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1
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Ladin K. Utility and bias in psychosocial evaluations for transplant listing. Curr Opin Organ Transplant 2025; 30:114-119. [PMID: 39760141 DOI: 10.1097/mot.0000000000001198] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/07/2025]
Abstract
PURPOSE OF REVIEW Disparities in access to transplantation are persistent and pervasive among minoritized populations, and remain incompletely explained by socioeconomic status, insurance, geography, or medical factors. Although much attention has been paid to factors contributing to disparities in organ allocation, fewer studies have focused on barriers to the transplant waitlist. Given increasing calls for equity in organ transplantation, we examine the role of nonmedical factors used in transplant listing decisions, including psychosocial factors like social support, motivation, and knowledge in improving utility in transplant listing decisions, as well as their potential for reinforcing bias. RECENT FINDINGS Minoritized groups are more likely to be declined from transplant listing owing to psychosocial criteria. Lack of consistent definitions, screening tools with differential subgroup validity, and insufficient evidence-base contribute to concerns about reliance on psychosocial factors in transplant listing decisions. SUMMARY Improving consistency and evidence-based approaches in patient evaluation and listing decisions will require greater efforts to identify which psychosocial risk factors are predictive of posttransplant outcomes. Social needs screening presents a strengths-based framework for incorporating psychosocial factors in transplant listing decisions.
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Affiliation(s)
- Keren Ladin
- Department of Community Health
- Research on Ethics, Aging, and Community Health (REACH Lab), Tufts University, Medford, Massachusetts, USA
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2
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Philibert R, Beach SRH, Andersen AM. Two Clinically Implementable Digital PCR Assessments of DNA Methylation for Diagnosing Heavy Alcohol Consumption. EPIGENOMES 2024; 9:1. [PMID: 39846568 PMCID: PMC11755464 DOI: 10.3390/epigenomes9010001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2024] [Revised: 12/13/2024] [Accepted: 12/19/2024] [Indexed: 01/24/2025] Open
Abstract
BACKGROUND Heavy alcohol consumption (HAC) has a profound adverse effect on human health. Unfortunately, there is a relative lack of tools that are easily implementable in clinical settings and that can be used to supplement self-reporting in the diagnosis and management of HAC. In part, this paucity is due to limitations of currently available biological measures and a mismatch between available biological measures and the needs of clinicians managing HAC. OBJECTIVES We first review the pros and cons of existing biological measures. Next, we review the underlying theory and the performance characteristics of two recently developed methylation-sensitive digital PCR (MSdPCR) assays, referred to as the Alcohol T Score (ATS) and ZSCAN25, for the assessment of chronic and recent HAC, respectively. Finally, we outline a paradigm for improving the clinical diagnosis and management of alcohol use disorders by utilizing these new markers of alcohol consumption. CONCLUSIONS We conclude that further studies to understand the test performance characteristics of each of these epigenetic tools in larger, diverse populations are in order.
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Affiliation(s)
- Robert Philibert
- Department of Psychiatry, University of Iowa, Iowa City, IA 52246, USA;
- Behavioral Diagnostics LLC, Coralville, IA 52241, USA
| | | | - Allan M. Andersen
- Department of Psychiatry, University of Iowa, Iowa City, IA 52246, USA;
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3
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Kim DS, Yoon YI, Kim BK, Choudhury A, Kulkarni A, Park JY, Kim J, Sinn DH, Joo DJ, Choi Y, Lee JH, Choi HJ, Yoon KT, Yim SY, Park CS, Kim DG, Lee HW, Choi WM, Chon YE, Kang WH, Rhu J, Lee JG, Cho Y, Sung PS, Lee HA, Kim JH, Bae SH, Yang JM, Suh KS, Al Mahtab M, Tan SS, Abbas Z, Shresta A, Alam S, Arora A, Kumar A, Rathi P, Bhavani R, Panackel C, Lee KC, Li J, Yu ML, George J, Tanwandee T, Hsieh SY, Yong CC, Rela M, Lin HC, Omata M, Sarin SK. Asian Pacific Association for the Study of the Liver clinical practice guidelines on liver transplantation. Hepatol Int 2024; 18:299-383. [PMID: 38416312 DOI: 10.1007/s12072-023-10629-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/15/2023] [Accepted: 12/18/2023] [Indexed: 02/29/2024]
Abstract
Liver transplantation is a highly complex and challenging field of clinical practice. Although it was originally developed in western countries, it has been further advanced in Asian countries through the use of living donor liver transplantation. This method of transplantation is the only available option in many countries in the Asia-Pacific region due to the lack of deceased organ donation. As a result of this clinical situation, there is a growing need for guidelines that are specific to the Asia-Pacific region. These guidelines provide comprehensive recommendations for evidence-based management throughout the entire process of liver transplantation, covering both deceased and living donor liver transplantation. In addition, the development of these guidelines has been a collaborative effort between medical professionals from various countries in the region. This has allowed for the inclusion of diverse perspectives and experiences, leading to a more comprehensive and effective set of guidelines.
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Affiliation(s)
- Dong-Sik Kim
- Department of Surgery, Korea University College of Medicine, Seoul, Republic of Korea
| | - Young-In Yoon
- Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Beom Kyung Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea
| | | | | | - Jun Yong Park
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Jongman Kim
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Dong Hyun Sinn
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Dong Jin Joo
- Department of Surgery, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - YoungRok Choi
- Department of Surgery, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Jeong-Hoon Lee
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Ho Joong Choi
- Department of Surgery, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Ki Tae Yoon
- Department of Internal Medicine, Pusan National University College of Medicine, Yangsan, Republic of Korea
| | - Sun Young Yim
- Department of Internal Medicine, Korea University College of Medicine, Seoul, Republic of Korea
| | - Cheon-Soo Park
- Department of Surgery, Eunpyeong St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Deok-Gie Kim
- Department of Surgery, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Hae Won Lee
- Department of Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Republic of Korea
| | - Won-Mook Choi
- Department of Gastroenterology, Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Young Eun Chon
- Department of Internal Medicine, CHA Bundang Medical Center, CHA University, Seongnam, Republic of Korea
| | - Woo-Hyoung Kang
- Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Jinsoo Rhu
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Jae Geun Lee
- Department of Surgery, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Yuri Cho
- Center for Liver and Pancreatobiliary Cancer, National Cancer Center, Ilsan, Republic of Korea
| | - Pil Soo Sung
- Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Han Ah Lee
- Department of Internal Medicine, Ewha Womans University, Seoul, Republic of Korea
| | - Ji Hoon Kim
- Department of Internal Medicine, Korea University College of Medicine, Seoul, Republic of Korea
| | - Si Hyun Bae
- Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Jin Mo Yang
- Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
| | - Kyung-Suk Suh
- Department of Surgery, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea.
| | - Mamun Al Mahtab
- Department of Hepatology, Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh
| | - Soek Siam Tan
- Department of Medicine, Hospital Selayang, Batu Caves, Selangor, Malaysia
| | - Zaigham Abbas
- Sindh Institute of Urology and Transplantation, Karachi, Pakistan
| | - Ananta Shresta
- Department of Hepatology, Alka Hospital, Lalitpur, Nepal
| | - Shahinul Alam
- Crescent Gastroliver and General Hospital, Dhaka, Bangladesh
| | - Anil Arora
- Department of Gastroenterology and Hepatology, Sir Ganga Ram Hospital New Delhi, New Delhi, India
| | - Ashish Kumar
- Department of Gastroenterology and Hepatology, Sir Ganga Ram Hospital New Delhi, New Delhi, India
| | - Pravin Rathi
- TN Medical College and BYL Nair Hospital, Mumbai, India
| | - Ruveena Bhavani
- University of Malaya Medical Centre, Petaling Jaya, Selangor, Malaysia
| | | | - Kuei Chuan Lee
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Jun Li
- College of Medicine, Zhejiang University, Hangzhou, China
| | - Ming-Lung Yu
- Department of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | | | | | | | | | | | - H C Lin
- Endoscopy Center for Diagnosis and Treatment, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Masao Omata
- Department of Gastroenterology, Yamanashi Central Hospital, Yamanashi, Japan
- University of Tokyo, Bunkyo City, Japan
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4
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Affiliation(s)
- Michael R Lucey
- From the Department of Medicine, Division of Gastroenterology and Hepatology (M.R.L.), the Department of Pediatrics, Division of Gastroenterology, Hepatology, and Nutrition (K.N.F.), and the Department of Surgery, Division of Transplantation (D.P.F.), University of Wisconsin, Madison
| | - Katryn N Furuya
- From the Department of Medicine, Division of Gastroenterology and Hepatology (M.R.L.), the Department of Pediatrics, Division of Gastroenterology, Hepatology, and Nutrition (K.N.F.), and the Department of Surgery, Division of Transplantation (D.P.F.), University of Wisconsin, Madison
| | - David P Foley
- From the Department of Medicine, Division of Gastroenterology and Hepatology (M.R.L.), the Department of Pediatrics, Division of Gastroenterology, Hepatology, and Nutrition (K.N.F.), and the Department of Surgery, Division of Transplantation (D.P.F.), University of Wisconsin, Madison
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5
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Prince DS, Nash E, Liu K. Alcohol-Associated Liver Disease: Evolving Concepts and Treatments. Drugs 2023; 83:1459-1474. [PMID: 37747685 PMCID: PMC10624727 DOI: 10.1007/s40265-023-01939-9] [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] [Accepted: 09/03/2023] [Indexed: 09/26/2023]
Abstract
Alcohol is a prominent cause of liver disease worldwide with higher prevalence in developed nations. The spectrum of alcohol-associated liver disease (ALD) encompasses a diverse range of clinical entities, from asymptomatic isolated steatosis to decompensated cirrhosis, and in some cases, acute or chronic liver failure. Consequently, it is important for healthcare practitioners to maintain awareness and systematically screen for ALD. The optimal evaluation and management of ALD necessitates a collaborative approach, incorporating a multidisciplinary team and accounting for concurrent medical conditions. A repertoire of therapeutic interventions exists to support patients in achieving alcohol cessation and sustaining remission, with complete abstinence being the ultimate objective. This review explores the existing therapeutic options for ALD acknowledging geographical discrepancies in accessibility. Recent innovations, including the inclusion of alcohol consumption biomarkers into clinical protocols and the expansion of liver transplantation eligibility to encompass severe alcohol-associated hepatitis, are explored.
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Affiliation(s)
- David Stephen Prince
- AW Morrow Gastroenterology and Liver Centre, Royal Prince Alfred Hospital, Sydney, NSW, Australia.
- Department of Gastroenterology and Liver, Liverpool Hospital, Sydney, NSW, Australia.
- Liver Injury and Cancer Program, Centenary Institute, Sydney, NSW, Australia.
- The Ingham Institute for Applied Medical Research, Sydney, NSW, Australia.
- Faculty of Medicine and Health, The University of New South Wales, Sydney, NSW, Australia.
| | - Emily Nash
- AW Morrow Gastroenterology and Liver Centre, Royal Prince Alfred Hospital, Sydney, NSW, Australia
- Faculty of Medicine and Health, University of Sydney, Sydney, NSW, Australia
| | - Ken Liu
- AW Morrow Gastroenterology and Liver Centre, Royal Prince Alfred Hospital, Sydney, NSW, Australia
- Liver Injury and Cancer Program, Centenary Institute, Sydney, NSW, Australia
- Faculty of Medicine and Health, University of Sydney, Sydney, NSW, Australia
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6
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Puri P, Malik S. Liver Transplantation: Contraindication and Ineligibility. J Clin Exp Hepatol 2023; 13:1116-1129. [PMID: 37975058 PMCID: PMC10643298 DOI: 10.1016/j.jceh.2023.04.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/24/2023] [Accepted: 04/14/2023] [Indexed: 11/19/2023] Open
Abstract
Liver transplantation (LT) is a life-saving therapeutic modality for patients with various advanced liver diseases. It is crucial to identify that the patient's illness is sufficiently advanced and unlikely to improve with medical management to justify the need for transplantation. At the same time, it is crucial to identify patients with comorbidities and far advanced disease that would result in an unacceptable outcome after LT. Specific care also is required before deciding on LT in the elderly, acute on chronic liver disease, patients with comorbidities, and hepatocellular carcinoma. Transplantation needs to be timed appropriately to avoid unnecessary LT and ensure that the decision is not left too late to avoid losing the patient without a transplant. Also, important is the decision as to when not to transplant. The current review explores some of these issues of contraindications and ineligibility for LT.
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Affiliation(s)
- Pankaj Puri
- Fortis Escorts Liver and Digestive Diseases Institute, Fortis Escorts Hospital, New Delhi 110025, India
| | - Sarthak Malik
- Department of Gastroenterology, Manipal Hospital, Dwarka, New Delhi 110075, India
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7
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Flamm S, Lawitz E, Borg B, Charlton M, Landis C, Reddy KR, Shiffman M, Alsina A, Chang C, Ravendhran N, Hernandez C, Hézode C, Scherbakovsky S, Mercier RC, Samuel D. Efficacy and Safety of Sofosbuvir/Velpatasvir Plus Ribavirin in Patients with Hepatitis C Virus-Related Decompensated Cirrhosis. Viruses 2023; 15:2026. [PMID: 37896803 PMCID: PMC10611233 DOI: 10.3390/v15102026] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2023] [Revised: 08/18/2023] [Accepted: 08/22/2023] [Indexed: 10/29/2023] Open
Abstract
A fixed-dose combination of sofosbuvir/velpatasvir (SOF/VEL) plus weight-based ribavirin (RBV) for 12 weeks is recommended for the treatment of patients with hepatitis C virus (HCV)-associated decompensated cirrhosis. However, large global studies, while confirming the effectiveness of SOF/VEL in a broad range of patients, often exclude these patients. This Phase 2, single-arm, open-label study in adult patients with HCV-associated decompensated cirrhosis in France and the USA aimed to provide further data on the safety and efficacy of SOF/VEL plus RBV for 12 weeks in this population. Patients were treated with a fixed-dose combination of SOF 400 mg/VEL 100 mg plus weight-based RBV once daily for 12 weeks. The inclusion criteria were chronic HCV infection (≥6 months), quantifiable HCV RNA at screening, Child-Turcotte-Pugh class B or C cirrhosis, and liver imaging within 6 months of Day 1 to exclude hepatocellular carcinoma. Among 32 patients who initiated treatment, 78.1% achieved sustained virologic response 12 weeks after the end of treatment (SVR12). Failure to achieve SVR12 was due to non-virologic reasons (investigator discretion, n = 1; death, n = 6). All 25 patients in the per-protocol population achieved SVR12 and all but one achieved sustained virologic response 24 weeks after the end of treatment. Adverse events (AEs) were as expected for a patient population with advanced liver disease. All Grade 3-4 and serious AEs and deaths were deemed unrelated to treatment. In patients with HCV-associated decompensated cirrhosis, SOF/VEL plus RBV achieved high SVR12 rates and was generally well tolerated.
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Affiliation(s)
- Steven Flamm
- Department of Internal Medicine, Division of Digestive Diseases and Nutrition, Rush University Medical Center, Chicago, IL 60612, USA
| | - Eric Lawitz
- Texas Liver Institute, University of Texas Health San Antonio, San Antonio, TX 78215, USA
| | - Brian Borg
- Southern Therapy and Advanced Research LLC, Jackson, MS 39216, USA
| | | | - Charles Landis
- Division of Gastroenterology and Hepatology, University of Washington, Seattle, WA 98101, USA
| | - K. Rajender Reddy
- Department of Medicine, Division of Gastroenterology and Hepatology, University of Pennsylvania, Philadelphia, PA 19104, USA
| | - Mitchell Shiffman
- Bon Secours Mercy Health, Liver Institute of Virginia, Richmond, VA 23226, USA
| | - Angel Alsina
- Tampa General Medical Group, Tampa, FL 33609, USA
| | - Charissa Chang
- Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA
| | | | | | | | | | | | - Didier Samuel
- Centre Hépatobiliaire, Hôpital Paul-Brousse, Inserm Research Unit 1193, Université Paris-Saclay, 94800 Villejuif, France
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8
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Gülcicegi DE, Goeser T, Kasper P. Prognostic assessment of liver cirrhosis and its complications: current concepts and future perspectives. Front Med (Lausanne) 2023; 10:1268102. [PMID: 37780566 PMCID: PMC10537916 DOI: 10.3389/fmed.2023.1268102] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2023] [Accepted: 08/28/2023] [Indexed: 10/03/2023] Open
Abstract
Liver cirrhosis is an irreversible stage of chronic liver disease with varying clinical course. Acute decompensation of liver cirrhosis represents a watershed in prognosis and is characterized by the occurrence of clinical complications such as ascites, jaundice, hepatic encephalopathy, infections, or portal-hypertensive hemorrhages. Emergent data indicate that an acute decompensation can be subdivided into stable decompensated cirrhosis (SDC), unstable decompensated cirrhosis (UDC), pre-acute-on chronic liver failure (pre-ACLF) and acute-on chronic liver failure (ACLF), while the mortality risk varies greatly between the respective subgroups. ACLF is the most severe form of acutely decompensated cirrhosis and characterized by the development of organ failure(s) and a high short-term mortality. Due to the dynamic disease course of acute decompensation, it is paramount to detect patients at particular risk for severe complications those at high risk for developing ACLF as early as possible in order to initiate optimal management. This review describes new concepts and perspectives in the definition and classification of decompensated cirrhosis and provides on overview on emerging predictive scoring systems, non-invasive measurement methods and new biomarkers, which allow an early identification of patients with acute decompensation at risk.
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Affiliation(s)
- Dilan Elcin Gülcicegi
- Department of Gastroenterology and Hepatology, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany
| | | | - Philipp Kasper
- Department of Gastroenterology and Hepatology, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany
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9
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Mitchell J, Herrick-Reynolds K, Motter JD, Teles M, Kates O, Sung H, Chen PH, King E, Cameron A. Transplant Center Attitudes Toward Early Liver Transplant for Alcohol-associated Liver Disease. Transplant Direct 2023; 9:e1532. [PMID: 37649789 PMCID: PMC10465102 DOI: 10.1097/txd.0000000000001532] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2023] [Revised: 06/29/2023] [Accepted: 07/14/2023] [Indexed: 09/01/2023] Open
Abstract
Background Many centers have removed 6-mo pretransplant alcohol abstinence requirements to provide early liver transplant (ELT) for individuals with severe alcohol-associated liver disease (ALD), but the practice remains controversial. Using data collected from a nationally distributed survey, this study examines the practices and attitudes of transplant centers in the United States regarding ELT. Methods A 20-item survey designed to assess center practices and provider attitudes was distributed to 225 medical and surgical directors from 143 liver transplant centers via email. Results Surveys were completed by 28.9% (n = 65) of directors and 39% (n = 56) of transplant centers. All responding centers reported evaluating patients for ELT. Circumstances for considering ELT included <6 mo of survival without a transplant (96.4%) and inability to participate in alcohol addiction therapy pretransplant (75%). Most (66%) directors indicated their center had established criteria for listing candidates with severe ALD for ELT. Regarding important factors for ELT candidate listing, 57.1% indicated patient survival, 37.5% indicated graft survival, and 55.4% indicated having a low risk of relapse. Only 12.7% of directors affirmed the statement, "Six months of pretransplant abstinence decreases the risk of relapse." Conclusions More centers are providing ELT for severe ALD. Inability to participate in alcohol addiction therapy and <6 mo of survival are commonly reported circumstances for considering ELT. Continued investigation of posttransplant outcomes in patients receiving ELT is essential to establishing a national consensus for distributing this valuable resource.
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Affiliation(s)
- Jonathan Mitchell
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD
| | | | - Jennifer D. Motter
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD
| | - Mayan Teles
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD
| | - Olivia Kates
- Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD
| | - Hannah Sung
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD
| | - Po-Hung Chen
- Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD
| | - Elizabeth King
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD
| | - Andrew Cameron
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD
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Germani G, D’Arcangelo F, Grasso M, Burra P. Advances and Controversies in Acute Alcohol-Related Hepatitis: From Medical Therapy to Liver Transplantation. Life (Basel) 2023; 13:1802. [PMID: 37763206 PMCID: PMC10532507 DOI: 10.3390/life13091802] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2023] [Revised: 08/10/2023] [Accepted: 08/18/2023] [Indexed: 09/29/2023] Open
Abstract
Alcohol-related hepatitis (AH) is a clinical syndrome characterized by recent-onset jaundice in the context of alcohol consumption. In patients with severe AH "unresponsive" to steroid therapy, mortality rates exceed 70% within six months. According to European and American guidelines, liver transplantation (LT) may be considered in highly selected patients who do not respond to medical therapy. The aim of this narrative review is to summarize current knowledge from medical therapy to liver transplantation in acute alcohol-related hepatitis. Due to the impossibility to guarantee six-month abstinence, LT for AH is controversial. Principal concerns are related to organ scarcity in the subset of stigma of "alcohol use disorder" (AUD) and the risk of relapse to alcohol use after LT. Return to alcohol use after LT is a complex issue that cannot be assessed as a yes/no variable with heterogeneous results among studies. In conclusion, present data indicate that well-selected patients have excellent outcomes, with survival rates of up to 100% at 24 and 36 months after LT. Behavioral therapy, ongoing psychological support, and strong family support seem essential to improve long-term outcomes after LT and reduce the risk in relapse of alcohol use.
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Affiliation(s)
- Giacomo Germani
- Multivisceral Transplant Unit, Azienda Ospedale—Università Padova, Department of Surgery, Oncology and Gastroenterology, University of Padova, 35122 Padova, Italy
| | - Francesca D’Arcangelo
- Gastroenterology and Multivisceral Transplant Unit, Azienda Ospedale—Università Padova, Department of Surgery, Oncology and Gastroenterology, University of Padova, 35122 Padova, Italy; (F.D.); (M.G.); (P.B.)
| | - Marco Grasso
- Gastroenterology and Multivisceral Transplant Unit, Azienda Ospedale—Università Padova, Department of Surgery, Oncology and Gastroenterology, University of Padova, 35122 Padova, Italy; (F.D.); (M.G.); (P.B.)
| | - Patrizia Burra
- Gastroenterology and Multivisceral Transplant Unit, Azienda Ospedale—Università Padova, Department of Surgery, Oncology and Gastroenterology, University of Padova, 35122 Padova, Italy; (F.D.); (M.G.); (P.B.)
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11
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Kalairajan S, K K K, P G. Red Cell Distribution Width in Chronic Liver Disease: An Observational Study. Cureus 2023; 15:e40158. [PMID: 37431329 PMCID: PMC10329736 DOI: 10.7759/cureus.40158] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2023] [Accepted: 06/08/2023] [Indexed: 07/12/2023] Open
Abstract
BACKGROUND Chronic liver diseases (CLDs) encompass a group of conditions that are marked by diminished liver function due to ongoing inflammation or damage. This study aimed to establish a relationship between the red cell distribution width (RDW) and two scoring systems, namely the Model for End-Stage Liver Disease (MELD) score and Child-Turcotte-Pugh (CTP) score, in individuals diagnosed with CLDs. METHODS The study was carried out at Aarupadai Veedu Medical College & Hospital, Pondicherry, India, following approval from the Institutional Ethical Committee in the Department of General Medicine and Gastroenterology. It involved 50 patients aged 18 years and above who were diagnosed with CLD. The RDW of all selected patients was measured using a three-part autoanalyzer, and its correlation with the MELD and CTP scores was examined. Data analysis was performed using IBM SPSS (Statistical Package for Social Sciences), version 21.0 (IBM Corp., Armonk, NY), with a significance level set at p < 0.05. RESULTS When comparing the baseline characteristics including age, gender, and encephalopathy, no statistically significant differences were found between RDW-standard deviation (RDW-SD) and RDW-corpuscular value (RDW-CV) (p > 0.05). However, a statistically significant correlation was observed between the presence of ascites and RDW-CV values (p = 0.029). Furthermore, there was a significant association between the CTP score and RDW-SD (p < 0.0001). The association between the MELD score and RDW-SD was also found to be statistically significant (p = 0.006). Similarly, statistically significant results were obtained between the MELD score and RDW-CV (p = 0.034). CONCLUSION The utilization of RDW holds promise as a convenient and effective tool for evaluating the severity of individuals with CLD.
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Affiliation(s)
- Sankar Kalairajan
- Department of Internal Medicine, Aarupadai Veedu Medical College and Hospital, Vinayaka Mission's Research Foundation (DU), Pondicherry, IND
| | - Kavitha K K
- Department of Microbiology, Swamy Vivekanandha Medical College Hospital and Research Institute, Tiruchengode, IND
| | - Govindaraj P
- Department of Internal Medicine, Aarupadai Veedu Medical College and Hospital, Vinayaka Mission's Research Foundation (DU), Pondicherry, IND
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12
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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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13
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Alcoholic Hepatitis. Med Clin North Am 2023; 107:533-554. [PMID: 37001952 DOI: 10.1016/j.mcna.2022.12.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/22/2023]
Abstract
Alcoholic hepatitis (AH) is a unique clinical syndrome on the spectrum of alcohol-associated liver disease (ALD). It constitutes a rising epidemic with increasing incidence and major public health implications. In severe AH, 30-day mortality approaches 30%, yet therapeutic options remain limited. Survival benefit from corticosteroids, the mainstay of medical treatment, is short-lived. Among corticosteroid nonresponders, the use of early liver transplantation is heterogeneous across centers and remains limited by significant barriers. Long-term prognosis is largely dictated by abstinence; however, comorbid alcohol use disorder remains undertreated. Efforts to address these challenges are required to curb the AH epidemic.
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14
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Adekunle AD, Adejumo A, Singal AK. Therapeutic targets in alcohol-associated liver disease: progress and challenges. Therap Adv Gastroenterol 2023; 16:17562848231170946. [PMID: 37187673 PMCID: PMC10176580 DOI: 10.1177/17562848231170946] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/27/2022] [Accepted: 04/04/2023] [Indexed: 05/17/2023] Open
Abstract
Alcohol-associated liver disease (ALD) is a complex disease with rapidly increasing prevalence. Although there are promising therapeutic targets on the horizon, none of the newer targets is currently close to an Food and Drug Administration approval. Strategies are needed to overcome challenges in study designs and conducting clinical trials and provide impetus to the field of drug development in the landscape of ALD and alcoholic hepatitis. Management of ALD is complex and should include therapies to achieve and maintain alcohol abstinence, preferably delivered by a multidisciplinary team. Although associated with clear mortality benefit in select patients, the use of early liver transplantation still requires refinement to create uniformity in selection protocols across transplant centers. There is also a need for reliable noninvasive biomarkers for prognostication. Last but not the least, strategies are urgently needed to implement integrated multidisciplinary care models for treating the dual pathology of alcohol use disorder and of liver disease for improving the long-term outcomes of patients with ALD.
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Affiliation(s)
- Ayooluwatomiwa Deborah Adekunle
- Department of Internal Medicine, St. Luke’s
Hospital, Chesterfield, Missouri, USA
- Division of Hepatology, University of
Pittsburgh Medical Center, Pittsburgh, PA, USA
- Division of Transplant Hepatology, University
of South Dakota Sanford Medical School, Sioux Falls, SD
| | - Adeyinka Adejumo
- Department of Internal Medicine, St. Luke’s
Hospital, Chesterfield, Missouri, USA
- Division of Hepatology, University of
Pittsburgh Medical Center, Pittsburgh, PA, USA
- Division of Transplant Hepatology, University
of South Dakota Sanford Medical School, Sioux Falls, SD
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15
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El Sheref SEDM, Afify S, Berengy MS. Clinical characteristics and predictors of esophagogastric variceal bleeding among patients with HCV-induced liver cirrhosis: An observational comparative study. PLoS One 2022; 17:e0275373. [PMID: 36227871 PMCID: PMC9560135 DOI: 10.1371/journal.pone.0275373] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2022] [Accepted: 09/15/2022] [Indexed: 11/27/2022] Open
Abstract
OBJECTIVES To investigate the clinical characteristics, risk factors, and predictors of esophagogastric variceal bleeding in patients with hepatitis C virus (HCV)-induced liver cirrhosis. METHODS This comparative observational study was carried out on 100 patients suffering from post hepatitis cirrhosis and portal hypertension who were admitted to the Internal Medicine Department, Al-Azhar University Hospital, Damietta Egypt. Patients were classified into two groups: 50 of them presented with esophagogastric varices with acute variceal bleeding, and 50 patients presented without bleeding. Data were collected, coded, revised, and entered into the Stata software version 16. RESULTS The mean age of patients with bleeding was slightly higher than those without bleeding (55.58 ± 5.89 vs. 52.54 ± 9.01 years), p = 0.049. Mild ascites, positive H.Pylori, and Child-Pugh score B and C were an independent predictors of esophagogastric variceal bleeding (OR = 0.036, 95% CI: 0.0004-0.36; p = 0.005), (OR = 7.36, 95% CI: 1.44-37.59; p = 0.016), (OR = 19.0, 95% CI: 2.02-186.3; p = 0.010), and (OR = 40.51, 95% CI: 2.18-751.31; p = 0.013). The sensitivity of this model was 93.88%, specificity was 53.85%, PPV was 88.46%, NPV was 70.0%, correctly classified patients were 85.48%, and AUC was 90.27%. In the second model, pepsinogen level higher than 43.5 μg/l, AST (>54.5), Bilirubin (>1.45), and Hemoglobin (>11.5) were a significant independent predictors of esophagogastric variceal bleeding (OR = 1.18, 95% CI: 1.09-1.27; p<0.001), (OR = 1.14, 95% CI: 1.03-1.27; p = 0.007), (OR = 5.55, 95% CI: 1.21-25.43; p = 0.027), and (OR = 0.05, 95% CI: 0.008-0.32; p = 0.002), respectively. The sensitivity of this model was 92%, specificity was 98%, PPV was 97.87%, NPV was 92.45%, correctly classified patients were 95%, and AUC was 98.68%. CONCLUSION The independent predictors of esophagogastric variceal bleeding were ascites, positive H. pylori, Child-Pugh score B and C, pepsinogen level higher than 43.5 μg/l, AST (>54.5), bilirubin (>1.45), and hemoglobin (>11.5). Laboratory investigations are more reliable in predicting variceal bleeding and excluding non-variceal bleeding; however, clinical symptoms should not be neglected, especially H. pylori infection, ascites, and Child-Pugh score.
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Affiliation(s)
| | - Shimaa Afify
- Gastroenterology Department, National Hepatology and Tropical Medicine Research Institute, Cairo, Egypt
| | - Mahmoud S. Berengy
- Internal Medicine Department, Faculty of Medicine, Al-Azhar University Hospital, New Damietta, Egypt
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16
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Chang WJ, Hsieh CE, Hung YJ, Hsu YL, Lin KH, Chen YL. Length of Alcohol Abstinence Predicts Posttransplant Delirium in Living Donor Liver Transplant Recipients with Alcoholic Cirrhosis. EXP CLIN TRANSPLANT 2022; 20:750-756. [DOI: 10.6002/ect.2022.0199] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
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17
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Abstract
Pediatric patients constitute an important group within the general transplant population, given the opportunity to significantly extend their lives with successful transplantation. Children have historically received special consideration under the various abdominal solid organ allocation algorithms, but matching patients with size and weight restrictions with appropriate donors remains an ongoing issue. Here, we describe the historical trends in pediatric organ allocation policies for liver, kidney, intestine, and pancreas transplantation. We also review recent changes to these allocation policies, with particular attention to recent amendments to geographical prioritization, with the dissolution of donor service areas and United Network for Organ Sharing (UNOS) regions and the subsequent creation of acuity circles.
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Affiliation(s)
- Leah Ott
- Department of General Surgery, Boston Children's Hospital, 300 Longwood Avenue, Fegan 3, Boston, MA 02115, United States
| | - Khashayar Vakili
- Department of General Surgery, Boston Children's Hospital, 300 Longwood Avenue, Fegan 3, Boston, MA 02115, United States
| | - Alex G Cuenca
- Department of General Surgery, Boston Children's Hospital, 300 Longwood Avenue, Fegan 3, Boston, MA 02115, United States.
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18
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Daniel KE, Matthews LA, Deiss-Yehiely N, Myers J, Garvey M, Rice JP, Eickhoff J, Lucey MR. Psychosocial Assessment Rather Than Severity of Liver Failure Dominates Selection for Liver Transplantation in Patients With Alcohol-Related Liver Disease. Liver Transpl 2022; 28:936-944. [PMID: 34596955 DOI: 10.1002/lt.26324] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/26/2021] [Revised: 09/10/2021] [Accepted: 09/17/2021] [Indexed: 12/12/2022]
Abstract
The Stanford Integrated Psychosocial Assessment for Transplant (SIPAT) is a validated interview tool to assess psychosocial well-being in candidates for solid organ transplants, with higher scores indicating greater vulnerability. We hypothesized that patients with alcohol-related liver disease (ALD) undergoing liver transplantation (LT) evaluation would have higher SIPAT scores than candidates with non-ALD, but that only patients with ALD who have low scores would be selected. We analyzed retrospectively consecutive adults undergoing LT evaluation from June 2018 to December 2019. Comparisons between patients with ALD and patients with non-ALD were made using the nonparametric Wilcoxon rank sum test plus a multivariate analysis to determine independent predictors for approval. In the study cohort of 358 patients, there were 199 (56%) patients with ALD with a mean age of 55 years, and 133 (67%) were men. There were 159 (44%) patients with non-ALD with a mean age of 57 years, and 95 (60%) were men. Mean Model for End-Stage Liver Disease-sodium scores were similar for selected versus not selected patients with ALD (25 versus 25.6) and selected versus not selected patients with non-ALD (18.3 versus 17.4), although the ALD group had substantially higher Model for End-Stage Liver Disease scores. Patients with ALD had higher mean SIPAT composite and individual domain scores compared with their non-ALD counterparts. SIPAT scores were not affected by age or sex. Proportionately more candidates with non-ALD were selected compared to candidates with ALD (68% versus 42%; P < 0.001; odds ratio for approval of non-ALD versus ALD, 2.9; 95% confidence interval, 1.8-4.7; P < 0.001). Composite SIPAT scores were lower in the selected versus nonselected in both ALD and non-ALD groups, although the SIPAT scores were significantly higher in selected patients with ALD (median, 39) than selected patients with non-ALD (median, 23; P = 0.001). Psychosocial assessment has a greater influence than acuity of liver failure on the selection of patients with ALD for LT listing, whereas psychosocial assessment has a minor influence on the selection of non-ALD candidates.
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Affiliation(s)
- Kimberly E Daniel
- Division of Gastroenterology and Hepatology, University of Wisconsin School of Medicine and Public Health, Madison, WI
| | - Lindsay A Matthews
- Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI
| | - Nimrod Deiss-Yehiely
- Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI
| | - Jaime Myers
- Division of Transplantation, University of Wisconsin School of Medicine and Public Health, Madison, WI
| | - Maureen Garvey
- Division of Transplantation, University of Wisconsin School of Medicine and Public Health, Madison, WI
| | - John P Rice
- Division of Gastroenterology and Hepatology, University of Wisconsin School of Medicine and Public Health, Madison, WI
| | - Jens Eickhoff
- Department of Biostatistics and Medical Informatics, University of Wisconsin School of Medicine and Public Health, Madison, WI
| | - Michael R Lucey
- Division of Gastroenterology and Hepatology, University of Wisconsin School of Medicine and Public Health, Madison, WI
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19
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Kotha S, Berry P. The writing was on the wall: Decision making near the end of life in advanced liver disease. PROGRESS IN PALLIATIVE CARE 2022. [DOI: 10.1080/09699260.2022.2067702] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/18/2022]
Affiliation(s)
- Sreelakshmi Kotha
- Department of Gastroenterology, Guy’s and St Thomas’ Foundation Trust, London, UK
| | - Philip Berry
- Department of Gastroenterology, Guy’s and St Thomas’ Foundation Trust, London, UK
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20
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Jowsey-Gregoire S, Jannetto PJ, Jesse MT, Fleming J, Winder GS, Balliet W, Kuntz K, Vasquez A, Weinland S, Hussain F, Weinrieb R, Fireman M, Nickels MW, Peipert JD, Thomas C, Zimbrean PC. Substance use screening in transplant populations: Recommendations from a consensus workgroup. Transplant Rev (Orlando) 2022; 36:100694. [DOI: 10.1016/j.trre.2022.100694] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2022] [Accepted: 04/20/2022] [Indexed: 02/07/2023]
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21
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Musto J, Stanfield D, Ley D, Lucey MR, Eickhoff J, Rice JP. Recovery and outcomes of patients denied early liver transplantation for severe alcohol-associated hepatitis. Hepatology 2022; 75:104-114. [PMID: 34387875 DOI: 10.1002/hep.32110] [Citation(s) in RCA: 24] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/12/2021] [Revised: 07/06/2021] [Accepted: 07/18/2021] [Indexed: 12/20/2022]
Abstract
BACKGROUND AND AIMS Liver transplantation (LT) in alcohol-associated hepatitis (AH) remains controversial, in part because spontaneous recovery (SR) can occur. There is a paucity of data on SR in patients with severe AH who undergo LT evaluation. The purpose of this study was to determine factors associated with SR and survival in patients with severe AH who undergo LT evaluation. APPROACH AND RESULTS This is a retrospective study of ALD patients with Model for End-Stage Liver Disease (MELD) >25 and <90 days abstinence who underwent LT evaluation at a single center between 2012 and 2018. One hundred forty-four patients (median age, 45.5 years; 68.1% male) were included. Forty-nine (34%) underwent LT and 95 (66%) patients did not undergo LT, and of those, 34 (23.6%) experienced SR. Factors associated with recovery were younger age (OR, 0.92; p = 0.004), lower index international normalized ratio (INR; 0.31; p = 0.03), and lower peak MELD (OR, 0.83; p = 0.02). Only 7 patients (20.6%) achieved a compensated state with a MELD <15 and absence of therapy for ascites or HE. Survival was improved in patients who underwent early LT when compared to SR. Survival was impaired in SR following relapse to alcohol use when compared to SR patients who abstained and LT recipients. Among all 6-month survivors of AH, alcohol use trended toward an association with mortality (HR, 2.05; p = 0.17), but only LT was associated with decreased mortality risk (HR, 0.20; p = 0.005). CONCLUSIONS SR from AH after LT evaluation is associated with age, index INR, and lower peak MELD. Most recovered patients continue to experience end-stage complications. LT is the only factor associated with lower mortality.
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Affiliation(s)
- Jessica Musto
- Department of Medicine, School of Medicine and Public Health, University of Wisconsin, Madison, Wisconsin, USA
| | - Dylan Stanfield
- Department of Medicine, School of Medicine and Public Health, University of Wisconsin, Madison, Wisconsin, USA
| | - Dana Ley
- Department of Medicine, School of Medicine and Public Health, University of Wisconsin, Madison, Wisconsin, USA
| | - Michael R Lucey
- Department of Medicine, School of Medicine and Public Health, University of Wisconsin, Madison, Wisconsin, USA
| | - Jens Eickhoff
- Department of Biostatistic and Medical Informatics, School of Medicine and Public Health, University of Wisconsin, Madison, Wisconsin, USA
| | - John P Rice
- Department of Medicine, School of Medicine and Public Health, University of Wisconsin, Madison, Wisconsin, USA
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22
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Khan S, Cain O, Rajoriya N. Alcohol Related Liver Disease. MEN’S HEALTH AND WELLBEING 2022:163-191. [DOI: 10.1007/978-3-030-84752-4_11] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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23
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Abstract
The liver comprises both parenchymal and non-parenchymal cells with varying functions. Cirrhosis is often complicated by the development of portal hypertension and its associated complications. Hence, assessment of liver in cirrhosis should include assessment of its structural, function of both hepatic and non-hepatic tissue and haemodynamic assessment of portal hypertension. There is no single test that can evaluate all functions of liver and assess prevalence and severity of portal hypertension. Commonly available tests like serum bilirubin, liver enzymes (alanine [ALT] and aspartate aminotransferase [AST], serum alkaline phosphatase [ALP], gamma glutamyl transpeptidase [GGT]), serum albumin and prothrombin time for assessment of liver functions partly assess liver functions. quantitative liver functions like indocyanine clearance tests [ICG-K], methacetin breath test [MBT] were developed to assess dynamic status of liver but has its own limitation and availability. Imaging based assessment of liver by transient elastography, MRI based 99 mTc-coupled asialoglycoprotein mebrofenin scan help the clinician to assess liver function, functional volume of liver left after surgery and portal hypertension [PH]. Hepatic venous pressure gradient still remains the gold standard for the assessment of portal hypertension but is invasive and not available in all centres. Combinations of blood parameters in form of various indices like fibrosis score of 4 [FIB-4], Lok index, scores like model for end stage liver disease (MELD) and Child-Turcotte Pugh score are commonly used for assessing liver function in clinical practice.
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Key Words
- 99mTc-GSA, technetium-99m galactosyl human serum albumin
- ALP, alkaline phosphatase
- ALT, alanine aminotransferase
- ARFI, Acoustic Radiation Force Impulse
- AST, aspartate aminotransferase
- BUN, blood urea nitrogen
- CLD, chronic liver disease
- ESLD, end-stage liver disease
- FIB-4, fibrosis score of 4
- GGT, gamma glutamyl transpeptidase
- HVPG, Hepatic venous pressure gradient
- ICG-K, indocyanine clearance tests
- INR, International normalised ratio
- LFTs, liver function tests
- MBT, methacetin breath test
- NAFLD, non-alcoholic fatty liver disease
- PBS, primary biliary cholangitis
- PHT, portal hypertension
- PSC, primary Sclerosing cholangitis
- cirrhosis
- liver function tests
- portal hypertension
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Affiliation(s)
- Praveen Sharma
- Address for correspondence: Praveen Sharma, Associate Professor, Department of Gastroenterology, Sir Ganga Ram Hospital, New Delhi, India.
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24
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German MN, Brown R, Lucey MR. Out With the Old, in With the New: Replacing the "6-Month Abstinence Rule" With Integrated Care for Alcohol-Associated Liver Disease. Gastroenterology 2021; 161:1795-1797. [PMID: 34563475 DOI: 10.1053/j.gastro.2021.09.041] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/24/2021] [Accepted: 09/21/2021] [Indexed: 12/19/2022]
Affiliation(s)
- Margarita N German
- Department of Medicine, Division of Gastroenterology and Hepatology, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin.
| | - Randall Brown
- Department of Family Medicine and Community Health, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin
| | - Michael R Lucey
- Department of Medicine, Division of Gastroenterology and Hepatology, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin
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25
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Carrique L, Quance J, Tan A, Abbey S, Sales I, Lilly L, Bhat M, Galvin Z, Cattral M, Ghanekar A, McGilvray I, Reichman T, Sapisochin G, Sayed B, Selzner M, Lynch MJ, Selzner N. Results of Early Transplantation for Alcohol-Related Cirrhosis: Integrated Addiction Treatment With Low Rate of Relapse. Gastroenterology 2021; 161:1896-1906.e2. [PMID: 34370999 DOI: 10.1053/j.gastro.2021.08.004] [Citation(s) in RCA: 43] [Impact Index Per Article: 10.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/16/2021] [Revised: 07/28/2021] [Accepted: 08/02/2021] [Indexed: 12/19/2022]
Abstract
BACKGROUND & AIMS In 2018, our team initiated a prospective pilot program to challenge the paradigm of the "6-month rule" of abstinence for patients with alcohol-related liver disease (ALD) requiring transplant. Our pilot involved an in-depth examination of patients' alcohol use, social support, and psychiatric comorbidity, as well as the provision of pre- and post-transplantation addiction treatment. METHODS Patients with ALD were assessed for inclusion in the pilot by a multidisciplinary team. Relapse prevention therapy was provided directly to all patients deemed to meet the program's inclusion criteria. Random biomarker testing for alcohol was used pre and post transplantation. RESULTS We received 703 referrals from May 1, 2018 to October 31, 2020. After fulfilling the program's criteria, 101 patients (14%) were listed for transplantation and 44 (6.2%) received transplants. There were no significant differences in survival rates between those receiving transplants through the pilot program compared with a control group with more than 6 months of abstinence (P = .07). Three patients returned to alcohol use during an average post-transplantation follow-up period of 339 days. In a multivariate analysis, younger age and lower Model for End-Stage Liver Disease scores at listing were associated with an increased likelihood of a return to alcohol use (P < .05); length of abstinence was not a predictor. CONCLUSIONS Our prospective program provided direct monitoring and relapse prevention treatment for patients with ALD and with less than 6 months of abstinence and resulted in a reduction of post-transplantation return to drinking. This pilot study provides a framework for the future of more equitable transplant care.
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Affiliation(s)
- Lauren Carrique
- Ajmera Transplant Centre, University Health Network, Toronto, Canada
| | - Jill Quance
- Ajmera Transplant Centre, University Health Network, Toronto, Canada
| | - Adrienne Tan
- Ajmera Transplant Centre, University Health Network, Toronto, Canada; Department of Psychiatry, University of Toronto, Toronto, Canada; Centre for Mental Health, University Health Network, Toronto, Canada
| | - Susan Abbey
- Ajmera Transplant Centre, University Health Network, Toronto, Canada; Department of Psychiatry, University of Toronto, Toronto, Canada
| | - Isabel Sales
- Ajmera Transplant Centre, University Health Network, Toronto, Canada
| | - Les Lilly
- Ajmera Transplant Centre, University Health Network, Toronto, Canada; Department of Medicine, University of Toronto, Toronto, Canada
| | - Mamatha Bhat
- Ajmera Transplant Centre, University Health Network, Toronto, Canada; Department of Medicine, University of Toronto, Toronto, Canada
| | - Zita Galvin
- Ajmera Transplant Centre, University Health Network, Toronto, Canada; Department of Medicine, University of Toronto, Toronto, Canada
| | - Mark Cattral
- Ajmera Transplant Centre, University Health Network, Toronto, Canada
| | - Anand Ghanekar
- Ajmera Transplant Centre, University Health Network, Toronto, Canada
| | - Ian McGilvray
- Ajmera Transplant Centre, University Health Network, Toronto, Canada
| | - Trevor Reichman
- Ajmera Transplant Centre, University Health Network, Toronto, Canada
| | | | - Blayne Sayed
- Ajmera Transplant Centre, University Health Network, Toronto, Canada
| | - Markus Selzner
- Ajmera Transplant Centre, University Health Network, Toronto, Canada
| | - Marie-Josée Lynch
- Ajmera Transplant Centre, University Health Network, Toronto, Canada; Department of Psychiatry, University of Toronto, Toronto, Canada; Centre for Mental Health, University Health Network, Toronto, Canada
| | - Nazia Selzner
- Ajmera Transplant Centre, University Health Network, Toronto, Canada; Department of Medicine, University of Toronto, Toronto, Canada.
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26
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Petagine L, Zariwala MG, Patel VB. Alcoholic liver disease: Current insights into cellular mechanisms. World J Biol Chem 2021; 12:87-103. [PMID: 34630912 PMCID: PMC8473419 DOI: 10.4331/wjbc.v12.i5.87] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/30/2021] [Revised: 07/20/2021] [Accepted: 08/12/2021] [Indexed: 02/06/2023] Open
Abstract
Alcoholic liver disease (ALD) due to chronic alcohol consumption is a significant global disease burden and a leading cause of mortality. Alcohol abuse induces a myriad of aberrant changes in hepatocytes at both the cellular and molecular level. Although the disease spectrum of ALD is widely recognized, the precise triggers for disease progression are still to be fully elucidated. Oxidative stress, mitochondrial dysfunction, gut dysbiosis and altered immune system response plays an important role in disease pathogenesis, triggering the activation of inflammatory pathways and apoptosis. Despite many recent clinical studies treatment options for ALD are limited, especially at the alcoholic hepatitis stage. We have therefore reviewed some of the key pathways involved in the pathogenesis of ALD and highlighted current trials for treating patients.
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Affiliation(s)
- Lucy Petagine
- Center for Nutraceuticals, School of Life Sciences, University of Westminster, London W1W 6UW, United Kingdom
| | - Mohammed Gulrez Zariwala
- Center for Nutraceuticals, School of Life Sciences, University of Westminster, London W1W 6UW, United Kingdom
| | - Vinood B Patel
- Center for Nutraceuticals, School of Life Sciences, University of Westminster, London W1W 6UW, United Kingdom
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27
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El-Khateeb E, Achour B, Al-Majdoub ZM, Barber J, Rostami-Hodjegan A. Non-uniformity of Changes in Drug-Metabolizing Enzymes and Transporters in Liver Cirrhosis: Implications for Drug Dosage Adjustment. Mol Pharm 2021; 18:3563-3577. [PMID: 34428046 PMCID: PMC8424631 DOI: 10.1021/acs.molpharmaceut.1c00462] [Citation(s) in RCA: 43] [Impact Index Per Article: 10.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
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Liver cirrhosis is
a chronic disease that affects the liver structure,
protein expression, and overall metabolic function. Abundance data
for drug-metabolizing enzymes and transporters (DMET) across all stages
of disease severity are scarce. Levels of these proteins are crucial
for the accurate prediction of drug clearance in hepatically impaired
patients using physiologically based pharmacokinetic (PBPK) models,
which can be used to guide the selection of more precise dosing. This
study aimed to experimentally quantify these proteins in human liver
samples and assess how they can impact the predictive performance
of the PBPK models. We determined the absolute abundance of 51 DMET
proteins in human liver microsomes across the three degrees of cirrhosis
severity (n = 32; 6 mild, 13 moderate, and 13 severe),
compared to histologically normal controls (n = 14),
using QconCAT-based targeted proteomics. The results revealed a significant
but non-uniform reduction in the abundance of enzymes and transporters,
from control, by 30–50% in mild, 40–70% in moderate,
and 50–90% in severe cirrhosis groups. Cancer and/or non-alcoholic
fatty liver disease-related cirrhosis showed larger deterioration
in levels of CYP3A4, 2C8, 2E1, 1A6, UGT2B4/7, CES1, FMO3/5, EPHX1,
MGST1/3, BSEP, and OATP2B1 than the cholestasis set. Drug-specific
pathways together with non-uniform changes of abundance across the
enzymes and transporters under various degrees of cirrhosis necessitate
the use of PBPK models. As case examples, such models for repaglinide,
dabigatran, and zidovudine were successful in recovering disease-related
alterations in drug exposure. In conclusion, the current study provides
the biological rationale behind the absence of a single dose adjustment
formula for all drugs in cirrhosis and demonstrates the utility of
proteomics-informed PBPK modeling for drug-specific dose adjustment
in liver cirrhosis.
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Affiliation(s)
- Eman El-Khateeb
- Centre for Applied Pharmacokinetic Research, University of Manchester, Manchester M13 9PT, U.K.,Clinical Pharmacy Department, Faculty of Pharmacy, Tanta University, Tanta 31527, Egypt
| | - Brahim Achour
- Centre for Applied Pharmacokinetic Research, University of Manchester, Manchester M13 9PT, U.K
| | - Zubida M Al-Majdoub
- Centre for Applied Pharmacokinetic Research, University of Manchester, Manchester M13 9PT, U.K
| | - Jill Barber
- Centre for Applied Pharmacokinetic Research, University of Manchester, Manchester M13 9PT, U.K
| | - Amin Rostami-Hodjegan
- Centre for Applied Pharmacokinetic Research, University of Manchester, Manchester M13 9PT, U.K.,Certara UK Ltd. (Simcyp Division), Sheffield S1 2BJ, U.K
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Greenberg R, Goldberg A, Anthony S, Buchman DZ, Delaney S, Gruben V, Holdsworth S, Le Foll B, Leung M, Lien D, Lynch MJ, Selzner N, Chandler JA, Fortin MC. Canadian Society of Transplantation White Paper: Ethical and Legal Considerations for Alcohol and Cannabis Use in Solid Organ Listing and Allocation. Transplantation 2021; 105:1957-1964. [PMID: 33587429 PMCID: PMC8376271 DOI: 10.1097/tp.0000000000003618] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2020] [Revised: 11/16/2020] [Accepted: 11/20/2020] [Indexed: 11/26/2022]
Abstract
Alcohol and cannabis use as a contraindication to organ transplantation is a controversial issue. Until recently, patients in Canada with alcohol-associated liver disease were required to demonstrate abstinence for 6 mo to receive a liver transplant. There is no equivalent rule that is applied consistently for cannabis use. There is some evidence that alcohol and cannabis use disorder pretransplant could be associated with worse outcomes posttransplantation. However, early liver transplantation for patients with alcohol-associated liver disease in France and in the United States has led to challenges of the 6-mo abstinence rule in Canada in the media. It has also resulted in several legal challenges arguing that the rule violates human rights laws regarding discrimination in the provision of medical services and that the rule is also unconstitutional (this challenge is still before the court). Recent legalization of cannabis use for adults in Canada has led to questions about the appropriateness of limiting transplant access based on cannabis use. The ethics committee of the Canadian Society of Transplantation was asked to provide an ethical analysis of cannabis and alcohol abstinence policies. Our conclusions were as follows: neither cannabis use nor the 6-mo abstinence rule for alcohol use should be an absolute contraindication to transplantation, and transplant could be offered to selected patients, further research should be conducted to ensure evidence-based policies; and the transplant community has a duty not to perpetuate stigma associated with alcohol and cannabis use disorders.
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Affiliation(s)
- Rebecca Greenberg
- Faculty of Medicine, University of Toronto, Toronto, ON, Canada
- Mount Sinai Hospital, Toronto, ON, Canada
| | - Aviva Goldberg
- Max Rady College of Medicine, University of Manitoba, Winnipeg, MB, Canada
- Canadian Donation and Transplantation Research Program, Edmonton, AB, Canada
| | - Samantha Anthony
- Faculty of Medicine, University of Toronto, Toronto, ON, Canada
- Canadian Donation and Transplantation Research Program, Edmonton, AB, Canada
- Factor-Inwentash Faculty of Social Work, University of Toronto, ON, Canada
| | - Daniel Z. Buchman
- Dalla Lana School of Public Health, University of Toronto, Toronto, ON, Canada
- University Health Network, Toronto, ON, Canada
| | | | - Vanessa Gruben
- Canadian Donation and Transplantation Research Program, Edmonton, AB, Canada
- Faculty of Law, University of Ottawa, Ottawa, ON, Canada
| | - Sandra Holdsworth
- Canadian Donation and Transplantation Research Program, Edmonton, AB, Canada
| | - Bernard Le Foll
- Faculty of Medicine, University of Toronto, Toronto, ON, Canada
- Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, ON, Canada
| | | | - Dale Lien
- Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB, Canada
| | - Marie-Josee Lynch
- Faculty of Medicine, University of Toronto, Toronto, ON, Canada
- Toronto General Research Institute, Toronto, ON, Canada
| | - Nazia Selzner
- Faculty of Medicine, University of Toronto, Toronto, ON, Canada
- Canadian Donation and Transplantation Research Program, Edmonton, AB, Canada
- Toronto General Research Institute, Toronto, ON, Canada
| | - Jennifer A. Chandler
- Canadian Donation and Transplantation Research Program, Edmonton, AB, Canada
- Faculty of Law, University of Ottawa, Ottawa, ON, Canada
| | - Marie-Chantal Fortin
- Canadian Donation and Transplantation Research Program, Edmonton, AB, Canada
- Centre de recherche du CHUM, Montreal, QC, Canada
- Faculty of Medicine, University of Montreal, QC, Canada
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29
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Herrick-Reynolds KM, Punchhi G, Greenberg RS, Strauss AT, Boyarsky BJ, Weeks-Groh SR, Krach MR, Anders RA, Gurakar A, Chen PH, Segev DL, King EA, Philosophe B, Ottman SE, Wesson RN, Garonzik-Wang JM, Cameron AM. Evaluation of Early vs Standard Liver Transplant for Alcohol-Associated Liver Disease. JAMA Surg 2021; 156:1026-1034. [PMID: 34379106 DOI: 10.1001/jamasurg.2021.3748] [Citation(s) in RCA: 47] [Impact Index Per Article: 11.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
Importance Traditionally, liver transplant (LT) for alcohol-associated liver disease (ALD) requires 6 months of abstinence. Although early LT before 6 months of abstinence has been associated with decreased mortality for decompensated ALD, this practice remains controversial and concentrated at a few centers. Objective To define patient, allograft, and relapse-free survival in early LT for ALD, and to investigate the association between these survival outcomes and early vs standard LT. Design, Setting, and Participants This cohort study analyzed all patients with ALD who underwent their first LT at a single academic referral center between October 1, 2012, and November 13, 2020. Patients with known pretransplant hepatocellular carcinoma, hepatitis B or C, or an alternative cause of liver failure were excluded. Follow-up period was defined as the time from LT to the most recent encounter with a transplant center or death. Exposures The exposure of interest was early LT, which was defined as less than 180 days of pre-LT abstinence. Standard LT was defined as 180 days or more of pre-LT abstinence. Patients were separated into early LT and standard LT by time from abstinence to LT. Main Outcomes and Measures The outcomes were patient, allograft, relapse-free, and hazardous relapse-free survival for patients who underwent early LT or standard LT. These groups were compared by log-rank testing of Kaplan-Meier estimates. Hazardous relapse was defined as binge, at-risk, or frequent drinking. Abstinence was reassessed at the most recent follow-up visit for all patients. Results Of the 163 patients with ALD included in this study, 88 (54%) underwent early LT and 75 (46%) underwent standard LT. This cohort had a mean (SD) age at transplant of 52 (10) years and was predominantly composed of 108 male patients (66%). Recipients of early LT vs standard LT were younger (median [interquartile range (IQR)] age, 49.7 [39.0-54.2] years vs 54.6 [48.7-60.0] years; P < .001) and had a higher median (IQR) Model for End-stage Liver Disease score at listing (35.0 [29.0-39.0] vs 20.0 [13.0-26.0]; P < .001). Both recipients of early LT and standard LT had similar 1-year patient survival (94.1% [95% CI, 86.3%-97.5%] vs 95.9% [95% CI, 87.8%-98.7%]; P = .60), allograft survival (92.7% [95% CI, 84.4%-96.7%] vs 90.5% [95% CI, 81.0%-95.3%]; P = .42), relapse-free survival (80.4% [95% CI, 69.1%-88.0%] vs 83.5% [95% CI, 72.2%-90.6%]; P = .41), and hazardous relapse-free survival (85.8% [95% CI, 75.1%-92.2%] vs 89.6% [95% CI, 79.5%-94.9%]; P = .41). Conclusions and Relevance Adherence to the 6-month rule was not associated with superior patient survival, allograft survival, or relapse-free survival among selected patients. This finding suggests that patients with ALD should not be categorically excluded from LT solely on the basis of 6 months of abstinence, but rather alternative selection criteria should be identified that are based on need and posttransplant outcomes.
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Affiliation(s)
- Kayleigh M Herrick-Reynolds
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland.,Department of Surgery, Walter Reed National Military Medical Center, Bethesda, Maryland
| | - Gopika Punchhi
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Ross S Greenberg
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Alexandra T Strauss
- Division of Gastroenterology and Hepatology, Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Brian J Boyarsky
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Sharon R Weeks-Groh
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Michelle R Krach
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Robert A Anders
- Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Ahmet Gurakar
- Division of Gastroenterology and Hepatology, Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Po-Hung Chen
- Division of Gastroenterology and Hepatology, Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Dorry L Segev
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland.,Department of Epidemiology, Johns Hopkins School of Public Health, Baltimore, Maryland
| | - Elizabeth A King
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Benjamin Philosophe
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Shane E Ottman
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Russell N Wesson
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland
| | | | - Andrew M Cameron
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland
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30
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Cotter TG, Sandıkçı B, Paul S, Gampa A, Wang J, Te H, Pillai A, Reddy KG, di Sabato D, Little EC, Sundaram V, Fung J, Lucey MR, Charlton M. Liver transplantation for alcoholic hepatitis in the United States: Excellent outcomes with profound temporal and geographic variation in frequency. Am J Transplant 2021; 21:1039-1055. [PMID: 32531107 DOI: 10.1111/ajt.16143] [Citation(s) in RCA: 68] [Impact Index Per Article: 17.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2020] [Revised: 05/28/2020] [Accepted: 06/06/2020] [Indexed: 01/25/2023]
Abstract
Medical-refractory severe alcoholic hepatitis (AH) has a high mortality. The national frequency, longer term outcomes and regional practices of AH liver transplantation (LT) in the United States are not well described, despite the increasing mortality from alcohol-associated liver disease. We analyzed the trends in frequency and outcomes of UNOS data on 39 455 adult patients who underwent LT from 2014 to 2019, including AH LT recipients. LTs for AH increased 5-fold, from 28 in 2014 to 138 in 2019, varying 8-fold between UNOS regions. Three transplant centers accounted for 50%-90% of AH LTs within each region. The number of transplant centers performing AH LTs increased from 14 in 2014 to 47 in 2019. AH patients were younger (mean = 39.4 years), had higher MELD scores (mean = 36.8), and were more often on dialysis (46.0%) and in ICU (38.4%), compared to other indications (all P < .05). One- and 5-year graft survivals for AH LT recipients were 91.7% and 81.9%, respectively. The frequency of AH LT is increasing rapidly, with excellent medium-term outcomes. An impact of AH recurrence on patient or graft survival is not apparent in this national analysis. There are marked geographic variations in practices, highlighting the lack of selection criteria standardization.
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Affiliation(s)
- Thomas G Cotter
- Center for Liver Diseases, The University of Chicago Medicine, Chicago, Illinois
| | | | - Sonali Paul
- Center for Liver Diseases, The University of Chicago Medicine, Chicago, Illinois
| | - Anuhya Gampa
- Division of Gastroenterology, NorthShore University Health System, University of Chicago, Evanston, Illinois
| | - Jennifer Wang
- Center for Liver Diseases, The University of Chicago Medicine, Chicago, Illinois
| | - Helen Te
- Center for Liver Diseases, The University of Chicago Medicine, Chicago, Illinois
| | - Anjana Pillai
- Center for Liver Diseases, The University of Chicago Medicine, Chicago, Illinois
| | - Kapuluru G Reddy
- Center for Liver Diseases, The University of Chicago Medicine, Chicago, Illinois
| | - Diego di Sabato
- Department of Surgery, Section of Abdominal Organ Transplantation, The University of Chicago Medicine, Chicago, Illinois
| | | | - Vinay Sundaram
- Division of Gastroenterology and Comprehensive Transplant Center, Cedars-Sinai Medical Center, Los Angeles, California
| | - John Fung
- Department of Surgery, Section of Abdominal Organ Transplantation, The University of Chicago Medicine, Chicago, Illinois
| | - Michael R Lucey
- Division of Gastroenterology and Hepatology, School of Medicine and Public Health, University of Wisconsin, Madison, Wisconsin
| | - Michael Charlton
- Center for Liver Diseases, The University of Chicago Medicine, Chicago, Illinois
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31
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Yohanathan L, Heimbach JK. The Impact of Allocation Changes on Patients with Hepatocellular Carcinoma. Clin Liver Dis 2020; 24:657-663. [PMID: 33012451 DOI: 10.1016/j.cld.2020.07.003] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
Since the establishment of the Milan criteria, liver transplantation (LT) has been identified as an optimal therapy for selected patients with early stage, unresectable hepatocellular carcinoma (HCC) complicating cirrhosis, although a major limitation is the critical shortage of available deceased donor liver allografts. This review focuses on the evolution of liver allocation for HCC in the United States and what the most recent revisions to the allocation system mean for patients with HCC.
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Affiliation(s)
- Lavanya Yohanathan
- Mayo Clinic College of Medicine, 200 First Street Southwest, Rochester, MN 55905, USA
| | - Julie K Heimbach
- Mayo Clinic College of Medicine, 200 First Street Southwest, Rochester, MN 55905, USA.
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32
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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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33
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Ishigami M, Honda T, Kuzuya T, Ishizu Y, Ito T, Kamei H, Ogura Y, Fujishiro M. Revisiting the indications for liver transplantation in cirrhotic patients considering the long‐term outcomes of cirrhotic patients. JOURNAL OF HEPATO-BILIARY-PANCREATIC SCIENCES 2020; 27:655-662. [DOI: 10.1002/jhbp.777] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/18/2020] [Revised: 05/16/2020] [Accepted: 05/26/2020] [Indexed: 12/15/2022]
Affiliation(s)
- Masatoshi Ishigami
- Department of Gastroenterology and Hepatology Nagoya University School of Medicine Nagoya Japan
| | - Takashi Honda
- Department of Gastroenterology and Hepatology Nagoya University School of Medicine Nagoya Japan
| | - Teiji Kuzuya
- Department of Gastroenterology and Hepatology Nagoya University School of Medicine Nagoya Japan
| | - Yoji Ishizu
- Department of Gastroenterology and Hepatology Nagoya University School of Medicine Nagoya Japan
| | - Takanori Ito
- Department of Gastroenterology and Hepatology Nagoya University School of Medicine Nagoya Japan
| | - Hideya Kamei
- Department of Transplant Surgery Nagoya University School of Medicine Nagoya Japan
| | - Yasuhiro Ogura
- Department of Transplant Surgery Nagoya University School of Medicine Nagoya Japan
| | - Mitsuhiro Fujishiro
- Department of Gastroenterology and Hepatology Nagoya University School of Medicine Nagoya Japan
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34
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Kitajima T, Nagai S, Moonka D, Segal A, Abouljoud MS. It Is Not All About Pretransplant Factors: Posttransplant Complications Alter the Risk of Alcohol Relapse. Clin Liver Dis (Hoboken) 2020; 15:239-242. [PMID: 32617157 PMCID: PMC7326636 DOI: 10.1002/cld.959] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/28/2020] [Revised: 03/25/2020] [Accepted: 04/03/2020] [Indexed: 02/04/2023] Open
Abstract
Watch a video presentation of this article.
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Affiliation(s)
- Toshihiro Kitajima
- Division of Transplant and Hepatobiliary SurgeryHenry Ford HospitalDetroitMI
| | - Shunji Nagai
- Division of Transplant and Hepatobiliary SurgeryHenry Ford HospitalDetroitMI
| | - Dilip Moonka
- Divisions of Gastroenterology and HepatologyHenry Ford HospitalDetroitMI
| | - Antu Segal
- Transplant PsychologyHenry Ford HospitalDetroitMI
| | - Marwan S. Abouljoud
- Division of Transplant and Hepatobiliary SurgeryHenry Ford HospitalDetroitMI
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35
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Kitajima T, Nagai S, Segal A, Magee M, Blackburn S, Ellithorpe D, Yeddula S, Qadeer Y, Yoshida A, Moonka D, Brown K, Abouljoud MS. Posttransplant Complications Predict Alcohol Relapse in Liver Transplant Recipients. Liver Transpl 2020; 26:379-389. [PMID: 31872969 DOI: 10.1002/lt.25712] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/04/2019] [Accepted: 12/05/2019] [Indexed: 02/07/2023]
Abstract
Alcohol relapse after liver transplantation (LT) in patients with alcohol-related liver disease (ALD) is a major challenge. Although its association with pretransplant psychosocial factors was extensively studied, the impacts of posttransplant courses on alcohol relapse have not been well investigated. The aim of this study is to analyze peritransplant factors associated with posttransplant alcohol relapse in patients with ALD. This study evaluated 190 adult LT patients with ALD from 2013 to 2019. Risk factors for alcohol relapse were analyzed, focusing on posttransplant chronic complications, which were classified as Clavien-Dindo classification 3a or higher that lasted over 30 days. The posttransplant alcohol relapse rate was 13.7% (26/190) with a median onset time of 18.6 months after transplant. Multivariate Cox regression analysis revealed that posttransplant chronic complications were an independent risk factor for posttransplant alcohol relapse (hazard ratio [HR], 5.40; P = 0.001), along with psychiatric comorbidity (HR, 3.93; P = 0.001), history of alcohol relapse before LT (HR, 3.00; P = 0.008), and an abstinence period <1.5 years (HR, 12.05; P = 0.001). A risk prediction model was created using 3 pretransplant risk factors (psychiatric comorbidity, alcohol relapse before LT, and abstinence period <1.5 years). This model clearly stratified the risk of alcohol relapse into high-, moderate-, and low-risk groups (P < 0.001). Of the 26 patients who relapsed, 11 (42.3%) continued drinking, of whom 3 died of severe alcoholic hepatitis, and 13 (50.0%) achieved sobriety (outcomes for 2 patients were unknown). In conclusion, posttransplant chronic complications increased the risk of alcohol relapse. Recognition of posttransplant chronic complications in conjunction with the risk stratification model by pretransplant psychosocial factors would help with the prediction of posttransplant alcohol relapse.
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Affiliation(s)
- Toshihiro Kitajima
- Department of Transplant and Hepatobiliary Surgery, Henry Ford Hospital, Detroit, MI
| | - Shunji Nagai
- Department of Transplant and Hepatobiliary Surgery, Henry Ford Hospital, Detroit, MI
| | - Antu Segal
- Department of Transplant Psychology, Henry Ford Hospital, Detroit, MI
| | - Michelle Magee
- Henry Ford Transplant Institute, Henry Ford Hospital, Detroit, MI
| | | | - Donna Ellithorpe
- Henry Ford Transplant Institute, Henry Ford Hospital, Detroit, MI
| | - Siri Yeddula
- Department of Transplant and Hepatobiliary Surgery, Henry Ford Hospital, Detroit, MI
| | - Yusuf Qadeer
- Department of Transplant and Hepatobiliary Surgery, Henry Ford Hospital, Detroit, MI
| | - Atsushi Yoshida
- Department of Transplant and Hepatobiliary Surgery, Henry Ford Hospital, Detroit, MI
| | - Dilip Moonka
- Department of Gastroenterology and Hepatology, Henry Ford Hospital, Detroit, MI
| | - Kimberly Brown
- Department of Gastroenterology and Hepatology, Henry Ford Hospital, Detroit, MI
| | - Marwan S Abouljoud
- Department of Transplant and Hepatobiliary Surgery, Henry Ford Hospital, Detroit, MI
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36
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Walker S, Shojaee S. Nonmalignant pleural effusions: are they as benign as we think? PLEURAL DISEASE 2020. [DOI: 10.1183/2312508x.10024119] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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Deltenre P, Trépo E, Fujiwara N, Goossens N, Marot A, Dubois M, Spahr L, Henrion J, Moreno C, Hoshida Y. Gene signature-MELD score and alcohol relapse determine long-term prognosis of patients with severe alcoholic hepatitis. Liver Int 2020; 40:565-570. [PMID: 31568650 PMCID: PMC7056530 DOI: 10.1111/liv.14265] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/18/2019] [Revised: 09/03/2019] [Accepted: 09/19/2019] [Indexed: 12/16/2022]
Abstract
BACKGROUND The gene-signature-model for end stage liver disease (gs-MELD) score has been shown to be a strong predictor of 6-month survival in severe alcoholic hepatitis (AH). Currently, only a few studies have evaluated the long-term prognosis of patients with severe AH. AIM To assess the prognostic value of the gs-MELD score at 5 years in patients with severe AH. METHODS Forty-eight consecutive patients with AH (25 males, median age 52 years [95% IC: 48-56]) were included. RESULTS The median gs-MELD score was 2.6 (95% CI: 2.2-3.0). According to the gs-MELD score, 22 patients (46%) were considered to have a poor prognosis. During a median follow-up of 29 months (95% CI: 4-43), 19 patients (40%) were abstinent and 24 patients (50%) died. At 5 years, rates of survival were 61% (95% CI: 41-81) and 26% (95% CI: 11-55) in patients with low and high gs-MELD scores (P = .001), and 81% (95% CI: 58-96) and 22% (95% CI: 10-47) in abstainers and in consumers (P < .001) respectively. In multivariable competing risk regression modelling, gs-MELD score (subdistribution hazard ratio: 5.78, 95% CI: 2.17-15.38, P < .001) and recurrent alcohol consumption (subdistribution hazard ratio: 12.18, 95% CI: 3.16-46.95, P < .001) were independently associated with 5-year mortality. CONCLUSIONS Both gs-MELD score and alcohol consumption drive AH long-term prognosis. The gs-MELD score may guide the development of molecularly targeted therapies in AH.
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Affiliation(s)
- Pierre Deltenre
- Department of Gastroenterology, Hepatopancreatology, and Digestive Oncology, C.U.B. Hôpital Erasme, Université Libre de Bruxelles, Brussels, Belgium.,Department of Gastroenterology and Hepatology, Clinique St Luc, Bouge, Belgium,Correspondence: Pierre Deltenre, M.D., Ph.D., Department of Gastroenterology, Hepatopancreatology, and Digestive Oncology, C.U.B. Hôpital Erasme, Université Libre de Bruxelles, Brussels, Belgium; ; Yujin Hoshida, M.D., Ph.D., Division of Digestive and Liver Diseases, Department of Internal Medicine, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, TX 75390, USA;
| | - Eric Trépo
- Department of Gastroenterology, Hepatopancreatology, and Digestive Oncology, C.U.B. Hôpital Erasme, Université Libre de Bruxelles, Brussels, Belgium.,Laboratory of Experimental Gastroenterology, Université Libre de Bruxelles, Brussels, Belgium
| | - Naoto Fujiwara
- Division of Digestive and Liver Diseases, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, USA
| | - Nicolas Goossens
- Division of Digestive and Liver Diseases, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, USA.,Division of Gastroenterology and Hepatology, Geneva University Hospital, Geneva, Switzerland
| | - Astrid Marot
- Department of Gastroenterology and Hepatology, CHU UCL Namur, Université Catholique de Louvain, Yvoir, Belgium
| | - Margaux Dubois
- Division of Gastroenterology and Hepatology, Centre Hospitalier Universitaire Vaudois, University of Lausanne, Lausanne, Switzerland
| | - Laurent Spahr
- Division of Gastroenterology and Hepatology, Geneva University Hospital, Geneva, Switzerland
| | - Jean Henrion
- Department of Gastroenterology and Hepatology, Hôpital de Jolimont, Haine-Saint-Paul, Belgium
| | - Christophe Moreno
- Department of Gastroenterology, Hepatopancreatology, and Digestive Oncology, C.U.B. Hôpital Erasme, Université Libre de Bruxelles, Brussels, Belgium.,Laboratory of Experimental Gastroenterology, Université Libre de Bruxelles, Brussels, Belgium
| | - Yujin Hoshida
- Division of Digestive and Liver Diseases, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, USA.,Correspondence: Pierre Deltenre, M.D., Ph.D., Department of Gastroenterology, Hepatopancreatology, and Digestive Oncology, C.U.B. Hôpital Erasme, Université Libre de Bruxelles, Brussels, Belgium; ; Yujin Hoshida, M.D., Ph.D., Division of Digestive and Liver Diseases, Department of Internal Medicine, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, TX 75390, USA;
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38
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39
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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. Hepatology 2020; 71:306-333. [PMID: 31314133 DOI: 10.1002/hep.30866] [Citation(s) in RCA: 532] [Impact Index Per Article: 106.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/30/2019] [Accepted: 05/31/2019] [Indexed: 12/12/2022]
Affiliation(s)
- David W Crabb
- Indiana University School of Medicine, Indianapolis, IN
| | - Gene Y Im
- Icahn School of Medicine at Mount Sinai, New York, NY
| | - Gyongyi Szabo
- University of Massachusetts Medical School, Worcester, MA
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Notini L, Vasileva D, Orchanian-Cheff A, Buchman DZ. Ethical issues associated with solid organ transplantation and substance use: a scoping review. Monash Bioeth Rev 2019; 37:111-135. [PMID: 31749129 DOI: 10.1007/s40592-019-00100-1] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022]
Abstract
While solid organ transplantation for patients with substance use issues has attracted ethical discussion, a typology of the ethics themes has not been articulated in the literature. We conducted a scoping review of peer-reviewed literature on solid organ transplantation and substance use published between January 1997 and April 2016. We aimed to identify and develop a typology of the main ethical themes discussed in this literature and to identify gaps worthy of future research. Seventy articles met inclusion criteria and underwent inductive content analysis. Four main ethical themes were identified: (1) personal responsibility; (2) utility; (3) moral character; and (4) fairness. Each theme had multiple sub-themes and there was substantial overlap between themes. This scoping review identified a disproportionate emphasis in the literature regarding personal responsibility, which was referenced by each of the other themes, and a narrow focus on alcohol and liver. We recommend future research further investigate these connections between ethical themes and focus on ethical issues associated with transplants from organ groups other than liver for patients who use substances other than alcohol.
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Affiliation(s)
- Lauren Notini
- Joint Centre for Bioethics, University of Toronto, 155 College Street, Suite 754, Toronto, ON, M5T 1P8, Canada
- Melbourne Law School, The University of Melbourne, 185 Pelham Street, Carlton, VIC, 3053, Australia
- Biomedical Ethics Research Group, Murdoch Children's Research Institute, 50 Flemington Road, Parkville, VIC, 3052, Australia
| | | | - Ani Orchanian-Cheff
- Library and Information Services, University Health Network, Toronto, ON, Canada
| | - Daniel Z Buchman
- Joint Centre for Bioethics, University of Toronto, 155 College Street, Suite 754, Toronto, ON, M5T 1P8, Canada.
- Bioethics Department, Toronto Western Hospital, University Health Network, 399 Bathurst Street, Toronto, ON, M5T 2S8, Canada.
- Dalla Lana School of Public Health, University of Toronto, Toronto, ON, Canada.
- Krembil Research Institute, Toronto, ON, Canada.
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The Impact of Previous Acute Decompensation on the Long-Term Prognosis of Alcoholic Hepatitis in Cirrhotic Patients. J Clin Med 2019; 8:jcm8101600. [PMID: 31623316 PMCID: PMC6832392 DOI: 10.3390/jcm8101600] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2019] [Revised: 09/27/2019] [Accepted: 09/29/2019] [Indexed: 12/02/2022] Open
Abstract
Recurrent episodes of liver injury may either waste hepatic reserve or induce tolerance to further injury. We aimed to investigate whether the previous acute decompensation (AD) in liver cirrhosis (LC) affects the long-term transplant-free survival of patients with alcoholic hepatitis (AH). The survival data of 894 alcoholic LC cohort who had been admitted with acute deterioration in 21 academic hospitals in Korea were prospectively followed up. Enrolled patients were divided into three groups: Group 1, without AH; group 2, with nonsevere AH; and group 3, with severe AH. Although the baseline liver function was not different between the groups with or without previous AD, it was a significant predictor of poor long-term outcomes. The presence of previous AD negatively affected long-term overall survival (HR 1.62, 95% C.I. 1.20–2.18, p = 0.002) in groups 1 and 2 as a whole, independent of the Model for End-stage Liver Disease score. The three-month conditional survival was significantly worse in group 3 for up to 12 months in the presence of previous AD (p < 0.05). We concluded that not only the severity of AH, but also the prior AD is an important predictor of long-term outcomes in alcoholic LC patients with acute deterioration.
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Shasthry SM, Sharma MK, Shasthry V, Pande A, Sarin SK. Efficacy of Granulocyte Colony-stimulating Factor in the Management of Steroid-Nonresponsive Severe Alcoholic Hepatitis: A Double-Blind Randomized Controlled Trial. Hepatology 2019; 70:802-811. [PMID: 30664267 DOI: 10.1002/hep.30516] [Citation(s) in RCA: 63] [Impact Index Per Article: 10.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/17/2018] [Accepted: 01/15/2019] [Indexed: 12/17/2022]
Abstract
Severe alcoholic hepatitis (SAH) is often a progressive disease with high mortality and limited steroid responsiveness. Management options of steroid nonresponsive SAH (day 7 Lille score > 0.45) are limited. We assessed the efficacy and safety of granulocyte colony-stimulating factor (G-CSF) in steroid nonresponders. A randomized, double-blind, single-center trial (NCT01820208) was conducted between March 2013 and June 2016 in patients with histologically proven SAH, nonresponsive to 40 mg/day of prednisolone were randomized to G-CSF (12 doses, 300 μg each in 28 days) or placebo. Responders were continued with prednisolone. Of the 430 patients with SAH, 132 received steroid therapy. Of these, 33 (25%) were nonresponders and were randomized to G-CSF or placebo (14 in each group after exclusions). The baseline characteristics of both groups were comparable. The 28-day mortality was comparable between the groups (21.4%, G-CSF; 28.6%, placebo; P = 0.69). At 90 days, in the G-CSF but not in the placebo group, the Model for End-Stage Liver Disease reduced from 24.6 ± 3.9 to 19.4 ± 3.7 (P = 0.002) and Maddrey's discriminant function from 74.8 ± 22.8 to 57.4 ± 31 (P = 0.26). Infections were less common (28% versus 71%; P < 0.001) with lower 90-day mortality (35.7% versus 71.4%; P = 0.04) in the G-CSF than in the placebo group. On Cox regression analysis, receiving G-CSF (hazard ratio, 0.37; SD, 0.14-0.98; P = 0.04), and high baseline serum creatinine (hazard ratio, 4.12; SD, 1.7-10.3; P = 0.002) predicted day-90 outcomes in steroid nonresponsive SAH. Patients tolerated G-CSF without any major adverse events. Conclusion: Approximately one-quarter of patients with SAH do not respond to corticosteroid therapy. Administration of G-CSF is safe and helps to reduce the disease severity and 90-day mortality in these patients.
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Affiliation(s)
| | - Manoj Kumar Sharma
- Department of Hepatology, Institute of Liver & Biliary Sciences, New Delhi, India
| | - Varsha Shasthry
- Department of Hepatology, Institute of Liver & Biliary Sciences, New Delhi, India
| | - Apurva Pande
- Department of Hepatology, Institute of Liver & Biliary Sciences, New Delhi, India
| | - Shiv Kumar Sarin
- Department of Hepatology, Institute of Liver & Biliary Sciences, New Delhi, India
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Shipley LC, Kodali S, Singal AK. Recent updates on alcoholic hepatitis. Dig Liver Dis 2019; 51:761-768. [PMID: 31010745 DOI: 10.1016/j.dld.2019.03.023] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/17/2019] [Revised: 03/17/2019] [Accepted: 03/22/2019] [Indexed: 02/07/2023]
Abstract
Alcoholic hepatitis (AH) is a unique clinical syndrome that affects patients with chronic and active harmful alcohol consumption, and is associated with a high mortality of up to 40% at 1 month from presentation. It is important to assess disease severity and prognosis at time of presentation to identify patients at risk for high mortality and potential candidates for specific therapies. The cornerstone therapy for AH is enteral nutrition and abstinence. Steroids remain the only pharmacological option for severe AH however, adverse effects and lack of long-term benefit limit their routine use. Early liver transplantation is a potential salvage therapy for select severe AH patients. This review article comprehensively covers recent advances on the clinical unmet needs in the field including newer therapies and therapeutic targets, role of liver transplantation, and emerging biomarkers throughout the disease process from diagnosis, assessing prognosis and disease severity, and predicting responsiveness to medical therapies for severe AH.
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Affiliation(s)
- Lindsey C Shipley
- University of South Dakota Sanford School of Medicine, United States; Avera Transplant Institute, United States
| | - Sudha Kodali
- Division of Gastroenterology and Hepatology, Methodist Hospital, Houston, TX, United States
| | - Ashwani K Singal
- Division of Gastroenterology and Hepatology, University of South Dakota, Avera McKennan University Health Center and Transplant Institute, Sioux Falls, SD 57105, United States.
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Kubiliun MJ, Rich NE, Singal A, Mufti AR. Pro: Liver Transplantation Should Be Considered in Select Patients With Acute Alcoholic Hepatitis. Clin Liver Dis (Hoboken) 2019; 13:140-143. [PMID: 31236262 PMCID: PMC6544410 DOI: 10.1002/cld.780] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/15/2018] [Accepted: 11/02/2018] [Indexed: 02/04/2023] Open
Affiliation(s)
- Maddie J. Kubiliun
- Division of Digestive and Liver Diseases, Department of Internal MedicineUniversity of Texas Southwestern Medical CenterDallasTX
| | - Nicole E. Rich
- Division of Digestive and Liver Diseases, Department of Internal MedicineUniversity of Texas Southwestern Medical CenterDallasTX
| | - Amit Singal
- Division of Digestive and Liver Diseases, Department of Internal MedicineUniversity of Texas Southwestern Medical CenterDallasTX
| | - Arjmand R. Mufti
- Division of Digestive and Liver Diseases, Department of Internal MedicineUniversity of Texas Southwestern Medical CenterDallasTX
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Lee J, Lee JG, Jung I, Joo DJ, Kim SI, Kim MS. Development of a Korean Liver Allocation System using Model for End Stage Liver Disease Scores: A Nationwide, Multicenter study. Sci Rep 2019; 9:7495. [PMID: 31097768 PMCID: PMC6522508 DOI: 10.1038/s41598-019-43965-2] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2018] [Accepted: 05/01/2019] [Indexed: 02/08/2023] Open
Abstract
The previous Korean liver allocation system was based on Child-Turcotte-Pugh scores, but increasing numbers of deceased donors created a pressing need to develop an equitable, objective allocation system based on model for end-stage liver disease scores (MELD scores). A nationwide, multicenter, retrospective cohort study of candidates registered for liver transplantation from January 2009 to December 2011 was conducted at 11 transplant centers. Classification and regression tree (CART) analysis was used to stratify MELD score ranges according to waitlist survival. Of the 2702 patients that registered for liver transplantation, 2248 chronic liver disease patients were eligible. CART analysis indicated several MELD scores significantly predicted waitlist survival. The 90-day waitlist survival rates of patients with MELD scores of 31-40, 21-30, and ≤20 were 16.2%, 64.1%, and 95.9%, respectively (P < 0.001). Furthermore, the 14-day waitlist survival rates of severely ill patients (MELD 31-40, n = 240) with MELD scores of 31-37 (n = 140) and 38-40 (n = 100) were 64% and 43.4%, respectively (P = 0.001). Among patients with MELD > 20, presence of HCC did not affect waitlist survival (P = 0.405). Considering the lack of donor organs and geographic disparities in Korea, we proposed the use of a national broader sharing of liver for the sickest patients (MELD ≥ 38) to reduce waitlist mortality. HCC patients with MELD ≤ 20 need additional MELD points to allow them equitable access to transplantation. Based on these results, the Korean Network for Organ Sharing implemented the MELD allocation system in 2016.
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Affiliation(s)
- Juhan Lee
- Department of Surgery, Yonsei University College of Medicine, Seoul, Republic of Korea
- The Advisory Committee on Improving Liver Allocation, Seoul, Republic of Korea
| | - Jae Geun Lee
- Department of Surgery, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Inkyung Jung
- Department of Biostatistics and Medical Informatics, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Dong Jin Joo
- Department of Surgery, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Soon Il Kim
- Department of Surgery, Yonsei University College of Medicine, Seoul, Republic of Korea
- The Advisory Committee on Improving Liver Allocation, Seoul, Republic of Korea
| | - Myoung Soo Kim
- Department of Surgery, Yonsei University College of Medicine, Seoul, Republic of Korea.
- The Advisory Committee on Improving Liver Allocation, Seoul, Republic of Korea.
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Abstract
Identifying the optimal allocation policy with regard to hepatocellular carcinoma has been a persistent and evolving challenge. The current criteria for LT for HCC endorsed by the United Network of Organ Sharing (UNOS) are based on the Milan Criteria: a solitary tumor < 5 cm, or maximum of three tumors ≤ 3 cm each, without vascular invasion or evidence of extrahepatic spread. Contraindications to HCC exception points include: stage 1 HCC, ruptured HCC, extrahepatic HCC, and main portal or hepatic vein HCC invasion. Based upon projected waitlist dropout rates due to tumor growth, patients with HCC are assigned MELD standardized exception points. In addition to tumor size and number, AFP levels are an important predictor of recurrence of HCC following liver transplantation. Standardized exception points for HCC patients are not awarded to patients with AFP levels > 1000 ng/mL that do not decrease to < 500 ng/mL with treatment. Appeals for MELD exception points for patients with HCC vary widely between UNOS regions, with success of nonstandardized exception point appeals varying from 3.1 to 21% between regions. In an effort to make prioritization for HCC more consistent, a national liver review board (NLRB)is being convened that will focus on developing a national guidance for assessing common requests and addressing exception points, including for HCC.
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Outcomes of pancreatoduodenectomy in the cirrhotic patient: risk stratification and meta-analysis. HPB (Oxford) 2019; 21:301-309. [PMID: 30269948 DOI: 10.1016/j.hpb.2018.08.002] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/12/2018] [Revised: 07/26/2018] [Accepted: 08/01/2018] [Indexed: 12/12/2022]
Abstract
BACKGROUND Cirrhosis increases the risk of perioperative mortality in gastrointestinal surgery. Though cirrhosis is sometimes considered a contraindication to pancreatoduodenectomy (PD), few data are available in this patient population. The aim of the present study is to identify predictors of outcome in cirrhotic patients undergoing PD. METHODS Patients undergoing PD with biopsy-proved cirrhosis were evaluated. Primary endpoints were morbidity and mortality. Child score, MELD score, and radiographic evidence of portal hypertension (pHTN) were assessed for accuracy in preoperative risk stratification. A systematic review of the literature with meta-analysis was also performed to query morbidity and mortality of patients with cirrhosis reported to undergo PD. RESULTS Between 2005 and 2015, 36 cirrhotic patients underwent PD; three year follow-up was complete. Median Child score was 6 (range 5-10); median MELD score was 9 (range 7-18). Perioperative (90-day) mortality was 6/36. Median survival was 37 months (range 0.2-116). MELD ≥ 10 was associated with increased mortality (4/13 vs. 2/13, p = 0.004). Irrespective of Child or MELD score, those with pHTN had poor outcomes including significantly greater intraoperative blood loss, increased incidence of major complication, and length of stay. Postoperative mortality was significantly higher with pHTN (3/16 vs. 1/13, p = 0.012). CONCLUSION Pancreatoduodenectomy may be considered in carefully selected cirrhotic patients. MELD ≥ 10 predicts increased risk of postoperative mortality. Specific attention should be afforded to patients with preoperative radiographic evidence of portal hypertension as this group experiences poor outcomes irrespective of MELD or Child score.
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Liver transplantation for alcoholic hepatitis. J Hepatol 2019; 70:328-334. [PMID: 30658734 DOI: 10.1016/j.jhep.2018.11.007] [Citation(s) in RCA: 72] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/08/2018] [Revised: 11/05/2018] [Accepted: 11/08/2018] [Indexed: 12/19/2022]
Abstract
While liver transplantation (LT) has become a standard therapy for life-threatening alcohol related cirrhosis, LT as a treatment for severe alcoholic hepatitis (AH) has remained a taboo owing to concerns about the limited organ supply and the risk that the AH liver recipient will return to harmful drinking. The adoption of a 6-month abstinence requirement (the so-called '6-month rule') by many centres made AH a contraindication to LT. Given the high short-term mortality of severe AH, the lack of effective medical therapies and an increasing recognition that the 6-month rule unfairly excluded otherwise favourable candidates, a seminal European pilot study of LT for AH was performed. The success of the European study, which has been corroborated in retrospective analyses from the United States, represented a paradigm shift in therapy for highly selected patients with severe AH who are not responding to medical therapy. However, prospective studies are urgently needed to resolve the controversies that still surround the criteria for selection of patients with AH for LT and the long-term outcomes of the associated alcohol use disorder.
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Lin CC, Ou HY, Chuang YH, Chiang HJ, Yu CC, Lazo M, Tsang LLC, Huang TL, Lin CC, Chen CL, Cheng YF. Diffusion-Weighted Magnetic Resonance Imaging in Liver Graft Rejection. Transplant Proc 2018; 50:2675-2678. [PMID: 30401375 DOI: 10.1016/j.transproceed.2018.04.018] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/19/2018] [Revised: 03/22/2018] [Accepted: 04/06/2018] [Indexed: 01/24/2023]
Abstract
OBJECTIVE The purpose of this study is to evaluate the use of diffusion-weighted magnetic resonance imaging (DWMRI) in the assessment of graft rejection after liver transplantation (LT). METHODS From June 2017 to January 2018, 32 patients were included in the study with a mean age of 52.3 years. All patients underwent LT. The DWMRI was performed using the apparent diffusion coefficient map and measuring the different b-values (b-400, b-600, b-800, and b-1000). These measurements were compared with the histopathology results. Statistical analysis included t test, analysis of variance, and area under the curve for receiver operating characteristic (ROC). RESULTS There were 17 patients without rejection and 15 patients with liver graft rejection diagnosed by histopathology. The mean (SD) results between the nonrejection and rejection groups were as follows: b-400 = 1.568 (0.265) vs 1.519 (0.119) (P = .089), b-600 = 1.380 (0.181) vs 1.284 (0.106) (P = .039), b-800 = 1.262 (0.170) vs 1.170 (0.086) (P = .035), b-1000 = 1.109 (0.129) vs 1.098 (0.078) (P = .095); B-values × 10-3 mm2/s. Only b-600 (P = .04) and b-800 (P = .04) values have significant differences between the 2 groups. B-600 showed 90.48% sensitivity and 83.33% specificity (ROC area under the curve = 0.784; P < .001), and b-800 showed 90.38% sensitivity and 83.03% specificity (ROC area under the curve = 0.816; P < .001). The values obtained with the apparent diffusion coefficient in b-800 were clearly differentiated between the mild, moderate, and severe degrees of rejection (P < .001). CONCLUSION Measurement of b-600 and b-800 values using DWMRI may be used for the diagnosis of graft rejection after LT.
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Affiliation(s)
- C-C Lin
- Department of Diagnostic Radiology, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - H-Y Ou
- Department of Diagnostic Radiology, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Y-H Chuang
- Department of Diagnostic Radiology, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - H-J Chiang
- Department of Diagnostic Radiology, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - C-C Yu
- Department of Diagnostic Radiology, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - M Lazo
- Department of Diagnostic Radiology, St. Luke's Medical Center-Global City, Metro Malila, Philippines
| | - L L-C Tsang
- Department of Diagnostic Radiology, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - T-L Huang
- Department of Diagnostic Radiology, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - C-C Lin
- Liver Transplantation Program and Departments of Surgery, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - C-L Chen
- Liver Transplantation Program and Departments of Surgery, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Y-F Cheng
- Department of Diagnostic Radiology, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan.
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Pharmacokinetics and safety of glecaprevir and pibrentasvir in HCV-negative subjects with hepatic impairment. Eur J Clin Pharmacol 2018; 75:217-226. [PMID: 30341499 DOI: 10.1007/s00228-018-2576-4] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2018] [Accepted: 10/03/2018] [Indexed: 01/26/2023]
Abstract
PURPOSE This study characterized the effects of hepatic impairment on the pharmacokinetics and safety of glecaprevir and pibrentasvir, two direct-acting antivirals used for treatment of chronic HCV infection. METHODS HCV-negative subjects with normal hepatic function, or with mild (Child-Pugh [CP]-A), moderate (CP-B), or severe (CP-C) hepatic impairment received single doses of pibrentasvir 120 mg alone or with glecaprevir 200 mg or 300 mg (n = 6/functional group/dose). Plasma pharmacokinetics and protein binding were evaluated. Doses were separated by ≥ 14 days of washout. RESULTS For the approved combination of glecaprevir 300 mg with pibrentasvir 120 mg, glecaprevir AUC was increased by 33% (CP-A), to 2.0-fold (CP-B), and to 11-fold (CP-C) relative to normal subjects; pibrentasvir AUC was ≤ 26% different (CP-A or CP-B) and increased to 2.1-fold (CP-C). For glecaprevir 200 mg with pibrentasvir 120 mg, glecaprevir AUC was increased by 80% (CP-A) or to 2.8-fold (CP-B), while pibrentasvir AUC was unaffected in the same subjects (≤ 12% difference). Pibrentasvir 120 mg alone AUC increased 51% (CP-A), 31% (CP-B), and to 5.2-fold (CP-C). The unbound fraction of glecaprevir was higher in CP-C subjects than normal subjects and pibrentasvir protein binding was similar across groups. The most common adverse event was headache; no events were serious. CONCLUSION This study supported evaluation of the glecaprevir 300 mg with pibrentasvir 120-mg combination in HCV-infected subjects with CP-A hepatic impairment without dose adjustment. Elevated glecaprevir and/or pibrentasvir exposures are expected in HCV-infected patients with CP-B or CP-C hepatic impairment.
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