Genetic polymorphisms of the hepatic pathways of fatty liver disease after living donor liver transplantation

Chiu, King-Wah; Goto, Shigeru; Nakano, Toshiaki; Hu, Tsung–Hui; Chen, Ding-Wei; Huang, Kuang-Tzu; Hsu, Li-Wen; Chen, Chao‐Long

doi:10.1111/liv.13920

Cited by 5 publications

(5 citation statements)

References 23 publications

(28 reference statements)

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“…The strength of our current study is the clinical findings following our previous research, firstly suggesting the homogenous phenomenon of sequence changes in graft liver CYP2C19 from the different genotypes between the donors and the recipients [ 9 ], and then further observing an association between subclinical low serum 25(OH)D in donors and fatty liver disease in recipients after LDLT [ 13 ]. Based on the result of these two previous studies, we reported the correlation that the serum vitamin D level was significant lower in cases with genetic modification than those with non-modification [ 9 , 13 , 20 ]. This study demonstrated that the percentage of genetic modification was 33.4% (10/30) for the rejection and non-rejection groups in VDR rs2228530, and 66.7% (20/30) for both groups in CYP2R1 rs10741657.…”

Section: Discussionmentioning

confidence: 99%

Liver Graft Pathology and Low Serum 25-Hydroxyvitamin D after Living Donor Liver Transplantation

et al. 2022

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Background: Most cases of advanced liver diseases are associated with low serum 25-hydroxyvitamin D and vitamin D deficiency. This phenomenon may occur in living donor liver transplantation (LDLT). Aims: We conducted this study to explore the interplay between VDR and CYP2R1 in liver graft and compared our findings with the pathological interpretation of serum 25(OH)D concentration. Methods: In total, 60 patients received liver graft biopsy after LDLT and were separated (1:1) into two groups: graft rejection group and graft non-rejection group. We extracted both of the recipients’ and donors’ serum DNA to investigate the vitamin D receptor (VDR) rs2228530 and CYP2R1 rs10741657 single nucleotide polymorphisms (SNPs) using real-time polymerase chain reaction. We also extracted DNA from liver graft tissues to explore the genetic alleles of VDR rs2228530 and CYP2R1 rs10741657 after LDLT. Serum biochemistry profile and 25(OH)D concentrations were measured before and after LDLT. Results: There were no significant differences in serum VDR rs2228530 and CYP2R1 rs10741657 genetic alleles between recipients and donors. The percentage of genetic modification was 33.4% (10/30) for the rejection and non-rejection groups in VDR rs2228530, and 66.7% (20/30) for both groups in CYP2R1 rs10741657. Serum 25(OH)D concentrations were significantly lower after LDLT D30 than that before LDLT in the rejection (p = 0.0001) and non-rejection graft pathology (p = 0.0017) groups. Conclusions: The presence of low serum 25(OH)D concentrations after LDLT suggested that post-transplant low serum 25(OH)D concentrations may develop with the homogenous phenomenon of VDR rs2228530 and CYP2R1 rs10741657 genetic modifications in recipients regardless of graft pathology.

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Section: Discussionmentioning

confidence: 99%

Liver Graft Pathology and Low Serum 25-Hydroxyvitamin D after Living Donor Liver Transplantation

et al. 2022

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“…NAFLD was significantly associated with low serum vitamin D levels and progression of liver fibrosis [31,32]. The presence of the VDR polymorphism rs2228570 was shown to be related to low serum vitamin D levels and to influence the development of fatty liver disease in recipients after living donor transplantation [30] (Figure 1).…”

Section: Vdr Gene Polymorphisms In the Development Of Nafldmentioning

confidence: 99%

“…Development of fatty liver disease was reported after liver transplantation. Genotype analysis of selective graft biopsies from liver tissue after living donor liver transplantation was performed to investigate the effects of genetic variants in the vitamin D-VDR system on vitamin D maintenance after living donor liver transplantation [30]. NAFLD was significantly associated with low serum vitamin D levels and progression of liver fibrosis [31,32].…”

Section: Vdr Gene Polymorphisms In the Development Of Nafldmentioning

confidence: 99%

Gene Polymorphisms and Biological Effects of Vitamin D Receptor on Nonalcoholic Fatty Liver Disease Development and Progression

Tourkochristou

Mouzaki

Triantos

2023

IJMS

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Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease, with increasing prevalence worldwide. The genetic and molecular background of NAFLD pathogenesis is not yet clear. The vitamin D/vitamin D receptor (VDR) axis is significantly associated with the development and progression of NAFLD. Gene polymorphisms may influence the regulation of the VDR gene, although their biological significance remains to be elucidated. VDR gene polymorphisms are associated with the presence and severity of NAFLD, as they may influence the regulation of adipose tissue activity, fibrosis, and hepatocellular carcinoma (HCC) development. Vitamin D binds to the hepatic VDR to exert its biological functions, either by activating VDR transcriptional activity to regulate gene expression associated with inflammation and fibrosis or by inducing intracellular signal transduction through VDR-mediated activation of Ca2+ channels. VDR activity has protective and detrimental effects on hepatic steatosis, a characteristic feature of NAFLD. Vitamin D-VDR signaling may control the progression of NAFLD by regulating immune responses, lipotoxicity, and fibrogenesis. Elucidation of the genetic and molecular background of VDR in the pathophysiology of NAFLD will provide new therapeutic targets for this disease through the development of VDR agonists, which already showed promising results in vivo.

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“…LT offers a unique perspective to view hepatic and extrahepatic factors that define NAFLD with combination of donor graft and host factors. Genotypically, grafting of vitamin D receptor, VDR rs2228570, has lowers serum 25(OH)D, which influences NAFLD development (9,10). On the other side, graft PNPLA3 variant leads to liver steatosis phenotype and increases susceptibility to hepatic fat accumulation (11,12).…”

Section: Introductionmentioning

confidence: 99%

Extrahepatic organs in the development of non-alcoholic fatty liver disease in liver transplant patients

Su¹,

Wei²,

Wei³

et al. 2022

Hepatobiliary Surg Nutr

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Importance: Non-alcoholic fatty liver disease (NAFLD) is highly prevalent in patients who undergo liver transplantation (LT). Whereas there is huge data on NAFLD, little is known about NAFLD in LT.Objective: In this review, we aim to explore extrahepatic organs and their potential mechanisms in the development of NAFLD in LT patients and discuss current limitations in preclinical and clinical scenarios with suggestions for future study.Evidence Review: The following keywords, such as NAFLD, NASH, liver transplant, therapy, pathogenesis and biomarkers, were set for literature retrieval. The articles which were published articles in English till 25th June 2020 were included, and there is no limit for the study design type.Findings: Following LT, there are significant shifts in the microbiota and farnesoid X receptor may be a potential therapeutic target for NAFLD in LT settings. The roles of probiotics and diet on NALFD remain inconclusive in LT background. Nevertheless, the adipokines and cytokines disorder and local insulin resistance of adipose tissue may contribute to NAFLD process. Bariatric surgeries are promising in controlling de novo and recurrent NAFLD with significant reduction in abdominal adipose tissue, despite the optimal timing is inconclusive in LT cases. Furthermore, circumstantial evidence indicates that miRNA-33a may function as a mediator bridging sarcopenia and NAFLD of post-LT. β-Hydroxy-β-Methyl-Butyrate treatment could improve muscle status in graft recipients and shows protective potential for NAFLD in LT settings.Conclusions and Relevance: Gut, adipose tissue and muscle are intricately intertwined in promoting NAFLD in LT cases. Further animal studies are needed to deepen our understanding of mechanisms in multi-organ crosstalk. High quality clinical trials are warrant for making guidelines and developing management strategies on NAFLD after LT.

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Genetic polymorphisms of the hepatic pathways of fatty liver disease after living donor liver transplantation

Abstract: Donor/recipient CYP27A1 rs4674344 and graft VDR rs2228570 may be related to low serum 25(OH)D and may play a major role in the development of fatty liver disease in recipients after living donor liver transplantation.

Cited by 5 publications

References 23 publications

Liver Graft Pathology and Low Serum 25-Hydroxyvitamin D after Living Donor Liver Transplantation

Liver Graft Pathology and Low Serum 25-Hydroxyvitamin D after Living Donor Liver Transplantation

Gene Polymorphisms and Biological Effects of Vitamin D Receptor on Nonalcoholic Fatty Liver Disease Development and Progression

Extrahepatic organs in the development of non-alcoholic fatty liver disease in liver transplant patients

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