Pathogenesis Of Hyperbilirubinemia Research Articles

Hyperbilirubinemia after surgical repair for acute type a aortic dissection: A propensity score-matched analysis.

Background: Inflammation and oxidative stress are known to participate in the pathogenesis of hyperbilirubinemia. It has been known that acute type A aortic dissection (ATAAD) surgical repair often associates with complications which might affect the long-term prognosis. However, the clinical significance of postoperative hyperbilirubinemia (PH) has not been evaluated. Here in this study, we examined the incidence, risk factors, and prognosis of PH after ATAAD surgery. Methods: This retrospective study enrolled a total of 970 patients who received ATAAD surgical repair from January 2014 to December 2019. PH was defined as serum total bilirubin >3.0 mg/dl within the first week after the surgery. Propensity score matching was used to reduce selection bias and eliminate potential confounding factors. Kaplan–Meier survival and Cox proportional hazards regression analyses were conducted to explore the association between PH and postoperative long-term survival. Results: Development of PH (183 patients) was associated with a higher 30-Day mortality (20.8% vs. 9.0%, p < 0.001). Advanced age [odds ratio (OR) 1.538, p = 0.006], higher baseline total bilirubin level (OR 1.735, p = 0.026), preoperative pericardial tamponade (OR 3.192, p = 0.024), prolonged cardiopulmonary bypass (CPB) duration (OR 2.008, p = 0.005), and elevated postoperative central venous pressure (CVP) level (OR 2.183, p < 0.001) were associated with PH. The Kaplan-Meier analysis showed patients who developed PH were associated with poor long-term survival (p = 0.044). Cox analysis showed that the presence of PH (hazard ratio 2.006, p = 0.003) was an independent risk factor for increased mortality. Conclusion: PH is a common complication in patients undergoing ATAAD surgical repair that associates with worse short- and long-term prognosis. Our data indicated that age, preoperative total bilirubin level, pericardial tamponade, CPB duration, and postoperative CVP level were risk factors for the development of PH.

UGT1A1 gene mutations in Chinese Dong neonates in Sanjiang, Guangxi

To study the characteristics of UGT1A1 gene mutations in Dong neonates in Sanjiang County of Liuzhou and its association with the pathogenesis of hyperbilirubinemia in Dong neonates. A prospective analysis was performed on 84 neonates who were diagnosed with unexplained hyperbilirubinemia in the Department of Neonatology, Sanjiang County People's Hospital, from January 2021 to January 2022. Sixty healthy neonates born during the same period were enrolled as the control group. Peripheral blood genomic DNA was extracted for both groups, and UGT1A1 exon 1 was amplified by PCR and sequenced. In the case group, 33 neonates were found to have G71R missense mutation, with a mutation rate of 39%. The case group had a significantly higher frequency of A allele than the healthy control group (21% vs 10%, P<0.05). The risk of hyperbilirubinemia in Dong neonates carrying G71R missense mutation was 2.588 times as high as that in healthy neonates carrying wild-type UGT1A1 gene (P<0.05). Hardy-Weinberg equilibrium testing showed that the UGT1A1 G71R locus was in genetic equilibrium in both groups (P>0.05). UGT1A1 G71R mutation is a high-frequency gene mutation type in Dong neonates in Sanjiang County, and G71R missense mutation is associated with hyperbilirubinemia in Dong neonates.

Biliary drainage in pancreatic cancer: The endoscopic retrograde cholangiopancreatography perspective.

Biliary drainage in pancreatic cancer: The endoscopic retrograde cholangiopancreatography perspective.

Neonatal Hyperbilirubinemia: Don't Let Glucose-6-phosphate Dehydrogenase Deficiency off the Hook

To the Editor .— We read with great interest the recent article by Keren et al,1 in which factors predictive of neonatal hyperbilirubinemia were sought. We found it particularly surprising that glucose-6-phosphate dehydrogenase (G6PD) deficiency did not reach significance as a risk factor and seemed to be nonpredictive of jaundice. This finding is contrary to those of previous studies in which G6PD deficiency was found to be a major factor in the pathogenesis of hyperbilirubinemia and was highly associated with extreme hyperbilirubinemia and kernicterus. Recent examples of this association emanate from the United States, Canada, and the United Kingdom and …

Studies in hemolysis in glucose-6-phosphate dehydrogenase-deficient African American neonates

Background The role of hemolysis in the mechanism and prediction of hyperbilirubinemia was contrasted between glucose-6-phosphate dehydrogenase (G-6-PD)-deficient and -normal African American neonates. Methods Corrected end tidal carbon monoxide (ETCOc) values from the subset of male neonates born to non-smoking African American mothers, drawn from a previously published study, were analyzed. The relationship between ETCOc and bilirubin values, the latter represented as percentiles on the hour of life specific bilirubin nomogram, was determined. Hyperbilirubinemia was defined as any bilirubin value ≥ 95th percentile for hour of life. Results 18.6% of 59 G-6-PD-deficient neonates developed hyperbilirubinemia, compared with 7.5% of 362 controls (relative risk 2.50, 95% confidence interval 1.31 to 4.76). As reported, ETCOc values (median, interquartile range) were significantly higher among G-6-PD-deficient neonates than controls (2.4 [2.0–2.9] vs. 2.1 [1.7–2.5] ppm, p < 0.001. However, higher ETCOc values were limited to those G-6-PD-deficient neonates with lower bilirubin percentiles: among those whose bilirubin value did not exceed the 95th percentile ETCOc was 2.30 [2.00–2.85] vs. 2.00 [1.70–2.40] ppm in controls, p = 0.001. In contrast, among the hyperbilirubinemic neonates ETCOc values were similar between G-6-PD-deficient neonates and controls: 2.7 [2.03–3.33] vs. 2.6 [2.33–3.45] ppm, p = 0.9. In the G-6-PD-deficient neonates ETCOc ≥ 75th percentile contributed no additional predictive value for hyperbilirubinemia (likelihood ratio 1.8). Conclusions G-6-PD-deficient African American neonates have increased hemolysis and increased rate of hyperbilirubinemia, but the hemolysis is neither a predominant factor in the pathogenesis of hyperbilirubinemia nor is it predictive of hyperbilirubinemia, over and above the already increased risk conferred by G-6-PD deficiency.

Simultaneous Presence of Gilbert Syndrome and Hereditary Spherocytosis: Interaction in the Pathogenesis of Hyperbilirubinemia and Gallstone Formation

Simultaneous Presence of Gilbert Syndrome and Hereditary Spherocytosis: Interaction in the Pathogenesis of Hyperbilirubinemia and Gallstone Formation

Unusual hyperbilirubinemia associated with bacterial pneumonia and acute myeloid leukemia

A 77-year-old man with pneumonia associated with acute myeloid leukemia was introduced to the hepatology unit at our hospital for hyperbilirubinemia. He had been suffering from a high fever because of pneumonia. He was icteric and his serum concentrations of total and direct bilirubin were 13.1 and 7.9 mg/dl, respectively. However, the other standard biochemical examinations for hepatic function, such as serum concentrations of aspartate aminotransferase, alanine aminotransferase, gamma-glutamyl transpeptidase and alkaline phosphatase were normal except for lactate dehydrogenase. Lactate dehydrogenase isoenzyme analysis revealed that the high concentration was derived from leukemia cells. Ultrasonography of the abdomen revealed no abnormality in the liver or biliary tract. Administration of antibiotics for pneumonia decreased the serum bilirubin concentration, however, he died because of respiratory failure caused by the progression of pneumonia at 33 days after the admission. It was suggested that a disturbance in the bilirubin metabolism without hepatocyte necrosis or mechanical cholestasis might be involved in the pathogenesis of hyperbilirubinemia in patients with infectious diseases.

Simultaneous Presence of Gilbert Syndrome and Hereditary Spherocytosis: Interaction in the Pathogenesis of Hyperbilirubinemia and Gallstone Formation

(2003). Simultaneous Presence of Gilbert Syndrome and Hereditary Spherocytosis: Interaction in the Pathogenesis of Hyperbilirubinemia and Gallstone Formation. Pediatric Hematology and Oncology: Vol. 20, No. 6, pp. 493-495.

Tumor necrosis factor-α and interleukin-6 reduce bile canalicular contractions of rat hepatocytes

Background. Surgeons sometimes encounter hyperbilirubinemia without mechanical obstruction of the biliary tree postoperatively. Many of these patients have bacterial infections and endotoxemia. Kupffer's cells stimulated by endotoxin secrete inflammatory cytokines such as tumor necrosis factor (TNF)-α and interleukin (IL)-6. We hypothesized that TNF-α and IL-6 might be involved in the pathogenesis of hyperbilirubinemia. Methods. Effects of TNF-α and IL-6 on the contractions of bile canaliculi (BC) of rat hepatocyte couplets were examined and time-lapse images using phase-contrast microscopy were taken. Bile was collected from rats treated with or without the cytokines. The livers, perfused with lanthanum after the injection of cytokines, were examined ultrastructurally using electron microscopy. Results. The number of BC contractions decreased in the couplets treated with both cytokines. The rapid movement of a droplet from BC was observed at the intercellular space of the hepatocyte couplet treated with TNF-α. Systolic blood pressure and hepatic tissue blood flow of rats injected with TNF-α were not changed, whereas the hepatic tissue blood flow of rats treated with IL-6 decreased (Dunnett test, P <.05). Bile secretion was reduced in both groups of rats (Dunnett test, P <.05). In rats treated with TNF-α the total serum bile acid concentration increased and lanthanum temporarily accumulated in BC. Conclusions. These results suggest that TNF-α and IL-6 may reduce BC contractions and thereby decrease bile flow. (Surgery 2003;133:101-9).

Glucose-6-Phosphate Dehydrogenase Deficiency: A Worldwide Potential Cause of Severe Neonatal Hyperbilirubinemia

After completing this article, readers should be able to: 1. Explain methods of preventing the hyperbilirubinemia caused by glucose-6-phosphate dehydrogenase (G6PD) deficiency. 2. Compare and contrast the correlation between hemolysis and serum bilirubin levels in healthy infants and those who are G6PD-deficient. 3. Describe the role of deficient bilirubin conjugation in the pathogenesis of G6PD deficiency-associated neonatal hyperbilirubinemia. 4. Define the risk for neonatal hyperbilirubinemia in female G6PD-deficient heterozygotes, G6PD-deficient homozygotes, and hemizygote males. Glucose-6-phosphate dehydrogenase (G6PD) deficiency, a commonly occurring X-linked genetic enzyme defect, is notorious for its association with acute hemolytic crises occurring in response to a frequently identifiable trigger (favism). Another potentially devastating danger of this condition is severe neonatal hyperbilirubinemia with its accompanying bilirubin encephalopathy, kernicterus, and death. Far from being a condition limited to historical time epochs and developing countries, G6PD deficiency-associated kernicterus still is seen in modern times. Indeed, among 80 infants from 21 states in the United States documented in a pilot Kernicterus Registry between 1984 and 1998, 18 (22.5%) were reported to have G6PD deficiency. Furthermore, Maisels recently listed G6PD deficiency among the 10 factors that are associated most commonly with an increased risk of nonhemolytic jaundice. Because of the association with favism, G6PD-associated hyperbilirubinemia traditionally has been regarded as hemolytic in origin. However, recent research has shown that although acute hemolysis does play a role, its contribution in many cases may be smaller than previously thought. The emphasis now has been placed on decreased bilirubin conjugation, with promoter polymorphism for the gene for the bilirubin conjugating enzyme, UDP glucuronoslytransferase 1A1 (UGT1A1), being a major factor in production of the icterus. In this review we highlight key aspects of the pathogenesis of this type of hyperbilirubinemia, explain the relevance of the condition, and describe a particularly problematic group that has a recently recognized high incidence of …

Expression of a putative ATP-binding cassette region, homologous to that in multidrug resistance-associated protein (MRP), is hereditarily defective in Eisai hyperbilirubinemic rats (EHBR)

Abstract It is well established that several organic anions such as leukotriene C4 and S-(2,4-dinitrophenyl)-glutathione are excreted into the bile via an ATP-dependent primary active transporter located on the bile canalicular membrane. Although the molecular features of this transporter still remain to be clarified, this transporter might be a member of the ATP-binding cassette (ABC) transmembrane transporter superfamily which has a common ABC region. In the present study, a cDNA fragment was amplified from Sprague-Dawley (SD) rat liver by PCR using degenerate primers prepared from the conserved sequence in the COOH-terminal ABC region of human multidrug resistance-associated protein (MRP), a primary active transporter. The amplified 421 bp fragment exhibited homology with a human MRP and the human MRP-like fragment (yp75a11) with homology score of 66.3% and 83.0% at the cDNA level, and 73.3% and 84.7% deduced from the amino acid level, respectively. Northern blot analysis of poly(A)+ RNA prepared from SD rat liver revealed the presence of ~5 kb and 8.5 kb mRNA species which hybridized to this fragment. In contrast, poly(A)+ RNA from Eisai hyperbilirubinemic rats (EHBR), whose primary active transporter on the bile canalicular membrane is hereditarily defective, did not hybridize to this fragment. These results suggest (1) that the impaired expression of this particular region might be related to the pathogenesis of hyperbilirubinemia in EHBR and (2) that this region might encode part of the primary active transporter on the bile canalicular membrane.

肝切除術後の高ビリルビン血症の病態 肝汁中ビリルビン亜分画分析とその意義

肝切除術後の高ビリルビン血症の病態 肝汁中ビリルビン亜分画分析とその意義

Clinical significance and pathogenesis of hyperbilirubinemia associated with Staphylococcus aureus septicemia1

Clinical significance and pathogenesis of hyperbilirubinemia associated with Staphylococcus aureus septicemia1