2016, Number 4
<< Back Next >>
Ann Hepatol 2016; 15 (4)
Alcoholic hepatitis: How far are we and where are we going?
Prado V, Caballería J, Vargas V, Bataller R, Altamirano J
Language: English
References: 84
Page: 463-473
PDF size: 421.96 Kb.
ABSTRACT
The burden of alcoholic liver disease continues to be a major public health problem worldwide. The spectrum of disease ranges from
fatty liver to cirrhosis and hepatocellular carcinoma. Alcoholic hepatitis (AH) is a type of acute-on-chronic liver failure and the most
severe form of alcoholic liver disease. Severe AH carries a poor short-term prognosis and its management is still challenging, with
scarce advances in the last decades. Corticosteroids are still the first line of therapy in severe cases. Unfortunately, many patients
do not respond and novel targeted therapies are urgently needed. Liver transplantation has shown extraordinary results in non-responders
to corticosteroids however; its applicability is very low. This review summarizes the epidemiology, natural history, risk factors
and pathogenesis of alcoholic liver disease with special focus on the latest advances in prognostic stratification and therapy of
patients with alcoholic hepatitis.
REFERENCES
Gao B, Bataller R. Alcoholic liver disease: pathogenesis and new therapeutic targets. Gastroenterology 2011; 141: 1572-85.
Adam R, Karam V, Delvart V, O’Grady J, Mirza D, Klempnauer J, Castaing D, et al. Evolution of indications and results of liver transplantation in Europe. A report from the European Liver Transplant Registry (ELTR). J Hepatol 2012; 57: 675-88.
Moreau R, Jalan R, Gines P, Pavesi M, Angeli P, Cordoba J, Durand F, et al. Acute-on-chronic liver failure is a distinct syndrome that develops in patients with acute decompensation of cirrhosis. Gastroenterology 2013; 144: 1426-37.
Mathurin P, Beuzin F, Louvet A, Carrié-Ganne N, Balian A, Trinchet JC, Dalsoglio D, et al. Fibrosis progression occurs in a subgroup of heavy drinkers with typical histological features. Aliment Pharmacol Ther 2007; 25: 1047-54.
Ramaiah SK, Jaeschke H. Role of neutrophils in the pathogenesis of acute inflammatory liver injury. Toxicol Pathol 2007; 35: 757-66.
Burza MA, Molinaro A, Attilia ML, Rotondo C, Attilia F, Ceccanti M, Ferri F, et al. PNPLA3 I148M (rs738409) genetic variant and age at onset of at-risk alcohol consumption are independent risk factors for alcoholic cirrhosis. Liver Int 2014; 34: 514-20.
Stickel F, Buch S, Lau K, Meyer zu Schwabedissen H, Berg T, Ridinger M, Rietschel M, et al. Genetic variation in the PNPLA3 gene is associated with alcoholic liver injury in caucasians. Hepatology 2011; 53: 86-95.
Corradini SG, Burza MA, Molinaro A, Romeo S. Patatin-like phospholipase domain containing 3 sequence variant and hepatocellular carcinoma. Hepatology 2011; 53: 1776.
Trepo E, Guyot E, Ganne-Carrie N, Degre D, Gustot T, Franchimont D, Sutton A, et al. PNPLA3 (rs738409 C>G) is a common risk variant associated with hepatocellular carcinoma in alcoholic cirrhosis. Hepatology 2012; 55: 1307-8.
Altamirano J, Michelena J. Alcohol consumption as a cofactor for other liver diseases. Clin Liver Dis 2013; 2: 72-5.
Baraona E, Lieber CS. Effects of ethanol on lipid metabolism. J Lipid Res 1979; 20: 289-315.
You M, Matsumoto M, Pacold CM, Cho WK, Crabb DW. The role of AMP-activated protein kinase in the action of ethanol in the liver. Gastroenterology 2004; 127: 1798-808.
Gao B, Seki E, Brenner DA, Friedman S, Cohen JI, Nagy L, Szabo G, et al. Innate immunity in alcoholic liver disease. Am J Physiol Gastrointest Liver Physiol 2011; 300: G516-G525.
Szabo G. Gut-liver axis in alcoholic liver disease. Gastroenterology 2015; 148: 30-6.
Altamirano J, Bataller R. Alcoholic liver disease: pathogenesis and new targets for therapy. Nat Rev Gastroenterol Hepatol 2011; 8: 491-501.
Dominguez M, Miquel R, Colmenero J, Moreno M, García- Pagán J-C, Bosch J, Arroyo V, et al. Hepatic expression of CXC chemokines predicts portal hypertension and survival in patients with alcoholic hepatitis. Gastroenterology 2009; 136: 1639-50.
Morales-Ibanez O, Domínguez M, Ki SH, Marcos M, Chaves JF, Nguyen-Khac E, Houchi H, et al. Human and experimental evidence supporting a role for osteopontin in alcoholic hepatitis. Hepatology 2013; 58: 1742-56.
Affò S, Dominguez M, Lozano JJ, Sancho-Bru P, Rodrigo- Torres D, Morales-Ibanez O, Moreno M, et al. Transcriptome analysis identifies TNF superfamily receptors as potential therapeutic targets in alcoholic hepatitis. Gut 2013; 62: 452-60.
Affò S, Morales-Ibanez O, Rodrigo-Torres D, Altamirano J, Blaya D, Dapito DH, Millan C, et al. CCL20 mediates lipopolysaccharide induced liver injury and is a potential driver of inflammation and fibrosis in alcoholic hepatitis. Gut 2014; 63: 1782-92.
Feldstein AE, Gores GJ. Apoptosis in alcoholic and nonalcoholic steatohepatitis. Front Biosci 2005; 10: 3093-9.
Yip WW, Burt AD. Alcoholic liver disease. Semin Diagn Pathol 2006; 23: 149-60.
Wang J-H, Batey R-G, George J. Role of ethanol in the regulation of hepatic stellate cell function. World J Gastroenterol 2006; 12: 6926-32.
Friedman SL. Stellate cell activation in alcoholic fibrosis—an overview. Alcohol Clin Exp Res 1999; 23: 904-10.
Støy S, Sandahl TD, Dige AK, Agnholt J, Rasmussen TK, Grønbæk H, Deleuran B, et al. Highest frequencies of interleukin- 22-producing T helper cells in alcoholic hepatitis patients with a favourable short-term course. PLoS One 2013; 8: e55101.
Radaeva S, Sun R, Pan H-N, Hong F, Gao B. Interleukin 22 (IL-22) plays a protective role in T cell-mediated murine hepatitis: IL-22 is a survival factor for hepatocytes via STAT3 activation. Hepatology 2004; 39: 1332-42.
Kong X, Feng D, Wang H, Hong F, Bertola A, Wang F-S, Gao B, et al. Interleukin-22 induces hepatic stellate cell senescence and restricts liver fibrosis in mice. Hepatology 2012; 56: 1150-9.
Eidenschenk C, Rutz S, Liesenfeld O, Ouyang W. Role of IL- 22 in microbial host defense. Curr Top Microbiol Immunol 2014; 380: 213-36.
Xu M-J, Feng D, Wang H, Guan Y, Yan X, Gao B. IL-22 ameliorates renal ischemia-reperfusion injury by targeting proximal tubule epithelium. J Am Soc Nephrol 2014; 25: 967-77.
Rudler M, Mouri S, Charlotte F, Lebray P, Capocci R, Benosman H, Poynard T, et al. Prognosis of treated severe alcoholic hepatitis in patients with gastrointestinal bleeding. J Hepatol 2015; 62: 816-21.
EASL clinical practical guidelines: management of alcoholic liver disease. J Hepatol 2012; 57: 399-420.
Altamirano J, Miquel R, Katoonizadeh A, Abraldes JG, Duarte- Rojo A, Louvet A, Augustin S, et al. A histologic scoring system for prognosis of patients with alcoholic hepatitis. Gastroenterology 2014; 146: 1231-9.
Papastergiou V, Tsochatzis EA, Pieri G, Thalassinos E, Dhar A, Bruno S, Karatapanis S, et al. Nine scoring models for shortterm mortality in alcoholic hepatitis: cross-validation in a biopsyproven cohort. Aliment Pharmacol Ther 2014; 39: 721-32.
Sandahl TD, Jepsen P, Ott P, Vilstrup H. Validation of prognostic scores for clinical use in patients with alcoholic hepatitis. Scand J Gastroenterol 2011; 46: 1127-32.
Louvet A, Labreuche J, Artru F, Boursier J, Kim DJ, O’Grady J, Trépo E, et al. Combining Data From Liver Disease Scoring Systems Better Predicts Outcomes of Patients With Alcoholic Hepatitis. Gastroenterology 2015; 149: 398-406.
Altamirano J, Fagundes C, Dominguez M, García E, Michelena J, Cárdenas A, Guevara M, et al. Acute kidney injury is an early predictor of mortality for patients with alcoholic hepatitis. Clin Gastroenterol Hepatol 2012; 10: 65-71.
Sersté T, Njimi H, Degré D, Deltenre P, Schreiber J, Lepida A, Trépo E, et al. The use of beta-blockers is associated with the occurrence of acute kidney injury in severe alcoholic hepatitis. Liver Int 2015; 35: 1974-82.
Michelena J, Altamirano J, Abraldes JG, Affò S, Morales- Ibanez O, Sancho-Bru P, Dominguez M, et al. Systemic inflammatory response and serum lipopolysaccharide levels predict multiple organ failure and death in alcoholic hepatitis. Hepatology 2015; 62: 762-72.
Maiwall R, Chandel SS, Wani Z, Kumar S, Sarin SK. SIRS at admission is a predictor of AKI development and mortality in hospitalized patients with severe alcoholic hepatitis. Dig Dis Sci 2016; 61: 920-9.
Louvet A, Wartel F, Castel H, Dharancy S, Hollebecque A, Canva-Delcambre V, Deltenre P, 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.
Orntoft NW, Sandahl TD, Jepsen P, Vilstrup H. Short-term and long-term causes of death in patients with alcoholic hepatitis in Denmark. Clin Gastroenterol Hepatol 2014; 12: 1739-44.
Hmoud BS, Patel K, Bataller R, Singal AK. Corticosteroids and occurrence of and mortality from infections in severe alcoholic hepatitis: a meta-analysis of randomized trials. Liver Int 2016; 36: 721-8.
Gustot T, Maillart E, Bocci M, Surin R, Trépo E, Degré D, Lucidi V, et al. Invasive aspergillosis in patients with severe alcoholic hepatitis. J Hepatol 2014; 60: 267-74.
Moreno C, Deltenre P, Senterre C, Louvet A, Gustot T, Bastens B, Hittelet A, et al. Intensive Enteral Nutrition is Ineffective for Individuals with Severe Alcoholic Hepatitis Treated with Corticosteroids. Gastroenterology 2016; 150: 903-10.
Sanchez-Delgado J, Miquel M. Role of rifaximin in the treatment of hepatic encephalopathy. Gastroenterol Hepatol 2016; 39: 282-92.
Galbois A, Aegerter P, Martel-Samb P, Housset C, Thabut D, Offenstadt G, Ait-Oufella H, et al. Improved prognosis of septic shock in patients with cirrhosis: a multicenter study. Crit Care Med 2014; 42: 1666-75.
Porter HP, Simon FR, Pope CE, Volwiler W, Fenster LF. Corticosteroid therapy in severe alcoholic hepatitis. A doubleblind drug trial. N Engl J Med 1971; 284: 1350-5.
Blitzer BL, Mutchnick MG, Joshi PH, Phillips MM, Fessel JM, Conn HO. Adrenocorticosteroid therapy in alcoholic hepatitis. A prospective, double-blind randomized study. Am J Dig Dis 1977; 22: 477-84.
Ramond MJ, Poynard T, Rueff B, Mathurin P, Théodore C, Chaput JC, Benjamou JP, et al. A randomized trial of prednisolone in patients with severe alcoholic hepatitis. N Engl J Med 1992; 326: 507-12.
Mathurin P, Duchatelle V, Ramond MJ, Degott C, Bedossa P, Erlinger S, Benjamou JP, et al. Survival and prognostic factors in patients with severe alcoholic hepatitis treated with prednisolone. Gastroenterology 1996; 110: 1847-53.
Christensen E, Gluud C. Glucocorticoids are ineffective in alcoholic hepatitis: a meta-analysis adjusting for confounding variables. Gut 1995; 37: 113-8.
Rambaldi A, Saconato HH, Christensen E, Thorlund K, Wetterslev J, Gluud C. Systematic review: glucocorticosteroids for alcoholic hepatitis—a Cochrane Hepato-Biliary Group systematic review with meta-analyses and trial sequential analyses of randomized clinical trials. Aliment Pharmacol Ther 2008; 27: 1167-78.
Singh S, Murad MH, Chandar AK, Bongiorno CM, Singal AK, Atkinson SR, Thursz M, et al. Comparative effectiveness of pharmacological interventions for severe alcoholic hepatitis: A systematic review and network meta-analysis. Gastroenterology 2015; 149: 958-70.
Thursz MR, Richardson P, Allison M, Austin A, Bowers M, Day CP, Downs N, et al. Prednisolone or pentoxifylline for alcoholic hepatitis. N Engl J Med 2015; 372: 1619-28.
Akriviadis E, Botla R, Briggs W, Han S, Reynolds T, Shakil O. Pentoxifylline improves short-term survival in severe acute alcoholic hepatitis: a double-blind, placebo-controlled trial. Gastroenterology 2000; 119: 1637-48.
Mathurin P, Louvet A, Duhamel A, Nahon P, Carbonell N, Boursier J, Anty R, et al. Prednisolone with vs without pentoxifylline and survival of patients with severe alcoholic hepatitis: a randomized clinical trial. JAMA 2013; 310: 1033-41.
Louvet A, Diaz E, Dharancy S, Coevoet H, Texier F, Thévenot T, Deltenre P, et al. Early switch to pentoxifylline in patients with severe alcoholic hepatitis is inefficient in non-responders to corticosteroids. J Hepatol 2008; 48: 465-70.
Nguyen-Khac E, Thevenot T, Piquet M-A, Benferhat S, Goria O, Chatelain D, Tramier B, et al. Glucocorticoids plus N-acetylcysteine in severe alcoholic hepatitis. N Engl J Med 2011; 365: 1781-9.
Naveau S, Chollet-Martin S, Dharancy S, Mathurin P, Jouet P, Piquet M-A, Davion T, et al. A double-blind randomized controlled trial of infliximab associated with prednisolone in acute alcoholic hepatitis. Hepatology 2004; 39: 1390-7.
Boetticher NC, Peine CJ, Kwo P, Abrams GA, Patel T, Aqel B, Boardman L, et al. A randomized, double-blinded, placebocontrolled multicenter trial of etanercept in the treatment of alcoholic hepatitis. Gastroenterology 2008; 135: 1953-60.
Mendenhall C, Roselle GA, Gartside P, Moritz T. Relationship of protein calorie malnutrition to alcoholic liver disease: a reexamination of data from two Veterans Administration Cooperative Studies. Alcohol Clin Exp Res 1995; 19: 635-41.
Rambaldi A, Iaquinto G, Gluud C. Anabolic-androgenic steroids for alcoholic liver disease: a Cochrane review. Am J Gastroenterol 2002; 97: 1674-81.
Higuera-de la Tijera F, Servín-Caamaño AI, Cruz-Herrera J, Serralde-Zúñiga AE, Abdo-Francis JM, Gutiérrez-Reyes G, Pérez-Hernández J, et al. Treatment with metadoxine and its impact on early mortality in patients with severe alcoholic hepatitis. Ann Hepatol 2014; 13: 343-52.
Mezey E, Potter JJ, Rennie-Tankersley L, Caballeria J, Pares A. A randomized placebo controlled trial of vitamin E for alcoholic hepatitis. J Hepatol 2004; 40: 40-6.
Parés A, Planas R, Torres M, Caballería J, Viver JM, Acero D, Panés J, et al. Effects of silymarin in alcoholic patients with cirrhosis of the liver: results of a controlled, doubleblind, randomized and multicenter trial. J Hepatol 1998; 28: 615-21.
Hallé P, Paré P, Kaptein E, Kanel G, Redeker AG, Reynolds TB. Double-blind, controlled trial of propylthiouracil in patients with severe acute alcoholic hepatitis. Gastroenterology 1982; 82: 925-31.
Orrego H, Kalant H, Israel Y, Blake J, Medline A, Rankin JG, Armstrong A, et al. Effect of short-term therapy with propylthiouracil in patients with alcoholic liver disease. Gastroenterology 1979; 76: 105-15.
Rambaldi A, Gluud C. Propylthiouracil for alcoholic liver disease. Cochrane database Syst Rev. 2005; CD002800.
Laleman W, Wilmer A, Evenepoel P, Elst I Vander, Zeegers M, Zaman Z, Verslype C, et al. Effect of the molecular adsorbent recirculating system and Prometheus devices on systemic haemodynamics and vasoactive agents in patients with acute-on-chronic alcoholic liver failure. Crit Care 2006; 10: R108.
Sen S, Mookerjee RP, Cheshire LM, Davies NA, Williams R, Jalan R. Albumin dialysis reduces portal pressure acutely in patients with severe alcoholic hepatitis. J Hepatol 2005; 43: 142-8.
Jalan R, Sen S, Steiner C, Kapoor D, Alisa A, Williams R. Extracorporeal liver support with molecular adsorbents recirculating system in patients with severe acute alcoholic hepatitis. J Hepatol 2003; 38: 24-31.
Mathurin P, Moreno C, Samuel D, Dumortier J, Salleron J, Durand F, Castel H, et al. Early liver transplantation for severe alcoholic hepatitis. N Engl J Med 2011; 365: 1790-800. Alcoholic
Im GY, Kim-Schluger L, Shenoy A, Schubert E, Goel A, Friedman SL, Florman S, et al. Early Liver Transplantation for Severe Alcoholic Hepatitis in the United States-A Single- Center Experience. Am J Transplant 2016; 16: 841-9.
Potts JR, Goubet S, Heneghan MA, Verma S. Determinants of long-term outcome in severe alcoholic hepatitis. Aliment Pharmacol Ther 2013; 38: 584-95.
Addolorato G, Leggio L, Ferrulli A, Cardone S, Vonghia L, Mirijello A, Abenavoli L, et al. Effectiveness and safety of baclofen for maintenance of alcohol abstinence in alcoholdependent patients with liver cirrhosis: randomised, doubleblind controlled study. Lancet 2007; 370: 1915-22.
Yamini D, Lee SH, Avanesyan A, Walter M, Runyon B. 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.
Garbutt JC, Kranzler HR, O’Malley SS, Gastfriend DR, Pettinati HM, Silverman BL, Loewy J, et al. Efficacy and tolerability of long-acting injectable naltrexone for alcohol dependence: a randomized controlled trial. JAMA 2005; 293: 1617-25.
Mason BJ. Rationale for combining acamprosate and naltrexone for treating alcohol dependence. J Stud Alcohol Suppl 2005; 15: 148-56.
Maddrey WC, Boitnott JK, Bedine MS, Weber FL, Mezey E, White RI. Corticosteroid therapy of alcoholic hepatitis. Gastroenterology 1978; 75: 193-9.
Carithers RL, Herlong HF, Diehl AM, Shaw EW, Combes B, Fallon HJ, Maddrey W, et al. Methylprednisolone therapy in patients with severe alcoholic hepatitis. A randomized multicenter trial. Ann Intern Med 1989; 110: 685-90.
Jeong JY, Sohn JH, Son BK, Paik CH, Kim SH, Han DS, Jeong YC, et al. Comparison of model for end-stage liver disease score with discriminant function and child-Turcotte-Pugh scores for predicting short-term mortality in Korean patients with alcoholic hepatitis. Korean J Gastroenterol 2007; 49: 93-9.
Dunn W, Jamil LH, Brown LS, Wiesner RH, Kim WR, Menon KVN, Malinchoc M, et al. MELD accurately predicts mortality in patients with alcoholic hepatitis. Hepatology 2005; 41: 353-8.
Forrest EH, Evans CDJ, Stewart S, Phillips M, Oo YH, McAvoy NC, Fisher NC, et al. Analysis of factors predictive of mortality in alcoholic hepatitis and derivation and validation of the Glasgow alcoholic hepatitis score. Gut 2005; 54: 1174-9.
Dominguez M, Rincón D, Abraldes JG, Miquel R, Colmenero J, Bellot P, García-Pagán JC, et al. A new scoring system for prognostic stratification of patients with alcoholic hepatitis. Am J Gastroenterol 2008; 103: 2747-56.
Louvet A, Naveau S, Abdelnour M, Ramond M-J, Diaz E, Fartoux L, Dharancy S, 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.