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Durkin C, Schaubel DE, Kaplan DE, Mahmud N, Bittermann T. Survival Benefit From Corticosteroids in Severe Alcohol-associated Hepatitis Attributed to Clinical and Treatment Differences in a Large Multicenter Cohort. Clin Transl Gastroenterol 2025; 16:e00791. [PMID: 39620604 PMCID: PMC11756888 DOI: 10.14309/ctg.0000000000000791] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/12/2024] [Accepted: 11/01/2024] [Indexed: 12/13/2024] Open
Abstract
INTRODUCTION Corticosteroids are recommended by multiple society guidelines for the treatment of severe alcohol-associated hepatitis (AH). However, their use remains controversial due to inconsistent studies regarding their survival benefit. METHODS This was a retrospective cohort study of first-time hospitalizations for severe AH (Maddrey discriminant function ≥ 32) admitted to the Veterans Health Administration between January 3, 2005, and December 5, 2020, (i) evaluating the effect of corticosteroid therapy on all-cause survival, (ii) characterizing the clinical and psychosocial factors associated with corticosteroid use, and (iii) determining the effect of duration of corticosteroid therapy on all-cause survival among treatment-responsive patients (Lille score < 0.45). RESULTS During the study period, 2,618 patients were admitted with severe AH, of whom 1,083 (41.37%) received corticosteroids. Although corticosteroids were significantly associated with improved all-cause survival in the unadjusted model ( P = 0.022), no survival benefit was observed in the adjusted model after accounting for baseline and admission characteristics (adjusted hazard ratio [aHR] = 1.01, P = 0.818). Psychiatry consultation was the only factor evaluated that was protective against mortality (aHR = 0.67, P < 0.001). Among the 428 patients (49.7%) responsive to corticosteroids, duration of therapy was not associated with overall survival on unadjusted ( P = 0.696) or adjusted models (aHR = 1.12, P = 0.710 for a ≥28-day course compared with a ≤7-day reference). DISCUSSION Despite being recommended by clinical guidelines for severe AH, corticosteroids have low utilization with no survival benefit after accounting for differences in patient characteristics and practice patterns. Among patients with treatment response per the Lille score, no difference was observed in overall survival between shorter and longer durations of corticosteroid therapy.
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Affiliation(s)
- Claire Durkin
- Department of Medicine, Division of Gastroenterology and Hepatology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA
| | - Douglas E. Schaubel
- Department of Biostatistics, Epidemiology, and Informatics, Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania, Philadelphia, Pennsylvania, USA
| | - David E. Kaplan
- Department of Medicine, Division of Gastroenterology and Hepatology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA
- Section of Gastroenterology and Hepatology, Corporal Michael J. Crescenz VA Medical Center, Philadelphia, Pennsylvania, USA
| | - Nadim Mahmud
- Department of Medicine, Division of Gastroenterology and Hepatology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA
- Department of Biostatistics, Epidemiology, and Informatics, Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania, Philadelphia, Pennsylvania, USA
- Section of Gastroenterology and Hepatology, Corporal Michael J. Crescenz VA Medical Center, Philadelphia, Pennsylvania, USA
| | - Therese Bittermann
- Department of Medicine, Division of Gastroenterology and Hepatology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA
- Department of Biostatistics, Epidemiology, and Informatics, Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania, Philadelphia, Pennsylvania, USA
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Simonetto DA, Winder GS, Connor AA, Terrault NA. Liver transplantation for alcohol-associated liver disease. Hepatology 2024; 80:1441-1461. [PMID: 38889100 DOI: 10.1097/hep.0000000000000978] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/20/2024] [Accepted: 05/31/2024] [Indexed: 06/20/2024]
Abstract
Alcohol-associated liver disease (ALD) is a major cause of morbidity and mortality worldwide, and a leading indication for liver transplantation (LT) in many countries, including the United States. However, LT for ALD is a complex and evolving field with ethical, social, and medical challenges. Thus, it requires a multidisciplinary approach and individualized decision-making. Short-term and long-term patient and graft survival of patients undergoing LT for ALD are comparable to other indications, but there is a continued need to develop better tools to identify patients who may benefit from LT, improve the pretransplant and posttransplant management of ALD, and evaluate the impact of LT for ALD on the organ donation and transplantation systems. In this review, we summarize the current evidence on LT for ALD, from alcohol-associated hepatitis to decompensated alcohol-associated cirrhosis. We discuss the indications, criteria, outcomes, and controversies of LT for these conditions and highlight the knowledge gaps and research priorities in this field.
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Affiliation(s)
- Douglas A Simonetto
- Division of Gastroenterology and Hepatology, Department of Medicine, Mayo Clinic, Rochester, Minnesota, USA
| | | | - Ashton A Connor
- Department of Surgery, Houston Methodist Hospital, Houston, Texas, USA
| | - Norah A Terrault
- Division of Gastrointestinal and Liver Diseases, Department of Medicine, University of Southern California, Los Angeles, California, USA
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Colmenero J, Pose E, López-Pelayo H. Early liver transplantation in severe alcohol-associated hepatitis. REVISTA ESPANOLA DE ENFERMEDADES DIGESTIVAS 2024; 116:661-663. [PMID: 39530572 DOI: 10.17235/reed.2024.10881/2024] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/16/2024]
Abstract
Early liver transplantation for severe alcohol-associated hepatitis represents a transformative therapeutic approach that can significantly improve survival and achieves standard survival after LT compared to other indications. Early evaluation and an adequate selection of candidates, including organic and psychosocial criteria, are essential. Multidisciplinary management, including the addiction team for the treatment of alcohol use disorder, decreases the risk of alcohol relapse after liver transplantation and is associated with improved outcomes.
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Affiliation(s)
- Jordi Colmenero
- Liver Unit, Hospital Clínic Barcelona. IDIBAPS. CIBERehd. Universitat de Barcelona, España
| | - Elisa Pose
- Liver Unit, Hospital Clínic Barcelona. IDIBAPS. CIBERehd. Universitat de Barcelona, Spain
| | - Hugo López-Pelayo
- Addictions, Health and Addictions Research Group , Hospital Cliníc Barcelona. IDIBAPS, España
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Anouti A, Kerr TA, Mitchell MC, Cotter TG. Advances in the management of alcohol-associated liver disease. Gastroenterol Rep (Oxf) 2024; 12:goae097. [PMID: 39502523 PMCID: PMC11537353 DOI: 10.1093/gastro/goae097] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/29/2024] [Revised: 09/29/2024] [Accepted: 10/08/2024] [Indexed: 11/08/2024] Open
Abstract
Alcohol-associated liver disease (ALD) is a significant global health challenge, encompassing a spectrum from steatotic liver disease to cirrhosis and alcohol-associated hepatitis, and contributed to 25% of global cirrhosis deaths in 2019. The identification of both modifiable (e.g. heavy drinking, metabolic syndromes) and non-modifiable risk factors (e.g. genetic predispositions) is crucial for effective disease management. Alcohol use assessment and treatment, by using both behavioral therapy and pharmacotherapeutic modalities, nutrition support, and optimization of liver disease modifiers, form the cornerstone of management. Advances in medical therapies, such as fecal microbiota transplantation and novel agents such as IL-22, are being explored for their therapeutic potential. A unifying theme in ALD care is the need for a personalized approach to management, accounting for the spectrum of the disease and individual patient characteristics, to tailor interventions effectively. Finally, it is essential to address the challenges to effective ALD treatment, including socioeconomic, logistical, and stigma-related barriers, to improve patient outcomes. This review discusses the current knowledge on ALD, including epidemiology, pathophysiology, risk factors, and management strategies, highlighting the critical role of integrated care models.
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Affiliation(s)
- Ahmad Anouti
- Division of Digestive and Liver Diseases, UT Southwestern Medical Center, Dallas, TX, USA
| | - Thomas A Kerr
- Division of Digestive and Liver Diseases, UT Southwestern Medical Center, Dallas, TX, USA
| | - Mack C Mitchell
- Division of Digestive and Liver Diseases, UT Southwestern Medical Center, Dallas, TX, USA
| | - Thomas G Cotter
- Division of Digestive and Liver Diseases, UT Southwestern Medical Center, Dallas, TX, USA
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5
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Torosian K, Shahrvini B, Johnson WM, Vodkin I, Tincopa M, Lim N, Kwong A, Ajmera V. Psychosocial predictors of return to alcohol use after liver transplant: A multicenter cohort study. ALCOHOL, CLINICAL & EXPERIMENTAL RESEARCH 2024; 48:2137-2144. [PMID: 39256266 PMCID: PMC11560536 DOI: 10.1111/acer.15438] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/19/2024] [Accepted: 08/19/2024] [Indexed: 09/12/2024]
Abstract
BACKGROUND Alcohol use after liver transplant (LT) is associated with higher rates of graft loss and increased mortality; however, there are limited data evaluating predictors of return to alcohol use using biochemical markers like phosphatidylethanol (PEth). METHODS This multicenter retrospective cohort study evaluated psychosocial predictors of return to alcohol use using PEth testing in patients transplanted for alcohol-associated liver disease (ALD). The study included 223 patients at three centers who had received a LT for ALD and had at least one PEth measurement post-LT. RESULTS The rate of return to alcohol use was 6.9 cases per 100 person-years (26 patients total) over a median 555 days of follow-up after transplant. Younger age (HR 0.96; 95% CI 0.92-0.99, p = 0.02), mental health comorbidities (HR 2.83; 95% CI 1.25-6.39, p = 0.01), and non-Hispanic White race (HR 3.79; 95% CI 1.42-10.15, p = 0.01) were associated with return to alcohol use post-LT. There was no difference between post-LT return to alcohol use rates or short-term survival among patients with less than 6 months of sobriety prior to listing compared with those with more than 6 months. Patients with sustained alcohol use post-LT had increased odds of history of illicit substance use (OR 5.20; 95% CI 1.01-26.83, p = 0.04) but no significant difference in time from the last drink to listing (OR 1.03; 95% CI 0.18-5.80, p = 0.97). CONCLUSIONS These findings emphasize the importance of mental health comorbidities rather than period of sobriety in predicting post-LT return to alcohol use. Furthermore, the higher risk of return to alcohol use in non-Hispanic White patients suggests a potential disparity with referral and selection of higher risk White patients.
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Affiliation(s)
- Kelly Torosian
- Division of Gastroenterology and Hepatology, University of California, San Diego, 9500 Gilman Drive, San Diego, CA 92093, USA
| | - Bita Shahrvini
- Department of Medicine, University of California, San Diego, 9500 Gilman Drive, San Diego, CA 92093, USA
| | - Willie Mohammed Johnson
- Department of Medicine, University of Minnesota, 420 Delaware ST SE, Minneapolis, MN, 55455, USA
| | - Irine Vodkin
- Division of Gastroenterology and Hepatology, University of California, San Diego, 9500 Gilman Drive, San Diego, CA 92093, USA
| | - Monica Tincopa
- Division of Gastroenterology and Hepatology, University of California, San Diego, 9500 Gilman Drive, San Diego, CA 92093, USA
| | - Nicholas Lim
- Division of Gastroenterology, Hepatology, and Nutrition, University of Minnesota, 420 Delaware ST SE, Minneapolis, MN, 55455, USA
| | - Allison Kwong
- Division of Gastroenterology and Hepatology, Stanford University, 420 Broadway Street, Redwood City, CA 94063 USA
| | - Veeral Ajmera
- Division of Gastroenterology and Hepatology, University of California, San Diego, 9500 Gilman Drive, San Diego, CA 92093, USA
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Young K, Patel YA, Hoffman B, Peskoe S, Chow SC, Erhart K, Jackson J, Garbarino S. Alcohol Relapse After Liver Transplantation: Risk Factors, Outcomes, and a Comparison of Risk Stratification Models. GASTRO HEP ADVANCES 2024; 4:100550. [PMID: 39811674 PMCID: PMC11731465 DOI: 10.1016/j.gastha.2024.09.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/13/2024] [Accepted: 09/06/2024] [Indexed: 01/16/2025]
Abstract
Background and Aims Alcohol-related liver disease is a leading cause of liver transplantation (LT) in the United States; however, alcohol relapse remains a risk, and real-world assessment of relapse prediction scores is lacking. The primary aim of this study was to assess risk factors for alcohol relapse and compare effectiveness of pre-existing risk scores (e.g., Sustained Alcohol Use Post-Liver Transplant (SALT) and Harmful Alcohol Use Post-Liver Transplant (HALT) scores). Methods This was a retrospective chart review of 69 adults who underwent LT for alcohol-related liver disease at Duke University Hospital from January 1, 2018, to January 1, 2021. Outcome variables included relapse post-LT, severity of relapse, and graft dysfunction. Results Sixty-seven patients with a median follow-up time of 43 months were included. Eighteen (27%) experienced alcohol relapse. Of those, 16 (89%) had heavy alcohol use and 3 of those patients (17%) experienced graft dysfunction. Factors significantly associated with relapse included younger age, prior relapse, significant psychiatric comorbidities, alcohol use after cirrhosis diagnosis, shorter abstinence before LT listing, and prior alcohol treatment program. When applying SALT and HALT scores, the area under the curve was 0.69 (95% confidence interval 0.53-0.85) and 0.66 (95% confidence interval 0.50-0.81), respectively. Conclusion In our cohort, heavy alcohol use before transplantation and legal issues did not predict relapse, which are common components of prediction scores. Less than 5% of patients had graft dysfunction due to relapse, suggesting good graft outcomes. While the HALT and SALT scores were validated in our cohort, our finding of additional significant predictors of relapse, in addition to previously reported risk factors providing protective effect, suggests opportunity for further optimization of prediction scores.
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Affiliation(s)
- Karen Young
- Department of Medicine, Duke University, Durham, North Carolina
| | - Yuval A. Patel
- Division of Gastroenterology and Hepatology, Borland Groover, Saint Johns, Florida
| | - Benson Hoffman
- Division of Gastroenterology and Hepatology, Duke University, Durham, North Carolina
| | - Sarah Peskoe
- Division of Gastroenterology and Hepatology, Duke University, Durham, North Carolina
| | - Shein-Chung Chow
- Division of Gastroenterology and Hepatology, Duke University, Durham, North Carolina
| | - Karli Erhart
- Division of Gastroenterology and Hepatology, Duke University, Durham, North Carolina
| | - Jennifer Jackson
- Division of Gastroenterology and Hepatology, Duke University, Durham, North Carolina
| | - Stephanie Garbarino
- Division of Gastroenterology and Hepatology, Duke University, Durham, North Carolina
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7
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Sharma P, Shenoy A, Shroff H, Kwong A, Lim N, Pillai A, Devuni D, Haque LY, Balliet W, Serper M. Management of alcohol-associated liver disease and alcohol use disorder in liver transplant candidates and recipients: Challenges and opportunities. Liver Transpl 2024; 30:848-861. [PMID: 38471008 DOI: 10.1097/lvt.0000000000000362] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/14/2023] [Accepted: 03/01/2024] [Indexed: 03/14/2024]
Abstract
Alcohol-associated liver disease poses a significant global health burden, with rising alcohol consumption and prevalence of alcohol use disorder (AUD) contributing to increased morbidity and mortality. This review examines the challenges and opportunities in the care of candidates and recipients of liver transplant (LT) with AUD. Despite advancements in posttransplant patient survival, the risk of disease recurrence and alcohol relapse remains substantial. Several challenges have been identified, including (1) rising disease burden of alcohol-associated liver disease, variable transplant practices, and systemic barriers; (2) disparities in mental health therapy access and the impact on transplant; (3) variable definitions, underdiagnosis, and stigma affecting access to care; and (4) post-LT relapse, its risk factors, and consequential harm. The review focuses on the opportunities to improve AUD care for candidates and recipients of LT through effective biochemical monitoring, behavioral and pharmacologic approaches, creating Centers of Excellence for post-LT AUD care, advocating for policy reforms, and ensuring insurance coverage for necessary services as essential steps toward improving patient outcomes. The review also highlights unmet needs, such as the scarcity of addiction specialists, and calls for further research on personalized behavioral treatments, digital health, and value-based care models to optimize AUD care in the LT setting.
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Affiliation(s)
- Pratima Sharma
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA
| | - Akhil Shenoy
- Department of Psychiatry, Columbia University Medical Center, New York, New York, USA
| | - Hersh Shroff
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, University of North Carolina, Chapel Hill, North Carolina, USA
| | - Allison Kwong
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Stanford University, Stanford, California, USA
| | - Nicholas Lim
- Division of Gastroenterology, Hepatology and Nutrition, Department of Internal Medicine, University of Minnesota, Minneapolis, Minnesota, USA
| | - Anjana Pillai
- Division of Gastroenterology, Hepatology and Nutrition, Department of Internal Medicine, University of Chicago, Chicago, Illinois, USA
| | - Deepika Devuni
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, UMass Chan Medical School, Worcester, Massachusetts, USA
| | - Lamia Y Haque
- Department of Internal Medicine, Section of Digestive Diseases and Program in Addiction Medicine, Yale School of Medicine, New Haven, Connecticut, USA
| | - Wendy Balliet
- Department of Psychiatry and Behavioral Sciences, Medical University of South Carolina, Charleston, South Carolina, USA
| | - Marina Serper
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA
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8
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Segal A, Pearl E, Fatabhoy M, Zohr SJ, Bryce K, Gonzalez HC, Miller-Matero LR. Factors associated with a positive phosphatidylethanol test during liver transplantation evaluation. Clin Transplant 2023; 37:e15100. [PMID: 37577900 DOI: 10.1111/ctr.15100] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2023] [Revised: 07/14/2023] [Accepted: 08/07/2023] [Indexed: 08/15/2023]
Abstract
BACKGROUND Early identification of alcohol use is crucial for informing recommendations of appropriate follow-up treatment pre-liver transplant and optimizing post-liver transplant outcomes. The purpose of the study was to investigate whether there are psychosocial factors associated with a positive PEth test. METHODS All patients who underwent a routine pre-surgical psychological evaluation for liver transplant listing (all etiologies, including acute liver failure, dual organ, and re-transplantation) at a single health care system in 2020 were included in a retrospective chart review. Data extraction included results from PEth testing and information from the psychological evaluation (i.e., demographic, psychiatric symptoms, and cognitive functioning). RESULTS There were 158 patients (73.8%) who had a PEth test, of whom 21.5% had a positive result (n = 34). Younger age was associated with a positive PEth (p < .001). ALD status and type of ALD (hepatitis vs. cirrhosis) were also associated with a positive PEth test. Other demographic characteristics and psychiatric symptoms were not associated with a positive PEth result (p > .05). CONCLUSION Younger age was the only significant demographic variable associated with a positive PEth test. Given the difficulty of predicting who may be using alcohol, it may be useful to use PEth testing for all patients during the pre-liver transplant evaluation and while patients are listed for liver transplant. Early identification of alcohol use through routine PEth testing will help identify patients who are using alcohol and need further treatment for alcohol use to optimize health and post-transplant outcomes.
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Affiliation(s)
- Antú Segal
- Behavioral Health Department, Henry Ford Health, Detroit, Michigan, USA
- Transplant Institute, Henry Ford Health, Detroit, Michigan, USA
- Wayne State University, School of Medicine, Detroit, Michigan, USA
| | - Elise Pearl
- Behavioral Health Department, Henry Ford Health, Detroit, Michigan, USA
| | - Megha Fatabhoy
- Behavioral Health Department, Henry Ford Health, Detroit, Michigan, USA
| | - Samantha J Zohr
- Behavioral Health Department, Henry Ford Health, Detroit, Michigan, USA
| | - Kelly Bryce
- Behavioral Health Department, Henry Ford Health, Detroit, Michigan, USA
- Transplant Institute, Henry Ford Health, Detroit, Michigan, USA
- Wayne State University, School of Medicine, Detroit, Michigan, USA
| | - Humberto C Gonzalez
- Transplant Institute, Henry Ford Health, Detroit, Michigan, USA
- Wayne State University, School of Medicine, Detroit, Michigan, USA
- Department of Gastroenterology and Hepatology, Henry Ford Health, Detroit, Michigan, USA
| | - Lisa R Miller-Matero
- Behavioral Health Department, Henry Ford Health, Detroit, Michigan, USA
- Wayne State University, School of Medicine, Detroit, Michigan, USA
- Center for Health Policy and Health Services Research, Henry Ford Health, Detroit, Michigan, USA
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Durkin C, Bittermann T. Liver transplantation for alcohol-associated hepatitis. Curr Opin Organ Transplant 2023; 28:85-94. [PMID: 36512482 PMCID: PMC9992110 DOI: 10.1097/mot.0000000000001044] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
PURPOSE OF REVIEW Early liver transplantation is emerging as a treatment option for severe alcohol-associated hepatitis refractory to pharmacotherapies. This review outlines the current status of transplantation for alcohol-associated hepatitis and the treatment of alcohol use disorder after liver transplantation. RECENT FINDINGS Rates of early liver transplantation for alcohol-associated hepatitis are increasing with significant heterogeneity in practices across the Unites States. Recent studies have demonstrated a substantial survival benefit in patients transplanted for alcohol-associated hepatitis with improved outcomes in early vs. late transplantation, first vs. prior hepatic decompensation, and posttransplant abstinence/delayed relapse vs. early return to alcohol use. Several prediction algorithms have been developed to ascertain patients' risk of alcohol relapse and aid in candidate selection, though data on treatment of alcohol use disorders in transplant recipients remains limited. SUMMARY Although controversial, early liver transplantation for severe alcohol-associated hepatitis has shown to be a lifesaving intervention. Additional research is needed to evaluate its long-term outcomes, optimize candidate selection, and understand treatment of alcohol use disorder posttransplant.
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Affiliation(s)
- Claire Durkin
- Department of Medicine, Division of Gastroenterology and Hepatology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA
| | - Therese Bittermann
- Department of Medicine, Division of Gastroenterology and Hepatology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA
- Department of Biostatistics, Epidemiology, and Informatics, Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania, Philadelphia, PA
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10
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Fuochi E, Anastasio L, Lynch EN, Campani C, Dragoni G, Milani S, Galli A, Innocenti T. Main factors influencing long-term outcomes of liver transplantation in 2022. World J Hepatol 2023; 15:321-352. [PMID: 37034235 PMCID: PMC10075010 DOI: 10.4254/wjh.v15.i3.321] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/18/2022] [Revised: 11/24/2022] [Accepted: 02/22/2023] [Indexed: 04/11/2023] Open
Abstract
Liver transplant (LT) outcomes have markedly improved in the recent decades, even if long-term morbidity and mortality are still considerable. Most of late deaths are independent from graft function and different comorbidities, including complications of metabolic syndrome and de novo neoplasms, seem to play a key role in determining long-term outcomes in LT recipients. This review discusses the main factors associated with late mortality and suggests possible strategies to improve long-term management and follow-up after liver transplantation. In particular, the reduction of drug toxicity, the use of tools to identify high-risk patients, and setting up a multidisciplinary team also for long-term management of LT recipients may further improve survival after liver transplantation.
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Affiliation(s)
- Elisa Fuochi
- Gastroenterology Research Unit, Department of Experimental and Clinical Biomedical Sciences “Mario Serio”, University of Florence, Florence 50134, Italy
| | - Lorenzo Anastasio
- Gastroenterology Research Unit, Department of Experimental and Clinical Biomedical Sciences “Mario Serio”, University of Florence, Florence 50134, Italy
| | - Erica Nicola Lynch
- Gastroenterology Research Unit, Department of Experimental and Clinical Biomedical Sciences “Mario Serio”, University of Florence, Florence 50134, Italy
| | - Claudia Campani
- Department of Experimental and Clinical Medicine, University of Florence, Florence 50134, Italy
| | - Gabriele Dragoni
- Gastroenterology Research Unit, Department of Experimental and Clinical Biomedical Sciences “Mario Serio”, University of Florence, Florence 50134, Italy
- Department of Medical Biotechnologies, University of Siena, Siena 53100, Italy
| | - Stefano Milani
- Gastroenterology Research Unit, Department of Experimental and Clinical Biomedical Sciences “Mario Serio”, University of Florence, Florence 50134, Italy
| | - Andrea Galli
- Gastroenterology Research Unit, Department of Experimental and Clinical Biomedical Sciences “Mario Serio”, University of Florence, Florence 50134, Italy
| | - Tommaso Innocenti
- Gastroenterology Research Unit, Department of Experimental and Clinical Biomedical Sciences “Mario Serio”, University of Florence, Florence 50134, Italy
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11
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Early but not easy: recipients' experiences of alcohol-associated liver disease and early transplantation. Liver Transpl 2023:01445473-990000000-00095. [PMID: 36789649 DOI: 10.1097/lvt.0000000000000102] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/24/2023] [Accepted: 01/24/2023] [Indexed: 02/16/2023]
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12
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Scoring systems to assess relapse risk in alcohol use disorder presenting for early liver transplantation: A systematic review. Gen Hosp Psychiatry 2021; 72:23-30. [PMID: 34229280 DOI: 10.1016/j.genhosppsych.2021.06.012] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/15/2020] [Revised: 06/14/2021] [Accepted: 06/24/2021] [Indexed: 01/01/2023]
Abstract
OBJECTIVE Early liver transplantation (LT) is considered for patients with alcohol use disorder (AUD) despite limited sober time when acute mortality risk from liver disease is high. The objective of this paper is to find psychosocial tools that do not rely on extended sober time and predict alcohol relapse post-LT. METHODS We conducted a systematic review of Pubmed, Embase, and Scopus for studies testing psychosocial tools that used numeric scoring to predict post-LT alcohol relapse. Tools that afforded points for length of sobriety were excluded. Each study was analyzed for its clinical context, post-LT relapse outcomes and predictive validity. RESULTS Five scoring systems across fourteen samples showed varied validity in predicting post-LT alcohol relapse. Relapse to any alcohol use after LT revealed an average relapse rate of 23%. Most scoring systems were understudied but four of five provided cut-off scores with high negative predictive values for relapse. CONCLUSION Scoring systems may have a place in candidate selection but the data on cut-off scores and predictability are still lacking for their use alone in high stakes LT selection. Larger studies with prospective scoring and standardized follow ups for relapse post-LT will better allow the predictive validity of these psychosocial tools to be compared.
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13
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Ting PS, Gurakar A, Wheatley J, Chander G, Cameron AM, Chen PH. Approaching Alcohol Use Disorder After Liver Transplantation for Acute Alcoholic Hepatitis. Clin Liver Dis 2021; 25:645-671. [PMID: 34229846 PMCID: PMC8264137 DOI: 10.1016/j.cld.2021.03.008] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
Severe alcoholic hepatitis portends a high risk of mortality without liver transplantation. Transplant outcomes in patients with severe alcoholic hepatitis exhibit a strong inverse association with post-transplant alcohol relapse. The ingredients most central to ameliorating alcohol relapse risk may include destigmatized post-transplant alcohol monitoring, a nonpunitive clinician-patient partnership, and multimodal therapies to maintain abstinence and mitigate high-risk drinking. We here review the core principles of post-liver transplant management specific to alcohol use disorder.
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Affiliation(s)
- Peng-Sheng Ting
- Division of Gastroenterology and Hepatology, Johns Hopkins University School of Medicine, 1830 East Monument Street, Suite 431, Baltimore, MD 21287, USA
| | - Ahmet Gurakar
- Liver Transplant, Division of Gastroenterology and Hepatology, Johns Hopkins University School of Medicine, 720 Rutland Avenue, Ross Research Building, Suite 918, Baltimore, MD 21205, USA.
| | - Jason Wheatley
- Department of Social Work, Johns Hopkins Hospital, 600 North Wolfe Street, Carnegie Suite 100, Baltimore, MD 21287, USA
| | - Geetanjali Chander
- Division of General Internal Medicine, Johns Hopkins University School of Medicine, 1830 East Monument Street, Room 8047A, Baltimore, MD 21287, USA
| | - Andrew M Cameron
- Division of Liver Transplant Surgery, Department of Surgery, Johns Hopkins University School of Medicine, 720 Rutland Avenue, Ross 765, Baltimore, MD 21205, USA
| | - Po-Hung Chen
- Division of Gastroenterology and Hepatology, Johns Hopkins University School of Medicine, 1830 East Monument Street, Suite 429, Baltimore, MD 21287, USA
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Direct Alcohol Biomarkers Prediction Capacity on Relapse and Mortality in Liver Transplantation Candidates: A Follow-Up Study. TRANSPLANTOLOGY 2021. [DOI: 10.3390/transplantology2030023] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
Abstract
Liver transplantation is a complex procedure that requires multiple evaluations, including abstinence monitorization. While literature assessing the impact of different variables on relapse, survival, and graft loss exists, little is known about the predictive capacity of direct alcohol biomarkers. The primary aim of this study was to evaluate the prediction capacity of direct alcohol biomarkers regarding patient survival and clinical relapse. We hypothesized that patients screening positive for any of the experimental biomarkers would show an increased risk of clinical alcohol relapse and death. We conducted a retrospective data recollection from medical files of patients awaiting liver transplantation, who were at baseline screened with Peth, EtG in hair and urine, and EtS. We tested the prediction capacity of the biomarkers with two Cox-regression models. A total of 50 patients were included (84% men, mean age 59 years (SD = 6)). Biomarkers at baseline were positive in 18 patients. The mean follow-up time for this study was 26 months (SD = 10.4). Twelve patients died, liver transplantation was carried out in 12 patients, and clinical relapse was observed in eight patients. The only significant covariate in the Cox-regression models was age with clinical relapse, with younger patients being at greater risk of relapse. This study could not find a significant prediction capacity of direct alcohol biomarkers for mortality or clinical relapse during follow-up. Higher sample sizes might be needed to detect statistically significant differences. All in all, we believe that direct alcohol biomarkers should be widely used in liver transplantation settings due to their high sensitivity for the detection of recent drinking.
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Arun AC, Ilangovan N, Rajma J. Risk factors for alcohol use relapse after abstinence in patients with alcoholic liver disease. J Family Med Prim Care 2020; 9:5995-5999. [PMID: 33681032 PMCID: PMC7928087 DOI: 10.4103/jfmpc.jfmpc_1401_20] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2020] [Revised: 09/17/2020] [Accepted: 10/23/2020] [Indexed: 12/28/2022] Open
Abstract
INTRODUCTION In patients with alcoholic liver disease, abstinence from alcohol is an important aspect of treatment. Once abstinence is achieved, the challenge is to avoid relapse of alcohol use. This study aims to analyse the significant risk factors for alcohol relapse thereby identifying the patients with high risk for recidivism to have an early social and medical intervention. METHODOLOGY This was an observational and a retrospective type of study. Patients with chronic liver disease and had alcohol use relapse after abstinence were classified into Group A. Patients who did not have relapse after abstinence were classified into Group B. The two groups were compared for various social and personal and disease related factors. Student "t" test was used for raw data and Chi square test was used for consolidated data to find significant difference between variables. RESULTS Overall nine factors were analysed. The factors which were found to be significant for predicting relapse are quantity of alcohol consumption per week, duration of abstinence, associated smoking, marital status, severity of liver disease (Child-Pugh scoring system). The other factors like age of starting alcohol consumption, duration of alcohol consumption, family history of alcohol intake and MELD score were not statistically significant. CONCLUSION This study identifies the risk factors associated with alcohol relapse in patients with alcoholic liver disease. The data from this study can be used to identify individuals who are high risk for relapse and treat them with pharmacological and psychosocial methods to prevent relapse.
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Affiliation(s)
- AC Arun
- Department of Medical Gastroenterology, Velammal Medical College Hospital and Research Institute, Madurai, Tamil Nadu, India
| | - Nityashree Ilangovan
- Department of Medical Gastroenterology, Velammal Medical College Hospital and Research Institute, Madurai, Tamil Nadu, India
| | - Jenish Rajma
- Department of Paediatrics, Velammal Medical College Hospital and Research Institute, Madurai, Tamil Nadu, India
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Liver Transplantation for Alcohol-Related Liver Disease (ARLD): An Update on Controversies and Considerations. Can J Gastroenterol Hepatol 2020; 2020:8862152. [PMID: 33014915 PMCID: PMC7519455 DOI: 10.1155/2020/8862152] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/06/2020] [Revised: 08/27/2020] [Accepted: 08/29/2020] [Indexed: 12/15/2022] Open
Abstract
According to the recent data from the United Network for Organ Sharing database, alcohol-related liver disease (ARLD) accounts to be the most common indication of liver transplantation (LT) waiting lists in the United States among men without hepatocellular carcinoma (HCC). Severe alcoholic hepatitis (AH) is serious and the life-threatening form of ARLD and should be treated timely. However, the LT for severe AH remained to be controversial among the transplant community because of marked interests about the constrained organ supply and the hazard that the AH liver recipient will return to risky drinking. Early LT for ARLD refers for a patient with severe AH undergoing LT who are non-responder to medical treatments. These patients are generally on the existing waiting list but usually followed by 6-month duration of alcohol abstinence. However, the rule of 6-month alcohol abstinence need before the LT is ambiguous. The 6-month alcohol abstinence was consistently defended in light of the compelling fact that it would enable patients to recoup from the intense impacts of alcohol to the liver. In routine, however, the purported "6-month abstinence rule" turned into a surrogate for the forecast of future drinking by ARLD patients for the LT. Careful consideration should be given to the alcohol use disorder of craving and the hazard for recidivism after the LT. As for the current situation, there, urgently, is a specific need of standardized criteria for the evaluation of patients with severe AH for earlier LT. Moreover, further studies are required precisely to develop an accurate prediction model for posttransplant alcohol recidivism. Additionally, development of a standardized protocol for post-LT follow-up and management is further needed. We carefully outlined the published experience with the LT for ARLD in this review.
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