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Juanola A, Ma AT, Gratacós-Ginès J, Soria A, Solé C, Pose E, Ginès P. Renal Complications in Portal Hypertension. Clin Liver Dis 2024; 28:503-523. [PMID: 38945640 DOI: 10.1016/j.cld.2024.03.011] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 07/02/2024]
Abstract
Acute kidney injury (AKI) is a common complication among patients with decompensated cirrhosis and its development is associated with worse prognosis in terms of survival. Patients with decompensated cirrhosis may develop a unique type of AKI, known as hepatorenal syndrome (HRS-AKI), characterized by marked impairment of kidney function due to haemodynamic changes that occur in late stages of liver cirrhosis. Besides, patients with cirrhosis also may develop chronic alterations of kidney function (chronic kidney disease, CKD), the incidence of which is increasing markedly and may be associated with clinical complications. The aim of this review is to provide the reader with an update of the most relevant aspects of alterations of kidney function in patients with cirrhossi that may be useful for theri clinical practice.
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Affiliation(s)
- Adrià Juanola
- Liver Unit, Hospital Clínic of Barcelona, Barcelona, Catalunya, Spain; Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Catalunya, Spain; Centro de Investigación Biomédica en Red Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, Spain
| | - Ann Thu Ma
- Toronto Centre for Liver Disease Francis Family Liver Clinic, Toronto General Hospital, Toronto, Ontario, Canada
| | - Jordi Gratacós-Ginès
- Liver Unit, Hospital Clínic of Barcelona, Barcelona, Catalunya, Spain; Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Catalunya, Spain; Centro de Investigación Biomédica en Red Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, Spain
| | - Anna Soria
- Liver Unit, Hospital Clínic of Barcelona, Barcelona, Catalunya, Spain; Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Catalunya, Spain; Centro de Investigación Biomédica en Red Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, Spain
| | - Cristina Solé
- Department of Gastroenterology and Hepatology, Consorci Corporació Sanitària Parc Taulí, Sabadell, Spain
| | - Elisa Pose
- Liver Unit, Hospital Clínic of Barcelona, Barcelona, Catalunya, Spain; Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Catalunya, Spain; Centro de Investigación Biomédica en Red Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, Spain
| | - Pere Ginès
- Liver Unit, Hospital Clínic of Barcelona, Barcelona, Catalunya, Spain; Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Catalunya, Spain; Centro de Investigación Biomédica en Red Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, Spain; School of Medicine and Health Sciences, University of Barcelona, Barcelona, Catalunya, Spain.
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Becker EC, Siddique O, O'Sullivan DM, Dar W, Einstein M, Morgan G, Emmanuel B, Sotil EU, Richardson E, Serrano OK. Disparities in Liver Transplantation for Nonalcoholic Steatohepatitis in Women. Transplantation 2024; 108:e181-e186. [PMID: 38419160 DOI: 10.1097/tp.0000000000004964] [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: 03/02/2024]
Abstract
BACKGROUND Nonalcoholic steatohepatitis (NASH) is the fastest-growing indication for liver transplantation (LT). Sex disparities among patients with cirrhosis on the LT waitlist are well known. We wanted to understand these disparities further in women with end-stage liver disease patients listed for NASH cirrhosis in a contemporary cohort. METHODS We used data from the Scientific Registry of Transplant Recipients to assess sex racial, and ethnic differences in NASH patients listed for LT. Adults transplanted from August 1997 to June 2021 were included. Inferential statistics were used to evaluate differences with univariate and multivariate comparisons, including competitive risk analysis. RESULTS During the study time period, we evaluated 12 844 LT for NASH cirrhosis. Women were transplanted at a lower rate (46.5% versus 53.5%; P < 0.001) and higher model for end-stage liver disease (MELD) (23.8 versus 22.6; P < 0.001) than men. Non-White women were transplanted at a higher MELD (26.1 versus 23.1; P < 0.001) than White women and non-White male patients (26.1 versus 24.8; P < 0.001). Graft and patient survivals were significantly different ( P < 0.001) between non-White women and White women and men (White and non-White). CONCLUSIONS Evaluation of LT candidates in the United States demonstrates women with NASH cirrhosis have a higher MELD than men at LT. Additional disparities exist among non-White women with NASH as they have higher MELD and creatinine at LT compared with White women. After LT, non-White women have worse graft and patient survival compared with men or White women. These data indicate that non-White women with NASH are the most vulnerable on the LT waitlist.
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Affiliation(s)
- Erica C Becker
- Department of Internal Medicine, University of Connecticut Health, Farmington, CT
| | - Osama Siddique
- Department of Gastroenterology, Hartford Hospital, Hartford, CT
| | - David M O'Sullivan
- Department of Research Administration, Hartford HealthCare, Hartford, CT
| | - Wasim Dar
- Transplant Program, Hartford Hospital, Hartford, CT
- Department of Surgery, University of Connecticut Health, Farmington, CT
| | - Michael Einstein
- Department of Internal Medicine, University of Connecticut Health, Farmington, CT
- Transplant Program, Hartford Hospital, Hartford, CT
| | - Glyn Morgan
- Transplant Program, Hartford Hospital, Hartford, CT
- Department of Surgery, University of Connecticut Health, Farmington, CT
| | - Bishoy Emmanuel
- Transplant Program, Hartford Hospital, Hartford, CT
- Department of Surgery, University of Connecticut Health, Farmington, CT
| | - Eva U Sotil
- Department of Internal Medicine, University of Connecticut Health, Farmington, CT
- Transplant Program, Hartford Hospital, Hartford, CT
| | - Elizabeth Richardson
- Department of Internal Medicine, University of Connecticut Health, Farmington, CT
- Transplant Program, Hartford Hospital, Hartford, CT
| | - Oscar K Serrano
- Transplant Program, Hartford Hospital, Hartford, CT
- Department of Surgery, University of Connecticut Health, Farmington, CT
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Sanyal AJ, Husain M, Diab C, Mangla KK, Shoeb A, Lingvay I, Tapper EB. Cardiovascular disease in patients with metabolic dysfunction-associated steatohepatitis compared with metabolic dysfunction-associated steatotic liver disease and other liver diseases: A systematic review. AMERICAN HEART JOURNAL PLUS : CARDIOLOGY RESEARCH AND PRACTICE 2024; 41:100386. [PMID: 38623572 PMCID: PMC11016929 DOI: 10.1016/j.ahjo.2024.100386] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/05/2024] [Revised: 03/14/2024] [Accepted: 03/14/2024] [Indexed: 04/17/2024]
Abstract
The burden of cardiovascular disease (CVD) in patients with metabolic dysfunction-associated steatohepatitis (MASH) is poorly characterized, particularly vs other liver diseases including metabolic dysfunction-associated steatotic liver disease (MASLD). To identify available evidence, Embase, MEDLINE, and Cochrane database searches (main search: 2011-September 6, 2021; additional ad hoc search [MEDLINE only]: September 7, 2021-February 15, 2023), plus manual searches (2019-September 2021), were performed. Studies reporting CVD outcomes (angina, coronary artery disease [CAD], heart failure, myocardial infarction, peripheral artery disease, stroke, venous thromboembolic disease, and CV mortality) in adults with histologically confirmed MASH and MASLD or other liver diseases were identified, with studies of MASLD without confirmed MASH excluded. Of 8732 studies, 21 were included. An increased incidence or prevalence of CVD in patients with MASH vs other conditions was reported in 12 studies; odds ratios (OR), where reported, ranged from 3.12 (95 % CI: 1.33-5.32) to 4.12 (95 % CI: 1.91-8.90). The risk of CAD was increased in people with MASH in 6 of 7 studies, while the risk of stroke was increased in 6 of 6 studies, and heart failure in 2 of 4 studies. Three of 6 studies provided evidence of increased CVD-related mortality in patients with MASH vs those without. In conclusion, this literature review suggests that CVD is prevalent in patients with MASH and may contribute to increased mortality. Accordingly, cardiovascular risk factors should be aggressively managed in this population. Whether the CVD burden in patients with MASH is a direct consequence of MASH itself requires further study.
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Affiliation(s)
- Arun J. Sanyal
- Department of Internal Medicine, Medical College of Virginia, Richmond, VA, USA
| | - Mansoor Husain
- Ted Rogers Centre for Heart Research, Department of Medicine, University of Toronto, Toronto, ON, Canada
| | | | | | | | - Ildiko Lingvay
- Department of Internal Medicine/Endocrinology and Peter O'Donnel Jr School of Public Health, University of Texas Southwestern Medical Center, Dallas, TX, USA
| | - Elliot B. Tapper
- Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, MA, USA
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Gurun M, Brennan P, Handjiev S, Khatib A, Leith D, Dillon JF, Byrne CJ. Increased risk of chronic kidney disease and mortality in a cohort of people diagnosed with metabolic dysfunction associated steatotic liver disease with hepatic fibrosis. PLoS One 2024; 19:e0299507. [PMID: 38625981 PMCID: PMC11020899 DOI: 10.1371/journal.pone.0299507] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2023] [Accepted: 02/09/2024] [Indexed: 04/18/2024] Open
Abstract
BACKGROUND AND AIMS Metabolic dysfunction associated steatotic liver disease (MASLD) increases the risk of incident chronic kidney disease (CKD). However, the relative risk of CKD associated with increasing hepatic fibrosis, and consequent mortality risk, remains underexplored in real-world cohorts. In this study, we sought to establish whether hepatic fibrosis is associated with increased CKD risk and explore differences in mortality risk in a cohort of people living with MASLD, contingent on liver fibrosis and CKD status. METHODS This was an observational study of people who underwent routine liver function testing in Tayside, Scotland. MASLD was defined as: elevated ALT (>30 U/L) or GGT (>73 U/L); presence of diabetes, and/or hypertension, and/or obesity; weekly alcohol consumption <14 units (112g (+/-8g) alcohol); and negative screen for other aetiologies. Data was collected from digital health records. We used log-binomial models to quantify the risk of CKD among those with and without fibrosis, and Cox regression models to estimate differences in mortality risk dependent on fibrosis and CKD. RESULTS In our cohort (n = 2,046), 1,448 (70.8%) people had MASLD without fibrosis and 598 (29.2%) with fibrosis; 161 (11.1%) and 117 (19.6%) respectively also had CKD. After excluding individuals with structural, autoimmune, or malignant CKD (n = 22), liver fibrosis (n = 593; 18.9% with CKD) was associated with increased CKD risk (aRR = 1.31, 1.04-1.64, p = 0.021). Increased mortality risk was observed for those with liver fibrosis (aHR = 2.30, 1.49-3.56, p = <0.001) and was higher again among people with both fibrosis and CKD (aHR = 5.07, 3.07-8.39, p = <0.014). CONCLUSIONS Liver fibrosis was an independent risk factor for CKD in this cohort of people living with MASLD. Furthermore, those with MASLD with liver fibrosis had higher risk for mortality and this risk was further elevated among those with co-morbid CKD. Given the increased risk of CKD, and consequent mortality risk, among people living with MASLD fibrosis, renal function screening should be considered within liver health surveillance programmes and guidelines.
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Affiliation(s)
- Marc Gurun
- Molecular and Clinical Medicine, School of Medicine, University of Dundee, Ninewells Hospital and Medical School, Dundee, United Kingdom
| | - Paul Brennan
- Molecular and Clinical Medicine, School of Medicine, University of Dundee, Ninewells Hospital and Medical School, Dundee, United Kingdom
- Department of Gastroenterology, NHS Tayside, Ninewells Hospital and Medical School, Dundee, Scotland
| | - Sava Handjiev
- Department of Biochemical Medicine, NHS Tayside, Ninewells Hospital and Medical School, Dundee, Scotland
| | - Aseil Khatib
- Department of Gastroenterology, NHS Tayside, Ninewells Hospital and Medical School, Dundee, Scotland
| | - Damien Leith
- Population Health and Genomics, School of Medicine, University of Dundee, Ninewells Hospital and Medical School, Dundee, United Kingdom
| | - John F. Dillon
- Molecular and Clinical Medicine, School of Medicine, University of Dundee, Ninewells Hospital and Medical School, Dundee, United Kingdom
- Department of Gastroenterology, NHS Tayside, Ninewells Hospital and Medical School, Dundee, Scotland
| | - Christopher J. Byrne
- Molecular and Clinical Medicine, School of Medicine, University of Dundee, Ninewells Hospital and Medical School, Dundee, United Kingdom
- Directorate of Public Health, NHS Tayside, Kings Cross Hospital, Dundee, United Kingdom
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Pose E, Piano S, Juanola A, Ginès P. Hepatorenal Syndrome in Cirrhosis. Gastroenterology 2024; 166:588-604.e1. [PMID: 38246506 DOI: 10.1053/j.gastro.2023.11.306] [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: 06/16/2023] [Revised: 11/10/2023] [Accepted: 11/19/2023] [Indexed: 01/23/2024]
Abstract
Hepatorenal syndrome (HRS) is a form of kidney dysfunction that characteristically occurs in liver cirrhosis. It is characterized by a marked impairment of kidney function in response to circulatory and hemodynamic alterations that occur in advanced stages of liver cirrhosis, aggravated by systemic inflammation and bacterial translocation. The classical definitions of the types of HRS have been recently revisited and 2 forms of HRS have been redefined: the acute form, referred to as acute kidney injury (HRS-AKI), and the chronic form, referred to as chronic kidney disease. HRS-AKI is one of the most severe forms of AKI in patients with cirrhosis and it consists of an abrupt impairment of kidney function, frequently triggered by an infection, appearing in the setting of advanced decompensated cirrhosis. Differential diagnosis with other causes of AKI is crucial because HRS-AKI requires a specific treatment. Differential diagnosis with AKI-acute tubular necrosis may be challenging and kidney biomarkers may be useful in this setting. Treatment of HRS-AKI is based on the administration of vasoconstrictor drugs in combination with volume expansion with albumin. Prognosis of HRS-AKI is poor, and the ideal definitive treatment consists of liver transplantation or simultaneous liver-kidney transplantation. HRS-AKI has a big impact on patients' quality of life. Management of HRS-AKI remains challenging in specific situations such as alcohol-associated hepatitis or metabolic-associated steatotic liver disease cirrhosis. Developing preventive measures for HRS-AKI, improving its early identification, discovering new biomarkers for differential diagnosis, and improving the response to therapy are some of the unmet needs in the field of HRS-AKI.
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Affiliation(s)
- Elisa Pose
- Liver Unit, Hospital Clínic of Barcelona, Barcelona, Catalunya, Spain; Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Catalunya, Spain; Centro de Investigación Biomédica en Red Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, Spain
| | - Salvatore Piano
- Unit of Internal Medicine and Hepatology (UIMH), Department of Medicine - DIMED, University of Padova, Padova, Italy
| | - Adrià Juanola
- Liver Unit, Hospital Clínic of Barcelona, Barcelona, Catalunya, Spain; Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Catalunya, Spain; Centro de Investigación Biomédica en Red Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, Spain
| | - Pere Ginès
- Liver Unit, Hospital Clínic of Barcelona, Barcelona, Catalunya, Spain; School of Medicine and Health Sciences, University of Barcelona, Barcelona, Catalunya, Spain; Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Catalunya, Spain; Centro de Investigación Biomédica en Red Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, Spain.
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Danpanichkul P, Ng CH, Muthiah MD, Duangsonk K, Yong JN, Tan DJH, Lim WH, Wong ZY, Syn N, Tsusumi T, Takahashi H, Siddiqui MS, Wong VWS, Mantzoros CS, Huang DQ, Noureddin M, Loomba R, Sanyal AJ, Wijarnpreecha K. The silent burden of non-alcoholic fatty liver disease in the elderly: A global burden of disease analysis. Aliment Pharmacol Ther 2023; 58:1062-1074. [PMID: 37694808 DOI: 10.1111/apt.17714] [Citation(s) in RCA: 24] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/21/2023] [Revised: 07/25/2023] [Accepted: 08/30/2023] [Indexed: 09/12/2023]
Abstract
BACKGROUND Non-alcoholic fatty liver disease (NAFLD) represents a significant health threat worldwide. The growing trend towards an aging population, along with an alarming rise in obesity and diabetes, may have significant implications for the burden of NAFLD. AIM To assess the impact of NAFLD on the elderly. METHODS We utilised data from the Global Burden of Disease study between 2010 and 2019 to conduct a comprehensive analysis of the prevalence, mortality, and disability-adjusted life years (DALYs) associated with NAFLD in the elderly (65-89 years), stratified by region, nation, sociodemographic Index and sex. RESULTS Globally, there were an estimated 228 million cases, 87,230 deaths and 1.46 million DALYs attributed to NAFLD in the elderly. Geographically, the Western Pacific region had the highest burden of NAFLD in the elderly. From 2010 to 2019, there was an increasing prevalence rate in all areas, with the most pronounced change observed in the Western Pacific region (annual percentage change (APC) +0.95%, p < 0.001). Over the study period, there was a more rapid increase in NAFLD prevalence in men (APC +0.74%, p < 0.001) than in women (APC +0.63%, p < 0.001). In most regions, death and DALYs rates have declined, with the exception of the Americas, where there was a slight increase (APC +0.25%, p = 0.002 and 0.38%, p < 0.001, respectively). CONCLUSION Over the past decade, the burden of NAFLD in the elderly has been increasing, necessitating immediate and inclusive measures to tackle the rising burden.
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Affiliation(s)
- Pojsakorn Danpanichkul
- Immunology Unit, Department of Microbiology, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand
| | - Cheng Han Ng
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Mark D Muthiah
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore
- Division of Gastroenterology and Hepatology, Department of Medicine, National University Health System, Singapore
| | - Kwanjit Duangsonk
- Department of Microbiology, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand
| | - Jie Ning Yong
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Darren Jun Hao Tan
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Wen Hui Lim
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Zhen Yu Wong
- Nottingham City Hospital, Nottingham University Hospitals NHS Trust, Nottingham, UK
| | - Nicholas Syn
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Tsubasa Tsusumi
- Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, Kurume, Japan
| | - Hirokazu Takahashi
- Division of Metabolism and Endocrinology, Faculty of Medicine, Saga University, Saga, Japan
| | - Mohammad Shadab Siddiqui
- Department of Internal Medicine, Division of Gastroenterology, Hepatology and Nutrition, Virginia Commonwealth University, Richmond, Virginia, USA
| | - Vincent Wai-Sun Wong
- Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong, China
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, China
| | - Christos S Mantzoros
- Department of Internal Medicine, Boston VA Healthcare System, and Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA
- Faculty of Medicine, Harvard University, Boston, Massachusetts, USA
| | - Daniel Q Huang
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore
- Division of Gastroenterology and Hepatology, Department of Medicine, National University Health System, Singapore
| | | | - Rohit Loomba
- NAFLD Research Center, Division of Gastroenterology, University of California at San Diego, La Jolla, California, USA
- Division of Epidemiology, Department of Family Medicine and Public Health, University of California at San Diego, La Jolla, California, USA
| | - Arun J Sanyal
- Department of Internal Medicine, Division of Gastroenterology, Hepatology and Nutrition, Virginia Commonwealth University, Richmond, Virginia, USA
| | - Karn Wijarnpreecha
- Division of Gastroenterology and Hepatology, Department of Medicine, University of Arizona College of Medicine, Phoenix, Arizona, USA
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Banner University Medical Center, Phoenix, Arizona, USA
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Nysather J, Kaya E, Manka P, Gudsoorkar P, Syn WK. Nonalcoholic Fatty Liver Disease and Chronic Kidney Disease Cross Talk. ADVANCES IN KIDNEY DISEASE AND HEALTH 2023; 30:315-335. [PMID: 37657879 DOI: 10.1053/j.akdh.2023.04.001] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/12/2022] [Revised: 12/14/2022] [Accepted: 04/04/2023] [Indexed: 09/03/2023]
Abstract
Nonalcoholic fatty liver disease is a multisystem condition with effects beyond the liver. The identification of chronic kidney disease as an independent mediator of nonalcoholic fatty liver disease or associated entity with shared cardiometabolic risk factors remains controversial and continues to draw scientific interest. With increasing prevalence of nonalcoholic fatty liver disease and lack of Food and Drug Administration approved therapies, these shared cardiometabolic risk factors have drawn significant attention. In this article, we review shared pathophysiological mechanisms between nonalcoholic fatty liver disease and chronic kidney disease along with current treatment strategies that might be useful for both disease processes.
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Affiliation(s)
- Jacob Nysather
- Division of Nephrology and Kidney C.A.R.E. Program, University of Cincinnati, OH
| | - Eda Kaya
- Department of Internal Medicine, University Hospital Knappschaftskrankenhaus Bochum, Ruhr-University Bochum, Bochum, Germany
| | - Paul Manka
- Department of Internal Medicine, University Hospital Knappschaftskrankenhaus Bochum, Ruhr-University Bochum, Bochum, Germany
| | - Prakash Gudsoorkar
- Division of Nephrology and Kidney C.A.R.E. Program, University of Cincinnati, OH
| | - Wing-Kin Syn
- Division of Gastroenterology and Hepatology, Saint Louis University School of Medicine, St. Louis, MO; Division of Gastroenterology and Hepatology, Medical University of South Carolina, Charleston, SC; Department of Physiology, Faculty of Medicine and Nursing, University of the Basque Country, Euskal Herriko Unibertsitatea/Universidad del País Vasco, Leioa, Spain.
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Shalaby S, Battistella S, Zanetto A, Bizzaro D, Germani G, Paolo Russo F, Burra P. Changings and Challenges in Liver Transplantation for Nonalcoholic Fatty Liver Disease/Steatohepatitis. Clin Liver Dis 2023; 27:225-237. [PMID: 37024204 DOI: 10.1016/j.cld.2023.01.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/08/2023]
Abstract
Liver transplantation for nonalcoholic fatty liver disease/steatohepatitis (NAFLD/NASH) is increasing rapidly worldwide. Compared with alcohol and viral-related liver disease, NAFLD/NASH is more frequently associated with a systemic metabolic syndrome, which significantly affects other organs, requiring multidisciplinary management, in all phases of liver transplant.
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Affiliation(s)
- Sarah Shalaby
- Gastroenterology, Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, Padua University Hospital, Via Giustiniani 2, Padua 35128, Italy
| | - Sara Battistella
- Gastroenterology, Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, Padua University Hospital, Via Giustiniani 2, Padua 35128, Italy
| | - Alberto Zanetto
- Gastroenterology, Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, Padua University Hospital, Via Giustiniani 2, Padua 35128, Italy
| | - Debora Bizzaro
- Gastroenterology, Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, Padua University Hospital, Via Giustiniani 2, Padua 35128, Italy
| | - Giacomo Germani
- Gastroenterology, Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, Padua University Hospital, Via Giustiniani 2, Padua 35128, Italy
| | - Francesco Paolo Russo
- Gastroenterology, Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, Padua University Hospital, Via Giustiniani 2, Padua 35128, Italy
| | - Patrizia Burra
- Gastroenterology, Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, Padua University Hospital, Via Giustiniani 2, Padua 35128, Italy.
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9
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Yong JN, Lim WH, Ng CH, Tan DJH, Xiao J, Tay PWL, Lin SY, Syn N, Chew N, Nah B, Dan YY, Huang DQ, Tan EXX, Sanyal AJ, Noureddin M, Siddiqui MS, Muthiah MD. Outcomes of Nonalcoholic Steatohepatitis After Liver Transplantation: An Updated Meta-Analysis and Systematic Review. Clin Gastroenterol Hepatol 2023; 21:45-54.e6. [PMID: 34801743 DOI: 10.1016/j.cgh.2021.11.014] [Citation(s) in RCA: 30] [Impact Index Per Article: 15.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/01/2021] [Revised: 11/05/2021] [Accepted: 11/10/2021] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Nonalcoholic steatohepatitis (NASH) is the fastest growing indication of liver transplantation (LT) and is projected to be the leading cause of LT in the near future. The systemic pathogenesis of NASH increases risks of adverse clinical outcomes in patients with NASH receiving LT. Thus, this study aimed to conduct a time-dependent survival analysis between LT recipients with and without NASH using hazard ratios. METHODS A search was conducted on Medline and Embase databases for articles relating to LT outcomes for NASH recipients. A survival analysis was conducted of hazard ratios using the DerSimonian and Laird random-effects model with meta-regression. To account for censoring, survival data were reconstructed from published Kaplan-Meier curves and pooled to derive more accurate hazard estimates and all-cause mortality in NASH patients after LT. Pairwise meta-analysis was conducted to analyze secondary outcomes. RESULTS Fifteen studies involving 119,327 LT recipients were included in our analysis with a prevalence of NASH of 20.2% (95% CI, 12.9-30.2). The pooled 1-year, 5-year, and 10-year all-cause mortality in NASH patients after LT were 12.5%, 24.4%, and 37.9%, respectively. Overall survival was comparable between LT recipients for NASH vs non-NASH (hazard ratio, 0.910; 95% CI, 0.760 to 1.10; P = .34). Meta-regression showed that a higher model for end-stage liver disease score was associated with significantly worse overall survival in NASH compared with non-NASH after LT (95% CI, -0.0856 to -0.0181; P = .0026). CONCLUSIONS This study shows that patients undergoing LT for NASH cirrhosis have comparable complication rates, overall survival, and graft survival compared with non-NASH patients, although close monitoring may be indicated for those with higher model for end-stage liver disease scores.
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Affiliation(s)
| | | | | | | | | | | | | | | | - Nicholas Chew
- Department of Cardiology, National University Heart Centre
| | - Benjamin Nah
- Division of Gastroenterology and Hepatology, Department of Medicine, National University Hospital, Singapore; National University Centre for Organ Transplantation, National University Health System, Singapore
| | - Yock Young Dan
- Yong Loo Lin School of Medicine; Division of Gastroenterology and Hepatology, Department of Medicine, National University Hospital, Singapore; National University Centre for Organ Transplantation, National University Health System, Singapore; Cancer Science Institute of Singapore, National University of Singapore, Singapore
| | - Daniel Q Huang
- Yong Loo Lin School of Medicine; Division of Gastroenterology and Hepatology, Department of Medicine, National University Hospital, Singapore; National University Centre for Organ Transplantation, National University Health System, Singapore
| | - Eunice Xiang Xuan Tan
- Yong Loo Lin School of Medicine; Division of Gastroenterology and Hepatology, Department of Medicine, National University Hospital, Singapore; National University Centre for Organ Transplantation, National University Health System, Singapore
| | - Arun J Sanyal
- Division of Gastroenterology, Hepatology and Nutrition, Department of Internal Medicine, Virginia Commonwealth University, Richmond, Virginia
| | - Mazen Noureddin
- Cedars-Sinai Fatty Liver Program, Division of Digestive and Liver Diseases, Department of Medicine, Comprehensive Transplant Center, Cedars-Sinai Medical Centre, Los Angeles, California
| | - Mohammad Shadab Siddiqui
- Division of Gastroenterology, Hepatology and Nutrition, Department of Internal Medicine, Virginia Commonwealth University, Richmond, Virginia
| | - Mark D Muthiah
- Yong Loo Lin School of Medicine; Division of Gastroenterology and Hepatology, Department of Medicine, National University Hospital, Singapore; National University Centre for Organ Transplantation, National University Health System, Singapore.
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10
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Nah EH, Shin SK, Cho S, Park H, Kim S, Kwon E, Cho HI. Chronic kidney disease in nonalcoholic fatty liver disease at primary healthcare centers in Korea. PLoS One 2022; 17:e0279367. [PMID: 36538567 PMCID: PMC9767345 DOI: 10.1371/journal.pone.0279367] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2022] [Accepted: 12/05/2022] [Indexed: 12/24/2022] Open
Abstract
BACKGROUND The prevalence rates of nonalcoholic fatty liver disease (NAFLD) and chronic kidney disease (CKD) are expected to increase with the rising trends in diabetes and obesity associated with aging populations. Considering the impacts of coexistent NAFLD and CKD on morbidity and mortality rates, screening strategies for groups at high-risk of CKD are needed in community-dwelling individuals with NAFLD. The aims of this study were to determine the prevalence and distribution of CKD in NAFLD, as well as the risk factors for CKD and the correlation with liver fibrosis in asymptomatic individuals with NAFLD at primary healthcare centers in Korea. METHODS This retrospective cross-sectional study used data from 13 health-promotion centers in 10 Korean cities. Liver steatosis and stiffness were assessed using ultrasonography and magnetic resonance elastography (MRE), respectively. CKD was defined as an estimated glomerular filtration rate of <60 mL/min/1.73m2, and urine albumin-to-creatinine ratio or proteinuria. CKD was categorized into four stages: no CKD, mild, moderate, and severe. Comparisons according to the CKD stages in NAFLD were performed using Student's t-test or the chi-square test. Multivariable logistic regression analyses were performed to identify the risk factors for CKD and the correlation with liver fibrosis in NAFLD. RESULTS The prevalence of CKD was 12.4% in NAFLD. Albuminuria (16.2%) and proteinuria (8.0%) were more prevalent in NAFLD. NAFLD (odd ratio = 1.27, 95% CI = 1.09-1.48, P = 0.003) was independently associated with CKD of at least mild stage. However, there was no significant association between CKD of at least moderate stage and NAFLD after adjusting for age and a metabolically unhealthy status. CKD was associated with significant liver fibrosis as measured by MRE in NAFLD. CONCLUSION The presence of NAFLD and liver fibrosis were independent risk factors for CKD, but NAFLD was not an independent risk factor for the later stages of CKD.
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Affiliation(s)
- Eun-Hee Nah
- Health Promotion Research Institute, Korea Association of Health Promotion, Seoul, Korea
- * E-mail: ,
| | - Sug Kyun Shin
- Department of Internal Medicine, National Health Insurance Service Ilsan Hospital, Goyang, Korea
| | - Seon Cho
- Health Promotion Research Institute, Korea Association of Health Promotion, Seoul, Korea
| | - Hyeran Park
- Health Promotion Research Institute, Korea Association of Health Promotion, Seoul, Korea
| | - Suyoung Kim
- Health Promotion Research Institute, Korea Association of Health Promotion, Seoul, Korea
| | - Eunjoo Kwon
- Health Promotion Research Institute, Korea Association of Health Promotion, Seoul, Korea
| | - Han-Ik Cho
- MEDIcheck LAB, Korea Association of Health Promotion, Seoul, Korea
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11
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Aghemo A, Lai Q. Waiting list trends for liver transplantation in Italy: A snapshot from the future. Dig Liver Dis 2022; 54:1662-1663. [PMID: 36241534 DOI: 10.1016/j.dld.2022.09.013] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/26/2022] [Accepted: 09/29/2022] [Indexed: 11/13/2022]
Affiliation(s)
- Alessio Aghemo
- Division of Internal Medicine and Hepatology, Department of Gastroenterology, IRCCS Humanitas Research Hospital, Rozzano, Italy; Department of Biomedical Sciences, Humanitas University, Pieve Emanuele (MI), Italy
| | - Quirino Lai
- General Surgery and Organ Transplantation Unit, AOU Policlinico Umberto I, Sapienza University of Rome, Italy.
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12
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Sharma S, Stine JG, Verbeek T, Bezinover D. Management of Patients With Non-alcoholic Steatohepatitis Undergoing Liver Transplantation: Considerations for the Anesthesiologist. J Cardiothorac Vasc Anesth 2022; 36:2616-2627. [PMID: 34391652 DOI: 10.1053/j.jvca.2021.07.020] [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: 04/21/2021] [Revised: 06/24/2021] [Accepted: 07/09/2021] [Indexed: 11/11/2022]
Abstract
Non-alcoholic fatty liver disease (NAFLD) currently affects more than 25% of the world population and is rising. NAFLD can progress to non-alcoholic steatohepatitis that is associated with hepatic inflammation and fibrosis and can result in cirrhosis with subsequent liver failure. Non-alcoholic steatohepatitis (NASH) has now emerged as one of the leading etiologies for a liver transplant among adults in the United States. Given the rising incidence of liver transplants in patients with NASH-related cirrhosis, it is essential for anesthesiologists to be familiar with this condition as well as with NASH-related comorbidities and perioperative complications. Not only is NASH linked to metabolic syndrome, but it also is independently associated with cardiovascular disease, renal and thyroid dysfunction, obstructive sleep apnea (OSA), and a hypercoagulable state. The association with these conditions can affect the perioperative outcome of these patients, particularly because of increased mortality from major adverse cardiovascular events and sepsis. In order to decrease the perioperative morbidity and mortality of patients with NASH undergoing a liver transplant, a multidisciplinary approach to their perioperative management is essential, along with careful preoperative evaluation and aggressive intraoperative and postoperative monitoring. The focus of this review article is to provide a comprehensive overview of challenges associated with liver transplants in patients with NASH and to provide suggestions for appropriate patient selection and perioperative management.
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Affiliation(s)
- Sonal Sharma
- Department of Anesthesiology and Perioperative Medicine, Penn State Health Milton S. Hershey Medical Center, Hershey, PA.
| | - Jonathan G Stine
- Liver Center, Pennsylvania State University, Penn State Health Milton S Hershey Medical Center, Hershey, PA; Department of Medicine and Public Health Sciences, Pennsylvania State University, Penn State Milton S Hershey Medical Center, Hershey, PA; Division of Gastroenterology and Hepatology, Department of Medicine, Pennsylvania State University, Penn State Milton S Hershey Medical Center, Hershey, PA; Cancer Institute, Pennsylvania State University, Penn State Milton S Hershey Medical Center, Hershey, PA
| | - Thomas Verbeek
- Department of Anesthesiology and Perioperative Medicine, Penn State Health Milton S. Hershey Medical Center, Hershey, PA
| | - Dmitri Bezinover
- Department of Anesthesiology and Perioperative Medicine, Penn State Health Milton S. Hershey Medical Center, Hershey, PA; Liver Center, Pennsylvania State University, Penn State Health Milton S Hershey Medical Center, Hershey, PA
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13
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Zhou GP, Jiang YZ, Sun LY, Zhu ZJ. Clinical evidence of outcomes following liver transplantation in patients with nonalcoholic steatohepatitis: An updated meta-analysis and systematic review. Int J Surg 2022; 104:106752. [PMID: 35803515 DOI: 10.1016/j.ijsu.2022.106752] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/04/2022] [Revised: 06/18/2022] [Accepted: 06/20/2022] [Indexed: 12/29/2022]
Abstract
OBJECTIVE Nonalcoholic steatohepatitis (NASH) is a dramatically growing indication for liver transplantation (LT) worldwide and the posttransplant outcomes of NASH patients are currently under intensive investigation. This quantitative meta-analysis aimed to update the clinical evidence on outcomes of transplanted patients with NASH. METHODS We performed a systematic review and meta-analysis of studies (published up to September 15, 2021) that focused on LT outcomes for NASH versus non-NASH patients. Random-effect meta-analysis was conducted to calculate pooled odds ratios (ORs) and 95% confidence intervals (CIs). Subgroup analyses based on crucial baseline clinical characteristics and leave-one-out sensitivity analyses were conducted to assess the robustness of the pooled results. Meta-regression was used to evaluate study-level demographic, clinical, and biochemical characteristics to identify potential confounders affecting patient survival. RESULTS Twenty-two non-randomized comparative studies with 1,538 NASH and 6,014 non-NASH patients were included. 1- (OR, 0.94; 95% CI, 0.77-1.14), 3- (OR, 0.82; 95% CI, 1.00-1.22), and 5- (OR, 1.05; 95% CI, 0.84-1.31) year patient survival was equivalent between NASH and non-NASH recipients. NASH patients were associated with similar cardiovascular mortality (OR, 1.36; 95% CI, 0.89-2.09) and retransplantation rates (OR, 0.69; 95% CI, 1.03-1.53), lower graft failure-related mortality (OR, 0.11; 95% CI, 0.29-0.74), but higher sepsis-related mortality (OR, 1.53; 95% CI, 1.13-2.06). Meta-regression revealed that a higher proportion of patients with hepatocellular carcinoma (HCC) were associated with significantly superior overall patient survival at 1 (P = 0.044), 3 (P = 0.035) and 5 (P = 0.049) years after LT in NASH compared with non-NASH. CONCLUSIONS This study shows no difference in posttransplant survival between NASH and non-NASH patients. Carefully selected patients with NASH-related HCC may benefit from LT. NASH recipients should be managed with caution posttransplant, especially regarding the potentially high risk of sepsis-related death.
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Affiliation(s)
- Guang-Peng Zhou
- Liver Transplantation Center, National Clinical Research Center for Digestive Diseases, Beijing Friendship Hospital, Capital Medical University, Beijing, 101100, China; Clinical Center for Pediatric Liver Transplantation, Capital Medical University, Beijing, 101100, China
| | - Yi-Zhou Jiang
- Liver Transplantation Center, National Clinical Research Center for Digestive Diseases, Beijing Friendship Hospital, Capital Medical University, Beijing, 101100, China; Department of Critical Liver Diseases, Liver Research Center, Beijing Friendship Hospital, Capital Medical University, Beijing, 101100, China; Clinical Center for Pediatric Liver Transplantation, Capital Medical University, Beijing, 101100, China
| | - Li-Ying Sun
- Liver Transplantation Center, National Clinical Research Center for Digestive Diseases, Beijing Friendship Hospital, Capital Medical University, Beijing, 101100, China; Department of Critical Liver Diseases, Liver Research Center, Beijing Friendship Hospital, Capital Medical University, Beijing, 101100, China; Clinical Center for Pediatric Liver Transplantation, Capital Medical University, Beijing, 101100, China.
| | - Zhi-Jun Zhu
- Liver Transplantation Center, National Clinical Research Center for Digestive Diseases, Beijing Friendship Hospital, Capital Medical University, Beijing, 101100, China; Clinical Center for Pediatric Liver Transplantation, Capital Medical University, Beijing, 101100, China.
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14
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Burra P, Bizzaro D, Gonta A, Shalaby S, Gambato M, Morelli MC, Trapani S, Floreani A, Marra F, Brunetto MR, Taliani G, Villa E. Clinical impact of sexual dimorphism in non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH). Liver Int 2021; 41:1713-1733. [PMID: 33982400 DOI: 10.1111/liv.14943] [Citation(s) in RCA: 96] [Impact Index Per Article: 24.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/08/2020] [Revised: 05/05/2021] [Accepted: 05/06/2021] [Indexed: 12/11/2022]
Abstract
NAFLD/NASH is a sex-dimorphic disease, with a general higher prevalence in men. Women are at reduced risk of NAFLD compared to men in fertile age, whereas after menopause women have a comparable prevalence of NAFLD as men. Indeed, sexual category, sex hormones and gender habits interact with numerous NAFLD factors including cytokines, stress and environmental factors and alter the risk profiles and phenotypes of NAFLD. In the present review, we summarized the last findings about the influence of sex on epidemiology, pathogenesis, progression in cirrhosis, indication for liver transplantation and alternative therapies, including lifestyle modification and pharmacological strategies. We are confident that an appropriate consideration of sex, age, hormonal status and sociocultural gender differences will lead to a better understanding of sex differences in NAFLD risk, therapeutic targets and treatment responses and will aid in achieving sex-specific personalized therapies.
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Affiliation(s)
- Patrizia Burra
- Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, University Hospital of Padua, Padua, Italy
| | - Debora Bizzaro
- Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, University Hospital of Padua, Padua, Italy
| | - Anna Gonta
- Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, University Hospital of Padua, Padua, Italy
| | - Sarah Shalaby
- Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, University Hospital of Padua, Padua, Italy
| | - Martina Gambato
- Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, University Hospital of Padua, Padua, Italy
| | | | - Silvia Trapani
- Italian National Transplant Center, Italian National Institute of Health, Rome, Italy
| | - Annarosa Floreani
- University of Padova, Padua, Italy.,IRCCS Ospedale Sacro Cuore Don Calabria, Negrar, Italy
| | - Fabio Marra
- Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy
| | - Maurizia Rossana Brunetto
- Hepatology and Liver Physiopathology Laboratory and Internal Medicine, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy
| | - Gloria Taliani
- Infectious Diseases Unit, Department of Translational and Precision Medicine, Sapienza University of Rome, Rome, Italy
| | - Erica Villa
- Gastroenterology Unit, Azienda Ospedaliero-Universitaria Policlinico di Modena, Modena, Italy
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15
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Heda R, Yazawa M, Shi M, Bhaskaran M, Aloor FZ, Thuluvath PJ, Satapathy SK. Non-alcoholic fatty liver and chronic kidney disease: Retrospect, introspect, and prospect. World J Gastroenterol 2021; 27:1864-1882. [PMID: 34007127 PMCID: PMC8108029 DOI: 10.3748/wjg.v27.i17.1864] [Citation(s) in RCA: 26] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/10/2021] [Revised: 03/07/2021] [Accepted: 04/07/2021] [Indexed: 02/06/2023] Open
Abstract
With the growing prevalence of obesity and diabetes in the United States and across the world, a rise in the overall incidence and prevalence of non-alcoholic fatty liver disease (NAFLD) is expected. The risk factors for NAFLD are also associated with the development of chronic kidney disease (CKD). We review the epidemiology, risk factors, genetics, implications of gut dysbiosis, and specific pathogenic mechanisms linking NAFLD to CKD. Mechanisms such as ectopic lipid accumulation, cellular signaling abnormalities, and the interplay between fructose consumption and uric acid accumulation have led to the emergence of potential therapeutic implications for this patient population. Transplant evaluation in the setting of both NAFLD and CKD is also reviewed. Potential strategies for surveillance and management include the monitoring of comorbidities, the use of non-invasive fibrosis scoring systems, and the measurement of laboratory markers. Lastly, we discuss the management of patients with NAFLD and CKD, from preventative measures to experimental interventions.
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Affiliation(s)
- Rajiv Heda
- Department of Internal Medicine, Tulane University School of Medicine, New Orleans, LA 70112, United States
| | - Masahiko Yazawa
- Department of Nephrology and Hypertension, St. Marianna University School of Medicine, Kawasaki 216-8511, Japan
| | - Michelle Shi
- Department of Internal Medicine, Donald and Barbara Zucker School of Medicine, Northwell Health, Manhasset, NY 11030, United States
| | - Madhu Bhaskaran
- Department of Nephrology, Northwell Health/Zucker School of Medicine at Hosftra, Manhasset, NY 11030, United States
| | - Fuad Zain Aloor
- Department of Internal Medicine, Baylor College of Medicine, Houston, TX 77030, United States
| | - Paul J Thuluvath
- Institute of Digestive Health & Liver Diseases, Mercy Medical Center, Baltimore, MD 21202, United States
| | - Sanjaya K Satapathy
- Department of Internal Medicine, Donald and Barbara Zucker School of Medicine, Northwell Health, Manhasset, NY 11030, United States
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16
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Steggerda JA, Mahendraraj K, Todo T, Noureddin M. Clinical considerations in the management of non-alcoholic steatohepatitis cirrhosis pre- and post-transplant: A multi-system challenge. World J Gastroenterol 2020; 26:4018-4035. [PMID: 32821068 PMCID: PMC7403794 DOI: 10.3748/wjg.v26.i28.4018] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/06/2020] [Revised: 05/07/2020] [Accepted: 07/14/2020] [Indexed: 02/06/2023] Open
Abstract
Non-alcoholic steatohepatitis (NASH) is the most common chronic liver disease worldwide, and the fastest growing indication for liver transplantation in the United States. NASH is now the leading etiology for liver transplantation in women, the second leading indication for men, and the most common cause amongst recipients aged 65 years and older. Patients with end-stage liver disease related to NASH represent a unique and challenging patient population due the high incidence of associated comorbid diseases, including obesity, type 2 diabetes (T2D), and hypertension. These challenges manifest in the pre-liver transplantation period with increased waitlist times and waitlist mortality. Furthermore, these patients carry considerable risk of morbidity and mortality both before after liver transplantation, with high rates of T2D, cardiovascular disease, chronic kidney disease, poor nutrition, and disease recurrence. Successful transplantation for these patients requires identification and management of their comorbidities in the face of liver failure. Multidisciplinary evaluations include a thorough pre-transplant workup with a complete cardiac evaluation, control of diabetes, nutritional support, and even, potentially, consultation with a bariatric surgeon. This article provides a comprehensive review of the conditions and challenges facing patients with NASH cirrhosis undergoing liver transplantation and provides recommendations for evaluation and management to optimize them before liver transplantation to produce successful outcomes.
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Affiliation(s)
- Justin A Steggerda
- Department of Surgery, Division of Transplantation, Cedars-Sinai Medical Center, Los Angeles, CA 90048, United States
| | - Krishnaraj Mahendraraj
- Department of Surgery, Division of Transplantation, Cedars-Sinai Medical Center, Los Angeles, CA 90048, United States
| | - Tsuyoshi Todo
- Department of Surgery, Division of Transplantation, Cedars-Sinai Medical Center, Los Angeles, CA 90048, United States
| | - Mazen Noureddin
- Division of Digestive and Liver Diseases, Comprehensive Transplant Center, Cedars-Sinai Medical Center, Los Angeles, CA 90048, United States
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17
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Mantovani A, Zusi C, Dalbeni A, Grani G, Buzzetti E. Risk of Kidney Dysfunction IN Nafld. Curr Pharm Des 2020; 26:1045-1061. [DOI: 10.2174/1381612825666191026113119] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2019] [Accepted: 10/21/2019] [Indexed: 02/06/2023]
Abstract
Background:
The timely identification of traditional and non-traditional precursors and risk factors for
chronic kidney disease (CKD) (a common systemic disease defined as a decreased kidney function documented
by reduced glomerular filtration rate, or markers of kidney damage, or both) is relevant in clinical practice, as
CKD increases the risk of end-stage renal disease and other serious comorbidities. A possible relationship between
non-alcoholic fatty liver disease (NAFLD) (which is to date the most common chronic disease worldwide)
and CKD has recently gained significant attention of researchers.
Methods :
A systematic literature search using appropriate keywords was made in order to identify relevant articles
that have investigated the association between NAFLD and CKD.
Results:
Several observational studies and meta-analyses have reported the existence of an independent association
between NAFLD and risk of CKD in patients with and without diabetes. However, whilst the association
between NAFLD and risk of prevalent CKD is strong across various patient populations, whether NAFLD is
independently associated with the development and progression of CKD is still debatable. Moreover, emerging
evidence now suggests a potential association between patatin-like phospholipase domain-containing protein-3
(PNPLA3) rs738409 genotype (the most important genetic variant associated to NAFLD) and decreasing kidney
function, independent of NAFLD.
Conclusions :
Convincing evidence now indicates that CKD is increased among patients with NAFLD. For this
reason, patients with NAFLD should be regularly monitored for renal function and, on the other hand , NAFLD
should be considered in all patients with CKD, especially if they are obese or have type 2 diabetes.
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Affiliation(s)
- Alessandro Mantovani
- Section of Endocrinology, Diabetes and Metabolism, University and Azienda Ospedaliera Universitaria Integrata of Verona, Verona, Italy
| | - Chiara Zusi
- Section of Endocrinology, Diabetes and Metabolism, University and Azienda Ospedaliera Universitaria Integrata of Verona, Verona, Italy
| | - Andrea Dalbeni
- Section of General Medicine, Hypertension and Liver Unit, University and Azienda Ospedaliera Universitaria Integrata of Verona, Verona, Italy
| | - Giorgio Grani
- Department of Translational and Precision Medicine, Sapienza University of Rome, Rome, Italy
| | - Elena Buzzetti
- Division of Internal Medicine 2 and Center for Hemochromatosis, University of Modena and Reggio Emilia, Modena, Italy
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18
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Byrne CD, Targher G. NAFLD as a driver of chronic kidney disease. J Hepatol 2020; 72:785-801. [PMID: 32059982 DOI: 10.1016/j.jhep.2020.01.013] [Citation(s) in RCA: 286] [Impact Index Per Article: 57.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/09/2019] [Revised: 12/27/2019] [Accepted: 01/10/2020] [Indexed: 02/07/2023]
Abstract
Non-alcoholic fatty liver disease (NAFLD) and chronic kidney disease (CKD) are worldwide public health problems, affecting up to 25-30% (NAFLD), and up to 10-15% (CKD) of the general population. Recently, it has also been established that there is a strong association between NAFLD and CKD, regardless of the presence of potential confounding diseases such as obesity, hypertension and type 2 diabetes. Since NAFLD and CKD are both common diseases that often occur alongside other metabolic conditions, such as type 2 diabetes or metabolic syndrome, elucidating the relative impact of NAFLD on the risk of incident CKD presents a substantial challenge for investigators working in this research field. A growing body of epidemiological evidence suggests that NAFLD is an independent risk factor for CKD and recent evidence also suggests that associated factors such as metabolic syndrome, dysbiosis, unhealthy diets, platelet activation and processes associated with ageing could also contribute mechanisms linking NAFLD and CKD. This narrative review provides an overview of the literature on: a) the evidence for an association and causal link between NAFLD and CKD and b) the underlying mechanisms by which NAFLD (and factors strongly linked with NAFLD) may increase the risk of developing CKD.
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Affiliation(s)
- Christopher D Byrne
- Nutrition and Metabolism, Faculty of Medicine, University of Southampton, Southampton, UK; Southampton National Institute for Health Research Biomedical Research Centre, University Hospital Southampton, UK.
| | - Giovanni Targher
- Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, Verona, Italy.
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19
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Patrono D, Martini S, Romagnoli R. Liver Transplantation and NAFLD/NASH. NON-ALCOHOLIC FATTY LIVER DISEASE 2020:343-362. [DOI: 10.1007/978-3-319-95828-6_19] [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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20
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Samji NS, Verma R, Keri KC, Singal AK, Ahmed A, Rinella M, Bernstein D, Abdelmalek MF, Satapathy SK. Liver Transplantation for Nonalcoholic Steatohepatitis: Pathophysiology of Recurrence and Clinical Challenges. Dig Dis Sci 2019; 64:3413-3430. [PMID: 31312990 DOI: 10.1007/s10620-019-05716-1] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/06/2019] [Accepted: 07/02/2019] [Indexed: 02/08/2023]
Abstract
Nonalcoholic steatohepatitis is the fastest-growing indication for the liver transplant and a leading cause of hepatocellular carcinoma among patients listed for liver transplantation in the USA. Post-transplant nonalcoholic hepatic steatosis and steatohepatitis are frequent complications of liver transplantation. Nonalcoholic steatohepatitis poses a significant challenge in both pre- and post-transplant period due to its association with metabolic syndrome, coronary artery disease, chronic kidney disease, and obstructive sleep apnea. While optimal therapy is not yet available in the post-liver transplant setting, lifestyle interventions continue to remain as the mainstay of therapy for post-transplant nonalcoholic steatohepatitis. Early recognition with protocol biopsies and noninvasive modalities, along with modification of known risk factors, are the most effective methods to curtail the progression of nonalcoholic steatohepatitis in the absence of FDA-approved pharmacologic therapy.
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Affiliation(s)
- Naga Swetha Samji
- Tennova Cleveland Hospital, 2305 Chambliss Ave NW, Cleveland, TN, 37311, USA
| | - Rajanshu Verma
- Division of Transplant Surgery, Department of Surgery, Methodist University Hospital Transplant Institute, University of Tennessee Health Sciences Center, Memphis, TN, USA
| | | | - Ashwani K Singal
- University of South Dakota Sanford School of Medicine, Avera Transplant Institute, S. Cliff Ave, Sioux Falls, SD, 57105, USA
| | - Aijaz Ahmed
- Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, CA, USA
| | - Mary Rinella
- Department of Medicine, Northwestern University, Feinberg School of Medicine, Chicago, IL, USA
| | - David Bernstein
- Division of Hepatology and Sandra Atlas Bass Center for Liver Diseases, Northwell Health, Manhasset, NY, USA
| | - Manal F Abdelmalek
- Division of Gastroenterology/Hepatology, Duke University, 40 Duke Medicine Cir, Durham, NC, USA
| | - Sanjaya K Satapathy
- Division of Hepatology at Sandra Atlas Bass Center for Liver Diseases and Transplantation, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell Health, 400 Community Drive, Manhasset, NY, 11030, USA.
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21
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Qin S, Wang J, Zhou C, Zhang Y, Xu Y, Wang X, Wang S. The association between a non-invasive hepatic fibrosis score and urolithiasis among non-alcoholic fatty liver disease (NAFLD) patients in China: a cross-sectional study. BMJ Open 2019; 9:e027702. [PMID: 31471434 PMCID: PMC6721644 DOI: 10.1136/bmjopen-2018-027702] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/20/2022] Open
Abstract
OBJECTIVE Mounting data now support a strong link between the presence of non-alcoholic fatty liver disease (NAFLD) and an increased risk of urolithiasis. However, little is known on the association between hepatic fibrosis and the risk of urolithiasis among NAFLD patients. Therefore, this study aimed to investigate the prevalence of urolithiasis among NAFLD patients and determine whether the Fibrosis-4 (FIB-4) score, a surrogate marker of hepatic fibrosis, is associated with urolithiasis among NAFLD patients. DESIGN Cross-sectional studies. SETTING China. METHODS A total of 2058 adult patients with NAFLD were included in this study. Logistic regression analysis was used to detect the association between FIB-4 score and urolithiasis. Receiver operating characteristic (ROC) curve analysis was used to assess the diagnostic value of FIB-4 score for the detection of urolithiasis among NAFLD patients. RESULTS 200 (9.7%) individuals had ultrasonography-diagnosed urolithiasis among 2058 NAFLD patients. FIB-4 score (OR=1.58; 95% CI 1.06 to 2.31), age (OR=1.11; 95% CI 1.08 to 1.13), obesity (OR=3.16; 95% CI 2.29 to 4.39) and hyperuricemia (OR=3.79; 95% CI 2.67 to 5.36) were independent factors associated with urolithiasis among NAFLD patients. Moreover, a novel algorithm including multiple variables (FIB-4 score, age, obesity and hyperuricemia) showed an area under a ROC curve of 0.813 (95% CI 0.795 to 0.829) for identifying urolithiasis among NAFLD patients. The optimal cut-off value of > -2.23 for the multivariate model provides a sensitivity of 76% and a specificity of 74% for predicting urolithiasis among NAFLD patients. CONCLUSION Urolithiasis among NAFLD patients is associated with FIB-4 score. Further, a novel algorithm based on FIB-4 score could serve as a useful tool for identifying individuals with a higher risk of urolithiasis among NAFLD patients, although prospective cohort studies are still needed in the future.
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Affiliation(s)
- Shaoyou Qin
- Department of Gastroenterology and Hepatology, China-Japan Union Hospital of Jilin University, Changchun, China
| | - Jiangbin Wang
- Department of Gastroenterology and Hepatology, China-Japan Union Hospital of Jilin University, Changchun, China
| | - Changyu Zhou
- Department of Gastroenterology and Hepatology, China-Japan Union Hospital of Jilin University, Changchun, China
| | - Yonggui Zhang
- Department of Gastroenterology and Hepatology, China-Japan Union Hospital of Jilin University, Changchun, China
| | - Yan Xu
- Department of Gastroenterology and Hepatology, China-Japan Union Hospital of Jilin University, Changchun, China
| | - Xu Wang
- Department of Gastroenterology and Hepatology, China-Japan Union Hospital of Jilin University, Changchun, China
| | - Song Wang
- Department of Urology, the First Hospital of Jilin University, Changchun, China
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22
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Wilechansky RM, Pedley A, Massaro JM, Hoffmann U, Benjamin EJ, Long MT. Relations of liver fat with prevalent and incident chronic kidney disease in the Framingham Heart Study: A secondary analysis. Liver Int 2019; 39:1535-1544. [PMID: 31033142 PMCID: PMC6675651 DOI: 10.1111/liv.14125] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/17/2019] [Revised: 04/13/2019] [Accepted: 04/16/2019] [Indexed: 02/06/2023]
Abstract
BACKGROUND & AIMS Prior studies demonstrated an association between non-alcoholic fatty liver disease and chronic kidney disease (CKD), though data are conflicting. We examined the association between liver fat and prevalent and incident CKD in the Framingham Heart Study (FHS). METHODS We included FHS participants who underwent computed tomography (CT) from 2002 to 2005 (n = 1315). After excluding heavy alcohol use (n = 211) and missing covariates (n = 117), the final sample included 987 participants. For the incident CKD analysis, we excluded 73 participants with prevalent CKD. Liver fat was measured by the average liver attenuation on CT. Estimated glomerular filtration rate (eGFR) was obtained using the CKD Epidemiology Collaboration Creatinine-Cystatin C equation, and CKD was defined as eGFR < 60 ml/min/1.73 m2 . Microalbuminuria was defined by sex-specific urinary albumin-creatinine ratio cut-offs. Multivariable-adjusted regression models were performed to determine the association between liver fat and CKD. RESULTS The prevalence of hepatic steatosis and CKD were 19% and 14% respectively (55.9% women, mean age 60 ± 9 years). After adjusting for covariates, we observed no significant associations between liver fat and CKD, microalbuminuria or eGFR in cross-sectional analyses. We observed positive associations between liver fat, incident microalbuminuria and reduced eGFR in age- and sex-adjusted models; these relationships were not significant in multivariable-adjusted models. CONCLUSIONS In this community-based cohort study, we did not observe significant associations between liver fat and prevalent or incident CKD with a median follow-up time of 12.5 years. The association between NAFLD and CKD may be accounted for by shared risk factors; confirmatory studies are needed.
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Affiliation(s)
| | - Alison Pedley
- National Heart, Lung, and Blood Institute’s and Boston University’s Framingham Heart Study, Framingham, MA
| | - Joseph M. Massaro
- Department of Mathematics and Statistics, Boston University, Boston, MA
| | - Udo Hoffmann
- Radiology Department, Massachusetts General Hospital, Harvard Medical School, Boston, MA
| | - Emelia J. Benjamin
- National Heart, Lung, and Blood Institute’s and Boston University’s Framingham Heart Study, Framingham, MA,Evans Department of Medicine, Whitaker Cardiovascular Institute and Cardiology Section, Boston University School of Medicine, Boston, MA,Department of Epidemiology, Boston University School of Public Health, Boston, MA
| | - Michelle T. Long
- National Heart, Lung, and Blood Institute’s and Boston University’s Framingham Heart Study, Framingham, MA,Section of Gastroenterology, Boston Medical Center, Boston University School of Medicine, Boston, MA
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23
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Danford CJ, Iriana S, Shen C, Curry MP, Lai M. Evidence of bias during liver transplant evaluation of non-alcoholic steatohepatitis cirrhosis patients. Liver Int 2019; 39:1165-1173. [PMID: 30809932 DOI: 10.1111/liv.14080] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/20/2018] [Revised: 01/14/2019] [Accepted: 02/11/2019] [Indexed: 12/14/2022]
Abstract
BACKGROUND & AIMS Cardiovascular disease (CVD) is the leading cause of death among non-alcoholic steatohepatitis (NASH) patients and a major source of post-transplant mortality. We sought to examine the effect of comorbidities on listing for orthotopic liver transplant (OLT) in NASH patients. METHODS In this retrospective cohort study, we included all patients (n = 955) referred to Beth Israel Deaconess Medical Center for OLT between January 2002 and September 2011 and followed their outcomes through March 2018. RESULTS Compared with non-NASH patients (n = 881), NASH patients (n = 74) were older, more likely female, more overweight, with higher rates of diabetes, hypertension and CVD. NASH patients were less likely to be listed for OLT (55% vs 68.9%, P = 0.01) and were more often declined for 'medical comorbidities' (36.1% vs 15.7%, P < 0.001). However, on multivariate analysis, the only significant predictors of listing were model for end-stage liver disease (MELD) score (OR 1.04, P = 0.01), HCC (OR 2.16, P = 0.01), and diagnosis of non-NASH cirrhosis (OR 2.56, P = 0.003) while controlling for comorbidities. NASH patients declined for OLT died primarily from their liver disease and were not more likely to die from CVD than non-NASH patients. There was no difference in outcomes of NASH vs non-NASH patients on the waitlist and post-transplant. CONCLUSIONS This study demonstrates potential bias against NASH patients referred for OLT arising from heightened concern for comorbidities. Despite being declined for comorbidities, NASH patients are likely to die of their liver disease.
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Affiliation(s)
- Christopher J Danford
- Division of Gastroenterology and Hepatology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts
| | - Sentia Iriana
- Division of Gastroenterology and Hepatology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts
| | - Changyu Shen
- Division of Cardiology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts
| | - Michael P Curry
- Division of Gastroenterology and Hepatology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts
| | - Michelle Lai
- Division of Gastroenterology and Hepatology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts
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24
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International Liver Transplantation Consensus Statement on End-stage Liver Disease Due to Nonalcoholic Steatohepatitis and Liver Transplantation. Transplantation 2019; 103:45-56. [PMID: 30153225 DOI: 10.1097/tp.0000000000002433] [Citation(s) in RCA: 70] [Impact Index Per Article: 11.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Nonalcoholic steatohepatitis (NASH)-related cirrhosis has become one of the most common indications for liver transplantation (LT), particularly in candidates older than 65 years. Typically, NASH candidates have concurrent obesity, metabolic, and cardiovascular risks, which directly impact patient evaluation and selection, waitlist morbidity and mortality, and eventually posttransplant outcomes. The purpose of these guidelines is to highlight specific features commonly observed in NASH candidates and strategies to optimize pretransplant evaluation and waitlist survival. More specifically, the working group addressed the following clinically relevant questions providing recommendations based on the Grading of Recommendation, Assessment, Development and Evaluation (GRADE) system supported by rigorous systematic reviews and consensus: (1) Is the outcome after LT similar to that of other etiologies of liver disease? (2) Is the natural history of NASH-related cirrhosis different from other etiologies of end-stage liver disease? (3) How should cardiovascular risk be assessed in the candidate for LT? Should the assessment differ from that done in other etiologies? (4) How should comorbidities (hypertension, diabetes, dyslipidemia, obesity, renal dysfunction, etc.) be treated in the candidate for LT? Should treatment and monitoring of these comorbidities differ from that applied in other etiologies? (5) What are the therapeutic strategies recommended to improve the cardiovascular and nutritional status of a NASH patient in the waiting list for LT? (6) Is there any circumstance where obesity should contraindicate LT? (7) What is the optimal time for bariatric surgery: before, during, or after LT? (8) How relevant is donor steatosis for LT in NASH patients?
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25
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El Hadi H, Di Vincenzo A, Vettor R, Rossato M. Cardio-Metabolic Disorders in Non-Alcoholic Fatty Liver Disease. Int J Mol Sci 2019; 20:ijms20092215. [PMID: 31064058 PMCID: PMC6539803 DOI: 10.3390/ijms20092215] [Citation(s) in RCA: 37] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2019] [Revised: 04/19/2019] [Accepted: 04/28/2019] [Indexed: 12/16/2022] Open
Abstract
With the progressive epidemics of obesity, non-alcoholic fatty liver disease (NAFLD) has become the most common cause of chronic liver disease in adults and children. The increasing prevalence and incidence of NAFLD with advanced fibrosis is concerning because patients appear to experience higher non-liver-related morbidity and mortality than the general population. Recent clinical evidence suggests that NAFLD is directly associated with an increased risk of cardio-metabolic disorders. This mini review describes briefly the current understanding of the pathogenesis of NAFLD, summarizing the link between NAFLD and cardio-metabolic complications, focusing mainly upon ischemic stroke, type 2 diabetes mellitus (DM), hypertension, chronic kidney disease (CKD) and cardiac arrhythmias. In addition, it describes briefly the current understanding of the pathogenesis of NAFLD.
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Affiliation(s)
- Hamza El Hadi
- Internal Medicine 3, Department of Medicine DIMED, University of Padova, 35122 Padova, Italy.
- Department of Medicine, Klinikum Rheine, 48431 Rheine, Germany.
| | - Angelo Di Vincenzo
- Internal Medicine 3, Department of Medicine DIMED, University of Padova, 35122 Padova, Italy.
| | - Roberto Vettor
- Internal Medicine 3, Department of Medicine DIMED, University of Padova, 35122 Padova, Italy.
| | - Marco Rossato
- Internal Medicine 3, Department of Medicine DIMED, University of Padova, 35122 Padova, Italy.
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26
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Gitto S, Marra F, De Maria N, Bihl F, Villa E, Andreone P, Burra P. Nonalcoholic steatohepatitis before and after liver transplant: keeping up with the times. Expert Rev Gastroenterol Hepatol 2019; 13:173-178. [PMID: 30791778 DOI: 10.1080/17474124.2019.1551132] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/30/2018] [Accepted: 11/19/2018] [Indexed: 02/06/2023]
Abstract
In the last years, nonalcoholic steatohepatitis (NASH) has become a leading indication for liver transplant (LT). After transplant, both recurrent and de novo nonalcoholic fatty liver disease (NAFLD) can be commonly diagnosed. However, dedicated surveillance programs for patients with pre- or post-transplant NAFLD are not available. Areas covered: Patients waiting for LT for NASH show specific peculiarities and would deserve targeted stratification of mortality risk. Obesity, hyperlipidemia, and diabetes mellitus can be often found after transplant. These conditions, together with immunosuppressive regimen, make LT recipients a high-risk population for both recurrent and de novo NAFLD. Development of fatty liver disease after LT has a relevant impact on both morbidity and mortality. Expert commentary: A targeted stratification of neoplastic and cardiovascular risk for patients with NASH waiting for LT would be mandatory. In both pre- and post-transplant period, NAFLD should be considered not only a liver disease but also a cardiovascular risk factor. Patients within Transplant Program, especially those with known metabolic risk factors, should be followed with personalized diagnostic and life-style interventions before and after LT.
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Affiliation(s)
- Stefano Gitto
- a Department of Experimental and Clinical Medicine , University of Florence , Florence , Italy
| | - Fabio Marra
- a Department of Experimental and Clinical Medicine , University of Florence , Florence , Italy
| | - Nicola De Maria
- b Department of Gastroenterology , Azienda Ospedaliero-Universitaria and University of Modena and Reggio Emilia , Modena , Italy
| | - Florian Bihl
- c Hepatology Service , EOC , Bellinzona , Switzerland
| | - Erica Villa
- b Department of Gastroenterology , Azienda Ospedaliero-Universitaria and University of Modena and Reggio Emilia , Modena , Italy
| | - Pietro Andreone
- d Department of Medical and Surgical Sciences , University of Bologna and Azienda Ospedaliero-Universitaria di Bologna , Bologna , Italy
| | - Patrizia Burra
- e Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology , Padua University Hospital , Padua , Italy
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27
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Loy VM, Joyce C, Bello S, VonRoenn N, Cotler SJ. Gender disparities in liver transplant candidates with nonalcoholic steatohepatitis. Clin Transplant 2018; 32:e13297. [DOI: 10.1111/ctr.13297] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 05/20/2018] [Indexed: 12/15/2022]
Affiliation(s)
- Veronica M. Loy
- Department of Hepatology; Loyola University Medical Center; Maywood IL USA
- Loyola University Chicago; Maywood IL USA
| | - Cara Joyce
- Loyola University Chicago; Maywood IL USA
| | | | - Natasha VonRoenn
- Department of Hepatology; Loyola University Medical Center; Maywood IL USA
- Loyola University Chicago; Maywood IL USA
| | - Scott J. Cotler
- Department of Hepatology; Loyola University Medical Center; Maywood IL USA
- Loyola University Chicago; Maywood IL USA
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28
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Mikolasevic I, Filipec-Kanizaj T, Mijic M, Jakopcic I, Milic S, Hrstic I, Sobocan N, Stimac D, Burra P. Nonalcoholic fatty liver disease and liver transplantation - Where do we stand? World J Gastroenterol 2018; 24:1491-1506. [PMID: 29662288 PMCID: PMC5897854 DOI: 10.3748/wjg.v24.i14.1491] [Citation(s) in RCA: 83] [Impact Index Per Article: 11.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/18/2019] [Revised: 03/19/2018] [Accepted: 03/25/2018] [Indexed: 02/06/2023] Open
Abstract
Nonalcoholic fatty liver disease/nonalcoholic steatohepatitis (NAFLD/NASH) is a challenging and multisystem disease that has a high socioeconomic impact. NAFLD/NASH is a main cause of macrovesicular steatosis and has multiple impacts on liver transplantation (LT), on patients on the waiting list for transplant, on post-transplant setting as well as on organ donors. Current data indicate new trends in the area of chronic liver disease. Due to the increased incidence of metabolic syndrome (MetS) and its components, NASH cirrhosis and hepatocellular carcinoma caused by NASH will soon become a major indication for LT. Furthermore, due to an increasing incidence of MetS and, consequently, NAFLD, there will be more steatotic donor livers and less high quality organs available for LT, in addition to a lack of available liver allografts. Patients who have NASH and are candidates for LT have multiple comorbidities and are unique LT candidates. Finally, we discuss long-term grafts and patient survival after LT, the recurrence of NASH and NASH appearing de novo after transplantation. In addition, we suggest topics and areas that require more research for improving the health care of this increasing patient population.
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Affiliation(s)
- Ivana Mikolasevic
- Department of Gastroenterology, UHC Rijeka, School of Medicine, University of Rijeka, Rijeka 51000, Croatia
| | - Tajana Filipec-Kanizaj
- Department of Gastroenterology, University Hospital Merkur, School of Medicine, University of Zagreb, Zagreb 10000, Croatia
| | - Maja Mijic
- Department of Gastroenterology, University Hospital Merkur, School of Medicine, University of Zagreb, Zagreb 10000, Croatia
| | - Ivan Jakopcic
- Department of Gastroenterology, UHC Rijeka, School of Medicine, University of Rijeka, Rijeka 51000, Croatia
| | - Sandra Milic
- Department of Gastroenterology, UHC Rijeka, School of Medicine, University of Rijeka, Rijeka 51000, Croatia
| | - Irena Hrstic
- Department of Internal medicine, General Hospital Pula, Pula, School of Medicine, University of Rijeka and Zagreb, Pula 52100, Croatia
| | - Nikola Sobocan
- Department of Gastroenterology, University Hospital Merkur, School of Medicine, University of Zagreb, Zagreb 10000, Croatia
| | - Davor Stimac
- Department of Gastroenterology, UHC Rijeka, School of Medicine, University of Rijeka, Rijeka 51000, Croatia
| | - Patrizia Burra
- Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, Padua University Hospital, Padua 35128, Italy
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29
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Carter D, Dieterich DT, Chang C. Nonalcoholic Fatty Liver Disease/Nonalcoholic Steatohepatitis in Liver Transplantation. Clin Liver Dis 2018; 22:213-227. [PMID: 29128058 DOI: 10.1016/j.cld.2017.08.015] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
The number of transplants caused by nonalcoholic fatty liver disease/nonalcoholic steatohepatitis (NASH) has been progressively increasing and this is expected to become the most common indication for liver transplant in the United States. Patients with NASH show many features of the metabolic syndrome and, as a result, are at higher risk for postoperative cardiovascular morbidity and mortality. Despite this, patients with NASH have long-term graft and patient survival rates comparable with other causes of chronic liver disease. Posttransplant metabolic syndrome is a common occurrence that increases the risk of steatosis in the graft liver.
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Affiliation(s)
- Danielle Carter
- Division of Liver Diseases, Icahn School of Medicine at Mount Sinai, 17 East 102nd Street, 2nd Floor, New York, NY 10029, USA.
| | - Douglas T Dieterich
- Division of Liver Diseases, Icahn School of Medicine at Mount Sinai, 17 East 102nd Street, 2nd Floor, New York, NY 10029, USA
| | - Charissa Chang
- Division of Liver Diseases, Icahn School of Medicine at Mount Sinai, 17 East 102nd Street, 2nd Floor, New York, NY 10029, USA
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30
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Pang N, Kow W, Law J, Pan L, Lim B, Wong C, Chang K, Ganpathi I, Madhavan K. Role of Coronary Angiography in Pre–Liver Transplantation Cardiac Evaluation: Experience From an Asian Transplant Institution. Transplant Proc 2017; 49:1797-1805. [DOI: 10.1016/j.transproceed.2017.04.021] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2016] [Revised: 04/02/2017] [Accepted: 04/27/2017] [Indexed: 02/09/2023]
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31
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Adams LA, Anstee QM, Tilg H, Targher G. Non-alcoholic fatty liver disease and its relationship with cardiovascular disease and other extrahepatic diseases. Gut 2017; 66:1138-1153. [PMID: 28314735 DOI: 10.1136/gutjnl-2017-313884] [Citation(s) in RCA: 791] [Impact Index Per Article: 98.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/01/2017] [Revised: 02/14/2017] [Accepted: 02/16/2017] [Indexed: 02/07/2023]
Abstract
Key physiological functions of the liver, including glucose and lipid metabolism, become disturbed in the setting of non-alcoholic fatty liver disease (NAFLD) and may be associated with a systemic inflammatory 'milieu' initiated in part by liver-secreted cytokines and molecules. Consequently, the pathophysiological effects of NAFLD extend beyond the liver with a large body of clinical evidence demonstrating NAFLD to be independently associated with both prevalent and incident cardiovascular disease (CVD), chronic kidney disease (CKD) and type 2 diabetes mellitus (T2DM). The magnitude of risk of developing these extrahepatic diseases parallels the underlying severity of NAFLD, such that patients with non-alcoholic steatohepatitis (NASH) appear to be at greater risk of incident CVD, CKD and T2DM than those with simple steatosis. Other modifiers of risk may include genetic variants (eg, patatin-like phospholipase domain-containing 3 and trans-membrane 6 superfamily member 2 polymorphisms), visceral adipose tissue accumulation, dietary intake and the gut microbiome. Emerging data also suggest that NAFLD may be a risk factor for colonic neoplasia and reduced bone mineral density, especially among men. Importantly, improvement/resolution of NAFLD is associated with a reduced incidence of T2DM and improved kidney function, adding weight to causality and suggesting liver focused treatments may reduce risk of extrahepatic complications. Awareness of these associations is important for the clinicians such that CVD risk factor management, screening for T2DM and CKD are part of the routine management of patients with NAFLD.
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Affiliation(s)
- Leon A Adams
- School of Medicine and Pharmacology, The University of Western Australia, Nedlands, Western Australia, Australia
| | - Quentin M Anstee
- Faculty of Medical Sciences, Institute of Cellular Medicine, Newcastle University, Newcastle Upon Tyne, UK.,Liver Unit, Newcastle Upon Tyne Hospitals NHS Trust, Freeman Hospital, Newcastle upon Tyne, UK
| | - Herbert Tilg
- Department of Internal Medicine I, Gastroenterology, Hepatology & Metabolism, Medical University Innsbruck, Innsbruck, Austria
| | - Giovanni Targher
- Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, Verona, Italy
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32
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Targher G, Byrne CD. Non-alcoholic fatty liver disease: an emerging driving force in chronic kidney disease. Nat Rev Nephrol 2017; 13:297-310. [PMID: 28218263 DOI: 10.1038/nrneph.2017.16] [Citation(s) in RCA: 233] [Impact Index Per Article: 29.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Non-alcoholic fatty liver disease (NAFLD) is caused by an accumulation of fat in the liver; the condition can progress over time to increase the risk of developing cirrhosis, end-stage liver disease and hepatocellular carcinoma. The prevalence of NAFLD is increasing rapidly owing to the global epidemics of obesity and type 2 diabetes mellitus (T2DM), and NAFLD has been predicted to become the most important indication for liver transplantation over the next decade. It is now increasingly clear that NAFLD not only affects the liver but can also increase the risk of developing extra-hepatic diseases, including T2DM, cardiovascular disease and chronic kidney disease (CKD), which have a considerable impact on health-care resources. Accumulating evidence indicates that NAFLD exacerbates insulin resistance, predisposes to atherogenic dyslipidaemia and releases a variety of proinflammatory factors, prothrombotic factors and profibrogenic molecules that can promote vascular and renal damage. Furthermore, communication or 'crosstalk' between affected organs or tissues in these diseases has the potential to further harm function and worsen patient outcomes, and increasing amounts of evidence point to a strong association between NAFLD and CKD. Whether a causal relationship between NAFLD and CKD exists remains to be definitively established.
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Affiliation(s)
- Giovanni Targher
- Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, Piazzale Stefani 1, 37126 Verona, Italy
| | - Christopher D Byrne
- Nutrition and Metabolism, Faculty of Medicine, University of Southampton.,Southampton National Institute for Health Research Biomedical Research Centre, University Hospital Southampton, Southampton General Hospital, Tremona Road, Southampton SO16 6YD, UK
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33
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La Non Alcoholic Fatty Liver Disease (NAFLD) et la Non Alcoholic Steato-Hepatitis (NASH) des pathologies de système : revue pour le réanimateur. MEDECINE INTENSIVE REANIMATION 2016. [DOI: 10.1007/s13546-016-1253-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
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34
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Pais R, Barritt AS, Calmus Y, Scatton O, Runge T, Lebray P, Poynard T, Ratziu V, Conti F. NAFLD and liver transplantation: Current burden and expected challenges. J Hepatol 2016; 65:1245-1257. [PMID: 27486010 PMCID: PMC5326676 DOI: 10.1016/j.jhep.2016.07.033] [Citation(s) in RCA: 322] [Impact Index Per Article: 35.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/16/2016] [Revised: 07/17/2016] [Accepted: 07/22/2016] [Indexed: 12/26/2022]
Abstract
Because of global epidemics of obesity and type 2 diabetes, the prevalence of non-alcoholic fatty liver disease (NAFLD) is increasing both in Europe and the United States, becoming one of the most frequent causes of chronic liver disease and predictably, one of the leading causes of liver transplantation both for end-stage liver disease and hepatocellular carcinoma. For most transplant teams around the world this will raise many challenges in terms of pre- and post-transplant management. Here we review the multifaceted impact of NAFLD on liver transplantation and will discuss: (1) NAFLD as a frequent cause of cryptogenic cirrhosis, end-stage chronic liver disease, and hepatocellular carcinoma; (2) prevalence of NAFLD as an indication for liver transplantation both in Europe and the United States; (3) the impact of NAFLD on the donor pool; (4) the access of NAFLD patients to liver transplantation and their management on the waiting list in regard to metabolic, renal and vascular comorbidities; (5) the prevalence and consequences of post-transplant metabolic syndrome, recurrent and de novo NAFLD; (6) the alternative management and therapeutic options to improve the long-term outcomes with particular emphasis on the correction and control of metabolic comorbidities.
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Affiliation(s)
- Raluca Pais
- Service Hépatogastroentérologie, Assistance Publique Hôpitaux de Paris, Hôpital Pitié-Salpétrière - Université Pierre et Marie Curie, Paris, France; UMR_S 938, INSERM - CDR Saint Antoine, Institute of Cardiometabolism and Nutrition (ICAN), Paris, France.
| | - A Sidney Barritt
- Division of Gastroenterology and Hepatology, UNC School of Medicine, University of North Carolina at Chapel Hill, 8004 Burnett Womack, CB #7584, Chapel Hill, NC 27599-7584, USA
| | - Yvon Calmus
- Service Hépatogastroentérologie, Assistance Publique Hôpitaux de Paris, Hôpital Pitié-Salpétrière - Université Pierre et Marie Curie, Paris, France; UMR_S 938, INSERM - CDR Saint Antoine, Institute of Cardiometabolism and Nutrition (ICAN), Paris, France
| | - Olivier Scatton
- Service de Chirurgie Hépato-biliaire et Transplantation Hépatique, Assistance Publique Hôpitaux de Paris, Hôpital Pitié-Salpétrière - Université Pierre et Marie Curie, Paris, France
| | - Thomas Runge
- Division of Gastroenterology and Hepatology, UNC School of Medicine, University of North Carolina at Chapel Hill, 8004 Burnett Womack, CB #7584, Chapel Hill, NC 27599-7584, USA
| | - Pascal Lebray
- Service Hépatogastroentérologie, Assistance Publique Hôpitaux de Paris, Hôpital Pitié-Salpétrière - Université Pierre et Marie Curie, Paris, France
| | - Thierry Poynard
- Service Hépatogastroentérologie, Assistance Publique Hôpitaux de Paris, Hôpital Pitié-Salpétrière - Université Pierre et Marie Curie, Paris, France; UMR_S 938, INSERM - CDR Saint Antoine, Institute of Cardiometabolism and Nutrition (ICAN), Paris, France
| | - Vlad Ratziu
- Service Hépatogastroentérologie, Assistance Publique Hôpitaux de Paris, Hôpital Pitié-Salpétrière - Université Pierre et Marie Curie, Paris, France; UMR_S 938, INSERM - CDR Saint Antoine, Institute of Cardiometabolism and Nutrition (ICAN), Paris, France
| | - Filomena Conti
- Service Hépatogastroentérologie, Assistance Publique Hôpitaux de Paris, Hôpital Pitié-Salpétrière - Université Pierre et Marie Curie, Paris, France; UMR_S 938, INSERM - CDR Saint Antoine, Institute of Cardiometabolism and Nutrition (ICAN), Paris, France
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Teegen EM, Krebs I, Langelotz C, Pratschke J, Rau B. Gender Mainstreaming and Transplant Surgery. Visc Med 2016; 32:286-289. [PMID: 27722166 DOI: 10.1159/000446357] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
BACKGROUND Gender differences in medicine are gaining in importance. In transplant surgery, not only the patient's gender but also that of the donor play an important role in the outcome of transplantation due to sociocultural and genetic factors. METHODS This review article gives an overview of the latest investigations into gender-related influences in the field of visceral transplantation. For this purpose, a systematic review of the literature was performed. RESULTS In general, women are less often evaluated for and subjected to transplantation worldwide. Significantly poorer outcome can be observed in women with liver transplantation following hepatitis C cirrhosis. Furthermore, female renal grafts are less favorable in terms of outcome and survival. Gender disparities affect transplant medicine due to subtle gender-specific immunological factors. Sociocultural factors also lead to differences in the clinical treatment of men and women, which may influence overall survival. CONCLUSION For a better understanding of gender-specific differences in transplant medicine and a possible improvement in outcome, further research in this field is necessary.
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Affiliation(s)
- Eva Maria Teegen
- Department of General, Visceral and Transplant Surgery, Campus Virchow, Charité - Universitätsmedizin Berlin, Berlin, Germany
| | - Isabell Krebs
- Department of General, Visceral, Vascular and Thoracic Surgery, Campus Mitte, Charité - Universitätsmedizin Berlin, Berlin, Germany
| | - Corinna Langelotz
- Department of General, Visceral, Vascular and Thoracic Surgery, Campus Mitte, Charité - Universitätsmedizin Berlin, Berlin, Germany
| | - Johann Pratschke
- Department of General, Visceral and Transplant Surgery, Campus Virchow, Charité - Universitätsmedizin Berlin, Berlin, Germany; Department of General, Visceral, Vascular and Thoracic Surgery, Campus Mitte, Charité - Universitätsmedizin Berlin, Berlin, Germany
| | - Beate Rau
- Department of General, Visceral, Vascular and Thoracic Surgery, Campus Mitte, Charité - Universitätsmedizin Berlin, Berlin, Germany
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Atla PR, Sheikh MY, Gill F, Kundu R, Choudhury J. Predictors of hospital re-admissions among Hispanics with hepatitis C-related cirrhosis. Ann Gastroenterol 2016; 29:515-520. [PMID: 27708520 PMCID: PMC5049561 DOI: 10.20524/aog.2016.0072] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/17/2016] [Accepted: 06/23/2016] [Indexed: 12/23/2022] Open
Abstract
Background Hospital re-admissions in decompensated cirrhosis are associated with worse patient outcomes. Hispanics have a disproportionately high prevalence of hepatitis C virus (HCV)-related morbidity and mortality. The goal of this study was to evaluate the factors affecting re-admission rates among Hispanics with HCV-related cirrhosis. Methods A total of 292 consecutive HCV-related cirrhosis admissions (Hispanics 189, non-Hispanics 103) from January 2009 to December 2012 were retrospectively reviewed; 132 were cirrhosis-related re-admissions. The statistical analysis was performed using STATA version 11.1. Chi-square/Fisher’s exact and Student’s t-tests were used to compare categorical and continuous variables, respectively. Multivariate logistic regression analysis was performed to identify predictors for hospital readmissions. Results Among the 132 cirrhosis-related readmissions, 71% were Hispanics while 29% were non-Hispanics (P=0.035). Hepatic encephalopathy (HE) and esophageal variceal hemorrhage were the most frequent causes of the first and subsequent readmissions. Hispanics with readmissions had a higher Child-Turcotte-Pugh (CTP) class (B and C) and higher model for end-stage liver disease (MELD) scores (≥15), as well as a higher incidence of alcohol use, HE, spontaneous bacterial peritonitis, hepatocellular carcinoma, and varices (P<0.05). The majority of the study patients (81%) had MELD scores <15. Multivariate regression analysis identified alcohol use (OR 2.63; 95%CI 1.1-6.4), HE (OR 5.5; 95%CI 2-15.3), varices (OR 3.2; 95%CI 1.3-8.2), and CTP class (OR 3.3; 95%CI 1.4–8.1) as predictors for readmissions among Hispanics. Conclusion CTP classes B and C, among other factors, were the major predictors for hospital readmissions in Hispanics with HCV-related cirrhosis. The majority of these readmissions were due to HE and variceal hemorrhage.
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Affiliation(s)
- Pradeep R Atla
- Division of Gastroenterology, Hepatology and Nutrition, University of California San Francisco, Fresno MEP (Pradeep R. Atla, Muhammad Y. Sheikh, Rabindra Kundu, Jayanta Choudhury), Fresno, California, USA
| | - Muhammad Y Sheikh
- Division of Gastroenterology, Hepatology and Nutrition, University of California San Francisco, Fresno MEP (Pradeep R. Atla, Muhammad Y. Sheikh, Rabindra Kundu, Jayanta Choudhury), Fresno, California, USA
| | - Firdose Gill
- Department of Medicine, Kaiser Permanente Fresno Medical Center (Firdose Gill), Fresno, California, USA
| | - Rabindra Kundu
- Division of Gastroenterology, Hepatology and Nutrition, University of California San Francisco, Fresno MEP (Pradeep R. Atla, Muhammad Y. Sheikh, Rabindra Kundu, Jayanta Choudhury), Fresno, California, USA
| | - Jayanta Choudhury
- Division of Gastroenterology, Hepatology and Nutrition, University of California San Francisco, Fresno MEP (Pradeep R. Atla, Muhammad Y. Sheikh, Rabindra Kundu, Jayanta Choudhury), Fresno, California, USA
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Nonalcoholic Steatohepatitis is the Most Rapidly Growing Indication for Simultaneous Liver Kidney Transplantation in the United States. Transplantation 2016; 100:607-12. [PMID: 26479282 DOI: 10.1097/tp.0000000000000945] [Citation(s) in RCA: 73] [Impact Index Per Article: 8.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Abstract
BACKGROUND Frequency of liver transplantation (LT) is increasing in nonalcoholic steatohepatitis (NASH) with good post-transplant outcomes. Similar data on simultaneous liver kidney (SLK) transplants are limited. METHODS United Network for Organ Sharing database (2002-2011) queried for deceased donor first LT for primary biliary cirrhosis, primary sclerosing cholangitis, or alcoholic cirrhosis (group I), NASH, and cryptogenic cirrhosis with body mass index greater than 30 (group II), and hepatitis C virus with and without alcohol, hepatitis B virus, and hepatocellular carcinoma (group III). RESULTS Of 38 533 LT (9495, 3665, and 25 383 in groups I-III, respectively), about 5.6% (N = 2162) received SLK with 584 (6.2%), 320 (8.7%), and 1258 (5%) in groups I-III, respectively. The SLK performed for group II increased from 6.3% in 2002 to 2003 to 19.2% in 2010 to 2011. Similar trends remained unchanged in group I (26.1 to 26.6%) and decreased in group III (67.6 to 54.5%). Five-year outcomes were similar comparing group II versus group I for liver graft (78 vs 74%, P = 0.14) and patient survival (81 vs 76%, P = 0.07). In contrast, kidney graft outcome was worse for group II (70 vs 79%, P = 0.002). Risk of kidney graft loss was over 1.5-fold higher among group II SLK recipients compared to group I after controlling for recipient characteristics. Estimated glomerular filtration rate remained lower in group II compared with group I at various time points after SLK transplantation. CONCLUSIONS The NASH is the most rapidly growing indication for SLK transplantation with poor renal outcomes. Studies are needed to examine mechanisms of these findings and develop strategies to improve renal outcomes in SLK recipients for NASH.
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Gitto S, Vukotic R, Vitale G, Pirillo M, Villa E, Andreone P. Non-alcoholic steatohepatitis and liver transplantation. Dig Liver Dis 2016; 48:587-591. [PMID: 27038703 DOI: 10.1016/j.dld.2016.02.014] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/29/2015] [Revised: 01/22/2016] [Accepted: 02/23/2016] [Indexed: 02/08/2023]
Abstract
Non-alcoholic steatohepatitis is a growing liver-related health problem. In Europe, non-alcoholic fatty liver disease is the most usual reason of chronic liver illness while steatohepatitis, its progressive form, affects 1% of Europeans and North Americans. In the United States steatohepatitis-related cirrhosis is one of the main indications for liver transplant. A targeted stratification for patients waiting for transplant and affected by this disease is mandatory especially because of their increased cardiovascular and cancer risk. The adequate treatment of NAFLD is crucial for the reduction of the disease related morbidity and mortality. In post-transplant setting, the recurrent or de novo steatosis might seriously affect the allograft short- and long-term outcome. Many conditions can represent the basis of the post-transplant steatohepatitis: obesity, hyperlipidaemia, diabetes mellitus, arterial hypertension, immunosuppressant treatment, alcoholic habit and liver graft steatosis. Today, the only consolidated therapy is represented by a deep life-style intervention since the use of drug-based alternative strategies is still limited and a very few data are available for the post-transplant period. Targeted and personalized behaviour and pharmacological interventions have to be developed for both the pre- and post-transplant phase.
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Affiliation(s)
- Stefano Gitto
- Department of Gastroenterology, Azienda Ospedaliero-Universitaria and University of Modena and Reggio Emilia, Modena, Italy
| | - Ranka Vukotic
- Dipartimento di Scienze Mediche e Chirurgiche, Centro Studi e Ricerche sulle Epatiti, Alma Mater Studiorum, Univesity of Bologna, Bologna, Italy
| | - Giovanni Vitale
- Dipartimento di Scienze Mediche e Chirurgiche, Centro Studi e Ricerche sulle Epatiti, Alma Mater Studiorum, Univesity of Bologna, Bologna, Italy
| | - Martina Pirillo
- Dipartimento di Scienze Mediche e Chirurgiche, Centro Studi e Ricerche sulle Epatiti, Alma Mater Studiorum, Univesity of Bologna, Bologna, Italy
| | - Erica Villa
- Department of Gastroenterology, Azienda Ospedaliero-Universitaria and University of Modena and Reggio Emilia, Modena, Italy
| | - Pietro Andreone
- Dipartimento di Scienze Mediche e Chirurgiche, Centro Studi e Ricerche sulle Epatiti, Alma Mater Studiorum, Univesity of Bologna, Bologna, Italy.
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Patel YA, Berg CL, Moylan CA. Nonalcoholic Fatty Liver Disease: Key Considerations Before and After Liver Transplantation. Dig Dis Sci 2016; 61:1406-16. [PMID: 26815171 PMCID: PMC5344743 DOI: 10.1007/s10620-016-4035-3] [Citation(s) in RCA: 43] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/12/2015] [Accepted: 01/09/2016] [Indexed: 02/06/2023]
Abstract
Nonalcoholic fatty liver disease (NAFLD) is the most common etiology of chronic liver disease in developed countries and is on trajectory to become the leading indication for liver transplantation in the USA and much of the world. Patients with NAFLD cirrhosis awaiting liver transplant face unique challenges and increased risk for waiting list stagnation and dropout due to burdensome comorbidities including obesity, diabetes, cardiovascular disease, and kidney disease. Thus far, patients transplanted for NAFLD cirrhosis have excellent mid- and long-term patient and graft survival, but concerns regarding short-term morbidity and mortality continue to exist. Post-liver transplantation, NAFLD occurs as both a recurrent and de novo manifestation, each with unique outcomes. NAFLD in the donor population is of concern given the growing demand for liver transplantation and mounting pressure to expand the donor pool. This review addresses key issues surrounding NAFLD as an indication for transplantation, including its increasing prevalence, unique patient demographics, outcomes related to liver transplantation, development of post-liver transplantation NAFLD, and NAFLD in the liver donor population. It also highlights exciting areas where further research is needed, such as the role of bariatric surgery and preconditioning of marginal donor grafts.
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Affiliation(s)
- Yuval A. Patel
- Division of Gastroenterology, Department of Medicine, Duke University School of Medicine, Duke University Medical Center, 905 South LaSalle Street, DUMC 3256, GSRB1, Durham, NC 27710, USA
| | - Carl L. Berg
- Division of Gastroenterology, Department of Medicine, Duke University School of Medicine, Duke University Medical Center, 905 South LaSalle Street, DUMC 3256, GSRB1, Durham, NC 27710, USA
| | - Cynthia A. Moylan
- Division of Gastroenterology, Department of Medicine, Duke University School of Medicine, Duke University Medical Center, 905 South LaSalle Street, DUMC 3256, GSRB1, Durham, NC 27710, USA,Division of Gastroenterology, Department of Medicine, Durham Veterans Affairs Medical Center, Durham, NC 27705, USA
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Traussnigg S, Kienbacher C, Halilbasic E, Rechling C, Kazemi-Shirazi L, Hofer H, Munda P, Trauner M. Challenges and Management of Liver Cirrhosis: Practical Issues in the Therapy of Patients with Cirrhosis due to NAFLD and NASH. Dig Dis 2015; 33:598-607. [PMID: 26159280 DOI: 10.1159/000375353] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/02/2023]
Abstract
Nonalcoholic fatty liver disease (NAFLD) is the hepatic manifestation of the metabolic syndrome and comprises a liver disease spectrum ranging from steatosis to nonalcoholic steatohepatitis (NASH) with risk of progression to liver cirrhosis and hepatocellular carcinoma (HCC). Associated metabolic conditions and comorbidities such as obesity, diabetes and cardiovascular diseases are common and require concerted management. Adiponutrin (PNPLA3) variants may help to identify NAFLD patients at higher risk for liver disease progression towards advanced fibrosis and HCC. The therapeutic options in NAFLD/NASH include lifestyle modification, pharmacological treatment, bariatric surgery for patients with morbid obesity and treatment of complications of liver cirrhosis and HCC, including liver transplantation. Insulin sensitizers and antioxidative treatment strategies with vitamin E are among the best-established pharmacological approaches, but both drugs have long-term safety issues and there is limited evidence in cirrhotic patients. Treatment of concomitant/underlying metabolic conditions with statins or metformin may also have beneficial effects on portal hypertension, complications of liver cirrhosis and HCC prevention. The bile acid receptor FXR may be a promising novel therapeutic target for the treatment of NAFLD/NASH, fibrosis and portal hypertension, but the prognostic implications of associated changes in low- and high-density lipoprotein cholesterol require further studies. Morbidly obese NASH patients can benefit from bariatric surgery which may reduce liver fibrosis but carries a risk of decompensation in patients with advanced liver cirrhosis. When carefully selected, patients with NASH cirrhosis undergoing liver transplantation have a good outcome. This review summarizes recent progress in the management of patients with liver cirrhosis due to NASH.
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Affiliation(s)
- Stefan Traussnigg
- Division of Gastroenterology and Hepatology, Medical University of Vienna, Vienna, Austria
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Fitzmorris P, Shoreibah M, Anand BS, Singal AK. Management of hepatocellular carcinoma. J Cancer Res Clin Oncol 2015; 141:861-876. [PMID: 25158999 DOI: 10.1007/s00432-014-1806-0] [Citation(s) in RCA: 79] [Impact Index Per Article: 7.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2014] [Accepted: 08/08/2014] [Indexed: 02/07/2023]
Abstract
PURPOSE Hepatocellular carcinoma (HCC), a common cause for cancer-related death, is increasing worldwide. Over the past decade, survival and quality of life of HCC patients have significantly improved due to better prevention strategies, early diagnosis, and improved treatment options. We performed this narrative review to synthesize current status on the HCC management. METHODS Literature search for publications especially over the last decade, which has changed the paradigm on the management of HCC. RESULTS Hepatitis B vaccination and treatment of chronic hepatitis B and C are important measures for HCC prevention. Screening and surveillance for HCC using ultrasonogram and alpha-fetoprotein estimation are directed toward cirrhotics and hepatitis B patients at high risk of HCC. If detected at an early stage, curative treatments for HCC can be used such as tumor resection, ablation and liver transplantation. HCC patients without curative options are managed by loco-regional therapies and systemic chemotherapy. Loco-regional treatments include trans-arterial chemoembolization, radioembolization and combinations of loco-regional plus systemic therapies. Currently, sorafenib is the only FDA-approved systemic therapy and newer better chemotherapeutic agents are being investigated. Palliative care for terminally ill patients with metastatic disease and/or poor functional status focusses on comfort care and symptom control. CONCLUSIONS In spite of significant advancement in HCC management, its incidence continues to rise. There remains an urgent need to continue refining understanding of HCC and develop strategies to increase utilization of the available preventive measures and curative treatment modalities for HCC.
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MESH Headings
- Antineoplastic Agents/therapeutic use
- Antiviral Agents/therapeutic use
- Carcinoma, Hepatocellular/drug therapy
- Carcinoma, Hepatocellular/epidemiology
- Carcinoma, Hepatocellular/prevention & control
- Carcinoma, Hepatocellular/virology
- Disease Management
- Hepatitis B/complications
- Hepatitis C/complications
- Hepatitis, Viral, Human/complications
- Hepatitis, Viral, Human/drug therapy
- Hepatitis, Viral, Human/prevention & control
- Humans
- Incidence
- Liver Neoplasms/drug therapy
- Liver Neoplasms/epidemiology
- Liver Neoplasms/prevention & control
- Liver Neoplasms/virology
- Mass Screening/methods
- Niacinamide/analogs & derivatives
- Niacinamide/therapeutic use
- Palliative Care/methods
- Phenylurea Compounds/therapeutic use
- Population Surveillance/methods
- Quality of Life
- Sorafenib
- Viral Hepatitis Vaccines/administration & dosage
- alpha-Fetoproteins/metabolism
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Affiliation(s)
- P Fitzmorris
- Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA
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Rodríguez-Castro KI, De Martin E, Gambato M, Lazzaro S, Villa E, Burra P. Female gender in the setting of liver transplantation. World J Transplant 2014; 4:229-242. [PMID: 25540733 PMCID: PMC4274594 DOI: 10.5500/wjt.v4.i4.229] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/08/2014] [Revised: 05/27/2014] [Accepted: 07/15/2014] [Indexed: 02/05/2023] Open
Abstract
The evolution of liver diseases to end-stage liver disease or to acute hepatic failure, the evaluation process for liver transplantation, the organ allocation decision-making, as well as the post-transplant outcomes are different between female and male genders. Women’s access to liver transplantation is hampered by the use of model for end-stage liver disease (MELD) score, in which creatinine values exert a systematic bias against women due to their lower values even in the presence of variable degrees of renal dysfunction. Furthermore, even when correcting MELD score for gender-appropriate creatinine determination, a quantifiable uneven access to transplant prevails, demonstrating that other factors are also involved. While some of the differences can be explained from the epidemiological point of view, hormonal status plays an important role. Moreover, the pre-menopausal and post-menopausal stages imply profound differences in a woman’s physiology, including not only the passage from the fertile age to the non-fertile stage, but also the loss of estrogens and their potentially protective role in delaying liver fibrosis progression, amongst others. With menopause, the tendency to gain weight may contribute to the development of or worsening of pre-existing metabolic syndrome. As an increasing number of patients are transplanted for non-alcoholic steatohepatitis, and as the average age at transplant increases, clinicians must be prepared for the management of this particular condition, especially in post-menopausal women, who are at particular risk of developing metabolic complications after menopause.
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Agarwal B, Davenport A. Difficulties in diagnosing acute kidney injury post liver transplantation using serum creatinine based diagnostic criteria. World J Hepatol 2014; 6:696-703. [PMID: 25349641 PMCID: PMC4209415 DOI: 10.4254/wjh.v6.i10.696] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/22/2014] [Revised: 06/16/2014] [Accepted: 09/10/2014] [Indexed: 02/06/2023] Open
Abstract
Renal function in patients with advanced cirrhosis is an important prognostic factor for survival both prior to and following liver transplantation. The importance of renal function is reflected by the introduction of the model for end stage liver disease (MELD) score, which includes serum creatinine. The MELD score has been shown to predict the short term risk of death for transplant wait listed patients and is currently used by many countries to allocate liver transplants on the basis of severity of underlying illness. Changes in serum creatinine are also used to stage acute kidney injury. However prior to liver transplantation the serum creatinine typically over estimates underlying renal function, particularly when a colorimetric Jaffe based assay is used, and paradoxically then under estimates renal function post liver transplantation, particularly when immunophyllins are started early as part of transplant immunosuppression. As acute kidney injury is defined by changes in serum creatinine, this potentially leads to over estimation of the incidence and severity of acute kidney injury in the immediate post-operative period.
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Targher G, Chonchol MB, Byrne CD. CKD and nonalcoholic fatty liver disease. Am J Kidney Dis 2014; 64:638-52. [PMID: 25085644 DOI: 10.1053/j.ajkd.2014.05.019] [Citation(s) in RCA: 160] [Impact Index Per Article: 14.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2014] [Accepted: 05/30/2014] [Indexed: 02/06/2023]
Abstract
The possible link between nonalcoholic fatty liver disease and chronic kidney disease (CKD) recently has attracted considerable scientific interest. Accumulating clinical evidence indicates that the presence and severity of nonalcoholic fatty liver disease is associated significantly with CKD (defined as decreased estimated glomerular filtration rate and/or proteinuria) and that nonalcoholic fatty liver disease predicts the development and progression of CKD, independently of traditional cardiorenal risk factors. Experimental evidence also suggests that nonalcoholic fatty liver disease itself may exacerbate systemic and hepatic insulin resistance, cause atherogenic dyslipidemia, and release a variety of proinflammatory, procoagulant, pro-oxidant, and profibrogenic mediators that play important roles in the development and progression of CKD. However, despite the growing evidence linking nonalcoholic fatty liver disease with CKD, it has not been definitively established whether a causal association exists. The clinical implication for these findings is that patients with nonalcoholic fatty liver disease may benefit from more intensive surveillance or early treatment interventions to decrease the risk of CKD. In this review, we discuss the evidence linking nonalcoholic fatty liver disease with CKD and the putative mechanisms by which nonalcoholic fatty liver disease contributes to kidney damage. We also briefly discuss current treatment options for this increasingly prevalent disease that is likely to have an important future impact on the global burden of disease.
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Affiliation(s)
- Giovanni Targher
- Section of Endocrinology, Diabetes and Metabolism, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, Verona, Italy.
| | - Michel B Chonchol
- Division of Renal Diseases and Hypertension, University of Colorado Denver, Aurora, CO
| | - Christopher D Byrne
- Nutrition and Metabolism, Faculty of Medicine, University of Southampton, Southampton, United Kingdom; Southampton National Institute for Health Research Biomedical Research Centre, Southampton, United Kingdom
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Musso G, Gambino R, Tabibian JH, Ekstedt M, Kechagias S, Hamaguchi M, Hultcrantz R, Hagström H, Yoon SK, Charatcharoenwitthaya P, George J, Barrera F, Hafliðadóttir S, Björnsson ES, Armstrong MJ, Hopkins LJ, Gao X, Francque S, Verrijken A, Yilmaz Y, Lindor KD, Charlton M, Haring R, Lerch MM, Rettig R, Völzke H, Ryu S, Li G, Wong LL, Machado M, Cortez-Pinto H, Yasui K, Cassader M. Association of non-alcoholic fatty liver disease with chronic kidney disease: a systematic review and meta-analysis. PLoS Med 2014; 11:e1001680. [PMID: 25050550 PMCID: PMC4106719 DOI: 10.1371/journal.pmed.1001680] [Citation(s) in RCA: 516] [Impact Index Per Article: 46.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/15/2013] [Accepted: 06/12/2014] [Indexed: 12/13/2022] Open
Abstract
BACKGROUND Chronic kidney disease (CKD) is a frequent, under-recognized condition and a risk factor for renal failure and cardiovascular disease. Increasing evidence connects non-alcoholic fatty liver disease (NAFLD) to CKD. We conducted a meta-analysis to determine whether the presence and severity of NAFLD are associated with the presence and severity of CKD. METHODS AND FINDINGS English and non-English articles from international online databases from 1980 through January 31, 2014 were searched. Observational studies assessing NAFLD by histology, imaging, or biochemistry and defining CKD as either estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m2 or proteinuria were included. Two reviewers extracted studies independently and in duplicate. Individual participant data (IPD) were solicited from all selected studies. Studies providing IPD were combined with studies providing only aggregate data with the two-stage method. Main outcomes were pooled using random-effects models. Sensitivity and subgroup analyses were used to explore sources of heterogeneity and the effect of potential confounders. The influences of age, whole-body/abdominal obesity, homeostasis model of insulin resistance (HOMA-IR), and duration of follow-up on effect estimates were assessed by meta-regression. Thirty-three studies (63,902 participants, 16 population-based and 17 hospital-based, 20 cross-sectional, and 13 longitudinal) were included. For 20 studies (61% of included studies, 11 cross-sectional and nine longitudinal, 29,282 participants), we obtained IPD. NAFLD was associated with an increased risk of prevalent (odds ratio [OR] 2.12, 95% CI 1.69-2.66) and incident (hazard ratio [HR] 1.79, 95% CI 1.65-1.95) CKD. Non-alcoholic steatohepatitis (NASH) was associated with a higher prevalence (OR 2.53, 95% CI 1.58-4.05) and incidence (HR 2.12, 95% CI 1.42-3.17) of CKD than simple steatosis. Advanced fibrosis was associated with a higher prevalence (OR 5.20, 95% CI 3.14-8.61) and incidence (HR 3.29, 95% CI 2.30-4.71) of CKD than non-advanced fibrosis. In all analyses, the magnitude and direction of effects remained unaffected by diabetes status, after adjustment for other risk factors, and in other subgroup and meta-regression analyses. In cross-sectional and longitudinal studies, the severity of NAFLD was positively associated with CKD stages. Limitations of analysis are the relatively small size of studies utilizing liver histology and the suboptimal sensitivity of ultrasound and biochemistry for NAFLD detection in population-based studies. CONCLUSION The presence and severity of NAFLD are associated with an increased risk and severity of CKD. Please see later in the article for the Editors' Summary.
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Affiliation(s)
| | - Roberto Gambino
- Dept. of Medical Sciences, San Giovanni Battista Hospital, University of Turin, Turin, Italy
| | - James H. Tabibian
- Division of Gastroenterology and Hepatology Mayo Clinic, Rochester, Minnesota, United States of America
| | - Mattias Ekstedt
- Division of Gastroenterology and Hepatology, Linköping University, Linköping, Sweden
| | - Stergios Kechagias
- Division of Cardiovascular Medicine, Department of Medical and Health Sciences, Linköping University, Linköping, Sweden
| | - Masahide Hamaguchi
- Department of Experimental Immunology, World Premier International Immunology Frontier Research Center, Osaka University, Osaka, Japan
| | - Rolf Hultcrantz
- Departments of Gastroenterology and Hepatology, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden
| | - Hannes Hagström
- Departments of Gastroenterology and Hepatology, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden
| | - Seung Kew Yoon
- Division of Hepato-Gastroenterology, Department of Internal Medicine, Kangnam St. Mary Hospital, Catholic University Medical College, Seoul, Korea
| | | | - Jacob George
- Storr Liver Unit, Westmead Millennium Institute, University of Sydney and Department of Gastroenterology and Hepatology, Westmead Hospital, Westmead, New South Wales, Australia
| | - Francisco Barrera
- Storr Liver Unit, Westmead Millennium Institute, University of Sydney and Department of Gastroenterology and Hepatology, Westmead Hospital, Westmead, New South Wales, Australia
| | - Svanhildur Hafliðadóttir
- Dept of Gastroenterology and Hepatology, Landspitali University Hospital, Hringbrau, Reykjavik, Iceland
| | - Einar Stefan Björnsson
- Dept of Gastroenterology and Hepatology, Landspitali University Hospital, Hringbrau, Reykjavik, Iceland
| | - Matthew J. Armstrong
- Centre for Liver Research and NIHR Biomedical Research Unit in Liver Disease, Institute of Biomedical Research, University of Birmingham, Birmingham, United Kingdom
| | - Laurence J. Hopkins
- Centre for Liver Research and NIHR Biomedical Research Unit in Liver Disease, Institute of Biomedical Research, University of Birmingham, Birmingham, United Kingdom
| | - Xin Gao
- Department of Endocrinology and Metabolism, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Sven Francque
- Department of Gastroenterology and Hepatology, Antwerp University Hospital, University of Antwerp, Antwerp, Belgium
| | - An Verrijken
- Department of Endocrinology, Diabetology and Metabolism, Antwerp University Hospital, University of Antwerp, Antwerp, Belgium
| | - Yusuf Yilmaz
- Department of Gastroenterology, Marmara University, School of Medicine, Istanbul, Turkey
| | - Keith D. Lindor
- Division of Gastroenterology and Hepatology Mayo Clinic, Rochester, Minnesota, United States of America
| | - Michael Charlton
- Division of Gastroenterology and Hepatology Mayo Clinic, Rochester, Minnesota, United States of America
| | - Robin Haring
- Institute of Clinical Chemistry and Laboratory Medicine, Ernst-Moritz-Arndt University Greifswald, Greifswald, Germany
| | - Markus M. Lerch
- Department of Medicine A, University Medicine Greifswald, Greifswald, Germany
| | - Rainer Rettig
- Institute of Physiology, Ernst-Moritz-Arndt-University Medicine Greifswald, Karlsburg, Germany
| | - Henry Völzke
- Institute for Community Medicine, Ernst-Moritz-Arndt University Medicine Greifswald, Greifswald, Germany
| | - Seungho Ryu
- Department of Occupational and Environmental Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University, School of Medicine, Seoul, Republic of Korea
| | - Guolin Li
- College of Life Sciences, Hunan Normal University, Changsha, China
| | - Linda L. Wong
- John A. Burns School of Medicine at University of Hawaii, Transplant Institute, Hawaii Medical Center, Honolulu, Hawaii, United States of America
| | - Mariana Machado
- Department of Gastroenterology, University Hospital of Santa Maria, Institute of Molecular Medicine, Lisbon, Portugal
| | - Helena Cortez-Pinto
- Department of Gastroenterology, University Hospital of Santa Maria, Institute of Molecular Medicine, Lisbon, Portugal
| | - Kohichiroh Yasui
- Department of Molecular Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Japan
| | - Maurizio Cassader
- Dept. of Medical Sciences, San Giovanni Battista Hospital, University of Turin, Turin, Italy
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Outcomes of liver transplantation for nonalcoholic steatohepatitis: a systematic review and meta-analysis. Clin Gastroenterol Hepatol 2014; 12:394-402.e1. [PMID: 24076414 DOI: 10.1016/j.cgh.2013.09.023] [Citation(s) in RCA: 145] [Impact Index Per Article: 13.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/11/2013] [Revised: 09/01/2013] [Accepted: 09/04/2013] [Indexed: 02/06/2023]
Abstract
BACKGROUND & AIMS Little is known about outcomes of patients with nonalcoholic steatohepatitis (NASH) who receive liver transplants. We performed a systematic review and meta-analysis to estimate post-transplant outcomes, survival times, and mortality from cardiovascular complications, sepsis, and graft failure in these patients. METHODS We searched PubMed and EMBASE, and Cochrane library and Web of Science databases for studies published through September 1, 2012 of patients who underwent liver transplantation for NASH or nonalcoholic fatty liver disease (NAFLD). All original studies from single institutions that reported outcomes of patients with or without NASH after liver transplantation were considered. Odds ratios (ORs) were calculated for patients with NASH, compared with patients without NASH; 95% confidence intervals (CIs) were calculated. RESULTS Our final analysis included 9 publications, on 717 patients with NASH and 3520 without, all of whom underwent liver transplantation. Similar proportions of patients with and without NASH who received liver transplants survived for 1, 3, and 5 years (OR for survival of patient with NASH 1 year after liver transplantation, 0.77; 95% CI, 0.59-1.00; P = .05; OR 3 years after transplantation, 0.97; 95% CI, 0.67-1.40; P = .86; OR 5 years after transplantation, 1.09; 95% CI, 0.77-1.56; P = .63). Patients with NASH had a greater risk of death from cardiovascular complications after liver transplantation (OR, 1.65; 95% CI, 1.01-2.70; P = .05) and from sepsis (OR, 1.71; 95% CI, 1.17-2.50; P = .006). However, patients with NASH were at lower risk of graft failure compared with patients without NASH (OR, 0.21; 95% CI, 0.05-0.89; P = .03). CONCLUSIONS Similar proportions of patients with and without NASH survive for 1, 3, and 5 years after liver transplantation. However, patients with NASH are more likely to die from cardiovascular complications or sepsis. More attention and careful consideration are therefore required in selecting patients with NASH for liver transplantation, along with aggressive management of cardiovascular complications and sepsis after transplantation.
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Weight loss interventions for morbidly obese patients with compensated cirrhosis: a Markov decision analysis model. J Gastrointest Surg 2014; 18:321-7. [PMID: 23918085 DOI: 10.1007/s11605-013-2298-y] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/05/2013] [Accepted: 07/16/2013] [Indexed: 01/31/2023]
Abstract
Many transplant centers require that patients maintain a BMI below 40 kg/m(2) in order to be eligible for listing, rendering many morbidly obese patients with end-stage liver disease unable to access liver transplantation as a method of treatment. In order to determine the safest and most efficacious weight loss regimen in this challenging population, Roux-en-Y gastric bypass (RYGB), adjustable gastric banding (AGB), and diet and exercise were modeled to assess their impact on life expectancy in morbidly obese patients with cirrhosis. A Markov state transition model was developed to assess the survival benefit of undergoing RYGB, AGB, or 1 year of diet and exercise in morbidly obese patients with compensated cirrhosis. A base case analysis of no weight loss intervention in a 45-year-old patient with compensated cirrhosis and a BMI of 45 kg/m(2) revealed an average survival of 7.93 years. The average survival for the weight loss simulations was 9.14, 8.84, and 8.16 years for RYGB, AGB, and diet and exercise, respectively. In morbidly obese patients with compensated cirrhosis, RYGB allows patients to lose more weight more rapidly than is probable with either AGB or diet and exercise, thus having the greatest impact on survival.
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Said A. Non-alcoholic fatty liver disease and liver transplantation: Outcomes and advances. World J Gastroenterol 2013; 19:9146-9155. [PMID: 24409043 PMCID: PMC3882389 DOI: 10.3748/wjg.v19.i48.9146] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/01/2013] [Revised: 10/28/2013] [Accepted: 11/03/2013] [Indexed: 02/07/2023] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) is one of the most prevalent causes of chronic liver disease worldwide. In the last decade it has become the third most common indication for liver transplantation in the United States. Increasing prevalence of NAFLD in the general population also poses a risk to organ donation, as allograft steatosis can be associated with non-function of the graft. Post-transplant survival is comparable between NAFLD and non-NAFLD causes of liver disease, although long term outcomes beyond 10 year are lacking. NAFLD can recur in the allograft frequently although thus far post transplant survival has not been impacted. De novo NAFLD can also occur in the allograft of patients transplanted for non-NAFLD liver disease. Predictors for NAFLD post-transplant recurrence include obesity, hyperlipidemia and diabetes as well as steroid dose after liver transplantation. A polymorphism in PNPLA3 that mediates triglyceride hydrolysis and is linked to pre-transplant risk of obesity and NAFLD has also been linked to post transplant NAFLD risk. Although immunosuppression side effects potentiate obesity and the metabolic syndrome, studies of immunosuppression modulation and trials of specific immunosuppression regimens post-transplant are lacking in this patient population. Based on pre-transplant data, sustained weight loss through diet and exercise is the most effective therapy for NAFLD. Other agents occasionally utilized in NAFLD prior to transplantation include vitamin E and insulin-sensitizing agents. Studies of these therapies are lacking in the post-transplant population. A multimodality and multidisciplinary approach to treatment should be utilized in management of post-transplant NAFLD.
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Abstract
Model for end-stage liver disease (MELD) score, initially developed to predict survival following transjugular intrahepatic portosystemic shunt was subsequently found to be accurate predictor of mortality amongst patents with end-stage liver disease. Since 2002, MELD score using 3 objective variables (serum bilirubin, serum creatinine, and institutional normalized ratio) has been used worldwide for listing and transplanting patients with end-stage liver disease allowing transplanting sicker patients first irrespective of the wait time on the list. MELD score has also been shown to be accurate predictor of survival amongst patients with alcoholic hepatitis, following variceal hemorrhage, infections in cirrhosis, after surgery in patients with cirrhosis including liver resection, trauma, and hepatorenal syndrome (HRS). Although, MELD score is closest to the ideal score, there are some limitations including its inaccuracy in predicting survival in 15-20% cases. Over the last decade, many efforts have been made to further improve and refine MELD score. Until, a better score is developed, liver allocation would continue based on the currently used MELD score.
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Key Words
- AH, alcoholic hepatitis
- BAR, balance risk
- CTP, Child–Pugh–Turcotte
- Cirrhosis
- DFI, discriminate function index
- EDC, extended donor criteria
- ESLD, end-stage liver disease
- FHF, fulminant hepatic failure
- GFR, glomerular filtration rate
- HVPG, hepatic venous pressure gradient
- LT, liver transplantation
- Liver transplantation
- MDRD, modification of diet in renal disease
- MELD
- MELD, model for end-stage liver disease
- MLP, multi-layer perceptron
- QALY, quality adjusted life years
- SLK, simultaneous liver kidney transplantation
- SOFA, sequential organ failure assessment
- SOFT, survival outcomes following transplantation
- TIPS, transjugular intrahepatic portosystemic
- UKELD, UK end stage liver disease score
- UNOS, United Network for Organ Sharing
- VH, variceal hemorrhage
- deMELD, drop-out equivalent MELD
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Affiliation(s)
| | - Patrick S. Kamath
- Address for correspondence: Patrick S. Kamath, Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA.
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50
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Burra P, De Martin E, Gitto S, Villa E. Influence of age and gender before and after liver transplantation. Liver Transpl 2013; 19:122-34. [PMID: 23172830 DOI: 10.1002/lt.23574] [Citation(s) in RCA: 51] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/24/2012] [Accepted: 11/08/2012] [Indexed: 12/15/2022]
Abstract
Women constitute a particular group among patients with chronic liver disease and in the post-liver transplantation (LT) setting: they are set apart not only by traditional differences with respect to men (ie, body mass index, different etiologies of liver disease, and accessibility to transplantation) but also in increasingly evident ways related to hormonal changes that characterize first the fertile age and subsequently the postmenopausal period (eg, disease course variability and responses to therapy). The aim of this review is, therefore, to evaluate the role of the interplay of factors such as age, gender, and hormones in influencing the natural history of chronic liver disease before and after LT and their importance in determining outcomes after LT. As the population requiring LT ages and the mean age at transplantation increases, older females are being considered for transplantation. Older patients are at greater risk for nonalcoholic steatohepatitis, osteoporosis, and a worse response to antiviral therapy. Female gender per se is associated with a greater risk for osteoporosis because of metabolic changes after menopause, the bodily structure of females, and, in the population of patients with chronic liver disease, the greater prevalence of cholestatic and autoimmune liver diseases. With menopause, the fall of protective estrogen levels can lead to increased fibrosis progression, and this represents a negative turning point for women with chronic liver disease and especially for patients with hepatitis C. Therefore, the notion of gender as a binary female/male factor is now giving way to the awareness of more complex disease processes within the female gender that follow hormonal, social, and age patterns and need to be addressed directly and specifically.
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Affiliation(s)
- Patrizia Burra
- Multivisceral Transplant Unit, Department of Surgery, Oncology, and Gastroenterology, Padua University Hospital, Padua, Italy.
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