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Arora A, Sharma P, Kumar A, Acharya S, Sarin SK, Duseja A, Puri P, Shah S, Chawla Y, Rao P, Saraya A, Mohanka R, Singh S, Saighal S, Rela M, Vij V, Asthana S, Shukla A, Bhangui P, Saraf N, Maiwall R, Mandot A, Saraswat V, Madan K, Shalimar, Kapoor D, Anand AC, Gupta S, Varghese J, Mehta N. Indian National Association for the Study of Liver (INASL) Guidance Statements for Determining Futility in Liver Transplantation. J Clin Exp Hepatol 2025; 15:102539. [PMID: 40343081 PMCID: PMC12056968 DOI: 10.1016/j.jceh.2025.102539] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/22/2024] [Accepted: 02/24/2025] [Indexed: 05/10/2025] Open
Abstract
Liver transplantation (LT) is a life-saving procedure for patients with end-stage liver disease; however, with the growing shortage of organ donors, the need to identify futile transplants has become increasingly urgent. Futility in liver transplantation refers to situations where the expected post-transplant survival or quality of life is poor, making the procedure unlikely to yield a meaningful benefit. Various definitions of futility are used across different countries and transplant centers, with criteria often based on clinical factors such as age, comorbidities, MELD score, and functional status. For hepatologists and transplant surgeons, clearer guidelines are essential to make informed decisions and avoid unnecessary transplants that may place patients at risk without improving their prognosis. While some studies have proposed futility scores, there is currently no universal consensus on a standardized definition or set of criteria. This highlights the need for further prospective trials to evaluate the predictors of futility in liver transplantation, aiming to refine decision-making processes, optimize organ allocation, and improve patient outcomes. Future research should focus on the development of universally accepted futility criteria and explore interventions to mitigate the factors contributing to transplant futility.
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Affiliation(s)
- Anil Arora
- Institute of Liver Gastroenterology & Pancreatico Biliary Sciences. Sir Ganga Ram Hospital, Rajinder Nagar, New Delhi, 110060, India
| | - Praveen Sharma
- Institute of Liver Gastroenterology & Pancreatico Biliary Sciences. Sir Ganga Ram Hospital, Rajinder Nagar, New Delhi, 110060, India
| | - Ashish Kumar
- Institute of Liver Gastroenterology & Pancreatico Biliary Sciences. Sir Ganga Ram Hospital, Rajinder Nagar, New Delhi, 110060, India
| | - S.K. Acharya
- Kalinga Institute of Medical Sciences (KIMS), Kushabhadra Campus (KIIT Campus-5), Patia, Bhubaneswar, 751024, Odisha, India
| | - Shiv K. Sarin
- Institute of Liver and Biliary Sciences, Delhi, India
| | - Ajay Duseja
- Post Institute of Medical Sciences, Chandigarh, India
| | | | - Samir Shah
- Institute of Liver Disease, HPB Surgery and Transplant, Global Hospitals, Dr E Borges Road, Parel, Mumbai, 400012, India
| | - Y.K. Chawla
- Kalinga Institute of Medical Sciences (KIMS), Kushabhadra Campus (KIIT Campus-5), Patia, Bhubaneswar, 751024, Odisha, India
| | - P.N. Rao
- Asian Institute of Gsstroenterology, Hyderabad, India
| | - Anoop Saraya
- All India Institute of Medical Sciences, New Delhi, India
| | - Ravi Mohanka
- Sir HN Reliance Foundation Hospital, Mumbai, India
| | | | | | - Mohamed Rela
- Dr. Rela Institute & Medical Centre, #7, CLC Works Road, Chromepet, Chennai, 600044, India
| | - Vivek Vij
- Fortis Hospital, Noida, Delhi, India
| | - Sonal Asthana
- Aster CMI Bangalore, Aster RV Bangalore, Aster Whitefield, Bangalore, India
| | - Akash Shukla
- Reliance Foundation Hospital and Research Centre, Mumbai, India
- Seth GSMC & KEM Hospital, Mumbai, 400022, India
| | | | | | - Rakhi Maiwall
- Institute of Liver and Biliary Sciences, Delhi, India
| | - Amit Mandot
- Institute of Liver Disease, HPB Surgery and Transplant, Global Hospitals, Dr E Borges Road, Parel, Mumbai, 400012, India
| | | | | | - Shalimar
- All India Institute of Medical Sciences, New Delhi, India
| | - Dharmesh Kapoor
- Mahatma Gandhi Medical College and Hospital, RIICO Institutional Area, Sitapura, Tonk Road, Jaipur, 302022, Rajasthan, India
- Yashoda Hospital, Hyderabad, India
| | - Anil C. Anand
- Kalinga Institute of Medical Sciences (KIMS), Kushabhadra Campus (KIIT Campus-5), Patia, Bhubaneswar, 751024, Odisha, India
| | | | - Joy Varghese
- Gleneagles Global Health City, 439, Cheran Nagar, Perumbakkam, Chennai, Tamil Nadu, 600100, India
| | - Naimish Mehta
- Institute of Liver Gastroenterology & Pancreatico Biliary Sciences. Sir Ganga Ram Hospital, Rajinder Nagar, New Delhi, 110060, India
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Junna S, Nasser S, Sharma P. Renal Dysfunction and Liver Transplantation. Clin Liver Dis 2025; 29:273-285. [PMID: 40287271 DOI: 10.1016/j.cld.2024.12.009] [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: 04/29/2025]
Abstract
Renal dysfunction is common in patients undergoing liver transplant (LT) evaluation, thereby making it imperative for hepatologists to know how to diagnose, manage, and optimize treatment of acute kidney injury (AKI) and chronic kidney disease. This article reviews pre-transplant, peri-transplant, and post-transplant AKI diagnosis and management, and the role of renal replacement therapy in LT candidates.
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Affiliation(s)
- Shilpa Junna
- Mikati Center for Liver Diseases, Cleveland Clinic Foundation, Cleveland, OH, USA. https://twitter.com/gishilpz
| | - Sarah Nasser
- Department of Internal Medicine, University of Michigan Health System, Ann Arbor, MI, USA
| | - Pratima Sharma
- Department of Internal Medicine, University of Michigan Health System, Ann Arbor, MI, USA; Division of Gastroenterology and Hepatology, University of Michigan Health System, Ann Arbor, MI, USA.
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Pădureanu V, Dop D, Radu L, Rădulescu D, Pădureanu R, Pîrșcoveanu DFV, Caragea DC. Nephrological, Pulmonary, and Dermatological Complications in the Context of MAFLD/NAFLD: A Narrative Review. Metabolites 2025; 15:272. [PMID: 40278401 PMCID: PMC12029749 DOI: 10.3390/metabo15040272] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2025] [Revised: 04/07/2025] [Accepted: 04/11/2025] [Indexed: 04/26/2025] Open
Abstract
Background: The most common cause of chronic liver disease is now known to be non-alcoholic fatty liver disease (NAFLD), recently redefined as metabolic-associated fatty liver disease (MAFLD). This review aims to synthesize current evidence on the pathophysiology and clinical implications of nephrological, pulmonary, and dermatological manifestations among NAFLD/MAFLD patients. In order to find safe and efficient treatments, NAFLD/MAFLD has emerged as a primary concern for hepatologists worldwide. Methods: We conducted a comprehensive review of the literature from major databases, focusing on studies that evaluated the extrahepatic manifestations of NAFLD/MAFLD. Emphasis was placed on identifying pathophysiological mechanisms and assessing their clinical impact on renal, pulmonary, and dermatological systems. Results: Recent developments in the management of chronic viral hepatitis have lowered the mortality rate associated with chronic liver disease. However, the prevalence of NAFLD/MAFLD continues to rise, making chronic liver disease a significant health concern for the future. An increasing percentage of patients on liver transplant waiting lists now have cirrhosis and hepatocellular carcinoma due to non-alcoholic liver disease. Furthermore, the incidence and prevalence of chronic kidney disease have surged, linking NAFLD/MAFLD to higher morbidity, mortality, and healthcare costs. Conclusions: NAFLD/MAFLD is underdiagnosed and underappreciated, yet its incidence is rapidly increasing, raising concerns about a potential global epidemic. Given its multisystemic impact-extending to renal, pulmonary, and dermatological complications-it is crucial to develop interdisciplinary strategies for early detection and effective management of the disease.
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Affiliation(s)
- Vlad Pădureanu
- Department of Internal Medicine, University of Medicine and Pharmacy Craiova, 200349 Craiova, Romania;
| | - Dalia Dop
- Department of Pediatrics, University of Medicine and Pharmacy Craiova, 200349 Craiova, Romania;
| | - Lucrețiu Radu
- Department of Hygiene, University of Medicine and Pharmacy Craiova, 200349 Craiova, Romania;
| | - Dumitru Rădulescu
- Department of Surgery, University of Medicine and Pharmacy Craiova, 200349 Craiova, Romania
| | - Rodica Pădureanu
- Department of Internal Medicine, University of Medicine and Pharmacy Craiova, 200349 Craiova, Romania;
| | | | - Daniel Cosmin Caragea
- Department of Nephrology, University of Medicine and Pharmacy Craiova, 200349 Craiova, Romania;
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Satapathy SK, Elwir S, Brandman D, Smith C, Jiang Y, Vanatta J, Ha NB, Cheung AC, Bhat M, Patel P, Siddiqui MS, Rinella ME, Watt KD. Risk Stratification for Chronic Kidney Disease After Liver Transplant for Metabolic Dysfunction-associated Steatohepatitis (MASH) Cirrhosis: Results From the NailMASH Consortium. Transplantation 2025; 109:484-495. [PMID: 39434206 DOI: 10.1097/tp.0000000000005236] [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: 10/23/2024]
Abstract
BACKGROUND Chronic kidney disease (CKD) is a well-recognized complication in patients undergoing liver transplantation (LT), particularly those with metabolic dysfunction-associated steatohepatitis (MASH), a leading cause of cirrhosis in the modern era. This study sought to refine risk stratification for CKD events post-LT in cirrhosis patients with MASH by leveraging baseline renal function at transplant. METHODS A total of 717 MASH cirrhosis patients who had LT (1997-2017) at 7 US centers (NailMASH Consortium) were analyzed. Patients were categorized by estimated glomerular filtration rate (eGFR) at transplant: low (LGFR, eGFR ≤30 mL/min/1.73 m²), medium (MGFR, eGFR >30-≤60 mL/min/1.73 m²), and high (HGFR, eGFR >60 mL/min/1.73 m²). Time-related eGFR intercepts, slopes, and assessments of advanced-stage CKD (aCKD) events, defined as 2 eGFR levels <30 mL/min/1.73 m² separated by ≥90 d, were examined. RESULTS Post-LT, LGFR group showed increased eGFR, whereas the HGFR group experienced a decline. The 3-mo mark was identified as a "reset point," signifying a new reference level, beyond which a different rate of decline was observed. After 3 mo, mean eGFRs of the LGFR group approached MGFRs, whereas the mean eGFR of the HGFR group continued to decrease but remained higher than other groups during a 60-mo follow-up. LGFR patients had significantly higher aCKD probability than MGFR and HGFR groups. Subanalysis at 3 mo post-LT revealed more aCKD events in the LGFR group compared with MGFR and HGFR groups ( P < 0.0001). CONCLUSIONS The study underscores renal impact of LT in MASH cirrhosis, indicating unique eGFR trajectories post-LT tied to baseline eGFR, with a reset point at 3 mo. Monitoring post-LT renal function, especially in those at aCKD risk, is crucial. Renal-sparing immunosuppression may help, regardless of baseline eGFR. Further studies are needed for interventions addressing renal dysfunction of patients with MASH post-LT.
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Affiliation(s)
- Sanjaya K Satapathy
- Northwell Health Center for Liver Diseases and Transplantation, Northshore University Hospital/Northwell Health, Manhasset, NY
| | - Saleh Elwir
- Annette C. and Harold C. Simmons Transplant Institute, Baylor University Medical Center, Dallas, TX
| | - Danielle Brandman
- Center for Liver Disease and Transplantation, New York Presbyterian-Weill Cornell Medicine, New York, NY
| | - Coleman Smith
- MedStar Georgetown Transplant Institute, Washington, DC
| | - Yu Jiang
- University of Tennessee/Methodist University Hospital, Memphis, TN
| | - Jason Vanatta
- University of Tennessee/Methodist University Hospital, Memphis, TN
| | - Nghiem B Ha
- Division of Gastroenterology and Hepatology, University of California, San Francisco, San Francisco, CA
| | - Amanda C Cheung
- Northwestern University Feinberg School of Medicine, Chicago, IL
| | | | - Pratik Patel
- Annette C. and Harold C. Simmons Transplant Institute, Baylor University Medical Center, Dallas, TX
| | | | - Mary E Rinella
- Pritzker School of Medicine, University of Chicago, Chicago, IL
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Zhang IW, Lurje I, Lurje G, Knosalla C, Schoenrath F, Tacke F, Engelmann C. Combined Organ Transplantation in Patients with Advanced Liver Disease. Semin Liver Dis 2024; 44:369-382. [PMID: 39053507 PMCID: PMC11449526 DOI: 10.1055/s-0044-1788674] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 07/27/2024]
Abstract
Transplantation of the liver in combination with other organs is an increasingly performed procedure. Over the years, continuous improvement in survival could be realized through careful patient selection and refined organ preservation techniques, in spite of the challenges posed by aging recipients and donors, as well as the increased use of steatotic liver grafts. Herein, we revisit the epidemiology, allocation policies in different transplant zones, indications, and outcomes with regard to simultaneous organ transplants involving the liver, that is combined heart-liver, liver-lung, liver-kidney, and multivisceral transplantation. We address challenges surrounding combined organ transplantation such as equity, utility, and logistics of dual organ implantation, but also advantages that come along with combined transplantation, thereby focusing on molecular mechanisms underlying immunoprotection provided by the liver to the other allografts. In addition, the current standing and knowledge of machine perfusion in combined organ transplantation, mostly based on center experience, will be reviewed. Notwithstanding all the technical advances, shortage of organs, and the lack of universal eligibility criteria for certain multi-organ combinations are hurdles that need to be tackled in the future.
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Affiliation(s)
- Ingrid Wei Zhang
- Department of Hepatology and Gastroenterology, Charité Universitätsmedizin Berlin, Berlin, Germany
- Berlin Institute of Health (BIH) at Charité - Universitätsmedizin, Berlin, Germany
- European Foundation for the Study of Chronic Liver Failure (EF CLIF) and Grifols Chair, Barcelona, Spain
| | - Isabella Lurje
- Department of Hepatology and Gastroenterology, Charité Universitätsmedizin Berlin, Berlin, Germany
| | - Georg Lurje
- Department of Surgery, Charité Universitätsmedizin Berlin, Berlin, Germany
| | - Christoph Knosalla
- Department of Cardiothoracic and Vascular Surgery, Deutsches Herzzentrum der Charité, Berlin, Germany
- Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany
- DZHK (German Centre for Cardiovascular Research), Partner Site Berlin, Berlin, Germany
| | - Felix Schoenrath
- Department of Cardiothoracic and Vascular Surgery, Deutsches Herzzentrum der Charité, Berlin, Germany
- Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany
- DZHK (German Centre for Cardiovascular Research), Partner Site Berlin, Berlin, Germany
| | - Frank Tacke
- Department of Hepatology and Gastroenterology, Charité Universitätsmedizin Berlin, Berlin, Germany
| | - Cornelius Engelmann
- Department of Hepatology and Gastroenterology, Charité Universitätsmedizin Berlin, Berlin, Germany
- Berlin Institute of Health (BIH) at Charité - Universitätsmedizin, Berlin, Germany
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Moon JJ, Hong SK, Kim YC, Hong SY, choi Y, Yi NJ, Lee KW, Han SS, Lee H, Kim DK, Kim YS, Yang SH, Suh KS. Soluble suppression of tumorigenicity 2 is a potential predictor of post-liver transplant renal outcomes. PLoS One 2023; 18:e0293844. [PMID: 37917773 PMCID: PMC10621951 DOI: 10.1371/journal.pone.0293844] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/21/2023] [Accepted: 10/18/2023] [Indexed: 11/04/2023] Open
Abstract
Acute kidney injury is considered an independent prognostic factor for mortality in patients with liver cirrhosis. Non-treated acute kidney injury can progress to hepatorenal syndrome with a poor prognosis. As suppression of tumorigenicity 2 (ST2) is a member of the interleukin-1 receptor family that aggravates inflammation and fibrotic changes in multiple organs, we measured soluble ST2 (sST2) level in the serum and urine of liver-transplant recipients at the time of transplantation. The serum sST2 level significantly increased in liver-transplant recipients with suppressed kidney function compared with that in recipients with normal function. In recipients with severely decreased liver function (model for end-stage liver disease score ≥ 30), the serum sST2 level was higher than that in recipients with preserved liver function (model for end-stage liver disease score ≤ 20, P = 0.028). The serum sST2 level in recipients with hepatorenal syndrome was higher than that in liver-transplant recipients without hepatorenal syndrome (P = 0.003). The serum sST2 level in patients with hepatorenal syndrome was higher than that in recipients without a history of acute kidney injury (P = 0.004). Recipients with hepatorenal syndrome and recovered kidney function showed higher sST2 levels than those who did not recover (P = 0.034). Collectively, an increase in the serum sST2 level reflects a decrease in both kidney and liver functions. Thus, measuring sST2 level at the time of liver transplantation can help predict renal outcomes.
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Affiliation(s)
- Jong Joo Moon
- Seoul National University Biomedical Research Institute, Seoul, Korea
| | - Suk Kyun Hong
- Department of Surgery, Seoul National University College of Medicine, Seoul, Korea
| | - Yong Chul Kim
- Division of Nephrology, Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea
| | - Su young Hong
- Department of Surgery, Seoul National University College of Medicine, Seoul, Korea
| | - YoungRok choi
- Department of Surgery, Seoul National University College of Medicine, Seoul, Korea
| | - Nam-Joon Yi
- Department of Surgery, Seoul National University College of Medicine, Seoul, Korea
| | - Kwang-Woong Lee
- Department of Surgery, Seoul National University College of Medicine, Seoul, Korea
| | - Seung Seok Han
- Division of Nephrology, Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea
| | - Hajeong Lee
- Division of Nephrology, Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea
| | - Dong Ki Kim
- Division of Nephrology, Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea
- Kidney Research Institute, Seoul National University Medical Research Center, Seoul, Korea
| | - Yon Su Kim
- Division of Nephrology, Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea
- Kidney Research Institute, Seoul National University Medical Research Center, Seoul, Korea
| | - Seung Hee Yang
- Seoul National University Biomedical Research Institute, Seoul, Korea
- Kidney Research Institute, Seoul National University Medical Research Center, Seoul, Korea
| | - Kyung-Suk Suh
- Department of Surgery, Seoul National University College of Medicine, Seoul, Korea
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Fernández-Carrillo C, Li Y, Ventura-Cots M, Argemi J, Dai D, Clemente-Sánchez A, Duarte-Rojo A, Behari J, Ganesh S, Jonassaint NL, Tevar AD, Hughes CB, Humar A, Molinari M, Landsittel DP, Bataller R. Poor Outcomes of Patients With NAFLD and Moderate Renal Dysfunction or Short-Term Dialysis Receiving a Liver Transplant Alone. Transpl Int 2022; 35:10443. [PMID: 36568138 PMCID: PMC9784907 DOI: 10.3389/ti.2022.10443] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2022] [Accepted: 10/27/2022] [Indexed: 12/13/2022]
Abstract
The outcomes of patients with moderate renal impairment and the impact of liver disease etiology on renal function recovery after liver transplant alone (LTA) are largely unknown. We explored whether NAFLD patients with pre-LTA moderate renal dysfunction (GFR 25-45 ml/min/1.73 m2) may be more susceptible to develop post-LTA severe renal dysfunction (GFR<15 ml/min/1.73 m2) than ALD patients, as well as other overall outcomes. Using the UNOS/OPTN database, we selected patients undergoing liver transplant for NAFLD or ALD (2006-2016), 15,103 of whom received LTA. NAFLD patients with moderate renal dysfunction were more likely to develop subsequent GFR<15 ml/min/1.73 m2 than ALD patients (11.1% vs. 7.38%, p < 0.001). Patients on short-term dialysis pre-LTA (≤12 weeks) were more likely to develop severe renal dysfunction (31.7% vs. 18.1%), especially in NAFLD patients, and were more likely to receive a further kidney transplant (15.3% vs. 3.7%) and had lower survival (48.6% vs. 50.4%) after LTA (p < 0.001 for all). NAFLD was an independent risk factor for post-LTA severe renal dysfunction (HR = 1.2, p = 0.02). NAFLD patients with moderate renal dysfunction and those receiving short-term dialysis prior to LTA are at a higher risk of developing subsequent severe renal dysfunction. Underlying etiology of liver disease may play a role in predicting development and progression of renal failure in patients receiving LTA.
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Affiliation(s)
- Carlos Fernández-Carrillo
- Center for Liver Diseases, Division of Gastroenterology, Hepatology and Nutrition, Department of Medicine, University of Pittsburgh Medical Center, Pittsburgh, PA, United States,CIBERehd. Instituto de Salud Carlos III, Madrid, Spain,Gastroenterología y Hepatología, IDIPHISA, Hospital Universitario Puerta de Hierro-Majadahonda, Madrid, Spain
| | - Yaming Li
- Department of Biomedical Informatics, University of Pittsburgh, Pittsburgh, PA, United States
| | - Meritxell Ventura-Cots
- Center for Liver Diseases, Division of Gastroenterology, Hepatology and Nutrition, Department of Medicine, University of Pittsburgh Medical Center, Pittsburgh, PA, United States,CIBERehd. Instituto de Salud Carlos III, Madrid, Spain
| | - Josepmaria Argemi
- Center for Liver Diseases, Division of Gastroenterology, Hepatology and Nutrition, Department of Medicine, University of Pittsburgh Medical Center, Pittsburgh, PA, United States,CIBERehd. Instituto de Salud Carlos III, Madrid, Spain
| | - Dongling Dai
- Center for Liver Diseases, Division of Gastroenterology, Hepatology and Nutrition, Department of Medicine, University of Pittsburgh Medical Center, Pittsburgh, PA, United States
| | - Ana Clemente-Sánchez
- Center for Liver Diseases, Division of Gastroenterology, Hepatology and Nutrition, Department of Medicine, University of Pittsburgh Medical Center, Pittsburgh, PA, United States,CIBERehd. Instituto de Salud Carlos III, Madrid, Spain
| | - Andres Duarte-Rojo
- Center for Liver Diseases, Division of Gastroenterology, Hepatology and Nutrition, Department of Medicine, University of Pittsburgh Medical Center, Pittsburgh, PA, United States,Thomas E. Starzl Transplant Institute, Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA, United States
| | - Jaideep Behari
- Center for Liver Diseases, Division of Gastroenterology, Hepatology and Nutrition, Department of Medicine, University of Pittsburgh Medical Center, Pittsburgh, PA, United States
| | - Swaytha Ganesh
- Center for Liver Diseases, Division of Gastroenterology, Hepatology and Nutrition, Department of Medicine, University of Pittsburgh Medical Center, Pittsburgh, PA, United States,Thomas E. Starzl Transplant Institute, Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA, United States
| | - Naudia L. Jonassaint
- Center for Liver Diseases, Division of Gastroenterology, Hepatology and Nutrition, Department of Medicine, University of Pittsburgh Medical Center, Pittsburgh, PA, United States,Thomas E. Starzl Transplant Institute, Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA, United States
| | - Amit D. Tevar
- Thomas E. Starzl Transplant Institute, Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA, United States
| | - Christopher B. Hughes
- Thomas E. Starzl Transplant Institute, Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA, United States
| | - Abhinav Humar
- Thomas E. Starzl Transplant Institute, Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA, United States
| | - Michele Molinari
- Thomas E. Starzl Transplant Institute, Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA, United States
| | - Douglas P. Landsittel
- Department of Biomedical Informatics, University of Pittsburgh, Pittsburgh, PA, United States
| | - Ramon Bataller
- Center for Liver Diseases, Division of Gastroenterology, Hepatology and Nutrition, Department of Medicine, University of Pittsburgh Medical Center, Pittsburgh, PA, United States,*Correspondence: Ramon Bataller,
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8
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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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9
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Heda R, Kovalic AJ, Satapathy SK. Peritransplant Renal Dysfunction in Liver Transplant Candidates. Clin Liver Dis 2022; 26:255-268. [PMID: 35487609 DOI: 10.1016/j.cld.2022.01.010] [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: 01/31/2023]
Abstract
Renal function is intricately tied to Model for End-Stage Liver Disease score and overall prognosis among patients with cirrhosis. The estimation of glomerular filtration rate (GFR) and etiology of renal impairment are even more magnified among cirrhotic patients in the period surrounding liver transplantation. Novel biomarkers including cystatin C and urinary neutrophil gelatinase-associated lipocalin have been demonstrated to more accurately assess renal dysfunction and aid in the diagnosis of competing etiologies. Accurately identifying the severity and chronicity of renal dysfunction among transplant candidates is an imperative component with respect to stratifying patients toward simultaneous liver-kidney transplantation versus liver transplantation alone.
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Affiliation(s)
- Rajiv Heda
- Department of Internal Medicine, Tulane University School of Medicine, New Orleans, LA 70112, USA
| | - Alexander J Kovalic
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Northwell Health, Manhasset, NY 11030, USA
| | - Sanjaya K Satapathy
- Department of Medicine, Division of Hepatology, Sandra Atlas Bass Center for Liver Diseases and Transplantation, Manhasset, NY 11030, USA; Donald and Barbara Zucker School of Medicine at Hofstra/Northwell Health, 400 Community Drive, Manhasset, NY 11030, USA.
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10
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Minjares RO, Martin P, Carrion AF. Chronic Kidney Disease After Liver Transplantation. Clin Liver Dis 2022; 26:323-340. [PMID: 35487614 DOI: 10.1016/j.cld.2022.01.006] [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: 01/31/2023]
Abstract
Improved survival after liver transplantation has led to an aging cohort of recipients at risk of renal dysfunction. The etiology of renal dysfunction is typically multifactorial; calcineurin inhibitors nephrotoxicity, pretransplant renal dysfunction, and perioperative acute kidney injury are important risk factors. Metabolic complications such as hypertension, diabetes mellitus, and metabolic-associated fatty liver disease also contribute to the development of renal disease. Most LT recipients will eventually develop some degree of renal dysfunction. Criteria to select candidates for simultaneous liver and kidney transplantation have been established. Both delayed introduction of CNIs and renal-sparing immunosuppressive regimens may reduce progression of renal dysfunction.
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Affiliation(s)
- Ramon O Minjares
- Department of Internal Medicine, University of Miami Miller School of Medicine, 1611 NW 12th Avenue, Suite 600-D, Miami, FL 33136, USA.
| | - Paul Martin
- Division of Digestive Health and Liver Diseases, Department of Medicine, University of Miami Miller School of Medicine, 1611 NW 12th Avenue, Suite 600-D, Miami, FL 33136, USA
| | - Andres F Carrion
- Division of Digestive Health and Liver Diseases, Department of Medicine, University of Miami Miller School of Medicine, 1611 NW 12th Avenue, Suite 600-D, Miami, FL 33136, USA
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11
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Wadei HM, Burcin Taner C, Keaveny AP, Mai ML, Hodge DO, White LJ, Harnois DM, Mao SA, Jarmi T, Croome KP. The changing impact of pre-liver transplant renal dysfunction on post-transplant survival: results of 2 decades from a single center. Ann Hepatol 2022; 24:100317. [PMID: 33545403 DOI: 10.1016/j.aohep.2021.100317] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/20/2020] [Revised: 12/27/2020] [Accepted: 01/04/2021] [Indexed: 02/04/2023]
Abstract
INTRODUCTION AND OBJECTIVES Renal dysfunction before liver transplantation (LT) is associated with higher post-LT mortality. We aimed to study if this association still persisted in the contemporary transplant era. MATERIALS AND METHODS We retrospectively reviewed data on 2871 primary LT performed at our center from 1998 to 2018. All patients were listed for LT alone and were not considered to be simultaneous liver-kidney (SLK) transplant candidates. SLK recipients and those with previous LT were excluded. Patients were grouped into 4 eras: era-1 (1998-2002, n = 488), era-2 (2003-2007, n = 889), era-3 (2008-2012, n = 703) and era-4 (2013-2018, n = 791). Pre-LT renal dysfunction was defined as creatinine (Cr) >1.5 mg/dl or on dialysis at LT. The effect of pre-LT renal dysfunction on post-LT patient survival in each era was examined using Kaplan Meier estimates and univariate and multivariate Cox proportional hazard analyses. RESULTS Pre-LT renal dysfunction was present in 594 (20%) recipients. Compared to patients in era-1, patients in era-4 had higher Cr, lower eGFR and were more likely to be on dialysis at LT (P < 0.001). Pre-LT renal dysfunction was associated with worse 1, 3 and 5-year survival in era-1 and era-2 (P < 0.005) but not in era-3 or era-4 (P = 0.13 and P = 0.08, respectively). Multivariate analysis demonstrated the lack of independent effect of pre-LT renal dysfunction on post-LT mortality in era-3 and era-4. A separate analysis using eGFR <60 mL/min/1.73 m2 at LT to define renal dysfunction showed similar results. CONCLUSIONS Pre-LT renal dysfunction had less impact on post-LT survival in the contemporary transplant era.
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Affiliation(s)
- Hani M Wadei
- Department of Transplant, Mayo Clinic Florida, United States.
| | - C Burcin Taner
- Department of Transplant, Mayo Clinic Florida, United States
| | | | - Martin L Mai
- Department of Transplant, Mayo Clinic Florida, United States
| | - David O Hodge
- Department of Health Sciences Research, Mayo Clinic Florida, United States
| | - Launia J White
- Department of Health Sciences Research, Mayo Clinic Florida, United States
| | - Denis M Harnois
- Department of Transplant, Mayo Clinic Florida, United States
| | - Shennen A Mao
- Department of Transplant, Mayo Clinic Florida, United States
| | - Tambi Jarmi
- Department of Transplant, Mayo Clinic Florida, United States
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12
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Wadei HM, Keaveny AP, Taner CB, Yang L, Mai ML, Hodge DO, White LJ, Mao SA, Jarmi T, Croome KP. Post-Liver Transplant Early Allograft Dysfunction Modifies the Effect of Pre-Liver Transplant Renal Dysfunction on Post-Liver Transplant Survival. Liver Transpl 2021; 27:1291-1301. [PMID: 33687745 DOI: 10.1002/lt.26047] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/16/2020] [Revised: 02/13/2021] [Accepted: 03/01/2021] [Indexed: 01/13/2023]
Abstract
Pre-liver transplantation (LT) renal dysfunction is associated with poor post-LT survival. We studied whether early allograft dysfunction (EAD) modifies this association. Data on 2,856 primary LT recipients who received a transplant between 1998 and 2018 were retrospectively reviewed. Patients who died within the first post-LT week or received multiorgan transplants and previous LT recipients were excluded. EAD was defined as (1) total bilirubin ≥ 10 mg/dL on postoperative day (POD) 7, (2) international normalized ratio ≥1.6 on POD 7, and/or (3) alanine aminotransferase or aspartate aminotransferase ≥2000 IU/mL in the first postoperative week. Pre-LT renal dysfunction was defined as serum creatinine >1.5 mg/dL or on renal replacement therapy at LT. Patients were divided into 4 groups according to pre-LT renal dysfunction and post-LT EAD development. Recipients who had both pre-LT renal dysfunction and post-LT EAD had the worst unadjusted 1-year, 3-year, and 5-year post-LT patient and graft survival, whereas patients who had neither renal dysfunction nor EAD had the best survival (P < 0.001). After adjusting for multiple factors, the risk of death was significantly higher only in those with both pre-LT renal dysfunction and post-LT EAD (adjusted hazard ratio [aHR], 2.19; 95% confidence interval [CI], 1.58-3.03; P < 0.001), whereas those with renal dysfunction and no EAD had a comparable risk of death to those with normal kidney function at LT (aHR, 1.12; 95% CI, 0.86-1.45; P = 0.41). Results remained unchanged when pre-LT renal dysfunction was redefined using different glomerular filtration rate cutoffs. Pre-LT renal dysfunction negatively impacts post-LT survival only in patients who develop EAD. Livers at higher risk of post-LT EAD should be used with caution in recipients with pre-LT renal dysfunction.
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Affiliation(s)
- Hani M Wadei
- Department of Transplantation, Mayo Clinic Florida, Jacksonville, FL
| | - Andrew P Keaveny
- Department of Transplantation, Mayo Clinic Florida, Jacksonville, FL
| | - C Burcin Taner
- Department of Transplantation, Mayo Clinic Florida, Jacksonville, FL
| | - Liu Yang
- Department of Transplantation, Mayo Clinic Florida, Jacksonville, FL
| | - Martin L Mai
- Department of Transplantation, Mayo Clinic Florida, Jacksonville, FL
| | - David O Hodge
- Department of Health Sciences Research, Mayo Clinic Florida, Jacksonville, FL
| | - Launia J White
- Department of Health Sciences Research, Mayo Clinic Florida, Jacksonville, FL
| | - Shennen A Mao
- Department of Transplantation, Mayo Clinic Florida, Jacksonville, FL
| | - Tambi Jarmi
- Department of Transplantation, Mayo Clinic Florida, Jacksonville, FL
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13
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Altshuler PJ, Shah AP, Frank AM, Glorioso J, Dang H, Shaheen O, Patel K, Ramirez CB, Maley WR, Bodzin AS. Simultaneous liver kidney allocation policy and the Safety Net: an early examination of utilization and outcomes in the United States. Transpl Int 2021; 34:1052-1064. [PMID: 33884677 DOI: 10.1111/tri.13891] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2021] [Accepted: 04/12/2021] [Indexed: 01/31/2023]
Abstract
Rates of simultaneous liver kidney (SLK) transplantation in the United States have progressively risen. On 8/10/17, the Organ Procurement and Transplantation Network implemented a policy defining criteria for SLK, with a "Safety Net" to prioritize kidney allocation to liver recipients with ongoing renal failure. We performed a retrospective review of the United Network for Organ Sharing (UNOS) database to evaluate policy impact on SLK, kidney after liver (KAL) and kidney transplant alone (KTA). Rates and outcomes of SLK and KAL transplants were compared, as was utilization of high-quality kidney allografts with Kidney Donor Profile Indices (KDPI) <35%. Here, SLK transplants comprised 9.0% and 4.5% of total postpolicy liver and kidney transplants compared to 10.2% and 5.5% prior. Policy enactment did not affect 1-year graft or patient survival for SLK and KAL populations. Less postpolicy SLK transplants utilized high-quality kidney allografts; in all transplant settings, outcomes using high-quality grafts remained stable. These findings suggest that policy implementation has reduced kidney allograft use in SLK transplantation, although both SLK and KAL rates have recently increased. Despite decreased high-quality kidney allograft use, SLK and KAL outcomes have remained stable. Additional studies and long-term follow-up will ensure optimal organ access and sharing.
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Affiliation(s)
- Peter J Altshuler
- Department of Surgery, Thomas Jefferson University, Philadelphia, PA, USA
| | - Ashesh P Shah
- Department of Surgery, Thomas Jefferson University, Philadelphia, PA, USA
| | - Adam M Frank
- Department of Surgery, Thomas Jefferson University, Philadelphia, PA, USA
| | - Jaime Glorioso
- Department of Surgery, Thomas Jefferson University, Philadelphia, PA, USA
| | - Hien Dang
- Department of Surgery, Thomas Jefferson University, Philadelphia, PA, USA
| | - Osama Shaheen
- Department of Surgery, Thomas Jefferson University, Philadelphia, PA, USA
| | - Keyur Patel
- Department of Surgery, Thomas Jefferson University, Philadelphia, PA, USA
| | - Carlo B Ramirez
- Department of Surgery, Thomas Jefferson University, Philadelphia, PA, USA
| | - Warren R Maley
- Department of Surgery, Thomas Jefferson University, Philadelphia, PA, USA
| | - Adam S Bodzin
- Department of Surgery, Thomas Jefferson University, Philadelphia, PA, USA
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14
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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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15
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Kwong AJ, Devuni D, Wang C, Boike J, Jo J, VanWagner L, Serper M, Jones L, Sharma R, Verna EC, Shor J, German MN, Hristov A, Lee A, Spengler E, Koteish AA, Sehmbey G, Seetharam A, John N, Patel Y, Kappus MR, Couri T, Paul S, Salgia RJ, Nhu Q, Frenette CT, Lai JC, Goel A. Outcomes of Liver Transplantation Among Older Recipients With Nonalcoholic Steatohepatitis in a Large Multicenter US Cohort: the Re-Evaluating Age Limits in Transplantation Consortium. Liver Transpl 2020; 26:1492-1503. [PMID: 33047893 PMCID: PMC7960487 DOI: 10.1002/lt.25863] [Citation(s) in RCA: 23] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/11/2020] [Revised: 05/20/2020] [Accepted: 06/14/2020] [Indexed: 12/11/2022]
Abstract
The liver transplantation (LT) population is aging, with the need for transplant being driven by the growing prevalence of nonalcoholic steatohepatitis (NASH). Older LT recipients with NASH may be at an increased risk for adverse outcomes after LT. Our objective is to characterize outcomes in these recipients in a large multicenter cohort. All primary LT recipients ≥65 years from 2010 to 2016 at 13 centers in the Re-Evaluating Age Limits in Transplantation (REALT) consortium were included. Of 1023 LT recipients, 226 (22.1%) were over 70 years old, and 207 (20.2%) had NASH. Compared with other LT recipients, NASH recipients were older (68.0 versus 67.3 years), more likely to be female (47.3% versus 32.8%), White (78.3% versus 68.0%), Hispanic (12.1% versus 9.2%), and had higher Model for End-Stage Liver Disease-sodium (21 versus 18) at LT (P < 0.05 for all). Specific cardiac risk factors including diabetes with or without chronic complications (69.6%), hypertension (66.3%), hyperlipidemia (46.3%), coronary artery disease (36.7%), and moderate-to-severe renal disease (44.4%) were highly prevalent among NASH LT recipients. Graft survival among NASH patients was 90.3% at 1 year and 82.4% at 3 years compared with 88.9% at 1 year and 80.4% at 3 years for non-NASH patients (log-rank P = 0.58 and P = 0.59, respectively). Within 1 year after LT, the incidence of graft rejection (17.4%), biliary strictures (20.9%), and solid organ cancers (4.9%) were comparable. Rates of cardiovascular (CV) complications, renal failure, and infection were also similar in both groups. We observed similar posttransplant morbidity and mortality outcomes for NASH and non-NASH LT recipients. Certain CV risk factors were more prevalent in this population, although posttransplant outcomes within 1 year including CV events and renal failure were similar to non-NASH LT recipients.
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Affiliation(s)
- Allison J. Kwong
- Division of Gastroenterology and Hepatology, Department of Medicine, Stanford University, Palo Alto, CA
| | - Deepika Devuni
- University of Massachusetts Medical Center, Worcester, MA
| | - Connie Wang
- Division of Gastroenterology and Hepatology, Department of Medicine, University of California, San Francisco, San Francisco, CA
| | - Justin Boike
- Division of Gastroenterology and Hepatology, Department of Medicine, Northwestern University, Chicago, IL
| | - Jennifer Jo
- Division of Gastroenterology and Hepatology, Department of Medicine, Northwestern University, Chicago, IL
| | - Lisa VanWagner
- Division of Gastroenterology and Hepatology, Department of Medicine, Northwestern University, Chicago, IL
| | - Marina Serper
- Division of Gastroenterology and Hepatology, Department of Medicine, University of Pennsylvania, Philadelphia, PA
| | - Lauren Jones
- Division of Gastroenterology and Hepatology, Department of Medicine, University of Pennsylvania, Philadelphia, PA
| | - Rajani Sharma
- Center for Liver Disease and Transplantation, Columbia University Medical Center, New York, NY
| | - Elizabeth C. Verna
- Center for Liver Disease and Transplantation, Columbia University Medical Center, New York, NY
| | - Julia Shor
- Division of Gastroenterology and Hepatology, Department of Medicine, University of California, San Francisco, San Francisco, CA
| | - Margarita N. German
- Division of Gastroenterology and Hepatology, Department of Medicine, School of Medicine and Public Health, University of Wisconsin, Madison, WI
| | - Alexander Hristov
- Division of Gastroenterology and Hepatology, Department of Medicine, School of Medicine and Public Health, University of Wisconsin, Madison, WI
| | - Alexander Lee
- Division of Gastroenterology and Hepatology, Department of Medicine, School of Medicine and Public Health, University of Wisconsin, Madison, WI
| | - Erin Spengler
- Division of Gastroenterology and Hepatology, Department of Medicine, School of Medicine and Public Health, University of Wisconsin, Madison, WI
| | | | - Gurbir Sehmbey
- Transplant Hepatology, Banner University Medical Center, Phoenix, AZ
| | - Anil Seetharam
- Transplant Hepatology, Banner University Medical Center, Phoenix, AZ
| | - Nimy John
- Division of Gastroenterology and Hepatology, Department of Medicine, Stanford University, Palo Alto, CA
| | - Yuval Patel
- Division of Gastroenterology, Department of Medicine, School of Medicine, Duke University, Durham, NC
| | - Matthew R. Kappus
- Division of Gastroenterology, Department of Medicine, School of Medicine, Duke University, Durham, NC
| | - Thomas Couri
- Center for Liver Diseases, University of Chicago, Chicago, IL
| | - Sonali Paul
- Center for Liver Diseases, University of Chicago, Chicago, IL
| | - Reena J. Salgia
- Division of Gastroenterology, Department of Medicine, Henry Ford, Detroit, MI
| | | | | | | | - Aparna Goel
- Division of Gastroenterology and Hepatology, Department of Medicine, Stanford University, Palo Alto, CA
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16
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Mann JP, Carter P, Armstrong MJ, Abdelaziz HK, Uppal H, Patel B, Chandran S, More R, Newsome PN, Potluri R. Hospital admission with non-alcoholic fatty liver disease is associated with increased all-cause mortality independent of cardiovascular risk factors. PLoS One 2020; 15:e0241357. [PMID: 33108366 PMCID: PMC7591046 DOI: 10.1371/journal.pone.0241357] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2019] [Accepted: 10/13/2020] [Indexed: 12/14/2022] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) is common and strongly associated with the metabolic syndrome. Though NAFLD may progress to end-stage liver disease, the top cause of mortality in NAFLD is cardiovascular disease (CVD). Most of the data on liver-related mortality in NAFLD derives from specialist liver centres. It is not clear if the higher reported mortality rates in individuals with non-cirrhotic NAFLD are entirely accounted for by complications of atherosclerosis and diabetes. Therefore, we aimed to describe the CVD burden and mortality in NAFLD when adjusting for metabolic risk factors using a ‘real world’ cohort. We performed a retrospective study of patients followed-up after an admission to non-specialist hospitals with a NAFLD-spectrum diagnosis. Non-cirrhotic NAFLD and NAFLD-cirrhosis patients were defined by ICD-10 codes. Cases were age-/sex-matched with non-NAFLD hospitalised patients. All-cause mortality over 14-years follow-up after discharge was compared between groups using Cox proportional hazard models adjusted for demographics, CVD, and metabolic syndrome components. We identified 1,802 patients with NAFLD-diagnoses: 1,091 with non-cirrhotic NAFLD and 711 with NAFLD-cirrhosis, matched to 24,737 controls. There was an increasing burden of CVD with progression of NAFLD: for congestive heart failure 3.5% control, 4.2% non-cirrhotic NAFLD, 6.6% NAFLD-cirrhosis; and for atrial fibrillation 4.7% control, 5.9% non-cirrhotic NAFLD, 12.1% NAFLD-cirrhosis. Over 14-years follow-up, crude mortality rates were 14.7% control, 13.7% non-cirrhotic NAFLD, and 40.5% NAFLD-cirrhosis. However, after adjusting for demographics, non-cirrhotic NAFLD (HR 1.3 (95% CI 1.1–1.5)) as well as NAFLD-cirrhosis (HR 3.7 (95% CI 3.0–4.5)) patients had higher mortality compared to controls. These differences remained after adjusting for CVD and metabolic syndrome components: non-cirrhotic NAFLD (HR 1.2 (95% CI 1.0–1.4)) and NAFLD-cirrhosis (HR 3.4 (95% CI 2.8–4.2)). In conclusion, from a large non-specialist registry of hospitalised patients, those with non-cirrhotic NAFLD had increased overall mortality compared to controls even after adjusting for CVD.
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Affiliation(s)
- Jake P. Mann
- MRC Epidemiology Unit, Institute of Metabolic Science, University of Cambridge, Cambridge, United Kingdom
- Department of Paediatrics, University of Cambridge, Cambridge, United Kingdom
- ACALM Study Unit in collaboration with Aston Medical School, Aston University, Birmingham, United Kingdom
- * E-mail:
| | - Paul Carter
- ACALM Study Unit in collaboration with Aston Medical School, Aston University, Birmingham, United Kingdom
- Division of Cardiovascular Medicine, Department of Medicine, University of Cambridge, Cambridge, United Kingdom
| | - Matthew J. Armstrong
- Liver Unit, University Hospitals Birmingham NHS Foundation Trust, Birmingham, United Kingdom
| | - Hesham K. Abdelaziz
- Lancashire Cardiac Centre, Blackpool Victoria Hospital, Blackpool, United Kingdom
- Department of Cardiovascular Medicine, Ain Shams University Hospital, Cairo, Egypt
| | - Hardeep Uppal
- ACALM Study Unit in collaboration with Aston Medical School, Aston University, Birmingham, United Kingdom
| | - Billal Patel
- Lancashire Cardiac Centre, Blackpool Victoria Hospital, Blackpool, United Kingdom
| | - Suresh Chandran
- Department of Medicine, Pennine Acute Hospitals NHS Trust, Manchester, United Kingdom
| | - Ranjit More
- Lancashire Cardiac Centre, Blackpool Victoria Hospital, Blackpool, United Kingdom
| | - Philip N. Newsome
- National Institute for Health Research Liver Biomedical Research Unit at University Hospitals Birmingham NHS Foundation Trust and the University of Birmingham, Birmingham, United Kingdom
- Centre for Liver Research, Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, United Kingdom
| | - Rahul Potluri
- ACALM Study Unit in collaboration with Aston Medical School, Aston University, Birmingham, United Kingdom
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17
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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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18
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Yazawa M, Maliakkal B, Nair S, Podila PSB, Agbim UA, Karri S, Khan SD, Maluf D, Eason JD, Molnar MZ, Satapathy SK. Longitudinal Renal Function in Liver Transplant Recipients With Acute-on-Chronic Liver Failure. Clin Transl Gastroenterol 2020; 11:e00185. [PMID: 32568475 PMCID: PMC7339195 DOI: 10.14309/ctg.0000000000000185] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/05/2020] [Accepted: 04/17/2020] [Indexed: 12/22/2022] Open
Abstract
INTRODUCTION To analyze the impact of acute-on-chronic liver failure (ACLF) immediately before liver transplantation (LT) on short-term kidney function. METHODS In this retrospective study, we included 416 of 687 consecutive patients who had an estimated glomerular filtration rates (eGFRs) at 3-month post-LT. We compared the non-ACLF (N = 356), ACLF with eGFR ≥30 mL/min/1.73 m (A-HGFR, N = 32), and ACLF with eGFR <30 mL/min/1.73 m (A-LGFR, N = 28) groups at LT and for 2 kidney-related outcomes: (i) slope of eGFR by linear mixed model and (ii) time to development of composite kidney outcomes (eGFR < 15 mL/min/1.73 m or need for dialysis). RESULTS The mean eGFRs at LT in non-ACLF, A-HGFR, and A-LGFR groups were significantly different as follows: 83.9 ± 29.5, 56.5 ± 31.2, and 21.6 ± 5.0 mL/min/1.73 m, respectively. The eGFR slope significantly increased in A-LGFR group (+7.26 mL/min/1.73 m/mo), whereas it remained stable in A-HGFR group (+1.05 mL/min/1.73 m/mo) and significantly declined in non-ACLF group (-7.61 mL/min/1.73 m/mo) by the first 3-month period. On the other hand, the eGFR slope in all groups stabilized after 3 months post-LT. A-LGFR group showed significantly increased risk of developing composite kidney outcomes in adjusted analysis (hazard ratio = 3.61, 95% confidence interval: 1.35-9.70) compared with the non-ACLF group. However, this significance disappeared after the further adjustment for eGFR at 3-month post-LT (hazard ratio = 1.91, 95% confidence interval: 0.70-5.23). DISCUSSION The slopes of eGFR before 3-month post-LT were significantly different among non-ACLF, A-HGFR, and A-LGFR groups. The renal dysfunction in A-LGFR group stabilized after partial recovery by 3-month post-LT (eGFR reset point).
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Affiliation(s)
- Masahiko Yazawa
- James D. Eason Transplant Institute, Methodist University Hospital, Memphis, Tennessee, USA
- Division of Transplant Surgery, Department of Surgery, University of Tennessee Health Science Center, Memphis, Tennessee, USA
- Division of Nephrology and Hypertension, Department of Internal Medicine, St. Marianna University School of Medicine, Kawasaki, Japan
| | - Benedict Maliakkal
- James D. Eason Transplant Institute, Methodist University Hospital, Memphis, Tennessee, USA
- Division of Transplant Surgery, Department of Surgery, University of Tennessee Health Science Center, Memphis, Tennessee, USA
| | - Satheesh Nair
- James D. Eason Transplant Institute, Methodist University Hospital, Memphis, Tennessee, USA
- Division of Transplant Surgery, Department of Surgery, University of Tennessee Health Science Center, Memphis, Tennessee, USA
| | - Pradeep S. B. Podila
- Faith & Health Division, Methodist Le Bonheur Healthcare, Memphis, Tennessee, USA
- Division of Health Systems Management & Policy, School of Public Health, The University of Memphis, Memphis, Tennessee, USA
| | - Uchenna A. Agbim
- James D. Eason Transplant Institute, Methodist University Hospital, Memphis, Tennessee, USA
- Division of Transplant Surgery, Department of Surgery, University of Tennessee Health Science Center, Memphis, Tennessee, USA
| | - Saradasri Karri
- Department of Medicine, University of Tennessee Health Science Center, Memphis, Tennessee, USA
| | - Sabrina D. Khan
- Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, New York, USA
| | - Daniel Maluf
- James D. Eason Transplant Institute, Methodist University Hospital, Memphis, Tennessee, USA
- Division of Transplant Surgery, Department of Surgery, University of Tennessee Health Science Center, Memphis, Tennessee, USA
| | - James D. Eason
- James D. Eason Transplant Institute, Methodist University Hospital, Memphis, Tennessee, USA
- Division of Transplant Surgery, Department of Surgery, University of Tennessee Health Science Center, Memphis, Tennessee, USA
| | - Miklos Z. Molnar
- James D. Eason Transplant Institute, Methodist University Hospital, Memphis, Tennessee, USA
- Division of Transplant Surgery, Department of Surgery, University of Tennessee Health Science Center, Memphis, Tennessee, USA
- Department of Transplantation and Surgery, Semmelweis University, Budapest, Hungary
- Division of Nephrology, Department of Medicine, University of Tennessee Health Science Center, Memphis, Tennessee, USA
| | - Sanjaya K. Satapathy
- Sandra Atlas Bass Center for Liver Diseases & Transplantation, Department of Medicine, Northshore University Hospital/Northwell Health, Manhasset, New York, USA
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19
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Cullaro G, Verna EC, Lee BP, Lai JC. Chronic Kidney Disease in Liver Transplant Candidates: A Rising Burden Impacting Post-Liver Transplant Outcomes. Liver Transpl 2020; 26:498-506. [PMID: 31785069 PMCID: PMC8056970 DOI: 10.1002/lt.25694] [Citation(s) in RCA: 50] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/17/2019] [Accepted: 11/12/2019] [Indexed: 12/21/2022]
Abstract
The burden of chronic kidney disease (CKD) is rising among patients with cirrhosis, though it is not known what impact this has had on outcomes after liver transplantation (LT). All patients listed for LT in the United States between 2002 and 2017 were analyzed, excluding those listed with Model for End-Stage Liver Disease (MELD) exceptions. The primary outcome was post-LT mortality. We defined pre-LT CKD as an estimated glomerular filtration rate <60 mL/minute for 90 days or ≥42 days of hemodialysis. Cox regression determined the association between pre-LT CKD and post-LT mortality. Of 78,640 LT candidates, the proportion with CKD among LT recipients increased from 7.8% in 2002 to 14.6% in 2017 (test for trend, P < 0.001). Among the 39,719 LT recipients, pre-LT CKD was significantly associated with post-LT mortality (hazard ratio [HR], 1.16; P < 0.001) even after adjusting for donor risk index (DRI), age, MELD, etiology, hepatic encephalopathy, simultaneous liver-kidney transplantation (SLKT), and diabetes. There was no mediating influence of SLKT on the effect of pre-LT CKD on post-LT survival (P > 0.05). Therefore, pre-LT CKD has a deleterious impact on post-LT outcomes, which is an impact that is not mediated through SLKT. These findings highlight the need for the identification of CKD when preventative measures are possible.
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Affiliation(s)
- Giuseppe Cullaro
- Division of Gastroenterology and Hepatology, Department of Medicine, University of California, San Francisco, CA, USA
| | - Elizabeth C. Verna
- Center for Liver Disease and Transplantation, Columbia University, Vagelos College of Physicians and Surgeons, New York, NY, USA
| | - Brian P. Lee
- Division of Gastroenterology and Hepatology, Department of Medicine, University of California, San Francisco, CA, USA
| | - Jennifer C. Lai
- Division of Gastroenterology and Hepatology, Department of Medicine, University of California, San Francisco, CA, USA
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20
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Samji NS, Heda R, Satapathy SK. Peri-transplant management of nonalcoholic fatty liver disease in liver transplant candidates . Transl Gastroenterol Hepatol 2020; 5:10. [PMID: 32190778 PMCID: PMC7061181 DOI: 10.21037/tgh.2019.09.09] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/10/2019] [Accepted: 09/23/2019] [Indexed: 12/12/2022] Open
Abstract
The incidence of non-alcoholic fatty liver disease (NAFLD) is rapidly growing, affecting 25% of the world population. Non-alcoholic steatohepatitis (NASH) is the most severe form of NAFLD and affects 1.5% to 6.5% of the world population. Its rising incidence will make end-stage liver disease (ESLD) due to NASH the number one indication for liver transplantation (LT) in the next 10 to 20 years, overtaking Hepatitis C. Patients with NASH also have a high prevalence of associated comorbidities such as type 2 diabetes, obesity, metabolic syndrome, cardiovascular disease, and chronic kidney disease (CKD), which must be adequately managed during the peritransplant period for optimal post-transplant outcomes. The focus of this review article is to provide a comprehensive overview of the unique challenges these patients present in the peritransplant period, which comprises the pre-transplant, intraoperative, and immediate postoperative periods.
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Affiliation(s)
- Naga Swetha Samji
- Tennova Cleveland Hospital, 2305 Chambliss Ave NW, Cleveland, TN, USA
| | - Rajiv Heda
- University of Tennessee Health Science Center, College of Medicine, Memphis, TN, USA
| | - Sanjaya K. Satapathy
- Division of Hepatology and Sandra Atlas Bass Center for Liver Diseases, Northwell Health, Manhasset, NY, USA
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21
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Tariq R, Axley P, Singal AK. Extra-Hepatic Manifestations of Nonalcoholic Fatty Liver Disease: A Review. J Clin Exp Hepatol 2020; 10:81-87. [PMID: 32025167 PMCID: PMC6995895 DOI: 10.1016/j.jceh.2019.07.008] [Citation(s) in RCA: 29] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/25/2019] [Accepted: 07/17/2019] [Indexed: 02/08/2023] Open
Abstract
Nonalcoholic fatty liver disease (NAFLD) is now the leading cause of chronic liver disease worldwide with a strong association with metabolic syndrome. NAFLD is truly a systemic disease and is associated with a plethora of extra-hepatic manifestations or comorbidities. These are either related to secondary effects of associated obesity or from pathophysiological effects of insulin resistance in NAFLD. Three most common causes of increased morbidity and mortality associated with NAFLD are cardiovascular disease, liver disease, and cancer. In this narrative review, we will discuss comprehensively on cardiovascular disease, type 2 diabetes mellitus, and chronic kidney disease and will also highlight on malignancy especially colorectal cancer, pulmonary disorders including obstructive sleep apnea, endocrine disorders such as hypothyroidism and polycystic ovarian syndrome, dermatological disorders especially psoriasis, and hematological associations including iron overload and susceptibility to thrombosis. In addition to focusing on pathogenesis of these extrahepatic manifestations, we will highlight their clinical implications for physicians in routine clinical practice. Further, there remains an unmet need for safe and effective therapies and examining their benefits on these extra-hepatic manifestations among patients with NAFLD.
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Key Words
- CKD, chronic kidney disease
- CT, computed tomography
- CVD, cardiovascular disease
- HCC
- MetS, metabolic syndrome
- NAFL, nonalcoholic fatty liver
- NAFLD, nonalcoholic fatty liver disease
- NASH
- NASH, nonalcoholic steatohepatitis
- OSA, obstructive sleep apnea
- PCOS, polycystic ovarian syndrome
- T2DM, type 2 diabetes mellitus
- insulin resistance
- metabolic syndrome
- steatosis
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Affiliation(s)
- Raseen Tariq
- Department of Medicine, University of Rochester, Rochester, NY, USA
| | - Page Axley
- Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA
| | - Ashwani K. Singal
- Division of Gastroenterology and Hepatology, University of South Dakota Sanford School of Medicine, Transplant Hepatologist Avera University Hospital & Transplant Institute, Chief Clinical Research Affairs, Transplant Hepatology & Institute of Human Genetics Research, Sioux Falls, SD, 57105, USA,Address for correspondence: Ashwani K. Singal, MD Associate Professor of Medicine, Division of Gastroenterology and Hepatology, University of South Dakota Sanford School of Medicine, Transplant Hepatologist Avera University Hospital & Transplant Institute, Chief Clinical Research Affairs, Transplant Hepatology & Institute of Human Genetics Research, Sioux Falls, SD, 57105, USA.
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22
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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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23
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Durand F, Pavesi M, Cheung R. Liver transplantation for non-alcoholic steatohepatitis in Europe: Where do we stand? J Hepatol 2019; 71:240-242. [PMID: 31229271 DOI: 10.1016/j.jhep.2019.05.018] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/23/2019] [Accepted: 05/24/2019] [Indexed: 12/28/2022]
Affiliation(s)
- François Durand
- Hepatology & Liver Intensive Care, Hospital Beaujon, Clichy, France; University Paris Diderot, Paris France.
| | - Marco Pavesi
- Data Management Centre, EF-CLIF, Barcelona, Spain
| | - Ramsey Cheung
- Division of Gastroenterology and Hepatology, VA Palo Alto HCS and Stanford University, Palo Alto, CA, USA
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24
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Samji NS, Verma R, Satapathy SK. Magnitude of Nonalcoholic Fatty Liver Disease: Western Perspective. J Clin Exp Hepatol 2019; 9:497-505. [PMID: 31516266 PMCID: PMC6728535 DOI: 10.1016/j.jceh.2019.05.001] [Citation(s) in RCA: 25] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/20/2019] [Accepted: 05/07/2019] [Indexed: 12/12/2022] Open
Abstract
The incidence of nonalcoholic fatty liver disease (NAFLD) is continuing to rise worldwide, and it is estimated that this disquieting trend will continue for another 10-15 years before prevalence begins to decrease. NAFLD is the hepatic manifestation of metabolic syndrome. As obesity, diabetes, and other lifestyle-related diseases continue to rise, the spectrum of NAFLD, e.g., nonalcoholic steatohepatitis, liver fibrosis, liver cirrhosis, liver-related morbidity, and mortality, will increase in parallel. Its widespread prevalence and associated economic burden have drawn significant attention, and a multitude of pharmaceutical companies are participating in active research trying to find a "cure". Unfortunately, as of now, no targeted treatment exists to treat this condition, and therefore, emphasis has been on its prevention. The current review focuses on the epidemiology, clinical characteristics, risk factors, and clinical outcomes of NAFLD in Western countries. It is important to understand the magnitude of NAFLD and its risk factors in Western countries where the prevalence of NAFLD has now reached epidemic proportions to identify the best strategy to prevent and possibly control this epidemic.
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Affiliation(s)
- Naga S. Samji
- Tenova Cleveland Hospital, 2305 Chambliss Ave NW, Cleveland, TN, 37311, USA
| | - Rajanshu Verma
- Tenova Cleveland Hospital, 2305 Chambliss Ave NW, Cleveland, TN, 37311, USA
- Division of Transplant Surgery, Department of Surgery, Methodist University Hospital Transplant Institute, University of Tennessee Health Sciences Center, Memphis, TN, 38139, USA
| | - Sanjaya K. Satapathy
- Division of Hepatology and Sandra Atlas Bass Center for Liver Diseases, Northwell Health, Manhasset, NY, 11030, USA
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25
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Piano S, Tonon M, Angeli P. Predicting Outcomes of Liver Transplantation in Patients With Nonalcoholic Steatohepatitis: Pretransplant Renal Function Is Key. Liver Transpl 2019; 25:362-364. [PMID: 30657244 DOI: 10.1002/lt.25413] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/14/2019] [Accepted: 01/14/2019] [Indexed: 01/13/2023]
Affiliation(s)
- Salvatore Piano
- Unit of Internal Medicine and Hepatology, Department of Medicine, University of Padua, Padua, Italy
| | - Marta Tonon
- Unit of Internal Medicine and Hepatology, Department of Medicine, University of Padua, Padua, Italy
| | - Paolo Angeli
- Unit of Internal Medicine and Hepatology, Department of Medicine, University of Padua, Padua, Italy
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26
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Li X, Gou C, Pang Y, Wang Y, Liu Y, Wen T. Extracellular histones are clinically associated with primary graft dysfunction in human liver transplantation. RSC Adv 2019; 9:10264-10271. [PMID: 35520915 PMCID: PMC9062399 DOI: 10.1039/c9ra00425d] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2019] [Revised: 08/22/2019] [Accepted: 03/28/2019] [Indexed: 12/14/2022] Open
Abstract
Extracellular histones have been involved in numerous inflammatory conditions such as ischemia/reperfusion (I/R) injury, trauma, and infection. There is growing evidence of I/R injury associated with primary graft dysfunction (PGD) following organ transplantation. Here we investigated whether extracellular histones are clinically involved with PGD in human liver transplantation. In total 58 patients undergoing liver transplantation were studied. We collected blood samples from the recipients before and serially after transplantation (24 h, 72 h). We measured extracellular histones, myeloperoxidase (MPO), S100A8/A9, and multiple inflammatory cytokines. Additionally, we exposed human L02 hepatocytes or U937 monocytic cells to the recipient's sera overnight, and assessed cellular viability and cytokine production respectively. Lastly, we assessed the effect of histone-targeted interventions by administration of heparin or an anti-histone antibody. It showed that extracellular histones increased immediately after transplantation, peaked within 24 hours and remained at high levels up to 72 hours (all p < 0.01). Notably, extracellular histone levels were significantly higher in recipients with PGD (n = 9) than recipients without PGD (n = 49, p = 0.004). Extracellular histones correlated positively with MPO, S100A8/A9 and most detected cytokines. Ex vivo analysis demonstrated that the patients' sera after graft markedly induced L02 cell death and caused profound cytokine production in cultured U937 cells, which could be abrogated by heparin or an anti-histone antibody. Collectively, extracellular histones were increased significantly after liver transplantation, which may contribute to the occurrence of PGD through direct cytotoxicity and enhancement of systemic inflammation. Targeting extracellular histones may provide a promising approach for preventing PGD or other complications in clinical practice. Extracellular histones have been involved in numerous inflammatory conditions such as ischemia/reperfusion (I/R) injury, trauma, and infection.![]()
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Affiliation(s)
- Xiuhui Li
- Department of Liver Diseases
- Beijing Youan Hospital
- Capital Medical University
- Beijing 100069
- P. R. China
| | - Chunyan Gou
- Department of Liver Diseases
- Beijing Youan Hospital
- Capital Medical University
- Beijing 100069
- P. R. China
| | - Yanhua Pang
- Department of Gastroenterology
- Beijing Chaoyang Hospital
- Capital Medical University
- Beijing 100020
- P. R. China
| | - Yakun Wang
- Medical Research Center
- Beijing Chao-Yang Hospital
- Capital Medical University
- Beijing 100020
- P. R. China
| | - Yan Liu
- Department of Liver Diseases
- Beijing Youan Hospital
- Capital Medical University
- Beijing 100069
- P. R. China
| | - Tao Wen
- Medical Research Center
- Beijing Chao-Yang Hospital
- Capital Medical University
- Beijing 100020
- P. R. China
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