• MeSH
• alanintransaminasa krev   MeSH
• aspartátaminotransferasy krev   MeSH
• bilirubin krev   MeSH
• gama-glutamyltransferasa krev   MeSH
• jaterní testy * metody   MeSH
• krevní obraz MeSH
• lidé MeSH
• nemoci jater diagnóza   MeSH
• sérový albumin analýza   MeSH
• Check Tag
• lidé MeSH

• MeSH
• alanintransaminasa krev   MeSH
• alkalická fosfatasa fyziologie   krev   MeSH
• aspartátaminotransferasy krev   MeSH
• bilirubin fyziologie   krev   MeSH
• diferenciální diagnóza MeSH
• gama-glutamyltransferasa fyziologie   krev   MeSH
• hyperbilirubinemie klasifikace   MeSH
• jaterní testy * klasifikace   MeSH
• lidé MeSH
• nemoci jater diagnóza   prevence a kontrola   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• přehledy MeSH

BACKGROUND AND AIMS: Disease progression in children with primary sclerosing cholangitis (PSC) is variable. Prognostic and risk-stratification tools exist for adult-onset PSC, but not for children. We aimed to create a tool that accounts for the biochemical and phenotypic features and early disease stage of pediatric PSC. APPROACH AND RESULTS: We used retrospective data from the Pediatric PSC Consortium. The training cohort contained 1,012 patients from 40 centers. We generated a multivariate risk index (Sclerosing Cholangitis Outcomes in Pediatrics [SCOPE] index) that contained total bilirubin, albumin, platelet count, gamma glutamyltransferase, and cholangiography to predict a primary outcome of liver transplantation or death (TD) and a broader secondary outcome that included portal hypertensive, biliary, and cancer complications termed hepatobiliary complications (HBCs). The model stratified patients as low, medium, or high risk based on progression to TD at rates of <1%, 3%, and 9% annually and to HBCs at rates of 2%, 6%, and 13% annually, respectively (P < 0.001). C-statistics to discriminate outcomes at 1 and 5 years were 0.95 and 0.82 for TD and 0.80 and 0.76 for HBCs, respectively. Baseline hepatic fibrosis stage was worse with increasing risk score, with extensive fibrosis in 8% of the lowest versus 100% with the highest risk index (P < 0.001). The model was validated in 240 children from 11 additional centers and performed well. CONCLUSIONS: The SCOPE index is a pediatric-specific prognostic tool for PSC. It uses routinely obtained, objective data to predict a complicated clinical course. It correlates strongly with biopsy-proven liver fibrosis. SCOPE can be used with families for shared decision making on clinical care based on a patient's individual risk, and to account for variable disease progression when designing future clinical trials.

• MeSH
• bilirubin krev   MeSH
• biopsie MeSH
• cholangiografie MeSH
• dítě MeSH
• gama-glutamyltransferasa krev   MeSH
• lidé MeSH
• mladiství MeSH
• počet trombocytů MeSH
• prognóza MeSH
• progrese nemoci MeSH
• retrospektivní studie MeSH
• rizikové faktory MeSH
• sérový albumin analýza   MeSH
• sklerozující cholangitida diagnóza   mortalita   patologie   chirurgie   MeSH
• transplantace jater MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH

Neonatal hyperbilirubinemia or jaundice is associated with kernicterus, resulting in permanent neurological damage or even death. Conventional phototherapy does not prevent hyperbilirubinemia or eliminate the need for exchange transfusion. Here we investigated the potential of therapeutic bile acids ursodeoxycholic acid (UDCA) and obeticholic acid (OCA, 6-α-ethyl-CDCA), a farnesoid-X-receptor (FXR) agonist, as preventive treatment options for neonatal hyperbilirubinemia using the hUGT1*1 humanized mice and Ugt1a-deficient Gunn rats. Treatment of hUGT1*1 mice with UDCA or OCA at postnatal days 10-14 effectively decreased bilirubin in plasma (by 82% and 62%) and brain (by 72% and 69%), respectively. Mechanistically, our findings indicate that these effects are mediated through induction of protein levels of hUGT1A1 in the intestine, but not in liver. We further demonstrate that in Ugt1a-deficient Gunn rats, UDCA but not OCA significantly decreases plasma bilirubin, indicating that at least some of the hypobilirubinemic effects of UDCA are independent of UGT1A1. Finally, using the synthetic, non-bile acid, FXR-agonist GW4064, we show that some of these effects are mediated through direct or indirect activation of FXR. Together, our study shows that therapeutic bile acids UDCA and OCA effectively reduce both plasma and brain bilirubin, highlighting their potential in the treatment of neonatal hyperbilirubinemia.

• MeSH
• bilirubin krev   MeSH
• ileum účinky léků   metabolismus   MeSH
• isoxazoly farmakologie   MeSH
• játra účinky léků   metabolismus   MeSH
• kyselina chenodeoxycholová analogy a deriváty   terapeutické užití   MeSH
• kyselina ursodeoxycholová terapeutické užití   MeSH
• myši MeSH
• novorozenecká hyperbilirubinemie krev   farmakoterapie   MeSH
• potkani Gunn MeSH
• receptory cytoplazmatické a nukleární agonisté   metabolismus   MeSH
• výsledek terapie MeSH
• žlučové kyseliny a soli terapeutické užití   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Invasive bilirubin measurements remain the gold standard for the diagnosis and treatment of infants with severe neonatal hyperbilirubinemia. The present paper describes different methods currently available to assess hyperbilirubinemia in newborn infants. Novel point-of-care bilirubin measurement methods, such as the BiliSpec and the Bilistick, would benefit many newborn infants, especially in low-income and middle-income countries where the access to costly multi-analyzer in vitro diagnostic instruments is limited. Total serum bilirubin test results should be accurate within permissible limits of measurement uncertainty to be fit for clinical purposes. This implies correct implementation of internationally endorsed reference measurement systems as well as participation in external quality assessment programs. Novel analytic methods may, apart from bilirubin, include the determination of bilirubin photoisomers and bilirubin oxidation products in blood and even in other biological matrices. IMPACT: Key message: Bilirubin measurements in blood remain the gold standard for diagnosis and treatment of severe neonatal hyperbilirubinemia (SNH). External quality assessment (EQA) plays an important role in revealing inaccuracies in diagnostic bilirubin measurements. What does this article add to the existing literature? We provide analytic performance data on total serum bilirubin (TSB) as measured during recent EQA surveys. We review novel diagnostic point-of-care (POC) bilirubin measurement methods and analytic methods for determining bilirubin levels in biological matrices other than blood. Impact: Manufacturers should make TSB test results traceable to the internationally endorsed total bilirubin reference measurement system and should ensure permissible limits of measurement uncertainty.

• MeSH
• bilirubin krev   MeSH
• biologické markery krev   MeSH
• lidé MeSH
• novorozenec MeSH
• novorozenecká hyperbilirubinemie krev   diagnóza   terapie   MeSH
• novorozenecká žloutenka krev   diagnóza   terapie   MeSH
• novorozenecký screening * MeSH
• point of care testing * MeSH
• prediktivní hodnota testů MeSH
• prognóza MeSH
• reprodukovatelnost výsledků MeSH
• stupeň závažnosti nemoci MeSH
• upregulace MeSH
• Check Tag
• lidé MeSH
• novorozenec MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH

Severe neonatal hyperbilirubinemia (SNH) is a serious condition that occurs worldwide. Timely recognition with bilirubin determination is key in the management of SNH. Visual assessment of jaundice is unreliable. Fortunately, transcutaneous bilirubin measurement for screening newborn infants is routinely available in many hospitals and outpatient settings. Despite a few limitations, the use of transcutaneous devices facilitates early recognition and appropriate management of neonatal jaundice. Unfortunately, however, advanced and often costly screening modalities are not accessible to everyone, while there is an urgent need for inexpensive yet accurate instruments to assess total serum bilirubin (TSB). In the near future, novel icterometers, and in particular optical bilirubin estimates obtained with a smartphone camera and processed with a smartphone application (app), seem promising methods for screening for SNH. If proven reliable, these methods may empower outpatient health workers as well as parents at home to detect jaundice using a simple portable device. Successful implementation of ubiquitous bilirubin screening may contribute substantially to the reduction of the worldwide burden of SNH. The benefits of non-invasive bilirubin screening notwithstanding, any bilirubin determination obtained through non-invasive screening must be confirmed by a diagnostic method before treatment. IMPACT: Key message: Screening methods for neonatal hyperbilirubinemia facilitate early recognition and timely treatment of severe neonatal hyperbilirubinemia (SNH). Any bilirubin screening result obtained must be confirmed by a diagnostic method. What does this article add to the existing literature? Data on optical bilirubin estimation are summarized. Niche research strategies for prevention of SNH are presented. Impact: Transcutaneous screening for neonatal hyperbilirubinemia contributes to the prevention of SNH. A smartphone application with optical bilirubin estimation seems a promising low-cost screening method, especially in low-resource settings or at home.

• MeSH
• bilirubin krev   MeSH
• biologické markery krev   MeSH
• časná diagnóza MeSH
• chytrý telefon MeSH
• lidé MeSH
• mobilní aplikace MeSH
• novorozenec MeSH
• novorozenecká hyperbilirubinemie krev   diagnóza   terapie   MeSH
• novorozenecká žloutenka krev   diagnóza   terapie   MeSH
• novorozenecký screening * přístrojové vybavení   MeSH
• prediktivní hodnota testů MeSH
• prognóza MeSH
• reprodukovatelnost výsledků MeSH
• stupeň závažnosti nemoci MeSH
• upregulace MeSH
• Check Tag
• lidé MeSH
• novorozenec MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH

BACKGROUND: The potential antiatherogenic role of bilirubin is generally acknowledged, so the aim of this study was to determine serum bilirubin concentrations and the prevalence of Gilbert syndrome (GS) in the Czech general population with particular reference to its relationship to the risk of myocardial infarction (MI). Methods and Results: Biochemical markers were analyzed in 2 independent Czech post-MONICA studies (in total, n=3,311), and in 741 male MI patients. TheUGT1A1promoter gene variant (rs81753472) was analyzed in these MI patients and in the first control population cohort (n=717). Medians of serum bilirubin concentrations in the 2 Czech general population cohorts were 9.6 and 9.8 mumol/L (10.7 and 11.3 mumol/L in males, and 8.3 and 8.8 mumol/L in females; P<0.01). The prevalence of GS was 8.9%, twice as high in males compared with females (11.6 vs. 6.1%; P<0.01). TheUGT1A1(TA)7/7promoter repeats significantly influenced serum bilirubin concentrations in the controls, but not in the MI patients. Serum bilirubin concentrations were significantly lower in MI patients (7.7 vs. 10.7 mumol/L; P<0.01), with almost 5-fold lower prevalence of GS. CONCLUSIONS: Serum bilirubin concentrations and the prevalence of GS were determined in the Czech general population. Significantly lower serum bilirubin concentrations were observed in male MI patients.

• MeSH
• bilirubin * krev   MeSH
• dospělí MeSH
• genotyp MeSH
• Gilbertova nemoc * epidemiologie   genetika   krev   MeSH
• glukuronosyltransferasa genetika   MeSH
• infarkt myokardu * epidemiologie   genetika   krev   MeSH
• lidé středního věku MeSH
• lidé MeSH
• polymorfismus genetický MeSH
• prevalence MeSH
• promotorové oblasti (genetika) MeSH
• prospektivní studie MeSH
• průřezové studie MeSH
• retrospektivní studie MeSH
• rizikové faktory MeSH
• sexuální faktory MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Geografické názvy
• Česká republika MeSH

BACKGROUND: The potential antiatherogenic role of bilirubin is generally acknowledged, so the aim of this study was to determine serum bilirubin concentrations and the prevalence of Gilbert syndrome (GS) in the Czech general population with particular reference to its relationship to the risk of myocardial infarction (MI).Methods and Results:Biochemical markers were analyzed in 2 independent Czech post-MONICA studies (in total, n=3,311), and in 741 male MI patients. TheUGT1A1promoter gene variant (rs81753472) was analyzed in these MI patients and in the first control population cohort (n=717). Medians of serum bilirubin concentrations in the 2 Czech general population cohorts were 9.6 and 9.8 μmol/L (10.7 and 11.3 μmol/L in males, and 8.3 and 8.8 μmol/L in females; P<0.01). The prevalence of GS was 8.9%, twice as high in males compared with females (11.6 vs. 6.1%; P<0.01). TheUGT1A1(TA)7/7promoter repeats significantly influenced serum bilirubin concentrations in the controls, but not in the MI patients. Serum bilirubin concentrations were significantly lower in MI patients (7.7 vs. 10.7 μmol/L; P<0.01), with almost 5-fold lower prevalence of GS. CONCLUSIONS: Serum bilirubin concentrations and the prevalence of GS were determined in the Czech general population. Significantly lower serum bilirubin concentrations were observed in male MI patients.

• MeSH
• bilirubin krev   MeSH
• dospělí MeSH
• genotyp MeSH
• Gilbertova nemoc krev   epidemiologie   genetika   MeSH
• glukuronosyltransferasa genetika   MeSH
• infarkt myokardu krev   epidemiologie   genetika   MeSH
• lidé středního věku MeSH
• lidé MeSH
• polymorfismus genetický MeSH
• prevalence MeSH
• promotorové oblasti (genetika) MeSH
• prospektivní studie MeSH
• průřezové studie MeSH
• retrospektivní studie MeSH
• rizikové faktory MeSH
• sexuální faktory MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Česká republika MeSH

BACKGROUND: Neonatal hyperbilirubinemia is a common condition that frequently requires treatment with phototherapy and less commonly by exchange transfusion, especially in preterm infants. It is important to identify and monitor infants at risk of severe unconjugated hyperbilirubinemia early in the postnatal period to instigate appropriate management plans. AIMS: To evaluate transcutaneous bilirubinometry (TCB) as a screening tool at 24 and 48 h of age to predict the need for phototherapy during hospital stay in preterm infants. STUDY DESIGN: A single centre prospective cohort study in a level III perinatal centre. SUBJECTS: Preterm infants (23+0 to 36+6 weeks of gestation) were eligible for enrolment. OUTCOME MEASURES: Primary outcome was to assess the predictive value of TCB at 24 and 48 h of age for the need of phototherapy during hospital stay. RESULTS: A total of 338 preterm infants were enrolled. The majority of infants (98.1%) born below 32 weeks of gestation required phototherapy. For infants born at >31 + 6 weeks of gestation, TCB at 24 h of age ≥81 μmol/l had sensitivity 83%, specificity 56%, positive predictive value (PPV) 54.7% and negative predictive value (NPV) 84%. TCB at 48 h of age ≥145 μmol/l had sensitivity 65%, specificity 62%, PPV 24% and NPV 90%. CONCLUSION: TCB performed poorly at 24 and 48 h of age as a predictor of phototherapy during hospital stay in preterm infants. The negative predictive value of the test at 48 h of age might be helpful for infants born after 31 + 6 weeks of gestation.

• MeSH
• bilirubin krev   MeSH
• biochemická analýza krve přístrojové vybavení   metody   MeSH
• délka pobytu MeSH
• dospělí MeSH
• fototerapie MeSH
• lidé MeSH
• novorozenci extrémně nezralí MeSH
• novorozenec nedonošený MeSH
• novorozenec MeSH
• novorozenecká hyperbilirubinemie diagnóza   terapie   MeSH
• novorozenecký screening metody   MeSH
• prospektivní studie MeSH
• senzitivita a specificita MeSH
• věk matky MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mužské pohlaví MeSH
• novorozenec MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• pozorovací studie MeSH
• práce podpořená grantem MeSH

Although phototherapy (PT) is a standard treatment for neonatal jaundice, no validated clinical methods for determination of bilirubin phototherapy products are available. Thus, the aim of our study was to establish a such method for clinical use. To achieve this aim, a LC-MS/MS assay for simultaneous determination of Z-lumirubin (LR) and unconjugated bilirubin (UCB) was conducted. LR was purified after irradiation of UCB at 460 nm. The assay was tested on human sera from PT-treated neonates. Samples were separated on a HPLC system with a triple quadrupole mass spectrometer detector. The instrument response was linear up to 5.8 and 23.4 mg/dL for LR and UCB, respectively, with submicromolar limits of detection and validity parameters relevant for use in clinical medicine. Exposure of newborns to PT raised serum LR concentrations three-fold (p < 0.01), but the absolute concentrations were low (0.37 ± 0.16 mg/dL), despite a dramatic decrease of serum UCB concentrations (13.6 ± 2.2 vs. 10.3 ± 3.3 mg/dL, p < 0.01). A LC-MS/MS method for the simultaneous determination of LR and UCB in human serum was established and validated for clinical use. This method should help to monitor neonates on PT, as well as to improve our understanding of both the kinetics and biology of bilirubin phototherapy products.

• MeSH
• bilirubin analogy a deriváty   krev   chemie   MeSH
• chromatografie kapalinová MeSH
• fototerapie metody   MeSH
• lidé MeSH
• molekulární struktura MeSH
• novorozenec MeSH
• novorozenecká žloutenka krev   terapie   MeSH
• sérum chemie   MeSH
• tandemová hmotnostní spektrometrie MeSH
• Check Tag
• lidé MeSH
• novorozenec MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH