INTRODUCTION AND OBJECTIVES: Hepatocellular carcinoma (HCC) represents one of the most common cancers worldwide. A considerable proportion of HCC is caused by cirrhosis related to metabolic dysfunction-associated steatohepatitis (MASH). Due to the increasing prevalence of metabolic syndrome, it is estimated that MASH-related HCC will become the most prevalent etiology of HCC. Currently, HCC screening is based on liver ultrasonography; however, the sensitivity of ultrasonography for early HCC stages in obese patients only reaches 23 %. To date, no studied biomarker shows sufficient efficacy for screening purposes. Nevertheless, the usage of spectroscopic methods offers a new perspective, as its potential use would provide cheap, fast analysis of samples such as blood plasma. MATERIAL AND METHODS: We employed a combination of conventional and chiroptical spectroscopic methods to study differences between the blood plasma of obese cirrhotic patients with and without HCC. We included 20 subjects with HCC and 17 without evidence of liver cancer, all of them with body mass index ≥ 30. RESULTS: Sensitivities and specificities reached values as follows: 0.780 and 0.905 for infrared spectroscopy, 0.700 and 0.767 for Raman spectroscopy, 0.840 and 0.743 for electronic circular dichroism, and 0.805 and 0.923 for Raman optical activity. The final combined classification model based on all spectroscopic methods reached a sensitivity of 0.810 and a specificity of 0.857, with the highest area under the receiver operating characteristic curve among all models (0.961). CONCLUSIONS: We suggest that this approach can be used effectively as a diagnostic tool in patients who are not examinable by liver ultrasonography. CLINICAL TRIAL REGISTRATION: NCT04221347.
- MeSH
- časná detekce nádoru * metody MeSH
- dospělí MeSH
- hepatocelulární karcinom * krev diagnóza diagnostické zobrazování MeSH
- index tělesné hmotnosti MeSH
- jaterní cirhóza krev komplikace diagnóza MeSH
- lidé středního věku MeSH
- lidé MeSH
- nádorové biomarkery krev MeSH
- nádory jater * krev diagnóza diagnostické zobrazování MeSH
- obezita * komplikace krev MeSH
- prediktivní hodnota testů MeSH
- Ramanova spektroskopie MeSH
- ROC křivka MeSH
- senioři MeSH
- studie případů a kontrol MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- pozorovací studie MeSH
Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related deaths in the world. HCC is often diagnosed late because patients with early-stage cancer have no apparent symptoms. Therefore, it is desirable to find a reliable method for an early diagnosis based on the detection of metabolites - biomarkers, that can be detected in the early stages of the disease. Untargeted metabolomics is often used as a tool to find a suitable biomarker for several diseases. In this work, untargeted metabolomics was performed on blood plasma samples of HCC patients and compared with healthy individuals and patients with liver cirrhosis. A combination of liquid chromatography and high-resolution mass spectrometry was used as an analytical method. More than a thousand peaks were detected in the blood plasma samples, from which mainly amino acids, carboxylic acids, lipids, and their derivatives were evaluated as potential biomarkers. The data obtained were statistically processed using the analysis of variance, correlation analysis, and principal component analysis.
- MeSH
- analýza hlavních komponent MeSH
- chromatografie kapalinová metody MeSH
- dospělí MeSH
- hepatocelulární karcinom * krev MeSH
- hmotnostní spektrometrie metody MeSH
- jaterní cirhóza krev diagnóza MeSH
- lidé středního věku MeSH
- lidé MeSH
- metabolomika * metody MeSH
- nádorové biomarkery * krev MeSH
- nádory jater * krev MeSH
- senioři MeSH
- studie případů a kontrol MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
BACKGROUND & AIMS: Patients with decompensated cirrhosis suffer from recurrent infections and inadequate responses to prophylactic vaccinations. However, many patients present with hypergammaglobulinemia (HGG), indicating a sustained ability to generate antibody responses. As follicular T helper (Tfh) cells are central facilitators of humoral immunity, we hypothesized that Tfh cell responses may be altered in advanced liver disease and we aimed to identify the mechanisms underlying any such alterations. METHODS: Tfh, regulatory T (Treg) cells, B cells, circulating cytokines and immunoglobulins were analyzed in cohorts of patients with compensated (n = 37) and decompensated cirrhosis (n = 82) and in non-cirrhotic controls (n = 45). Intrahepatic T cells were analyzed in 8 decompensated patients. The influence of IL-2 on Tfh cell function was evaluated in vitro, including Tfh cell cloning and T cell-B cell co-cultures with clones and primary tonsil-derived Tfh cells. RESULTS: Tfh cell frequencies were reduced in patients with decompensated cirrhosis, with phenotypic signatures indicative of increased IL-2 signaling. Soluble IL-2 receptor (sCD25) was elevated in these patients and CD4 T cells were more responsive to IL-2 signaling, as characterized by STAT5 phosphorylation. IL-2 exposure in vitro diminished the Tfh phenotype and resulted in impaired Tfh helper function in co-culture experiments with naïve B cells. Tfh cells were barely detectable in cirrhotic livers. IL-2 signatures on Tfh cells in decompensated patients correlated with immunoglobulin levels, which were found to be associated with improved survival. CONCLUSIONS: Tfh cell impairment represents a previously underestimated feature of cirrhosis-associated immune dysfunction that is driven by IL-2. The presence of HGG in decompensated patients predicts an intact Tfh cell compartment and is associated with a favorable outcome. LAY SUMMARY: Patients with advanced cirrhosis often fail to generate protective immunity after prophylactic vaccinations and suffer from recurring infections that are associated with high mortality. Follicular T helper (Tfh) cells are specialized CD4 T cells that enable the emergence of antibody responses against microbial pathogens. This report demonstrates that Tfh cells are impaired in patients with advanced cirrhosis due to interleukin-2 signaling, a cytokine that is known to impair the generation of Tfh cells.
- MeSH
- B-lymfocyty imunologie MeSH
- dospělí MeSH
- folikulární pomocné T-buňky imunologie MeSH
- hypergamaglobulinemie komplikace MeSH
- imunoglobulin G krev MeSH
- interleukin-2 krev MeSH
- jaterní cirhóza krev komplikace imunologie MeSH
- kohortové studie MeSH
- kokultivační techniky MeSH
- kultivované buňky MeSH
- lidé středního věku MeSH
- lidé MeSH
- nádorové supresorové proteiny metabolismus MeSH
- prognóza MeSH
- průřezové studie MeSH
- regulační T-lymfocyty imunologie MeSH
- senioři MeSH
- signální transdukce imunologie MeSH
- transkripční faktor STAT5 metabolismus 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
Nonalcoholic steatohepatitis (NASH) is characterized by hepatic steatosis with inflammation and fibrosis. Membrane endoglin (Eng) expression is shown to participate in fibrosis, and plasma concentrations of soluble endoglin (sEng) are increased in patients with hypercholesterolemia and type 2 diabetes mellitus. We hypothesize that NASH increases both hepatic Eng expression and sEng in blood and that high levels of sEng modulate cholesterol and bile acid (BA) metabolism and affect NASH progression. Three-month-old transgenic male mice overexpressing human sEng and their wild type littermates are fed for six months with either a high-saturated fat, high-fructose high-cholesterol (FFC) diet or a chow diet. Evaluation of NASH, Liquid chromatography-mass spectrometry (LC/MS) analysis of BA, hepatic expression of Eng, inflammation, fibrosis markers, enzymes and transporters involved in hepatic cholesterol and BA metabolism are assessed using Real-Time Quantitative Reverse Transcription Polymerase Chain reaction (qRT-PCR) and Western blot. The FFC diet significantly increases mouse sEng levels and increases hepatic expression of Eng. High levels of human sEng results in increased hepatic deposition of cholesterol due to reduced conversion into BA, as well as redirects the metabolism of triglycerides (TAG) to its accumulation in the liver, via reduced TAG elimination by β-oxidation combined with reduced hepatic efflux. We propose that sEng might be a biomarker of NASH development, and the presence of high levels of sEng might support NASH aggravation by impairing the essential defensive mechanism protecting NASH liver against excessive TAG and cholesterol accumulation, suggesting the importance of high sEng levels in patients prone to develop NASH.
- MeSH
- alkalická fosfatasa metabolismus MeSH
- aspartátaminotransferasy metabolismus MeSH
- biologické markery krev metabolismus MeSH
- biologické modely MeSH
- cholesterol krev metabolismus MeSH
- dieta s vysokým obsahem tuků MeSH
- endoglin krev metabolismus MeSH
- fruktosa MeSH
- jaterní cirhóza krev komplikace patologie MeSH
- játra metabolismus patologie MeSH
- lidé MeSH
- modely nemocí na zvířatech MeSH
- myši MeSH
- nealkoholová steatóza jater krev komplikace metabolismus MeSH
- oxidační stres MeSH
- rozpustnost MeSH
- triglyceridy metabolismus MeSH
- zánět patologie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
BACKGROUND: The roles of sphingosine in various cancers have not been fully investigated. Our aim was to identify the relationship between serum sphingosine and the risk of hepatocellular carcinoma (HCC). METHODS: Serum sphingosine in 34 normal people and 73 HCC patients were reviewed retrospectively. Receiver operating characteristic curve analysis was performed to determine the cut-off values of sphingosine in the serum. Chi-square test, t test and regression analysis were used to test the association between serum sphingosine and individual clinicopathologic parameters. RESULTS: Serum sphingosine was higher in HCC patients (155.91±331.5 ng/mL) with normal persons as the control (30.92±29.4 ng/mL). The sphingosine threshold according to ROC curve was set at 22.5 ng/mL with a sensitivity of 74%, and a specificity of 55.9%. Meanwhile, sphingosine in HCC patients with abnormal albumin was significantly higher than that in patients with normal albumin (t=2.452, P=0.019). When HCC patients were divided into two groups serum sphingosine was negatively associated with albumin in HCC patients (χ2=4.469, P=0.035). Moreover, the logistic regression analysis showed that large tumor size (P=0.018, OR=0.13) and a low albumin (P=0.005, OR=8.856) were two independent risk factors for serum sphingosine upregulation. High AFP coupled with high serum sphingosine, high sphingosine and high AFP respectively were found in 91.2%, 75.4%, 73% of the HCC patients. CONCLUSIONS: These results suggest that serum sphingosine could be treated as a marker for the risk of HCC. AFP and sphingosine in the serum could be used together for HCC diagnosis.
- MeSH
- alfa-fetoproteiny metabolismus MeSH
- hepatocelulární karcinom krev komplikace diagnóza patologie MeSH
- jaterní cirhóza krev komplikace MeSH
- lidé středního věku MeSH
- lidé MeSH
- mnohočetné primární nádory krev komplikace diagnóza MeSH
- nádory jater krev komplikace diagnóza patologie MeSH
- riziko MeSH
- ROC křivka MeSH
- sérový albumin metabolismus MeSH
- sfingosin krev MeSH
- studie případů a kontrol MeSH
- tumor burden MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
BACKGROUND: Cholesterol is derived via de novo synthesis and dietary absorption. Both processes can be monitored by determination of non-cholesterol sterol concentrations (lathosterol for synthesis; sitosterol and campesterol for absorption). The hypocholesterolemia that occurs during acute illness is a result of a multifactorial inability to compensate for the increased needs for this metabolite. The aim of this study was to examine the plasma cholesterol profile and both processes of cholesterol acquisition during acute upper gastrointestinal haemorrhage with emphasis on liver cirrhosis. MATERIAL AND METHODS: Thirty five patients with acute upper gastrointestinal bleeding (cirrhosis n=14, non-cirrhosis n=21) were evaluated over a 6 day period. The control cohort consisted of 100 blood donors. Serum concentrations of total, LDL (low-density lipoprotein) and HDL (high-density lipoprotein) cholesterol were measured enzymatically. Sterol concentrations were analysed using gas chromatography, data were statistically analysed. RESULTS: In all patients, we found lower plasma levels of total cholesterol (P Conclusion: Our results showed substantial abnormalities in the cholesterol plasma profile including both the processes of cholesterol acquisition in patients with upper acute gastrointestinal bleeding. The patients with or without liver cirrhosis had similar trends in cholesterol plasma levels. Depression of cholesterol synthesis was, however, prolonged in the cirrhotic group and the data also suggest a different phytosterol metabolism.
- MeSH
- akutní nemoc MeSH
- cholesterol metabolismus MeSH
- dyslipidemie krev etiologie MeSH
- fytosteroly metabolismus MeSH
- gastrointestinální krvácení krev MeSH
- HDL-cholesterol metabolismus MeSH
- jaterní cirhóza krev MeSH
- LDL-cholesterol metabolismus MeSH
- lidé středního věku MeSH
- lidé MeSH
- studie případů a kontrol MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- srovnávací studie MeSH
AIM: The aim of this study was to evaluate the clinical contribution of protein induced by vitamin K absence (PIVKA-II) for hepatocellular carcinoma (HCC) diagnostics and compare it with alpha-foetoprotein (AFP), a routinely used tumour marker. MATERIALS AND METHODS: A total of 332 participants were enrolled in this study: 64 with HCC, 48 with liver metastases of colorectal cancer origin, 42 with liver cirrhosis and 178 healthy individuals. Serum levels of PIVKA-II were measured using the chemiluminescent assay of the Architect 1000i System (Abbott, USA) and AFP levels using the chemiluminescent assay by DxI 800 (Beckman Coulter, USA). RESULTS: PIVKA-II achieved better clinical sensitivity than AFP and the difference in this sensitivity was statistically significant. PIVKA-II achieved the best sensitivity (96.9%) in distinguishing between the HCC and control groups with the proposed cut-off value of 60 mAU/ml. CONCLUSION: Our recommendation is for addition of PIVKA-II to the routine panel of HCC tumour markers.
- MeSH
- biologické markery krev MeSH
- diferenciální diagnóza MeSH
- dospělí MeSH
- hepatocelulární karcinom krev genetika patologie MeSH
- jaterní cirhóza krev genetika patologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- nádorové biomarkery krev MeSH
- nádory jater krev genetika patologie MeSH
- pilotní projekty MeSH
- proteinové prekurzory krev genetika MeSH
- protrombin genetika MeSH
- senioři nad 80 let MeSH
- senioři 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
The aim of the study was to assess serum hyaluronic acid (HA) and transforming growth factor beta 1 (TGF-β1) concentrations: 1) to differentiate hepatic fibrosis from other forms of liver disease, and 2) for the non-invasive staging of canine liver fibrosis. We also evaluated the association between serum HA concentration and the size of the shunt vessel as an indirect marker of decreased liver clearance in patients with single congenital vascular anomaly. Forty-one healthy client-owned dogs and forty dogs diagnosed with hepatobiliary disease were enrolled in the prospective study. Patients were divided into 4 subgroups: 1) congenital portosystemic shunts (CPSS); 2) parenchymal diseases (a. mild and moderate fibrosis, b. advanced fibrosis and cirrhosis); 3) hepatic neoplasia; 4) biliary tract disorders based on thorough clinical, ultrasound and histopathological examination. Serum HA and TGF-β1 concentrations were measured using ELISA. The HA concentration was significantly increased in patients with advanced liver fibrosis/cirrhosis (P < 0.001) and CPSS (P < 0.001) compared to healthy dogs. Using a cut-off HA concentration of 135.94 ng/ml, the sensitivity and specificity for diagnosis for advanced liver fibrosis/cirrhosis was 100% (95% CI, 50.6–100) and 90.8% (95% CI, 81.6–95.7), respectively. The TGF-β1 levels did not significantly differ among groups (P = 0.180). Negligible correlation was found between serum HA concentration and the size of portosystemic shunt vessel (rs = 0.07; P = 0.831). These findings suggest that serum HA concentration is a potential non-invasive biomarker for advanced liver fibrosis and/or cirrhosis in dogs. The utility of measuring serum concentration of TGF-β1 for diagnosing canine liver fibrosis was not supported.
- MeSH
- biologické markery krev MeSH
- biopsie metody MeSH
- chronická hepatitida krev veterinární MeSH
- diferenciální diagnóza MeSH
- ELISA MeSH
- jaterní cirhóza diagnóza krev veterinární MeSH
- kyselina hyaluronová * krev MeSH
- laparoskopie metody MeSH
- nemoci jater diagnóza klasifikace krev veterinární MeSH
- nemoci trávicího systému diagnóza klasifikace krev veterinární MeSH
- prospektivní studie MeSH
- psi MeSH
- ROC křivka MeSH
- senzitivita a specificita MeSH
- statistika jako téma MeSH
- transformující růstový faktor beta1 * krev MeSH
- Check Tag
- psi MeSH
- Publikační typ
- práce podpořená grantem MeSH
Prognóza, péče a terapie chronických jaterních onemocnění značně závisí na stupni a rychlosti progrese jaterní fibrózy. Dlouhá léta bylo zlatým standardem pro vyšetření pokročilosti jaterní fibrózy histologické hodnocení. Jaterní biopsie je metoda invazivní, její sériové opakování u jednoho nemocného za účelem posouzení progrese onemocnění naráží na celou řadu problémů, vč. etických. Mnoho úsilí proto bylo věnováno nalezení neinvazivního postupu, který by většinu těchto problémů odstranil. Jako velice nadějné se v posledních letech ukazují metody hodnotící jaterní elasticitu. Tyto tzv. elastografické metody využívají střižných vln šířících se jaterní tkání. Samotný princip elastografie je znám již řadu desítek let, ale až zhruba v posledním 10letí dochází k rozvoji přístrojů schopných tento princip přenést do diagnostiky v hepatologii.
Prognosis, care, and treatment of chronic liver diseases greatly depend on the degree and rate of progression of hepatic fibrosis. For many years, histological evaluation has been the gold standard for measuring the advancement of liver fibrosis. Liver biopsy is an invasive method, the serial repetition of which in a single patient raises a number of problematic issues, including ethical ones. Therefore, much effort has been devoted to finding a non-invasive procedure. A very promising method in recent years involves the evaluation of liver elasticity. These elastography-based methods use shear waves propagating through hepatic tissues to measure liver elasticity. The principle of elastography itself has been known for many decades, but has only been applied in the last decade in the development of devices capable of providing a diagnosis in hepatology.
- Klíčová slova
- tranzientní elastografie, ultrazvuková elastografie, FibroScan®,
- MeSH
- algoritmy MeSH
- biochemická analýza krve MeSH
- biologické markery MeSH
- elastografie * klasifikace metody využití MeSH
- jaterní cirhóza * diagnóza krev MeSH
- lidé MeSH
- senzitivita a specificita MeSH
- stupeň závažnosti nemoci MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy MeSH
