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

ATP-binding cassette (ABC) subfamily B member 4 (ABCB4), also known as multidrug resistance protein 3 (MDR3), encoded by ABCB4, is involved in biliary phospholipid secretion, protecting hepatobiliary system from deleterious detergent and lithogenic properties of the bile. ABCB4 mutations altering canalicular ABCB4 protein function and expression may have variable clinical presentation and predispose to several human liver diseases. Well-established phenotypes of ABCB4 deficit are: progressive familial intrahepatic cholestasis type 3, gallbladder disease 1 (syn. low phospholipid associated cholelithiasis syndrome), high ɣ-glutamyl transferase intrahepatic cholestasis of pregnancy, chronic cholangiopathy, and adult biliary fibrosis/cirrhosis. Moreover, ABCB4 aberrations may be involved in some cases of drug induced cholestasis, transient neonatal cholestasis, and parenteral nutrition-associated liver disease. Recently, genome-wide association studies have documented occurrence of malignant tumours, predominantly hepatobiliary malignancies, in patients with ABCB4/MDR3 deficit. The patient's age at the time of the first presentation of cholestatic disease, as well as the severity of liver disorder and response to treatment are related to the ABCB4 allelic status. Mutational analysis of ABCB4 in patients and their families should be considered in all individuals with cholestasis of unknown aetiology, regardless of age and/or time of onset of the first symptoms.

• MeSH
• alely MeSH
• biliární cirhóza genetika   MeSH
• cholagoga a choleretika terapeutické užití   MeSH
• cholelitiáza genetika   MeSH
• cholestáza genetika   MeSH
• intrahepatální cholestáza genetika   MeSH
• komplikace těhotenství genetika   MeSH
• kyselina ursodeoxycholová terapeutické užití   MeSH
• lékové postižení jater genetika   MeSH
• lidé MeSH
• nemoci jater etiologie   genetika   MeSH
• nemoci žlučníku genetika   MeSH
• nemoci žlučových cest genetika   MeSH
• P-glykoproteiny nedostatek   genetika   metabolismus   MeSH
• parenterální výživa škodlivé účinky   MeSH
• věk při počátku nemoci MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH

Cirrhosis is a primary cause of liver-related mortality and morbidity. The basic process driving chronic liver disease to cirrhosis is accelerated fibrogenesis. Although the pathogenesis of liver cirrhosis is a multifactorial process, the essential step in the evolution of liver fibrosis is the activation of hepatic stellate cells, which are the main source of collagen produced in the extracellular matrix. This activation process is mediated by multiple growth factors, cytokines, and chemokines. One of the hepatic stellate cell-activating signaling molecules (and also one associated with cell injury and fibrosis) is osteopontin (OPN). OPN concentration in the plasma has been found to be predictive of liver fibrosis in various liver diseases. OPN concentrations correlate significantly with the stage of fibrosis, liver insufficiency, portal hypertension, and the presence of hepatocellular cancer. However, due to its versatile signaling functions, OPN not only contributes to the development of liver cirrhosis, but is also implicated in the pathogenesis of other chronic hepatic diseases such as viral hepatitis, both alcoholic and non-alcoholic steatohepatitis, drug-induced liver injury, and hepatocellular cancer. Thus, the targeting of OPN pathways seems to be a promising approach in the treatment of chronic liver diseases.

• MeSH
• biologické markery MeSH
• hepatocelulární karcinom MeSH
• jaterní cirhóza metabolismus   MeSH
• jaterní hvězdicovité buňky metabolismus   MeSH
• jaterní insuficience metabolismus   MeSH
• lékové postižení jater metabolismus   MeSH
• lidé MeSH
• nádory jater metabolismus   MeSH
• nealkoholová steatóza jater metabolismus   MeSH
• nemoci jater metabolismus   MeSH
• osteopontin metabolismus   MeSH
• portální hypertenze metabolismus   MeSH
• signální transdukce MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH

INTRODUCTION AND AIM: It has been proposed that plasma concentration of bilirubin, an endogenous antioxidant, is protective against diseases mediated by increased oxidative stress, including cardiovascular diseases (CVD) and cancer. To examine this hypothesis, we investigated the relationship between plasma bilirubin concentrations and bilirubin UDP-glucuronosyl transferase (UGT1A1) promoter gene variations (associated with increased bilirubin concentrations) with total/CVD and cancer mortality. MATERIALS AND METHODS: A nested case-control study was conducted within the Polish arm of the HAPIEE cohort. At baseline in 2002-2005, participants were examined in detail. Mortality follow-up (median (IQR) between blood draw and death was 3.7 (2.1-5.1) years) was performed by linkage with regional and national death registers. Plasma biomarkers were analysed in all subjects who died from any cause (cases, n=447) and in a random subsample of survivors (controls, n=1423). RESULTS: There was a strong negative association between plasma bilirubin levels and total and cancer mortality, expressed more profoundly in men. The adjusted OR of deaths from all causes and cancer, comparing the highest vs. lowest plasma bilirubin categories were 0.61 (95% CI: 0.42-0.87) and 0.39 (0.24-0.65), respectively. There was no association of bilirubin with CVD mortality. The UGT1A1*28 allele, a genetic marker of raised bilirubin, was also negatively associated with total/cancer mortality, although the associations were not statistically significant. DISCUSSION: Both the observational and genetic associations support the negative relationship between bilirubin and total mortality; this association appears to be driven by cancer mortality, while that with CVD mortality is not evident. Copyright © 2019 Fundacion Clinica Medica Sur, A.C. Published by Elsevier Espana, S.L.U. All rights reserved.

• MeSH
• bilirubin * krev   MeSH
• biologické markery krev   MeSH
• časové faktory MeSH
• glukuronosyltransferasa genetika   MeSH
• hodnocení rizik MeSH
• kardiovaskulární nemoci * MeSH
• lidé středního věku MeSH
• lidé MeSH
• mendelovská randomizace MeSH
• nádory * MeSH
• polymorfismus genetický MeSH
• prediktivní hodnota testů MeSH
• příčina smrti MeSH
• prognóza MeSH
• promotorové oblasti (genetika) MeSH
• rizikové faktory MeSH
• senioři MeSH
• sexuální faktory MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Geografické názvy
• Polsko MeSH

INTRODUCTION AND AIM: It has been proposed that plasma concentration of bilirubin, an endogenous antioxidant, is protective against diseases mediated by increased oxidative stress, including cardiovascular diseases (CVD) and cancer. To examine this hypothesis, we investigated the relationship between plasma bilirubin concentrations and bilirubin UDP-glucuronosyl transferase (UGT1A1) promoter gene variations (associated with increased bilirubin concentrations) with total/CVD and cancer mortality. MATERIALS AND METHODS: A nested case-control study was conducted within the Polish arm of the HAPIEE cohort. At baseline in 2002-2005, participants were examined in detail. Mortality follow-up (median (IQR) between blood draw and death was 3.7 (2.1-5.1) years) was performed by linkage with regional and national death registers. Plasma biomarkers were analysed in all subjects who died from any cause (cases, n=447) and in a random subsample of survivors (controls, n=1423). RESULTS: There was a strong negative association between plasma bilirubin levels and total and cancer mortality, expressed more profoundly in men. The adjusted OR of deaths from all causes and cancer, comparing the highest vs. lowest plasma bilirubin categories were 0.61 (95% CI: 0.42-0.87) and 0.39 (0.24-0.65), respectively. There was no association of bilirubin with CVD mortality. The UGT1A1*28 allele, a genetic marker of raised bilirubin, was also negatively associated with total/cancer mortality, although the associations were not statistically significant. DISCUSSION: Both the observational and genetic associations support the negative relationship between bilirubin and total mortality; this association appears to be driven by cancer mortality, while that with CVD mortality is not evident.

• MeSH
• bilirubin krev   MeSH
• biologické markery krev   MeSH
• časové faktory MeSH
• glukuronosyltransferasa genetika   MeSH
• hodnocení rizik MeSH
• kardiovaskulární nemoci krev   diagnóza   genetika   mortalita   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mendelovská randomizace MeSH
• nádory krev   diagnóza   genetika   mortalita   MeSH
• polymorfismus genetický MeSH
• prediktivní hodnota testů MeSH
• příčina smrti MeSH
• prognóza MeSH
• promotorové oblasti (genetika) MeSH
• rizikové faktory MeSH
• senioři MeSH
• sexuální faktory MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• pozorovací studie MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Polsko MeSH

Mucinous cystic neoplasm of the liver (MCN-L) and intraductal papillary mucinous neoplasm of the bile duct (IPMN-B) are diagnoses that were classified by the World Health Organization in 2010 as mucin-producing bile duct tumors of the hepatobiliary system. The preoperative differential diagnosis between these two entities is difficult; the presence of a communication with the bile duct is usually considered as a typical sign of IPMN-B. However, the presence of an ovarian-like stroma (OLS) has been established to define the diagnosis of MCN-L. We present the case of a 33-year-old woman with a rapid progression of a cystic tumor of the liver. In 2 years, the lesion increased from 27 to 64 mm and a dilation of the left hepatic duct appeared. Percutaneous transhepatic drainage with a biopsy was performed. No malignant cells were found on biopsy. Because of the rapid progression of the cystic tumor and unclear malignant potential, left hemihepatectomy was performed. Even though tumor masses were present in the biliary duct, on the basis of the presence of OLS, histology finally confirmed MCN-L with intermediate-grade intraepithelial dysplasia to high-grade intraepithelial dysplasia. The patient is currently under oncologic follow-up with no signs of recurrence of the disease. We present a rare case where MCN-L caused a dilation of the left hepatic duct, a sign that is usually a characteristic of IPMN-B.

• MeSH
• biopsie MeSH
• cholangiografie MeSH
• diferenciální diagnóza MeSH
• dilatace patologická MeSH
• dospělí MeSH
• ductus hepaticus communis patologie   MeSH
• hepatektomie MeSH
• karcinom in situ komplikace   diagnóza   patologie   chirurgie   MeSH
• lidé MeSH
• magnetická rezonanční tomografie MeSH
• nádory cystické, mucinózní a serózní komplikace   diagnóza   patologie   chirurgie   MeSH
• nádory jater komplikace   diagnóza   patologie   chirurgie   MeSH
• nádory žlučových cest diagnóza   patologie   MeSH
• počítačová rentgenová tomografie MeSH
• prediktivní hodnota testů MeSH
• progrese nemoci MeSH
• tumor burden MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH
• přehledy MeSH

Bile acids (BA), for decades considered only to have fat-emulsifying functions in the gut lumen, have recently emerged as novel cardio-metabolic modulators. They have real endocrine effects, acting via multiple intracellular receptors in various organs and tissues. BA affect energy homeostasis through the modulation of glucose and lipid metabolism, predominantly by activating the nuclear farnesoid X receptor (FXR), as well as the cytoplasmic membrane G protein-coupled BA receptor TGR5 in a variety of tissues; although numerous other intracellular targets of BA are also in play.The roles of BA in the pathogenesis of diabetes, obesity, metabolic syndrome, and cardiovascular diseases are seriously being considered, and BA and their derivatives seem to represent novel potential therapeutics to treat these diseases of civilization.

• MeSH
• hypoglykemika terapeutické užití   MeSH
• hypolipidemika terapeutické užití   MeSH
• kardiovaskulární látky terapeutické užití   MeSH
• kardiovaskulární nemoci farmakoterapie   metabolismus   MeSH
• látky proti obezitě terapeutické užití   MeSH
• lidé MeSH
• metabolické nemoci farmakoterapie   metabolismus   MeSH
• metabolismus lipidů účinky léků   MeSH
• objevování léků MeSH
• probiotika terapeutické užití   MeSH
• signální transdukce účinky léků   MeSH
• střeva účinky léků   metabolismus   mikrobiologie   MeSH
• střevní mikroflóra MeSH
• žlučové kyseliny a soli metabolismus   terapeutické užití   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

Introduction and Aim: Hepatic encephalopathy (HE) is a common complication of transjugular intrahepatic portosystemic shunting (TIPS). It is associated with a reduced quality of life and poor prognosis. The aim of this study was to compare two groups of patients who did and did not develop overt HE after TIPS. We looked for differences between these groups before TIPS. MATERIALS AND METHODS: A study of 895 patients was conducted based on a retrospective analysis of clinical data. Data was analyzed using Fisher's exact test, Chi-square, Mann Whitney test, unpaired t-test and logistic regression. After the initial analyses, we have looked at a regression models for the factors associated with development of HE after TIPS. RESULTS: 257 (37.9%) patients developed HE after TIPS. Patients' age, pre-TIPS portal venous pressure, serum creatinine, aspartate transaminase, albumin, presence of diabetes mellitus and etiology of portal hypertension were statistically significantly associated with the occurrence of HE after TIPS (p < 0.01). However, only the age, pre-TIPS portal venous pressure, serum creatinine, presence of diabetes mellitus and etiology of portal hypertension contributed to the regression model. Patients age, serum creatinine, presence of diabetes mellitus and portal vein pressure formed the model describing development of HE after TIPS for a subgroup of patients with refractory ascites. CONCLUSION: we have identified, using a substantial sample, several factors associated with the development of HE after TIPS. This could be helpful in further research.

• MeSH
• biologické markery krev   MeSH
• časové faktory MeSH
• dospělí MeSH
• jaterní encefalopatie diagnóza   etiologie   MeSH
• komplikace diabetu etiologie   MeSH
• kreatinin krev   MeSH
• lidé středního věku MeSH
• lidé MeSH
• logistické modely MeSH
• mladiství MeSH
• mladý dospělý MeSH
• portální hypertenze diagnóza   etiologie   patofyziologie   chirurgie   MeSH
• retrospektivní studie MeSH
• rizikové faktory MeSH
• rozdělení chí kvadrát MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• transjugulární intrahepatální portosystémový zkrat škodlivé účinky   MeSH
• věkové faktory MeSH
• venózní tlak MeSH
• výsledek terapie MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• pozorovací studie MeSH
• srovnávací studie MeSH
• Geografické názvy
• Česká republika MeSH

UNLABELLED: Background and aims. Patients with intrahepatic cholestasis of pregnancy (ICP) benefit from ursodeoxycholic acid (UDCA) treatment. Since there is still certain reluctance to use UDCA in pregnant women, mainly due to warnings in the official SPC information in respective drug leaflets, our objective was to assess the efficacy and safety of UDCA during pregnancy. MATERIAL AND METHODS: Our retrospective multicentric study was performed on 191 consecutive pregnant women with ICP treated with UDCA. Any maternal and/or fetal complications of the UDCA treatment were searched for; healthy pregnant women (n = 256) served as controls. RESULTS: The UDCA treatment improved liver disease status in the majority of the affected women (86.1%). This treatment was well tolerated, with only negligible skin reactions (0.5%) and mild diarrhea (4.7%). No complications attributable to UDCA treatment were detected during the fetal life, delivery, or the early neonatal period. CONCLUSION: We confirmed the good efficacy and safety of UDCA treatment in pregnancy for both mothers and fetuses/neonates.

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• MeSH
• cholagoga a choleretika škodlivé účinky   terapeutické užití   MeSH
• dospělí MeSH
• hodnocení rizik MeSH
• intrahepatální cholestáza * diagnóza   farmakoterapie   MeSH
• komplikace těhotenství diagnóza   farmakoterapie   MeSH
• kyselina ursodeoxycholová škodlivé účinky   terapeutické užití   MeSH
• lidé MeSH
• retrospektivní studie MeSH
• rizikové faktory MeSH
• těhotenství MeSH
• výsledek terapie MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• těhotenství MeSH
• ženské pohlaví MeSH

Introduction and aim. Hepatocellular carcinoma (HCC) is the most common primary malignant liver tumor. It is primarily caused by hepatic cirrhosis or chronic viral hepatitis. Hepatic carcinogenesis is associated with increased oxidative stress. Thus, the aim of our study was to assess expression of the genes involved in the homeostasis of oxidative stress in patients with HCC. MATERIAL AND METHODS: The study was performed on 32 patients with primary HCC (verified by liver histology in 29 patients) and 27 control subjects (in 11 subjects, liver histology was available either with no or minimal changes in the liver tissue). Gene expressions of heme oxygenase 1 (HMOX1), biliverdin reductase A/B (BLVRA/B), NADPH oxidase 2 (NOX2) and p22phox were analyzed in the liver and peripheral blood leukocytes (PBL) in the subjects. RESULTS: Compared to controls, almost a 3 times higher mRNA level of BLVRA was detected in livers of HCC patients (p = 0.002); while those of BLVRB as well as HMOX1 were unchanged (p > 0.05). In accord with these results in the liver tissue, BLVRA mRNA levels in PBL were also significantly increased in HCC patients (p = 0.012). mRNA levels of NOX2 and p22phox in the liver tissue, although higher in HCC patients, did not differ significantly compared to control subjects (p > 0.05). Nevertheless, NOX2 mRNA level in PBL was significantly higher in HCC patients (p = 0.003). CONCLUSIONS: BLVRA mRNA levels in the liver as well as in PBL are significantly higher in HCC patients most likely as a feedback mechanism to control increased oxidative stress associated with HCC progression.

• MeSH
• hemoxygenasa-1 genetika   MeSH
• hepatocelulární karcinom krev   enzymologie   genetika   patologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• membránové glykoproteiny genetika   MeSH
• messenger RNA genetika   MeSH
• nádorové biomarkery krev   genetika   MeSH
• nádory jater krev   enzymologie   genetika   patologie   MeSH
• NADPH-oxidasy genetika   MeSH
• oxidační stres genetika   MeSH
• oxidoreduktasy působící na CH-CH vazby krev   genetika   MeSH
• progrese nemoci MeSH
• regulace genové exprese enzymů MeSH
• regulace genové exprese u nádorů MeSH
• senioři MeSH
• signální transdukce MeSH
• studie případů a kontrol MeSH
• upregulace MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH