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Gilbert syndrome is the most common hyperbilirubinemia, associated with a mutation in the UGT1A1 bilirubin gene, which produces an enzyme that conjugates bilirubin with glucuronic acid. Episodes of jaundice occurring in GS negatively affect patients' quality of life. This systematic review aimed to analyze clinical studies regarding nutrition in people with GS. The study followed the PRISMA guidelines and utilized the Ebsco, Embase, Cochrane, PubMed, Scopus, and Web of Science databases to search clinical trials focused on diet/nutrition in GS (1963–2023 years). The methodological quality of selected studies was assessed using the Jadad scale. As a result, 19 studies met the inclusion criteria. The research mainly focused on the impact of caloric restriction, consumption of various diet variants, and vegetables and fruits on hyperbilirubinemia and metabolic health. A nutritional intervention consisting of not applying excessive calorie restrictions and consuming fats and biologically active compounds in vegetables and fruits (Cruciferae, Apiaceous, Rutaceae) may prevent the occurrence of jaundice episodes. It is justified to conduct further research on detecting such compounds in food, which, by influencing the expression of the UGT liver enzyme gene, could contribute to regulating bilirubin concentration in the blood of people with GS. [ABSTRACT FROM AUTHOR]

Aim: This study aimed to compare dynamic thiol/disulfide homeostasis and myeloperoxidase (MPO) levels in patients with Gilbert's syndrome (GS) and healthy controls. Background: Thiol/disulfide homeostasis and MPO levels are both associated with increased progression of atherosclerosis. Methods: The study included a total of 130 voluntary participants comprising 65 patients with GS and 65 healthy controls. These patients were selected randomly and dynamic thiol/disulfide homeostasis, MPO, complete blood count results, and biochemistry and lipid parameters were evaluated. Patients with known chronic diseases, medication usage, and acute infections were excluded from the study. Serum total thiol and native thiol levels were measured using the fully automated colorimetric method, while serum MPO levels were measured using the sandwich ELISA method. Results: We found that patients with GS had significantly higher total thiol (352.3±38.6 vs. 317.9±47.9, p<0.001) and native thiol (386.6±42.6 vs. 348.0±51.1, p<0.001) and significantly lower disulfide (15.7±4.0 vs. 17.3±4.0, p=0.022) and MPO (130.7 vs. 166.3, p=0.006). In patients with bilirubin of <1 mg/dL, total thiol and native thiol levels were lower and disulfide, disulfide/native thiol (DNT) and disulfide/total thiol (DTT) ratios, and MPO levels were higher. Patients with bilirubin of <1 mg/dL also had higher total cholesterol. Conclusion: In these patients with GS, the thiol/disulfide balance shifted towards thiols and proinflammatory MPO levels were lower. When bilirubin was <1 mg/dL, disulfide, DNT and DTT ratios, and MPO were higher. Bilirubin levels affected all parameters of thiol/disulfide homeostasis and MPO levels independently of other risk factors. In light of our results, we suggest that mild hyperbilirubinemia in cases of GS has an anti-inflammatory and antioxidant effect and may be protective against atherosclerosis. [ABSTRACT FROM AUTHOR]

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Gilbert’s syndrome is a hereditary disease with raised levels of unconjugated bilirubin. The disorder is generally asymptomatic and often misdiagnosed, which can lead to unnecessary anxiety in patients, particularly during pregnancy. There is a case report of a 24-year-old pregnant woman with jaundice and elevated bilirubin levels without any history of hyperbilirubinaemia. Diagnosis of Gilbert’s syndrome was made according to the patient’s clinical features and laboratory results after ruling out other diseases. The patient was reassured that Gilbert’s syndrome posed no significant risk to her or the foetus, and appropriate surveillance and management were provided. Accurate diagnosis is essential to alleviate worries and confirm appropriate management. Healthcare providers should consider Gilbert’s syndrome as a potential cause of hyperbilirubinaemia in pregnant women and impact reassurance regarding the promising prognosis and normal life expectancy. This case emphasises the significance of considering Gilbert’s syndrome in a differential diagnosis of hyperbilirubinaemia in pregnancy.

Objective: Unusual clinical course Background: In the absence of liver transplantation, the natural history of acetaminophen-induced liver failure is characterized by a progressive increase of liver function tests, including bilirubin mainly as its conjugated form. The presence of high levels of unconjugated bilirubin is more unusual; its etiology is unclear and its prognostic factor has been poorly investigated. Case Report: A 52-year-old man with a history of chronic analgesics, alcohol, and illicit drug abuse developed acute liver failure in relationship with the ingestion of largely supra-therapeutic doses of acetaminophen over the days preceding admission. The patient received the classical N-acetylcysteine treatment regimen for acetaminophen overdose. Clinical course was characterized by a progressive worsening of the neurological condition, evolving to grade IV encephalopathy. Coagulation disorders persisted, with factor V level <10%. He fulfilled the criteria for liver transplantation, but this option was rejected after a careful psychiatric evaluation. Laboratory investigations revealed a progressive increase in serum unconjugated bilirubin until his death. As evidence for hemolysis was lacking, acquired deficit in bilirubin glucuronidation appeared likely and diagnosis of Gilbert's syndrome was excluded.** Conclusions: After the exclusion of other causes of high unconjugated bilirubin levels, the progressive increase in unconjugated bilirubin can reflect a persistent defect in bilirubin conjugation in relationship with liver centrilobular injury, but the relationship with acetaminophen-glucuronidation is not known and there are insufficient data to affirm that the ratio unconjugated/conjugated bilirubin could be used as a prognostic factor. [ABSTRACT FROM AUTHOR]

Gilbert's syndrome is a hereditary disease with raised levels of unconjugated bilirubin. The disorder is generally asymptomatic and often misdiagnosed, which can lead to unnecessary anxiety in patients, particularly during pregnancy. There is a case report of a 24-year-old pregnant woman with jaundice and elevated bilirubin levels without any history of hyperbilirubinaemia. Diagnosis of Gilbert's syndrome was made according to the patient's clinical features and laboratory results after ruling out other diseases. The patient was reassured that Gilbert's syndrome posed no significant risk to her or the foetus, and appropriate surveillance and management were provided. Accurate diagnosis is essential to alleviate worries and confirm appropriate management. Healthcare providers should consider Gilbert's syndrome as a potential cause of hyperbilirubinaemia in pregnant women and impact reassurance regarding the promising prognosis and normal life expectancy. This case emphasises the significance of considering Gilbert's syndrome in a differential diagnosis of hyperbilirubinaemia in pregnancy. [ABSTRACT FROM AUTHOR]

Modern research in psychiatry is increasingly focusing on the possible identification of potentially useful biomarkers for early and differential diagnosis and patient-tailored therapy. In this context, old and new biomarkers are gaining attention, and bilirubin could represent a low-cost and widespread tool in this regard. In the following paper, we present a case report of a patient with juvenile-onset schizophrenia successfully treated with oral risperidone on 2 separate occasions, whose clinical exacerbation phases overlapped with hyperbilirubinemia peaks, while comfort phases were associated with serum bilirubin within the normal range. The patient was later diagnosed with Gilbert's syndrome, a benign, congenital condition of hyperbilirubinemia, with alternating phases of mostly asymptomatic bilirubin levels. This case highlights a possible relationship between psychotic symptoms and plasma bilirubin levels. While not representing by itself a sufficient condition to determine a relationship between the 2 phenomena, it poses a relevant question for future clinical and research investigations. [ABSTRACT FROM AUTHOR]

Introduction: Bilirubin was supposed to have cardio‐metabolic protective role by signaling functions. Indeed, mild hyperbilirubinemia has immunosuppressive and endocrine activities and may offer protection against oxidative stress‐mediated diseases. Gilbert syndrome (GS) has been hypothesized to provide cardio‐metabolic benefits. Objective: To investigate the prevalence of hyperbilirubinemia and its cardio‐metabolic effects in a cohort of elite Italian athletes engaged in different sports disciplines. Methods: We enrolled 1492 elite athletes (age 25.8 ± 5.1) practising different disciplines (power, skills, endurance, and mixed) underwent blood, echocardiographic, and exercise tests. GS was diagnosed per exclusionem in athletes with isolated asymptomatic unconjugated hyperbilirubinemia. Results: GS was highlighted in 91 athletes (6%; globally 9% male and 2.4% female); 82% were males (p < 0.0001) showing higher indirect bilirubin (0.53 ± 0.4 vs. 0.36 ± 0.24 mg/dL in females, p < 0.0001). GS athletes had fewer platelets (201 ± 35 vs. 214 ± 41, p = 0.01), higher iron (male: 124 ± 44 vs. 100.9 ± 34 mcg/dL, p < 0.0001; female: 143.3 ± 35 vs. 99.9 ± 42 mcg/dL, p < 0.0001), and lower erythrocyte sedimentation rate, (1.93 ± 0.9 vs. 2.80 ± 2.7 mm/H, p = 0.03). At multivariate analysis, male (OR 3.89, p = 0.001) and iron (OR 3.47, p = 0.001) were independently associated with GS. No significant differences were found in cardiac remodeling, heart rate, blood pressure, arrhythmias, or power capacity at stress test. Endurance athletes (313) presented higher total (p = 0.003) and indirect bilirubin (p = 0.001). Conclusion: Bilirubin has several metabolic effects (including immunosuppressive and endocrine) and plays a role in regulating antioxidant pathways exercise‐related with hematological consequences but seems not to affect significantly cardiovascular remodeling. Endurance athletes present higher bilirubin concentrations, likely as an adaptive mechanism to counteract increased oxidative stress. [ABSTRACT FROM AUTHOR]

In this study, we aim to evaluate the presence of endothelial dysfunction in Gilbert syndrome patients with left ventricular mass index (LVMI) and endocan levels. The study included 60 patients who diagnosed with Gilbert syndrome and 60 healthy controls who did not have any known diseases. Human endocan levels were measured using a sandwich ELISA method. The endocan and LVMI levels were lower in the Gilbert syndrome group than in the healthy controls. In the Gilbert syndrome group, total bilirubin level was negatively correlated with LVMI (r = −0246; P =.007) and endocan levels (r = −.270; P =.046). In the Gilbert syndrome group, increasing age (β ± SE = 20.78 ± 7.47; P =.006), was a positive independent predictor of LVMI, and increasing high-density lipoprotein cholesterol (HDL-C) (β ± SE = −.27 ±.09; P =.007), and total bilirubin levels (β ± SE = −6.09 ± 3.02; P =.046) were found to be a negative independent predictor. These results support that endothelial dysfunction is decreased in Gilbert Syndrome patients with mild hyperbilirubinemia compared with the healthy control group. [ABSTRACT FROM AUTHOR]

Gilbert’s syndrome is a genetic disorder characterised by non-hemolytic unconjugated hyperbilirubinemia. It is caused by mutations in the UGT1A1 gene which codes for the enzyme uridine diphosphate glucoronosyl transferase-1, which conjugates bilirubin for excretion. Affected individuals are usually asymptomatic apart from a mild jaundice and investigations reveal a mild isolated indirect hyperbilirubinemia. This may be exacerbated in the face of environmental and physical stressors. It is very similar in presentation to Criggler-Najjar syndrome (CNS) type 2. There is a small risk of kernicterus in patients with CNS type 2 needing daily phenobarbitone therapy. This risk is miniscule in Gilbert’s syndrome. Genetic testing for polymorphisms of the UGT1A1 gene is the diagnostic clincher for Gilbert’s syndrome, but it can also be picked up by evaluating the response to phenobarbitone and fasting, particularly in resource poor settings. Due to limited availability, case reports documenting the genetic mutational analysis are sparse. We reported one such rare case with an unusually high indirect hyperbilirubinemia in Gilbert’s syndrome confirmed by both phenobarbitone response and genetic analysis. [ABSTRACT FROM AUTHOR]

Objectives: Bilirubin is a potent endogenous antioxidant and immunomodulating substance, which is also implicated in both cell signalling and various metabolic pathways. Mild elevation of systemic bilirubin concentrations provides substantial protection against many diseases of civilization. Rare published reports have suggested that serum bilirubin might also be relevant to sports performance. The purpose of the current study was to evaluate serum bilirubin concentrations and the prevalence of Gilbert syndrome (GS) in elite athletes. Methods: The study was carried out in 536 consecutive healthy elite athletes and in 2594 individuals of the Czech post-MONICA study representing the general Czech population. Serum bilirubin concentrations, the prevalence of benign hyperbilirubinemia > 17 µmol/L (1 mg/dL, a phenotypic sign of GS), and a variant of the UGT1A1 gene promoter responsible for GS manifestation in Caucasians (rs81753472) were evaluated in study subjects. Results: Compared to the general Czech population, significantly higher serum bilirubin concentrations were found in elite athletes (9.6 vs. 11.6 µmol/L, p < 0.001), both in men (11.3 vs. 12.6 µmol/L, p < 0.001) and women (8.3 vs. 10.5 µmol/L, p < 0.001). Furthermore, the prevalence of GS was also significantly higher in elite athletes (9.6 vs. 22%, p < 0.001) together with the tendency to higher frequencies of the genotypes (TA)7/7 and (TA)6/7UGT1A1. Conclusion: Elite athletes have significantly higher concentrations of serum bilirubin, the most potent endogenous antioxidant substance known. Simultaneously, the prevalence of GS syndrome is also much higher in elite athletes, suggesting that a mild elevation of serum bilirubin might predispose to better sports performance. [ABSTRACT FROM AUTHOR]

Objective: Gilbert syndrome (GS) is a disease characterized by mildly elevated indirect serum bilirubin levels due to mutation in the promoter of the UGT1A1 gene, which causes a decrease in uridine diphosphate glucuronyltransferase enzyme activity. Gilbert syndrome should be considered based on clinical and laboratory findings in differential diagnosis, which can be supported by genetic analysis. This study aimed to evaluate the clinical findings and UGT1A1 mutations of children with Gilbert syndrome. Materials and Methods: Patients who were admitted to the pediatric gastroenterology clinic and who were considered to have Gilbert syndrome based on clinical and laboratory findings were included in the study. The UGT1A1 analysis was performed by Sanger sequence analysis. What this study adds on this topic? This study is important due to the limited Gilbertsyndrome(GS) data in children in Turkey. A mild bilirubin elevation can be observed in the cases with 6 TA repetitions that were considered non-risky in terms of GS. We suggested that the variant [c.880_893delinsA (p.Tyr294MetfsTer69)] was causing partial enzyme deficiency leading to the GS phenotype. Results: A total of 56 children were included in the study. A(TA)7TAA, A(TA)6TAA, and (TA)6/7 allele promoter polymorphism was detected in 75.5%, 22.5%, and 2% of the patients, respectively. Other than these, in 3 patients, 3 different sequence variants associated with GS [c.880_893delinsA (p.Tyr294MetfsTer69) and c.1091C>T(p.Pro365Leu)] were detected. Conclusion: We detected 7 TA repeats in the majority of our patients. A mild bilirubin elevation was determined in cases with 6 repetitions that were not considered risky for Gilbert syndrome. We concluded that the c.880_893delinsA (p.Tyr294MetfsTer69) variant, previously shown to be associated with Crigler-Najjar syndrome type I, may also be associated with partial enzyme deficiency leading to the Gilbert syndrome phenotype. [ABSTRACT FROM AUTHOR]

Background: Several mutations of bilirubin uridine diphosphate-glucuronosyltransferase gene (UGT1A1) have been reported in patients with unconjugated hyperbilirubinemia. Few reports are available about the p.Pro364Leu mutation (P364L, c.1091C > T) in homozygous newborns. We describe the clinical, laboratory and therapeutic approach in two Chinese neonates with severe jaundice, homozygous for the P364L mutation. Case presentation: Two Chinese breastfed female infants presented prolonged unconjugated hyperbilirubinemia at the age of 1 month. Total bilirubin was higher than 15 mg/dl (D < 1). An exhaustive etiological work-up to detect possible causes of hyperbilirubinemia (notably hemolytic ones) was negative. The promoter and coding regions of UGT1A1 were amplified by polymerase chain reaction (PCR) from genomic DNA isolated from leukocytes. Both patients resulted homozygous for a variant site within the coding region of the gene in the 4 exon, c.1091C > T, p.Pro364Leu. In front of the persistently high level of unconjugated bilirubin, phototherapy was performed without persistent results. A treatment with phenobarbital was then begun and bilirubin level progressively decreased, with a complete and persistent normalization. The therapy was stopped. Conclusion: UGT1A1 enzyme activity associated with the P364L mutation has been described as 35.6% of the wild-type enzyme activity. Photo-therapy and phenobarbital can be useful in front of persistently high level of unconjugated bilirubin. Our cases presented high bilirubin values, overlapping between Gilbert syndrome (GS) and Crigler-Najjar syndrome type II (CNS), but the complete normalization of bilirubin makes GS more likely. Homozygous P364L variant can be associated with severe neonatal unconjugated hyperbilirubinemia in Chinese infants, but jaundice can completely resolve in a few months, contrary to what happens in Crigler-Najjar syndrome type II. [ABSTRACT FROM AUTHOR]

Objective To investigate the differences in UGT1 A1 gene mutation sites, haplotypes, and diplotypes between patients with Gilbert syndrome（GS） and those with Crigler-Najjar syndrome type II（CN-2）. Methods A retrospective analysis was performed for the clinical data of 138 patients with GS or CN-2 who attended Beijing YouAn Hospital, Capital Medical University, from January 1, 2010 to December 31, 2019, with 109 patients in the GS group and 29 patients in the CN-2 group, and the differences in mutation sites were analyzed between the two phenotypes. The Mann-Whitney U test was used for comparison of continuous data between two groups, and the chi-square test or the Fisher’s exact test was used for comparison of categorical data between groups. SNPStats software was used to perform linkage disequilibrium（LD） and haplotype analyses of mutation sites. Strong LD was defined as both |D′| and r² >0.8, and moderate LD was defined as |D′|>0.8 and r²>0.4. Results UGT1 A1 gene detection was performed for all patients, and mutations mainly included-3279 T>G mutation（104 patients, 75.36%） and-3152 G>A mutation（82 patients, 59.42%） in the upstream promoter PBREM region, a promoter TATA box TA insertion mutation（88 patients, 63.77%）, and c.211 G>A mutation in Exon 1 of the coding region（66 patients, 47.83%）. Compared with the CN-2 group, the GS group had a significantly higher proportion of PBREM region-3279 T>G mutation（82.57% vs 48.28%, χ²=14.508, P<0.001）, PBREM region-3152 G>A mutation（68.81% vs 24.14%, χ²=18.955, P<0.001）, and promoter TATA box（TA）6>（TA）7 mutation（72.48% vs 31.03%, χ²=17.027, P<0.001）, and compared with the GS group, the CN-2 group had a significantly higher proportion of mutations at the c.211 locus（68.97% vs 42.20%, χ²=6.575, P=0.010） and the c.1456 locus（51.72% vs 7.34%, χ²=29.372, P<0.001）. LD analysis of different mutation sites of the UGT1 A1 gene showed strong LD（|D′|>0.8, r²>0.8） between（TA）6>（TA）7 and-3152 G>A and moderate LD（|D′|>0.8, r²>0.4） between（TA）6>（TA）7 and-3279 T>G, between-3152 G>A and-3279 T>G, between（TA）6>（TA）7 and c.211 G>A, and between-3279 T>G and c.211 G>A. Haplotype frequency analysis showed that compared with the CN-2 group, the GS group had a significantly higher frequency of haplotype-3279 G—-3152 A—（TA）7（45.72% vs 17.24%, χ²=7.833, P=0.005） and significantly lower frequencies of c.1456 G（4.10% vs 16.48%, χ²=4.873, P=0.027） and c.211 A—c.1456 G（1.86% vs 24.90%, χ²=15.210, P<0.001）. The diplotype analysis showed that diplotypes consisting of haplotype c.1456 G or c.211 A—c.1456 G were associated with a higher level of total bilirubin（TBil）. Conclusion There are differences in common mutation sites and major haplotypes of the UGT1 A1 gene between patients with GS and those with CN-2, and the common diplotypes of CN-2 correspond to a higher level of TBil. [ABSTRACT FROM AUTHOR]

This paper reports a child with Gilbert's syndrome who underwent cholecystectomy and endoscopic retrograde cholangiopancreatography, magnetic resonance cholangiopancreaticography to removal of the gallstones, then experienced increase in bilirubin of unknown cause. [ABSTRACT FROM AUTHOR]

Background: Glucose-6-phosphate dehydrogenase deficiency (G6PDd) newborn screening is still a matter of debate due to its highly heterogeneous birth prevalence and clinical expression, as well as, the lack of enough knowledge on its natural history. Herein, we describe the early natural clinical course and the underlying GDPD genotypes in infants with G6PDd detected by newborn screening and later studied in a single follow-up center. G6PDd newborns were categorized into three groups: group 1: hospitalized with or without neonatal jaundice (NNJ); group 2: non-hospitalized with NNJ; and group 3: asymptomatic. Frequencies of homozygous UGT1A1*28 (rs34983651) genotypes among G6PDd patients with or without NNJ were also explored.Results: A total of 81 newborns (80 males, one female) were included. Most individuals (46.9%) had NNJ without other symptoms, followed by asymptomatic (42.0%) and hospitalized (11.1%) patients, although the hospitalization of only 3 of these patients was related to G6PDd, including NNJ or acute hemolytic anemia (AHA). Nine different G6PDd genotypes were found; the G6PD A-202A/376G genotype was the most frequent (60.5%), followed by the G6PD A-376G/968C (22.2%) and the Union-Maewo (rs398123546, 7.4%) genotypes. These genotypes produce a wide range of clinical and biochemical phenotypes with significant overlapping residual enzymatic activity values among class I, II or III variants. Some G6PD A-202A/376G individuals had enzymatic values that were close to the cutoff value (5.3 U/g Hb, 4.6 and 4.8 U/g Hb in the groups with and without NNJ, respectively), while others showed extremely low enzymatic values (1.1 U/g Hb and 1.4 U/g Hb in the groups with and without NNJ, respectively). Homozygosity for UGT1A1*28 among G6PDd patients with (11.9%, N = 5/42) or without (10.3%, N = 4/39) NNJ did not shown significant statistical difference (p = 0.611).Conclusion: Wide variability in residual enzymatic activity was noted in G6PDd individuals with the same G6PD genotype. This feature, along with a documented heterogeneous mutational spectrum, makes it difficult to categorize G6PD variants according to current WHO classification and precludes the prediction of complications such as AHA, which can occur even with > 10% of residual enzymatic activity and/or be associated with the common and mild G6PD A-376G/968C and G6PD A-202A/376G haplotypes. [ABSTRACT FROM AUTHOR]

Congenital non - hemolytic jaundice is an important type of jaundice diseases, and except breast milk jaundice, the other types of this disease are relatively rare in clinical practice. Most of them belong to genetic and metabolic liver diseases, including Gilbert syndrome, Crigler - Najjar syndrome, and Lucey - Driscoll syndrome with an increase in unconjugated bilirubin and Dubin - Johnson syndrome and Rotor syndrome with an increase in conjugated bilirubin. With reference to the recent literature in China and foreign countries, this article reviews the pathogenesis, genetic characteristics, diagnosis, treatment, and differential diagnosis of six types of hereditary congenital unconjugated jaundice. [ABSTRACT FROM AUTHOR]

Nine people with cystic fibrosis (pwCF) were found to have isolated elevations in serum total bilirubin after starting elexacaftor/tezacaftor/ivacaftor (ETI) that were associated with Gilbert's Syndrome. In longitudinal examination, total bilirubin levels increased substantially after initiation of ETI without elevations in liver transaminases in those with this syndrome. Because elevated bilirubin levels in Gilbert's Syndrome are benign, ETI was able to be continued in these individuals. Genetic testing for this relatively common syndrome should be strongly considered for pwCF experiencing isolated hyperbilirubinemia after starting ETI, since appropriate diagnosis may help pwCF avoid unnecessary interruption in this therapy with significant health benefits in CF., (© 2024 Wiley Periodicals LLC.)

UDP-glucuronosyltransferases 1 A (UGT1A) enzymes are capable of detoxifying a broad range of endo- and xenobiotic compounds, which contributes to antioxidative effects, modulation of inflammation and cytoprotection. In the presence of low-function genetic UGT1A variants fibrosis development is increased in various diseases. This study aimed to examine the role of common UGT1A polymorphisms in NASH. Therefore, htgUGT1A-WT mice and htgUGT1A-SNP mice (carrying a common human haplotype present in 10% of the white population) were fed a high-fat Paigen diet for 24 weeks. Serum aminotransferase activities, hepatic triglycerides, fibrosis development and UGT1A expression were assessed. Microscopic examination revealed higher hepatic fat deposition and a significant induction of UGT1A gene expression in htgUGT1A-WT mice. In agreement with these observations, lower serum aminotransferase activities and lower expression levels of fibrosis-related genes were measured in htgUGT1A-SNP mice. This was accompanied by reduced PPARα protein levels in htgUGT1A-WT but not in SNP mice. Our data demonstrate a protective effect of a UGT1A SNP haplotype, leading to milder hepatic steatosis and NASH. Higher PPARα protein levels in animals with impaired UGT1A activity are the likely result of reduced glucuronidation of ligands involved in PPARα-mediated fatty acid oxidation and may lead to the observed protection in htgUGT1A-SNP mice. [ABSTRACT FROM AUTHOR]

Objective  This study aimed to assess the probable relationship between icter in neonates with ABO incompatibility hemolysis and UGT1A1 gene polymorphism. Study Design  There were 65 ABO hemolytic disease of the newborn (HDN) neonates of full term in the study group and 82 non-ABO HDN neonates of full term in the compared group. We tested the UGT1A1 gene mutation of neonates of ABO HDN and non-ABO HDN. We compared the incidence of hyperbilirubinemia between neonates with and without UGT1A1 mutations in the ABO HDN and non-ABO HDN, to determine the relationship between icter in neonates with ABO HDN and UGT1A1 gene polymorphism. SPSS 13.0 were used to analyze those two groups' data. Results  There was statistically significant difference of the serum bilirubin level between the Gly71Arg homozygous and no mutation group in the ABO HDN patients (p  < 0.05). When hyperbilirubinemia was defined as serum bilirubin concentration >342 μmol/L, the incidence of hyperbilirubinemia between patients of UGT1A1 and non-UGT1A1 mutations in the ABO HDN group was significantly different (p  < 0.05). But in the non-ABO HDN group, no significant difference was found. Conclusion  Individuals with Gly71Arg homozygous contributed to their hyperbilirubinemia in ABO HDN patients. [ABSTRACT FROM AUTHOR]

Aim: This study aimed to determine oxidant status and left ventricular mass index (LVMI) and their relationship with mild hyperbilirubinemia in patients with Gilbert syndrome (GS). Background: Gilbert syndrome (GS) presents with mild indirect hyperbilirubinemia, normal liver function tests, and normal hepatic histology. Methods: A total of 84 patients, including 41 (48.8%) patients with GS and 43 (51.2%) patients without GS, were included in the study. Total antioxidant status (TAS), total oxidant status (TOS), and oxidative stress index (OSI) were examined for oxidant status. Results: TAS was found to be higher in the GS patients compared to the non-GS patients (1.7±0.1 vs. 1.5±0.2; p=0.002); there was no significant difference between the groups in terms of mean TOS and mean OSI (p>0.05). No significant difference was observed either between the GS and non-GS patients in terms of mean left ventricular volume and mean LVMI (p>0.05). However, subgroup analysis based on sex revealed that GS patients had a lower LVMI for both sexes. In GS patients, TAS level had a positive correlation with albumin (r=0.319; p=0.042), triglyceride (r=0.392; p=0.011), total bilirubin (r=0.420; p=0.006), direct bilirubin (r=0.361; p=0.020), and indirect bilirubin (r=0.338; p=0.0311) levels; no correlation was found between TAS level and other laboratory findings (p>0.05). The regression model indicated that risk factors of direct bilirubin (β±SE=0.13±0.03; p<0.001), uric acid (β±SE=0.04±0.01; p=0.001), and albumin (β±SE=0.17±0.04; p<0.001) were independent predictors of TAS level. Conclusion: This study revealed a relationship between mild hyperbilirubinemia and antioxidant balance in GS. Although statistical significance was not reached, LVMI was found to be lower in the GS group compared to the non-GS group for both sexes. [ABSTRACT FROM AUTHOR]

After reading an article in the journal, regarding affective disorders in patients with rare illnesses, the authors would like to discuss a case of non-affective psychosis, presenting with olfactory reference and Truman symptoms, in a patient with three unusual conditions: Gilbert disease, Hughes syndrome and Lyme neuroborreliosis. [ABSTRACT FROM AUTHOR]

The article presents a case study of a 21-year-old male swimmer with a history of Gilbert's syndrome presenting to the sports medicine clinic. Topics include patient presenting to the emergency department (ED) with fatigue, dark urine, and jaundice; and profounding transaminitis and splenomegaly in the setting of a confirmed recurrent acute IM.

The article presents a case study of a 17-year-old girl, the first pediatric case of Familial Mediterranean fever (FMF) due to MEFV novel missense mutation (N679H mutation in exon 10 with Gilbert's syndrome. Topics include the hospital because of complaints of chest and abdominal pain along with fever, and the experienced a short duration of menstrual attacks at 11 years of age and visited our hospital because of frequent attacks with additional symptoms of headache and vomiting.

Objective. The spectrum of UDP-glucuronyl transferase A1 (UGT1A1) variants in hereditary unconjugated hyperbilirubinemia varies markedly between different ethnic populations. This study evaluated the UGT1A1 genotypes in hyperbilirubinemia patients from southeastern China. Methods. We enrolled 60 patients from southeastern China (44 men and 16 women; age range: 3–76 years) with unconjugated hyperbilirubinemia and performed genetic analysis of the UGT1A1 gene by direct sequencing. Results. For patients with Gilbert syndrome, 85% (47/55) harbored pathogenic variants of UGT1A1⁎60. Both UGT1A1⁎28 and UGT1A1⁎81 were detected in the promoter region of UGT1A1. Additionally, 83% (20/24) of patients with Gilbert syndrome heterozygous for UGT1A1⁎60 had an association with heterozygous variation of UGT1A1⁎28 or UGT1A1⁎81, while 91% (21/23) of Gilbert syndrome patients homozygous for UGT1A1⁎60 had biallelic variations of UGT1A1⁎28 and UGT1A1⁎81. We detected 213 UGT1A1 allelic variants, including six novel variations, with the most frequent allele being the UGT1A1⁎60, followed by UGT1A1⁎28 and UGT1A1⁎6. All of the patients showed multiple sites of variants in UGT1A1; however, variation number was not associated with bilirubin levels (P>0.05). Conclusions. The spectrum of UGT1A1 variants in southeastern Chinese patients was distinct from other ethnic populations. Our findings broaden the knowledge concerning traits associated with UGT1A1 variants and help profile genotype–phenotype correlations in hyperbilirubinemia patients. [ABSTRACT FROM AUTHOR]

Hereditary hiperbilirrubinemias (HBH) are pathologies originated from the defect of the enzymes and proteins involved in the metabolism of bilirubin. The bilirubin clearance includes uptake and storage in hepatocytes, conjugation, excretion into bile and recapture of its conjugated form by hepatocytes. HBH vary according to their pathogenesis, clinical presentation, levels of bilirubin and available treatments. Generally they are infrequent, except for Gilbert Syndrome. There are those with indirect bilirubin predominance, such as Gilbert and Crigler-Najjar syndromes, and those with direct bilirubin predominance, including Dubin-Johnson and Rotor syndromes. In general, they do not require specific treatment and have a benign course, with the exception of the Crigler-Najjar Syndrome, for which there are specific therapeutic measures to consider, as well as a reserved prognosis for some of their forms of presentation. The knowledge of these syndromes is important given the high index of suspicion required for its diagnosis and for its differentiation from other hepatobiliary pathologies of greater risk and severity. [ABSTRACT FROM AUTHOR]

Background/objectives Individuals with Gilbert's syndrome (GS) harbor mutations in the UGT1A1 gene and are known to have elevated levels of bilirubin, which enhances the risk for gall stone formation. The aim of this study is to screen Indian patients with GS for the incidence of gall stone disease. Methods Individuals with persistently elevated serum bilirubin levels were genotyped for two polymorphisms (rs8175347; rs4148323) in UGT1A1 gene to confirm GS in them. Flanking regions of the above polymorphisms were amplified followed by direct sequencing. Ultrasonography was done to detect gallstone disease. Clinical data, including assessment of liver function, circulating levels of total and direct bilirubin, as well as routine hematological parameters were obtained as per standard procedures (Autoanalyzer). Results Of the total 1621 individuals subjected to genotyping, 1191 (1149 males of 29.6 ± 11.3 years with mean BMI of 22.1 ± 3.7 kg/m2 and 42 females of 30.8 ± 14.8 years with mean BMI of 20.9 ± 3.7 kg/m2) were confirmed to have GS. Gall bladder abnormalities including cholelithiasis (n = 106/1191; 8.9%), polyps (n = 18/1191; 1.5%) and gallbladder wall thickening (n = 17/1191; 1.4%) were noted. Incidence of gall stone disease was observed in 103 males (out of 1149) and 3 females (out of 42) indicating the risk of the disease to be 9.0% and 7.1% respectively in males and females with GS. Conclusion Early recognition of GS by genetic analysis is required before these patients with intermittent episodes of jaundice run the risk of unnecessary operations on their bile ducts from the mistaken assumption ascribing the jaundice to a stone which has been left behind. [ABSTRACT FROM AUTHOR]

Small cell lung cancer (SCLC) was highly malignant and lack effective treatment after the failure of radiotherapy and chemotherapy. Antiangiogenic therapy had shown a certain effect in advanced SCLC. Apatinib, a new potent oral small-molecule tyrosine kinase inhibitor targeting the intracellular domain of vascular endothelial growth factor receptor 2 (VEGFR-2), showed the effect of anti-angiogenesis. However, the efficacy in SCLC was rarely reported. We reported 1 case of advanced SCLC with Gilbert syndrome, the patient received Apatinib after the failure of 4 lines of chemotherapy, and achieved a partial response according to the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 standard after one month. The progression-free survival (PFS) was 5 months. Apatinib was well tolerated except recurrent grade 3 hyperbilirubinemia because of the metabolic disorder of Bilirubin. Salvage treatment with Apatinib for advanced SCLC deserved further exploration. [ABSTRACT FROM AUTHOR]

This review focuses on the perioperative anesthetic management of patients having liver transplantation (LT) performed for several uncommon indications or in combination with rare pathology. Conditions discussed in the article include Alagille syndrome, hypertrophic cardiomyopathy, Gilbert's syndrome, porphyria, Wilson's disease, and Budd-Chiari syndrome. In comparison to other indications, LT in these settings is infrequent because of the low incidence of these pathologies. Most of these conditions (with the exception of Gilbert syndrome) are associated with a high probability of significant perioperative complications and increased mortality and morbidity. Experience in management of these unusual conditions is only gained over time. Developing clinical pathways for patients with these conditions should result in outcomes similar to LT performed for more common indications. [ABSTRACT FROM AUTHOR]

Hyperbilirubinemia is a well-known condition in the clinical setting; however, the causes of elevated serum bilirubin are diverse, as are the clinical ramifications of this condition. For example, diagnoses of individuals vary depending on whether they exhibit an unconjugated or conjugated hyperbilirubinemia. Diagnoses can include conditions of disordered bilirubin metabolism (Gilbert’s, Crigler-Najjar, Rotor, or Dubin-Johnson syndromes) or an acquired disease, including alcoholic/non-alcoholic fatty liver disease, hepatotropic hepatitis, cirrhosis, or hepato-biliary malignancy. Assessment of bilirubin concentrations is typically conducted as part of routine liver function testing. Mildly elevated total bilirubin with normal serum activities of liver transaminases, biliary damage markers, and red blood cell counts, however, may indicate the presence of Gilbert’s syndrome (GS), a benign condition that is present in ∼5–10% of the population. In this case, mildly elevated unconjugated bilirubin in GS is strongly associated with “reduced” prevalence of chronic diseases, particularly cardiovascular diseases (CVD) and type 2 diabetes mellitus (and associated risk factors), as well as CVD-related and all-cause mortality. These reports challenge the dogma that bilirubin is simply a potentially neurotoxic by-product of heme catabolism and emphasize the importance of understanding its potential beneficial physiologic and detrimental pathophysiologic effects, in order to appropriately consider bilirubin test results within the clinical laboratory setting. With this information, we hope to improve the understanding of disorders of bilirubin metabolism, emphasize the diagnostic importance of these conditions, and outline the potential impact GS may have on resistance to disease. [ABSTRACT FROM AUTHOR]

Background and aims Mild endogenous elevation of unconjugated bilirubin (UCB) as seen in Gilbert's syndrome (GS), might mitigate cardiovascular disease (CVD) risk factors including overweight/obesity. This study aimed to determine whether hyperbilirubinaemia is linked to improved anthropometric data and lipid profile. Methods Our study considered GS and age-/gender-matched healthy controls (n = 248). Additionally, obese female type 2 diabetic patients (DM2) (n = 26) were included as a “disease control group”. Results BMI, hip circumference (HC), and lipid profile were significantly lower in GS. UCB was inversely correlated with BMI ( p  <0 .001), HC as well as with fat mass (FM) and lipid variables ( p  < 0.05). Moreover, DM2 patients had significantly lower UCB compared to GS and healthy controls. Older GS subjects (≥35 years) had significantly reduced anthropometric data and improved lipid profile. Conclusions Our results propose that the health promoting potential of mild hyperbilirubinaemia may extend to protection from age-related weight gain and dyslipidaemia. [ABSTRACT FROM AUTHOR]

Due to a liver defect in lipid metabolism, patients with inherited heterozygous familial hypercholesterolemia (FH) are especially at risk for atherosclerotic cardiovascular disease (ASCVD). This likelihood is due to the cumulative effect of high cholesterol which starts at a young age. Gilbert's Syndrome (GS) is a separate genetic liver disease that results in mildly increased serum unconjugated bilirubin which is postulated to be cardioprotective for ASCVD. Both GS and FH represent two separate genetic liver diseases, one beneficial and one a leading cause of morbidity and mortality. It appears that the deleterious effect of one mutation may be offset by the beneficial effect of the second mutation resulting in an inverse relationship between the two diseases. The incidence of GS is reported to be 16%, however, that figure is probably an underestimate. GS is underdiagnosed and under reported as it is considered benign and is usually an incidental finding. Identifying concurrent GS and FH is important because it can affect treatment choices for hypercholesteremia. This review examined the recent literature and analyzed the current evidence that suggests that the combination of FH and concurrent GS affords cardiovascular protection. 37 publications were reviewed to synthesize and evaluate the quality of existing evidence and to shed some light on the possible mechanisms of this association, identify research gaps, and shape future research. This was a systematic review of peer-reviewed publications. Publications were identified using databases: EBSCO Discovery, World Cat, PubMed, OVID, Google Scholar, Springer, Theime, Elsevier/Scopus, Science Direct, and Cochrane Collaboration. Publications ranged from 2003-2021 and included studies on adults from age 18-80 and bench studies using Gunn rats. Recent retrospective and prospective studies indicate that mildly elevated levels of serum bilirubin (especially the UGTA1A*28 allele), in patients with concurrent GS and FH, are protective against ASCVD. Gilbert's Syndrome is postulated be cardioprotective for ASCVD. The inverse relationship between ASCVD and GS has not become mainstream and is overdue. This review underscores the importance of identifying patients with circulating bilirubin from GS and with concurrent hypercholesteremia, especially FH. These are not uncommon diseases, and their co-existence has been underestimated because GS is considered benign and underreported. The potential exists for patients with hypercholesteremia and silent Gilbert's Syndrome to be overtreated or unnecessarily treated with statins. It is recommended that both FH and Gilbert's Syndrome be routinely screened for in pediatric and adult populations especially prior to statin prescribing. Special thanks to Michael Brown, M.D., 1985 Nobel Prize recipient, for his interest and encouragement. No [ABSTRACT FROM AUTHOR]

Background Gilbert syndrome (GS) is a common hereditary condition, characterized by intermittent unconjugated hyperbilirubinemia. In adults with type 2 diabetes and GS, a markedly lower prevalence of nephropathy was documented, suggesting a beneficial effect of hyperbilirubinemia. We investigated the prevalence of GS among individuals with type 1 diabetes mellitus (T1DM), and the prevalence of microalbuminuria. Methods The prevalence of GS was assessed in 401 (204 female) patients with T1DM, median age 21.0 years, (interquartile range [IQR], 15.7-27.9), median disease duration 10.8 years (IQR, 5.7-15.8); and was compared with GS prevalence in 181 children (control). The prevalence of microalbuminuria was assessed in patients with T1DM and GS (group I) and compared with that of patients with T1DM alone (group II), in a ratio of 1:2 matched by gender, age, and duration of diabetes. Results The prevalence of GS in TIDM patients was significantly higher than in the control group (10.7% vs 3.3% respectively, p = .004), with no gender difference. Patients with T1DM and GS had significantly lower HbA1c levels than did those with T1DM alone 7.3 ± 1.2 vs 7.9 ± 1.3% respectively (56 ± 13 vs 63 ± 14 mmol/mol), p = .02. The rate of microalbuminuria was 14.0% vs 11.0% for patients with T1DM and GS, compared with those with T1DM alone (p = .6). Conclusions The occurrence of GS was 3-fold higher among individuals with T1DM than in a healthy control group. Despite better glycemic control, the rate of microalbuminuria was similar among young individuals with T1DM and GS, and those with T1DM alone, suggesting no protective value to elevated bilirubin. [ABSTRACT FROM AUTHOR]

Gilbert’s syndrome (GS) is associated with a mild unconjugated hyperbilirubinemia, increased circulating antioxidant capacity, and reduced cardiovascular disease (CVD) risk. The current study investigated whether mildly elevated circulating unconjugated bilirubin (UCB) is negatively associated with multiple thrombotic risk factors including platelet activity, hemostatic function, and inflammation in individuals with GS. Blood samples were collected from matched GS and control subjects (14 per group). Activation-dependent platelet surface marker expression of PAC-1 (binds to GPIIb/IIIa surface receptors on activated platelets) and CD62P (marker for P-selectin released from activated degranulated platelets) was assessed in adenosine diphosphate (ADP)-stimulated platelets using flow cytometry. Exogenous agonists, ADP, collagen, and arachidonic acid (AA), were used to stimulate platelet aggregation. A statistically significant decrease in the expression of P-selectin (P= 0.030) on activated platelets was observed in GS subjects. Collagen and AA-induced platelet aggregation were significantly (P =0.018;P= 0.032 for respective agonists) reduced in GS versus control group. Elevated UCB (P= 0.001) and high density lipoprotein (P= 0.033) in addition to reduced low density lipoprotein (P= 0.024) and high sensitive C-reactive protein (P =0.043) were also observed in GS when compared to the control group. Reduced P-selectin expression suggests decreased platelet activation-dependent degranulation, while reduced platelet aggregation by AA and collagen indicates a quantitative decrease in platelet aggregation consequently targeting the cyclooxygenase-1 and GP VI pathways, respectively. These findings are the first to demonstrate that the activation of platelets is mildly inhibited in individuals with GS, an effect that might contribute to protection from platelet hyperactivation-induced thrombosis and thus cardiovascular mortality in individuals with benign hyperbilirubinemia. [ABSTRACT FROM AUTHOR]

The article presents a case study of a 28-year-old man who presented with abdominal pain, nausea, and vomiting, discussing his stages of condition and response. Indirect hyperbilirubinemia and Gilbert's syndrome were primary diagnosis and reticulocytosis as a response to hemolysis. Further evaluation of hemolysis suggested uncommon cause, hereditary spherocytosis.

Aims Bilirubin is associated with reduced risk of cardiovascular disease, as evidenced in conditions of mild hyperbilirubinaemia (Gilbert's Syndrome). Little is known regarding myocardial stress resistance in hyperbilirubinaemic conditions or whether life-long exposure modifies cardiac function, which might contribute to protection from cardiovascular disease. Methods Hyperbilirubinaemic rats and littermate controls underwent echocardiography at 3, 6 and 12 months of age, with hearts subsequently assessed for resistance to 30 min of ischaemia. Heart tissue was then collected for assessment of bilirubin content. Results No difference in baseline cardiac function was evident until 6 months onwards, where Gunn rats demonstrated aortic dilatation and reduced peak ejection velocities. Additionally, duration of ventricular ejection increased progressively, indicating a negative inotropic effect of bilirubin in vivo. Ex vivo analysis of baseline function revealed reduced left ventricular pressure development ( LVDP) and contractility in hyperbilirubinaemic rats. Furthermore, stress resistance was improved in Gunn hearts: post-ischaemic recoveries of LVDP (76 ± 22% vs. 29 ± 17% Control, P < 0.01) and coronary flow (96 ± 9% vs. 86 ± 16% Control, P < 0.01) were improved in Gunn hearts, accompanied by reduced infarct area (21 ± 5% vs. 47 ± 15% Control, P < 0.01), and ventricular malondialdehyde and protein carbonyl content. Expression of myocardial nitric oxide-regulating genes including Nos1 and Noa1 were not significantly different. Conclusions These data reveal life-long hyperbilirubinaemia induces age-dependent hypocontractility in male Gunn rats, and improved stress resistance. In addition, bilirubin exerts sex-independent effects on vascular structure, myocardial function and ischaemic tolerance, the latter likely mediated via bilirubin's antioxidant properties. [ABSTRACT FROM AUTHOR]

Objective(s): Mutations in the UGT1A1 gene are responsible for hyperbilirubinemia syndromes including Crigler-Najjar type 1 and 2 and Gilbert syndrome. In view of the genetic heterogeneity and involvement of large numbers of the disease causing mutations, the applicat ion of polymorphic markers in the UGTA1 gene could be useful in molecular diagnosis of the disease. Materials and Methods: In the present study, two polymorphic markers including rs4148326 and rs4124874 in the UGT1A1 gene region were characterized. The markers were selected using bioinformatics analysis of the UGT1A1 gene region and genotyped in 212 unrelated healthy individuals and 13 family trios in the Iranian population using Tetra-Primer ARMS PCR technique. The allele frequency and population status of the alleles were estimated using GENEPOP, FBAT, PowerMarker and Arlequin software. Results: The results indicated that in the case of rs4148326 marker, allele frequency for T and C allele was 66.04% and 33.96%, respectively. For rs4124874 marker, allele frequency for G and T alleles was 39.4% and 60.6%, respectively. The values of heterozygosity index for the markers examined were 64.1 for rs4148326 and 72.1 for rs4124874, respectively. The haplotype estimation analysis of the markers resulted in three informative haplotypes with frequencies =0.05. Moreover, the results suggested the presence of linkage disequilibrium between two markers. Conclusion: Altogether, the data suggested that rs4148326 and rs4124874 could be introduced as informative markers for molecular diagnosis of Crigler-Najjar type 1 and 2 and Gilbert syndrome in the Iranian population. [ABSTRACT FROM AUTHOR]