BACKGROUND: Early identification of those with NAFLD activity score ≥ 4 and significant fibrosis (≥F2) or at-risk metabolic dysfunction-associated steatohepatitis (MASH) is a priority as these patients are at increased risk for disease progression and may benefit from therapies. We developed and validated a highly specific metabolomics-driven score to identify at-risk MASH. METHODS: We included derivation (n = 790) and validation (n = 565) cohorts from international tertiary centers. Patients underwent laboratory assessment and liver biopsy for metabolic dysfunction-associated steatotic liver disease. Based on 12 lipids, body mass index, aspartate aminotransferase, and alanine aminotransferase, the MASEF score was developed to identify at-risk MASH and compared to the FibroScan-AST (FAST) score. We further compared the performance of a FIB-4 + MASEF algorithm to that of FIB-4 + liver stiffness measurements (LSM) by vibration-controlled transient elastography (VCTE). RESULTS: The diagnostic performance of the MASEF score showed an area under the receiver-operating characteristic curve, sensitivity, specificity, and positive and negative predictive values of 0.76 (95% CI 0.72-0.79), 0.69, 0.74, 0.53, and 0.85 in the derivation cohort, and 0.79 (95% CI 0.75-0.83), 0.78, 0.65, 0.48, and 0.88 in the validation cohort, while FibroScan-AST performance in the validation cohort was 0.74 (95% CI 0.68-0.79; p = 0.064), 0.58, 0.79, 0.67, and 0.73, respectively. FIB-4+MASEF showed similar overall performance compared with FIB-4 + LSM by VCTE ( p = 0.69) to identify at-risk MASH. CONCLUSION: MASEF is a promising diagnostic tool for the assessment of at-risk MASH. It could be used alternatively to LSM by VCTE in the algorithm that is currently recommended by several guidance publications.
Liver fibrosis is characterized by the activation of perivascular hepatic stellate cells (HSCs), the release of fibrogenic nanosized extracellular vesicles (EVs), and increased HSC glycolysis. Nevertheless, how glycolysis in HSCs coordinates fibrosis amplification through tissue zone-specific pathways remains elusive. Here, we demonstrate that HSC-specific genetic inhibition of glycolysis reduced liver fibrosis. Moreover, spatial transcriptomics revealed a fibrosis-mediated up-regulation of EV-related pathways in the liver pericentral zone, which was abrogated by glycolysis genetic inhibition. Mechanistically, glycolysis in HSCs up-regulated the expression of EV-related genes such as Ras-related protein Rab-31 (RAB31) by enhancing histone 3 lysine 9 acetylation on the promoter region, which increased EV release. Functionally, these glycolysis-dependent EVs increased fibrotic gene expression in recipient HSC. Furthermore, EVs derived from glycolysis-deficient mice abrogated liver fibrosis amplification in contrast to glycolysis-competent mouse EVs. In summary, glycolysis in HSCs amplifies liver fibrosis by promoting fibrogenic EV release in the hepatic pericentral zone, which represents a potential therapeutic target.
- MeSH
- extracelulární vezikuly * metabolismus MeSH
- glykolýza * MeSH
- jaterní cirhóza * metabolismus patologie genetika MeSH
- jaterní hvězdicovité buňky * metabolismus patologie MeSH
- játra metabolismus patologie MeSH
- lidé MeSH
- modely nemocí na zvířatech MeSH
- myši inbrední C57BL MeSH
- myši MeSH
- Rab proteiny vázající GTP metabolismus genetika MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
A combination of liver and heart dysfunction worsens the prognosis of human survival. The aim of this study was to investigate whether empagliflozin (a sodium-glucose transporter-2 inhibitor) has beneficial effects not only on cardiac and renal function but also on hepatic function. Adult (6-month-old) male spontaneously hypertensive rats (SHR) were fed a high-fat diet (60% fat) for four months to induce hepatic steatosis and mild heart failure. For the last two months, the rats were treated with empagliflozin (empa, 10 mg.kg-1.day-1 in the drinking water). Renal function and oral glucose tolerance test were analyzed in control (n=8), high-fat diet (SHR+HF, n=10), and empagliflozin-treated (SHR+HF+empa, n=9) SHR throughout the study. Metabolic parameters and echocardiography were evaluated at the end of the experiment. High-fat diet feeding increased body weight and visceral adiposity, liver triglyceride and cholesterol concentrations, and worsened glucose tolerance. Although the high-fat diet did not affect renal function, it significantly worsened cardiac function in a subset of SHR rats. Empagliflozin reduced body weight gain but not visceral fat deposition. It also improved glucose sensitivity and several metabolic parameters (plasma insulin, uric acid, and HDL cholesterol). In the liver, empagliflozin reduced ectopic lipid accumulation, lipoperoxidation, inflammation and pro-inflammatory HETEs, while increasing anti-inflammatory EETs. In addition, empagliflozin improved cardiac function (systolic, diastolic and pumping) independent of blood pressure. The results of our study suggest that hepatoprotection plays a decisive role in the beneficial effects of empagliflozin in preventing the progression of cardiac dysfunction induced by high-fat diet feeding.
- MeSH
- benzhydrylové sloučeniny * farmakologie MeSH
- dieta s vysokým obsahem tuků * škodlivé účinky MeSH
- glifloziny * farmakologie MeSH
- glukosidy * farmakologie MeSH
- hypertenze farmakoterapie MeSH
- játra * účinky léků metabolismus patologie MeSH
- kardiotonika farmakologie MeSH
- krevní glukóza metabolismus účinky léků MeSH
- krevní tlak účinky léků MeSH
- krysa rodu rattus MeSH
- ledviny účinky léků metabolismus patologie MeSH
- ochranné látky farmakologie MeSH
- potkani inbrední SHR * MeSH
- ztučnělá játra prevence a kontrola farmakoterapie MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Once absorbed through lung tissues, smog-soluble substances are readily distributable throughout organ system reaching approximately all cells perturbing the subcellular events at mitochondrial level. The present study aimed to detect the deleterious impact of smog-containing materials on mitochondrial and thereby serum pyruvate/lactate levels coincidentally with liver proper functionality. To do so, chronic smokers were recruited and sub-classified into groups based on chronicity of smoking; control (never smoked), G1=smokers for up to 5 years, G2=smokers for up to 10 years, and G3=smokers for up to 15 years. Serum samples were collected and stored for later on analysis. Results have confirmed that serum pyruvate/lactate and liver enzymes modulated reciprocally with smoking compared to control. The results also confirmed that liver enzymes were strongly modulated, GOT elevated while GPT reduced in a way reciprocal to chronicity, while ALP elevated in first few years of smoking in G1 group compared to other groups or control group. Serum albumin was significantly elevated in studied groups compared to control group with no changes appeared in total plasma protein and the bilirubin levels were higher in G2 group compared to G1 or G3 or control groups. Serum lactate and to certain extent serum pyruvate were also significantly perturbed showing higher levels in smokers compared to control or junior smokers. In conclusion, mitochondrial subcellular machinery are strongly affected following smoking indicated by serum pyruvate/lactate measurement and this in turn strongly affect liver functionality as an important organ involved in pyruvate-lactate demarcation and pertaining to the liver functionality indicated by bilirubin and total plasma protein or albumin measurements.
- MeSH
- dospělí MeSH
- játra * enzymologie patologie účinky léků MeSH
- kouření * krev patologie škodlivé účinky MeSH
- lidé středního věku MeSH
- lidé MeSH
- mitochondrie patologie účinky léků MeSH
- mladý dospělý MeSH
- sérum chemie enzymologie účinky léků MeSH
- statistika jako téma MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- Publikační typ
- klinická studie MeSH
BACKGROUND AND AIMS: Schistosoma mansoni infection is one of the worldwide leading causes of liver fibrosis and portal hypertension. The objective of this study was to evaluate whether polyhydroxylated bile acids (BAs), known to protect mice from the development of acquired cholestatic liver injury, counteract S. mansoni-induced inflammation and fibrosis. METHODS: Adult FVB/N wild type (WT) and Abcb11/Bsep-/- mice were infected with either 25 or 50 S. mansoni cercariae. Eight weeks post infection, effects on liver histology, serum biochemistry, gene expression profile of proinflammatory cytokines and fibrotic markers, hepatic hydroxyproline content and FACS analysis were performed. RESULTS: Bsep-/- mice infected with S. mansoni showed significantly less hepatic inflammation and tendentially less fibrosis compared to infected WT mice. Despite elevated alanine aminotransferase, aspartate aminotransferase and alkaline phosphatase levels in infected Bsep-/- mice, inflammatory cells such as M2 macrophages and Mac-2/galectin-3+ cells were reduced in these animals. Accordingly, mRNA-expression levels of anti-inflammatory cytokines (IL-4 and IL-13) were increased in Bsep-/- mice upon infection. Furthermore, infected Bsep-/- mice exhibited decreased hepatic egg load and parasite fecundity, consequently affecting the worm reproduction rate. This outcome could arise from elevated serum BA levels and lower blood pH in Bsep-/- mice. CONCLUSIONS: The loss of Bsep and the resulting changes in bile acid composition and blood pH are associated with the reduction of parasite fecundity, thus attenuating the development of S. mansoni-induced hepatic inflammation and fibrosis.
- MeSH
- cytokiny metabolismus MeSH
- fertilita MeSH
- jaterní cirhóza prevence a kontrola etiologie MeSH
- játra patologie MeSH
- myši MeSH
- paraziti * MeSH
- Schistosoma mansoni MeSH
- schistosomiasis mansoni * komplikace MeSH
- zánět patologie MeSH
- žlučové kyseliny a soli metabolismus MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
BACKGROUND: Solitary fibrous tumour of the liver is a rare mesenchymal tumour, occurring usually in women and with various symptomatology. The symptoms mostly result from pressure of the tumour mass on surrounding organs. Due to unknown biological behaviour and gradual increase of tumour volume, surgical resection is mostly the preferred treatment option. CASE: A 75-year-old woman with a history of endometrial cancer, presenting with an incidental finding of a liver mass, initially considered of infectious origin (either echinococcosis or cysticercosis). Further diagnostics did not clarify the aetiology, a surgical revision was rejected at the time. The subsequent follow-up was interrupted by the development of symptoms of gastrointestinal and renal obstruction, which led to a complete surgical removal of the tumour, sized 30 × 25 × 20 cm. A histopathological examination showed a CD34 and STAT6 positivity, leading to a diagnosis of a giant solitary fibrous tumour of the liver. The patient recovered well, without any signs of recurrence. CONCLUSION: The solitary fibrous tumour of the liver is a rare, often incidental finding. It is considered benign, but malignant growth was also reported. A gradual growth mostly results in pressure on other organs. A surgical resection is the treatment of choice. Transarterial embolization is another treatment possibility. Due to indeterminate malignant potential a regular follow-up is necessary, including tumour markers and imaging methods.
- MeSH
- játra patologie MeSH
- lidé MeSH
- nádorové biomarkery MeSH
- senioři MeSH
- solitární fibrózní tumory * diagnóza chirurgie patologie MeSH
- transkripční faktor STAT6 MeSH
- Check Tag
- lidé MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- kazuistiky MeSH
Východiska: Adenomatóza jater je velmi vzácné onemocnění. V literatuře se nám podařilo najít pouze dvě kazuistiky dokumentující obraz tohoto onemocnění na PET/CT s 18F-fludeoxyglukózou (FDG-PET/CT). Případ: U 52leté pacientky s necharakteristickými bolestmi v epigastriu bez onkologické anamnézy s negativními onkomarkery a bez klinických známek generalizované neoplazie byla při sonografii zachycena četná jaterní ložiska. Doplněné MR vyšetření vyjádřilo podezření na metastatický původ ložisek a bylo indikováno FDG-PET/CT s cílem identifikovat primární tumor a posoudit rozsah onemocnění. Při celotělovém FDG-PET/CT vyšetření se v játrech zobrazila mnohočetná (> 20) výrazně hypermetabolická ložiska velikosti 3–20 mm v průměru dosahující relativní akumulace SUVBWmax = 13 spolu s několika ametabolickými cystami; jinde v rozsahu vyšetření ložiskově patologicky zvýšená metabolická aktivita nebyla patrná. Následně pacientka podstoupila biopsii cílenou na jedno z hypermetabolických jaterních ložisek s nálezem HNF 1A inaktivované varianty hepatocelulárního adenomu; maligní primární ani sekundární bujení nebylo prokázáno. S ohledem na histologický nález a velký počet jaterních ložisek byla jako konečná diagnóza stanovena adenomatóza jater. Pacientka zůstává v trvalém sledování. Závěr: Adenomatózní ložiska byla při FDG-PET/CT vyšetření výrazně hypermetabolická a touto metodou je nebylo možno odlišit od nádorových metastáz. Náš nález je v souladu s dalšími dvěma pozorováními, která se nám podařilo dohledat v literatuře.
Background: Liver adenomatosis is a very rare disease. In the literature, we were able to find only two case reports documenting the appearance of this disease on PET/CT with 18F-fludeoxyglucose (FDG-PET/CT). Case: Numerous liver foci were detected during sonography in a 52-year-old female patient with uncharacteristic pain in the epigastrium without oncological history, with negative oncomarkers and without clinical signs of generalized neoplasia. Complementary MRI examination expressed the suspicion of metastatic origin of the foci, and FDG-PET/CT was indicated in order to identify the primary tumour and assess the extent of the disease. A whole-body FDG-PET/CT examination showed multiple (> 20) markedly hypermetabolic liver foci with 3–20 mm in diameter, reaching a relative accumulation of SUVBWmax = 13, together with several ametabolic cysts; elsewhere in the scope of the examination, focally pathologically increased metabolic activity was not evident. Subsequently, the patient underwent a biopsy targeted at one of the hypermetabolic liver foci with the finding of HNF 1A inactivated variant of hepatocellular adenoma; primary or secondary malignancy was not demonstrated. Considering the histological findings and the large number of liver foci, the final diagnosis of liver adenomatosis was set. The patient remains under continuous observation. Conclusion: Adenomatous foci were markedly hypermetabolic during FDG-PET/CT examination and could not be distinguished from tumour metastases by this method. Our finding is consistent with two other observations we were able to find in the literature.
- Klíčová slova
- adenomatóza,
- MeSH
- hepatocelulární karcinom diagnóza MeSH
- játra * diagnostické zobrazování patologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- PET/CT metody MeSH
- pozitronová emisní tomografie metody MeSH
- výsledek terapie MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- kazuistiky MeSH
Background and objectives: Recently, rapid progress has been made in the development of noninvasive methods for liver fibrosis assessment. The study aimed to assess the correlation between LSM and serum fibrosis markers to identify patients with advanced liver fibrosis in daily clinical practice. Methods: Between 2017 and 2019, 89 patients with chronic liver disease of various etiology, 58 males and 31 females, were enrolled in the study and underwent ultrasound examination, vibration-controlled transient elastography (VCTE), AST to Platelet Ratio Index (APRI score), Fibrosis-4 (FIB-4) score, and enhanced liver fibrosis (ELF) test. Results: The diagnoses were as follows: NAFLD (30.3%), HCV (24.3%), HBV (13.1%), ALD (10.1%), other (7.8%). Their median age was 49 (21-79), and their median BMI was 27.5 (18.4-39.5). The median liver stiffness measurement (LSM) was 6.7 kPa (2.9-54.2 kPa), the median of the ELF test was 9.0 (7.3-12.6), and the median APRI was 0.40 (0.13-3.13). Advanced fibrosis assessed by LSM was present in 18/89 (20.2%) patients. The LSM values correlated with the ELF test results (r2 = 0.31, p < 0.0001), with the APRI score (r2 = 0.23, p < 0.0001), the age of the patients (r2 = 0.14, p < 0.001), and with the FIB-4 values (r2 = 0.58, p < 0.0001). The ELF test values correlated with the APRI score (r2 = 0.14, p = 0.001), the age (r2 = 0.38, p < 0.0001), and the FIB-4 (r2 = 0.34, p < 0.0001). By determining the confidence intervals of the linear model, we proved that patients younger than 38.1 years have a 95% probability of absence of advanced liver fibrosis when assessed by VCTE. Conclusions: We identified APRI and FIB-4 as simple tools for screening liver disease in primary care in an unselected population of patients. The results also showed that individuals younger than 38.1 years had a negligible risk of advanced liver fibrosis.
- MeSH
- biologické markery MeSH
- biopsie metody MeSH
- elastografie * škodlivé účinky metody MeSH
- fibróza MeSH
- jaterní cirhóza diagnostické zobrazování etiologie MeSH
- játra patologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
Úvod: Polycystická autozomálne recesívna choroba obličiek (ARPCHO) je raritná, značne fenotypovo variabilná primárna cíliopatia. Poškodenie obličiek a pečene sú typickými prejavmi a prognóza ochorenia závisí od ich progresie v čase. Hlavným extrarenálnym prejavom je fibrocystická prestavba pečene, ktorá sa prejavuje intrahepatálnou portálnouhypertenziou a cholangitídou. Metódy: Retrospektívne zhodnotenie výskytu a vývoja hepatobiliárnych prejavov ochorenia. Výsledky: Do súboru bolo zaradených 8 detí s polycystickou autozomálne recesívnou chorobou obličiek. Poškodenie obličiek a hypertenzia boli prítomné u všetkých detí v súbore. Hepatobiliárne prejavy boli popísané u 5 detí (62,5 %). Trombocytopénia predchádzala splenomegáliu v časovom období jeden rok. Súčasťou výsledkov sú aj tri kazuistiky. Záver: Pacienti s ARPCHO by mali byť cielene vyšetrení so zameraním na posúdenie hepatálnych prejavov ochorenia. #938486
Introduction: Autosomal recessive polycystic kidney disease (ARPKD) is a rare, phenotypically variable primary ciliopathy. Kidney and liver damage are typical manifestations, and the prognosis of the disease depends on their progression over time. The main extrarenal manifestation is fibrocystic rebuilding of the liver, which is manifested by intrahepatic portal hypertension and cholangitis. Methods: The aim of the retrospective study was to evaluate the incidence and development hepatobiliary manifestations. Results: Eight children with polycystic autosomal recessive kidney disease were included in the group. Renal damage and hypertension were present in all children. Hepatobiliary manifestations were described in five children (62.5%). Thrombocytopenia preceded splenomegaly by one year. The results also include three case reports. Conclusion: Patients with ARPKD should be examined with a focus on the presence of hepatic manifestations of the disease.
Úvod: Distribuční šíře objemu erytrocytů (RDW) popisuje různorodost v objemech erytrocytů a je součástí celkového krevního obrazu. Nedávné studieovšem ukázaly na vztah mezi RDW a zvýšenou úmrtností u mnoha klinických stavů a zjistily, že vysoký RDW navyšuje pravděpodobnost úmrtí z jakýchkoli příčin. Některé studie také popisují vztah mezi hodnotami RDW a závažností jaterních onemocnění. Byla popsána přímá úměrnost mezi hodnotami RDW a MELD skóre u různých stadií infekce virem hepatitidy B. Zároveň s tím se hodnota RDW zvyšovala úměrně zhoršujícímu se stupni Child-Pugh skóre jaterní cirhózy. Metoda: Tato studie zkoumala klinické využití hodnot RDW pro určování přítomnosti jaterní fibrózy u dětí s chronickým onemocněním jater. Provedli jsme retrospektivní studii zahrnující 413 pacientů. Posbírali jsme demografická, klinická a laboratorní data a histologické nálezy stadií fibrózy z lékařských záznamů a analyzovali jsme je pomocí SPSS. Výsledky: Naše studie neukázala významnou korelaci mezi hodnotami RDW a stupněm jaterní fibrózy. Naproti tomu asociace mezi RDW a zhoršujícím se Child-Pugh skóre, APRI, RPR, FIB-4, a PELD skóre významná je. Závěr: Nenašli jsme žádný vztah mezi hodnotami RDW a stadiem jaterní fibrózy.
Background: Red cell distribution width (RDW) demonstrates the heterogeneity of red cell volume and is a component of the complete blood count. Recent studies, however, have reported that RDW is associated with increased mortality in many clinical conditions and found that high RDW is associated with an increase in all-cause mortality. Some studies have also reported the association between RDW values and the severity of liver diseases. It has been claimed that elevated RDW values positively correlate with MELD scores in different disease statuses of hepatitis B virus infection. In addition, RDW increased with the worsening of Child-Pugh grade in hepatic cirrhosis. Methods: This study investigated the clinical utility of RDW values for indicating the presence of liver fibrosis in children with chronic liver diseases. We have conducted a retrospective study on 413 patients. We collected demographic, clinical, and laboratory data and pathologic reports of the liver fibrosis stage from the medical record and analyzed them with SPSS. Result: In our study, there was no significant association between the values of RDW and different stages of fibrosis, but the association between the values of RDW and worsening of Child-Pugh score, APRI, RPR, FIB-4, and PELD score was significant. Conclusion: We cannot find any correlation between RDW and the stage of liver fibrosis.
