Along with global epidemics of obesity and type 2 diabetes mellitus (T2DM), the prevalence of non-alcoholic fatty liver disease (NAFLD) is increasing worldwide. NAFLD is becoming one of the leading causes of liver transplantation (LT) both for end-stage liver disease (ESLD) and hepatocellular carcinoma [
1,
2]. NAFLD is commonly associated with metabolic risk factors such as obesity and T2DM and poses unique challenges when considering LT. Therefore, comprehensive cardiovascular risk assessment and proper management of comorbid conditions are crucial in the LT evaluation process and post-LT management to improve outcomes. Liver transplantation can cure ESLD but not the underlying metabolic risk factors associated with NAFLD. Thus, long-term strategies to address these comorbidities are of importance in patient management. Furthermore, the use of postoperative steroids and other immunosuppressive agents frequently aggravates metabolic derangement and fosters development of obesity, insulin resistance, T2DM, hypertension, and dyslipidemia [
3].
Because of the increasing prevalence of NAFLD and its impact on LT, efforts should be made to improve liver-related outcomes and prevent the development of metabolic-related complications following LT [
4]. However, present guidelines make no specific recommendation for LT recipients with NAFLD other than correction and optimal control of individual components of metabolic syndrome and cardiovascular risk factors [
5,
6]. The European Association for the Study of the Liver (EASL) recommends that metabolic comorbidities be assessed and controlled in pre- and post-transplant settings [
5]. In the American Association for the Study of Liver Disease (AASLD) and American Society for Transplantation practice guidelines for LT, there are no NAFLD-specific directives other than that LT is an effective therapy for NAFLD cirrhosis [
7]. This comprehensive review article focuses on indications of LT for NAFLD, pre-LT risk assessment, management of patients on the waiting list, optimal management of metabolic disorder, immunosuppressive agent use, prevention of recurrent non-alcoholic steatohepatitis/NAFLD, and short- and long-term outcomes after LT [
8].
Patients with NAFLD have a higher prevalence of cardiovascular disease with an increased risk of cardiovascular mortality than the general population because of common meta bolic risk factors and shared pathogenic pathways [
9,
10]. Comprehensive cardiovascular risk assessment and testing are essential during the LT evaluation process, which warrants a multidisciplinary team approach, including cardiology, cardiac anesthesiology, and nutrition in addition to hepatology and transplant surgery, to appropriately stratify risk and optimize patient management.
Older age, higher Model for End-Stage Liver Disease score, and extreme body mass index, but not NAFLD itself, are risk factors for lower rate of survival after LT [
11]. However, NAFLD recurrence is frequent after LT because of persistence of metabolic risk factors and immunosuppressive agent use [
2]. Efforts should be made to achieve optimal control of metabolic comorbidities through a multidisciplinary team approach including nutrition, physical activity, and immunosuppressive agent modulation.
Unlike previous reviews, this study comprehensively describes research regarding association between post-LT outcomes and sarcopenia (pre-LT sarcopenia, post-LT sarcopenia, sarcopenic obesity, and changes in sarcopenic status). Sarcopenia has been increasingly reported to be associated with adverse outcome such as mortality, hospital stay, and infection after LT [
12]. Thus, nutritional status and physical activity assessment should be considered as part of the standard care. Also, specific recommendations and practical advice on diet and physical activity would be useful and relevant from a clinical point of view and have been briefly covered by another review article [
13].
This review systematically describes management and therapeutic options to improve long-term outcomes with a particular emphasis on correction and control of metabolic comorbidities. Considering the growing impact of NAFLD on all aspects of LT, this review will provide useful information to optimize patient management in LT for NAFLD.
FOOTNOTES
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Authors’ contributions
Manuscript draft: Byeong Geun Song. Critical revision of manuscript: Dong Hyun Sinn.
-
Conflicts of Interest
The authors have no conflicts to disclose.
Abbreviations
non-alcoholic fatty liver disease
American Association for the Study of Liver Disease
European Association for the Study of the Liver
REFERENCES
- 1. Younossi ZM, Stepanova M, Afendy M, Fang Y, Younossi Y, Mir H, et al. Changes in the prevalence of the most common causes of chronic liver diseases in the United States from 1988 to 2008. Clin Gastroenterol Hepatol 2011;9:524-530.e1 quiz e60.
- 2. Pais R, Barritt AS 4th, Calmus Y, Scatton O, Runge T, Lebray P, et al. NAFLD and liver transplantation: Current burden and expected challenges. J Hepatol 2016;65:1245-1257.
- 3. Gadiparthi C, Spatz M, Greenberg S, Iqbal U, Kanna S, Satapathy SK, et al. NAFLD epidemiology, emerging pharmacotherapy, liver transplantation implications and the trends in the United States. J Clin Transl Hepatol 2020;8:215-221.
- 4. Choi HJ. Current status and outcome of liver transplantation in South Korea. Clin Mol Hepatol 2022;28:117-119.
- 5. European Association for the Study of the Liver. EASL Clinical Practice Guidelines: Liver transplantation. J Hepatol 2016;64:433-485.
- 6. Newsome PN, Allison ME, Andrews PA, Auzinger G, Day CP, Ferguson JW, et al.; British Transplant Society. Guidelines for liver transplantation for patients with non-alcoholic steatohepatitis. Gut 2012;61:484-500.
- 7. Martin P, DiMartini A, Feng S, Brown R Jr, Fallon M. Evaluation for liver transplantation in adults: 2013 practice guideline by the American Association for the Study of Liver Diseases and the American Society of Transplantation. Hepatology 2014;59:1144-1165.
- 8. Battistella S, D’Arcangelo F, Grasso M, Zanetto A, Gambato M, Germani G, et al. Liver transplantation for non-alcoholic fatty liver disease: indications and post-transplant management. Clin Mol Hepatol 2023;29(Suppl):S286-S301.
- 9. Anstee QM, Targher G, Day CP. Progression of NAFLD to diabetes mellitus, cardiovascular disease or cirrhosis. Nat Rev Gastroenterol Hepatol 2013;10:330-344.
- 10. Söderberg C, Stål P, Askling J, Glaumann H, Lindberg G, Marmur J, et al. Decreased survival of subjects with elevated liver function tests during a 28-year follow-up. Hepatology 2010;51:595-602.
- 11. Wang X, Li J, Riaz DR, Shi G, Liu C, Dai Y. Outcomes of liver transplantation for nonalcoholic steatohepatitis: a systematic review and meta-analysis. Clin Gastroenterol Hepatol 2014;12:394-402 e1.
- 12. Kaido T, Ogawa K, Fujimoto Y, Ogura Y, Hata K, Ito T, et al. Impact of sarcopenia on survival in patients undergoing living donor liver transplantation. Am J Transplant 2013;13:1549-1556.
- 13. Burra P, Becchetti C, Germani G. NAFLD and liver transplantation: Disease burden, current management and future challenges. JHEP Rep 2020;2:100192.
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