Gene Network Profiling Before and After Transplantation in Alcoholic Cirrhosis Liver Transplant Recipients

Muffak-Granero, K.; Olmedo, C.; García-Alcalde, Fernando; Comino, A.; Villegas, T.; Villar, Jesús; Garrote, Daniel; Blanco, A.; Bueno, Pablo; Ferrón, José Antonio

doi:10.1016/j.transproceed.2012.05.017

Cited by 7 publications

(6 citation statements)

References 19 publications

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“…These include two members of the aldehyde dehydrogenase family, ALDH1A1 and ALDH1L1, enzymes playing major roles in alcohol metabolism 22. ALDH1L1 mRNA has been reported elevated in alcoholic cirrhosis,23 and single‐nucleotide polymorphisms (SNPs) of ALDH1A1 were associated with alcohol dependence 24, 25. ALDH1 is a marker for stem cell or cancer stem‐like cell, which also has high telomerase activity 26, 27.…”

Section: Discussionmentioning

confidence: 99%

Telomerase reverse transcriptase mutations in plasma DNA in patients with hepatocellular carcinoma or cirrhosis: Prevalence and risk factors

Jiao

Watt

Stevenson

et al. 2018

Hepatology Communications

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Telomerase reverse transcriptase (TERT) mutation is the most frequent genetic alteration in hepatocellular carcinoma (HCC). Our aims were to investigate whether TERT mutations can be detected in circulating cell‐free DNA (cfDNA) of patients with HCC and/or cirrhosis and characterize clinical parameters associated with these mutations. We retrieved data on TERT C228T and C250T promoter mutations in 196 HCCs from The Cancer Genome Atlas. We measured these TERT mutations in plasma cfDNA in 218 patients with HCC and 81 patients with cirrhosis without imaging evidence of HCC. The prevalence of TERT mutations in The Cancer Genome Atlas HCC specimens was 44.4%. TERT mutations were detected with similar prevalence (47.7%) in plasma cfDNAs from 218 patients with HCC. TERT mutations, either within the HCC or in cfDNA, were associated with male sex, hepatitis C virus (HCV), alcoholic cirrhosis, family history of cancer, and poor prognosis. The high prevalence of TERT mutations in HCCs in male patients with cirrhosis caused by HCV and/or alcohol was confirmed in an independent set of HCCs (86.6%). Finally, TERT mutations were detected in cfDNA of 7 out of 81 (8.6%) patients with cirrhosis without imaging evidence of HCC, including 5 male patients with cirrhosis due to HCV and/or alcohol. Genes involved in xenobiotic and alcohol metabolism were enriched in HCCs with TERT mutations, and vitamin K2 was identified as an upstream regulator. Conclusion: TERT mutations are detectable in plasma cfDNA. Long‐term imaging surveillance of patients with cirrhosis with cfDNA TERT mutations without evidence of HCC is required to assess their potential as early biomarkers of HCC. (Hepatology Communications 2018;2:718‐731)

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Section: Discussionmentioning

confidence: 99%

Telomerase reverse transcriptase mutations in plasma DNA in patients with hepatocellular carcinoma or cirrhosis: Prevalence and risk factors

Jiao

Watt

Stevenson

et al. 2018

Hepatology Communications

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“…The contributions of PPARγ specifically have been well-documented in the progression of ALD. In addition to being up-regulated in alcohol-related cirrhosis patients, 32 PPARγ and many of its target genes have been shown to be up-regulated in the liver in response to alcohol in murine models of alcoholism. 33 , 34 , 35 Most notably, the hepatic deletion of Pparg itself has been shown to attenuate alcohol-induced steatosis and inflammation.…”

Section: Resultsmentioning

confidence: 99%

Inhibition of Abelson Tyrosine-Protein Kinase 2 Suppresses the Development of Alcohol-Associated Liver Disease by Decreasing PPARgamma Expression

Malnassy¹,

Keating²,

Gad³

et al. 2023

Cellular and Molecular Gastroenterology and Hepatology

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“…One study on 5 liver allograft recipients transplanted for alcoholic cirrhosis showed a significantly increased expression of JAK2 in the peripheral blood of patients at 7 days post‐transplant. This was correlated with the gene expression of interferon‐gamma receptor 2 (IFNGR2) 61 . Another study recruiting 36 patients transplanted for idiopathic Budd–Chiari syndrome (BCS) showed that JAK2 mutations did not affect the 1‐year survival of the allograft.…”

Section: Jak Inhibitors In Solid Organ Transplantationmentioning

confidence: 99%

“…This was correlated with the gene expression of interferongamma receptor 2 (IFNGR2). 61 Another study recruiting 36 patients transplanted for idiopathic Budd-Chiari syndrome (BCS) showed that JAK2 mutations did not affect the 1-year survival of the allograft. However, 12 patients developed post-transplant thrombotic complications, which was significantly associated with the JAK2V617F mutation of the JAK2 gene.…”

Section: Jak Inhibitors In Liver Transplantationmentioning

confidence: 99%

JAK Inhibitors in Solid Organ Transplantation

Assadiasl

Mojtahedi

Nicknam

2023

The Journal of Clinical Pharma

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Janus kinase (JAK) inhibitors are a novel group of immunosuppressive drugs approved to treat certain rheumatic and allergic disorders; however, their efficacy in the regulation of alloimmune responses after solid organ transplantation has not yet been elucidated. In the present review, we have summarized the results of in vitro, in vivo, experimental, and clinical trial studies about the efficacy and safety of JAK inhibitors in improving allograft survival in solid organ transplantations, including kidney, heart, lung, and liver transplants. Moreover, reports on administering JAK inhibitors to steroid‐resistant patients with graft versus host disease (GvHD) after solid organ transplantation have been reviewed. Overall findings are suggestive of a beneficial role for JAK inhibitors in organ transplantation: for example, they have been shown to improve allograft function, reduce the rate and score of acute rejection, downregulate the expression of proinflammatory cytokines and adhesion molecules, and decrease oxidative stress. However, the adverse effects of these drugs, in particular bone marrow suppression and infection, remain an obstacle.

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Gene Network Profiling Before and After Transplantation in Alcoholic Cirrhosis Liver Transplant Recipients

Cited by 7 publications

References 19 publications

Telomerase reverse transcriptase mutations in plasma DNA in patients with hepatocellular carcinoma or cirrhosis: Prevalence and risk factors

Telomerase reverse transcriptase mutations in plasma DNA in patients with hepatocellular carcinoma or cirrhosis: Prevalence and risk factors

Inhibition of Abelson Tyrosine-Protein Kinase 2 Suppresses the Development of Alcohol-Associated Liver Disease by Decreasing PPARgamma Expression

JAK Inhibitors in Solid Organ Transplantation

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