Úvod: Varianty rs738409 c.444C>G (p.I148M) v patatin-like phospholipase domain-containing 3 (PNPLA3) a rs58542926 c.499G>A (p.E167K) v TM6SF2 (transmembrane 6 superfamily member 2) jsou významnými genetickými faktory vzniku a progrese nealkoholové tukové nemoci jater (NAFLD). U obou variant byla popsána vyšší mortalita na jaterní onemocnění, vliv na celkovou mortalitu nebyl prokázán. Cílem této studie bylo posoudit význam genotypů PNPLA3 rs738409 a TM6SF2 rs58542926 dárce a příjemce na dlouhodobé přežívání pacientů po LT. Metody: V kohortě 268 dospělých pacientů po LT, u kterých byly k dispozici genotypy PNPLA3 rs738409 a TM6SF2 rs58542926 dárce a příjemce a byl histologicky zhodnocen výskyt steatózy 6–30 měsíců po LT, jsme hodnotili dlouhodobé přežívání pacientů. Medián sledování byl 17,0 let. Odhady funkcí přežití byly vytvořeny pomocí Kaplan-Meierova modelu a pro zkoumání prediktivní hodnoty vybraných proměnných byl použit Coxův model proporcionálního hazardu. Výsledky: Na přežívání pacientů po LT měly negativní vliv vyšší věk příjemce (p < 0,001), mužské pohlaví (p = 0,014), alkoholická (p = 0,021) nebo HCV (p = 0,042) etiologie jaterní cirhózy a přítomnost hepatocelulárního karcinomu v explantátu jater (p = 0,009). Genotypy PNPLA3 rs738409 a TM6SF2 rs58542926 příjemce ani dárce neměly na přežívání pacientů žádný vliv. Závěr: Ačkoli varianty PNPLA3 c.444G a TM6SF2 c.499A dárce zvyšují riziko steatózy jaterního štěpu po LT, nebyl pro tyto genotypy dárce ani příjemce prokázán negativní vliv na dlouhodobé přežívání pacientů po LT.
Introduction: The variants rs738409 c.444C>G (p.I148M) in patatin-like phospholipase domain-containing 3 (PNPLA3) and rs58542926 c.499G>A (p.E167K) in TM6SF2 (transmembrane 6 superfamily member 2) are significant genetic risk factors of development and progression of non-alcoholic fatty liver dis ease (NAFLD). In both variants, increased liver-specific mortality was described, while the impact on all-cause mortality was not proved. The aim of the study was to evaluate the impact of PNPLA3 rs738409 and TM6SF2 rs58542926 genotypes of the donor and recipient respectively on long-term patient survival after LT. Methods: We evaluated long-term patient survival in a cohort of 268 adult LT recipients, in whom PNPLA3 rs738409 and TM6SF2 rs58542926 genotypes of the donor and recipient respectively were available and steatosis was evaluated in liver graft biopsy 6–30 months after LT. The median fol low-up was 17 years. The Kaplan-Meier model was used for the survival estimates and the Cox proportional hazard model was used to assess the predictive value of the chosen variables. Results: Increased recipient age (P < 0.001), male sex (P = 0.014), alcoholic (P = 0.021) or HCV (P = 0.042) etiology of liver cirrhosis, and presence of hepatocellular carcinoma (P = 0.009) negatively influenced long-term patient survival after LT. PNPLA3 rs738409 and TM6SF2 rs58542926 genotypes of the recipient and donor respectively had no effect on patient survival. Conclusion: Although PNPLA3 c.444G and TM6SF2 c.499A variants of the donor increase the risk of steatosis of the liver graft after LT, we did not prove a negative impact of these genotypes of the donor and recipient on long-term patient survival after LT.
The pathogenesis of non-alcoholic fatty liver disease (NAFLD) is associated with abnormalities of liver lipid metabolism. On the contrary, a diet enriched with n-3 polyunsaturated fatty acids (n-3-PUFAs) has been reported to ameliorate the progression of NAFLD. The aim of our study was to investigate the impact of dietary n-3-PUFA enrichment on the development of NAFLD and liver lipidome. Mice were fed for 6 weeks either a high-fat methionine choline-deficient diet (MCD) or standard chow with or without n-3-PUFAs. Liver histology, serum biochemistry, detailed plasma and liver lipidomic analyses, and genome-wide transcriptome analysis were performed. Mice fed an MCD developed histopathological changes characteristic of NAFLD, and these changes were ameliorated with n-3-PUFAs. Simultaneously, n-3-PUFAs decreased serum triacylglycerol and cholesterol concentrations as well as ALT and AST activities. N-3-PUFAs decreased serum concentrations of saturated and monounsaturated free fatty acids (FAs), while increasing serum concentrations of long-chain PUFAs. Furthermore, in the liver, the MCD significantly increased the hepatic triacylglycerol content, while the administration of n-3-PUFAs eliminated this effect. Administration of n-3-PUFAs led to significant beneficial differences in gene expression within biosynthetic pathways of cholesterol, FAs, and pro-inflammatory cytokines (IL-1 and TNF-α). To conclude, n-3-PUFA supplementation appears to represent a promising nutraceutical approach for the restoration of abnormalities in liver lipid metabolism and the prevention and treatment of NAFLD.
- MeSH
- cholesterol metabolismus MeSH
- cholin metabolismus MeSH
- dieta s vysokým obsahem tuků škodlivé účinky MeSH
- játra metabolismus MeSH
- kyseliny mastné neesterifikované metabolismus MeSH
- kyseliny mastné omega-3 * farmakologie terapeutické užití metabolismus MeSH
- methionin metabolismus MeSH
- myši inbrední C57BL MeSH
- myši MeSH
- nealkoholová steatóza jater * etiologie genetika MeSH
- nenasycené mastné kyseliny metabolismus MeSH
- Racemethionin metabolismus farmakologie MeSH
- triglyceridy metabolismus MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- MeSH
- cvičení MeSH
- dietoterapie MeSH
- jaterní cirhóza diagnóza etiologie komplikace MeSH
- kyselina ursodeoxycholová aplikace a dávkování farmakologie terapeutické užití MeSH
- lidé MeSH
- nealkoholová steatóza jater * diagnóza etiologie terapie MeSH
- probiotika aplikace a dávkování terapeutické užití MeSH
- rizikové faktory MeSH
- střevní mikroflóra MeSH
- žlučové kyseliny a soli metabolismus terapeutické užití MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- novinové články MeSH
Ultra-spracované potraviny (UPF) sa často vyznačujú nízkou nutričnou kvalitou, vysokou energetickou hustotou a prítomnosťou prídavných látok, látok z obalov a zlúčenín, ktoré vznikajú počas výroby, spracovania a skladovania. UPF zahŕňa priemyselné receptúry a zvyčajne obsahuje mnoho zložiek. UPF obsahuje cukor, oleje, tuky, soľ, antioxidanty, stabilizátory a konzervačné látky, potravinárske prísady a emulgátory. Okrem nízkej výživovej hodnoty spracovanie potravín podporuje tvorbu škodlivých zlúčenín v potravinách. Potravinové prísady v rámci UPF, podporujú zápaly, poruchy funkcie pečene a metabolický syndróm, ktoré sú založené na zmenách mikrobiómu. Obezogény sú látky z prostredia, ktoré menia rovnováhu medzi príjmom a výdajom energie. Obezogény sú podskupinou environmentálnych chemických látok, ktoré pôsobia ako endokrinné disruptory ovplyvňujúce koncové metabolické ukazovatele. V posledných desaťročiach sa na celom svete dramaticky zvýšila spotreba ultra-spracovaných výrobkov. UPF sa na priemernom energetickom príjme podieľali viac ako 60 %. Priemerný obsah bielkovín, vlákniny, vitamínov a vápnika v strave výrazne klesá. Energetický príspevok UPF, zatiaľ čo obsah sacharidov, pridaného cukru a nasýtených tukov sa zvyšuje. Ultra-spracované potraviny sa podieľajú na väčšine pridaných cukrov v západnej strave. Fruktóza – najčastejší obezogén, sa spája so zvýšeným rizikom fibrózy pečene. V posledných rokoch pribúdajú dôkazy o škodlivom vplyve UPF. Konzumácia UPF sa spája s metabolickými zmenami, výskytom chronických ochorení a nadmernou úmrtnosťou. Existujú aj dôkazy o súvislosti s NAFLD, NASH a fibrózou. Vysoká spotreba UPF súvisí so škodlivými metabolickými a hepatálnymi parametrami v populácii NAFLD. Okrem toho kombinácia fajčenia a vysokého príjmu UPF môže zosilniť poškodenie pečene. Na základe dôkazov zo štúdií by sa vo výživových usmerneniach malo zvážiť odporúčanie znížiť príjem ultra- -spracovaných potravín na minimum a implementovať opatrenia v oblasti verejného zdravotníctva.
Ultra-processed foods (UPF) are often characterized by low nutritional quality, high energy density, and the presence of additives, substances from packaging, and compounds formed during production, processing, and storage. UPF includes industrial formulations, and usually contains many ingredients. UPF includes sugar, oils, fats, salt, antioxidants, stabilizers and preservatives, food additives, and emulsifiers. Beyond the poor nutritional value, food processing promotes the creation of harmful compounds in the food. Food additives within UPF, promote inflammation, liver dysfunction, and metabolic syndrome, which are based on changes in the microbiome. Obesogens are environmental substances that alter the balance between energy intake and energy expenditure. Obesogens are a subset of environmental chemicals that act as endocrine disruptors affecting metabolic endpoints. The consumption of ultra-processed products has increased dramatically worldwide in the last decades. UPF contributed more than 60% of the mean energy intake. The average content of protein, fiber, vitamins, and calcium in the diet decreases significantly. The roducy contribution of UPFs, while carbohydrate, added sugar, and saturated fat contents increase. Ultra-processed foods contribute most of the added sugars in the western diet. Fructose – the most frequent obesogen, is associated with an increased risk of liver fibrosis. In recent years, there has been growing evidence about the harmful effect of UPF. UPF consumption is associated with metabolic alterations, the incidence of chronic diseases, and excess mortality. There is also evidence for an association with NAFLD, NASH, and fibrosis. High UPF consumption is related to harmful metabolic and hepatic parameters in NAFLD population. Furthermore, the combination of smoking and high UPF intake may amplify liver damage. The evidence from studies, a recommendation to reduce ultra-processed food intake to a minimum should be considered in nutritional guidelines and implemented by public health policy measures.
- MeSH
- lidé MeSH
- metabolický syndrom etiologie MeSH
- nealkoholová steatóza jater * etiologie MeSH
- průmyslově zpracované potraviny * škodlivé účinky MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy MeSH
Nealkoholová tuková choroba jater (NAFLD) se stala jedním z nejdiskutovanějších hepatologických témat posledních let díky své vysoké a nadále stoupající celosvětové prevalenci kopírující vysoký výskyt obezity a metabolického syndromu. Za poslední dvě dekády se významně rozšířily naše znalosti o patofyziologii NAFLD, které jsou klíčové pro pochopení této jednotky a pro identifikování účinné léčby a tím zmírnění socioekonomických důsledků spojených s morbiditou a mortalitou pacientů s NAFLD. Genetické rizikové faktory hrají v patofyziologii NAFLD významnou roli, dědičnost onemocnění je odhadována kolem 40 %. Celogenomovými asociačními studiemi byly identifikovány polymorfismy genů, které u svých nositelů významně zvyšují riziko vzniku NAFLD (například PNPLA3, TM6SF2, GCKR). Zlatým standardem diagnostiky je i nadále necílená biopsie jater. Jedná se o invazivní metodu, proto je snaha identifikovat spolehlivé a široce dostupné neinvazivní diagnostické metody. Řada slibných testů úzce souvisí právě s objasněním patofyziologie NAFLD (například specifické miRNA, sérový cytokeratin 18). V tomto přehledu shrnujeme aktuální pohled na patofyziologii NAFLD, včetně hlavních genetických rizikových faktorů, aktuálních diagnostických metod a stručně i léčebných možností onemocnění.
Nonalcoholic fatty liver disease (NAFLD) is nowadays one of the most discussed issues in hepatology due to its high and still raising prevalence reflecting the increasing prevalence of obesity and metabolic syndrome. In last two decades our knowledge of NAFLD pathophysiology expanded substantially. Understanding the pathophysiology is essential for identification of effective treatment, that is currently lacking, which could then reduce morbidity and mortality and eventually also mitigate the socioeconomical consequences of NAFLD. Genetic risk factors are crucial part of pathophysiology in NAFLD. Heritability of NAFLD is estimated to be around 40% and genome-wide association studies (GWAS) identified several single-nucleotide polymorphisms linked to the risk of NAFLD (e.g. PNPLA3, TM6SF2, GCKR). A gold standard for diagnosing NAFLD is a liver biopsy. Since liver biopsy is an invasive method a lot of effort is focused on finding reliable and accessible noninvasive diagnostic methods. Some of the promising methods are targeted to researched pathophysiological mechanisms (e.g. detecting the specific microRNA, serum cytokeratin-18). In this review we attempted to summarize the current knowledge about NAFLD pathophysiology, including the genetic risk factors, discuss the available diagnostic methods and also briefly cover the treatment options.
- MeSH
- genetická predispozice k nemoci MeSH
- inzulinová rezistence MeSH
- lidé MeSH
- metabolismus lipidů MeSH
- nealkoholová steatóza jater * diagnóza etiologie genetika MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy MeSH
Prevalence of non-alcoholic fatty liver disease (NAFLD) increases in line with obesity and type 2 diabetes, and there is no approved drug therapy. Polyunsaturated fatty acids of n-3 series (omega-3) are known for their hypolipidaemic and anti-inflammatory effects. Existing clinical trials suggest varying effectiveness of triacylglycerol- or ethyl ester-bound omega-3 in the treatment of NAFLD, without affecting advanced stages such as non-alcoholic steatohepatitis. Preclinical studies suggest that the lipid class used to supplement omega-3 may determine the extent and nature of their effects on metabolism. Phospholipids of marine origin represent an alternative source of omega-3. The aim of this review is to summarise the available evidence on the use of omega-3 phospholipids, primarily in obesity-related NAFLD, and to outline perspectives of their use in the prevention/treatment of NAFLD. A PubMed literature search was conducted in May 2021. In total, 1088 articles were identified, but based on selection criteria, 38 original papers were included in the review. Selected articles describing the potential mechanisms of action of omega-3 phospholipids have also been included. Preclinical evidence clearly indicates that omega-3 phospholipids have strong antisteatotic effects in the liver, which are stronger compared to omega-3 administered as triacylglycerols. Multiple mechanisms are likely involved in the overall antisteatotic effects, involving not only the liver but also adipose tissue and the gut. Robust preclinical evidence for strong antisteatotic effects of omega-3 phospholipids in the liver should be confirmed in clinical trials. Further research is needed on the possible effects of omega-3 phospholipids on advanced NAFLD.
- MeSH
- fosfolipidy MeSH
- kyseliny mastné omega-3 terapeutické užití MeSH
- lidé MeSH
- nealkoholová steatóza jater farmakoterapie etiologie MeSH
- obezita komplikace MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
Úvod: Nealkoholová tuková choroba pečene (NAFLD) je najrýchlejšie rastúcou príčinou ochorení pečene. Pri vzniku po transplantácii pečene (LT) pre iné indikácie nesie názov de novo NAFLD. Cieľ: Stanoviť incidenciu de novo NAFLD a jej asociáciu s BMI a fibrózou po LT v jednom transplantačnom centre. Metódy: Medzi januárom 2015 a decembrom 2020 sme realizovali propektívnu observačnú štúdiu u po sebe nasledujúcich pacientov po LT pre iné indikácie ako NAFLD. Sledovali sme demografické ukazovatele, etiológiu cirhózy pečene, MELD sklóre a Child Pugh skóre. Šesť, 12 a 24 mesiacov po LT sme hodnotili BMI, MR spektroskopiu (MRS, [≥ 5 % = NAFLD]) a MR elastografiu (MRE, [≥ 2,88 kPa = signifikantná fibróza, ≥ 3,54 kPa = pokročilá fibróza]). Výsledky: V sledovanom intervale sme do štúdie zaradili 164 pacientov po LT. Na základe vopred definovaných kritérií sme vylúčili 37 pacientov, do finálnej analýzy sme zaradili 104 pacientov s mediánom 53 rokov, 38 % žien, s mediánom MELD 15 bodov a BMI 25,4. Medián BMI – 6, 12 a 24 mes. po LT bol 25,5 vs. 27,3 (p = 0,032) a 26 vs. 27,8 (p = 0,062). MRS % – 6, 12 a 24 mes. po LT boli 4,5 oproti 5,1 (p = 0,2) a 4,4 oproti 7 (p = 0,012). Šesť, 12 a 24 mesiacov po LT sme signifikantnú fibrózu zistili u 27 %, 35 % a 46 % (p = 0,09) a pokročilú fibrózu u 4,7 %, 1,2 % a 15 % pacientov (p = 0,003). Závery: Počas dvoch rokov po LT pre iné indikácie ako NAFLD sme zaznamenali stúpajúci trend BMI, stúpajúci výskyt de novo NAFLD, signifikantnej a pokročilej fibrózy.
Background: Non-alcoholic fatty liver disease (NAFLD) is the fastest-growing cause of liver diseases; after liver transplantation (LT) for another indications bears the name de novo NAFLD. Aims: We set out to determine the incidence of de novo NAFLD and its associations with BMI and fibrosis in patients (pts) after LT at a single transplant centre. Methods: We organized an observational study of consecutive pts after LT for non-NAFLD causes between January 2015 and December 2020. At the baseline, we recorded the demographics, etiology of cirrhosis, MELD and Child-Pugh score; 6, 12 and 24 months after LT we recorded BMI, MR spectroscopy (MRS, [≥5% = NAFLD]) and MR Elastography (MRE, [≥2.88 kPa = significant fibrosis, ≥3.54 kPa = advanced fibrosis]). Results: We enrolled 164 pts after LT, excluded 37% for pre-defined criteria and analysed 104 pts with median age 53 years, 38% women, with median MELD 15 points and BMI 25.4. The median BMI – 6, 12 and 24 months after LT – were 25.5 vs 27.3 (P = 0.032) and 26 vs 27.8 (p = 0.062). MRS % – 6, 12, and 24 months after LT were 4.5 vs 5.1 (P = 0.2) and 4.4 vs 7 (P = 0.012). Significant fibrosis 6, 12 and 24 months after LT were found in 27%, 35% and 46%, respectively (P = 0.09), and advanced fibrosis in 4.7%, 1.2% and 15%, respectively (P = 0.003). Conclusions: Over 2 years after LT for various non-NAFLD indications, we identified rising BMI and rising incidence of de novo NAFLD and of significant and advanced fibrosis.
BACKGROUND: Non-alcoholic fatty liver disease (NAFLD), often associated with obesity and metabolic syndrome, manifests itself as steatosis, hepatic fibrosis, cirrhosis, or even end-stage liver disease. NAFLD causes inflammation, insulin resistance and cardiovascular complications. The current study aimed to evaluate the beneficial effects of bariatric surgery on biochemical parameters of hepatic functions in obese patients by comparing them before and one-year after the surgery. METHODS: A total of 72 morbidly obese patients underwent bariatric surgery between 2016 and 2018. The incidence of diabetes mellitus in this group was 29%, median body weight was 124.5 kg (109.0-140.0) and mean body mass index (BMI) was 44.38 ± 6.770 kg/m2. The used surgical procedures included gastric bypass, sleeve gastrectomy, laparoscopic gastric plication, and single anastomosis duodeno-ileal bypass-sleeve gastrectomy. Biochemical parameters including ALT/AST ratio (AAR), NAFLD fibrosis score (NFS), hepatic fibrosis index (FIB-4) and Fatty Liver Index (FLI) were evaluated in all patients at the time of surgery and one year after the intervention. RESULTS: Significant improvement after the intervention was observed in 64 patients. A significant reduction in body weight (P<0.0001), waist circumference (P<0.0001), and body mass index (P<0.0001) were observed. NAFLD liver fibrosis index changed significantly (P<0.0001), suggesting a trend of improvement from advanced fibrosis towards stages 0-2. The FIB-4 fibrosis index indicated significant improvement (P=0.0136). Besides, a significant decline in hepatic steatosis (P<0.0001) was observed after bariatric surgery as compared to the pre-surgery fatty liver conditions. CONCLUSION: Among the strategies to overcome NAFLD-associated impediments, bariatric surgery can be considered effective in reducing obesity and metabolic co-morbidities. TRIAL REGISTRATION: ClinicalTrials.gov (NCT04569396).
- MeSH
- bariatrická chirurgie * škodlivé účinky MeSH
- fibróza MeSH
- jaterní cirhóza komplikace MeSH
- játra MeSH
- lidé MeSH
- morbidní obezita * komplikace patologie chirurgie MeSH
- následné studie MeSH
- nealkoholová steatóza jater * etiologie chirurgie MeSH
- prospektivní studie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
