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Falari SS, Mohapatra N, Patil NS, Pattnaik B, Varshney M, Choudhury A, Sarin SK, Pamecha V. Incidence and predictors of alcohol relapse following living donor liver transplantation for alcohol related liver disease. JOURNAL OF HEPATO-BILIARY-PANCREATIC SCIENCES 2023; 30:1015-1024. [PMID: 36866490 DOI: 10.1002/jhbp.1325] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/21/2022] [Revised: 02/18/2023] [Accepted: 02/21/2023] [Indexed: 03/04/2023]
Abstract
BACKGROUND Alcohol relapse after liver transplantation has a negative impact on outcomes. There is limited data on its burden, the predictors, and impact following live donor liver transplantation (LDLT). METHODS A single-center observational study was carried out between July 2011 and March 2021 for patients undergoing LDLT for alcohol associated liver disease (ALD). The incidence, predictors of alcohol relapse, and post-transplant outcomes were assessed. RESULTS Altogether 720 LDLT were performed during the study period, 203 (28.19%) for ALD. The overall relapse rate was 9.85% (n = 20) with a median follow-up of 52 months (range, 12-140 months). Sustained harmful alcohol use was seen in 4 (1.97%). On multivariate analysis, pre-LT relapse (P = .001), duration of abstinence period (P = .007), daily intake of alcohol (P = .001), absence of life partner (P = .021), concurrent tobacco abuse before transplant (P = .001), the donation from second-degree relative (P = .003) and poor compliance with medications (P = .001) were identified as predictors for relapse. Alcohol relapse was associated with the risk of graft rejection (HR 4.54, 95% CI: 1.751-11.80, P = .002). CONCLUSION Our results show that the overall incidence of relapse and rate of harmful drinking following LDLT is low. Donation from spouse and first degree relative was protective. History of daily intake, prior relapse, shorter pretransplant abstinence duration and lack of family support significantly predicted relapse.
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Affiliation(s)
- Sanyam Santosh Falari
- Department of Hepato-Pancreato-Biliary and Liver Transplant Surgery, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Nihar Mohapatra
- Department of Hepato-Pancreato-Biliary and Liver Transplant Surgery, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Nilesh Sadashiv Patil
- Department of Hepato-Pancreato-Biliary and Liver Transplant Surgery, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Bramhadatta Pattnaik
- Department of Hepato-Pancreato-Biliary and Liver Transplant Surgery, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Mohit Varshney
- Department of Psychiatry, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Ashok Choudhury
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Shiv K Sarin
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Viniyendra Pamecha
- Department of Hepato-Pancreato-Biliary and Liver Transplant Surgery, Institute of Liver and Biliary Sciences, New Delhi, India
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Ceci L, Han Y, Krutsinger K, Baiocchi L, Wu N, Kundu D, Kyritsi K, Zhou T, Gaudio E, Francis H, Alpini G, Kennedy L. Gallstone and Gallbladder Disease: Biliary Tract and Cholangiopathies. Compr Physiol 2023; 13:4909-4943. [PMID: 37358507 DOI: 10.1002/cphy.c220028] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/27/2023]
Abstract
Cholestatic liver diseases are named primarily due to the blockage of bile flow and buildup of bile acids in the liver. Cholestasis can occur in cholangiopathies, fatty liver diseases, and during COVID-19 infection. Most literature evaluates damage occurring to the intrahepatic biliary tree during cholestasis; however, there may be associations between liver damage and gallbladder damage. Gallbladder damage can manifest as acute or chronic inflammation, perforation, polyps, cancer, and most commonly gallstones. Considering the gallbladder is an extension of the intrahepatic biliary network, and both tissues are lined by biliary epithelial cells that share common mechanisms and properties, it is worth further evaluation to understand the association between bile duct and gallbladder damage. In this comprehensive article, we discuss background information of the biliary tree and gallbladder, from function, damage, and therapeutic approaches. We then discuss published findings that identify gallbladder disorders in various liver diseases. Lastly, we provide the clinical aspect of gallbladder disorders in liver diseases and ways to enhance diagnostic and therapeutic approaches for congruent diagnosis. © 2023 American Physiological Society. Compr Physiol 13:4909-4943, 2023.
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Affiliation(s)
- Ludovica Ceci
- Division of Gastroenterology and Hepatology, Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana, USA
- Department of Anatomical, Histological, Forensic Medicine and Orthopedics Sciences, Sapienza University of Rome, Rome, Italy
| | - Yuyan Han
- School of Biological Sciences, University of Northern Colorado, Greeley, Colorado, USA
| | - Kelsey Krutsinger
- School of Biological Sciences, University of Northern Colorado, Greeley, Colorado, USA
| | | | - Nan Wu
- Division of Gastroenterology and Hepatology, Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana, USA
| | - Debjyoti Kundu
- Division of Gastroenterology and Hepatology, Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana, USA
| | - Konstantina Kyritsi
- Division of Gastroenterology and Hepatology, Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana, USA
| | - Tianhao Zhou
- Division of Gastroenterology and Hepatology, Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana, USA
| | - Eugenio Gaudio
- Department of Anatomical, Histological, Forensic Medicine and Orthopedics Sciences, Sapienza University of Rome, Rome, Italy
| | - Heather Francis
- Division of Gastroenterology and Hepatology, Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana, USA
- Department of Research, Richard L. Roudebush VA Medical Center, Indianapolis, Indiana, USA
| | - Gianfranco Alpini
- Division of Gastroenterology and Hepatology, Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana, USA
- Department of Research, Richard L. Roudebush VA Medical Center, Indianapolis, Indiana, USA
| | - Lindsey Kennedy
- Division of Gastroenterology and Hepatology, Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana, USA
- Department of Research, Richard L. Roudebush VA Medical Center, Indianapolis, Indiana, USA
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3
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Nishio T, Ito T, Hata K, Taura K, Hatano E. Current status of liver transplantation for non-B non-C liver cirrhosis and hepatocellular carcinoma. Ann Gastroenterol Surg 2023; 7:42-52. [PMID: 36643372 PMCID: PMC9831911 DOI: 10.1002/ags3.12612] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/12/2022] [Accepted: 08/05/2022] [Indexed: 01/18/2023] Open
Abstract
Recently, non-B non-C chronic liver diseases, including alcoholic liver disease (ALD) and nonalcoholic fatty liver disease (NAFLD)/nonalcoholic steatohepatitis (NASH), have markedly increased worldwide. Liver transplantation (LT) is an effective curative therapy for hepatocellular carcinoma (HCC) as well as decompensated liver cirrhosis. In Japan, where the source of liver grafts is strongly dependent on living donors, efforts have been made to unify the indications for eligibility of HCC patients for LT, leading to the development of 5-5-500 criteria. Along with the expansion of eligibility for LT, the current changing trends in underlying liver diseases of LT recipients, which are related to the rising tide of non-B non-C cirrhosis and HCC, are highlighting the importance of peri-transplant management of patients with various comorbidities. The post-LT prognosis of patients with ALD is significantly affected by de novo malignancies and metabolic syndrome-related complications as well as posttransplant alcohol relapse. NAFLD/NASH patients often suffer from obesity, type 2 diabetes mellitus, and other metabolic syndrome-related disorders, and nonneoplastic factors such as cardiovascular events and recurrence of NAFLD/NASH have a significant impact on post-LT outcomes. Patient management in the peri-transplant period as well as risk assessment for LT are key to improving post-LT outcomes in the era of a growing number of cases of LT for non-B non-C liver diseases.
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Affiliation(s)
- Takahiro Nishio
- Department of Surgery, Graduate School of MedicineKyoto UniversityKyotoJapan
| | - Takashi Ito
- Department of Surgery, Graduate School of MedicineKyoto UniversityKyotoJapan
| | - Koichiro Hata
- Department of Surgery, Graduate School of MedicineKyoto UniversityKyotoJapan
| | - Kojiro Taura
- Department of Surgery, Graduate School of MedicineKyoto UniversityKyotoJapan
| | - Etsuro Hatano
- Department of Surgery, Graduate School of MedicineKyoto UniversityKyotoJapan
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4
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Bailey P, Vergis N, Allison M, Riddell A, Massey E. Psychosocial Evaluation of Candidates for Solid Organ Transplantation. Transplantation 2021; 105:e292-e302. [PMID: 33675318 DOI: 10.1097/tp.0000000000003732] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
Transplant candidates should undergo an assessment of their mental health, social support, lifestyle, and behaviors. The primary aims of this "psychosocial evaluation" are to ensure that transplantation is of benefit to life expectancy and quality of life, and to allow optimization of the candidate and transplant outcomes. The content of psychosocial evaluations is informed by evidence regarding pretransplant psychosocial predictors of transplant outcomes. This review summarizes the current literature on pretransplant psychosocial predictors of transplant outcomes across differing solid organ transplants and discusses the limitations of existing research. Pretransplant depression, substance misuse, and nonadherence are associated with poorer posttransplant outcomes. Depression, smoking, and high levels of prescription opioid use are associated with reduced posttransplant survival. Pretransplant nonadherence is associated with posttransplant rejection, and nonadherence may mediate the effects of other psychosocial variables such as substance misuse. There is evidence to suggest that social support is associated with likelihood of substance misuse relapse after transplantation, but there is a lack of consistent evidence for an association between social support and posttransplant adherence, rejection, or survival across all organ transplant types. Psychosocial evaluations should be undertaken by a trained individual and should comprise multiple consultations with the transplant candidate, family members, and healthcare professionals. Tools exist that can be useful for guiding and standardizing assessment, but research is needed to determine how well scores predict posttransplant outcomes. Few studies have evaluated interventions designed to improve psychosocial functioning specifically pretransplant. We highlight the challenges of carrying out such research and make recommendations regarding future work.
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Affiliation(s)
- Pippa Bailey
- Department of Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK
- Renal and Transplant Service, Southmead Hospital, North Bristol NHS Trust, Bristol, UK
| | - Nikhil Vergis
- Liver Services Department, St Mary's Hospital, Imperial College Healthcare NHS Trust, London, UK
- Department of Metabolism Digestion and Reproduction, Imperial College London, UK
| | - Michael Allison
- Cambridge Liver Unit, Addenbrooke's Hospital, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK
| | - Amy Riddell
- Renal and Transplant Service, Southmead Hospital, North Bristol NHS Trust, Bristol, UK
- University of Exeter Medical School, Exeter, UK
| | - Emma Massey
- Department of Internal Medicine, Nephrology and Transplantation, Erasmus Medical Center, Rotterdam, The Netherlands
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5
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Abstract
Although short- and medium-term outcomes after liver transplantation for alcohol-related liver disease (ARLD) are generally excellent and similar to outcomes for transplantation for other indications, a return to alcohol consumption commonly occurs even though rates of alcohol consumption after transplantation for ARLD are comparable to those seen in other indications. Transplant recipients should be questioned about alcohol use post-transplantation and, where appropriate, monitored; those drinking significant amounts should be offered treatment with the help of a multi-disciplinary team. Although short-term significant alcohol use is associated with an increased risk of non-compliance and rejection, medium-term outcomes are similar to other groups. Patients transplanted for ARLD have a greater risk of some de novo malignancies, especially of the lung and the upper GI tract. More work is required both to identify those at risk of a return to destructive patterns of alcohol use at an early stage and to develop effective treatments aimed at reaching and maintaining abstinence.
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Affiliation(s)
- James Neuberger
- Liver Unit, Queen Elizabeth Hospital, Birmingham, B15 2TH, UK.
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6
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Liver transplantation in patients with alcohol-related liver disease: current status and future directions. Lancet Gastroenterol Hepatol 2020; 5:507-514. [DOI: 10.1016/s2468-1253(19)30451-0] [Citation(s) in RCA: 30] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/03/2019] [Revised: 12/15/2019] [Accepted: 12/19/2019] [Indexed: 12/19/2022]
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Ronan PJ, Strait SA, Palmer GM, Beresford TP. Central Administration of Cyclosporine A Decreases Ethanol Drinking. Alcohol Alcohol 2018; 53:193-199. [PMID: 29281037 DOI: 10.1093/alcalc/agx102] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/16/2017] [Accepted: 11/13/2017] [Indexed: 01/08/2023] Open
Abstract
Aims Abstinence among alcohol dependent liver graft recipients is remarkably high. The routine use of anti-immune agents in these patients led to rodent studies showing that immunosuppressants acting through inhibition of calcineurin (CLN) are highly effective in decreasing alcohol consumption. It remained unclear, however, whether the decreased alcohol consumption in rodent models is mediated through peripheral suppression of immune response or centrally through direct inhibition of cyclophilin-CLN in the brain. We tested the hypothesis that direct brain inhibition of CLN with intracerebroventricular (ICV) injections of the immunosuppressant cyclosporine A (CsA) is sufficient to decrease ethanol consumption in a rodent model of binge-like drinking. Methods Male C57BL/6NHsd mice were put through a modified 'drinking in the dark' (DID) paradigm. Effects of both peripheral (IP) and central (ICV) injections of CsA on ethanol consumption were assessed. Results Here, as in earlier work, IP CsA administration significantly decreased alcohol consumption. Supporting our hypothesis, central administration of CsA was sufficient to decrease alcohol consumption in a dose-dependent manner. There was no significant effect of CsA on water or sucrose consumption. Conclusions These results clearly implicate a CLN-mediated mechanism in brain in the inhibitory effects of CsA on ethanol consumption and provide novel targets for investigation of treatment for Alcohol Use Disorders (AUD). These results also add to the growing body of literature implicating neuroimmune mechanisms in the etiology, pathophysiology and behaviors driving AUD. Short Summary The unusually high abstinence rate and routine use of immunosuppressants in AUD liver graft recipients led us to rodent studies showing that immunosuppressants acting through inhibition of calcineurin (CLN) are highly effective in decreasing drinking. Here we demonstrate that this effect is mediated by brain rather than peripheral immune mechanisms.
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Affiliation(s)
- Patrick J Ronan
- Laboratory for Clinical and Translational Research in Psychiatry, Research Service and Psychiatry, Denver VA Medical Center, 1050 Clermont Street, Denver, CO 80220-0116, USA.,Sioux Falls VA Research Service, 2501 W. 22nd St., Sioux Falls, SD 57105, USA.,Department of Psychiatry and Division of Basic Biomedical Sciences, Sanford USD School of Medicine, MC151, 2501 W. 22nd St., Sioux Falls, SD 57105, USA
| | - Sydney A Strait
- Sioux Falls VA Research Service, 2501 W. 22nd St., Sioux Falls, SD 57105, USA
| | - Geralyn M Palmer
- Sioux Falls VA Research Service, 2501 W. 22nd St., Sioux Falls, SD 57105, USA
| | - Thomas P Beresford
- Laboratory for Clinical and Translational Research in Psychiatry, Research Service and Psychiatry, Denver VA Medical Center, 1050 Clermont Street, Denver, CO 80220-0116, USA.,Department of Psychiatry, University of Colorado Denver School of Medicine, Anschutz Medical Campus, 13001 East 17th Place, Aurora, CO 80045, USA
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8
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Burra P, Zanetto A, Germani G. Liver Transplantation for Alcoholic Liver Disease and Hepatocellular Carcinoma. Cancers (Basel) 2018; 10:E46. [PMID: 29425151 PMCID: PMC5836078 DOI: 10.3390/cancers10020046] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2017] [Revised: 02/01/2018] [Accepted: 02/07/2018] [Indexed: 12/11/2022] Open
Abstract
Hepatocellular carcinoma is one of the main important causes of cancer-related death and its mortality is increasingly worldwide. In Europe, alcohol abuse accounts for approximately half of all liver cancer cases and it will become the leading cause of hepatocellular carcinoma in the next future with the sharp decline of chronic viral hepatitis. The pathophysiology of alcohol-induced carcinogenesis involves acetaldehyde catabolism, oxidative stress and chronic liver inflammation. Genetic background plays also a significant role and specific patterns of gene mutations in alcohol-related hepatocellular carcinoma have been characterized. Survival is higher in patients who undergo specific surveillance programmes than in patients who do not. However, patients with alcohol cirrhosis present a significantly greater risk of liver decompensation than those with cirrhosis due to other aetiologies. Furthermore, the adherence to screening program can be suboptimal. Liver transplant for patients with Milan-in hepatocellular carcinoma represents the best possible treatment in case of tumour recurrence/progression despite loco-regional or surgical treatments. Long-term result after liver transplantation for alcohol related liver disease is good. However, cardiovascular disease and de novo malignancies can significantly hamper patients' survival and should be carefully considered by transplant team. In this review, we have focused on the evolution of alcohol-related hepatocellular carcinoma epidemiology and risk factors as well as on liver transplantation in alcoholic patients with and without hepatocellular carcinoma.
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Affiliation(s)
- Patrizia Burra
- Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, Padua University Hospital, Via Giustiniani 2, 35128 Padua, Italy.
| | - Alberto Zanetto
- Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, Padua University Hospital, Via Giustiniani 2, 35128 Padua, Italy.
| | - Giacomo Germani
- Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, Padua University Hospital, Via Giustiniani 2, 35128 Padua, Italy.
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9
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Lim J, Curry MP, Sundaram V. Risk factors and outcomes associated with alcohol relapse after liver transplantation. World J Hepatol 2017; 9:771-780. [PMID: 28660011 PMCID: PMC5474723 DOI: 10.4254/wjh.v9.i17.771] [Citation(s) in RCA: 36] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/26/2016] [Revised: 03/07/2017] [Accepted: 04/24/2017] [Indexed: 02/06/2023] Open
Abstract
Alcoholic liver disease (ALD) is the second most common indication for liver transplantation (LT) in the United States and Europe. Unlike other indications for LT, transplantation for ALD may be controversial due to the concern for alcohol relapse and non-compliance after LT. However, the overall survival in patients transplanted for ALD is comparable or higher than in patients transplanted for other etiologies of liver disease. While the rate of alcohol use after liver transplantation does not differ among various etiologies of liver disease, alcohol relapse after transplantation for ALD has been associated with complications such as graft rejection, graft loss, recurrent alcoholic cirrhosis and reduced long-term patient survival. Given these potential complications, our review aimed to discuss risk factors associated with alcohol relapse and the efficacy of various interventions attempted to reduce the risk of alcohol relapse. We also describe the impact of alcohol relapse on post-transplant outcomes including graft and patient survival. Overall, alcohol liver disease remains an appropriate indication for liver transplantation, and long-term mortality in this group of patients is primarily attributed to cardiovascular disease or de novo malignancies rather than alcohol related hepatic complications, among those who relapse.
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Mathurin P, Bataller R. Trends in the management and burden of alcoholic liver disease. J Hepatol 2015; 62:S38-46. [PMID: 25920088 PMCID: PMC5013530 DOI: 10.1016/j.jhep.2015.03.006] [Citation(s) in RCA: 225] [Impact Index Per Article: 22.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/09/2015] [Revised: 03/05/2015] [Accepted: 03/05/2015] [Indexed: 12/16/2022]
Abstract
Alcoholic liver disease (ALD) is the most prevalent cause of advanced liver disease in Europe and is the leading cause of death among adults with excessive alcohol consumption. There is a dose-response relationship between the amount of alcohol consumed and the risk of ALD. The relative risk of cirrhosis increases in subjects who consume more than 25 g/day. The burden of alcohol-attributable liver cirrhosis and liver cancer is high and is entirely preventable. Health agencies should develop population-based policies to reduce the prevalence of harmful and/or hazardous alcohol consumption and foster research in this field to provide new diagnostic and therapeutic tools. Disease progression of patients with ALD is heavily influenced by both genetic and environmental factors. Non-invasive methods for the diagnosis of fibrosis have opened new perspectives in the early detection of advanced ALD in asymptomatic patients. Alcoholic hepatitis, the most severe form of ALD, carries a high short-term mortality (around 30-50% at 3 months). Corticosteroids improve short-term survival in patients with severe alcoholic hepatitis but duration of therapy should be adapted to early response. Liver transplantation is the best option for patients with severe liver dysfunction. However, alcohol relapse after transplantation remains a critical issue and drinking habits of transplanted patients need to be routinely screened.
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Affiliation(s)
- Philippe Mathurin
- Service Maladie de l'Appareil Digestif and INSERM U995, Univ Lille 2, CHRU Lille, France.
| | - Ramon Bataller
- Departments of Medicine and Nutrition, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
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11
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Khan R, Singal AK, Anand BS. Outcomes after liver transplantation for combined alcohol and hepatitis C virus infection. World J Gastroenterol 2014; 20:11935-11938. [PMID: 25232228 PMCID: PMC4161779 DOI: 10.3748/wjg.v20.i34.11935] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/28/2014] [Revised: 03/28/2014] [Accepted: 05/29/2014] [Indexed: 02/06/2023] Open
Abstract
Alcohol abuse and chronic hepatitis C virus (HCV) infection are two major causes of chronic liver disease in the United States. About 10%-15% of liver transplants performed in the United States are for patients with cirrhosis due to combined alcohol and HCV infection. Data on outcomes on graft and patient survival, HCV recurrence, and relapse of alcohol use comparing transplants in hepatitis C positive drinkers compared to alcohol abuse or hepatitis C alone are conflicting in the literature. Some studies report a slightly better overall outcome in patients who were transplanted for alcoholic cirrhosis vs those transplanted for HCV alone or for combined HCV and alcohol related cirrhosis. However, some other studies do not support these observations. However, most studies are limited to a retrospective design or small sample size. Larger prospective multicenter studies are needed to better define the outcomes in hepatitis C drinkers.
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12
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Masson S, Marrow B, Kendrick S, Elsharkawy AM, Latimer S, Hudson M. An ‘alcohol contract’ has no significant effect on return to drinking after liver transplantation for alcoholic liver disease. Transpl Int 2014; 27:475-81. [DOI: 10.1111/tri.12283] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2013] [Revised: 11/22/2013] [Accepted: 02/11/2014] [Indexed: 12/18/2022]
Affiliation(s)
- Steven Masson
- Liver Transplant Unit; Freeman Hospital; Newcastle Upon Tyne UK
- Institute of Cellular Medicine; Newcastle University Medical School; Newcastle upon Tyne UK
| | - Benjamin Marrow
- Liver Transplant Unit; Freeman Hospital; Newcastle Upon Tyne UK
| | - Stuart Kendrick
- Liver Transplant Unit; Freeman Hospital; Newcastle Upon Tyne UK
- Institute of Cellular Medicine; Newcastle University Medical School; Newcastle upon Tyne UK
| | | | - Sandra Latimer
- Liver Transplant Unit; Freeman Hospital; Newcastle Upon Tyne UK
| | - Mark Hudson
- Liver Transplant Unit; Freeman Hospital; Newcastle Upon Tyne UK
- Institute of Cellular Medicine; Newcastle University Medical School; Newcastle upon Tyne UK
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13
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Alcoholism: diagnosis, prognosis, epidemiology, and burden of the disease. HANDBOOK OF CLINICAL NEUROLOGY 2014; 125:3-13. [PMID: 25307565 DOI: 10.1016/b978-0-444-62619-6.00001-x] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/30/2023]
Abstract
To the clinician, alcoholism can appear as an amorphous entity that is confusing with respect to diagnosis, treatment prognosis, and the role of the health professional, despite its high incidence and associated morbidities and mortality when unrecognized or untreated. This chapter focuses on the clinical application of current knowledge, with the aim of being useful to the practitioner in working directly with patients for whom alcoholism may or may not be an already identified problem. It briefly reviews large-scale studies and then focuses on diagnosis and prognosis assessment and decision making. Also considered are current controversies in nomenclature and the chapter ends with an economic perspective with respect to healthcare and cost to society. As the introductory chapter, the goal is to provide a context of the scope of alcoholism and attendant problems for the rest of the chapters.
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14
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Outcome after liver transplantation for cirrhosis due to alcohol and hepatitis C: comparison to alcoholic cirrhosis and hepatitis C cirrhosis. J Clin Gastroenterol 2013; 47:727-33. [PMID: 23751845 DOI: 10.1097/mcg.0b013e318294148d] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
Abstract
BACKGROUND AND AIM Data on outcome of patients after liver transplantation (LT) for cirrhosis due to hepatitis C virus (HCV+) alcohol are limited. METHODS AND RESULTS Analysis from United Network for Organ sharing data set (1991 to 2010) for cirrhotics with first LT for HCV (group I, N=17,722), alcohol or alcoholic cirrhosis (AC; group II, N=9617), and alcohol+HCV (group III, N=6822). Five-year graft and patient survival for group III were similar to group I (73% vs. 69%; P=0.33 and 76% vs. 76%; P=0.87) and worse than group II (70% vs. 74%; P<0.0001 and 76% vs. 79%; P<0.0001). Cox regression analysis adjusted for recipient and donor characteristics showed (a) graft survival for group III similar to group I [hazard ratio (HR) 1.03 (95% confidence interval (CI), 0.97-1.09)] and worse than group II [HR 1.27 (95% CI, 1.19-1.35)] and (b) patient survival for group III worse than both groups I [HR 1.09 (95% CI, 1.02-1.15)] and II [HR 1.27 (95% CI, 1.19-1.36)]. In group III, graft failure was common for graft and patient loss and de novo malignancy more common compared with group I. CONCLUSIONS Patients undergoing LT for cirrhosis due to combined alcohol and HCV have (a) graft survival similar to patients with HCV cirrhosis and worse than AC and (b) worse patient survival compared with AC and HCV cirrhosis. Better strategies for anti-HCV treatment and screening for tumors are needed for patients undergoing LT for combined alcohol and HCV.
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15
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Beresford T, Fay T, Serkova NJ, Wu PH. Immunophyllin ligands show differential effects on alcohol self-administration in C57BL mice. J Pharmacol Exp Ther 2012; 341:611-6. [PMID: 22375069 PMCID: PMC3362882 DOI: 10.1124/jpet.111.188169] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2011] [Accepted: 02/27/2012] [Indexed: 12/24/2022] Open
Abstract
High abstinence rates characterize alcohol-dependent liver graft recipients. The immunosuppressants cyclosporine A (CsA) and tacrolimus (TRL) also inhibit calcineurin (CLN) in the brain. Previously, we found that CsA reduces alcohol consumption in C57BL/6J mice. The goals of the present study were: 1) to compare the ethanol preference effects of CsA against TRL, as well as sirolimus (SRL), an immunosuppressant without CLN inhibition and 2) to establish that reduction of alcohol consumption is not caused by caloric reinforcement from these ligands. C57BL/6J mice trained to imbibe ethanol consumed ethanol or sucrose in a modified limited-access drinking-in-the-dark paradigm; test groups received vehicle or doses of CsA (5-50 mg/kg), TRL (0.5-2.5 mg/kg), or SRL (1.0-5.0 mg/kg) for 5 consecutive days, 30 min before each 2-h limited-access session. Brain CsA, TRL, and SRL concentrations were measured. CsA (p < 0.001) and TRL (p < 0.01) each decreased ethanol consumption, whereas SRL showed no significant effects at any dose. Effective doses included CsA at 10 mg/kg and above and TRL at 2.5 mg/kg. CsA (50 mg/kg) did not reduce sucrose consumption. Both CsA and TRL reached significant brain concentrations compared with very low values of SRL. These data suggest that CsA and TRL may reduce alcohol preference through central CLN inhibition rather than by immunosuppression.
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Affiliation(s)
- Thomas Beresford
- Psychiatry and Research Services, Department of Veterans Affairs Medical Center, Denver, Colorado, USA.
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Carbone M, Neuberger J. Liver transplantation for hepatitis C and alcoholic liver disease. J Transplant 2010; 2010:893893. [PMID: 21209701 PMCID: PMC3010646 DOI: 10.1155/2010/893893] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2010] [Accepted: 11/16/2010] [Indexed: 02/08/2023] Open
Abstract
End-stage liver disease due to hepatitis C (HCV) and cirrhosis from alcohol (ALD) are the commonest indications for liver transplantation in the western countries. Up to one third of HCV-infected transplant candidates have a history of significant alcohol intake prior to transplantation. However, there are few data available about the possible interaction between alcohol and HCV in the post-transplant setting. Patients with both HCV and alcohol are more likely to die on the waiting list than those with ALD and HCV alone. However, after transplantation, non-risk adjusted graft and patient survival of patients with HCV + ALD are comparable to those of patients with HCV cirrhosis or ALD cirrhosis alone. In the short and medium term HCV recurrence after transplant in patients with HCV + ALD cirrhosis does not seem more aggressive than that in patients with HCV cirrhosis alone. A relapse in alcohol consumption in patients with HCV + ALD cirrhosis does not have a major impact on graft survival. The evidence shows that, as is currently practiced, HCV + ALD as an appropriate indication for liver transplantation. However, these data are based on retrospective analyses with relatively short follow-up so the conclusions must be treated with caution.
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Affiliation(s)
- Marco Carbone
- Liver Unit, Queen Elizabeth Hospital, Birmingham B152TH, UK
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Lucey MR, Schaubel DE, Guidinger MK, Tome S, Merion RM. Effect of alcoholic liver disease and hepatitis C infection on waiting list and posttransplant mortality and transplant survival benefit. Hepatology 2009; 50:400-6. [PMID: 19472315 DOI: 10.1002/hep.23007] [Citation(s) in RCA: 74] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
UNLABELLED Disease-specific analysis of liver transplant survival benefit, which encompasses both pre- and posttransplant events, has not been reported. Therefore, we evaluated the effect of alcoholic liver disease (ALD) and hepatitis C virus (HCV) infection on waiting list mortality, posttransplant mortality, and the survival benefit of deceased donor liver transplantation using United States data from the Scientific Registry of Transplant Recipients on 38,899 adults placed on the transplant waiting list between September 2001 and December 2006. Subjects were classified according to the presence/absence of HCV and ALD. Cox regression was used to estimate waiting list mortality and posttransplant mortality separately. Survival benefit was assessed using sequential stratification. Overall, the presence of HCV significantly increased waiting list mortality, with a covariate-adjusted hazard ratio (HR) for HCV-positive (HCV+) compared with HCV-negative (HCV-) HR = 1.19 (P = 0.0001). The impact of HCV+ was significantly more pronounced (P = 0.001) among ALD-positive (ALD+) patients (HR = 1.36; P < 0.0001), but was still significant among ALD-negative (ALD-) patients (HR = 1.11; P = 0.02). The contrast between ALD+ and ALD- waiting list mortality was significant only among HCV+ patients (HR = 1.14; P = 0.006). Posttransplant mortality was significantly increased among HCV+ (versus HCV-) patients (HR = 1.26; P = 0.0009), but not among ALD+ (versus ALD-) patients. Survival benefit of transplantation was significantly decreased among HCV+ compared with HCV- recipients with model for end-stage liver disease (MELD) scores 9-29, but was significantly increased at MELD >or=30. ALD did not influence the survival benefit of transplantation at any MELD score. CONCLUSION Except in patients with very low or very high MELD scores, HCV status has a significant negative impact on the survival benefit of liver transplantation. In contrast, the presence of ALD does not influence liver transplant survival benefit.
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Affiliation(s)
- Michael R Lucey
- Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI 53792-5124, USA.
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Affiliation(s)
- Michael R Lucey
- Section of Gastroenterology and Hepatology, Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI 53792, USA.
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Bajaj JS, Saeian K, Hafeezullah M, Franco J, Thompson A, Anderson R. Failure to fully disclose during pretransplant psychological evaluation in alcoholic liver disease: a driving under the influence corroboration study. Liver Transpl 2008; 14:1632-6. [PMID: 18975271 DOI: 10.1002/lt.21574] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
The prevention of recidivism in alcoholic liver disease is one of the aims of pretransplant psychological evaluation (PE). Failure to fully disclose the extent of alcohol use is evidence of ongoing alcoholism. Driving under the influence (DUI) represents objective evidence of alcohol abuse, but verifying DUIs through official records is not standard during PE. The aim of this study was to determine whether there was failure to fully disclose alcohol abuse on the part of patients on the basis of the Wisconsin Department of Transportation (DOT) DUI rate. Demographics, alcohol abuse/abstinence history, and DUIs admitted by the patient on PE were collected for 82 alcoholic patients with cirrhosis. The DOT was queried for DUIs before PE for all patients. Discrepancies between PE and DOT DUI numbers were evaluated and re-presented to the psychologist without identifiers. Psychosocial recommendation was then evaluated in light of DOT/PE DUI discrepancies. Six patients did not drive. The remaining 76 had 29 +/- 8 years of alcohol abuse and reported sobriety for 55 +/- 64 months before PE. Eighteen DUIs that were not originally admitted were discovered; 63% of DUIs occurred in the period during which patients claimed to be sober. Two patients had been rejected for transplant for other causes. Re-presenting the case to the psychologist with the new knowledge of DUIs would have prevented transplant clearance for the remaining 16 (21%, P = 0.000005 versus prior PE). In conclusion, official DUI records in prospective transplant candidates may identify patients who do not fully disclose the extent of their alcohol abuse and may be at risk for adverse outcomes.
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Affiliation(s)
- Jasmohan S Bajaj
- Division of Gastroenterology and Hepatology, Medical College of Wisconsin, Milwaukee, WI 53226, USA.
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Kalaitzakis E, Wallskog J, Björnsson E. Abstinence in patients with alcoholic liver cirrhosis: A follow-up study. Hepatol Res 2008; 38:869-76. [PMID: 18507691 DOI: 10.1111/j.1872-034x.2008.00353.x] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
AIM To investigate the proportion of patients with alcoholic cirrhosis who abstained from alcohol after contact with a hepatology unit, the predictors for abstinence, and the role of clinical and psychosocial factors in short-term mortality in these patients. METHODS Eighty-seven consecutive patients with alcoholic cirrhosis from a transplant center were included. Data on cirrhosis severity and complications, as well as on abstinence and psychosocial factors were collected. Patients were followed up for 19 (12-25) months. Data on abstinence during follow up, alcohol abuse treatment, psychiatric contact, severity of cirrhosis, mortality, and liver transplantation were analyzed. RESULTS Prior to inclusion, 53/87 (61%) patients had abstained from alcohol for 24 months (interquartile range: 18-33). Twenty percent had a history of other substance abuse, 47% had undergone alcohol abuse treatment, and 21% had a previous psychiatric diagnosis. Forty-eight percent lived with a partner, 23% worked/studied, and 53% were pensioners. During follow up, 26% died, 20% received a liver transplant, 55% abstained from alcohol, 47% received alcohol abuse treatment, and 33% had psychiatric contact. In a multivariate analysis, abstinence during follow up was found to be related to abstinence upon inclusion in the study, to the model for end-stage liver disease (MELD) score at follow up, and to no abuse treatment in a detoxification unit, whereas mortality was related to index MELD and alcohol abuse treatment during follow up. Neither abstinence nor mortality was related to psychosocial factors. CONCLUSION More than half of patients with alcoholic cirrhosis were found to abstain from alcohol during follow up, which was related to prior documentation of abstinence and cirrhosis severity. Cirrhosis severity (expressed as the MELD) and alcohol abuse treatment during follow up were related to short-term mortality.
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Affiliation(s)
- Evangelos Kalaitzakis
- Department of Internal Medicine, Sahlgrenska University Hospital, Gothenburg, Sweden
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Dew MA, DiMartini AF, Steel J, De Vito Dabbs A, Myaskovsky L, Unruh M, Greenhouse J. Meta-analysis of risk for relapse to substance use after transplantation of the liver or other solid organs. Liver Transpl 2008; 14:159-72. [PMID: 18236389 PMCID: PMC2883859 DOI: 10.1002/lt.21278] [Citation(s) in RCA: 195] [Impact Index Per Article: 11.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
For patients receiving liver or other organ transplants for diseases associated with substance use, risk for relapse posttransplantation is a prominent clinical concern. However, there is little consensus regarding either the prevalence or risk factors for relapse to alcohol or illicit drug use in these patients. Moreover, the evidence is inconsistent as to whether patients with pretransplantation substance use histories show poorer posttransplantation medical adherence. We conducted a meta-analysis of studies published between 1983 and 2005 to estimate relapse rates, rates of nonadherence to the medical regimen, and the association of potential risk factors with these rates. The analysis included 54 studies (50 liver, 3 kidney, and 1 heart). Average alcohol relapse rates (examined only in liver studies) were 5.6 cases per 100 patients per year (PPY) for relapse to any alcohol use and 2.5 cases per 100 PPY for relapse with heavy alcohol use. Illicit drug relapse averaged 3.7 cases per 100 PPY, with a significantly lower rate in liver vs. other recipients (1.9 vs. 6.1 cases). Average rates in other areas (tobacco use, immunosuppressant and clinic appointment nonadherence) were 2 to 10 cases per 100 PPY. Risk factors could be examined only for relapse to any alcohol use. Demographics and most pretransplantation characteristics showed little correlation with relapse. Poorer social support, family alcohol history, and pretransplantation abstinence of < or =6 months showed small but significant associations with relapse (r = 0.17-0.21). Future research should focus on improving the prediction of risk for substance use relapse, and on testing interventions to promote continued abstinence posttransplantation.
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Affiliation(s)
- Mary Amanda Dew
- Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA.
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Mathurin P, Lucey MR. A patient with alcoholic liver failure referred for liver transplantation. Liver Transpl 2007; 13:S83-6. [PMID: 17969071 DOI: 10.1002/lt.21338] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Affiliation(s)
- Philippe Mathurin
- Service d'Hépato-Gastroentérologie, Höpital Claude Huriez, Lille, France.
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