Non-alcoholic fatty liver disease and obesity among adult donors are major challenges to living-donor liver transplantation: A single-center experience

Rajaram, Ruveena; Jayaraman, Thevaraajan; Yoong, Boon-Koon; Koh, Peng Soon; Loh, Pui San; Koong, Jun Kit; Khalil, Alizan Abdul; Hashim, Noorjahan Haneem Md; Jamaluddin, Fadhil Hadi; Mahadeva, Sanjiv

doi:10.1016/j.asjsur.2021.07.046

Cited by 5 publications

(6 citation statements)

References 44 publications

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“…In previous studies, the detection rate of NAFLD in living donor livers was between 14.5-53% ( 4). An evaluation of potential donors for living donor liver transplantation (LDLT) programs in Malaysia showed that NAFLD and obesity were significant reasons for low donor utilization (5). Severe steatosis liver (>60%) excludes donor liver range, while the use of moderate steatosis (30-60%) remains controversial (6,7).…”

Section: Introductionmentioning

confidence: 99%

Reactive Oxygen Species Induce Fatty Liver and Ischemia-Reperfusion Injury by Promoting Inflammation and Cell Death

et al. 2022

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Liver transplantation is the ultimate method for treating end-stage liver disease. With the increasing prevalence of obesity, the number of patients with non-alcoholic fatty liver, a common cause of chronic liver disease, is on the rise and may become the main cause of liver transplantation in the future. With the increasing gap between the number of donor livers and patients waiting for liver transplantation and the increasing prevalence of non-alcoholic fatty liver, the proportion of steatosis livers among non-standard donor organs is also increasing. Ischemia-reperfusion injury has historically been the focus of attention in the liver transplantation process, and severe ischemia-reperfusion injury leads to adverse outcomes of liver transplantation. Studies have shown that the production of reactive oxygen species and subsequent oxidative stress play a key role in the pathogenesis of hepatic ischemia and reperfusion injury and non-alcoholic fatty liver. Furthermore, the sensitivity of fatty liver transplantation to ischemia-reperfusion injury has been suggested to be related to the production of reactive oxygen species (ROS) and oxidative stress. In ischemia-reperfusion injury, Kupffer cell and macrophage activation along with mitochondrial damage and the xanthine/xanthine oxidase system promote marked reactive oxygen species production and the inflammatory response and apoptosis, resulting in liver tissue injury. The increased levels of ROS and lipid peroxidation products, vicious circle of ROS and oxidative stress along with mitochondrial dysfunction promoted the progress of non-alcoholic fatty liver. In contrast to the non-fatty liver, a non-alcoholic fatty liver produces more reactive oxygen species and suffers more serious oxidative stress when subjected to ischemia-reperfusion injury. We herein review the effects of reactive oxygen species on ischemia-reperfusion injury and non-alcoholic fatty liver injury as well as highlight several treatment approaches.

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Section: Introductionmentioning

confidence: 99%

Reactive Oxygen Species Induce Fatty Liver and Ischemia-Reperfusion Injury by Promoting Inflammation and Cell Death

et al. 2022

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“…Worldwide, the increasing incidence of NAFLD is affecting the suitability of potential living donor candidates. A recent study reported that 68.3% of potential LDLT donors were not suitable due to NAFLD 16 . Thus, fatty liver is a considerable problem in the LDLT setting.…”

Section: Discussionmentioning

confidence: 99%

Long‐term risk of a fatty liver in liver donors

Goto

Kawamura

Watanabe

et al. 2023

Annals of Gastroent Surgery

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Aim Approximately 30 years have passed since the first experience of living donor liver transplantation. The time to evaluate the long‐term safety of living donors has been fulfilled. Meanwhile, nonalcoholic fatty liver disease is increasingly common and a critical problem. The aim of this study was to evaluate the safety of living donor, focusing on fatty liver postdonation hepatectomy. Methods Living donors (n = 212, 1997–2019) were evaluated by computed tomography (CT) at >1‐year postdonation. A liver to spleen (L/S) ratio of <1.1 was defined as fatty liver. Results Among 212 living liver donors, 30 (14.2%) detected fatty liver at 5.3 ± 4.2 years postdonation. The cumulative incidence rates of fatty liver were 3.1%, 12.1%, 22.1%, and 27.7% at 2, 5, 10, and 15 years postdonation, respectively. Of 30 subjects who developed fatty liver, 18 (60%) displayed a severe steatosis (L/S ratio <0.9). Five (16.7%) had a prior history of excessive alcohol abuse. More than 30% developed metabolic syndrome including obesity, hyperlipidemia, and diabetes. Although six (20%) had a Fib‐4 index of >1.3, which included a case with a Fib‐4 index of >2.67, no significant increased Fib‐4 index was observed in the subjects with fatty liver as compared to those without fatty liver (p = 0.66). The independent predictive risk factors for developing fatty liver were male sex, pediatric recipient, and higher body mass index (>25) at donation. Conclusion Living donors with risk factors for developing fatty liver should be carefully followed‐up for the prevention and management of metabolic syndrome.

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“…The FGF21 gene plays an important role in the mechanism of glucose and lipid metabolism and is involved in many metabolic diseases, such as obesity, diabetes, and non-alcoholic fatty liver [ 4 , 7 , 8 ]. FGF21 is a promising therapeutic target for these metabolic diseases [ 25 , 26 , 27 ].…”

Section: Discussionmentioning

confidence: 99%

“…FGF21 is a hormone that regulates glucose–lipid metabolic pathways, including stimulating the oxidation of fatty acids, production of ketone bodies, inhibition of lipogenesis, glucose uptake, amino acid transport, and energy expenditure [ 4 , 5 , 6 ]. Thus, FGF21 is involved in many metabolic diseases, such as obesity, diabetes, and non-alcoholic fatty liver [ 7 , 8 , 9 ], making it a promising therapeutic target for these metabolic diseases. Actually, FGF21 analogs LY2405319, PF-05231023, etc., were proven to be effective therapeutic agents in obesity, type 2 diabetes mellitus (T2DM), non-alcohol fatty liver disease (NAFLD) and cholestatic liver disease [ 10 , 11 ].…”

Section: Introductionmentioning

confidence: 99%

Analysis of Functional Promoter of Camel FGF21 Gene and Identification of Small Compounds Targeting FGF21 Protein

Fang

Yan

Zhang

et al. 2023

Veterinary Sciences

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The fibroblast growth factor 21 (FGF21) gene plays an important role in the mechanism of glucose and lipid metabolism and is a promising therapeutic target for metabolic disease. Camels display a unique regulation characteristic of glucose and lipid metabolism, endowing them with the ability to adapt to survive drought and chronic hunger. However, the knowledge about the camel FGF21 gene regulation and its differences between humans and mice is still limited. In this study, camel FGF21 gene promoter was obtained for ~2000 bp upstream of the transcriptional start site (TSS). Bioinformatics analysis showed that the proximal promoter region sequences near the TSS between humans and camels have high similarity. Two potential core active regions are located in the −445–612 bp region. In addition, camel FGF21 promoter contains three CpG islands (CGIs), located in the −435~−1168 bp regions, significantly more and longer than in humans and mice. The transcription factor binding prediction showed that most transcription factors, including major functional transcription factors, are the same in different species although the binding site positions in the promoter are different. These results indicated that the signaling pathways involved in FGF21 gene transcription regulation are conservative in mammals. Truncated fragments recombinant vectors and luciferase reporter assay determined that camel FGF21 core promoter is located within the 800 bp region upstream of the TSS and an enhancer may exist between the −1000 and −2000 bp region. Combining molecular docking and in silico ADMET druggability prediction, two compounds were screened as the most promising candidate drugs specifically targeting FGF21. This study expanded the functions of these small molecules and provided a foundation for drug development targeting FGF21.

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Non-alcoholic fatty liver disease and obesity among adult donors are major challenges to living-donor liver transplantation: A single-center experience

Cited by 5 publications

References 44 publications

Reactive Oxygen Species Induce Fatty Liver and Ischemia-Reperfusion Injury by Promoting Inflammation and Cell Death

Reactive Oxygen Species Induce Fatty Liver and Ischemia-Reperfusion Injury by Promoting Inflammation and Cell Death

Long‐term risk of a fatty liver in liver donors

Analysis of Functional Promoter of Camel FGF21 Gene and Identification of Small Compounds Targeting FGF21 Protein

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