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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 2025; 109:832-843. [PMID: 39658843 DOI: 10.1097/tp.0000000000005276] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 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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Vogel AS, Roediger R, von Ahrens D, Fortune BE, Schwartz JM, Frager S, Chacko KR, Tow CY. The Impact of Metabolic Health and Obesity on Liver Transplant Candidates and Recipients. Life (Basel) 2024; 14:685. [PMID: 38929668 PMCID: PMC11204519 DOI: 10.3390/life14060685] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2024] [Revised: 04/12/2024] [Accepted: 05/21/2024] [Indexed: 06/28/2024] Open
Abstract
Poor metabolic health and obesity have significant impacts on the outcomes of patients suffering from chronic liver disease, particularly those with metabolic dysfunction-associated steatotic liver disease. Patients with such comorbidities who require liver transplant evaluation for advancing liver disease or liver failure require special consideration due to increased risk of cardiovascular disease, renal dysfunction, sarcopenic obesity, and cancer. Those who have had a history of prior bariatric surgery pose specific anatomical constraints and may also be at increased risk of alcohol use disorder. Pre-operative risk assessment as well as strict control of metabolic risk factors are essential to reduce intra-operative and post-liver transplant complications. As immunosuppressive therapy exacerbates metabolic dysfunction and risk for cancer, post-liver transplant care must focus on balancing the need to prevent rejection and the impact of progressive metabolic dysfunction in this unique, but growing, patient population.
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Affiliation(s)
| | | | | | | | | | | | | | - Clara Y. Tow
- Correspondence: ; Tel.: +1-888-795-4837; Fax: +1-602-563-8224
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3
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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: 13] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [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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Karnam RS, Azhie A, Yang C, Rogalsky A, Chen S, Xu W, Patel K, Selzner N, Lilly L, Cattral M, Bhat M. Impact of living donor liver transplantation on long-term cardiometabolic and graft outcomes in cirrhosis due to nonalcoholic steatohepatitis. Clin Transplant 2023; 37:e15008. [PMID: 37143204 DOI: 10.1111/ctr.15008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2022] [Revised: 11/04/2022] [Accepted: 04/09/2023] [Indexed: 05/06/2023]
Abstract
BACKGROUND AND AIM Non-alcoholic steatohepatitis (NASH) is a leading indication for liver transplantation (LT). This study aimed to determine whether living donor LT (LDLT) recipients experienced less recurrent NASH, cirrhosis, and cardiometabolic complications compared to deceased donor LT (DDLT). METHOD Patients with LDLT and DDLT for NASH between February 2002 and May 2018 at University Health Network (UHN) were compared. Cox Proportional Hazard model was used to analyze overall survival (OS), Fine and Gray's Competing Risk models were conducted to analyze cumulative incidence of post LT outcomes. RESULTS One hundred and ninety-nine DDLTs and 66 LDLTs were performed for NASH cirrhosis. Time and rate of recurrence of NAFLD and NASH were comparable in both groups. Graft cirrhosis was more common in DDLT recipients (n = 14) versus LDLT (n = 0) (p < .0001). Significant fibrosis (Fibrosis ≥ F2) developed in 50 recipients (12 LDLT and 38 DDLT) post LT (DDLT vs. LDLT: HR = 1.00, 95% CI = (.52-1.93), p = .91) and there was no difference in time to significant fibrosis (p = .57). There was no difference in development of post-transplant diabetes, dyslipidemia, metabolic syndrome, cardiovascular disease, and cancers. LDLT group had better renal function at 10 years (MDRD eGFR of 57.0 mL/min vs. 48.5 mL/min, p = .047). Both groups had a comparable OS (HR = 1.83 (95% CI = .92-3.62), p = .08). CONCLUSION Overall, LDLT recipients had significantly better renal function by virtue of having early transplantation in their disease course. LDLT was also associated with significantly less graft cirrhosis, although OS and cardiometabolic outcomes were comparable between LDLT and DDLT.
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Affiliation(s)
- Ravikiran S Karnam
- Ajmera Transplant Program, University Health Network, Toronto, Ontario, Canada
- Narayana Health, Bengaluru, India
| | - Amirhossein Azhie
- Ajmera Transplant Program, University Health Network, Toronto, Ontario, Canada
| | - Cathy Yang
- Ajmera Transplant Program, University Health Network, Toronto, Ontario, Canada
| | - Andrew Rogalsky
- Ajmera Transplant Program, University Health Network, Toronto, Ontario, Canada
| | - Shiyi Chen
- Department of Biostatistics, Princess Margaret Cancer Center, University Health Network, Toronto, Ontario, Canada
- Division of Biostatistics, Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada
| | - Wei Xu
- Department of Biostatistics, Princess Margaret Cancer Center, University Health Network, Toronto, Ontario, Canada
- Division of Biostatistics, Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada
| | - Keyur Patel
- Ajmera Transplant Program, University Health Network, Toronto, Ontario, Canada
- Division of Gastroenterology and Hepatology, Department of Medicine, University of Toronto, Toronto, Canada
| | - Nazia Selzner
- Ajmera Transplant Program, University Health Network, Toronto, Ontario, Canada
- Division of Gastroenterology and Hepatology, Department of Medicine, University of Toronto, Toronto, Canada
| | - Leslie Lilly
- Ajmera Transplant Program, University Health Network, Toronto, Ontario, Canada
- Division of Gastroenterology and Hepatology, Department of Medicine, University of Toronto, Toronto, Canada
| | - Mark Cattral
- Ajmera Transplant Program, University Health Network, Toronto, Ontario, Canada
- Department of Surgery, University of Toronto, Toronto, Canada
| | - Mamatha Bhat
- Ajmera Transplant Program, University Health Network, Toronto, Ontario, Canada
- Division of Gastroenterology and Hepatology, Department of Medicine, University of Toronto, Toronto, Canada
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5
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Nonalcoholic Steatohepatitis: A Rapidly Increasing Indication for Liver Transplantation in India. J Clin Exp Hepatol 2022; 12:908-916. [PMID: 35677507 PMCID: PMC9168702 DOI: 10.1016/j.jceh.2021.09.017] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/07/2021] [Accepted: 09/17/2021] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND AND AIMS Recently, there has been a considerable increase in patients with nonalcoholic fatty liver disease. Availability of high-efficacy drugs for hepatitis B and hepatitis C virus (HCV) infection may have changed the disease prevalence. We aimed to study the impact of this changing epidemiology in patients undergoing liver transplantation (LT) over a 10-year period. METHODS The study population was stratified into Period 1 (2009-2014) and Period 2 (2015-2019). Demographics, indications for LT and changes in the epidemiology between two periods were analysed. Aetiology-based posttransplant survival analysis was carried out. RESULTS Indication for LT among 1017 adult patients (277 in Period 1 and 740 in Period 2) showed a significant increase in nonalcoholic steatohepatitis (NASH; 85 [30.7%] and 311 [42%]; P = 0.001), decrease in hepatitis C (49 [17.7%] and 75 [10.1%]; P = 0.002), and increase in hepatocellular carcinoma from Period 1 to Period 2 (13 [26.5%] to 38 [50.7%]; P = 0.009) among HCV patients. Patients transplanted for NASH had a lower 5-year survival compared with viral hepatitis (75.9% vs 87.4%; P = 0.03). There was a strong association between coronary artery disease and NASH (hazard ratio = 1.963, 95% confidence interval, 1.19-3.22). CONCLUSION NASH is the leading indication for liver transplantation in India, surpassing viral hepatitis in recent years.
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Key Words
- ASH, Non-alcoholic steatohepatitis
- CAD, Coronary artery disease
- CLD, Chronic liver disease
- DAA, Direct acting antiviral drugs
- DM, Diabetes mellitus
- HBV, Hepatitis B virus infection
- HCC, Hepatocellular carcinoma
- HCV, Hepatitis C virus infection
- LT, Liver transplantation
- NAFLD, Non-alcoholic fatty liver disease
- SVR, Sustained virological response
- cardiovascular disease
- hepatocellular carcinoma
- liver transplantation
- nonalcoholic steatohepatitis
- viral hepatitis
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6
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Eguchi Y, Wong G, Lee IH, Akhtar O, Lopes R, Sumida Y. Hepatocellular carcinoma and other complications of non-alcoholic fatty liver disease and non-alcoholic steatohepatitis in Japan: A structured review of published works. Hepatol Res 2021; 51:19-30. [PMID: 33091191 DOI: 10.1111/hepr.13583] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/02/2020] [Revised: 08/27/2020] [Accepted: 09/08/2020] [Indexed: 02/08/2023]
Abstract
AIMS Hepatocellular carcinoma (HCC) is a significant cause of morbidity and mortality in Japan. As the treatment of viral hepatitis improves, non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) are rapidly becoming leading causes of HCC in Japan. This structured review aims to characterize the morbidity and mortality of HCC and other malignant and non-malignant complications among Japanese NAFLD and NASH patients. METHODS An English and Japanese structured search of published works was undertaken in PubMed, Embase, and Ichushi Web databases, identifying 6553 studies, 34 of which met predefined inclusion criteria. RESULTS Hepatocellular carcinoma was the most common incident malignancy among NAFLD/NASH patients, with higher incidence in patients with advanced/severe fibrosis (F3/F4) of 10.5%-20.0%. Although NASH results in a lower HCC cumulative incidence than hepatitis C virus (HCV) (11.3% vs. 30.5%), they have similar impacts on health outcomes, including overall mortality. Among Japanese NASH patients, HCC was found to be the main driver of mortality (40.0% in 2.7 years in NASH-HCC). With longer follow-up, higher mortality rates are observed in F3/4 patients: 25.0% in NASH F3/F4 versus 0.0% in NASH F0/2 over 7.7 years. The NASH-HCC patients also have a higher post-operative mortality than HCV-HCC patients. Additionally, NAFLD/NASH patients had higher rates of cardiovascular disease than non-NAFLD/NASH controls, and slightly higher rates of gastric cancer than HCV patients. CONCLUSION Hepatocellular carcinoma is the most common malignancy and cause of death among NAFLD/NASH patients in Japan, with higher mortality observed among those with advanced disease and complications. Early identification and effective treatments are needed.
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Affiliation(s)
- Yuichiro Eguchi
- Liver Center, Saga University Hospital, Saga, Japan.,Department of Internal Medicine, Saga University, Japan
| | | | - I-Heng Lee
- Gilead Sciences Inc, Foster City, CA, USA
| | | | | | - Yoshio Sumida
- Division of Hepatology and Pancreatology, Department of Internal Medicine, Aichi Medical University, Japan
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7
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Batisti J, Mehal WZ. Nonalcoholic Fatty Liver Disease in the Post Liver Transplant Patient. CURRENT TRANSPLANTATION REPORTS 2020. [DOI: 10.1007/s40472-020-00303-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/23/2022]
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8
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Samji NS, Verma R, Keri KC, Singal AK, Ahmed A, Rinella M, Bernstein D, Abdelmalek MF, Satapathy SK. Liver Transplantation for Nonalcoholic Steatohepatitis: Pathophysiology of Recurrence and Clinical Challenges. Dig Dis Sci 2019; 64:3413-3430. [PMID: 31312990 DOI: 10.1007/s10620-019-05716-1] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/06/2019] [Accepted: 07/02/2019] [Indexed: 02/08/2023]
Abstract
Nonalcoholic steatohepatitis is the fastest-growing indication for the liver transplant and a leading cause of hepatocellular carcinoma among patients listed for liver transplantation in the USA. Post-transplant nonalcoholic hepatic steatosis and steatohepatitis are frequent complications of liver transplantation. Nonalcoholic steatohepatitis poses a significant challenge in both pre- and post-transplant period due to its association with metabolic syndrome, coronary artery disease, chronic kidney disease, and obstructive sleep apnea. While optimal therapy is not yet available in the post-liver transplant setting, lifestyle interventions continue to remain as the mainstay of therapy for post-transplant nonalcoholic steatohepatitis. Early recognition with protocol biopsies and noninvasive modalities, along with modification of known risk factors, are the most effective methods to curtail the progression of nonalcoholic steatohepatitis in the absence of FDA-approved pharmacologic therapy.
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Affiliation(s)
- Naga Swetha Samji
- Tennova Cleveland Hospital, 2305 Chambliss Ave NW, Cleveland, TN, 37311, USA
| | - Rajanshu Verma
- Division of Transplant Surgery, Department of Surgery, Methodist University Hospital Transplant Institute, University of Tennessee Health Sciences Center, Memphis, TN, USA
| | | | - Ashwani K Singal
- University of South Dakota Sanford School of Medicine, Avera Transplant Institute, S. Cliff Ave, Sioux Falls, SD, 57105, USA
| | - Aijaz Ahmed
- Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, CA, USA
| | - Mary Rinella
- Department of Medicine, Northwestern University, Feinberg School of Medicine, Chicago, IL, USA
| | - David Bernstein
- Division of Hepatology and Sandra Atlas Bass Center for Liver Diseases, Northwell Health, Manhasset, NY, USA
| | - Manal F Abdelmalek
- Division of Gastroenterology/Hepatology, Duke University, 40 Duke Medicine Cir, Durham, NC, USA
| | - Sanjaya K Satapathy
- Division of Hepatology at Sandra Atlas Bass Center for Liver Diseases and Transplantation, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell Health, 400 Community Drive, Manhasset, NY, 11030, USA.
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9
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Vinaixa C, Selzner N, Berenguer M. Fat and liver transplantation: clinical implications. Transpl Int 2018; 31:828-837. [DOI: 10.1111/tri.13288] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/20/2018] [Revised: 03/14/2018] [Accepted: 06/01/2018] [Indexed: 02/06/2023]
Affiliation(s)
- Carmen Vinaixa
- Hepatology and Liver Transplantation Unit; Hospital Universitario y Politécnico La Fe; Valencia Spain
| | - Nazia Selzner
- Multi Organ Transplant Program; Liver Transplant Unit; University Health Network; University of Toronto; Toronto ON Canada
| | - Marina Berenguer
- Hepatology and Liver Transplantation Unit; Hospital Universitario y Politécnico La Fe; Valencia Spain
- CIBERehd; Instituto Carlos III; Madrid Spain
- Faculty of Medicine; University of Valencia; Valencia Spain
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10
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Andrade ARCFD, Cotrim HP, Bittencourt PL, Almeida CG, Sorte NCAB. Nonalcoholic steatohepatitis in posttransplantation liver: Review article. ACTA ACUST UNITED AC 2018; 64:187-194. [PMID: 29641680 DOI: 10.1590/1806-9282.64.02.187] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2017] [Accepted: 06/26/2017] [Indexed: 12/17/2022]
Abstract
INTRODUCTION Nonalcoholic steatohepatitis (NASH) associated or not with cirrhosis is the third leading indication for liver transplantation (LT) around the world. After transplants, NASH has a high prevalence and occurs as both recurrent and de novo manifestations. De novo NASH can also occur in allografts of patients transplanted for non-NASH liver disease. OBJECTIVE To evaluate recurrent or de novo NASH in post-LT patients. METHOD A literature review was performed using search engines of indexed scientific material, including Medline (by PubMed), Scielo and Lilacs, to identify articles published in Portuguese and English until August 2016. Eligible studies included: place and year of publication, prevalence, clinical characteristics, risk factors and survival. RESULTS A total of 110 articles were identified and 63 were selected. Most of the studies evaluated recurrence and survival after LT. Survival reached 90-100% in 1 year and 52-100% in 5 years. Recurrence of NAFLD (steatosis) was described in 15-100% and NASH, in 4-71%. NAFLD and de novo NASH were observed in 18-67% and 3-17%, respectively. Metabolic syndrome, diabetes mellitus, dyslipidemia and hypertension were seen in 45-58%, 18-59%, 25-66% and 52-82%, respectively. CONCLUSION After liver transplants, patients present a high prevalence of recurrent and de novo NASH. They also show a high frequence of metabolic disorders. Nevertheless, these alterations seem not to influence patient survival.
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Affiliation(s)
| | - Helma P Cotrim
- Medicine and Health Graduate Program, Faculdade de Medicina da Bahia, Universidade Federal da Bahia, Salvador, BA, Brazil
| | | | - Carolina G Almeida
- Medicine and Health Graduate Program, Faculdade de Medicina da Bahia, Universidade Federal da Bahia, Salvador, BA, Brazil
| | - Ney Christian Amaral Boa Sorte
- Medicine and Health Graduate Program, Faculdade de Medicina da Bahia, Universidade Federal da Bahia, Salvador, BA, Brazil
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11
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Losurdo G, Castellaneta A, Rendina M, Carparelli S, Leandro G, Di Leo A. Systematic review with meta-analysis: de novo non-alcoholic fatty liver disease in liver-transplanted patients. Aliment Pharmacol Ther 2018; 47:704-714. [PMID: 29359341 DOI: 10.1111/apt.14521] [Citation(s) in RCA: 43] [Impact Index Per Article: 6.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/29/2017] [Revised: 08/26/2017] [Accepted: 12/25/2017] [Indexed: 02/06/2023]
Abstract
BACKGROUND De novo non-alcoholic fatty liver disease (NAFLD) in liver-transplanted patients for cirrhosis not due to non-alcoholic steatohepatitis (NASH) is becoming a growing phenomenon. AIMS We performed a systematic review and evaluated the prevalence of this event and possible associated factors. METHODS A literature search in medical databases (PubMed, MEDLINE/OVIDSP, Science Direct and EMBASE) was performed in March 2017. Relevant publications were identified in most important databases. We estimated the pooled prevalence of NAFLD and NASH in patients with liver transplant. The data have been expressed as proportions/percentages, and 95% confidence intervals (CI) were calculated, using the inverse variance method. Odd ratios (OR) and 95% confidence intervals (95% CI) were estimated. RESULTS Twelve studies were selected, enrolling 2166 subjects overall undergoing post-liver transplant biopsy. The pooled weighted prevalence of de novo NAFLD was 26% (95% CI 20%-31%). The pooled weighted prevalence of NASH was 2% (95% CI 0%-3%). The highest prevalences of de novo NAFLD were found for patients transplanted for alcoholic cirrhosis (37%) and cryptogenic cirrhosis (35%) and for patients taking tacrolimus (26%). Tacrolimus showed a risk of NAFLD similar to ciclosporin (OR = 1.02, 95% CI 0.3-3.51). CONCLUSIONS Patients undergoing liver transplant are more prone to experience diabetes, hypertension or dyslipidaemia, and NAFLD may be an important element in this context. In this study, we show how the prevalence of NASH tends to remain significant and similar to the general population. Moreover, this study suggests a possible association with specific transplant indications. Further studies are required to confirm these findings.
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Affiliation(s)
- G Losurdo
- Gastroenterology Unit, Department of Emergency and Organ Transplantation, University of Bari, Bari, Italy
| | - A Castellaneta
- Gastroenterology Unit, Department of Emergency and Organ Transplantation, University of Bari, Bari, Italy
| | - M Rendina
- Gastroenterology Unit, Department of Emergency and Organ Transplantation, University of Bari, Bari, Italy
| | - S Carparelli
- Gastroenterology Unit, Department of Emergency and Organ Transplantation, University of Bari, Bari, Italy
| | - G Leandro
- Gastroenterology Unit, IRCCS "Saverio De Bellis", Castellana Grotte, BA, Italy
| | - A Di Leo
- Gastroenterology Unit, Department of Emergency and Organ Transplantation, University of Bari, Bari, Italy
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12
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Early Intervention With Live Donor Liver Transplantation Reduces Resource Utilization in NASH: The Toronto Experience. Transplant Direct 2017; 3:e158. [PMID: 28620642 PMCID: PMC5464777 DOI: 10.1097/txd.0000000000000674] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2017] [Accepted: 02/14/2017] [Indexed: 12/29/2022] Open
Abstract
Background In parallel with the obesity epidemic, liver transplantation for nonalcoholic steatohepatitis (NASH) is increasing dramatically in North America. Although survival outcomes are similar to other etiologies, liver transplantation in the NASH population has been associated with significantly increased resource utilization. We sought to compare outcomes between live donor liver transplantation (LDLT) and deceased donor liver transplantation (DDLT) at a high volume North American transplant center, with a particular focus on resource utilization. Methods The study population consists of primary liver transplants performed for NASH at Toronto General Hospital from 2000 to 2014. Recipient characteristics, perioperative outcomes, graft and patient survivals, and resource utilization were compared for LDLT versus DDLT. Results A total of 176 patients were included in the study (48 LDLT vs 128 DDLT). LDLT recipients had a lower model for end-stage liver disease score and were less frequently hospitalized prior to transplant. Estimated blood loss and early markers of graft injury were lower for LDLT. LDLT recipients had a significantly shorter hospitalization (intensive care unit, postoperative, and total hospitalization). Conclusions LDLT for NASH facilitates transplantation of patients at a less severe stage of disease, which appears to promote a faster postoperative recovery with less resource utilization.
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13
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Kappus M, Abdelmalek M. De Novo and Recurrence of Nonalcoholic Steatohepatitis After Liver Transplantation. Clin Liver Dis 2017; 21:321-335. [PMID: 28364816 DOI: 10.1016/j.cld.2016.12.006] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in developing countries. Approximately 25% of patients with NAFLD develop nonalcoholic steatohepatitis (NASH). NASH-related cirrhosis is now a leading listing indication for liver transplantation in the United States. Although posttransplant survival for NASH-related cirrhosis is comparable with that of other liver diseases, many patients have features of metabolic syndrome, which can contribute to a recurrence of NAFLD or NASH. This article reviews the epidemiology, pathophysiology, and treatment of de novo and recurrence of NASH after liver transplantation.
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Affiliation(s)
- Matthew Kappus
- Division of Gastroenterology, Duke University Medical Center, 40 Duke Medicine Circle, PO Box 3913, Durham, NC 27710, USA
| | - Manal Abdelmalek
- Division of Gastroenterology, Duke University Medical Center, 40 Duke Medicine Circle, PO Box 3913, Durham, NC 27710, USA.
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14
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Nonalcoholic fatty liver: optimizing pretransplant selection and posttransplant care to maximize survival. Curr Opin Organ Transplant 2016; 21:99-106. [PMID: 26825357 DOI: 10.1097/mot.0000000000000283] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
PURPOSE OF REVIEW Nonalcoholic steatohepatitis (NASH) is projected to become the most common indication for liver transplantation in the near future. NASH recipients have concurrent obesity, metabolic, and cardiovascular risks, which directly impact patient selection, posttransplant morbidity and potentially long-term outcomes. The purpose of this review is to highlight strategies to optimize pretransplant selection, outcomes, and posttransplant risk modification to optimize patient and graft survival. RECENT FINDINGS NASH recipients are at risk for pretransplant cardiovascular disease, diabetes mellitus, and related renovascular complications. Stringent selection criteria identify those patients most likely to benefit from liver transplantation without adverse cardiovascular events yet, the incidence of these events remains high in NASH recipients. High BMI imparts postoperative morbidity because of infections, wound complications, and longer lengths of hospital stay. Aggressive management of modifiable risk factors such as obesity, hyperlipidemia, diabetes mellitus, and hypertension is recommended. SUMMARY Although patient and graft survival in NASH recipients is excellent, long-term reduction in healthcare utilization and outcomes in these patients would benefit from risk factor modification. Periodic reassessment of coronary artery disease and early consideration of bariatric surgery is recommended in this population.
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15
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Khan RS, Newsome PN. Non-alcoholic fatty liver disease and liver transplantation. Metabolism 2016; 65:1208-23. [PMID: 26997540 DOI: 10.1016/j.metabol.2016.02.013] [Citation(s) in RCA: 38] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/30/2015] [Revised: 02/01/2016] [Accepted: 02/23/2016] [Indexed: 02/07/2023]
Abstract
Cirrhosis secondary to non-alcoholic steatohepatitis (NASH) is a common indication for liver transplant. In comparison to other cirrhotic patients, patients with NASH cirrhosis are more likely to be older and have the metabolic syndrome. Pre-transplant, patients require careful evaluation of cardiovascular risk. As the incidence of non-alcoholic fatty liver disease (NAFLD) is rising, a greater proportion of donor grafts have steatosis greater than 30%, which is associated with poor outcomes. Grafts with steatosis greater than 60% are unsuitable for transplant. Overall, post-transplant survival outcomes for patients with NASH cirrhosis are similar to those with cirrhosis without NASH. However, NASH cirrhosis is associated with a higher 30-day mortality, predominantly from an increase in cardiovascular events and infections. Following liver transplant, there is a significant risk of NASH recurrence, although this seldom results in allograft loss. Furthermore, a significant number of patients who had a liver transplant for other reasons develop NASH de novo. When patients with NASH cirrhosis are considered for transplant, one of the major challenges lies in identifying which patients are too high risk for surgery. This review aims to provide information to aid this decision making process, and to provide guidance on the peri-operative care strategies that can modify risk.
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Affiliation(s)
- Reenam S Khan
- Gastroenterology and Hepatology, NIHR Birmingham Liver BRU and Centre for Liver Research, University of Birmingham, Birmingham, UK, B15 2TH.
| | - Philip N Newsome
- Hepatology, NIHR Birmingham Liver BRU and Centre for Liver Research, University of Birmingham, Birmingham, UK, B15 2TH.
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Reichman TW, Therapondos G, Serrano MS, Seal J, Evers-Meltzer R, Bohorquez H, Cohen A, Carmody I, Ahmed E, Bruce D, Loss GE. “Weighing the risk”: Obesity and outcomes following liver transplantation. World J Hepatol 2015; 7:1484-1493. [PMID: 26085908 PMCID: PMC4462687 DOI: 10.4254/wjh.v7.i11.1484] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/29/2014] [Revised: 02/23/2015] [Accepted: 04/14/2015] [Indexed: 02/06/2023] Open
Abstract
Obesity is on the rise worldwide. As a result, unprecedented rates of patients are presenting with end stage liver disease in the setting of non-alcoholic fatty liver disease (NAFLD) and are requiring liver transplantation. There are significant concerns that the risk factors associated with obesity and the metabolic syndrome might have a detrimental effect on the long term outcomes following liver transplantation. In general, short term patient and graft outcomes for both obese and morbidly obese patients are comparable with that of non-obese patients, however, several studies report an increase in peri-operative morbidity and increased length of stay. Continued studies documenting the long-term outcomes from liver transplantation are needed to further examine the risk of recurrent disease (NAFLD) and also further define the role risk factors such cardiovascular disease might play long term. Effective weight reduction in the post liver transplant setting may mitigate the risks associated with the metabolic syndrome long-term.
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Khullar V, Dolganiuc A, Firpi RJ. Pre-and-post transplant considerations in patients with nonalcoholic fatty liver disease. World J Transplant 2014; 4:81-92. [PMID: 25032097 PMCID: PMC4094954 DOI: 10.5500/wjt.v4.i2.81] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/27/2013] [Revised: 02/17/2014] [Accepted: 03/12/2014] [Indexed: 02/05/2023] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) is currently the third most common indication for liver transplantation in the United States. With the growing incidence of obesity, NAFLD is expected to become the most common indication for liver transplantation over the next few decades. As the number of patients who have undergone transplantation for NAFLD increases, unique challenges have emerged in the management and long-term outcomes in patients. Risk factors such as obesity, hypertension, diabetes, and hyperlipidemia continue to play an important role in the pathogenesis of the disease and its recurrence. Patients who undergo liver transplantation for NAFLD have similar long-term survival as patients who undergo liver transplantation for other indications. Research shows that post-transplantation recurrence of NAFLD is commonplace with some patients progressing to recurrent non-alcoholic steatohepatitis and cirrhosis. While treatment of comorbidities is important, there is no consensus on the management of modifiable risk factors or the role of pharmacotherapy and immunosuppression in patients who develop recurrent or de novo NAFLD post-transplant. This review provides an outline of NAFLD as indication for liver transplantation with a focus on the epidemiology, pathophysiology and risk factors associated with this disease. It also provides a brief review on the pre-transplant considerations and post-transplant factors including patient characteristics, role of obesity and metabolic syndrome, recurrence and de novo NAFLD, outcomes post-liver transplantation, choice of medications, and options for immunosuppression.
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Said A. Non-alcoholic fatty liver disease and liver transplantation: Outcomes and advances. World J Gastroenterol 2013; 19:9146-9155. [PMID: 24409043 PMCID: PMC3882389 DOI: 10.3748/wjg.v19.i48.9146] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/01/2013] [Revised: 10/28/2013] [Accepted: 11/03/2013] [Indexed: 02/07/2023] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) is one of the most prevalent causes of chronic liver disease worldwide. In the last decade it has become the third most common indication for liver transplantation in the United States. Increasing prevalence of NAFLD in the general population also poses a risk to organ donation, as allograft steatosis can be associated with non-function of the graft. Post-transplant survival is comparable between NAFLD and non-NAFLD causes of liver disease, although long term outcomes beyond 10 year are lacking. NAFLD can recur in the allograft frequently although thus far post transplant survival has not been impacted. De novo NAFLD can also occur in the allograft of patients transplanted for non-NAFLD liver disease. Predictors for NAFLD post-transplant recurrence include obesity, hyperlipidemia and diabetes as well as steroid dose after liver transplantation. A polymorphism in PNPLA3 that mediates triglyceride hydrolysis and is linked to pre-transplant risk of obesity and NAFLD has also been linked to post transplant NAFLD risk. Although immunosuppression side effects potentiate obesity and the metabolic syndrome, studies of immunosuppression modulation and trials of specific immunosuppression regimens post-transplant are lacking in this patient population. Based on pre-transplant data, sustained weight loss through diet and exercise is the most effective therapy for NAFLD. Other agents occasionally utilized in NAFLD prior to transplantation include vitamin E and insulin-sensitizing agents. Studies of these therapies are lacking in the post-transplant population. A multimodality and multidisciplinary approach to treatment should be utilized in management of post-transplant NAFLD.
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