Expedited liver transplantation as first-line therapy for severe alcohol hepatitis: ELFSAH; deferring corticosteroids in the sickest subset of patients.


Journal

Clinical transplantation
ISSN: 1399-0012
Titre abrégé: Clin Transplant
Pays: Denmark
ID NLM: 8710240

Informations de publication

Date de publication:
Jul 2024
Historique:
revised: 03 05 2024
received: 02 04 2024
accepted: 10 05 2024
medline: 26 7 2024
pubmed: 26 7 2024
entrez: 25 7 2024
Statut: ppublish

Résumé

Severe alcohol-associated hepatitis (SAH) represents a lethal subset of alcohol-associated liver disease. Although corticosteroids are recommended by guidelines, their efficacy and safety remain questionable and so liver transplantation (LT) has been increasingly utilized. The timing and indication of corticosteroid use, specifically in patients being considered for LT requires further clarification. A retrospective analysis was conducted on 256 patients with SAH between 2018 and 2022 at a single US center. Twenty of these patients underwent LT. Of the 256 patients, 38% had what we termed "catastrophic" SAH, defined as a MELD-Na ≥35 and/or discriminant function (DF) ≥100, which carried a mortality of 90% without LT. Compared with 100 matched controls, patients undergoing LT exhibited a one-year survival rate of 100% versus 35% (p < .0005). LT provided an absolute risk reduction of 65%, with a number needed to treat of 1.5. Steroid utilization in the entire cohort was 19% with 60% developing severe complications. Patients administered steroids were younger with lower MELD and DF scores. Only 10% of those prescribed steroids derived a favorable response. Sustained alcohol use post-LT was 20%. We propose ELFSAH: Expedited LT as First Line Therapy for SAH; challenging the current paradigm with recommendations to defer steroids in patients with "catastrophic" SAH (defined as: MELD-Na ≥35 and/or DF ≥100). Patients should be seen urgently by hepatology, transplant surgery, psychiatry and social work. Patients without an absolute contraindication should be referred for LT as first-line therapy during their index admission.

Sections du résumé

BACKGROUND & AIMS OBJECTIVE
Severe alcohol-associated hepatitis (SAH) represents a lethal subset of alcohol-associated liver disease. Although corticosteroids are recommended by guidelines, their efficacy and safety remain questionable and so liver transplantation (LT) has been increasingly utilized. The timing and indication of corticosteroid use, specifically in patients being considered for LT requires further clarification.
METHODS METHODS
A retrospective analysis was conducted on 256 patients with SAH between 2018 and 2022 at a single US center.
RESULTS RESULTS
Twenty of these patients underwent LT. Of the 256 patients, 38% had what we termed "catastrophic" SAH, defined as a MELD-Na ≥35 and/or discriminant function (DF) ≥100, which carried a mortality of 90% without LT. Compared with 100 matched controls, patients undergoing LT exhibited a one-year survival rate of 100% versus 35% (p < .0005). LT provided an absolute risk reduction of 65%, with a number needed to treat of 1.5. Steroid utilization in the entire cohort was 19% with 60% developing severe complications. Patients administered steroids were younger with lower MELD and DF scores. Only 10% of those prescribed steroids derived a favorable response. Sustained alcohol use post-LT was 20%.
CONCLUSIONS CONCLUSIONS
We propose ELFSAH: Expedited LT as First Line Therapy for SAH; challenging the current paradigm with recommendations to defer steroids in patients with "catastrophic" SAH (defined as: MELD-Na ≥35 and/or DF ≥100). Patients should be seen urgently by hepatology, transplant surgery, psychiatry and social work. Patients without an absolute contraindication should be referred for LT as first-line therapy during their index admission.

Identifiants

pubmed: 39049597
doi: 10.1111/ctr.15340
doi:

Substances chimiques

Adrenal Cortex Hormones 0

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

e15340

Informations de copyright

© 2024 The Author(s). Clinical Transplantation published by John Wiley & Sons Ltd.

Références

Guirguis J, Chhatwal J, Dasarathy J, et al. Clinical impact of alcohol‐related cirrhosis in the next decade: estimates based on current epidemiological trends in the United States. Alcohol Clin Exp Res. 2015;39(11):2085‐2094.
Wong T, Dang K, Ladhani S, Singal AK, Wong RJ. Prevalence of alcoholic fatty liver disease among adults in the United States, 2001‐2016. JAMA. 2019;321(17):1723‐1725.
Morales‐Arráez D, Ventura‐Cots M, Altamirano J, et al. The MELD score is superior to the Maddrey discriminant function score to predict short‐term mortality in alcohol‐associated hepatitis: a global study. Am J Gastroenterol. 2022;117(2):301‐310.
Mathurin P, Moreno C, Samuel D, et al. Early liver transplantation for severe alcoholic hepatitis. N Engl J Med. 2011;365(19):1790‐1800.
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. Hepatol Baltim Md. 2007;45(6):1348‐1354.
Crabb DW, Im GY, Szabo G, Mellinger JL, Lucey MR. Diagnosis and treatment of alcohol‐associated liver diseases: 2019 practice guidance from the American association for the study of liver diseases. Hepatol Baltim Md. 2020;71(1):306‐333.
European Association for the Study of the Liver. Electronic address: easloffice@easloffice.eu, European Association for the Study of the Liver. EASL Clinical Practice Guidelines: management of alcohol‐related liver disease. J Hepatol. 2018;69(1):154‐181.
Thursz MR, Richardson P, Allison M, et al. Prednisolone or pentoxifylline for alcoholic hepatitis. N Engl J Med. 2015;372(17):1619‐1628.
Louvet A, Thursz MR, Kim DJ, et al. Corticosteroids reduce risk of death within 28 days for patients with severe alcoholic hepatitis, compared with pentoxifylline or placebo‐a meta‐analysis of individual data from controlled trials. Gastroenterology. 2018;155(2):458‐468.
Germani G, Angrisani D, Addolorato G, et al. Liver transplantation for severe alcoholic hepatitis: a multicenter Italian study. Am J Transplant Off J Am Soc Transplant Am Soc Transpl Surg. 2022;22(4):1191‐1200.
Sundaram V, Wu T, Klein AS, et al. Liver transplantation for severe alcoholic hepatitis: report of a single center pilot program. Transplant Proc. 2018;50(10):3527‐3532.
Lee BP, Mehta N, Platt L, et al. Outcomes of early liver transplantation for patients with severe alcoholic hepatitis. Gastroenterology. 2018;155(2):422‐430.
Crabb DW, Bataller R, Chalasani NP, et al. NIAAA alcoholic hepatitis consortia. standard definitions and common data elements for clinical trials in patients with alcoholic hepatitis: recommendation from the NIAAA alcoholic hepatitis consortia. Gastroenterology. 2016;150(4):785‐790.
Lee BP, Chen PH, Haugen C, et al. Three‐year results of a pilot program in early liver transplantation for severe alcoholic hepatitis. Ann Surg. 2017;265(1):20‐29.
Nahas J, Im GY. Early liver transplantation for severe alcoholic hepatitis. Clin Liver Dis. 2018;11(3):69‐72.
Hsu CC, Dodge JL, Weinberg E, et al. Multicentered study of patient outcomes after declined for early liver transplantation in severe alcohol‐associated hepatitis. Hepatol Baltim Md. 2023;77(4):1253‐1262.
Pavlov CS, Varganova DL, Casazza G, Tsochatzis E, Nikolova D, Gluud C. Glucocorticosteroids for people with alcoholic hepatitis. Cochrane Database Syst Rev. 2019;4(4):CD001511.
Singeap AM, Minea H, Petrea O, et al. Real‐world utilization of corticosteroids in severe alcoholic hepatitis: eligibility, response, and outcomes. Medicina (Kaunas). 2024 Feb 11;60(2):311.
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(2):541‐548.
Gawrieh S, Dasarathy S, Tu W, et al. Randomized‐controlled trial of anakinra plus zinc vs. prednisone for severe alcohol‐associated hepatitis. J Hepatol. 2024. S0168‐8278(24)00109‐0.
Dao A, Rangnekar AS. Steroids for severe alcoholic hepatitis: more risk than reward? Clin Liver Dis. 2018;12(6):151‐153.
U.S. Health Resources & Services Administration (HRSA). (2020). OPTN/SRTR 2020 Annual Data report: Liver. Retrieved from Liver (hrsa.gov)
Arab JP, Díaz LA, Baeza N, et al. Identification of optimal therapeutic window for steroid use in severe alcohol‐associated hepatitis: a worldwide study. J Hepatol. 2021;75(5):1026‐1033.
Bataller R, Arab JP, Shah VH. Alcohol‐associated hepatitis. N Engl J Med. 2022;387(26):2436‐2448.
Winder GS, Shenoy A, Dew MA, DiMartini AF. Alcohol and other substance use after liver transplant. Best Pract Res Clin Gastroenterol. 2020;46‐47:101685. doi:10.1016/j.bpg.2020.101685. Epub 2020 Sep 14. PMID: 33158473.
Winder GS, Fernandez AC, Klevering K, Mellinger JL. Confronting the crisis of comorbid alcohol use disorder and alcohol‐related liver disease with a novel multidisciplinary clinic. Psychosomatics. 2020;61(3):238‐253. doi:10.1016/j.psym.2019.12.004. Epub 2019 Dec 19. PMID: 32033835.
Asrani SK, Trotter J, Lake J, et al. Meeting report: the Dallas consensus conference on liver transplantation for alcohol associated hepatitis. Liver Transpl. 2020;26(1):127‐140. doi:10.1002/lt.25681
Carrique L, Quance J, Tan A, et al. Results of early transplantation for alcohol‐related cirrhosis: integrated addiction treatment with low rate of relapse. Gastroenterology. 2021;161(6):1896‐1906.
Laso ABF, Utility of the Use of N‐acetylcysteine Associated With Conventional Treatment in Patients With Severe Acute Alcoholic Hepatitis (Maddrey>32) [Internet]. clinicaltrials.gov; 2022 Mar [cited 2023 Aug 16]. Report No.: NCT05294744. Available from: https://clinicaltrials.gov/study/NCT05294744
Marot A, Singal AK, Moreno C, Deltenre P. Granulocyte colony‐stimulating factor for alcoholic hepatitis: a systematic review and meta‐analysis of randomized controlled trials. JHEP Rep. 2020;2(5):100139.
Fung JY. Liver transplantation for severe alcoholic hepatitis‐The CON view. Liver Int. 2017;37(3):340‐342.
Im GY, Neuberger J. Debate on selection criteria for liver transplantation for alcoholic hepatitis: tighten or loosen? Liver Transpl. 2020;26(7):916‐921. doi:10.1002/lt.25783
Choudhary NS, Saigal S, Gautam D, et al. Good outcome of living donor liver transplantation for severe alcoholic hepatitis not responding to medical management: a single center experience of 39 patients. Alcohol. 2019;77:27‐30.
Kulkarni AV, Reddy R, Arab JP, et al. Early living donor liver transplantation for alcohol‐associated hepatitis. Ann Hepatol. 2023;28(4):101098.
McElroy LM, Likhitsup A, Scott Winder G, et al. Gender disparities in patients with alcoholic liver disease evaluated for liver transplantation. Transplantation. 2020;104(2):293‐298.
Kaplan A, Wahid N, Fortune BE, et al. Black patients and women have reduced access to liver transplantation for alcohol‐associated liver disease. Liver Transpl. 2023;29(3):259‐267.

Auteurs

Nabeeha Mohy-Ud-Din (N)

Division of Gastroenterology, Hepatology and Nutrition, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA.

Fei-Pi Lin (FP)

Division of Gastroenterology, Hepatology and Nutrition, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA.

Vikrant Rachakonda (V)

Division of Gastroenterology and Hepatology, University of California Davis School of Medicine Veteran's Association Northern California Healthcare System, Sacramento, California, USA.

Ali Al-Khafaji (A)

Department of Critical Care Medicine, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA.

Scott W Biggins (SW)

Division of Gastroenterology, Hepatology and Nutrition, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA.

Swaytha Ganesh (S)

Division of Gastroenterology, Hepatology and Nutrition, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA.

Ramon Bataller (R)

Liver Unit, Hospital Clinic, Barcelona, Spain.

Andrea DiMartini (A)

Department of Psychiatry, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.

Christopher Hughes (C)

Thomas E. Starzl Transplantation Institute, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA.

Abhinav Humar (A)

Thomas E. Starzl Transplantation Institute, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA.

Shahid M Malik (SM)

Division of Gastroenterology, Hepatology and Nutrition, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA.

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