Steatotic donor livers: Where is the risk‐benefit maximized?

Hamar, Mátyás; Selzner, Markus

doi:10.1002/lt.24826

Cited by 13 publications

(12 citation statements)

References 46 publications

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“…Following the historical AF observations mentioned above on the yellowish, highly fluorescing material in cirrhotic livers, lipofuscins and lipofuscin‐like products in the liver parenchyma have recently regained attention as biomarkers of oxidative metabolic disorders. In fact, oxidative stress can favour disease progression or increase the risk of injury and functional impairment of normal and fatty livers faced with ischaemia and reperfusion in surgery and transplantation . The peroxidation of lipids has long been measured biochemically in terms of malondialdehyde, a thiobarbituric acid reactive substance (TBARS) .…”

Section: Optical Biopsy In Hepatologymentioning

confidence: 99%

“…In fact, oxidative stress can favour disease progression or increase the risk of injury and functional impairment of normal and fatty livers faced with ischaemia and reperfusion in surgery and transplantation. [113][114][115][116] The peroxidation of lipids has long been measured biochemically in terms of malondialdehyde, a thiobarbituric acid reactive substance (TBARS). 72,117 However, while TBARS is relatable to the short-lived and low weight oxidative product of lipids, the AF of lipofuscin-like lipopigments reflects the gathering of oxidative events, in a possible direct relationship with mitochondrial overproduction of oxygen reactive species.…”

Section: Op Ti C Al B I Opsy In Hepatologymentioning

confidence: 99%

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Autofluorescence‐based optical biopsy: An effective diagnostic tool in hepatology

Croce

Ferrigno

Bottiroli

et al. 2018

Liver International

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Autofluorescence emission of liver tissue depends on the presence of endogenous biomolecules able to fluoresce under suitable light excitation. Overall autofluorescence emission contains much information of diagnostic value because it is the sum of individual autofluorescence contributions from fluorophores involved in metabolism, for example, NAD(P)H, flavins, lipofuscins, retinoids, porphyrins, bilirubin and lipids, or in structural architecture, for example, fibrous proteins, in close relationship with normal, altered or diseased conditions of the liver. Since the 1950s, hepatocytes and liver have been historical models to study NAD(P)H and flavins as in situ, real-time autofluorescence biomarkers of energy metabolism and redox state. Later investigations designed to monitor organ responses to ischaemia/reperfusion were able to predict the risk of dysfunction in surgery and transplantation or support the development of procedures to ameliorate the liver outcome. Subsequently, fluorescent fatty acids, lipofuscin-like lipopigments and collagen were characterized as optical biomarkers of liver steatosis, oxidative stress damage, fibrosis and disease progression. Currently, serum AF is being investigated to improve non-invasive optical diagnosis of liver disease. Validation of endogenous fluorophores and in situ discrimination of cancerous from non-cancerous tissue belong to the few studies on liver in human subjects. These reports along with other optical techniques and the huge work performed on animal models suggest many optically based applications in hepatology. Optical diagnosis is currently offering beneficial outcomes in clinical fields ranging from the respiratory and gastrointestinal tracts, to dermatology and ophthalmology. Accordingly, this review aims to promote an effective bench to bedside transfer in hepatology.

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Section: Optical Biopsy In Hepatologymentioning

confidence: 99%

Section: Op Ti C Al B I Opsy In Hepatologymentioning

confidence: 99%

Autofluorescence‐based optical biopsy: An effective diagnostic tool in hepatology

Croce

Ferrigno

Bottiroli

et al. 2018

Liver International

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“…CREBZF functions as a transcriptional coregulator of other transcriptional factors or nuclear receptors, including ATF4, CREB3/Luman, and glucocorticoid receptor . Given the increased number of liver transplant candidates and severe shortage of available organs, it is urgently needed to develop therapeutic approaches to prevent steatosis‐related complications and improve the clinical outcome of liver transplantation . Therefore, we sought to investigate whether CREBZF, the lipid regulator, plays a role in regulating STAT3 activity and liver regeneration.…”

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confidence: 99%

CREBZF as a Key Regulator of STAT3 Pathway in the Control of Liver Regeneration in Mice

Han

Liu

et al. 2020

Hepatology

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Background and Aims STAT3, a member of the signal transducer and activator of transcription (STAT) family, is strongly associated with liver injury, inflammation, regeneration, and hepatocellular carcinoma development. However, the signals that regulate STAT3 activity are not completely understood. Approach and Results Here we characterize CREB/ATF bZIP transcription factor CREBZF as a critical regulator of STAT3 in the hepatocyte to repress liver regeneration. We show that CREBZF deficiency stimulates the expression of the cyclin gene family and enhances liver regeneration after partial hepatectomy. Flow cytometry analysis reveals that CREBZF regulates cell cycle progression during liver regeneration in a hepatocyte‐autonomous manner. Similar results were observed in another model of liver regeneration induced by intraperitoneal injection of carbon tetrachloride (CCl4). Mechanistically, CREBZF potently associates with the linker domain of STAT3 and represses its dimerization and transcriptional activity in vivo and in vitro. Importantly, hepatectomy‐induced hyperactivation of cyclin D1 and liver regeneration in CREBZF liver‐specific knockout mice was reversed by selective STAT3 inhibitor cucurbitacin I. In contrast, adeno‐associated virus–mediated overexpression of CREBZF in the liver inhibits the expression of the cyclin gene family and attenuates liver regeneration in CCl4‐treated mice. Conclusions These results characterize CREBZF as a coregulator of STAT3 to inhibit regenerative capacity, which may represent an essential cellular signal to maintain liver mass homeostasis. Therapeutic approaches to inhibit CREBZF may benefit the compromised liver during liver transplantation.

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“…Moreover, among discarded grafts, there are clinical similarities between donors with grafts that were biopsied and those that were not, representing yet an additional pool of grafts that have the potential to be used. Liver biopsy can provide a more accurate assessment as compared to clinical parameters in these borderline donors and should be considered, especially with trends toward more widespread utilization of extended criteria donors …”

Section: Discussionmentioning

confidence: 99%

The role of deceased donor liver biopsy: An analysis of 5449 liver transplant recipients

Patel

Mohebali

Coe

et al. 2020

Clinical Transplantation

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Background:No standard exists for the use of deceased donor liver biopsy during procurement. We sought to evaluate liver biopsy and the impact of findings on outcomes and graft utilization. Methods:A prospective observational study of donors after neurologic determination of death was conducted from 02/2012-08/2017 (16 OPOs). Donor data were collected through the UNOS Donor Management Goals Registry Web Portal and linked to the Scientific Registry of Transplant Recipients (SRTR) for recipient outcomes. Recipients of biopsied donor livers (BxDL) were studied and a Cox proportional hazard analysis was used to identify independent predictors of 1-year graft survival. Results: Data from 5449 liver transplant recipients were analyzed, of which 1791(33%) received a BxDL. There was no difference in graft or patient survival between the non-BxDL and BxDL recipient groups. On adjusted analysis of BxDL recipients, macrosteatosis (21%-30%[n = 148] and >30%[n = 92]) was not found to predict 1-year graft survival, whereas increasing donor age (HR1.02), donor Hispanic ethnicity (HR1.62), donor INR (HR1.18), and recipient life support (HR2.29) were.Conclusions: Excellent graft and patient survival can be achieved in recipients of BxDL grafts. Notably, as demonstrated by the lack of effect of macrosteatosis on survival, donor to recipient matching may contribute to these outcomes.

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Steatotic donor livers: Where is the risk‐benefit maximized?

Cited by 13 publications

References 46 publications

Autofluorescence‐based optical biopsy: An effective diagnostic tool in hepatology

Autofluorescence‐based optical biopsy: An effective diagnostic tool in hepatology

CREBZF as a Key Regulator of STAT3 Pathway in the Control of Liver Regeneration in Mice

The role of deceased donor liver biopsy: An analysis of 5449 liver transplant recipients

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