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Meta-analysis of patient survival and rate of alcohol relapse in liver-transplanted patients for acute alcoholic hepatitis

  • Systematic Review and Meta-Analysis
  • Published:
Langenbeck's Archives of Surgery Aims and scope Submit manuscript

Abstract

Purpose

This review investigated survival and alcoholic relapse following liver transplantation (LT) in patients with severe acute alcoholic hepatitis (AH) without 6 months of alcohol abstinence.

Methods

All studies comparing acute AH patients undergoing LT with a control group were included. CENTRAL, MEDLINE, and Web of Science databases were searched. Survival benefits or odds ratios (OR) and 95% confidence intervals (CI) were assessed by meta-analyses using a random effects model. The study was registered in PROSPERO (CRD42017057971). According to the search results, two separate meta-analyses were performed: meta-analysis A compared early LT with medical therapy alone in patients with severe AH that were not responding to medical therapy and meta-analysis B compared LT outcome in patients with AH and chronic alcoholic cirrhosis (AC).

Results

The search yielded 2232 articles. Eight studies were included in the two meta-analyses—two studies in meta-analysis A and six studies in meta-analysis B. The two studies (n = 70) included in meta-analysis A revealed that 1-year patient survival was significantly higher in the LT group compared with the medical therapy–alone group (survival benefit, 15.88; 95% CI, 3.98–63.35; p < 0.0001). The six studies in meta-analysis B (including 1091 patients) showed that 1-year (survival benefit, 1.65; 95% CI, 0.95–2.89; p = 0.08), 3-year (survival benefit, 1.31; 95% CI, 0.79–2.18; p = 0.30), and 5-year survival (survival benefit, 1.54; 95% CI, 0.92–2.56; p = 0.10) were not significantly different between AH and AC groups. There was no significant difference in the rate of alcohol relapse between the groups (OR, 1.26; 95% CI, 0.53–2.96; p = 0.60).

Conclusions

Early LT is a life-saving treatment for AH patients that do not respond to medical therapy. The chance of alcohol relapse after LT is not increased in selected patients.

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References

  1. Mandrekar P, Bataller R, Tsukamoto H, Gao B (2016) Alcoholic hepatitis: translational approaches to develop targeted therapies. Hepatology 64(4):1343–1355. https://doi.org/10.1002/hep.28530

    Article  PubMed  PubMed Central  Google Scholar 

  2. Fung P, Pyrsopoulos N (2017) Emerging concepts in alcoholic hepatitis. World J Hepatol 9(12):567–585. https://doi.org/10.4254/wjh.v9.i12.567

    Article  PubMed  PubMed Central  Google Scholar 

  3. Singal AK, Kamath PS, Gores GJ, Shah VH (2014) Alcoholic hepatitis: current challenges and future directions. Clin Gastroenterol Hepatol 12(4):555–564; quiz e531–552. https://doi.org/10.1016/j.cgh.2013.06.013

    Article  PubMed  Google Scholar 

  4. Thursz M, Morgan TR (2016) Treatment of severe alcoholic hepatitis. Gastroenterology 150(8):1823–1834. https://doi.org/10.1053/j.gastro.2016.02.074

    Article  PubMed  PubMed Central  Google Scholar 

  5. Aday AW, Mitchell MC, Casey LC (2017) Alcoholic hepatitis: current trends in management. Curr Opin Gastroenterol 33(3):142–148. https://doi.org/10.1097/mog.0000000000000359

    Article  CAS  PubMed  Google Scholar 

  6. Lanthier N, Starkel P (2017) Treatment of severe alcoholic hepatitis: past, present and future. Eur J Clin Investig 47(7):531–539. https://doi.org/10.1111/eci.12767

    Article  CAS  Google Scholar 

  7. European Association for the Study of Liver (2012) EASL clinical practical guidelines: management of alcoholic liver disease. J Hepatol 57(2):399–420. https://doi.org/10.1016/j.jhep.2012.04.004

    Article  Google Scholar 

  8. Im GY, Kim-Schluger L, Shenoy A, Schubert E, Goel A, Friedman SL, Florman S, Schiano TD (2016) Early liver transplantation for severe alcoholic hepatitis in the United States--a single-center experience. Am J Transplant 16(3):841–849. https://doi.org/10.1111/ajt.13586

    Article  CAS  PubMed  Google Scholar 

  9. Mathurin P, Moreno C, Samuel D, Dumortier J, Salleron J, Durand F, Castel H, Duhamel A, Pageaux GP, Leroy V, Dharancy S, Louvet A, Boleslawski E, Lucidi V, Gustot T, Francoz C, Letoublon C, Castaing D, Belghiti J, Donckier V, Pruvot FR, Duclos-Vallee JC (2011) Early liver transplantation for severe alcoholic hepatitis. N Engl J Med 365(19):1790–1800. https://doi.org/10.1056/NEJMoa1105703

    Article  CAS  PubMed  Google Scholar 

  10. Schneekloth TD, Niazi SK, Simonetto DA (2017) Alcoholic hepatitis: appropriate indication for liver transplantation? Curr Opin Organ Transplant 22(6):578–583. https://doi.org/10.1097/mot.0000000000000468

    Article  PubMed  Google Scholar 

  11. Jesudian AB, Brown RS Jr (2016) Acute alcoholic hepatitis as indication for liver transplantation. Curr Opin Organ Transplant 21(2):107–110. https://doi.org/10.1097/mot.0000000000000285

    Article  PubMed  Google Scholar 

  12. Hwang S, Lee SG, Kim KK, Kim KH, Ahn CS, Moon DB, Ha TY, Song GW (2006) Efficacy of 6-month pretransplant abstinence for patients with alcoholic liver disease undergoing living donor liver transplantation. Transplant Proc 38(9):2937–2940. https://doi.org/10.1016/j.transproceed.2006.08.139

    Article  CAS  PubMed  Google Scholar 

  13. Louvet A, Naveau S, Abdelnour M, Ramond MJ, Diaz E, Fartoux L, Dharancy S, Texier F, Hollebecque A, Serfaty L, Boleslawski E, Deltenre P, Canva V, Pruvot FR, Mathurin P (2007) The Lille model: a new tool for therapeutic strategy in patients with severe alcoholic hepatitis treated with steroids. Hepatology 45(6):1348–1354. https://doi.org/10.1002/hep.21607

    Article  CAS  PubMed  Google Scholar 

  14. Moher D, Shamseer L, Clarke M, Ghersi D, Liberati A, Petticrew M, Shekelle P, Stewart LA (2015) Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) 2015 statement. Syst Rev 4:1. https://doi.org/10.1186/2046-4053-4-1

    Article  PubMed  PubMed Central  Google Scholar 

  15. Goossen K, Tenckhoff S, Probst P, Grummich K, Mihaljevic AL, Buchler MW, Diener MK (2018) Optimal literature search for systematic reviews in surgery. Langenbeck’s Arch Surg 403(1):119–129. https://doi.org/10.1007/s00423-017-1646-x

    Article  Google Scholar 

  16. Sterne JA, Hernan MA, Reeves BC, Savovic J, Berkman ND, Viswanathan M, Henry D, Altman DG, Ansari MT, Boutron I, Carpenter JR, Chan AW, Churchill R, Deeks JJ, Hrobjartsson A, Kirkham J, Juni P, Loke YK, Pigott TD, Ramsay CR, Regidor D, Rothstein HR, Sandhu L, Santaguida PL, Schunemann HJ, Shea B, Shrier I, Tugwell P, Turner L, Valentine JC, Waddington H, Waters E, Wells GA, Whiting PF, Higgins JP (2016) ROBINS-I: a tool for assessing risk of bias in non-randomised studies of interventions. BMJ (Clinical Research Ed) 355:i4919. https://doi.org/10.1136/bmj.i4919

    Article  Google Scholar 

  17. Weeks SR, Sun Z, McCaul ME, Zhu H, Anders RA, Philosophe B, Ottmann SE, Garonzik Wang JM, Gurakar AO, Cameron AM (2018) Liver transplantation for severe alcoholic hepatitis, updated lessons from the world’s largest series. J Am Coll Surg 226(4):549–557. https://doi.org/10.1016/j.jamcollsurg.2017.12.044

    Article  PubMed  Google Scholar 

  18. Wells JT, Said A, Agni R, Tome S, Hughes S, Dureja P, Lucey MR (2007) The impact of acute alcoholic hepatitis in the explanted recipient liver on outcome after liver transplantation. Liver Transpl 13(12):1728–1735. https://doi.org/10.1002/lt.21298

    Article  PubMed  Google Scholar 

  19. Bonet H, Manez R, Kramer D, Wright HI, Gavaler JS, Baddour N, Van Thiel DH (1993) Survival of patients transplanted with alcoholic hepatitis plus cirrhosis as compared with those with cirrhosis alone. Transplant Proc 25(1 Pt 2):1126–1127

    CAS  PubMed  Google Scholar 

  20. Tome S, Martinez-Rey C, Gonzalez-Quintela A, Gude F, Brage A, Otero E, Abdulkader I, Forteza J, Bustamante M, Varo E (2002) Influence of superimposed alcoholic hepatitis on the outcome of liver transplantation for end-stage alcoholic liver disease. J Hepatol 36(6):793–798

    Article  Google Scholar 

  21. Shakil AO, Pinna A, Demetris J, Lee RG, Fung JJ, Rakela J (1997) Survival and quality of life after liver transplantation for acute alcoholic hepatitis. Liver Transpl 3(3):240–244

    CAS  Google Scholar 

  22. Singal AK, Bashar H, Anand BS, Jampana SC, Singal V, Kuo YF (2012) Outcomes after liver transplantation for alcoholic hepatitis are similar to alcoholic cirrhosis: exploratory analysis from the UNOS database. Hepatology 55(5):1398–1405. https://doi.org/10.1002/hep.25544

    Article  PubMed  Google Scholar 

  23. Lieber SR, Rice JP, Lucey MR, Bataller R (2017) Controversies in clinical trials for alcoholic hepatitis. J Hepatol 68:586–592. https://doi.org/10.1016/j.jhep.2017.09.013

    Article  PubMed  Google Scholar 

  24. Mathurin P, Bataller R (2015) Trends in the management and burden of alcoholic liver disease. J Hepatol 62(1 Suppl):S38–S46. https://doi.org/10.1016/j.jhep.2015.03.006

    Article  PubMed  PubMed Central  Google Scholar 

  25. Arsene D, Farooq O, Bataller R (2016) New therapeutic targets in alcoholic hepatitis. Hepatol Int 10(4):538–552. https://doi.org/10.1007/s12072-015-9701-6

    Article  PubMed  PubMed Central  Google Scholar 

  26. Thursz MR, Richardson P, Allison M, Austin A, Bowers M, Day CP, Downs N, Gleeson D, MacGilchrist A, Grant A, Hood S, Masson S, McCune A, Mellor J, O’Grady J, Patch D, Ratcliffe I, Roderick P, Stanton L, Vergis N, Wright M, Ryder S, Forrest EH (2015) Prednisolone or pentoxifylline for alcoholic hepatitis. N Engl J Med 372(17):1619–1628. https://doi.org/10.1056/NEJMoa1412278

    Article  CAS  PubMed  Google Scholar 

  27. Lee BP, Mehta N, Platt L, Gurakar A, Rice JP, Lucey MR, Im GY, Therapondos G, Han H, Victor DW, Fix OK, Dinges L, Dronamraju D, Hsu C, Voigt MD, Rinella ME, Maddur H, Eswaran S, Hause J, Foley D, Ghobrial RM, Dodge JL, Li Z, Terrault NA (2018) Outcomes of early liver transplantation for patients with severe alcoholic hepatitis. Gastroenterology 155:422–430.e1. https://doi.org/10.1053/j.gastro.2018.04.009

    Article  PubMed  Google Scholar 

  28. Cholankeril G, Perumpail RB, Hu M, Yoo ER, Liu A, Chalasani NP, Ahmed A (2016) Acute Alcoholic Hepatitis has comparable survival following liver transplantation to other causes of acute liver failure. In: Hepatology. vol 1 SUPP. WILEY-BLACKWELL 111 RIVER ST, HOBOKEN 07030–5774, NJ USA, pp 617A–617A

  29. Van Thiel DH, Bonet H, Gavaler J, Wright HI (1995) Effect of alcohol use on allograft rejection rates after liver transplantation for alcoholic liver disease. Alcohol Clin Exp Res 19(5):1151–1155

    Article  Google Scholar 

  30. Immordino G, Gelli M, Ferrante R, Ferrari C, Piaggio F, Ghinolfi D, Sturdevant M, Andorno E, Morelli N, Bottino G, Casaccia M, Valente U (2009) Alcohol abstinence and orthotopic liver transplantation in alcoholic liver cirrhosis. Transplant Proc 41(4):1253–1255. https://doi.org/10.1016/j.transproceed.2009.03.092

    Article  CAS  PubMed  Google Scholar 

  31. Bundesärztekammer B (2011) Richtlinien für die Wartelistenführung und die Organvermittlung gem. § 16 Abs. 1 S. 1 Nrn. 2 u. 5 TPG

  32. Dureja P, Lucey MR (2010) The place of liver transplantation in the treatment of severe alcoholic hepatitis. J Hepatol 52(5):759–764. https://doi.org/10.1016/j.jhep.2009.12.021

    Article  PubMed  Google Scholar 

  33. Obed A, Stern S, Jarrad A, Lorf T (2015) Six month abstinence rule for liver transplantation in severe alcoholic liver disease patients. World J Gastroenterol 21(14):4423–4426. https://doi.org/10.3748/wjg.v21.i14.4423

    Article  PubMed  PubMed Central  Google Scholar 

  34. BGH 5 StR 20/16 - Urteil vom 28. Juni 2017 (LG Göttingen). https://www.hrr-strafrecht.de/hrr/5/16/5-20-16.php

  35. DiMartini A, Day N, Dew MA, Javed L, Fitzgerald MG, Jain A, Fung JJ, Fontes P (2006) Alcohol consumption patterns and predictors of use following liver transplantation for alcoholic liver disease. Liver Transpl 12(5):813–820. https://doi.org/10.1002/lt.20688

    Article  PubMed  Google Scholar 

  36. Pfitzmann R, Schwenzer J, Rayes N, Seehofer D, Neuhaus R, Nussler NC (2007) Long-term survival and predictors of relapse after orthotopic liver transplantation for alcoholic liver disease. Liver Transpl 13(2):197–205. https://doi.org/10.1002/lt.20934

    Article  PubMed  Google Scholar 

  37. Hajifathalian K, Humberson A, Hanouneh MA, Barnes DS, Arora Z, Zein NN, Eghtesad B, Kelly D, Hanouneh IA (2016) Ohio solid organ transplantation consortium criteria for liver transplantation in patients with alcoholic liver disease. World J Hepatol 8(27):1149–1154. https://doi.org/10.4254/wjh.v8.i27.1149

    Article  PubMed  PubMed Central  Google Scholar 

  38. Weinrieb RM, Van Horn DH, McLellan AT, Lucey MR (2000) Interpreting the significance of drinking by alcohol-dependent liver transplant patients: fostering candor is the key to recovery. Liver Transpl 6(6):769–776. https://doi.org/10.1053/jlts.2000.18497

    Article  CAS  PubMed  Google Scholar 

  39. Starzl TE, Van Thiel D, Tzakis AG, Iwatsuki S, Todo S, Marsh JW, Koneru B, Staschak S, Stieber A, Gordon RD (1988) Orthotopic liver transplantation for alcoholic cirrhosis. JAMA 260(17):2542–2544

    Article  CAS  Google Scholar 

  40. Donckier V, Lucidi V, Gustot T, Moreno C (2014) Ethical considerations regarding early liver transplantation in patients with severe alcoholic hepatitis not responding to medical therapy. J Hepatol 60(4):866–871. https://doi.org/10.1016/j.jhep.2013.11.015

    Article  PubMed  Google Scholar 

  41. Lee BP, Chen PH, Haugen C, Hernaez R, Gurakar A, Philosophe B, Dagher N, Moore SA, Li Z, Cameron AM (2017) Three-year results of a pilot program in early liver transplantation for severe alcoholic hepatitis. Ann Surg 265(1):20–29. https://doi.org/10.1097/SLA.0000000000001831

    Article  PubMed  Google Scholar 

  42. Hasanin M, Dubay DA, McGuire BM, Schiano T, Singal AK (2015) Liver transplantation for alcoholic hepatitis: a survey of liver transplant centers. Liver Transpl 21(11):1449–1452. https://doi.org/10.1002/lt.24208

    Article  PubMed  Google Scholar 

  43. Stroh G, Rosell T, Dong F, Forster J (2015) Early liver transplantation for patients with acute alcoholic hepatitis: public views and the effects on organ donation. Am J Transplant 15(6):1598–1604. https://doi.org/10.1111/ajt.13176

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

The protocol of this study was registered prior to conducting the research in the international prospective register of systematic reviews (PROSPERO: CRD42017057971) on 23 February 2017.

Funding

This systematic review and meta-analysis was funded by a grant from the Heidelberg Stiftung Chirurgie (Heidelberg Foundation for Surgery).

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Author notes

  1. Markus K. Diener and Arianeb Mehrabi share senior authorship

Authors and Affiliations

  1. Department of General, Visceral, and Transplantation Surgery, University of Heidelberg, Im Neuenheimer Feld 110, 69120, Heidelberg, Germany

    Mohammed Al-Saeedi, Pascal Probst, Elias Khajeh, Markus K. Diener & Arianeb Mehrabi

  2. The Study Center of the German Surgical Society (SDGC), University of Heidelberg, Im Neuenheimer Feld 130/3, 69120, Heidelberg, Germany

    Muhammed H. Barout, Pascal Probst & Markus K. Diener

  3. Department of Internal Medicine IV, University of Heidelberg, Im Neuenheimer Feld 410, 69120, Heidelberg, Germany

    Karl Heinz Weiss

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  1. Mohammed Al-Saeedi
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Contributions

AM and MKD designed the study. MAS, MHB, PP, and EK performed the database search and acquired the data. MAS, MHB, and EK performed the statistical analysis and interpretation of the data and drafted the manuscript. KHW, MKD, and AM revised the manuscript critically for important intellectual content. All authors read and approved the final version of the manuscript to be published.

Corresponding author

Correspondence to Arianeb Mehrabi.

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The authors declare that they have no conflicts of interest.

Ethical approval

This manuscript is a meta-analysis; it does not contain any procedures involving human participants or animals performed by any of the authors.

Informed consent

Informed consent was obtained from all participants involved in this study.

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Al-Saeedi, M., Barout, M.H., Probst, P. et al. Meta-analysis of patient survival and rate of alcohol relapse in liver-transplanted patients for acute alcoholic hepatitis. Langenbecks Arch Surg 403, 825–836 (2018). https://doi.org/10.1007/s00423-018-1720-z

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  • DOI: https://doi.org/10.1007/s00423-018-1720-z

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