver disease. Liver Int. 2014;34:235–42.PubMedCrossRefGoogle Scholar
  87. 87.
    Takahashi H, Shigefuku R, Maeyama S, et al. Cirrhosis improvement to alcoholic liver fibrosis after passive abstinence. BMJ Case Rep. 2014. doi: 10.1136/bcr-2013-201618.PubMedCentralGoogle Scholar
  88. 88.
    Stickel F, Hoehn B, Schuppan D, et al. Review article: nutritional therapy in alcoholic liver disease. Aliment Pharmacol Ther. 2003;18:357–73.PubMedCrossRefGoogle Scholar
  89. 89.
    Maddrey WC, Boitnott JK, Bedine MS, et al. Corticosteroid therapy of alcoholic hepatitis. Gastroenterology. 1978;75:193–9.PubMedGoogle Scholar
  90. 90.
    Dunn W, Jamil LH, Brown LS, et al. MELD accurately predicts mortality in patients with alcoholic hepatitis. Hepatology. 2005;41:353–8.PubMedCrossRefGoogle Scholar
  91. 91.
    Forrest EH, Morris AJ, Stewart S, et al. The Glasgow alcoholic hepatitis score identifies patients who may benefit from corticosteroids. Gut. 2007;56:1743–6.PubMedCentralPubMedCrossRefGoogle Scholar
  92. 92.
    Dominguez M, Rincon D, Abraldes JG, et al. A new scoring system for prognostic stratification of patients with alcoholic hepatitis. Am J Gastroenterol. 2008;103:2747–56.PubMedCrossRefGoogle Scholar
  93. 93.
    Cabre E, Rodriguez-Iglesias P, Caballeria J, et al. Short- and long-term outcome of severe alcohol-induced hepatitis treated with steroids or enteral nutrition: a multicenter randomized trial. Hepatology. 2000;32:36–42.PubMedCrossRefGoogle Scholar
  94. 94.
    Foody W, Heuman DD, Mihas AA, et al. Nutritional therapy for alcoholic hepatitis: new life for an old idea. Gastroenterology. 2001;120:1053–4.PubMedCrossRefGoogle Scholar
  95. 95.
    Imperiale TF, McCullough AJ. Do corticosteroids reduce mortality from alcoholic hepatitis? A meta-analysis of the randomized trials. Ann Intern Med. 1990;113:299–307.PubMedCrossRefGoogle Scholar
  96. 96.
    Louvet A, Naveau S, Abdelnour M, et al. The Lille model: a new tool for therapeutic strategy in patients with severe alcoholic hepatitis treated with steroids. Hepatology. 2007;45:1348–54.PubMedCrossRefGoogle Scholar
  97. 97.
    Akriviadis E, Botla R, Briggs W, et al. Pentoxifylline improves short-term survival in severe acute alcoholic hepatitis: a double-blind, placebo-controlled trial. Gastroenterology. 2000;119:1637–48.PubMedCrossRefGoogle Scholar
  98. 98.
    Thursz MRP, Allison ME, Austin A, Bowers M, Day CP, et al. Steroids or pentoxifylline for alcoholic hepatitis: results of the STOPAH trial. Hepatology. 2014;60(S1):LB1.Google Scholar
  99. 99.
    Mathurin P, Louvet A, Duhamel A, et al. Prednisolone with vs without pentoxifylline and survival of patients with severe alcoholic hepatitis: a randomized clinical trial. JAMA. 2013;310:1033–41.PubMedCrossRefGoogle Scholar
  100. 100.
    Nguyen-Khac E, Thevenot T, Piquet MA, et al. Glucocorticoids plus N-acetylcysteine in severe alcoholic hepatitis. N Engl J Med. 2011;365:1781–9.PubMedCrossRefGoogle Scholar
  101. 101.
    Altamirano J, Fagundes C, Dominguez M, et al. Acute kidney injury is an early predictor of mortality for patients with alcoholic hepatitis. Clin Gastroenterol Hepatol. 2012;10:65–71. e3.PubMedCrossRefGoogle Scholar
  102. 102.
    Louvet A, Wartel F, Castel H, et al. Infection in patients with severe alcoholic hepatitis treated with steroids: early response to therapy is the key factor. Gastroenterology. 2009;137:541–8.PubMedCrossRefGoogle Scholar

Copyright information

© Springer International Publishing Switzerland 2016

Authors and Affiliations

  1. 1.Department of GastroenterologyAjou University of School of MedicineSuwonRepublic of Korea
  2. 2.Division of Gastroenterology and Hepatology, Department of MedicineUniversity of North CarolinaChapel HillUSA

Personalised recommendations