BACKGROUND: Faecal microbiota transplantation (FMT) is a developing therapy for disorders related to gut dysbiosis. Despite its growing application, standardised protocols for FMT filtrate preparation and quality assessment remain undeveloped. The viability of bacteria in the filtrate is crucial for FMT's efficacy and for validating protocol execution. We compared two methods-in vitro cultivation and membrane integrity assessment-for their accuracy, reproducibility and clinical applicability in measuring bacterial viability in frozen FMT stool filtrate. METHODS: Bacterial viability in stool filtrate was evaluated using (i) membrane integrity through fluorescent DNA staining with SYTO9 and propidium iodide, followed by flow cytometry and (ii) culturable bacteria counts (colony-forming units, CFU) under aerobic or anaerobic conditions. RESULTS: Using different types of samples (pure bacterial culture, stool of germ-free and conventionally bred mice, native and heat-treated human stool), we refined the bacterial DNA staining protocol integrated with flow cytometry for assessment of bacterial viability in frozen human stool samples. Both the membrane integrity-based and cultivation-based methods exhibited significant variability in bacterial viability across different FMT filtrates, without correlation. The cultivation-based method showed a mean coefficient of variance of 30.3%, ranging from 7.4% to 60.1%. Conversely, the membrane integrity approach yielded more reproducible results, with a mean coefficient of variance for viable cells of 6.4% ranging from 0.2% to 18.2%. CONCLUSION: Bacterial viability assessment in stool filtrate using the membrane integrity method offers robust and precise data, making it a suitable option for faecal material evaluation in FMT. In contrast, the cultivation-dependent methods produce inconsistent outcomes.
- MeSH
- Bacteria izolace a purifikace MeSH
- feces * mikrobiologie MeSH
- fekální transplantace * metody MeSH
- lidé MeSH
- mikrobiální viabilita * MeSH
- myši MeSH
- průtoková cytometrie * metody MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- srovnávací studie MeSH
Úvod: U pacientů s nealkoholovou tukovou chorobou jater (NAFLD), jejímž typickým znakem je inzulinová rezistence (IR), bylo popsáno horší dlouhodobé přežívání a častější výskyt chronického onemocnění ledvin (CKD) než u pacientů bez NAFLD. Cílem naší studie bylo zhodnotit, zda má NAFLD a IR vliv na přežívání a renální funkci u pacientů po transplantaci jater (LT – liver transplantation). Metody: Naše prospektivní studie zahrnula 96 kandidátů LT, kteří byli sledováni po LT. Hodnotili jsme přežívání pacientů a výskyt CKD (definované jako odhadovaná glomerulární filtraci [eGFR] ≤ 1,00 ml/s/1,73 m2 nebo zjevná proteinurie) 5 let po LT a ke konci sledování. U pacientů bylo provedeno klinické, laboratorní, MR a elastografické vyšetření před LT a 1 rok po LT a biopsie jater 1 rok po LT. Výsledky: Z faktorů přítomných 1 rok po LT zvyšovaly riziko úmrtí ke konci sledování vyšší ALT (p = 0,021), ALP (p = 0,012), léčba everolimem (p = 0,025), hraničně významné byly vyšší obvod pasu (p = 0,058), AST (p = 0,059), HOMA-IR (p = 0,056) a fibróza stupně ≥ 3 v biopsii (p = 0,055). Kromě přítomnosti CKD již 1 rok po LT (p < 0,001) patřila mezi potransplantační nezávislé rizikové faktory CKD 5 let po LT přítomnost IR definované jako HOMA-IR ≥ 3 (odds ratio [OR] 4,33; 95% konfidenční interval [CI] 1,25–15,04; p = 0,021) a vyšší sérový vysokomolekulární (HMW) adiponektin (OR 1,25; 95% CI 1,03–1,50; p = 0,021). Z faktorů 1 rok po LT byly s nižšími hodnotami eGFR ke konci sledování spojeny diabetes léčený antidiabetiky (p = 0,008), vyšší sérové hladiny triglyceridů (p = 0,031), C-peptidu (p = 0,022) a leptinu (p = 0,002) a nižší celkový bilirubin (p = 0,006). U pacientů léčených everolimem jsme pozorovali trend k vyšším hodnotám eGFR (p = 0,055). Stupeň steatózy nebo přítomnost steatohepatitidy v biopsii 1 rok po LT neměly vliv na přežívání nebo renální funkce. Závěr: Přítomnost IR 1 rok po LT nezávisle zvyšovala riziko CKD 5 let po LT. Pacienti s vyšším HOMA-IR 1 rok po LT vykazovali trend k horšímu přežívání ke konci sledování.
Introduction: Insulin resistance (IR) is a hallmark of non-alcoholic fatty liver disease (NAFLD), which has been associated with worse long-term survival and more frequent occurrence of chronic kidney disease (CKD) than in patients without NAFLD. The aim of our study was to evaluate the impact of NAFLD and IR on survival and renal function in patients after liver transplantation (LT). Methods: Our prospective study included 96 LT candidates who were observed after LT. We evaluated patient survival and occurrence of CKD (defined as estimated glomerular filtration [eGFR] ≤1.00 mL/s/1.73 m2 or overt proteinuria) 5 years after LT and at the end of follow-up. Clinical, laboratory, MR and elastographic evaluation before and 1 year after LT were performed as well as liver biopsy 1 year after LT. Results: Of the factors present 1 year after LT, higher ALT (P = 0.021), ALP (P = 0.012) and everolimus treatment (P = 0.025) increased the risk of death at the end of follow-up, borderline significance was found also for higher waist circumference (P = 0.058), AST (P = 0.059), HOMA-IR (P = 0.056) and presence of fibrosis stage ≥3 in biopsy (P = 0.055). In addition to the presence of CKD 1 year after LT (P <0.001), other independent posttransplant risk factors of CKD 5 years after LT included presence of IR defined as HOMA-IR ≥3 (OR 4.33; 95% CI 1.25–15.04; P = 0.021) and higher serum high-molecular-weight (HMW) adiponectin (OR 1.25; 95% CI 1.03–1.50; P = 0.021). Of the factors present 1 year after LT, diabetes treated by antidiabetics (P = 0.008), higher serum levels od triglycerides (P = 0.031), C-peptide (P = 0.022) and leptin (P = 0.002) and lower total bilirubin (P = 0.006) were associated with lower eGFR at the end of follow-up. We observed a trend towards higher eGFR levels in patients treated with everolimus (P = 0.055). We did not observe an impact of grade of steatosis and presence of steatohepatitis on biopsy 1 year after LT on survival or renal functions. Conclusion: Presence of IR 1 year after LT independently increased the risk of CKD 5 year after LT. Patients with higher HOMA-IR 1 year after LT had a trend towards worse survival at the end of follow-up.
BACKGROUND: Preclinical studies suggested that pharmacological inhibition of the renin-angiotensin-aldosterone system (RAAS) by ACE inhibitors (ACEis) or angiotensin II receptor blockers (ARBs) may increase local angiotensin-converting enzyme 2 (ACE2) expression. METHODS: In this study, we evaluated the effect of ACEi or ARB treatment on expression of ACE2, ACE, and AGTR1 in 3-month protocol kidney allograft biopsies of stable patients using RT-qPCR (n = 48). Protein ACE2 expression was assessed using immunohistochemistry from paraffin sections. RESULTS: The therapy with RAAS blockers was not associated with increased ACE2, ACE, or ATGR1 expression in kidney allografts and also ACE2 protein immunohistochemistry did not reveal differences among groups. CONCLUSIONS: ACEis or ARBs in kidney transplant recipients do not affect local ACE2 expression. This observation supports long-term RAAS treatment in kidney transplant recipients, despite acute complications such as COVID-19 where ACE2 serves as the entry protein for infection.
- MeSH
- alografty účinky léků metabolismus MeSH
- angiotensin konvertující enzym 2 analýza antagonisté a inhibitory genetika MeSH
- antagonisté receptorů pro angiotenzin farmakologie terapeutické užití MeSH
- antihypertenziva farmakologie terapeutické užití MeSH
- COVID-19 komplikace genetika MeSH
- dospělí MeSH
- exprese genu účinky léků MeSH
- ledviny účinky léků metabolismus MeSH
- lidé středního věku MeSH
- lidé MeSH
- messenger RNA analýza genetika MeSH
- renin-angiotensin systém účinky léků MeSH
- senioři MeSH
- transplantace ledvin MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
Omega-3 polyunsaturated fatty acids (ω-3PUFAs) are introduced into parenteral nutrition (PN) as hepatoprotective but may be susceptible to the lipid peroxidation while olive oil (OO) is declared more peroxidation resistant. We aimed to estimate how the lipid composition of PN mixture affects plasma and erythrocyte lipidome and the propensity of oxidative stress. A cross-sectional comparative study was performed in a cohort of adult patients who were long-term parenterally administered ω-3 PUFAs without (FO/-, n = 9) or with (FO/OO, n = 13) olive oil and healthy age- and sex-matched controls, (n = 30). Lipoperoxidation assessed as plasma and erythrocyte malondialdehyde content was increased in both FO/- and FO/OO groups but protein oxidative stress (protein carbonyls in plasma) and low redox status (GSH/GSSG in erythrocytes) was detected only in the FO/- subcohort. The lipidome of all subjects receiving ω-3 PUFAs was enriched with lipid species containing ω-3 PUFAs (FO/-˃FO/OO). Common characteristic of all PN-dependent patients was high content of fatty acyl-esters of hydroxy-fatty acids (FAHFAs) in plasma while acylcarnitines and ceramides were enriched in erythrocytes. Plasma and erythrocyte concentrations of plasmanyls and plasmalogens (endogenous antioxidants) were decreased in both patient groups with a significantly more pronounced effect in FO/-. We confirmed the protective effect of OO in PN mixtures containing ω-3 PUFAs.
- MeSH
- antioxidancia metabolismus MeSH
- dospělí MeSH
- erytrocyty metabolismus MeSH
- kyseliny mastné omega-3 farmakologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- lipidomika MeSH
- lipidy krev MeSH
- nemoci střev krev terapie MeSH
- olivový olej farmakologie MeSH
- oxidační stres účinky léků MeSH
- parenterální výživa škodlivé účinky metody MeSH
- průřezové studie MeSH
- rybí oleje farmakologie MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- studie případů a kontrol MeSH
- tukové emulze intravenózní farmakologie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
BACKGROUND: The gut microbiome and metabolome may significantly influence clinical outcomes in patients with short bowel syndrome (SBS). The study aimed to describe specific metagenomic/metabolomics profiles of different SBS types and to identify possible therapeutic targets. METHODS: Fecal microbiome (FM), volatile organic compounds (VOCs), and bile acid (BA) spectrum were analyzed in parenteral nutrition (PN)-dependent SBS I, SBS II, and PN-independent (non-PN) SBS patients. RESULTS: FM in SBS I, SBS II, and non-PN SBS shared characteristic features (depletion of beneficial anaerobes, high abundance of Lactobacilaceae and Enterobacteriaceae). SBS I patients were characterized by the abundance of oxygen-tolerant microrganisms and depletion of strict anaerobes. Non-PN SBS subjects showed markers of partial FM normalization. FM dysbiosis was translated into VOC and BA profiles characteristic for each SBS cohort. A typical signature of all SBS patients comprised high saturated aldehydes and medium-chain fatty acids and reduced short-chain fatty acid (SCFA) content. Particularly, SBS I and II exhibited low protein metabolism intermediate (indole, p-cresol) content despite the hypothetical presence of relevant metabolism pathways. Distinctive non-PN SBS marker was high phenol content. SBS patients' BA fecal spectrum was enriched by chenodeoxycholic and deoxycholic acids and depleted of lithocholic acid. CONCLUSIONS: Environmental conditions in SBS gut significantly affect FM composition and metabolic activity. The common feature of diverse SBS subjects is the altered VOC/BA profile and the lack of important products of microbial metabolism. Strategies oriented on the microbiome/metabolome reconstitution and targeted delivery of key compounds may represent a promising therapeutic strategy in SBS patients.
- MeSH
- Bacteria klasifikace MeSH
- dysbióza MeSH
- feces mikrobiologie MeSH
- lidé MeSH
- metabolom * MeSH
- parenterální výživa MeSH
- střevní mikroflóra * MeSH
- syndrom krátkého střeva mikrobiologie MeSH
- těkavé organické sloučeniny analýza MeSH
- žlučové kyseliny a soli analýza MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Parenteral nutrition (PN) is often associated with the deterioration of liver functions (PNALD). Omega-3 polyunsaturated fatty acids (PUFA) were reported to alleviate PNALD but the underlying mechanisms have not been fully unraveled yet. Using omics´ approach, we determined serum and liver lipidome, liver proteome, and liver bile acid profile as well as markers of inflammation and oxidative stress in rats administered either ω-6 PUFA based lipid emulsion (Intralipid) or ω-6/ω-3 PUFA blend (Intralipid/Omegaven) via the enteral or parenteral route. In general, we found that enteral administration of both lipid emulsions has less impact on the liver than the parenteral route. Compared with parenterally administered Intralipid, PN administration of ω-3 PUFA was associated with 1. increased content of eicosapentaenoic (EPA)- and docosahexaenoic (DHA) acids-containing lipid species; 2. higher abundance of CYP4A isoenzymes capable of bioactive lipid synthesis and the increased content of their potential products (oxidized EPA and DHA); 3. downregulation of enzymes involved CYP450 drug metabolism what may represent an adaptive mechanism counteracting the potential negative effects (enhanced ROS production) of PUFA metabolism; 4. normalized anti-oxidative capacity and 5. physiological BAs spectrum. All these findings may contribute to the explanation of ω-3 PUFA protective effects in the context of PN.
- MeSH
- emulze MeSH
- enterální výživa metody MeSH
- fosfolipidy MeSH
- játra metabolismus MeSH
- krysa rodu rattus MeSH
- kyselina eikosapentaenová chemie MeSH
- kyseliny dokosahexaenové chemie MeSH
- kyseliny mastné omega-3 chemie MeSH
- kyslík metabolismus MeSH
- lipidomika MeSH
- lipidy chemie MeSH
- malondialdehyd metabolismus MeSH
- metabolomika MeSH
- nenasycené mastné kyseliny metabolismus MeSH
- oxidační stres MeSH
- parenterální výživa metody MeSH
- potkani Wistar MeSH
- proteom metabolismus MeSH
- reaktivní formy kyslíku metabolismus MeSH
- rybí oleje MeSH
- sójový olej MeSH
- zánět MeSH
- žlučové kyseliny a soli analýza MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- srovnávací studie MeSH
BACKGROUND & AIMS: MiR-33a has emerged as a critical regulator of lipid homeostasis in the liver. Genetic deficiency of miR-33a aggravates liver steatosis in a preclinical model of non-alcoholic fatty liver disease (NAFLD), and relative expression of miR-33a is increased in the livers of patients with non-alcoholic steatohepatitis (NASH). It was unknown whether miR-33a is detectable in the serum of patients with NAFLD. We sought to determine whether circulating miR-33a is associated with histological hepatic steatosis, inflammation, ballooning or fibrosis, and whether it could be used as a serum marker in patients with NAFLD/NASH. METHODS: We analysed circulating miR-33a using quantitative PCR in 116 liver transplant recipients who underwent post-transplant protocol liver biopsy. Regression analysis was used to determine association of serum miR-33a with hepatic steatosis, inflammation, ballooning and fibrosis in liver biopsy. RESULTS: Liver graft steatosis and inflammation, but not ballooning or fibrosis, were significantly associated with serum miR-33a, dyslipidemia and insulin resistance markers on univariate analysis. Multivariate analysis showed that steatosis was independently associated with serum miR-33a, ALT, glycaemia and waist circumference, whereas inflammation was independently associated with miR-33a, HbA1 and serum triglyceride levels. Receiver operating characteristic analysis showed that exclusion of serum miR-33a from multivariate analysis resulted in non-significant reduction of prediction model accuracy of liver steatosis or inflammation. CONCLUSIONS: Our data indicate that circulating miR-33a is an independent predictor of liver steatosis and inflammation in patients after liver transplantation. Although statistically significant, its contribution to the accuracy of prediction model employing readily available clinical and biochemical variables was limited in our cohort.
- MeSH
- biologické markery MeSH
- biopsie MeSH
- cirkulující mikroRNA MeSH
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mikro RNA krev genetika MeSH
- nealkoholová steatóza jater krev etiologie metabolismus patologie MeSH
- ROC křivka MeSH
- senioři MeSH
- transplantace jater * škodlivé účinky MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Souhrn: Úvod: Inzulinová rezistence (IR) má velký význam v patogenezi nealkoholové tukové nemoci jater a dalších onemocnění. Údaje o prevalenci a vývoji IR u pacientů před transplantací jater (LT – liver transplantation) a po ní jsou omezené. Cílem naší prospektivní studie bylo zhodnocení prevalence a vývoje IR u pacientů před LT a v prvních 2 letech po LT. Metody: U 77 pacientů zařazených na čekací listinu k LT v období 5/ 2015–4/ 2017 bylo před LT, 6 měsíců (M), 1 rok (R) a 2R po LT provedeno klinické a laboratorní vyšetření a elastografie jater, 1H magnetickou rezonanční (1H MR) spektroskopií byl stanoven obsah tuku v játrech. V 1 a 2 letech po LT byla provedena necílená biopsie jater. Výsledky: IR definovanou jako HOMA-IR (Homeostasis Assessment Model) ≥ 3,0 mělo 26 pacientů (41,3 %) před LT, 16 pacientů (25,4 %) v 6M po LT, 22 pacientů (34,9 %) v 1R po LT a 29 pacientů (46,0 %) ve 2R po LT (p = 0,028 pro 2R vs. 6M). Předtransplantační IR korelovala s věkem, indikací k LT a přítomností metabolického syndromu. IR hodnocená 2R po LT korelovala s přítomností metabolického syndromu, hypertenze, diabetu, body mass indexu, gamaglutamyltransferázy, s množstvím jaterního tuku hodnoceného histologicky i 1H MR spektroskopií, se stupněm balonové degenerace v biopsii a se stupněm fibrózy dle shear wave elastografie. Závěr: Prevalence IR je vysoká u pacientů před i po LT, významně stoupá s rostoucí dobou od LT. Výskytu potransplantační IR a souvisejících faktorů je třeba věnovat maximální péči.
Introduction: Insulin resistance (IR) plays an important role in the pathogenesis of nonalcoholic fatty liver disease and other diseases. Data regarding the prevalence and evolution of IR in patients before and after liver transplantation (LT) are limited. This prospective study aimed to evaluate the prevalence and evolution of IR in patients before and within 2 years (Y) after LT. Methods: In 77 patients listed for LT from May 2015 to April 2017, clinical, laboratory, and elastographic evaluations were performed before LT and 6 months (M), 1Y, and 2Y after LT. The liver fat content was also determined by 1H magnetic resonance (1H MR) spectroscopy. Liver graft biopsy was performed at 1Y and 2Y after LT. Results: IR defined as HOMA-IR ≥ 3.0 was found in 26 patients (41.3%) before LT, 16 patients (25.4%) at 6M after LT, 22 patients (34.9%) at 1Y after LT, and 29 patients (46.0%) at 2Y after LT (P = 0.028 for 2Y vs. 6M). Pretransplant IR correlated with age, indication for LT, and the presence of metabolic syndrome. IR at 2Y after LT correlated with the presence of metabolic syndrome, hypertension, and diabetes mellitus, body mass index, the level of gamma-glutamyl transferase, the liver fat content estimated both histologically and by 1H MR spectroscopy, the grade of ballooning in liver biopsy, and the fibrosis stage estimated by shear wave elastography. Conclusion: The prevalence of IR is high in patients both before and after LT, and increases significantly with time after LT. Great attention should be paid to posttransplant IR and associated factors.
- MeSH
- elastografie MeSH
- inzulinová rezistence * MeSH
- metabolický syndrom MeSH
- nealkoholová steatóza jater diagnostické zobrazování diagnóza komplikace MeSH
- nemoci jater diagnostické zobrazování diagnóza komplikace MeSH
- prevalence MeSH
- prospektivní studie MeSH
- transplantace jater * MeSH
- Publikační typ
- práce podpořená grantem MeSH
Parenteral nutrition-associated liver disease (PNALD) is a severe complication in patients completely dependent on parenteral nutrition (PN). The gold diagnostic standard, liver biopsy, is associated with significant health risk and therefore its use is limited. MicroRNAs (miRNAs) are small non-coding regulatory RNA molecules with highly tissue-specific expression and the secreted miRNAs may serve as non-invasive diagnostic biomarkers. The aim of this study was to evaluate the expression of a panel of specific miRNAs associated with liver diseases of different origin in PN-dependent adult patients in order to design miRNA panel enabling to precise monitoring of PNALD progression. Twelve PN-dependent patients with short bowel syndrome (SBS) were monitored on three/four-month basis for up to 24 months. Forty-five age- and sex-matched subjects without any known liver pathology served as controls. Specific miRNAs expression was determined by RT-qPCR using TaqMan probes (Thermofisher). Liver function test parameters were determined in certified clinical laboratories. Six of the tested miRNAs exhibited significantly altered expression compared with healthy controls, three of them (MIR122, MIR1273g, and MIR500a) were upregulated while three were down-regulated (MIR505, MIR199a, MIR139). MIR122 positively correlated with serum AST and ALT activities while MIR1273g positively correlated with serum CRP concentration and GGT activity. MIR505, MIR199a, and MIR139 negatively correlated with serum GGT activity. Fluctuation of these parameters well paralleled serum miRNA concentrations in all patients throughout the whole observation period. We identified six miRNAs whose serum concentrations are significantly altered in PN-dependent patients with PNALD and correlate with markers of inflammation, cholestasis or hepatic injury. Their reliability as markers of PNALD progression needs to be further evaluated.
- MeSH
- biologické markery krev MeSH
- dospělí MeSH
- kohortové studie MeSH
- lidé středního věku MeSH
- lidé MeSH
- mikro RNA krev MeSH
- mladý dospělý MeSH
- nemoci jater diagnóza etiologie krev MeSH
- parenterální výživa škodlivé účinky trendy MeSH
- senioři MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
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.
- Publikační typ
- časopisecké články MeSH
