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1
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Jatana S, Krys D, Verhoeff K, Kung JY, Jogiat U, Montano-Loza AJ, Shapiro AMJ, Dajani K, Anderson B, Bigam DL. Liver Allograft Cirrhosis, Retransplant, and Mortality Secondary to Recurrent Disease After Transplant for MASH: A Systematic Review and Meta-analysis. Transplantation 2024:00007890-990000000-00954. [PMID: 39658843 DOI: 10.1097/tp.0000000000005276] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2024]
Abstract
BACKGROUND Recurrent disease after liver transplant is well recognized for many diseases. Metabolic dysfunction-associated steatotic liver disease (MASLD) and steatohepatitis (MASH) are leading indications for liver transplant, and there is scarce knowledge about recurrence-related end outcomes such as retransplant and mortality. This project aims to assess the proportion of patients transplanted for MASH who develop recurrent disease and adverse clinical outcomes. METHODS A systematic review and pooled proportions meta-analysis was performed by searching the following databases: MEDLINE, Embase, Scopus, Web of Science Core Collection, and Cochrane Library. Inclusion criteria were studies discussing adult patients with liver transplants secondary to MASH or presumed MASH with recurrent disease-related outcomes. Outcomes were assessed in time frames from <6 mo to ≥5 y. RESULTS Of 5859 records, 40 were included (16 157 patients). Recurrent MASLD and MASH (28 studies each) occurred in frequencies of 35%-49% and 11%-24%, respectively. Fibrosis occurred in 4%-25% (13 studies). Recurrent disease-related cirrhosis (13 studies), graft failure (8 studies), and retransplant (9 studies) occurred in 0%-2%, 3%-9%, and 0%-1%, respectively. Recurrent disease-related hepatocellular carcinoma (1 study) and mortality (17 studies) both had a prevalence of 0%. Studies were of moderate or high quality using the Methodological Index for Non-Randomized Studies tool. CONCLUSIONS Recurrent MASLD and MASH after liver transplant occur frequently, but adverse clinical outcomes due to disease recurrence are infrequent, maybe due to insufficient data on long-term follow-up. Long-term outcomes after transplantation for MASLD appear favorable; however, identifying those more likely to have progressive recurrent disease leading to adverse clinical outcomes may allow for pre- and posttransplant interventions to improve outcomes further.
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Affiliation(s)
- Sukhdeep Jatana
- Department of Surgery, University of Alberta, Edmonton, AB, Canada
| | - Daniel Krys
- Faculty of Medicine, University of Alberta, Edmonton, AB, Canada
| | - Kevin Verhoeff
- Department of Surgery, University of Alberta, Edmonton, AB, Canada
| | - Janice Y Kung
- Geoffrey and Robyn Sperber Health Sciences Library, University of Alberta, Edmonton, AB, Canada
| | - Uzair Jogiat
- Department of Surgery, University of Alberta, Edmonton, AB, Canada
| | - Aldo J Montano-Loza
- Division of Gastroenterology and Liver Unit, University of Alberta, Edmonton, AB, Canada
| | | | - Khaled Dajani
- Department of Surgery, University of Alberta, Edmonton, AB, Canada
| | - Blaire Anderson
- Department of Surgery, University of Alberta, Edmonton, AB, Canada
| | - David L Bigam
- Department of Surgery, University of Alberta, Edmonton, AB, Canada
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2
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Choudhury A, Singh SP, Desmukh A, Sahoo B, Eslam M. Post-Liver Transplant Metabolic Syndrome. J Clin Exp Hepatol 2024; 14:101368. [PMID: 38523736 PMCID: PMC10960134 DOI: 10.1016/j.jceh.2024.101368] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/09/2023] [Accepted: 02/14/2024] [Indexed: 03/26/2024] Open
Abstract
Non-alcoholic steatohepatitis (NASH) is the second most frequent cause of liver transplantation following alcoholic liver disease. With longer follow-up and increased survival rates, the occurrence rate of the metabolic syndrome is increasing with time among liver transplant recipients. Reappearances of non-alcoholic fatty liver disease after transplantation, both as recurring cases and new instances, are prevalent; nonetheless, the recurrence of fibrosis is minimal. Recognizing populations at elevated risk and enhancing the management of metabolic-related conditions are crucial for maintaining a healthy transplanted organ, particularly considering the prolonged utilization of immunosuppressive treatments. Furthermore, NASH-related cirrhosis patients who had transplant are at a greater risk of cardiovascular, renal events and increased incidence of cancer, necessitating a unique care strategy. This review discusses post-transplant metabolic syndrome, risk factors, pathogenesis, diagnosis, prevention strategy, recurrent and de novo NAFLD and customized immunosuppression.
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Affiliation(s)
- Ashok Choudhury
- Dept of Hepatology and Liver Transplantation, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Satender P. Singh
- Dept of Hepatology and Liver Transplantation, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Akhil Desmukh
- Dept of Hepatology and Liver Transplantation, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Bishnupriya Sahoo
- Associate Professor of Pediatrics, Consultant Pediatric Gastroenterology, Hepatology and Liver Transplant, SGT University, Gurugram, Haryana, India
| | - Mohammed Eslam
- Storr Liver Centre, Westmead Institute for Medical Research, Westmead Hospital and University of Sydney, NSW, Australia
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3
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Tiniakos DG, Anstee QM, Brunt EM, Burt AD. Fatty Liver Disease. MACSWEEN'S PATHOLOGY OF THE LIVER 2024:330-401. [DOI: 10.1016/b978-0-7020-8228-3.00005-3] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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4
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Paklar N, Mijic M, Filipec-Kanizaj T. The Outcomes of Liver Transplantation in Severe Metabolic Dysfunction-Associated Steatotic Liver Disease Patients. Biomedicines 2023; 11:3096. [PMID: 38002096 PMCID: PMC10669065 DOI: 10.3390/biomedicines11113096] [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: 08/31/2023] [Revised: 11/16/2023] [Accepted: 11/17/2023] [Indexed: 11/26/2023] Open
Abstract
The increasing prevalence of diabetes mellitus, obesity, and metabolic syndrome in the population can lead to metabolic dysfunction-associated steatohepatitis (MASH) and metabolic dysfunction-associated steatotic liver disease (MASLD). In Western industrialized countries, this has become a major problem with significant socioeconomic impacts. MASH is now a leading cause of liver transplantation (LT), especially in developed countries. However, the post-transplant outcomes of such patients are a major concern, and published data are limited and extremely variable. In this article, we discuss graft and patient survival after LT, complications, the recurrence of MASH, and MASH appearing de novo after transplantation. Recent studies suggest that patients with MASH have slightly worse short-term survival, potentially due to increased cardiovascular mortality. However, most studies found that longer-term outcomes for patients undergoing LT for MASH are similar or even better than those for other indications. Hepatocellular carcinoma due to MASH cirrhosis also has similar or even better outcomes after LT than other etiologies. In conclusion, we suggest questions and topics that require further research to enhance healthcare for this growing patient population.
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Affiliation(s)
- Natasa Paklar
- Department of Anesthesiology, Reanimatology and Intensive Care, University Hospital Merkur, 10000 Zagreb, Croatia
| | - Maja Mijic
- Department of Gastroenterology, University Hospital Merkur, 10000 Zagreb, Croatia
| | - Tajana Filipec-Kanizaj
- Department of Gastroenterology, University Hospital Merkur, 10000 Zagreb, Croatia
- School of Medicine, University of Zagreb, 10000 Zagreb, Croatia
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5
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Lim WH, Yong JN, Ong CEY, Ng CH, Tan DJH, Zeng RW, Chung CH, Kaewdech A, Chee D, Tseng M, Wijarnpreecha K, Syn N, Bonney GK, Kow A, Huang DQ, Noureddin M, Muthiah M, Tan E, Siddiqui MS. Ethnic disparities in waitlist outcomes of patients with nonalcoholic steatohepatitis listed for liver transplantation in the US. Liver Transpl 2023; 29:1181-1191. [PMID: 37039547 DOI: 10.1097/lvt.0000000000000148] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/07/2022] [Accepted: 03/06/2023] [Indexed: 04/12/2023]
Abstract
NASH is the fastest-growing cause of liver cirrhosis and is the leading indication for liver transplantation (LT). However, significant racial and ethnic disparities in waitlist outcomes and LT allocation may unfairly disadvantage minorities. Our aim was to characterize racial and ethnic disparities in waitlist mortality and transplantation probability among patients with NASH. This is a retrospective analysis of the United Network for Organ Sharing registry data of LT candidates from January 1, 2000 to December 31, 2021. Outcomes analysis was performed using competing risk analysis with the Fine and Gray model. The multivariable adjustment was conducted, and mixed-effect regression was used to compare the model for end-stage liver disease scores at listing and removal. Of 18,562 patients with NASH cirrhosis, there were 14,834 non-Hispanic Whites, 349 African Americans, 2798 Hispanics, 312 Asians, and 269 of other races/ethnicities; African American (effect size: 2.307, 95% CI: 1.561-3.053, and p < 0.001) and Hispanic (effect size: 0.332, 95% CI: 0.028-0.637, p = 0.032) patients were found to have a significantly higher model for end-stage liver disease scores at the time of listing than non-Hispanic Whites. African Americans had a higher probability of receiving LT relative to non-Hispanic Whites (subdistribution HR: 1.211, 95% CI: 1.051-1.396, and p = 0.008). However, Hispanic race/ethnicity was associated with a lower transplantation probability (subdistribution HR: 0.793, 95% CI: 0.747-0.842, and p < 0.001) and increased waitlist mortality (subdistribution HR: 1.173, CI: 1.052-1.308, and p = 0.004) compared with non-Hispanic Whites. There are significant racial and ethnic disparities in waitlist outcomes of patients with NASH in the US. Hispanic patients are less likely to receive LT and more likely to die while on the waitlist compared with non-Hispanic Whites despite being listed with a lower model for end-stage liver disease scores.
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Affiliation(s)
- Wen Hui Lim
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Jie Ning Yong
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Christen En Ya Ong
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Cheng Han Ng
- Department of Medicine, Division of Gastroenterology and Hepatology, National University Hospital, Singapore
| | - Darren Jun Hao Tan
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | | | - Charlotte Hui Chung
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Apichat Kaewdech
- Department of Medicine, Division of Internal Medicine, Gastroenterology and Hepatology Unit, Prince of Songkla University, Hat Yai, Thailand
| | - Douglas Chee
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore
- Department of Medicine, Division of Gastroenterology and Hepatology, National University Hospital, Singapore
- National University Centre for Organ Transplantation, National University Health System, Singapore
| | - Michael Tseng
- Department of Internal Medicine, Division of Gastroenterology, Hepatology and Nutrition, Virginia Commonwealth University, Richmond, Virginia, USA
| | - Karn Wijarnpreecha
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, University of Arizona College of Medicine Phoenix, Phoenix, Arizona, USA
| | - Nicholas Syn
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Glenn K Bonney
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore
- Department of Surgery, Division of Hepatobiliary and Pancreatic Surgery, National University Hospital Singapore, Singapore
- National University Centre for Organ Transplantation, National University Health System, Singapore
| | - Alfred Kow
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore
- Department of Surgery, Division of Hepatobiliary and Pancreatic Surgery, National University Hospital Singapore, Singapore
- National University Centre for Organ Transplantation, National University Health System, Singapore
| | - Daniel Q Huang
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore
- Department of Medicine, Division of Gastroenterology and Hepatology, National University Hospital, Singapore
- National University Centre for Organ Transplantation, National University Health System, Singapore
| | | | - Mark Muthiah
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore
- Department of Medicine, Division of Gastroenterology and Hepatology, National University Hospital, Singapore
- National University Centre for Organ Transplantation, National University Health System, Singapore
| | - Eunice Tan
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore
- Department of Medicine, Division of Gastroenterology and Hepatology, National University Hospital, Singapore
- National University Centre for Organ Transplantation, National University Health System, Singapore
| | - Mohammad Shadab Siddiqui
- Department of Internal Medicine, Division of Gastroenterology, Hepatology and Nutrition, Virginia Commonwealth University, Richmond, Virginia, USA
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6
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Bezinover D, Alhkouri N, Schumann R, Geyer N, Chinchilli V, Stine JG. Liver Transplant Outcomes in Young Adults with Cirrhosis Related to Nonalcoholic Fatty Liver Disease. Transplant Proc 2023; 55:2134-2142. [PMID: 37752016 PMCID: PMC10699163 DOI: 10.1016/j.transproceed.2023.08.020] [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: 04/09/2023] [Revised: 07/07/2023] [Accepted: 08/01/2023] [Indexed: 09/28/2023]
Abstract
BACKGROUND The prevalence of nonalcoholic fatty liver disease (NASH) and cryptogenic cirrhosis (CC) is constantly increasing in adolescents and young adults (AYAs). METHODS In a retrospective UNOS database evaluation, we analyzed postoperative outcomes of AYAs with nonalcoholic NASH/CC undergoing LT between January 1st, 2003 and March 5th, 2021. After exclusions, 85,970 LT recipients, 393 (47.1%) AYAs with NASH/CC and 441 (52.9%) AYAs with other metabolic conditions, were analyzed. RESULTS During the study period, the number of LTs performed for AYAs with NASH/CC increased from 4%-7% but decreased from 6.6%-5.3% compared to LTs performed for NASH/CC in all ages. In comparison to AYAs with other metabolic conditions, AYA LT recipients with NASH/CC had a higher prevalence of metabolic syndrome (MetS) components, including diabetes and increased body mass index (P < .0001 for both). Patient and graft survival in AYAs with NASH/CC were significantly lower in comparison to AYAs transplanted for other metabolic conditions (P < .0001) (Hazard Ratio = 1.93, P < .001). Patient survival in AYAs with NASH/CC was significantly better in comparison to older (40-65-year-old) patients with the same diagnosis (P = .01). CONCLUSIONS Our study found that the overall number of LTs in AYAs with NASH increased significantly, but to a lesser degree compared to the older population with the same diagnosis. Outcomes after LT in AYAs with NASH/CC were worse compared to LT for other metabolic conditions, but significantly better in comparison to older patients. The prevalence of LT for NASH/CC in AYAs is growing. MetS may contribute to worse outcomes in AYAs.
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Affiliation(s)
- Dmitri Bezinover
- Department of Anesthesiology and Critical Care, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
| | - Naim Alhkouri
- Department of Hepatology, Arizona Liver Health, Chandler, Arizona
| | - Roman Schumann
- Department of Anesthesiology, Critical Care and Pain Medicine, VA Boston Healthcare System, West Roxbury, Massachusetts
| | - Nathaniel Geyer
- The Pennsylvania State University, Department of Public Health Sciences, Hershey, Pennsylvania
| | - Vernon Chinchilli
- The Pennsylvania State University, Department of Public Health Sciences, Hershey, Pennsylvania
| | - Jonathan G Stine
- The Pennsylvania State University, Department of Public Health Sciences, Hershey, Pennsylvania; The Pennsylvania State University, Hershey Medical Center, Division of Gastroenterology and Hepatology, Department of Medicine, Hershey, Pennsylvania
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7
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Odenwald MA, Roth HF, Reticker A, Segovia M, Pillai A. Evolving challenges with long-term care of liver transplant recipients. Clin Transplant 2023; 37:e15085. [PMID: 37545440 DOI: 10.1111/ctr.15085] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2023] [Revised: 07/17/2023] [Accepted: 07/23/2023] [Indexed: 08/08/2023]
Abstract
The number of liver transplants (LT) performed worldwide continues to rise, and LT recipients are living longer post-transplant. This has led to an increasing number of LT recipients requiring lifelong care. Optimal care post-LT requires careful attention to both the allograft and systemic issues that are more common after organ transplantation. Common causes of allograft dysfunction include rejection, biliary complications, and primary disease recurrence. While immunosuppression prevents rejection and reduces incidences of some primary disease recurrence, it has detrimental systemic effects. Most commonly, these include increased incidences of metabolic syndrome, various malignancies, and infections. Therefore, it is of utmost importance to optimize immunosuppression regimens to prevent allograft dysfunction while also decreasing the risk of systemic complications. Institutional protocols to screen for systemic disease and heightened clinical suspicion also play an important role in providing optimal long-term post-LT care. In this review, we discuss these common complications of LT as well as unique considerations when caring for LT recipients in the years after transplant.
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Affiliation(s)
- Matthew A Odenwald
- Department of Medicine, Section of Gastroenterology, Hepatology, and Nutrition, University of Chicago Medicine, Chicago, USA
| | - Hannah F Roth
- Department of Medicine, Section of Gastroenterology, Hepatology, and Nutrition, University of Chicago Medicine, Chicago, USA
| | - Anesia Reticker
- Department of Pharmacy, University of Chicago Medicine, Chicago, USA
| | - Maria Segovia
- Department of Medicine, Section of Gastroenterology, Duke University School of Medicine, Durham, USA
| | - Anjana Pillai
- Department of Medicine, Section of Gastroenterology, Hepatology, and Nutrition, University of Chicago Medicine, Chicago, USA
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8
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Siddiqui MS, Parmar D, Shaikh F, Forsgren M, Patel S, Bui AT, Boyett S, Patel V, Sanyal AJ. Saroglitazar improves nonalcoholic fatty liver disease and metabolic health in liver transplant recipients. Liver Transpl 2023; 29:979-986. [PMID: 36847136 DOI: 10.1097/lvt.0000000000000110] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/02/2022] [Accepted: 01/23/2023] [Indexed: 03/01/2023]
Abstract
NAFLD is common after liver transplantation (LT) and is associated with an increased metabolic burden. Currently, there is a paucity of investigations into the treatment of post-LT NAFLD. In the present study, we evaluated the safety and efficacy of saroglitazar, a novel dual peroxisome proliferator-associated receptor α/γ agonist, on the treatment of post-LT NAFLD and metabolic burden. This is a phase 2A, single-center, open-label, single-arm study in which patients with post-LT NAFLD received saroglitazar magnesium 4 mg daily for 24 weeks. NAFLD was defined by a controlled attenuation parameter ≥264 dB/m. The primary endpoint was the reduction in liver fat as measured by MRI proton density fat fraction (MRI-PDFF). Secondary MRI-based metabolic endpoints included visceral adipose tissue, abdominal subcutaneous adipose tissue volumes, muscle fat infiltration, and fat-free muscle volume. Saroglitazar treatment led to a reduction in MRI-PDFF from 10.3±10.5% at baseline to 8.1±7.6%. A relative 30% reduction from baseline MRI-PDFF value was noted in 47% of all patients and 63% of patients with baseline MRI-PDFF >5%. Reduction in serum alkaline phosphatase was an independent predictor of MRI-PDFF response. Saroglitazar did not decrease fat-free muscle volume nor increase muscle fat infiltration, but did lead to a mild increase in visceral adipose tissue and abdominal subcutaneous adipose tissue. The study drug was well tolerated and a mild nonsignificant increase in serum creatinine was noted. Saroglitazar did not affect the weight. The study provides preliminary data demonstrating the safety and metabolic benefits of saroglitazar in LT recipients and underscores the importance of future studies to establish its efficacy after LT.
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Affiliation(s)
| | | | | | - Mikael Forsgren
- AMRA Medical AB, Centre for Medical Image Science and Visualization, Linköping University, Linköping, Sweden
- Department of Health, Medicine and Caring Sciences, Linköping University, Linköping, Sweden
| | - Samarth Patel
- Leigh Valley Health Network, Allentown, Pennsylvania, USA
| | - Anh Tuan Bui
- Department of Statistical Sciences and Operations Research, VCU, Richmond, Virginia, USA
| | - Sherry Boyett
- Division of Gastroenterology, Hepatology and Nutrition, VCU, Richmond, Virginia, USA
| | - Vaishali Patel
- Division of Gastroenterology, Hepatology and Nutrition, VCU, Richmond, Virginia, USA
| | - Arun J Sanyal
- Division of Gastroenterology, Hepatology and Nutrition, VCU, Richmond, Virginia, USA
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9
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Taneja S, Roy A, Duseja A. NASH After Liver Transplantation: Impact of Immunosuppression. J Clin Exp Hepatol 2023; 13:835-840. [PMID: 37693259 PMCID: PMC10483005 DOI: 10.1016/j.jceh.2023.03.013] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/19/2023] [Accepted: 03/28/2023] [Indexed: 09/12/2023] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) has emerged as one of the common causes of cirrhosis and hepatocellular carcinoma (HCC) and is a leading indication for liver transplantation (LT). Patients with NAFLD-related cirrhosis and HCC are at high risk for the development of recurrent NAFLD after LT. NAFLD can also develop de novo post-transplantation in patients subjected to LT for other indications. Besides the pretransplant presence of various components of metabolic syndrome (MS) use of immunosuppressive agents in the post-LT setting forms one of the major drivers for the development of post-LT NAFLD. Individual components of conventional immunosuppressive regimens (corticosteroids, calcineurin inhibitors, and m-TOR inhibitors) are all implicated in the development of post-LT metabolic derangement and follow unique mechanisms of action and degree of disturbances. The development of cardiovascular risk is associated with post-LT NAFLD, although graft outcomes do not seem to be influenced only by the presence of post-LT NAFLD. Measures in consonance with the management of NAFLD, in general, including lifestyle modifications and control of metabolic risk factors, hold true for post-LT NAFLD. Tailoring immunosuppression strategies with early corticosteroid withdrawal and calcineurin inhibitor minimization balancing against the risk of graft rejection constitutes important nuances in the individualized management of post-LT NAFLD.
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Affiliation(s)
- Sunil Taneja
- Department of Hepatology, Postgraduate Institute on Medical Education & Research, Chandigarh, India
| | - Akash Roy
- Institute of Gastrosciences and Liver Transplantation Apollo Multispeciality Hospitals, Kolkata, India
| | - Ajay Duseja
- Department of Hepatology, Postgraduate Institute on Medical Education & Research, Chandigarh, India
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10
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Silva AC, Nogueira P, Machado MV. Hepatic steatosis after liver transplantation: a systematic review and meta-analysis. Liver Transpl 2023; 29:431-448. [PMID: 36735478 DOI: 10.1097/lvt.0000000000000060] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/05/2022] [Accepted: 11/16/2022] [Indexed: 02/04/2023]
Abstract
NAFLD can occur after liver transplantation (LT), as recurrence or de novo hepatic steatosis (HS). We aimed to evaluate the literature on prevalence, risk factors, and prognosis of post-LT HS. Systematic review with meta-analysis through a search on: PUBMED, Scopus, and Web-of-Science, from inception until the September 30, 2021. Forty studies were included, representing 6979 patients. The post-LT HS prevalence was 39.76% (95% CI, 34.06-45.46), with a rising kinetics (11.06% increase per decade, p =0.04), and a geographical distribution (15.10% more prevalent in American continent compared with Europe and Asia). Recurrent HS was up to 5-fold more likely than de novo HS [OR: 5.38 (2.69-10.76)]. Metabolic disturbances were stronger risk factors in the post-LT recipient [obesity: OR: 4.62 (3.07-6.96); metabolic syndrome: OR: 3.26 (2.03-5.25)] as compared with pre-LT recipients, with the exception of diabetes mellitus, which doubled the risk at any set [pre-LT diabetes mellitus: OR: 2.06 (1.58-2.68); post-LT diabetes mellitus: OR: 2.12 (1.73-2.59)]. Donor factors were not the relevant risk factors for post-LT HS and the only immunosuppressive drug associated with increased risk was sirolimus [OR: 1.68 (1.07-2.64)]. The prevalence of post-LT steatohepatitis was 28.82% (19.62-38.03) and the strongest risk factor was pre-LT NAFLD. Limited outcomes data suggest that post-LT HS did not increase the risk for liver cirrhosis or mortality in these studies. Two out of 5 patients submitted to LT will develop post-LT HS, being recurrent HS more common than de novo HS. Diabetes mellitus and post-LT metabolic syndrome are the strongest risk factors for HS and baseline NAFLD for steatohepatitis. All transplanted patients should be enrolled in lifestyle interventions to prevent post-LT metabolic syndrome, and sirolimus should be avoided in high-risk patients.
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Affiliation(s)
- Ana C Silva
- Gastroenterology Department, Medicine School, Lisbon University, Lisbon, Portugal
| | - Paulo Nogueira
- Biostatistic Department, Medicine School, Lisbon University, Lisbon, Portugal
| | - Mariana V Machado
- Gastroenterology Department, Medicine School, Lisbon University, Lisbon, Portugal
- Gastroenterology Department, Vila Franca de Xira Hospital, Lisbon, Portugal
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11
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Fuochi E, Anastasio L, Lynch EN, Campani C, Dragoni G, Milani S, Galli A, Innocenti T. Main factors influencing long-term outcomes of liver transplantation in 2022. World J Hepatol 2023; 15:321-352. [PMID: 37034235 PMCID: PMC10075010 DOI: 10.4254/wjh.v15.i3.321] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/18/2022] [Revised: 11/24/2022] [Accepted: 02/22/2023] [Indexed: 04/11/2023] Open
Abstract
Liver transplant (LT) outcomes have markedly improved in the recent decades, even if long-term morbidity and mortality are still considerable. Most of late deaths are independent from graft function and different comorbidities, including complications of metabolic syndrome and de novo neoplasms, seem to play a key role in determining long-term outcomes in LT recipients. This review discusses the main factors associated with late mortality and suggests possible strategies to improve long-term management and follow-up after liver transplantation. In particular, the reduction of drug toxicity, the use of tools to identify high-risk patients, and setting up a multidisciplinary team also for long-term management of LT recipients may further improve survival after liver transplantation.
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Affiliation(s)
- Elisa Fuochi
- Gastroenterology Research Unit, Department of Experimental and Clinical Biomedical Sciences “Mario Serio”, University of Florence, Florence 50134, Italy
| | - Lorenzo Anastasio
- Gastroenterology Research Unit, Department of Experimental and Clinical Biomedical Sciences “Mario Serio”, University of Florence, Florence 50134, Italy
| | - Erica Nicola Lynch
- Gastroenterology Research Unit, Department of Experimental and Clinical Biomedical Sciences “Mario Serio”, University of Florence, Florence 50134, Italy
| | - Claudia Campani
- Department of Experimental and Clinical Medicine, University of Florence, Florence 50134, Italy
| | - Gabriele Dragoni
- Gastroenterology Research Unit, Department of Experimental and Clinical Biomedical Sciences “Mario Serio”, University of Florence, Florence 50134, Italy
- Department of Medical Biotechnologies, University of Siena, Siena 53100, Italy
| | - Stefano Milani
- Gastroenterology Research Unit, Department of Experimental and Clinical Biomedical Sciences “Mario Serio”, University of Florence, Florence 50134, Italy
| | - Andrea Galli
- Gastroenterology Research Unit, Department of Experimental and Clinical Biomedical Sciences “Mario Serio”, University of Florence, Florence 50134, Italy
| | - Tommaso Innocenti
- Gastroenterology Research Unit, Department of Experimental and Clinical Biomedical Sciences “Mario Serio”, University of Florence, Florence 50134, Italy
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12
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Fukushima M, Miyaaki H, Sasaki R, Haraguchi M, Miuma S, Hara T, Soyama A, Hidaka M, Eguchi S, Nakao K. Most Cases of Cryptogenic Cirrhosis May be Nonobese Nonalcoholic Steatohepatitis-Risk Factors of Liver Steatosis After Liver Transplantation for Cryptogenic Cirrhosis: A Retrospective Study. Intern Med 2022; 62:1415-1423. [PMID: 36171128 DOI: 10.2169/internalmedicine.0514-22] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/06/2022] Open
Abstract
Aim The course of cryptogenic cirrhosis (CC) after liver transplantation (LT) is unknown. We therefore clarified the natural course post-LT for CC and investigated the etiology of CC. Methods Eighteen patients who underwent LT for CC were included. To rule out the possibility of NASH in patients with CC, those with a history of obesity or liver steatosis found pretransplantation were excluded. A liver biopsy was performed one year after LT and annually thereafter. Results Liver steatosis and steatohepatitis were identified in 61% and 39% of patients after LT, respectively, with a median time to the onset of 12 and 27 months, respectively. There were no other pathological findings such as liver allograft rejection, autoimmune hepatitis, or primary biliary cholangitis. The body mass index after LT (28.5 vs. 22.4 kg/m2; P=0.002) and mean muscle attenuation at the time of LT were significantly higher (33.3 vs. 25.8 Hounsfield units, P=0.03) and the postoperative hospitalization period shorter (50 vs. 102 days; P=0.02) in the steatosis group than in the non-steatosis group. Recipients were significantly younger in the steatohepatitis subgroup than in the simple steatosis subgroup (55.0 vs. 63.5 years old; P=0.04). Conclusions Despite excluding CC patients with a history of obesity, we observed that patients with CC had a high prevalence of steatosis after LT than those without CC. Young patients with a favorable postoperative course were noted to have a high risk of NASH after LT for CC. Patients with CC may represent cases of non-obese NASH.
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Affiliation(s)
- Masanori Fukushima
- Department of Gastroenterology and Hepatology, Nagasaki University Graduate School of Biomedical Sciences, Japan
| | - Hisamitsu Miyaaki
- Department of Gastroenterology and Hepatology, Nagasaki University Graduate School of Biomedical Sciences, Japan
| | - Ryu Sasaki
- Department of Gastroenterology and Hepatology, Nagasaki University Graduate School of Biomedical Sciences, Japan
| | - Masafumi Haraguchi
- Department of Gastroenterology and Hepatology, Nagasaki University Graduate School of Biomedical Sciences, Japan
| | - Satoshi Miuma
- Department of Gastroenterology and Hepatology, Nagasaki University Graduate School of Biomedical Sciences, Japan
| | - Takanobu Hara
- Department of Surgery, Nagasaki University Graduate School of Biomedical Sciences, Japan
| | - Akihiko Soyama
- Department of Surgery, Nagasaki University Graduate School of Biomedical Sciences, Japan
| | - Masaaki Hidaka
- Department of Surgery, Nagasaki University Graduate School of Biomedical Sciences, Japan
| | - Susumu Eguchi
- Department of Surgery, Nagasaki University Graduate School of Biomedical Sciences, Japan
| | - Kazuhiko Nakao
- Department of Gastroenterology and Hepatology, Nagasaki University Graduate School of Biomedical Sciences, Japan
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13
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Kalogirou MS, Giouleme O. Growing challenge of post-liver transplantation non-alcoholic fatty liver disease. World J Transplant 2022; 12:281-287. [PMID: 36187880 PMCID: PMC9516490 DOI: 10.5500/wjt.v12.i9.281] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/13/2022] [Revised: 07/19/2022] [Accepted: 08/16/2022] [Indexed: 02/05/2023] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) is one of the leading causes of chronic liver disease, cirrhosis, and hepatocellular carcinoma worldwide, with an estimated prevalence of 25%. Post-liver transplantation (LT) recurrent or de novo hepatic steatosis is a common complication in recipients, irrespective of transplantation indication. Risk factors for graft steatosis mainly include obesity, immunosuppression, donor steatosis, and genetic factors. Liver transplant recipients are at high risk of developing insulin resistance, new-onset diabetes, and post-transplantation metabolic syndrome that is highly associated with immunosuppressive treatment. Post-LT NAFLD is often underdiagnosed due to the poor sensitivity of most routine imaging methods. The gold standard for the diagnosis of hepatic steatosis is liver biopsy, which is, however, limited to more complex cases due to its invasive nature. There is no approved pharmacotherapy in NAFLD. Lifestyle modification remains the cornerstone in NAFLD treatment. Other treatment strategies in post-LT NAFLD include lifestyle modifications, pharmacotherapy, bariatric surgery, and tailored immunosuppression. However, these approaches originate from recommendations in the general population, as there is scarce data regarding the safety and efficacy of current management strategies for NAFLD in liver transplant patients. Future prospective studies are required to achieve tailored treatment for these patients.
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Affiliation(s)
- Maria Styliani Kalogirou
- Gastroenterology and Hepatology Division of the Second Propedeutic Department of Internal Medicine, Hippokration General Hospital, Medical School, Aristotle University of Thessaloniki, Thessaloniki 54642, Greece
| | - Olga Giouleme
- Gastroenterology and Hepatology Division of the Second Propedeutic Department of Internal Medicine, Hippokration General Hospital, Medical School, Aristotle University of Thessaloniki, Thessaloniki 54642, Greece
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14
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Choudhary NS, Saraf N, Dhampalwar S, Mishra S, Gautam D, Lipi L, Rastogi A, Bhangui P, Chaudhary RJ, Gupta A, Yadav K, Soin AS. Nonalcoholic Fatty Liver Disease in Living Donor Liver Transplant Recipients: A Histology-Based Study. J Clin Exp Hepatol 2022; 12:1328-1332. [PMID: 36157151 PMCID: PMC9500106 DOI: 10.1016/j.jceh.2022.04.012] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/17/2022] [Accepted: 04/12/2022] [Indexed: 12/12/2022] Open
Abstract
Background Recurrent or de novo nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) are common after liver transplantation (LT) and may be associated with rapid progression to fibrosis; however, there is limited data in this regard after living donor liver transplantation (LDLT). Material and methods This is a retrospective study at a high volume LDLT center of all liver biopsies performed in patients with post-transplant NAFLD diagnosed on ultrasound of the abdomen. Liver biopsy was indicated for raised transaminases and/or high liver stiffness on TE. The association between these prebiopsy parameters and inflammation and fibrosis on histology was analyzed. Data are shown as mean ± standard deviation or median (25-75 interquartile range). Results The study cohort consisted of 31 males and 3 females, aged 43 ± 10 years. The LT to liver biopsy interval was 44 (28-68) months. The prebiopsy AST and ALT were 71 (38-119) and 66 (50-156), respectively. The histology suggested no nonalcoholic steatohepatitis (NASH) in 7 (20%), borderline NASH in 15 (44%), and NASH in 12 (35%) patients. A total of 15 patients (44%) had stage 1 or stage 2 fibrosis. The proportion of patients having fibrosis was significantly higher in patients with NASH (83%) compared to patients with borderline NASH (33%) or no NASH (none had fibrosis, P = 0.001). Among 18 patients who underwent TE (on FibroScan), liver stiffness was significantly higher in patients with fibrosis [18.1 (9.7-22.5)] than in those without fibrosis [9.7 (4.0-12.7); P = 0.043]. Conclusion Over a third of the LDLT recipients with post-transplant NAFLD developed NASH, and nearly half, borderline NASH 3-5 years after transplant. Most with established NASH also had fibrosis on histology. Prevention of risk factors and early diagnosis is warranted in these patients.
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Affiliation(s)
- Narendra S. Choudhary
- Institute of Liver Transplantation and Regenerative Medicine, Medanta The Medicity, Gurgaon, Delhi (NCR), India
| | - Neeraj Saraf
- Institute of Liver Transplantation and Regenerative Medicine, Medanta The Medicity, Gurgaon, Delhi (NCR), India
| | - Swapnil Dhampalwar
- Institute of Liver Transplantation and Regenerative Medicine, Medanta The Medicity, Gurgaon, Delhi (NCR), India
| | - Saurabh Mishra
- Institute of Liver Transplantation and Regenerative Medicine, Medanta The Medicity, Gurgaon, Delhi (NCR), India
| | - Dheeraj Gautam
- Department of Pathology, Medanta The Medicity, Gurgaon, Delhi (NCR), India
| | - Lipika Lipi
- Department of Pathology, Medanta The Medicity, Gurgaon, Delhi (NCR), India
| | - Amit Rastogi
- Institute of Liver Transplantation and Regenerative Medicine, Medanta The Medicity, Gurgaon, Delhi (NCR), India
| | - Prashant Bhangui
- Institute of Liver Transplantation and Regenerative Medicine, Medanta The Medicity, Gurgaon, Delhi (NCR), India
| | - Rohan J. Chaudhary
- Institute of Liver Transplantation and Regenerative Medicine, Medanta The Medicity, Gurgaon, Delhi (NCR), India
| | - Ankur Gupta
- Institute of Liver Transplantation and Regenerative Medicine, Medanta The Medicity, Gurgaon, Delhi (NCR), India
| | - Kamal Yadav
- Institute of Liver Transplantation and Regenerative Medicine, Medanta The Medicity, Gurgaon, Delhi (NCR), India
| | - Arvinder S. Soin
- Institute of Liver Transplantation and Regenerative Medicine, Medanta The Medicity, Gurgaon, Delhi (NCR), India
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15
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Balitzer D, Tsai JH, Gill RM. Clinicopathologic features of de novo non-alcoholic steatohepatitis in the post-transplant setting. Diagn Pathol 2022; 17:65. [PMID: 35948927 PMCID: PMC9367095 DOI: 10.1186/s13000-022-01247-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2022] [Accepted: 07/29/2022] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND Non-alcoholic steatohepatitis (NASH) has become an increasingly recognized problem in patients after orthotopic liver transplant. The aims of this study were to compare the clinicopathologic features of recurrent and de novo NASH. METHODS From 1995 to 2016, we performed a retrospective review of patients with a histological diagnosis of non-alcoholic steatohepatitis made more than 6 months after liver transplant at University of California, San Francisco. The cases were categorized into de novo (n = 19) or recurrent steatohepatitis (n = 37). RESULTS Hepatitis C virus (HCV) infection-related cirrhosis was the most common etiology of transplantation in de novo NASH (78% of cases, n = 29). There was no difference in glycogenosis or presence of grade 3 steatosis. More recurrent NASH biopsies had small ballooned hepatocytes (62.5% of cases) compared to de novo NASH (26.7%) (p = 0.03), and were less likely to show prominent portal inflammation (5% versus 40.5%, p = 0.0049). The diagnosis of recurrent NASH was made significantly sooner after transplantation than the diagnosis of de novo NASH (2.8 years versus 4.8 years, p = 0.02). CONCLUSIONS Overall, our results support that recurrent NASH demonstrates distinct clinicopathologic features compared to de novo NASH arising in the post-transplant setting.
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Affiliation(s)
- Dana Balitzer
- Department of Pathology, San Francisco VA Health Care System, San Francisco, CA, USA. .,Department of Pathology, University of California, San Francisco, CA, USA.
| | - Jia-Huei Tsai
- Department of Pathology, National Taiwan University Hospital, Taipei, Taiwan.,Graduate Institute of Pathology, College of Medicine, National Taiwan University, Taipei, Taiwan
| | - Ryan M Gill
- Department of Pathology, University of California, San Francisco, CA, USA
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16
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Safavi D, Creavin B, Gallagher TK, Kelly ME. The role of bariatric surgery in liver transplantation: timing and type. Langenbecks Arch Surg 2022; 407:3249-3258. [DOI: 10.1007/s00423-022-02606-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2022] [Accepted: 07/09/2022] [Indexed: 11/29/2022]
Abstract
Abstract
Introduction
The rise in obesity worldwide has shifted the indications for liver transplantation (LT), with non-alcoholic steatohepatitis (NASH) being the second most common indication for transplantation. There remains an underestimation of cirrhosis being attributed to NASH. Bariatric surgery (BS) is a reliable solution to overcome obesity and its associated comorbidities. The role of BS in LT has been investigated by different studies; however, the type of BS and timing of LT need further investigation.
Methods
A systemic review examining the role of BS in LT patients was performed. After selection of the studies based on inclusion and exclusion criteria, data extraction was performed by two independent reviewers. Primary outcomes included patient and graft survival.
Results
From a total of 2374 articles, five met the prefined criteria. One hundred sixty-two patients had both BS + LT and 1426 underwent LT alone. The percentage of female patients in the BS + LT and LT cohorts was 75% and 35% respectively. The average age in BS + LT and LT cohorts was 43.05 vs. 56.22 years respectively. Patients undergoing BS had comparable outcomes in terms of overall patient survival, graft survival and post-operative morbidity compared to LT alone. When comparing BMI change in patients with prior versus simultaneous BS + LT, no significant difference was found.
Conclusion
BS and LT patients achieve comparable outcomes to general LT populations. Further studies examining simultaneous BS + LT are needed to answer questions concerning patient selection and timing of surgery.
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17
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Siddiqui MS, Patel S, Forsgren M, Bui AT, Shen S, Syed T, Boyett S, Chen S, Sanyal AJ, Wolver S, Kirkman D, Celi FS, Bhati CS. Differential fuel utilization in liver transplant recipients and its relationship with non-alcoholic fatty liver disease. Liver Int 2022; 42:1401-1409. [PMID: 35129295 PMCID: PMC9189602 DOI: 10.1111/liv.15178] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/11/2021] [Revised: 12/21/2021] [Accepted: 01/09/2022] [Indexed: 02/13/2023]
Abstract
UNLABELLED Metabolic flexibility is the ability to match biofuel availability to utilization. Reduced metabolic flexibility, or lower fatty acid (FA) oxidation in the fasted state, is associated with obesity. The present study evaluated metabolic flexibility after liver transplantation (LT). METHODS Patients receiving LT for non-alcoholic steatohepatitis (NASH) (n = 35) and non-NASH (n = 10) were enrolled. NASH was chosen as these patients are at the highest risk of metabolic complications. Metabolic flexibility was measured using whole-body calorimetry and expressed as respiratory quotient (RQ), which ranges from 0.7 (pure FA oxidation) to 1.0 is (carbohydrate oxidation). RESULTS The two cohorts were similar except for a higher prevalence of obesity and diabetes in the NASH cohort. Post-prandially, RQ increased in both cohorts (i.e. greater carbohydrate utilization) but peak RQ and time at peak RQ was higher in the NASH cohort. Fasting RQ in NASH was significantly higher (0.845 vs. 0.772, p < .001), indicative of impaired FA utilization. In subgroup analysis of the NASH cohort, body mass index but not liver fat content (MRI-PDFF) was an independent predictor of fasting RQ. In NASH, fasting RQ inversely correlated with fat-free muscle volume and directly with visceral adipose tissue. CONCLUSION Reduced metabolic flexibility in patients transplanted for NASH cirrhosis may precede the development of non-alcoholic fatty liver disease after LT.
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Affiliation(s)
- Mohammad S. Siddiqui
- Division of Gastroenterology and HepatologyVirginia Commonwealth UniversityRichmondVirginiaUSA
| | - Samarth Patel
- Division of Gastroenterology and HepatologyVirginia Commonwealth UniversityRichmondVirginiaUSA,Division of Gastroenterology and HepatologyHunter‐Holmes McGuire VARichmondVirginiaUSA
| | - Mikael Forsgren
- Department of Health, Medicine and Caring SciencesLinköping UniversityLinköpingSweden
| | - Anh T. Bui
- Department of Statistical Sciences and Operations ResearchVirginia Commonwealth UniversityRichmondVirginiaUSA
| | - Steve Shen
- Division of Gastroenterology and HepatologyVirginia Commonwealth UniversityRichmondVirginiaUSA
| | - Taseen Syed
- Division of Gastroenterology and HepatologyVirginia Commonwealth UniversityRichmondVirginiaUSA
| | - Sherry Boyett
- Division of Gastroenterology and HepatologyVirginia Commonwealth UniversityRichmondVirginiaUSA
| | - Shanshan Chen
- Division of Endocrinology, Diabetes and MetabolismVirginia Commonwealth UniversityRichmondVirginiaUSA
| | - Arun J. Sanyal
- Division of Gastroenterology and HepatologyVirginia Commonwealth UniversityRichmondVirginiaUSA
| | - Susan Wolver
- Department of Internal MedicineVirginia Commonwealth UniversityRichmondVirginiaUSA
| | - Danielle Kirkman
- Department of Kinesiology and Health SciencesVirginia Commonwealth UniversityRichmondVirginiaUSA
| | - Francesco S. Celi
- Division of Endocrinology, Diabetes and MetabolismVirginia Commonwealth UniversityRichmondVirginiaUSA
| | - Chandra S. Bhati
- Division of Transplant SurgeryVirginia Commonwealth UniversityRichmondVirginiaUSA
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18
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Bharath Kumar C, Goel A, Jaleel R, David D, Zachariah U, Ramachandran J, Eapen CE. Prevalence of Risk Factors for Nonalcoholic Fatty Liver Disease in Middle-Aged and Elderly Patients With Cryptogenic Cirrhosis. J Clin Exp Hepatol 2022; 12:492-502. [PMID: 35535099 PMCID: PMC9077180 DOI: 10.1016/j.jceh.2021.05.008] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/28/2020] [Accepted: 05/22/2021] [Indexed: 12/12/2022] Open
Abstract
Aim of the study To study the prevalence of risk factors for nonalcoholic fatty liver disease (NAFLD) in middle-aged (40-59 years) and elderly patients (≥60 years) with cryptogenic cirrhosis as compared to those with hepatitis B or C virus (HBV or HCV) related cirrhosis. Methods and materials Between August 2013 and December 2014, cases (cryptogenic cirrhosis) and controls (HBV/HCV cirrhosis) above 40 years of age were prospectively recruited and assessed for the cause and prevalence of risk factors for NAFLD. Results One hundred eighteen cases (male-74%; age 55 (40-74) years; median (range); Child's class A:B:C-46:38:16) and 59 controls (male-80%; age 55.5 (40-69) years; Child's class A:B:C-56:30:14) were enrolled. Obesity (53% v/s 39%, P-0.081), diabetes mellitus (DM) (52% v/s 27%; P-0.002), family history of DM (30% v/s 13%; P-0.016), family history of Obesity (21% v/s 3.5%; P-0.002) and metabolic syndrome (65% v/s 44%; P-0.01) were more among cases than controls. Lifetime weight as obese was also longer in cases than in controls (5.9 ± 6.2 years v/s 3.2 ± 5.1 years, P-0.002). On subgroup analysis, in elderly age group, DM (55% v/s 17%, P-0.006), family history of DM (40% v/s 11%, P-0.025), metabolic syndrome (76% v/s 44%, P-0.017) and family history of obesity (19% v/s 0, P-0.047) were more common in cases as compared to controls, where as in the middle-age group, family history of obesity was the only significant factor (22% v/s 5%, P-0.025). Lifetime weight as obese was longer in cases than controls in both middle and elderly age groups. Conclusion Among middle-aged and elderly patients with cirrhosis, there was a higher prevalence of risk factors for NAFLD in those with cryptogenic cirrhosis, compared to those with HBV or HCV cirrhosis.
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Affiliation(s)
| | - Ashish Goel
- Department of Hepatology, Division of GI Sciences, CMC Hospital, Vellore, Tamil Nadu, India
| | - Rajeeb Jaleel
- Department of Gastroenterology, Division of GI Sciences, CMC Hospital, Vellore, Tamil Nadu, India
| | - Deepu David
- Department of Gastroenterology, Division of GI Sciences, CMC Hospital, Vellore, Tamil Nadu, India,Address for correspondence: Department of Gastroenterology, Division of GI Sciences, CMC Hospital, Vellore, Tamil Nadu, India. Tel.: +91 4162282148.
| | - Uday Zachariah
- Department of Hepatology, Division of GI Sciences, CMC Hospital, Vellore, Tamil Nadu, India
| | - Jeyamani Ramachandran
- Department of Hepatology, Division of GI Sciences, CMC Hospital, Vellore, Tamil Nadu, India
| | - Chundamannil E. Eapen
- Department of Hepatology, Division of GI Sciences, CMC Hospital, Vellore, Tamil Nadu, India
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19
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Han MAT, Olivo R, Choi CJ, Pyrsopoulos N. De novo and recurrence of metabolic dysfunction-associated fatty liver disease after liver transplantation. World J Hepatol 2021; 13:1991-2004. [PMID: 35070003 PMCID: PMC8727208 DOI: 10.4254/wjh.v13.i12.1991] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/28/2021] [Revised: 07/27/2021] [Accepted: 11/25/2021] [Indexed: 02/06/2023] Open
Abstract
Metabolic dysfunction-associated fatty liver disease (MAFLD) is a new acronym adopted from the consensus of international experts. Given the increasing prevalence of MAFLD in pre-transplant settings, de novo and recurrent graft steatosis/MAFLD are common in post-transplant settings. The impact of graft steatosis on long-term outcomes is unclear. The current knowledge of incidence rate, risk factors, diagnosis, long-term outcomes, and management of graft steatosis (both de novo and recurrent) is discussed in this review.
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Affiliation(s)
- Ma Ai Thanda Han
- Department of Gastroenterology and Hepatology, Rutgers New Jersey Medical School, Newark, NJ 07103, United States
| | - Raquel Olivo
- Department of Gastroenterology and Hepatology, Rutgers University, New Jersey Medical School, Newark, NJ 07103, United States
| | - Catherine J Choi
- Department of Medicine, Rutgers New Jersey Medical School, Newark, NJ 07101, United States
| | - Nikolaos Pyrsopoulos
- Department of Gastroenterology and Hepatology, Rutgers New Jersey Medical School, Newark, NJ 07103, United States
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20
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The Need to Update Endpoints and Outcome Analysis in the Rapidly Changing Field of Liver Transplantation. Transplantation 2021; 106:938-949. [PMID: 34753893 DOI: 10.1097/tp.0000000000003973] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
Liver transplantation (LT) survival rates have continued to improve over the last decades, mostly due to the reduction of mortality early after transplantation. The advancement is facilitating a liberalization of access to LT, with more patients with higher risk profiles being added to the waiting list. At the same time, the persisting organ shortage fosters strategies to rescue organs of high-risk donors. This is facilitated by novel technologies such as machine perfusion. Owing to these developments, reconsideration of the current and emerging endpoints for the assessment of the efficacy of existing and new therapies is warranted. While conventional early endpoints in LT have focused on the damage induced to the parenchyma, the fate of the bile duct and the recurrence of the underlying disease have a stronger impact on the long-term outcome. In light of this evolving landscape, we here attempt to reflect on the appropriateness of the currently used endpoints in the field of LT trials.
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21
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Sharpton SR, Terrault NA, Tavakol MM, Posselt AM. Sleeve gastrectomy prior to liver transplantation is superior to medical weight loss in reducing posttransplant metabolic complications. Am J Transplant 2021; 21:3324-3332. [PMID: 33780129 DOI: 10.1111/ajt.16583] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2020] [Revised: 02/23/2021] [Accepted: 03/15/2021] [Indexed: 01/25/2023]
Abstract
Strategies to optimize the management of obesity-related metabolic complications after liver transplantation (LT) are needed. We examined the effect of pre-LT sleeve gastrectomy (SG), as compared to medical weight loss (MWL), on post-LT outcomes. This is a cohort study of adults (≥18 years) with medically complicated obesity who were eligible for pre-LT SG and underwent LT from January 1, 2006 to June 1, 2016. Logistic regression models evaluated the association of SG on post-LT diabetes and hypertension, defined as new-onset or progressive disease post-LT. Cox regression models evaluated the association of SG on recurrent and de novo nonalcoholic fatty liver disease (NAFLD). Among 70 LT recipients who were eligible for pre-LT SG, 14 (20%) underwent SG and 56 (80%) underwent MWL only. Mean follow-up was 5.2 years post-LT. The SG cohort sustained higher % total body weight loss at 3 years post-LT (28.9% vs. 5.4%, p < .001). In multivariable analyses, SG was associated with significantly lower risk of post-LT diabetes (OR 0.04, 95% CI 0.00-0.41, p = .01), hypertension (OR 0.15, 95% CI 0.04-0.67, p = .01), and recurrent and de novo NAFLD (HR 0.19, 95% CI 0.04-0.91, p = .04). When compared to MWL, SG resulted in sustained weight loss and significantly lower risk of diabetes, hypertension, and recurrent and de novo NAFLD post-LT.
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Affiliation(s)
- Suzanne R Sharpton
- Division of Gastroenterology, Department of Medicine, University of California, San Diego, La Jolla, California, USA
| | - Norah A Terrault
- Division of Gastrointestinal and Liver Diseases, Keck School of Medicine at the University of Southern California, Los Angeles, California, USA
| | - Mehdi M Tavakol
- Department of Surgery, University of California San Francisco, San Francisco, California, USA
| | - Andrew M Posselt
- Department of Surgery, University of California San Francisco, San Francisco, California, USA
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22
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Czarnecka K, Czarnecka P, Tronina O, Bączkowska T, Durlik M. Multidirectional facets of obesity management in the metabolic syndrome population after liver transplantation. IMMUNITY INFLAMMATION AND DISEASE 2021; 10:3-21. [PMID: 34598315 PMCID: PMC8669703 DOI: 10.1002/iid3.538] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/02/2021] [Revised: 08/26/2021] [Accepted: 09/14/2021] [Indexed: 12/13/2022]
Abstract
The obesity pandemic has resulted in an increasing demand for liver transplantation and has significantly altered the profile of liver transplant candidates in addition to affecting posttransplantation outcomes. In this review, we discuss a broad range of clinical approaches that warrant attention to provide comprehensive and patient‐centred medical care to liver transplant recipients, and to be prepared to confront the rapidly changing clinical challenges and ensuing dilemmas. Adipose tissue is a complex and metabolically active organ. Visceral fat deposition is a key predictor of overall obesity‐related morbidity and mortality. Limited pharmacological options are available for the treatment of obesity in the liver transplant population. Bariatric surgery may be an alternative in eligible patients. The rapidly increasing prevalence of nonalcoholic fatty liver disease (NAFLD) is a global concern; NAFLD affects both pre‐ and posttransplantation outcomes. Numerous studies have investigated pharmacological and nonpharmacological management of NAFLD and some of these have shown promising results. Liver transplant recipients are constantly exposed to numerous factors that result in intestinal microbiota alterations, which were linked to the development of obesity, diabetes type 2, metabolic syndrome (MS), NAFLD, and hepatocellular cancer. Microbiota modifications with probiotics and prebiotics bring gratifying results in the management of metabolic complications. Fecal microbiota transplantation (FMT) is successfully performed in many medical indications. However, the safety and efficacy profiles of FMT in immunocompromised patients remain unclear. Obesity together with immunosuppressive treatment, may affect the pharmacokinetic and/or pharmacodynamic properties of coadministered medications. Individualized immunosuppressive regimens are recommended following liver transplantation to address possible metabolic concerns. Effective and comprehensive management of metabolic complications is shown to yield multiple beneficial results in the liver transplant population and may bring gratifying results in improving long‐term survival rates.
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Affiliation(s)
- Kinga Czarnecka
- Department of Transplant Medicine, Nephrology and Internal Diseases, Medical University of Warsa, Warsaw, Poland
| | - Paulina Czarnecka
- Department of Transplant Medicine, Nephrology and Internal Diseases, Medical University of Warsa, Warsaw, Poland
| | - Olga Tronina
- Department of Transplant Medicine, Nephrology and Internal Diseases, Medical University of Warsa, Warsaw, Poland
| | - Teresa Bączkowska
- Department of Transplant Medicine, Nephrology and Internal Diseases, Medical University of Warsa, Warsaw, Poland
| | - Magdalena Durlik
- Department of Transplant Medicine, Nephrology and Internal Diseases, Medical University of Warsa, Warsaw, Poland
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Li XY, Tan HK, Loh YH. New-onset cardiovascular risk factors following liver transplantation: A cohort analysis in Singapore. ANNALS OF THE ACADEMY OF MEDICINE, SINGAPORE 2021; 50:548-555. [PMID: 34342335 DOI: 10.47102/annals-acadmedsg.2020632] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/13/2023]
Abstract
INTRODUCTION The aims of this study were to establish weight change, incidence of non-alcoholic fatty liver disease (NAFLD) and cardiovascular risk factors (CvRF) in liver transplant recipients (LTRs). METHODS Eighty-three patients whose mean (standard deviation [SD]) age was 55.6 (8.4) years (median follow-up 73 months) and who underwent their first liver transplantation (LT) at Singapore General Hospital between February 2006 and March 2017 were included in the study. Anthropometric, clinical and demographic data were collected retrospectively from patients' medical records. Diabetes mellitus (DM), hyperlipidaemia and hypertension were regarded as CvRF. RESULTS Compared to baseline, mean (SD) body weight decreased significantly at 1 month post-LT (60.8kg [11.9] versus 64.3kg [13.7], P<0.001). There was a gradual recovery of body weight thereafter, increasing significantly at year 2 (64.3kg [12.3] vs 61.5kg [13.7], P<0.001) until year 5 (66.9kg [12.4] vs 62.2kg [13.9], P<0.001), respectively. The prevalence of CvRF was significantly higher post-LT. NAFLD occurred in 25.3% of LTRs and it was significantly associated with post-LT DM and hyperlipidaemia. CONCLUSION CvRF increased significantly post-LT, and NAFLD occurred in 25.3% of LTRs. Body weight dropped drastically within the first month post-LT, which then returned to baseline level just before the end of first year. This novel finding suggests that nutritional intervention needs to be tailored and individualised, based on events and time from transplant. Although long-term obesity is a significant problem, aggressive oral or enteral nutritional supplements take precedence in the early and immediate post-LT period, while interventions targeted at metabolic syndrome become necessary after the first year.
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Affiliation(s)
- Xiao Ying Li
- Department of Dietetics, Singapore General Hospital, Singapore
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Shetty A, Giron F, Divatia MK, Ahmad MI, Kodali S, Victor D. Nonalcoholic Fatty Liver Disease after Liver Transplant. J Clin Transl Hepatol 2021; 9:428-435. [PMID: 34221929 PMCID: PMC8237139 DOI: 10.14218/jcth.2020.00072] [Citation(s) in RCA: 1] [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: 07/26/2020] [Revised: 02/24/2021] [Accepted: 03/28/2021] [Indexed: 12/18/2022] Open
Abstract
Nonalcoholic fatty liver disease (NAFLD) is one of the most common causes of chronic liver disease in the world. The rising prevalence of nonalcoholic steatohepatitis (NASH) has led to a 170% increase in NASH cirrhosis as the listing indication for liver transplantation from 2004 to 2013. As of 2018, NASH has overtaken hepatitis C as an indication for liver transplantation in the USA. After liver transplantation, the allograft often develops recurrent NAFLD among patients with known NASH cirrhosis. In addition to recurrent disease, de novo NAFLD has been reported in patients with other indications for liver transplantation. In this review, we will discuss the risk factors associated with recurrent and de novo NAFLD, natural course of the disease, and management strategies after liver transplantation.
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Affiliation(s)
- Akshay Shetty
- Department of Medicine, Sherrie and Alan Conover Center for Liver Disease and Transplantation, Houston Methodist Hospital, Houston, TX, USA
| | - Fanny Giron
- Department of Medicine, Houston Methodist Hospital, Houston, TX, USA
| | - Mukul K. Divatia
- Department of Pathology and Genomic Medicine, Weill Cornell Medical College, Houston Methodist Hospital, Houston, TX, USA
| | - Muhammad I. Ahmad
- Department of Medicine, Sherrie and Alan Conover Center for Liver Disease and Transplantation, Houston Methodist Hospital, Houston, TX, USA
| | - Sudha Kodali
- Department of Medicine, Sherrie and Alan Conover Center for Liver Disease and Transplantation, Houston Methodist Hospital, Houston, TX, USA
| | - David Victor
- Department of Medicine, Sherrie and Alan Conover Center for Liver Disease and Transplantation, Houston Methodist Hospital, Houston, TX, USA
- Correspondence to: David Victor, Department of Medicine, Sherrie and Alan Conover Center for Liver Disease and Transplantation, Houston Methodist Hospital, Outpatient Center 22 Floor, Houston, TX 77030, USA. ORCID: https://orcid.org/0000-0003-1414-3128. Tel: +1-713-790-3089, E-mail:
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Bhat M, Usmani SE, Azhie A, Woo M. Metabolic Consequences of Solid Organ Transplantation. Endocr Rev 2021; 42:171-197. [PMID: 33247713 DOI: 10.1210/endrev/bnaa030] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/18/2020] [Indexed: 12/12/2022]
Abstract
Metabolic complications affect over 50% of solid organ transplant recipients. These include posttransplant diabetes, nonalcoholic fatty liver disease, dyslipidemia, and obesity. Preexisting metabolic disease is further exacerbated with immunosuppression and posttransplant weight gain. Patients transition from a state of cachexia induced by end-organ disease to a pro-anabolic state after transplant due to weight gain, sedentary lifestyle, and suboptimal dietary habits in the setting of immunosuppression. Specific immunosuppressants have different metabolic effects, although all the foundation/maintenance immunosuppressants (calcineurin inhibitors, mTOR inhibitors) increase the risk of metabolic disease. In this comprehensive review, we summarize the emerging knowledge of the molecular pathogenesis of these different metabolic complications, and the potential genetic contribution (recipient +/- donor) to these conditions. These metabolic complications impact both graft and patient survival, particularly increasing the risk of cardiovascular and cancer-associated mortality. The current evidence for prevention and therapeutic management of posttransplant metabolic conditions is provided while highlighting gaps for future avenues in translational research.
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Affiliation(s)
- Mamatha Bhat
- Multi Organ Transplant program and Division of Gastroenterology & Hepatology, University Health Network, Ontario M5G 2N2, Department of Medicine, University of Toronto, Ontario, Canada.,Toronto General Hospital Research Institute, University Health Network, Toronto, Ontario, Canada
| | - Shirine E Usmani
- Toronto General Hospital Research Institute, University Health Network, Toronto, Ontario, Canada.,Division of Endocrinology and Metabolism, Department of Medicine, University Health Network, Ontario, and Sinai Health System, Ontario, University of Toronto, Toronto, Ontario, Canada
| | - Amirhossein Azhie
- Multi Organ Transplant program and Division of Gastroenterology & Hepatology, University Health Network, Ontario M5G 2N2, Department of Medicine, University of Toronto, Ontario, Canada.,Toronto General Hospital Research Institute, University Health Network, Toronto, Ontario, Canada
| | - Minna Woo
- Toronto General Hospital Research Institute, University Health Network, Toronto, Ontario, Canada.,Division of Endocrinology and Metabolism, Department of Medicine, University Health Network, Ontario, and Sinai Health System, Ontario, University of Toronto, Toronto, Ontario, Canada
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Satapathy SK, Tran QT, Kovalic AJ, Bontha SV, Jiang Y, Kedia S, Karri S, Mupparaju V, Podila PSB, Verma R, Maluf D, Mas V, Nair S, Eason JD, Bridges D, Kleiner DE. Clinical and Genetic Risk Factors of Recurrent Nonalcoholic Fatty Liver Disease After Liver Transplantation. Clin Transl Gastroenterol 2021; 12:e00302. [PMID: 33555168 PMCID: PMC7864756 DOI: 10.14309/ctg.0000000000000302] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/18/2020] [Accepted: 12/18/2020] [Indexed: 12/12/2022] Open
Abstract
INTRODUCTION Nonalcoholic fatty liver disease (NAFLD) has been increasingly reported among recipients of liver transplantation (LT). We aimed to identify clinical and genetic risk factors responsible for the development of early recurrent NAFLD in nonalcoholic steatohepatitis transplant recipients. METHODS Forty-six total single nucleotide polymorphisms with known association with NAFLD were tested among both recipient and donor liver samples in 66 LT recipients with nonalcoholic steatohepatitis to characterize influences on NAFLD recurrence at ∼1 year post-LT (median interval from LT to biopsy: 377 days). RESULTS Recurrent NAFLD was identified in 43 (65.2%) patients, 20 (30.3%) with mild recurrence, and 23 (34.8%) with moderate to severe NAFLD. On adjusted analysis, change in the body mass index (BMI) (ΔBMI) was significantly associated with NAFLD recurrence, whereas post-LT diabetes mellitus was associated with increased severity of NAFLD recurrence. ADIPOR1 rs10920533 in the recipient was associated with increased risk of moderate to severe NAFLD recurrence, whereas the minor allele of SOD2 rs4880 in the recipient was associated with reduced risk. Similar reduced risk was noted in the presence of donor SOD2 rs4880 and HSD17B13 rs6834314 polymorphism. DISCUSSION Increased BMI post-LT is strongly associated with NAFLD recurrence, whereas post-LT diabetes mellitus was associated with increased severity of NAFLD recurrence. Both donor and recipient SOD2 rs4880 and donor HSD17B13 rs6834314 single nucleotide polymorphisms may be associated with reduced risk of early NAFLD recurrence, whereas presence of the minor allele form of ADIPOR1 rs10920533 in the recipient is associated with increased severity NAFLD recurrence.
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Affiliation(s)
- Sanjaya K. Satapathy
- Division of Hepatology and Sandra Atlas Bass Center for Liver Diseases, Northwell Health, Manhasset, New York, USA
- James D. Eason Transplant Institute, Methodist University Hospital, Memphis, Tennessee
- Division of Transplant Surgery, Department of Surgery, University of Tennessee Health Science Center, Memphis, Tennessee
| | - Quynh T. Tran
- Department of Preventive Medicine, University of Tennessee Health Sciences Center, College of Medicine, Memphis, Tennessee, USA
| | - Alexander J. Kovalic
- Department of Internal Medicine, University of Tennessee Health Sciences Center, College of Medicine, Memphis, Tennessee, USA
| | - Sai Vineela Bontha
- James D. Eason Transplant Institute, Methodist University Hospital, Memphis, Tennessee
| | - Yu Jiang
- School of Public Health, University of Memphis, Memphis, Tennessee, USA
| | - Satish Kedia
- School of Public Health, University of Memphis, Memphis, Tennessee, USA
| | - Saradashri Karri
- Division of Transplant Surgery, Department of Surgery, University of Tennessee Health Science Center, Memphis, Tennessee
| | - Vamsee Mupparaju
- James D. Eason Transplant Institute, Methodist University Hospital, Memphis, Tennessee
| | - Pradeep S. B. Podila
- James D. Eason Transplant Institute, Methodist University Hospital, Memphis, Tennessee
| | - Rajanshu Verma
- James D. Eason Transplant Institute, Methodist University Hospital, Memphis, Tennessee
- Division of Transplant Surgery, Department of Surgery, University of Tennessee Health Science Center, Memphis, Tennessee
| | - Daniel Maluf
- James D. Eason Transplant Institute, Methodist University Hospital, Memphis, Tennessee
- Division of Transplant Surgery, Department of Surgery, University of Tennessee Health Science Center, Memphis, Tennessee
- University of Maryland School of Medicine, Baltimore, MD, USA
| | - Valeria Mas
- James D. Eason Transplant Institute, Methodist University Hospital, Memphis, Tennessee
| | - Satheesh Nair
- James D. Eason Transplant Institute, Methodist University Hospital, Memphis, Tennessee
- Division of Transplant Surgery, Department of Surgery, University of Tennessee Health Science Center, Memphis, Tennessee
| | - James D. Eason
- James D. Eason Transplant Institute, Methodist University Hospital, Memphis, Tennessee
- Division of Transplant Surgery, Department of Surgery, University of Tennessee Health Science Center, Memphis, Tennessee
| | - Dave Bridges
- Department of Nutritional Sciences University of Michigan School of Public Health, Ann Arbor, Michigan, USA
| | - David E. Kleiner
- Center for Cancer Research, National Cancer Institute, Bethesda, Maryland
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Lombardi R, Pisano G, Fargion S, Fracanzani AL. Cardiovascular involvement after liver transplantation: role of non-alcoholic fatty liver disease and non-alcoholic steatohepatitis. EXPLORATION OF MEDICINE 2021. [DOI: 10.37349/emed.2021.00030] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/19/2022] Open
Abstract
Patients submitted to liver transplantation (LT) are exposed to high risk of cardiovascular (CV) complications which are the main determinants of both short-term and long-term morbidity and mortality in LT. Non-alcoholic fatty liver disease (NAFLD) is a very frequent condition in general population and is associated with a high risk of cardiovascular disease (CVD) which represents the first cause of death of these patients. NAFLD is predicted to become the first indication to LT and nowadays is also frequently detected in patients submitted to LT for other indications. Thus, the risk of CVD in patients submitted to LT is forecasted to increase in the next years. In this review the extent of CV involvement in patients submitted to LT and the role of NAFLD, either recurring after transplantation or as de novo presentation, in increasing CV risk is analysed. The risk of developing metabolic alterations, including diabetes, hypertension, dyslipidemia and weight gain, all manifestations of metabolic syndrome, occurring in the first months after LT, is depicted. The different presentations of cardiac involvement, represented by early atherosclerosis, coronary artery disease, heart failure and arrhythmias in patients with NAFLD submitted to LT is described. In addition, the tools to detect cardiac alterations either before or after LT is reported providing the possibility for an early diagnosis of CVD and an early therapy able to reduce morbidity and mortality for these diseases. The need for long-term concerted multidisciplinary activity with dietary counseling and exercise combined with drug treatment of all manifestations of metabolic syndrome is emphasized.
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Affiliation(s)
- Rosa Lombardi
- General Medicine and Metabolic Diseases, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy 2Department of Pathophysiology and Transplantation, University of the Study of Milan, 20122 Milan, Italy
| | - Giuseppina Pisano
- General Medicine and Metabolic Diseases, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy
| | - Silvia Fargion
- Department of Pathophysiology and Transplantation, University of the Study of Milan, 20122 Milan, Italy
| | - Anna Ludovica Fracanzani
- General Medicine and Metabolic Diseases, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy 2Department of Pathophysiology and Transplantation, University of the Study of Milan, 20122 Milan, Italy
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Abstract
Obesity is increasing in prevalence in liver transplant candidates and recipients. The rise in liver transplantation for nonalcoholic steatohepatitis reflects this increase. Management of obesity in liver transplant candidates can be challenging due to the presence of decompensated cirrhosis and sarcopenia. Obesity may increase peritransplant morbidity but does not have an impact on long-term post-transplant survival. Bariatric surgery may be a feasible option in select patients before, during, or after liver transplantation. Use of weight loss drugs and/or endoscopic therapies for obesity management ultimately may play a role in liver transplant patients, but more research is needed to determine safety.
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Spiritos Z, Abdelmalek MF. Metabolic syndrome following liver transplantation in nonalcoholic steatohepatitis. Transl Gastroenterol Hepatol 2021; 6:13. [PMID: 33409407 DOI: 10.21037/tgh.2020.02.07] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/22/2019] [Accepted: 10/16/2019] [Indexed: 12/13/2022] Open
Abstract
Metabolic syndrome is a major clinical disorder involving metabolic dysregulation characterized clinically with features of central obesity, insulin resistance (IR), type 2 diabetes, hypertension, and dyslipidemia. Metabolic syndrome is strongly associated with the rising prevalence nonalcoholic steatohepatitis, a leading indication for orthotopic liver transplantation in the Western world. The presence or recurrence of metabolic syndrome following liver transplantation can contribute to the development and recurrence of nonalcoholic fatty liver disease (NAFLD) in the liver allograft. In this review, we discuss the endogenous and exogenous drivers of post-transplant metabolic syndrome, role of chronic immunosuppression, and the prevalence and clinical significant of post-transplant metabolic syndrome on nonalcoholic steatohepatitis.
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Affiliation(s)
- Zachary Spiritos
- Division of Gastroenterology and Hepatology, Duke University, Durham, NC, USA
| | - Manal F Abdelmalek
- Division of Gastroenterology and Hepatology, Duke University, Durham, NC, USA
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30
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Sharma P, Arora A. Approach to prevention of non-alcoholic fatty liver disease after liver transplantation. Transl Gastroenterol Hepatol 2020; 5:51. [PMID: 33073046 DOI: 10.21037/tgh.2020.03.02] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/14/2019] [Accepted: 10/15/2019] [Indexed: 12/22/2022] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) is one of the most common causes of liver disease and non-alcoholic steatohepatitis (NASH) related cirrhosis is third common indication for liver transplantation (LT). Patients who have NASH related cirrhosis and are candidates for LT often have multiple comorbidities. These comorbidities need to be addressed before and after transplantation as it affects overall survival. Like hepatitis B, hepatitis C, primary biliary cirrhosis, autoimmune hepatitis which recurs after transplantation, NASH also recurs after transplant however the impact of the recurrence on allograft and patient outcomes is unclear. Limited data suggests that it does not affect graft and patient survival. De novo NAFLD which is defined as occurrence of fatty liver in a patient who did not have fatty liver prior to LT can also occur in the allograft of patients transplanted for non-NAFLD liver disease. Obesity, hyperlipidemia, diabetes as well as steroid dose and duration after LT are common predictors of recurrence of NAFLD after transplantation. Studies on prevention and treatment of NASH in post-transplant patients are lacking. Prevention of weight gain, regular exercises, weight reducing surgery, limited steroid use or steroid free regimen have been tried with varying success. Future studies for the prevention of NAFLD/NASH are required especially in post liver transplant patient.
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Affiliation(s)
- Praveen Sharma
- Department of Gastroenterology & Hepatology, Sir Ganga Ram Hospital, New Delhi, India
| | - Anil Arora
- Department of Gastroenterology & Hepatology, Sir Ganga Ram Hospital, New Delhi, India
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Abstract
INTRODUCTION Liver transplantation is a life-changing event for patients and survival following transplantation has improved significantly since the first transplantation in 1967. Following liver transplantation, patients face a unique set of healthcare management decisions including transplantation-specific complications, recurrence of primary liver disease, as well as metabolic and malignancy concerns related to immunosuppression. As more patients with liver disease receive transplantation and live longer, understanding and managing these patients will require not only transplant specialist but also local subspecialist and primary care physicians. AREAS COVERED This review covers common issues related to the management of patients following liver transplantation including immunosuppression, liver allograft dysfunction, metabolic complications, as well as routine health maintenance such as immunizations and cancer screening. EXPERT OPINION Optimizing medical care for patients following liver transplant will benefit from ensuring all providers, not just transplant specialist, have a basic understanding of the common issues encountered in the post-transplant patient. This review provides an overview of common healthcare concerns and management options for patients following liver transplantation.
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Affiliation(s)
- Nicholas Hoppmann
- Division of Gastroenterology and Hepatology, University of Alabama at Birmingham , Birmingham, Alabama, USA
| | - Omar Massoud
- Division of Gastroenterology and Hepatology, University of Alabama at Birmingham , Birmingham, Alabama, USA
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Santos BC, Correia MITD, Anastácio LR. Energy Expenditure and Liver Transplantation: What We Know and Where We Are. JPEN J Parenter Enteral Nutr 2020; 45:456-464. [DOI: 10.1002/jpen.1985] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/04/2020] [Revised: 07/24/2020] [Accepted: 07/27/2020] [Indexed: 12/17/2022]
Affiliation(s)
- Bárbara Chaves Santos
- Food Science Post Graduation Program Universidade Federal de Minas Gerais Belo Horizonte Brazil
| | - Maria Isabel Toulson Davisson Correia
- Food Science Post Graduation Program Universidade Federal de Minas Gerais Belo Horizonte Brazil
- Surgery Department Universidade Federal de Minas Gerais Belo Horizonte Brazil
| | - Lucilene Rezende Anastácio
- Food Science Post Graduation Program Universidade Federal de Minas Gerais Belo Horizonte Brazil
- Food Science Department Universidade Federal de Minas Gerais Belo Horizonte Brazil
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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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Chen YY, Yeh MM. Non-alcoholic fatty liver disease: A review with clinical and pathological correlation. J Formos Med Assoc 2020; 120:68-77. [PMID: 32654868 DOI: 10.1016/j.jfma.2020.07.006] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/08/2020] [Revised: 05/04/2020] [Accepted: 07/02/2020] [Indexed: 02/07/2023] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in North America and Europe, with increasing prevalence in other regions of the world. Its spectrum encompass steatosis, non-alcoholic steatohepatitis (NASH), fibrosis and cirrhosis. It is considered as the manifestation of metabolic syndrome in liver, and its development and progression is influenced by complex interaction of environmental and genetic factors. In this review we discuss the histopathological features, differential diagnoses, and the commonly used grading and staging systems of NAFLD. NAFLD associated with other diseases, histological changes after therapeutic intervention and recurrence or occurrence of NAFLD after liver transplantation are also addressed.
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Affiliation(s)
- Yen-Ying Chen
- Department of Pathology and Laboratory Medicine, Taipei Veterans General Hospital, Taipei, Taiwan; School of Medicine, National Yang-Ming University, Taipei, Taiwan
| | - Matthew M Yeh
- Department of Pathology, University of Washington School of Medicine, Seattle, United States; Department of Medicine, University of Washington School of Medicine, Seattle, United States.
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Incidence and Risks for Nonalcoholic Fatty Liver Disease and Steatohepatitis Post-liver Transplant: Systematic Review and Meta-analysis. Transplantation 2020; 103:e345-e354. [PMID: 31415032 DOI: 10.1097/tp.0000000000002916] [Citation(s) in RCA: 80] [Impact Index Per Article: 16.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
BACKGROUND The true incidence and unique risk factors for recurrent and de novo nonalcoholic fatty liver (NAFLD) and nonalcoholic steatohepatitis (NASH) post-liver transplant (LT) remain poorly characterized. We aimed to identify the incidence and risk factors for recurrent and de novo NAFLD/NASH post-LT. METHODS MEDLINE via PubMed, Embase, Scopus, and CINAHL were searched for studies from 2000 to 2018. Risk of bias was adjudicated using the Newcastle-Ottawa Scale. RESULTS Seventeen studies representing 2378 patients were included. All were retrospective analyses of patients with post-LT liver biopsies, with the exception of 2 studies that used imaging for outcome assessment. Seven studies evaluated occurrence of recurrent NAFLD/NASH, 3 evaluated de novo occurrence, and 7 evaluated both recurrent and de novo. In studies at generally high or moderate risk of bias, mean 1-, 3-, and ≥5-year incidence rates may be 59%, 57%, and 82% for recurrent NAFLD; 67%, 40%, and 78% for de novo NAFLD; 53%, 57.4%, and 38% for recurrent NASH; and 13%, 16%, and 17% for de novo NASH. Multivariate analysis demonstrated that post-LT body mass index (summarized odds ratio = 1.27) and hyperlipidemia were the most consistent predictors of outcomes. CONCLUSIONS There is low confidence in the incidence of recurrent and de novo NAFLD and NASH after LT due to study heterogeneity. Recurrent and de novo NAFLD may occur in over half of recipients as soon as 1 year after LT. NASH recurs in most patients after LT, whereas de novo NASH occurs rarely. NAFLD/NASH after LT is associated with metabolic risk factors.
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Cigrovski Berkovic M, Virovic-Jukic L, Bilic-Curcic I, Mrzljak A. Post-transplant diabetes mellitus and preexisting liver disease - a bidirectional relationship affecting treatment and management. World J Gastroenterol 2020; 26:2740-2757. [PMID: 32550751 PMCID: PMC7284186 DOI: 10.3748/wjg.v26.i21.2740] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/22/2020] [Revised: 04/24/2020] [Accepted: 05/13/2020] [Indexed: 02/06/2023] Open
Abstract
Liver cirrhosis and diabetes mellitus (DM) are both common conditions with significant socioeconomic burden and impact on morbidity and mortality. A bidirectional relationship exists between DM and liver cirrhosis regarding both etiology and disease-related complications. Type 2 DM (T2DM) is a well-recognized risk factor for chronic liver disease and vice-versa, DM may develop as a complication of cirrhosis, irrespective of its etiology. Liver transplantation (LT) represents an important treatment option for patients with end-stage liver disease due to non-alcoholic fatty liver disease (NAFLD), which represents a hepatic manifestation of metabolic syndrome and a common complication of T2DM. The metabolic risk factors including immunosuppressive drugs, can contribute to persistent or de novo development of DM and NAFLD after LT. T2DM, obesity, cardiovascular morbidities and renal impairment, frequently associated with metabolic syndrome and NAFLD, may have negative impact on short and long-term outcomes following LT. The treatment of DM in the context of chronic liver disease and post-transplant is challenging, but new emerging therapies such as glucagon-like peptide-1 receptor agonists (GLP-1RAs) and sodium–glucose cotransporter 2 inhibitors (SGLT2i) targeting multiple mechanisms in the shared pathophysiology of disorders such as oxidative stress and chronic inflammation are a promising tool in future patient management.
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Affiliation(s)
- Maja Cigrovski Berkovic
- Department of Kinesiological Anthropology and Methodology, Faculty of Kinesiology, University of Zagreb, Zagreb 10000, Croatia
- Clinical Hospital Dubrava, Zagreb 10000, Croatia
- Department of Pharmacology, Faculty of Medicine, University of J. J. Strossmayer Osijek, Osijek 31000, Croatia
| | - Lucija Virovic-Jukic
- School of Medicine, University of Zagreb, Zagreb 10000, Croatia
- Department of Medicine, Division of Gastroenterology and Hepatology, Sisters of Charity University Hospital, Zagreb 10000, Croatia
| | - Ines Bilic-Curcic
- Department of Pharmacology, Faculty of Medicine, University of J. J. Strossmayer Osijek, Osijek 31000, Croatia
- School of Medicine, University of Zagreb, Zagreb 10000, Croatia
- Clinical Hospital Center Osijek, Osijek 31000, Croatia
| | - Anna Mrzljak
- School of Medicine, University of Zagreb, Zagreb 10000, Croatia
- Department of Medicine, Merkur University Hospital, Zagreb 10000, Croatia
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Management of metabolic syndrome and cardiovascular risk after liver transplantation. Lancet Gastroenterol Hepatol 2020; 4:731-741. [PMID: 31387736 DOI: 10.1016/s2468-1253(19)30181-5] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/26/2019] [Revised: 04/22/2019] [Accepted: 04/23/2019] [Indexed: 12/11/2022]
Abstract
Cardiovascular events are the second most prevalent cause of non-hepatic mortality in liver transplant recipients. The incidence of these events is projected to rise because of the growing prevalence of non-alcoholic steatohepatitis as a transplant indication and the ageing population of liver transplant recipients. Recipients with metabolic syndrome are up to four times more likely to have a cardiovascular event than recipients without, therefore prevention and optimal treatment of the components of metabolic syndrome are key in reducing the risk of these events. Although data on the treatment of metabolic comorbidities specifically in liver transplant recipients are scarce, there is detailed guidance from learned societies that mostly mirrors the guidance for patients at increased cardiovascular risk in the general population. In this Review, we discuss the management of the components of metabolic syndrome following liver transplantation and provide practical stepwise guidance. We also emphasise the need for adequately powered studies for the treatment of metabolic comorbidities in liver transplant recipients.
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Taneja S, Roy A. Nonalcoholic steatohepatitis recurrence after liver transplant. Transl Gastroenterol Hepatol 2020; 5:24. [PMID: 32258528 DOI: 10.21037/tgh.2019.10.12] [Citation(s) in RCA: 20] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/04/2019] [Accepted: 10/15/2019] [Indexed: 12/20/2022] Open
Abstract
Nonalcoholic steatohepatitis (NASH) is the fastest growing indication for liver transplant (LT)worldwide and is deemed to be the foremost indication in the near future. Recurrence of NASH can occur post LT and has been observed to be a common phenomenon. Baseline metabolic co-morbidities and worsening of metabolic profile post LT are the principal drivers of NASH recurrence. Liver biopsy remains the gold standard for establishing the diagnosis. However, noninvasive methods including transient elastography (TE) and magnetic resonance imaging (MRI) seem to be promising. The implications of recurrent NASH on post LT outcomes, graft steatosis, progression to fibrosis, overall survival, and cardiovascular associations warrant careful evaluation. Control of metabolic parameters and weight gain along with tailored immunosuppression remain the cornerstone of management. Extrapolation of the ever-increasing armamentarium of NASH pharmacotherapy specifically in this population of recurrent NAFLD remains a challenge for the future.
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Affiliation(s)
- Sunil Taneja
- Department of Hepatology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Akash Roy
- Department of Hepatology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
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Eshraghian A, Nikeghbalian S, Kazemi K, Shamsaeefar A, Geramizadeh B, Malek-Hosseini SA. Non-alcoholic fatty liver disease after liver transplantation in patients with non-alcoholic steatohepatitis and cryptogenic cirrhosis: the impact of pre-transplant graft steatosis. HPB (Oxford) 2020; 22:521-528. [PMID: 31431413 DOI: 10.1016/j.hpb.2019.07.015] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/17/2019] [Accepted: 07/27/2019] [Indexed: 12/12/2022]
Abstract
BACKGROUND Nonalcoholic fatty liver disease (NAFLD) may occur in liver transplant recipients. This study aimed to investigate the prevalence and risk factors of NAFLD after liver transplantation in patients with NASH and cryptogenic cirrhosis, focusing on the impact of graft steatosis. METHODS Patients with NASH and cryptogenic cirrhosis who had undergone liver transplantation in Shiraz transplant center between March 2010 and March 2017 were included. NAFLD was diagnosed after liver transplantation using ultrasonography and transient elastography. RESULTS 73 patients with NASH and 389 with cryptogenic cirrhosis were included. NAFLD was diagnosed in 33 patients (56.9%) in NASH group and 96 patients (26.7%) in cryptogenic group (OR: 3.61; CI: 2.04-6.39; P-Value < 0.001), using ultrasound. Obesity and post-transplant hyperlipidemia were independent predictors of NAFLD after liver transplantation (P < 0.05). NAFLD was diagnosed in 32.9% of patients with graft macrosteatosis compared to 29.9% in patients without graft macrosteatosis (OR: 1.51; 95%CI: 0.755-1.753). 28% of the patients with macrosteatosis ≥30% had NAFLD after liver transplantation compared to 31.4% with macrosteatosis <30% (OR: 1.175; 95% CI: 0.346-2.091). CONCLUSION Liver graft steatosis before transplantation was not associated with the occurrence of NAFLD after liver transplantation.
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Affiliation(s)
- Ahad Eshraghian
- Avicenna Center for Medicine and Organ Transplant, Shiraz University of Medical Sciences, Shiraz, Iran.
| | - Saman Nikeghbalian
- Avicenna Center for Medicine and Organ Transplant, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Kourosh Kazemi
- Avicenna Center for Medicine and Organ Transplant, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Alireza Shamsaeefar
- Avicenna Center for Medicine and Organ Transplant, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Bita Geramizadeh
- Avicenna Center for Medicine and Organ Transplant, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Seyed Ali Malek-Hosseini
- Avicenna Center for Medicine and Organ Transplant, Shiraz University of Medical Sciences, Shiraz, Iran
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Chandrakumaran A, Siddiqui MS. Implications of Nonalcoholic Steatohepatitis as the Cause of End-Stage Liver Disease Before and After Liver Transplant. Gastroenterol Clin North Am 2020; 49:165-178. [PMID: 32033762 PMCID: PMC7008719 DOI: 10.1016/j.gtc.2019.09.005] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
Abstract
Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease. Nonalcoholic steatohepatitis (NASH) is the clinically aggressive variant of NAFLD and has a propensity for fibrosis progression and cirrhosis. The prevalence of NAFLD and NASH is projected to increase rapidly in the near future and dramatically add to the already substantial health care burden. Cirrhosis and end-stage liver disease resulting from NASH is now the fastest growing indication for liver transplant (LT) in the United States. Patients with NASH cirrhosis have higher prevalence of cardiometabolic diseases. Following LT, recurrence of NAFLD and NASH is common.
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Affiliation(s)
| | - Mohammad Shadab Siddiqui
- Department of Internal Medicine, Division of Gastroenterology, Hepatology, and Nutrition, Virginia Commonwealth University, Richmond, VA 23298-0341, USA.
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41
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Cotter TG, Charlton M. Nonalcoholic Steatohepatitis After Liver Transplantation. Liver Transpl 2020; 26:141-159. [PMID: 31610081 DOI: 10.1002/lt.25657] [Citation(s) in RCA: 45] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/29/2019] [Accepted: 10/07/2019] [Indexed: 02/07/2023]
Abstract
Currently, nonalcoholic steatohepatitis (NASH) is the second leading indication for liver transplantation (LT), behind alcohol-related liver disease. After transplant, both recurrent and de novo nonalcoholic fatty liver disease are common; however, recurrence rates of NASH and advanced fibrosis are low. Identification of high-risk groups and optimizing treatment of metabolic comorbidities both before and after LT is paramount to maintaining a healthy allograft, especially with the additional consequences of longterm immunosuppression. In addition, NASH LT recipients are at an increased risk of cardiovascular events and malignancy, and their condition warrants a tailored approach to management. The optimal approach to NASH LT recipients including metabolic comorbidities management, tailored immunosuppression, the role of bariatric surgery, and nutritional and pharmacotherapy of NASH are discussed in this review. Overall, aggressive management of metabolic syndrome after LT via medical and surgical modalities and a minimalist approach to immunosuppression is advised.
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Affiliation(s)
- Thomas G Cotter
- Center for Liver Diseases, The University of Chicago Medicine, Chicago, IL
| | - Michael Charlton
- Center for Liver Diseases, The University of Chicago Medicine, Chicago, IL
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42
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Siddiqui MB, Patel S, Bhati C, Reichman T, Williams K, Driscoll C, Liptrap E, Rinella ME, Sterling RK, Siddiqui MS. Range of Normal Serum Aminotransferase Levels in Liver Transplant Recipients. Transplant Proc 2019; 51:1895-1901. [PMID: 31399173 DOI: 10.1016/j.transproceed.2019.04.062] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2018] [Accepted: 04/05/2019] [Indexed: 02/07/2023]
Abstract
Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) are used to monitor liver transplant recipients (LTR) but the reference range and context of its use is not well defined. We aimed to determine the healthy ranges in LTR without chronic liver disease. METHODS One hundred and three LTR without chronic liver disease based on serology, transient elastography with controlled attenuated parameter, and ultrasound were included. A healthy range of aminotransferases was set to 95th percentile. An updated normal aminotransferase range was used to detect recurrence in post-liver transplantation (LT) with hepatitis C virus (HCV) and nonalcoholic fatty liver disease (NAFLD). RESULTS The normal ALT and AST range was 0 to 57 and 0 to 54 IU/L, respectively, in LTR and was not affected by age, sex, obesity, or choice of immunosuppressant. The diagnostic performance of serum ALT and AST to detect recurrence of NAFLD by a controlled attenuated parameter was poor with area under the receiver operating characteristic curve of 0.573 (95% confidence interval 0.493, 0.655; P = .08) and 0.537 (0.456, 0.618; P = .4), respectively. In contrast, the diagnostic performance of ALT and AST to detect recurrence of HCV after LT was 0.906 (0.868, 0.944; P < .001) and 0.925 (0.890, 0.959; P < .001), respectively. CONCLUSION The updated aminotransferase range in LTR is higher than the general population and accurate for detecting recurrent HCV, but not NAFLD.
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Affiliation(s)
- Mohammad Bilal Siddiqui
- Division of Gastroenterology and Hepatology, Virginia Commonwealth University, Richmond, Virginia.
| | - Samarth Patel
- Division of Gastroenterology and Hepatology, Virginia Commonwealth University, Richmond, Virginia
| | - Chandra Bhati
- Division of Transplant Surgery, Virginia Commonwealth University, Richmond, Virginia
| | - Trevor Reichman
- Division of Transplant Surgery, Virginia Commonwealth University, Richmond, Virginia
| | - Kenyada Williams
- Division of Gastroenterology and Hepatology, Virginia Commonwealth University, Richmond, Virginia
| | - Carolyn Driscoll
- Division of Gastroenterology and Hepatology, Virginia Commonwealth University, Richmond, Virginia
| | - Erika Liptrap
- Division of Transplant Surgery, Virginia Commonwealth University, Richmond, Virginia
| | - Mary E Rinella
- Division of Gastroenterology and Hepatology, Northwestern University, Chicago, Illinois
| | - Richard K Sterling
- Division of Gastroenterology and Hepatology, Virginia Commonwealth University, Richmond, Virginia
| | - M Shadab Siddiqui
- Division of Gastroenterology and Hepatology, Virginia Commonwealth University, Richmond, Virginia
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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] [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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Jain M, Venkataraman J, Varghese J, Vij M, Reddy MS, Rela M. Explant liver evaluation decodes the mystery of cryptogenic cirrhosis! JGH OPEN 2019; 4:39-43. [PMID: 32055695 PMCID: PMC7008160 DOI: 10.1002/jgh3.12200] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/31/2018] [Revised: 04/30/2019] [Accepted: 05/04/2019] [Indexed: 12/16/2022]
Abstract
Background and Aim To determine the concordance of liver explants with the pretransplant diagnosis. Methods This was a retrospective analysis of 251 liver explants. Patient information included demography, comorbidity, and etiological diagnosis. Final diagnosis was based on morphological and histological findings. For non‐alcoholic steatohepatitis (NASH) and cryptogenic cirrhosis, we investigated comorbid states such as obesity, hypertension, and diabetes. Chi square test and Cohen's Kappa value were used. A P value of <0.05 was considered significant. Results A total of 192 patients (76.5%) were males. A significant concordance of explant diagnosis with pretransplant diagnosis was present in 225 (89.6%) patients. It was 100% for alcohol‐related disease, hepatitis B, hepatitis C, autoimmune (AI) liver disease, biliary cirrhosis, and Budd–Chiari syndrome. Of 37 patients with a pretransplant diagnosis of cryptogenic cirrhosis, major discordance was observed in 23 (62.1%). On explant, seven patients each had hemochromatosis 5 (13.5%), AI hepatitis, and NASH (18.9%); two had noncirrhotic fibrosis (5.4%); and one each had Wilson's disease and congenital hepatic fibrosis (2.7%). Of the 20 explants, 3 with pretransplant diagnosis of NASH had a diagnosis of cryptogenic cirrhosis on explant specimens. Cohen's Kappa for the concordance of pretransplant diagnosis and explant diagnosis in NASH and cryptogenic cirrhosis patients was 0.75 and 0.47, respectively. An incidental hepatocellular carcinoma was picked up in 16 explants, and 18 had granulomas. Conclusion Concordance between pretransplant and explant diagnosis is lower for NASH and cryptogenic cirrhosis. The true prevalence of cryptogenic cirrhosis in our study was 5.6%.
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Affiliation(s)
- Mayank Jain
- Institute of GI Sciences and Liver Transplantation Gleneagles Global Health City Chennai India
| | - Jayanthi Venkataraman
- Institute of GI Sciences and Liver Transplantation Gleneagles Global Health City Chennai India
| | - Joy Varghese
- Institute of GI Sciences and Liver Transplantation Gleneagles Global Health City Chennai India
| | - Mukul Vij
- Institute of GI Sciences and Liver Transplantation Gleneagles Global Health City Chennai India
| | - Mettu S Reddy
- Institute of GI Sciences and Liver Transplantation Gleneagles Global Health City Chennai India
| | - Mohamed Rela
- Institute of GI Sciences and Liver Transplantation Gleneagles Global Health City Chennai India
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Recurrent or De Novo Allograft Steatosis and Long-term Outcomes After Liver Transplantation. Transplantation 2019; 103:e14-e21. [PMID: 29994981 DOI: 10.1097/tp.0000000000002317] [Citation(s) in RCA: 71] [Impact Index Per Article: 11.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
BACKGROUND Hepatic steatosis is strongly associated with cardiovascular disease in the general population. Whether recurrent or de novo, it can occur in the allograft, but the impact on survival and long-term clinical outcomes remains unclear. In this study, we aim to determine both the frequency and impact of allograft steatosis on long-term posttransplant outcomes. METHODS A retrospective review of 588 adult liver transplant (LT) recipients (1999-2006) was performed. Cox regression analysis (time-dependent) was used to evaluate differences in time to steatosis post-LT, patient survival, and cardiovascular outcomes. RESULTS Mean age 51.9 ± 10.6 years, 64.6% males, underlying nonalcoholic steatohepatitis (NASH) (9.4%), previous tobacco (52%), pre-LT diabetes mellitus (30.3%), pre-LT hypertension (23.2%), and known cardiovascular disease (9.7%). Overall, 254 recipients developed allograft steatosis (at 10 years: 77.6% NASH recipients, 44.7% Non-NASH recipients). Risk factors for allograft steatosis were female sex (hazard ratio [HR], 1.47; 95% confidence interval [CI], 1.09-2.00; P = 0.014), hepatitis C virus diagnosis (HR, 2.49; 95% CI, 1.77-3.94; P < 0.001), and time-dependent BMI (per unit: HR, 1.08; 95% CI, 1.05-1.10; P < 0.001). Allograft steatosis was not associated with post-LT survival (P = 0.25) nor cardiovascular events (HR, 1.08; 95% CI, 0.73-1.59; P = 0.70). Underlying NASH associated with cardiovascular events (HR, 2.04; 95% CI, 1.37-3.04; P < 0.001). CONCLUSIONS Allograft steatosis is common but not associated with survival or cardiovascular events in this study. Larger prospective studies are needed to better define the natural history of allograft steatosis.
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Germani G, Laryea M, Rubbia-Brandt L, Egawa H, Burra P, OʼGrady J, Watt KD. Management of Recurrent and De Novo NAFLD/NASH After Liver Transplantation. Transplantation 2019; 103:57-67. [PMID: 30335694 DOI: 10.1097/tp.0000000000002485] [Citation(s) in RCA: 43] [Impact Index Per Article: 7.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Nonalcoholic steatohepatitis (NASH) is a growing indication for liver transplant whether the primary or secondary cause of liver disease, and it is expected to be the leading indication in the years to come. Nonalcoholic steatohepatitis recurs after transplant but the impact of the recurrence on allograft and patient outcomes is unclear. A group of multidisciplinary transplant practice providers convened at the International Liver Transplantation Society NASH consensus conference with the purpose of determining the current knowledge and future directions for understanding the recurrence rates, risk and management of NASH in the transplant allograft. Specific questions relating to posttransplant NASH were proposed and reviewed in detail with recommendations on future actions to fill the knowledge gaps.
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Affiliation(s)
- Giacomo Germani
- Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, Padua University Hospital, Padua, Italy
| | - Marie Laryea
- University of Rochester Medical Center, Rochester NY
| | | | - Hiroto Egawa
- Department of Surgery, Institute of Gastroenterology, Tokyo Women's Medical University, Tokyo, Japan
| | - Patrizia Burra
- Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, Padua University Hospital, Padua, Italy
| | - John OʼGrady
- Institute of Liver Studies, King's College Hospital, London, United Kingdom
| | - Kymberly D Watt
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN
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Abstract
PURPOSE OF REVIEW Nonalcoholic fatty liver disease (NAFLD) is a growing cause of chronic liver disease globally and nonalcoholic steatohepatitis is projected to become the most common indication for liver transplantation. The purpose of this review is to highlight key issues surrounding NAFLD as an indication for liver transplantation, including its increasing prevalence, outcomes related to liver transplantation, development of post liver transplant NAFLD and NAFLD in the liver donor pool. RECENT FINDINGS With the advent of direct-acting antiviral therapies, the proportion of patients on the liver transplant list or undergoing liver transplant for chronic hepatitis C infection is steadily decreasing. In contrast, the number transplants performed for NAFLD is increasing. By 2030, it is estimated that the incidence of decompensated cirrhosis and hepatocellular carcinoma will increase by 168 and 137%, respectively, and the number of deaths will increase by 178%. SUMMARY Liver transplantation cures cirrhosis but does not treat the underlying metabolic disease associated with NAFLD. Thus, strategies to control comorbidities in patients with NAFLD prior to transplant are needed to decrease waitlist mortality and the recurrence of NAFLD after liver transplant. NAFLD in the donor pool is also a growing concern. Strategies to minimize steatosis and expand the number of donors are critical to meet the growing demand for liver transplantation.
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Outcomes of Non-Alcoholic Steatohepatitis Patients After Liver Transplantation: A Systematic Review and Meta-Analysis. HEPATITIS MONTHLY 2019. [DOI: 10.5812/hepatmon.82336] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/13/2023]
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The Changing Face of Liver Transplantation in the United States: The Effect of HCV Antiviral Eras on Transplantation Trends and Outcomes. Transplant Direct 2019; 5:e427. [PMID: 30882032 PMCID: PMC6411219 DOI: 10.1097/txd.0000000000000866] [Citation(s) in RCA: 20] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/02/2019] [Accepted: 01/04/2019] [Indexed: 02/07/2023] Open
Abstract
Background Hepatitis C virus (HCV) cirrhosis is the leading indication for liver transplantation in the United States, although nonalcoholic steatohepatitis (NASH) is on the rise. Increasingly effective HCV antivirals are available, but their association with diagnosis-specific liver transplantation rates and early graft survival is not known. Methods The Scientific Registry of Transplant Recipients database records were retrospectively stratified by HCV antiviral era: interferon (2003-2010), protease inhibitors (2011-2013), and direct-acting antivirals (2014 to present). Kaplan-Meier, χ2, and multivariable Cox proportional hazards regression models evaluated the effects of antiviral era and etiology of liver disease on transplantation rates and graft survival over 3 years. Results Liver transplants for HCV decreased (35.3% to 23.6%), whereas those for NASH and alcoholic liver disease increased (5.8% to 16.5% and 15.6% to 24.0%) with each advancing era (all P < 0.05). Early graft survival improved with each advancing era for HCV but not for hepatitis B virus, NASH, or alcoholic liver disease (multivariable model era by diagnosis interaction P < 0.001). Era-specific multivariable models demonstrated that the risk of early graft loss for NASH was 22% lower than for HCV in the interferon era (hazard ratio, 0.78; 95% confidence interval, 0.64-0.96; P = 0.02) but risks associated with these diagnoses did not differ significantly in the protease inhibitor (P = 0.06) or direct-acting antiviral eras (P = 0.08). Conclusions Increasing effectiveness of HCV antivirals corresponds with decreased rates of liver transplantation for HCV and improved early graft survival. As the rates of liver transplant for NASH continue to increase, focus will be needed on the prevention and effective therapies for this disease.
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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] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [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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