Fatty allograft and cardiovascular outcomes after liver transplantation

Bhanji, Rahima A.; Watt, Kymberly D.

doi:10.1002/lt.24843

Cited by 5 publications

(4 citation statements)

References 31 publications

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“…At our Center, we performed a study based on repeated liver graft biopsies up to 15 years from liver transplantation and diagnosed graft steatosis in 56.4% patients, a proportion significantly exceeding the NAFLD prevalence in general population (17). In that study, liver graft steatosis was associated with a trend for diminished survival (mostly due to cardiovascular and oncologic reasons), and graft steatosis is considered a risk factor for poor outcome (18).…”

Section: Introductionmentioning

confidence: 99%

Hepatic Gene Expression Profiles Differentiate Steatotic and Non-steatotic Grafts in Liver Transplant Recipients

et al. 2019

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Background: Liver transplantation leads to non-alcoholic fatty liver disease or non-alcoholic steatohepatitis in up to 40% of graft recipients. The aim of our study was to assess transcriptomic profiles of liver grafts and to contrast the hepatic gene expression between the patients after transplantation with vs. without graft steatosis. Methods: Total RNA was isolated from liver graft biopsies of 91 recipients. Clinical characteristics were compared between steatotic ( n = 48) and control ( n = 43) samples. Their transcriptomic profiles were assessed using Affymetrix HuGene 2.1 ST Array Strips processed in Affymetrix GeneAtlas. Data were analyzed using Partek Genomics Suite 6.6 and Ingenuity Pathway Analysis. Results: The individuals with hepatic steatosis showed higher indices of obesity including weight, waist circumference or BMI but the two groups were comparable in measures of insulin sensitivity and cholesterol concentrations. We have identified 747 transcripts (326 upregulated and 421 downregulated in steatotic samples compared to controls) significantly differentially expressed between grafts with vs. those without steatosis. Among the most downregulated genes in steatotic samples were P4HA1, IGF1 , or fetuin B while the most upregulated were PLIN1 and ME1 . Most influential upstream regulators included HNF1A, RXRA , and FXR . The metabolic pathways dysregulated in steatotic liver grafts comprised blood coagulation, bile acid synthesis and transport, cell redox homeostasis, lipid and cholesterol metabolism, epithelial adherence junction signaling, amino acid metabolism, AMPK and glucagon signaling, transmethylation reactions, and inflammation-related pathways. The derived mechanistic network underlying major transcriptome differences between steatotic samples and controls featured PPARA and SERPINE1 as main nodes. Conclusions: While there is a certain overlap between the results of the current study and published transcriptomic profiles of non-transplanted livers with steatosis, we have identified discrete characteristics of the non-alcoholic fatty liver disease in liver grafts potentially utilizable for the establishment of predictive signature.

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Section: Introductionmentioning

confidence: 99%

Hepatic Gene Expression Profiles Differentiate Steatotic and Non-steatotic Grafts in Liver Transplant Recipients

et al. 2019

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“…Necessity of intensive care unit, longer hospitalization, as well as increased risk of graft failure [77][78][79], especially for steatosis in more than 60% of the graft [79][80][81][82], is usually observed. Viceversa, presence of moderate steatosis seems to affect significantly neither the long-term liver-related outcome [83] nor the CV outcome [37].…”

Section: Liver Graft With Steatosismentioning

confidence: 88%

“…Risk factors for de novo steatosis include presence in LT recipients of sarcopenia and features of MS (especially insulin resistance, hypertension and obesity), tacrolimus based immunosuppressive therapy, hepatitis C virus and genetic predisposition as the genotype [83][84][85], as well as hypoadiponectinemia and high levels of free fatty acids [90]. Indeed, in transplanted patients who develop de novo steatosis, CV events are common with nearly 40% of transplant recipients experiencing an event within 10 years, one-third occurring within the first year.…”

Section: Risk Factors For De Novo Steatosismentioning

confidence: 99%

“…In addition, it has been reported that steatosis resolves in one-fifth of patients with de novo and only rarely in those with recurrent NAFLD [87]. However, data on the impact of recurrent NAFLD on long-term outcomes are conflicting, some showing a similar overall survival in patients with and without recurrent NAFLD [84,91,95], even in the presence of NASH [92], others an increase in mortality, mainly if patients had developed NASH [83,92,96].…”

Section: Recurrence Of Steatosismentioning

confidence: 99%

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Cardiovascular involvement after liver transplantation: role of non-alcoholic fatty liver disease and non-alcoholic steatohepatitis

Lombardi

Pisano

Fracanzani

2021

Exploration of Medicine

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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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Donor PNPLA3 rs738409 genotype is a risk factor for graft steatosis. A post-transplant biopsy-based study

Trunečka

Míková

Dlouhá

et al. 2018

Digestive and Liver Disease

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Fatty allograft and cardiovascular outcomes after liver transplantation

Cited by 5 publications

References 31 publications

Hepatic Gene Expression Profiles Differentiate Steatotic and Non-steatotic Grafts in Liver Transplant Recipients

Hepatic Gene Expression Profiles Differentiate Steatotic and Non-steatotic Grafts in Liver Transplant Recipients

Cardiovascular involvement after liver transplantation: role of non-alcoholic fatty liver disease and non-alcoholic steatohepatitis

Donor PNPLA3 rs738409 genotype is a risk factor for graft steatosis. A post-transplant biopsy-based study

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