Table Info

Table 1.

Evaluation of cardiovascular outcomes in transplanted patients with or without assessment of pre-LT steatosis, either receiving a graft with steatosis and/or with de novo/recurrent NAFLD post LT

Authors	Year	Type of study	Nation	Population	F-up after LT	CV endpoint	NAFLD	Results
Evaluation of CV outcomes in transplanted patients without data on pre-existing NAFLD
Alves et al. [35]	2019	Cross sectional	Brasil	79	1.4–6.3 years	cIMT	NA	Prevalence of increased cIMT 54% Independently associated with higher LDL, C-reactive protein and intake of saturated and trans fatty acids with diet
Bargehr et al. [53]	2018	Retrospective Case control	USA	717 -32 cases (AF) -63 controls	5–8 years	Intraoperative and postoperative cardiac complications (ventricular tachycardia, hemodynamic instability, cardiac arrest, death)	NA	Prevalence of intraoperative/postoperative cardiac complications in 28%/8% (cases) and 5%/2% (controls) Mortality for CV causes 9% cases, 0 controls
Josefsson et al. [44]	2014	Retrospective	UK	234	2–20 years	-CV events (arrhythmias, CAD) -Mortality from CV events	NA	Prevalence of CV events 29%, with mortality in 88% of them (26% of the cohort) Independently associated with pre-LT ECG abnormalities (prolonged QTc time, Q wave, ECG feature compatible with CAD)
Dowsley et al. [43]	2012	Retrospective	USA	107	2.6 ± 1.4 months	HF	NA	Prevalence of HF 24% Independently associated with pre-LT diastolic dysfunction
Eimer er al. [42]	2008	Prospective	USA	86	2 weeks -2 years	Systolic HF	NA	Incidence of systolic HF 7% Independently associated with age and pulmonary hypertension
Evaluation of CV outcomes in transplanted patients with data on pre-existing NAFLD but without analysis on the impact of NAFLD on CV assessment
Memaran et al. [71]	2019	Cross sectional	Germany	104 (children)	6.9 years	-Carotid-femoral pulse PWV -cIMT -LVMI	Pre-LT NASH 6%	Prevalence of alterations in PWV, cIMT, and LVMI in 21.9%, 57.0%, and 11.1%. Data separated in NASH not available PWV independently associated with diastolic BP and GFR; cIMT with age; LVMI with pre-LT BMI
Sonny et al. [47]	2018	Case control	USA	1,284 -45 cases (LVEF < 45% within 6 months from LT) -180 controls	6 months	Systolic HF (LVEF < 45%)	-Pre-LT NASH case: 22% -Controls: 23%	Prevalence of systolic HF 6%. Data separated in NASH not available Independently associated with pre-LT diastolic dysfunction
Roccaro et al. [62]	2018	Retrospective	USA	994	2-12 years	Major CV events (cardiac arrest, MI, stroke, PAD)	Pre-LT NASH 10%	Prevalence of major CV events 12%, mortality from CV events 4%. Data separated in NASH not available. Independently associated with post LT diabetes.
Perito et al. [37]	2018	Cross sectional	USA	88 (children)	11.2 ± 5.6 years	cIMT	Pre-LT NASH 17%	Increase in cIMT independently associated with glucose intolerance and diastolic hypertension.
VanWagner et al. [38]	2017	Retrospective	USA	1,024	10 years	Hospitalization or mortality from major CV events (MI, AF, HF, cardiac arrest, PE, TIA, stroke)	Pre-LT NASH 16%	Prevalence of hospitalization 32% and death from CV events 32% and 5%. Data separated in NASH not available. Independently associated with T2DM, hypertension, pre existing AF and HF, age > 65 years
VanWagner et al. [32]	2016	Retrospective	USA	32,810	90 days	Major CV events (MI, AF, PE, HF, cardiac arrest, stroke)	Pre-LT NASH 9.7%	Prevalence of major CV events 3%. Data separated in NASH not available Independently associate with NASH, age > 65 years, baseline AF and stroke
Fussner et al. [39]	2015	Retrospective	USA	455	8–12 years	CVD (CAD, arrythmias, congestive HF, symptomatic PAD)	Pre-LT NASH 10%	Prevalence of CVD 30%. Data separated in NASH not available Independently associated with age, diabetes, prior history of CVD and pre-LT serum troponin
VanWagner et al. [9]	2014	Retrospective	USA	54,697	30 days	Mortality from CV events	Pre-LT NASH 5%	Prevalence of death from CV events 1.1%. Data separated in NASH not available Independently associated with age, intensive care unit status, ventilator status, MELD, portal vein thrombosis, donor BMI, and cold ischemia time
Qureshi et al. [45]	2013	Prospective	USA	970	5.3 ± 3.4 years	HF	Pre-LT NASH 4.5%	Incidence of HF 10%. Data separated in NASH not available Independently associated with pre-LT grade 3 diastolic dysfunction, diabetes, hypertension, BNP, pulmonary hypertension, QT > 450
Watt et al. [5]	2010	Retrospective	USA	798	12.5 (9–13) years	Mortality from all causes and CV causes	Pre-LT NASH 29%	Prevalence of death 41%, from CV events 5%. Data separated in NASH not available CV mortality independently associated with age, criptogenetic cirrhosis and ALD
Evaluation of CV outcomes in transplanted patients with pre-existing NAFLD and with analysis on the impact of NAFLD on CV assessment
Kwong et al. [29]	2020	Retrospective	USA	1,023	1–3 years	-Survival -CV events (AF, MI, HF, stroke)	Pre-LT NASH in 21%	No difference in survival at 1 and 3 year among NASH (91.3% and 83.3%) compared to non-NASH (90% and 81%) No difference in incidence of CV events between NASH and non-NASH patients
Nagai et al. [95]	2019	Retrospective	USA	32,660 (6,344 NASH) (17,037 HCV) (9,279 ALD)	1–2 years	All cause and CV mortality	Pre-LT NASH 19%	Overall mortality 22% Significantly higher mortality in NASH compared to HCV or ALD, adjusted for HCC presence (especially in age 50–59 years) Mortality from CV disease highest among patients with NASH (11.5%), compared to 7.0% in HCV and 9.6% in ALD
D’Avola et al. [98]	2017	Prospective	Spain	1,819	5 years	All cause and CV mortality	-Cryptogenetic cirrhosis 2.9%. -Data on NASH NA	Overall mortality 22%, 12% from CV causes ALD was an independent predictors of CV events, HCV of mortality
Piazza et al. [104]	2016	Retrospective	Italy	143 (65 ALD) (78 NASH)	3 years	-All-cause mortality -CV events (sudden cardiac death, CAD, congestive HF, AF or arrhythmia, valvular heart disease, PAD, or stroke)	Pre-LT NASH 54%	No difference in prevalence of CV events at 3 years in patients with ALD (14.1%) and NASH (13.8%) No difference in survival between NASH and ALD patients (87.2% vs. 86.4%)
VanWagner et al. [8]	2012	Retrospective	USA	242 (115 NASH) (127 ALD)	5 years	-Survival -CV events (death from any cardiac cause, MI, acute HF, arrhythmia, stroke)	Pre-LT NASH in 47%	Increased CV events in NASH vs. ALD patients (26% vs. 8%) independently of confounding factors No difference in survival between two groups. The 1-, 3-, and 5- year patient survival were 81.3%, 73.3%, and 60.3% in the NASH group and 88.1%, 85.3%, and 68.8% in the ALD group
Contos et al. [83]	2001	Prospective	USA	58 (30 NASH) (16 ALD) (12 PBC)	30 days	Survival	Pre-LT NASH 51%	Overall survival 96% No difference in survival among groups
Evaluation of CV outcomes in transplanted patients receiving liver graft with NAFLD
Kulik et al. [79]	2017	Retrospective	Germany	1,205 [77 requiring re-LT, 39 due to primary non function (PNF) and 38 to vascular and biliary disease]	3 months-11 years	-In-hospital mortality in patients with re-LT -Survival in patients with re-LT	NAFLD in 69% of graft of with PNF	Overall survival 0.5 years in PNF and 5.3 years in patients with vascular and biliary disease In-hospital mortality was 53.8% vs. 26.4% PNF due to fatty liver allograft was the only independent factor associated with poor outcome.
Andert et al. [80]	2017	Retrospective	Germany	94	30 days-1 years	All cause mortality	Donor graft hepatic steatosis: < 30% (n = 27), 30%–60%(n = 41) > 60% (n = 26)	The 30-day survival rates were 100% in all groups. The 1-year patient survival rates were 94.4% in the group with steatosis < 30%, 87.9% 30%–60% and 90.9% in > 60% group (no difference among groups)
de Graaf et al. [76]	2012	Retrospective	Australia	291	3 months	Mortality	-NAFLD in 72% of graft -Data on pre-LT NASH NA	Increased prevalence of mortality in patients with steatosis graft compared to patients without steatosis graft and the higher the grade of steatosis the higher the mortality (steatosis grade 3 25%; grade 1 19%; absence 7%)
Evaluation of CV outcomes in transplanted patients with de novo/recurrent NAFLD
Pisano et al. [36]	2020	Prospective	Italy	54	2 years	-Carotid IMT, plaques and PWV -Diastolic dysfunction (E/A) -EAT	-New onset steatosis 26% -Pre-LT NAFLD 19% -Graft with steatosis 20%	Prevalence of carotid plaques increased before and after LT from 52% to 67%; cIMT from 0.78 mm to 0.83 mm; E/A 1.1 to 0.86; EAT 5.9 mm to 8.1 mm Worsening of indices of early damage of carotid (IMT), diastolic dysfunction and EAT not different between patients with or without post LT steatosis
Bhati et al. [91]	2017	Retrospective	USA	103	5–15 years	-All cause and CV mortality -Survival	-Recurrent NAFLD 87–88% -Pre-LT NASH 47%, criptogenetic cirrhosis 53%	Overall mortality 31%, CV mortality 6% 5, 10, and 15 years post-LT survival rates 86%, 71%, and 51%, respectively No difference in survival between patients with recurrent NAFL versus NASH as determined by biopsy
Hejlova et al. [85]	2016	Retrospective	Czech republic	548	15 years	Survival (comparison between grade 0–1 steatosis vs. 2–3 grade steatosis)	De novo NAFLD in 56% (17% grade 3)	Survival times did not differ between patients with significant steatosis and steatosis grades 0–1 CV mortality after the first year in patients with significant steatosis and steatosis grades 0–1 was 21.4% and 5.4% (NS)
Yalamanchili et al. [90]	2010	Retrospective	USA	2,052	1–10 years	Survival	-De novo NAFLD in 31% -Pre-LT NASH/criptogenetic cirrhosis in 12%	One-, 5-, and 10-year survival not different in patients transplanted for criptogenetic cirrhosis or NASH (86%, 71%, and 56%) vs. with other LT indications (86%, 71%, and 53%) Increased prevalence of CV death in patients transplanted for criptogenetic cirrhosis or NASH (21%) vs. with other LT indications (14%)
Dureja et al. [94]	2011	Cohort-study	USA	88	1–7 years	-All causes mortality and CV mortality -Survival	-Recurrent NAFLD 39% -Pre-LT NAFLD/criptogenetic cirrhosis 100%	Prevalence of mortality 27% (34% in patients with recurrent NAFLD vs. 24% not recurrent, NS) Survival and CV mortality, did not differ between those with and without NAFLD recurrence

PAD: peripheral artery disease; BMP: brain natriuretic peptide; MI: myocardial infarction; AF: atrial fibrillation, PE: pulmonary emobolism; PWV: pulse wave velocity; LVMI: left ventricular mass index; HF: heart failure; LVEF: left ventricular ejection fraction; TIA: transient ischemic attack; NAFL: non-alcoholic fatty liver; BP: blood pressure; GFR: glomerular filtrate rate; NS: not statistically significant; NA: not available; LDL: low density lipoproteins; BNP:brain natriuretic peptide; ALD: alcoholic liver disease; HCV: hepatitis C virus; HCC: hepatocellular carcinoma; PBC: primary biliary cholangitis; PNF: primary non function; E/A: E wave A wave ratio; EAT:epicardial adipose tissue

Declarations

Author contributions

RL and GP revised the literature, focusing on full text paper regarding CV involvement in post LT patients and role of NAFLD in increasing the CV risk and wrote the draft of the manuscript. SF and ALF were involved in the critical revision of the manuscript to its final form and contributed to the review for important intellectual content.

Conflicts of interest

The authors declare that they have no conflicts of interest.

Ethical approval

Not applicable.

Consent to participate

Not applicable.

Consent to publication

Not applicable.

Availability of data and materials

Not applicable.

Funding

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Copyright

References

Adam R, Karam V, Cailliez V, O’Grady JG, Mirza D, Cherqui D, et al. 2018 Annual Report of the European Liver Transplant Registry (ELTR)-50-year evolution of liver transplantation. Transpl Int. 2018;31:1293–317. [DOI] [PubMed]

Kim WR, Lake JR, Smith JM, Schladt DP, Skeans MA, Harper AM, et al. OPTN/SRTR 2016 annual data report: liver. Am J Transplant. 2018;18 Suppl 1:172–253. [DOI] [PubMed]

Jun DW, Kim SG, Park SH, Jin SY, Lee JS, Lee JW, et al. External validation of the nonalcoholic fatty liver disease fibrosis score for assessing advanced fibrosis in Korean patients. J Gastroenterol Hepatol. 2017;32:1094–9. [DOI] [PubMed]

Futagawa Y, Terasaki PI, Waki K, Cai J, Gjertson DW. No improvement in long-term liver transplant graft survival in the last decade: an analysis of the UNOS data. Am J Transplant. 2006;6:1398–406. [DOI] [PubMed]

Watt KD, Pedersen RA, Kremers WK, Heimbach JK, Charlton MR. Evolution of causes and risk factors for mortality post-liver transplant: results of the NIDDK long-term follow-up study. Am J Transplant. 2010;10:1420–7. [DOI] [PubMed] [PMC]

Carenco C, Assenat E, Faure S, Duny Y, Danan G, Bismuth M, et al. Tacrolimus and the risk of solid cancers after liver transplant: a dose effect relationship. Am J Transplant. 2015;15:678–86. [DOI] [PubMed]

VanWagner LB, Lapin B, Skaro AI, Lloyd-Jones DM, Rinella ME. Impact of renal impairment on cardiovascular disease mortality after liver transplantation for nonalcoholic steatohepatitis cirrhosis. Liver Int. 2015;35:2575–83. [DOI] [PubMed] [PMC]

Vanwagner LB, Bhave M, Te HS, Feinglass J, Alvarez L, Rinella ME. Patients transplanted for nonalcoholic steatohepatitis are at increased risk for postoperative cardiovascular events. Hepatology. 2012;56:1741–50. [DOI] [PubMed]

VanWagner LB, Lapin B, Levitsky J, Wilkins JT, Abecassis MM, Skaro AI, et al. High early cardiovascular mortality after liver transplantation. Liver Transpl. 2014;20:1306–16. [DOI] [PubMed] [PMC]

10.

Ampuero J, Romero-Gomez M. Influence of nonalcoholic fatty liver disease on cardiovascular disease. Gastroenterol Hepatologia. 2012;35:585–93. [DOI] [PubMed]

11.

Miura K, Ohnishi H. Role of gut microbiota and Toll-like receptors in nonalcoholic fatty liver disease. World J Gastroenterol. 2014;20:7381–91. [DOI] [PubMed] [PMC]

12.

Brea A, Mosquera D, Martin E, Arizti A, Cordero JL, Ros E. Nonalcoholic fatty liver disease is associated with carotid atherosclerosis: a case-control study. Arterioscler Thromb Vasc biol. 2005;25:1045–50. [DOI] [PubMed]

13.

Kim D, Choi SY, Park EH, Lee W, Kang JH, Kim W, et al. Nonalcoholic fatty liver disease is associated with coronary artery calcification. Hepatology. 2012;56:605–13. [DOI] [PubMed] [PMC]

14.

Puchner SB, Lu MT, Mayrhofer T, Liu T, Pursnani A, Ghoshhajra BB, et al. High-risk coronary plaque at coronary CT angiography is associated with nonalcoholic fatty liver disease, independent of coronary plaque and stenosis burden: results from the ROMICAT II trial. Radiology. 2015;274:693–701. [DOI] [PubMed] [PMC]

15.

Ampuero J, Gallego-Duran R, Romero-Gomez M. Association of NAFLD with subclinical atherosclerosis and coronary-artery disease: meta-analysis. Rev Esp Enferm Dig. 2015;107:10–6. [PubMed]

16.

Fracanzani AL, Tiraboschi S, Pisano G, Consonni D, Baragetti A, Bertelli C, et al. Progression of carotid vascular damage and cardiovascular events in nonalcoholic fatty liver disease patients compared to the general population during 10 years of follow-up. Atherosclerosis. 2016;246:208–13. [DOI] [PubMed]

17.

Lonardo A, Nascimbeni F, Mantovani A, Targher G. Hypertension, diabetes, atherosclerosis and NASH: cause or consequence? J Hepatol. 2018;68:335–52. [DOI] [PubMed]

18.

Ekstedt M, Hagstrom H, Nasr P, Fredrikson M, Stal P, Kechagias S, et al. Fibrosis stage is the strongest predictor for disease-specific mortality in NAFLD after up to 33 years of follow-up. Hepatology. 2015;61:1547–54. [DOI] [PubMed]

19.

Kardashian AA, Dodge JL, Roberts J, Brandman D. Weighing the risks: morbid obesity and diabetes are associated with increased risk of death on the liver transplant waiting list. Liv Int. 2018;38:553–63. [DOI]

20.

European Association for the Study of the Liver (EASL), European Association for the Study of Disease (EASD), European Association for the Study of Oesity (EASO). EASL-EASD-EASO Clinical Practice Guidelines for the management of nonalcoholic fatty liver disease. J Hepatol. 2016;64:1388–402. [DOI] [PubMed]

21.

European Association for the Study of the Liver, Asociacion Latinoamericana para el Estudio del H. EASL-ALEH Clinical Practice Guidelines: non-invasive tests for evaluation of liver disease severity and prognosis. J Hepatol. 2015;63:237–64. [DOI] [PubMed]

22.

Ballestri S, Nascimbeni F, Baldelli E, Marrazzo A, Romagnoli D, Lonardo A. NAFLD as a sexual dimorphic disease: role of gender and reproductive status in the development and progression of nonalcoholic fatty liver disease and inherent cardiovascular risk. Adv Ther. 2017;34:1291–326. [DOI] [PubMed] [PMC]

23.

Lonardo A, Nascimbeni F, Ballestri S, Fairweather D, Win S, Than TA, et al. Sex differences in nonalcoholic fatty liver disease: state of the art and identification of research gaps. Hepatology. 2019;70:1457–69. [DOI] [PubMed] [PMC]

24.

Kim HJ, Lim CW, Lee JH, Park HB, Suh Y, Cho YH, et al. Gender-based differences in the relationship between fatty liver disease and atherosclerosis. Cardiovasc J Afr. 2016;27:281–6. [DOI] [PubMed] [PMC]

25.

Labenz C, Huber Y, Michel M, Nagel M, Galle PR, Kostev K, et al. Impact of NAFLD on the incidence of cardiovascular diseases in a primary care population in germany. Dig Dis Sci. 2020;65:2112–9. [DOI] [PubMed]

26.

Niederseer D, Wernly S, Bachmayer S, Wernly B, Bakula A, Huber-Schonauer U, et al. Diagnosis of nonalcoholic fatty liver disease (NAFLD) is independently associated with cardiovascular risk in a large austrian screening cohort. J Clin Med. 2020;9:1065. [DOI]

27.

Kim MK, Ahn CW, Nam JS, Kang S, Park JS, Kim KR. Association between nonalcoholic fatty liver disease and coronary artery calcification in postmenopausal women. Menopause. 2015;22:1323–7. [DOI] [PubMed] [PMC]

28.

Allen AM, Therneau TM, Mara KC, Larson JJ, Watt KD, Hayes SN, et al. Women with nonalcoholic fatty liver disease lose protection against cardiovascular disease: a longitudinal cohort study. Ame J Gastroenterol. 2019;114:1764–71. [DOI]

29.

Khalid YS, Dasu NR, Suga H, Dasu KN, Reja D, Shah A, et al. Increased cardiovascular events and mortality in females with NAFLD: a meta-analysis. Am J Cardiovasc Dis. 2020;10:258–71. [PubMed] [PMC]

30.

Kwong AJ, Devuni D, Wang C, Boike J, Jo J, VanWagner L, et al. Outcomes of liver transplantation among older recipients with nonalcoholic steatohepatitis in a large multicenter US cohort: the re-evaluating age limits in transplantation consortium. Liver Transpl. 2020;26:1492–503. [DOI] [PubMed]

31.

Noureddin M, Vipani A, Bresee C, Todo T, Kim IK, Alkhouri N, et al. NASH leading cause of liver transplant in women: updated analysis of indications for liver transplant and ethnic and gender variances. Ame J Gastroenterol. 2018;113:1649–59. [DOI]

32.

VanWagner LB, Harinstein ME, Runo JR, Darling C, Serper M, Hall S, et al. Multidisciplinary approach to cardiac and pulmonary vascular disease risk assessment in liver transplantation: an evaluation of the evidence and consensus recommendations. Am J Transplant. 2018;18:30–42. [DOI] [PubMed] [PMC]

33.

VanWagner LB, Serper M, Kang R, Levitsky J, Hohmann S, Abecassis M, et al. Factors associated with major adverse cardiovascular events after liver transplantation among a national sample. Am J Transplant. 2016;16:2684–94. [DOI] [PubMed] [PMC]

34.

Konerman MA, Fritze D, Weinberg RL, Sonnenday CJ, Sharma P. Incidence of and risk assessment for adverse cardiovascular outcomes after liver transplantation: a systematic review. Transplantation. 2017;101:1645–57. [DOI] [PubMed] [PMC]

35.

Konerman MA, Price JC, Campbell CY, Eluri S, Gurakar A, Hamilton J, et al. Pre-liver transplant transthoracic echocardiogram findings and 6-month post-transplant outcomes: a case-control analysis. Ann Transplant. 2016;21:416–27. [DOI] [PubMed]

36.

Alves BC, Bruch-Bertani JP, Galinatti CBM, Garbin CC, Alvares-da-Silva MR, Dall’Alba V. Obesity, dynapenia and high cardiovascular risk co-exist in post-liver transplant setting: results of a cross-sectional study. Clin Res Hepatol Gastroenterol. 2019;43:140–7. [DOI] [PubMed]

37.

Pisano G, Donato MF, Consonni D, Oberti G, Borroni V, Lombardi R, et al. High prevalence of early atherosclerotic and cardiac damage in patients undergoing liver transplantation: preliminary results. Dig Liver Dis. 2020;52:84–90. [DOI] [PubMed]

38.

Perito ER, Phelps A, Vase T, Feldstein VA, Lustig RH, Rosenthal P. Subclinical atherosclerosis in pediatric liver transplant recipients: carotid and aorta intima-media thickness and their predictors. J Pediatr. 2018;193:119–27. [DOI] [PubMed] [PMC]

39.

VanWagner LB, Ning H, Whitsett M, Levitsky J, Uttal S, Wilkins JT, et al. A point-based prediction model for cardiovascular risk in orthotopic liver transplantation: the CAR-OLT score. Hepatology. 2017;66:1968–79. [DOI] [PubMed] [PMC]

40.

Fussner LA, Heimbach JK, Fan C, Dierkhising R, Coss E, Leise MD, et al. Cardiovascular disease after liver transplantation: when, what, and who is at risk. Liver Transpl. 2015;21:889–96. [DOI] [PubMed]

41.

Izzy M, VanWagner LB, Lee SS, Altieri M, Angirekula M, Watt KD. Understanding and managing cardiovascular outcomes in liver transplant recipients. Curr Opin Organ Transplant. 2019;24:148–55. [DOI] [PubMed] [PMC]

42.

Myers RP, Lee SS. Cirrhotic cardiomyopathy and liver transplantation. Liver Transpl. 2000;6:S44–52. [DOI] [PubMed]

43.

Eimer MJ, Wright JM, Wang EC, Kulik L, Blei A, Flamm S, et al. Frequency and significance of acute heart failure following liver transplantation. Am J Cardiol. 2008;101:242–4. [DOI] [PubMed]

44.

Dowsley TF, Bayne DB, Langnas AN, Dumitru I, Windle JR, Porter TR, et al. Diastolic dysfunction in patients with end-stage liver disease is associated with development of heart failure early after liver transplantation. Transplantation. 2012;94:646–51. [DOI] [PubMed]

45.

Josefsson A, Fu M, Bjornsson E, Kalaitzakis E. Prevalence of pre-transplant electrocardiographic abnormalities and post-transplant cardiac events in patients with liver cirrhosis. BMC Gastroenterol. 2014;14:65. [DOI] [PubMed] [PMC]

46.

Qureshi W, Mittal C, Ahmad U, Alirhayim Z, Hassan S, Qureshi S, et al. Clinical predictors of post-liver transplant new-onset heart failure. Liver Transpl. 2013;19:701–10. [DOI] [PubMed]

47.

Mittal C, Qureshi W, Singla S, Ahmad U, Huang MA. Pre-transplant left ventricular diastolic dysfunction is associated with post transplant acute graft rejection and graft failure. Dig Dis Sci. 2014;59:674–80. [DOI] [PubMed]

48.

Sonny A, Govindarajan SR, Jaber WA, Cywinski JB. Systolic heart failure after liver transplantation: incidence, predictors, and outcome. Clin Transplant. 2018;32:e13199. [DOI] [PubMed]

49.

Kia L, Shah SJ, Wang E, Sharma D, Selvaraj S, Medina C, et al. Role of pretransplant echocardiographic evaluation in predicting outcomes following liver transplantation. Am J Transplant. 2013;13:2395–401. [DOI] [PubMed]

50.

Izzy M, Oh J, Watt KD. Cirrhotic cardiomyopathy after transplantation: neither the transient nor innocent bystander. Hepatology. 2018;68:2008–15. [DOI] [PubMed]

51.

Liu H, Jayakumar S, Traboulsi M, Lee SS. Cirrhotic cardiomyopathy: implications for liver transplantation. Liver transpl. 2017;23:826–35. [DOI] [PubMed]

52.

Izzy M, VanWagner LB, Lin G, Altieri M, Findlay JY, Oh JK, et al. Redefining cirrhotic cardiomyopathy for the modern era. Hepatology. 2020;71:334–45. [DOI] [PubMed] [PMC]

53.

Mohamed R, Forsey PR, Davies MK, Neuberger JM. Effect of liver transplantation on QT interval prolongation and autonomic dysfunction in end-stage liver disease. Hepatology. 1996;23:1128–34. [DOI] [PubMed]

54.

Bargehr J, Trejo-Gutierrez JF, Patel T, Rosser B, Aranda-Michel J, Yataco ML, et al. Preexisting atrial fibrillation and cardiac complications after liver transplantation. Liver Transpl. 2015;21:314–20. [DOI] [PubMed]

55.

Fleisher LA, Fleischmann KE, Auerbach AD, Barnason SA, Beckman JA, Bozkurt B, et al. 2014 ACC/AHA guideline on perioperative cardiovascular evaluation and management of patients undergoing noncardiac surgery: executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation. 2014;130:2215–45. [DOI] [PubMed]

56.

Anstee QM, Mantovani A, Tilg H, Targher G. Risk of cardiomyopathy and cardiac arrhythmias in patients with nonalcoholic fatty liver disease. Nat Rev Gastroenterol Hepatol. 2018;15:425–39. [DOI] [PubMed]

57.

58.

D’Agostino RB Sr, Vasan RS, Pencina MJ, Wolf PA, Cobain M, Massaro JM, et al. General cardiovascular risk profile for use in primary care: the Framingham Heart Study. Circulation. 2008;117:743–53. [DOI] [PubMed]

59.

Lloyd-Jones DM, Huffman MD, Karmali KN, Sanghavi DM, Wright JS, Pelser C, et al. Estimating longitudinal risks and benefits from cardiovascular preventive therapies among medicare patients: the million hearts longitudinal ASCVD risk assessment tool: a special report from the American Heart Association and American College of Cardiology. J Am Coll Cardiol. 2017;69:1617–36. [DOI] [PubMed] [PMC]

60.

Ridker PM, Paynter NP, Rifai N, Gaziano JM, Cook NR. C-reactive protein and parental history improve global cardiovascular risk prediction: the Reynolds Risk Score for men. Circulation. 2008;118:2243–51. [DOI] [PubMed] [PMC]

61.

Assmann G, Cullen P, Schulte H. Simple scoring scheme for calculating the risk of acute coronary events based on the 10-year follow-up of the prospective cardiovascular Münster (PROCAM) study. Circulation. 2002;105:310–5. [DOI] [PubMed]

62.

Conroy RM, Pyorala K, Fitzgerald AP, Sans S, Menotti A, De Backer G, et al. Estimation of ten-year risk of fatal cardiovascular disease in Europe: the SCORE project. Eur Heart J. 2003;24:987–1003. [DOI] [PubMed]

63.

Roccaro GA, Goldberg DS, Hwang WT, Judy R, Thomasson A, Kimmel SE, et al. Sustained posttransplantation diabetes is associated with long-term major cardiovascular events following liver transplantation. Am J Transplant. 2018;18:207–15. [DOI] [PubMed] [PMC]

64.

Al Nasser Y, Moura MC, Mertens L, McCrindle BW, Parekh RS, Ng VL, et al. Subclinical cardiovascular changes in pediatric solid organ transplant recipients: a systematic review and meta-analysis. Pediatr transplant. 2016;20:530–9. [DOI] [PubMed]

65.

Siirtola A, Kallio T, Ala-Houhala M, Lehtimaki T, Solakivi T, Antikainen M, et al. Carotid intima-media thickness after pediatric renal or liver transplantation at high-resolution B-mode ultrasonography. Transplant Proc. 2010;42:1695–8. [DOI] [PubMed]

66.

Delucchi A, Dinamarca H, Gainza H, Whitttle C, Torrealba I, Iniguez G. Carotid intima-media thickness as a cardiovascular risk marker in pediatric end-stage renal disease patients on dialysis and in renal transplantation. Transplant Proc. 2008;40:3244–6. [DOI] [PubMed]

67.

Mitsnefes MM, Kimball TR, Witt SA, Glascock BJ, Khoury PR, Daniels SR. Abnormal carotid artery structure and function in children and adolescents with successful renal transplantation. Circulation. 2004;110:97–101. [DOI] [PubMed]

68.

Krmar RT, Balzano R, Jogestrand T, Cedazo-Minguez A, Englund MS, Berg UB. Prospective analysis of carotid arterial wall structure in pediatric renal transplants with ambulatory normotension and in treated hypertensive recipients. Pediatr Transplant. 2008;12:412–9. [DOI] [PubMed]

69.

Bilginer Y, Ozaltin F, Basaran C, Aki TF, Karabulut E, Duzova A, et al. Carotid intima-media thickness in children and young adults with renal transplant: internal carotid artery vs. common carotid artery. Pediatr transplant. 2007;11:888–94. [DOI] [PubMed]

70.

Litwin M, Wuhl E, Jourdan C, Trelewicz J, Niemirska A, Fahr K, et al. Altered morphologic properties of large arteries in children with chronic renal failure and after renal transplantation. J Am Soc Nephrol. 2005;16:1494–500. [DOI] [PubMed]

71.

Basiratnia M, Fazel M, Lotfi M, Hosseini Al-Hashemi G, Fallahzadeh MH, Derakhshan A, et al. Subclinical atherosclerosis and related risk factors in renal transplant recipients. Pediatr Nephrol. 2010;25:343–8. [DOI] [PubMed]

72.

Memaran N, Borchert-Morlins B, Schmidt BMW, Sugianto RI, Wilke H, Blote R, et al. High burden of subclinical cardiovascular target organ damage after pediatric liver transplantation. Liver Transpl. 2019;25:752–62. [DOI] [PubMed]

73.

Vinaixa C, Selzner N, Berenguer M. Fat and liver transplantation: clinical implications. Transpl Int. 2018;31:828–37. [DOI] [PubMed]

74.

Rinella ME, Alonso E, Rao S, Whitington P, Fryer J, Abecassis M, et al. Body mass index as a predictor of hepatic steatosis in living liver donors. Liver Transpl. 2001;7:409–14. [DOI] [PubMed]

75.

Selzner M, Rudiger HA, Sindram D, Madden J, Clavien PA. Mechanisms of ischemic injury are different in the steatotic and normal rat liver. Hepatology. 2000;32:1280–8. [DOI] [PubMed]

76.

Selzner N, Selzner M, Jochum W, Amann-Vesti B, Graf R, Clavien PA. Mouse livers with macrosteatosis are more susceptible to normothermic ischemic injury than those with microsteatosis. J Hepatol. 2006;44:694–701. [DOI] [PubMed]

77.

de Graaf EL, Kench J, Dilworth P, Shackel NA, Strasser SI, Joseph D, et al. Grade of deceased donor liver macrovesicular steatosis impacts graft and recipient outcomes more than the Donor Risk Index. J Gastroenterol Hepatol. 2012;27:540–6. [DOI] [PubMed]

78.

Spitzer AL, Lao OB, Dick AA, Bakthavatsalam R, Halldorson JB, Yeh MM, et al. The biopsied donor liver: incorporating macrosteatosis into high-risk donor assessment. Liver Transpl. 2010;16:874–84. [DOI] [PubMed]

79.

Cieslak B, Lewandowski Z, Urban M, Ziarkiewicz-Wroblewska B, Krawczyk M. Microvesicular liver graft steatosis as a risk factor of initial poor function in relation to suboptimal donor parameters. Transplant Proc. 2009;41:2985–8. [DOI] [PubMed]

80.

Kulik U, Lehner F, Klempnauer J, Borlak J. Primary non-function is frequently associated with fatty liver allografts and high mortality after re-transplantation. Liver Int. 2017;37:1219–28. [DOI] [PubMed]

81.

Andert A, Ulmer TF, Schoning W, Kroy D, Hein M, Alizai PH, et al. Grade of donor liver microvesicular steatosis does not affect the postoperative outcome after liver transplantation. Hepatobiliary Pancreat Dis Int. 2017;16:617–23. [DOI] [PubMed]

82.

Jamieson RW, Zilvetti M, Roy D, Hughes D, Morovat A, Coussios CC, et al. Hepatic steatosis and normothermic perfusion-preliminary experiments in a porcine model. Transplantation. 2011;92:289–95. [DOI] [PubMed]

83.

Bhanji RA, Watt KD. Fatty allograft and cardiovascular outcomes after liver transplantation. Liver Transpl. 2017;23:S76–80. [DOI] [PubMed]

84.

Contos MJ, Cales W, Sterling RK, Luketic VA, Shiffman ML, Mills AS, et al. Development of nonalcoholic fatty liver disease after orthotopic liver transplantation for cryptogenic cirrhosis. Liver Transpl. 2001;7:363–73. [DOI] [PubMed]

85.

Dumortier J, Giostra E, Belbouab S, Morard I, Guillaud O, Spahr L, et al. Nonalcoholic fatty liver disease in liver transplant recipients: another story of “seed and soil”. Am J Gastroenterol. 2010;105:613–20. [DOI] [PubMed]

86.

Hejlova I, Honsova E, Sticova E, Lanska V, Hucl T, Spicak J, et al. Prevalence and risk factors of steatosis after liver transplantation and patient outcomes. Liver Transpl. 2016;22:644–55. [DOI] [PubMed]

87.

Vallin M, Guillaud O, Boillot O, Hervieu V, Scoazec JY, Dumortier J. Recurrent or de novo nonalcoholic fatty liver disease after liver transplantation: natural history based on liver biopsy analysis. Liver Transpl. 2014;20:1064–71. [DOI] [PubMed]

88.

Seo S, Maganti K, Khehra M, Ramsamooj R, Tsodikov A, Bowlus C, et al. De novo nonalcoholic fatty liver disease after liver transplantation. Liver Transpl. 2007;13:844–7. [DOI] [PubMed]

89.

Losurdo G, Castellaneta A, Rendina M, Carparelli S, Leandro G, Di Leo A. Systematic review with meta-analysis: de novo fatty liver disease in liver-transplanted patients. Aliment Pharmacol Ther. 2018;47:704–14. [DOI] [PubMed]

90.

Idowu MO, Chhatrala R, Siddiqui MB, Driscoll C, Stravitz RT, Sanyal AJ, et al. De novo hepatic steatosis drives atherogenic risk in liver transplantation recipients. Liver Transpl. 2015;21:1395–402. [DOI] [PubMed]

91.

Yalamanchili K, Saadeh S, Klintmalm GB, Jennings LW, Davis GL. Nonalcoholic fatty liver disease after liver transplantation for cryptogenic cirrhosis or nonalcoholic fatty liver disease. Liver Transpl. 2010;16:431–9. [DOI] [PubMed]

92.

Bhati C, Idowu MO, Sanyal AJ, Rivera M, Driscoll C, Stravitz RT, et al. Long-term outcomes in patients undergoing liver transplantation for nonalcoholic steatohepatitis-related cirrhosis. Transplantation. 2017;101:1867–74. [DOI] [PubMed]

93.

Coss E, Watt KD, Pedersen R, Dierkhising R, Heimbach JK, Charlton MR. Predictors of cardiovascular events after liver transplantation: a role for pretransplant serum troponin levels. Liver transpl. 2011;17:23–31. [DOI] [PubMed]

94.

Targher G, Bertolini L, Padovani R, Rodella S, Tessari R, Zenari L, et al. Prevalence of nonalcoholic fatty liver disease and its association with cardiovascular disease among type 2 diabetic patients. Diabetes Care. 2007;30:1212–8. [DOI] [PubMed]

95.

Dureja P, Mellinger J, Agni R, Chang F, Avey G, Lucey M, et al. NAFLD recurrence in liver transplant recipients. Transplantation. 2011;91:684–9. [DOI] [PubMed]

96.

Nagai S, Collins K, Chau LC, Safwan M, Rizzari M, Yoshida A, et al. Increased risk of death in first year after liver transplantation among patients with nonalcoholic steatohepatitis vs liver disease of other etiologies. Clin Gastroenterol Hepatol. 2019;17:2759–68.e5. [DOI] [PubMed]

97.

Gitto S, Vukotic R, Vitale G, Pirillo M, Villa E, Andreone P. Nonalcoholic steatohepatitis and liver transplantation. Dig Liver Dis. 2016;48:587–91. [DOI] [PubMed]

98.

Kouz J, Vincent C, Leong A, Dorais M, Rakel A. Weight gain after orthotopic liver transplantation: is nonalcoholic fatty liver disease cirrhosis a risk factor for greater weight gain? Liver Transpl. 2014;20:1266–74. [DOI] [PubMed]

99.

D’Avola D, Cuervas-Mons V, Marti J, Ortiz de Urbina J, Llado L, Jimenez C, et al. Cardiovascular morbidity and mortality after liver transplantation: the protective role of mycophenolate mofetil. Liver Transpl. 2017;23:498–509. [DOI] [PubMed]

100.

Dongiovanni P, Petta S, Maglio C, Fracanzani AL, Pipitone R, Mozzi E, et al. Transmembrane 6 superfamily member 2 gene variant disentangles nonalcoholic steatohepatitis from cardiovascular disease. Hepatology. 2015;61:506–14. [DOI] [PubMed]

101.

Akoglu B, Kindl P, Weber N, Trojan J, Caspary WF, Faust D. Polymorphisms in the methylenetetrahydrofolate reductase gene are determinant for vascular complications after liver transplantation. Eur J Clin Nutr. 2008;62:430–5. [DOI] [PubMed]

102.

De Vincentis A, Mancina RM, Pihlajamaki J, Mannisto V, Petta S, Dongiovanni P, et al. Genetic variants in the MTHFR are not associated with fatty liver disease. Liver Int. 2020;40:1934–40. [DOI] [PubMed]

103.

Dongiovanni P, Valenti L. Genetics of nonalcoholic fatty liver disease. Metabolism. 2016;65:1026–37. [DOI] [PubMed]

104.

Liu ZT, Chen TC, Lu XX, Cheng J, Xie HY, Zhou L, et al. PNPLA3 I148M variant affects nonalcoholic fatty liver disease in liver transplant recipients. World J Gastroenterol. 2015;21:10054–6. [DOI] [PubMed] [PMC]

105.

Piazza NA, Singal AK. Frequency of cardiovascular events and effect on survival in liver transplant recipients for cirrhosis due to alcoholic or nonalcoholic steatohepatitis. Exp Clin Transplant. 2016;14:79–85. [DOI] [PubMed]

106.

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. [DOI] [PubMed]

107.

Targher G, Byrne CD, Lonardo A, Zoppini G, Barbui C. Nonalcoholic fatty liver disease and risk of incident cardiovascular disease: a meta-analysis. J Hepatology. 2016;65:589–600. [DOI]