Conjugated Bilirubin Levels Research Articles

Conjugated Hyperbilirubinemia in Children

A variety of anatomic, infectious, autoimmune, and metabolic diseases can lead to conjugated hyperbilirubinemia, both in the newborn period and later in childhood. The pediatric practitioner is most likely to encounter conjugated hyperbilirubinemia in the neonatal period.It is crucial to maintain a high degree of suspicion for cholestasis in the persistently jaundiced newborn. The goal is recognition of conjugated hyperbilirubinemia between 2 and 4 weeks after birth, allowing for the prompt identification and management of infants who have biliary atresia, which remains the most common cause of neonatal cholestasis.

Comparative serum biochemical changes in mongrel dogs following single and mixed infections of Trypanosoma congolense and Trypanosoma brucei brucei

The serum activities of alkaline phosphatase (AP), alanine aminotransferase (ALT), aspartate aminotransferase (AST) and the serum levels of conjugated bilirubin (CB), blood urea nitrogen (BUN) and creatinine were studied following single and mixed infections of mongrel dogs with Trypanosoma congolense and Trypanosoma brucei brucei.Twenty mongrel dogs of both sexes aged between 3 and 6 months, and weighing between 2.5 and 5.9kg were used for the study. The dogs were kept in clean metal cages in a fly-proof house and were fed and given water ad libitum. The twenty dogs were divided into four groups of five dogs each. Group I dogs were uninfected control, group II were infected with T. congolense, group III were infected with T. brucei brucei and group IV were infected with both T. congolense and T. brucei brucei. Each dog in the infected groups II and III was inoculated intraperitonealy (i/p) with 1.0ml of PBS diluted blood containing 1.0×106 trypanosomes whereas each infected dog in group IV (mixed infection) was inoculated with 0.5ml of the PBS diluted blood containing 0.5×106T. congolense and 0.5ml of the PBS diluted blood containing 0.5×106T. brucei brucei i/p.Parasites were detectable in the blood of the infected dogs in groups II, III, and IV 10–13 days post infection (PI) with the mean pre-patent period (PP) of 12, 10, and 11 days respectively. Trypanosome infection caused a significant (P<0.05) increase in the serum activities of AP, ALT, AST and the serum levels of creatinine, CB, and BUN. The significant increases in the serum levels of CB, BUN, and creatinine and serum activities of AP and AST became noticeable from day seven PI in all the infected groups whereas that of ALT became noticeable from day 14 PI and increased continuously until the experiment was terminated. These increases however did not differ significantly (P>0.05) between the infected groups in most cases.It was thus concluded that single or mixed infection of mongrel dogs with T. congolense and T. brucei brucei resulted in significant increases in the serum activities of AP, AST, ALT and serum levels of creatinine, CB and BUN which in most cases did not differ significantly (P>0.05) among the infected groups.

Change from intralipid to SMOF lipid is associated with improved liver function in infants with PN associated liver disease

<h3>Background and aims</h3> Parenteral nutrition associated liver disease (PNALD) accounts for substantial morbidity and mortality in infants with intestinal failure. Lipid formulations may be important determinants of PNALD development. Newer lipid preparations e.g. SMOF lipid (SMOF) containing omega-3 and medium chain triglycerides have theoretical benefits over standard soya-based lipid (eg: intralipid (IL) and may minimise PNALD. This study aimed to investigate the effects of a change in lipid formulation, from IL to SMOF, on liver function in infants with PNALD. <h3>Method</h3> This retrospective review was performed following an initial pilot study. Data were obtained by case-note review of infants with PNALD (conjugated bilirubin (CB) &gt;50 µmol/L) commenced initially on IL and subsequently changed to SMOF, as per Unit protocol. Liver function (CB, AST, ALT levels, and the change in each of these per week: ΔCB, ΔAST, ΔALT) was compared before and after change in lipid (figure 1). <h3>Results</h3> Data were obtained for 14 infants of median (range) gestation 29 (24-40) weeks, birth weight 1.23 (0.53-3.66) kg. Median duration of parenteral nutrition was 89 (19-212) days. Median age at change from IL to SMOF was 50 (22-142) days. Change from IL to SMOF was associated with a significant reduction in ΔCB after 2 weeks and 4 weeks of SMOF therapy (table 1 and figure 1) i.e. the weekly rate of increase in CB levels was reduced (and later reversed) after change to SMOF. Accordingly, absolute CB levels stabilised after change from IL to SMOF. ΔAST and ΔALT, and absolute levels of AST and ALT, also trended lower after 4 weeks of SMOF therapy. <h3>Conclusions</h3> Change from IL to SMOF was associated with improved liver function in infants with PNALD. This data supports the use of SMOF in infants requiring long-term PN therapy to minimise PNALD. Further study is required to determine the optimum timing for commencement of SMOF use.

Ezetimibe: A biomarker for efficacy of liver directed UGT1A1 gene therapy for inherited hyperbilirubinemia

As recently demonstrated in patients with factor IX deficiency, adeno‐associated virus (AAV)-mediated liver-directed therapy is a viable option for inherited metabolic liver disorders. Our aim is to treat Crigler-Najjar syndrome type I (CN I), an inherited severe unconjugated hyperbilirubinemia, as a rare recessive inherited disorder. Because the number of patients eligible for this approach is small, the efficacy can only be demonstrated by a beneficial effect on the pathophysiology in individual patients. Serum bilirubin levels in potential candidates have been monitored since birth, providing an indication of their pathophysiology. Adjuvant phototherapy to prevent brain damage reduces serum unconjugated bilirubin (UCB) levels in CN I patients to the level seen in the milder form of the disease, CN type II. This therapy increases the excretion of UCB, thereby complicating the use of UCB and conjugated bilirubin levels in serum as biomarkers for the gene therapy we try to develop. Therefore, a suitable biomarker that is not affected by phototherapy is currently needed. To this end, we have investigated whether estradiol, ethinylestradiol or ezetimibe could be used as markers for uridine 5'-di-phospho-glucuronosyltransferase isoform 1A1 (UGT1A1) activity restored by AAV gene therapy in Gunn rats, a relevant animal model for CN I. Of these compounds, ezetimibe appeared most suitable because its glucuronidation rate in untreated control Gunn rats is low. Subsequently, ezetimibe glucuronidation was studied in both untreated and AAV-treated Gunn rats and the results suggest that it may serve as a useful serum marker for restored hepatic UGT1A1 activity.

Lack of recovery from hepatic oxidative damage in rats treated with Nigerian bonny light crude oil

The use of Nigerian bonny light crude oil (BLCO) in the treatment of gastrointestinal disorders, burns, foot ulcers and reproductive capacity is a common practice in the southern part of Nigeria. Towards understanding the mechanism and the reversibility of hepatotoxicity induced by BLCO, adult male Wistar rats were orally administered with BLCO at 0, 50, 100 and 200 mg kg(-1) for 21 days. One-half of the rats were sacrificed on day 22, whereas the remaining half stayed for an additional 21 days without treatment. Whereas the activities of antioxidant enzymes such as superoxide dismutase, catalase, glutathione S-transferase were significantly (p < 0.05) increased, gamma glutamyl transferase activity was significantly decreased in a dose-dependent manner. The levels of glutathione, hydrogen peroxide and malondialdehyde were significantly elevated in BLCO-treated animals. In addition, hepatic degeneration was accompanied with elevation in serum aminotransferases activities without affecting bilirubin levels. Whereas most of the above-mentioned parameters were consistent in animals from withdrawal experiment, both total and conjugated bilirubin levels were significantly increased after 21 days of BLCO-treatment withdrawal. Taken together, BLCO-induced hepatotoxicity could be due to increased oxidative stress which was not reversible upon withdrawal of treatment within the time course of investigation in male rats.

The Beneficial Impact of Revision of Kasai Portoenterostomy for Biliary Atresia

To determine whether portoenterostomy (PE) revision in patients afflicted with biliary atresia (BA) is a viable treatment option and, if so, identify which patients may benefit. BA, the most common cause of neonatal liver disease, results in biliary tract obstruction and hepatic fibrosis. Kasai PE is the initial surgical intervention performed and, if successful, restores drainage and preserves the native liver. Portoenterostomy failure warrants liver transplantation, but because of complications related to transplantation, treatment strategies to salvage the native liver may be beneficial. Using uniformly applied criteria, we have revised PEs to delay or avoid transplantation. A retrospective review of medical records of patients diagnosed with BA since 1983 was performed. Patient demographics, symptoms, indications for revision, laboratory values, and outcomes were recorded. A cohort of patients who underwent revision after initial PE was identified. Survival rates were assessed using the Kaplan-Meier method. For patients who required transplantation, operative data from the revised PE cohort were compared with those from the unrevised PE cohort. A Cox proportional hazards model was used to determine covariates predictive of a favorable outcome. Of 181 children who underwent PE, 24 underwent revision. Adequate biliary drainage, as evidenced by normalized conjugated bilirubin levels, was achieved in 75% of revised patients. Overall survival in patients who underwent revision, regardless of transplantation, was 87%. Among patients who underwent PE revision, 46% have survived with their native liver. Experience at our center suggests that with appropriate patient selection, PE revision may delay the need for liver transplanation yielding encouraging patient outcomes.

Range of NICU Practice in England and Wales Regarding Thresholds for Neonatal Conjugated Hyperbilirubinaemia and Relevant Investigations

Background: Conjugated jaundice is a common problem in a neonatal intensive care. However, several investigations are performed to exclude underlying liver disease. Opinion differs on their diagnostic value. Aim: To evaluate practice related to investigation of conjugated jaundice Method: Questionnaire survey of lead neonatal consultants from all neonatal units in England and Wales. Results: 102/194 neonatal units (52%), responded to the survey of which 33 were level 3 units, 50 level 2 and 19 level 1 units. 96 units (94%) performed conjugated jaundice screen and 6 units (6 %) did not. 77 units (75%) had a written policy. 49% of responders defined conjugated jaundice as conjugated bilirubin >20% of total bilirubin and 46% as >15% of total bilirubin and 5% of units did not have a clear definition. Conjugated bilirubin levels that prompted investigations varied between units with 28 (30%) using conjugated bilirubin >20% of total, 33(36%) a conjugated bilirubin >15% of total and 20 (21%) with no definite threshold. Majority (>76%) of units performed liver and thyroid function tests, Galactosaemia screen, α-1 antitrypsin and liver ultrasound. 65% of units performed urine culture and hepatitis serology, 32% performed urine organic acids, NH3 and lactate. 19 units performed CF genetics and 23 HIDA scan. 71% of responders thought ‘diagnostic yield’ was ‘poor’ and 44% based this on their personal view, 29% on local data and 27% on anecdotal evidence. Conclusion: Our study identified a wide variation in definition and investigation of neonatal conjugated jaundice. National consensus guidelines are required to standardize practice.

A contemporary analysis of parenteral nutrition–associated liver disease in surgical infants

Background/purpose Despite advances in pediatric nutritional support and a renewed focus on management of intestinal failure, there are limited recent data regarding the risk of parenteral nutrition (PN)–associated liver disease in surgical infants. This study investigated the incidence of cholestasis from PN and risk factors for its development in this population. Methods A retrospective review was performed of all neonates in our institution who underwent abdominal surgery and required postoperative PN from 2001 to 2006. Cholestasis was defined as 2 conjugated bilirubin levels greater than 2 mg/dL over 14 days. Nonparametric univariate analyses and multivariate logistic regression were used to model the likelihood of developing cholestasis. Median values with range are presented. Results One hundred seventy-six infants met inclusion criteria, and patients received PN for 28 days (range, 2-256 days). The incidence of cholestasis was 24%. Cholestatic infants were born at an earlier gestational age (34 vs 36 weeks; P < .01), required a 3-fold longer PN duration (76 vs 21 days; P < .001), had longer inpatient stays (86 vs 29 days; P < .001), and were more likely to be discharged on PN. The median time to cholestasis was 23 days. Cholestasis was an early development; 77% of cholestatic infants developed cholestasis by 5 weeks of PN exposure. On multivariate regression, only prematurity was significantly associated with development of cholestasis ( P < .05). Conclusion In this analysis, the development of PN-associated liver disease occurred early in the course of exposure to PN. These data help to define the time course and prognosis for PN-associated cholestasis in surgical infants.

A Curious Case of Hyperbilirubinemia

A 60-year-old patient suffering from easy fatigability was noted to have high total but normal conjugated bilirubin level though serum colour was pale. On further investigation the patient was found to be suffering from multiple myeloma and gamma globulin was possibly interfering with total bilirubin estimation.

Dynamics of clinical-laboratory markers of cholestasis on the ursosan therapy in patients with organic abnormalities of the bile-excreting tracts drainage function

Study of the ursosan therapy influence on the efficiency of the surgical resolution of cholestasis in the early postoperative period on the bile-excreting tracts. 19 healthy people and 24 patients with organic abnormalities of the drainage function of the bile ducts are examined. The analysis of the clinical, laboratory and instrumental criteria of cholestasis is carried out in the tested groups before and after ursosan’s therapy and the surgical treatment. Ursosan’s prescription leads to 3 times increase of cases of full regression of clinicolaboratory markers of cholestasis during the first week of the surgery on the bile ducts. The ursosan’s therapy should be prolonged more than 8 days after operative restoration of the bile passage on the bile ducts considering high level of lithogenic factors of C bile on these patients as compared to healthy people. The criteria of the completed ursosan’s therapy can be the normalization of the conjugated bilirubin level in the serum and or relief of slagging effect according to the ultrasound results of the bile ducts and a gallbladder.

Effect of aqueous extract of the leaves of Acalypha wilkesiana ‘Godseffiana’ Muell Arg (Euphorbiaceae) on the hematology, plasma biochemistry and ocular indices of oxidative stress in alloxan induced diabetic rats

Ethnopharmacological relevanceThe leaves of Acalypha wilkesiana are used in Southern Nigeria for the management of hypertension and diabetes mellitus. In this study, the effect of aqueous extract of the leaves of Acalypha wilkesiana on the hematology, plasma biochemistry and ocular indices of oxidative stress was investigated in alloxan induced diabetic rats. MethodologyDiabetes mellitus was induced by injection of alloxan (80mg/kg body weight), via the tail vein. The extract was administered orally at 100, 200 and 300mg/kg (both to normal and diabetic rats), and metformin at 50mg/kg. ResultsOn gas chromatographic analysis of the extract, twenty nine known flavonoids were detected, consisting mainly of 29.77% apigenin, 14.97% quercetin, 11.12% naringenin, 10.62% kaempferol, 9.05% (−)-epicatechin and 4.04% (+)-catechin. Tannic acid and β-sitosterol were also detected. Compared to test control, the treatment lowered (significantly, P<0.05) plasma glucose, triglyceride, conjugated bilirubin levels, atherogenic index of plasma, plasma alanine transaminase activity, total protein and total bilirubin, aspartate transaminase activity and unconjugated bilirubin, plasma urea, blood urea nitrogen and ocular malondialdehyde contents, lymphocyte and monocyte counts, and not significantly, plasma very low density lipoprotein cholesterol, but increased (significantly, P<0.05) plasma calcium contents, total white cell and platelet counts, mean cell volume and ocular ascorbic acid content, and (though not significantly) plasma high density lipoprotein cholesterol level, red cell and neutrophil counts. ConclusionsThis study showed that the extract was hypoglycemic, positively affected the hemopoietic system and integrity and function (dose dependently) of the liver and kidney of the diabetic rats; improved the lipid profile and had no deleterious effect on red cell morphology. It also protected against oxidative stress in ocular tissues. This study also revealed the presence of pharmacologically active compounds in the leaf extract. All of these highlights the cardioprotective potential of the leaves of Acalypha wilkesiana and support its use in traditional health practices for the management of diabetes mellitus.

Effects of lipid formulation and sepsis on liver function in newborn infants with pn associated liver disease

BackgroundParenteral nutrition associated liver disease (PNALD) accounts for substantial morbidity and mortality in infants with intestinal failure. Lipid formulations and sepsis may be important determinants. Newer lipid preparations for example,...

Green teeth are a late complication of prolonged conjugated jaundice in extremely low birth weight infants

BackgroundEruption of green, discoloured teeth affecting the primary dentition has been described in association with congenital viral infection, neonatal bacterial and fungal sepsis, haemolytic jaundice, biliary atresia and cholestasis. Extreme...

Global arginine bioavailability in Tanzanian sickle cell anaemia patients at steady‐state: a nested case control study of deaths versus survivors

Global arginine bioavailability in Tanzanian sickle cell anaemia patients at steady‐state: a nested case control study of deaths <i>versus</i> survivors

Association of an overlap syndrome of autoimmune hepatitis and primary biliary cirrhosis with cytomegalovirus infection

A 63-year-old woman, who presented with severe jaundice and elevated serum conjugated bilirubin level, denied alcohol and drug use and showed no evidence of viral hepatitis. Based on clinical and laboratory features, she was diagnosed with autoimmune hepatitis with primary biliary cirrhosis. Hematological and immunochemical assays, radiographic imaging, clinical examination, and liver biopsy were conducted. Laboratory results were the following: negative for fluorescence antinuclear antibody, negative for antismooth muscle antibodies but positive for antinuclear antibody (enzyme-linked immunosorbent assay) and antimitochondrial M2 antibody, high titers of serum globulin, and positive for cytomegalovirus IgM. Liver biopsy showed submassive lobular necrosis, inflammation with broad areas of parenchymal collapse, and chronic nonsuppurative destructive cholangitis. The patient responded well to corticosteroid therapy. This case might illustrate an association between cytomegalovirus infection and the occurrence of autoimmune hepatitis.

ASSOCIATION OF UGT1A1 GLY71ARG WITH URINE UROBILINOGEN

Bilirubin is glucoronized by uridine diphosphate-glucuronosyl transferase 1A1 (UGT1A1) mainly in the liver, and excreted into bile. The conjugated form is metabolized into the unconjugated form, and then into urobilinogen by bacteria in the intestine. Unconjugated bilirubin and urobilinogen are absorbed into the blood stream. The kidney filtrates conjugated bilurubin and urobilinogen into urine. Accordingly, the reduced enzyme activity of UGTIAI may decrease serum conjugated bilirubin levels, resulting in a lower frequency of positive results of urine bilirubin and urobilinogen. This study examined the associations of UGTIAI Gly71Arg (UGTIAI *6) with urine bilirubin and urobilinogen, as well as serum AST, ALT and GGT. Subjects were 5,172 inhabitants 35 to 69 years old who participated in a cohort study in Nagoya from June 2008 to May 2010. Among them, data from 5,151 participants (1,465 males and 3,686 females) were available for analysis. The age-sex-adjusted odds ratio (OR) of ArgArg relative to GlyGly was 1.37 (95% confidence interval (95% CI), 0.55-1.23) for bilirubin, and 1.67 (95% CI, 0.86-3.26) for urobilinogen. Those of ArgArg+ArgGly were 0.87 (95% CI, 0.59-1.27) and 1.50 (95% CI, 1.17-1.94), respectively. AST, ALT and GGT levels had no associations with the genotype. Although the significant association for urobilinogen was contrary to the biological expectation, this study indicated that UGTIA1 Gly71Arg may be a genetic factor of urine urobilinogen.

Early Exclusive Diagnosis of Biliary Atresia among Infants with Cholestasis

The persistence of jaundice beyond the first 2 weeks of life require further investigation and this can be determined if the conjugated bilirubin levels are greater than 1.5 mg/dL or greater than 20% of the total bilirubin level. There is a diverse differential diagnosis for the cause of neonatal cholestasis due to hepatobiliary disease including biliary atresia, which eventually leads to liver cirrhosis if uncorrected before 60∼80 days of life. Long-established initial studies include abdominal ultrasonography, hepatobiliary scintigraphy and liver biopsy, but better diagnostic methods are needed. Promising new options are described including MRCP (magnetic resonance cholangiography), ERCP (endoscopic retrograde cholangiography), and PCC (percutaneous cholecysto-cholangiography). Though no single test can differentiate biliary atresia from other neonatal cholestasis with confidence, a combination of diagnostic methods is usually consistently beneficial. By excluding biliary atresia as early as possible, the risk of unnecessary explolaparotomy with intraoperative cholangiography is decreased. Further evaluation would be required for the diagnosis of neonatal cholestasis after excluding biliary atresia. (Korean J Pediatr Gastroenterol Nutr 2011; 14: 122∼129)

Phase 2 Results of Clofarabine In Combination with Etoposide and Cyclophosphamide In Pediatric Patients with Refractory or Relapsed Acute Lymphoblastic Leukemia

Phase 2 Results of Clofarabine In Combination with Etoposide and Cyclophosphamide In Pediatric Patients with Refractory or Relapsed Acute Lymphoblastic Leukemia

Interpreting Conjugated Bilirubin Levels in Newborns

To examine the clinical significance of elevated conjugated bilirubin (CB) levels in newborns. This retrospective study evaluated a birth cohort of 271 186 full-term newborns born within a Northern California hospital network from 1995 to 2004. All CB and direct bilirubin (DB) levels were available in a database and were correlated with the patients' inpatient and outpatient International Classification of Diseases, 9th Revision diagnoses. The 99th percentile for CB is 0.5 mg/dL, and the 99th percentile for DB is 2.1 mg/dL. CB levels between 0.5 and 1.9 mg/dL can be associated with infection, but most often remain unexplained. Liver and biliary disease become increasingly likely as CB levels increase; for CB ≥5 mg/dL, 47% of newborns have biliary disease and 43% have liver disease. CB and DB levels are not interchangeable. In newborns with CB levels ≥0.5 mg/dL and <2 mg/dL, infection must be ruled out, and the newborn should be observed. In newborns with levels ≥2 mg/dL, a more in-depth assessment of the hepatobiliary system is indicated.

Effect of Accessions ofColocasia esculenta-Based Diets on the Hepatic and Renal Functional Indices of Weanling Wistar Rats

The liver and kidney functional indices of weanling albino rats (Rattus norvegicus) maintained on different accessions (offspring of a variety planted/collected at a specific location and time but differing in certain morphological characteristics) of cooked Colocasia esculenta (cocoyam)-based diets (UFCe1-UFCe7) for 28 days were investigated. All the accessions of C. esculenta-based diets did not significantly (P > .05) alter the serum levels of albumin, globulin, inorganic phosphorus, calcium, magnesium, and uric acid of the animals.The total protein and total bilirubin levels decreased only in the UFCe3- and UFCe4-fed animals, respectively. Whereas UFCe1 and UFCe2 significantly decreased the conjugated bilirubin levels, UFCe3 and UFCe6 increased it. While all the accessions of C. esculenta-based diet decreased the serum alkaline phosphatase activity, γ-glutamyl transferase activity was increased. UFCe1 and UFCe5 increased the serum alanine aminotransferase activity, whereas UFCe4 decreased the activity of the enzyme. Again, UFCe3 and UFCe1 increased the serum creatinine and aspartate aminotransferase activity of the animals. Furthermore, the computed blood urea nitrogen:creatinine ratio was higher in animals maintained on UFCe1-, UFCe3-, UFCe4-, and UFCe5-based diets. Whereas UFCe6 and UFCe7 increased the level of sodium in the serum of the animals, UFCe4 and UFCe5 decreased the chloride level. The serum urea level was decreased by UFCe1, UFCe3, UFCe4, and UFCe5, whereas the potassium level increased in the UFCe4-, UFCe6-, and UFCe7-fed animals. Overall, the results revealed that all the accessions of C. esculenta produced selective effects on the hepatic and renal functional indices of the weanling rats. The highest alterations were produced by UFCe4, whereas the least was from UFCe2. These alterations may have consequential effects on the normal functioning of the liver and kidney of the animals. UFCe2 exhibited the least toxicity risk among the accessions of C. esculenta growing in the KwaZulu-Natal Province of South Africa.