technetium-tc-99m-mebrofenin and Biliary-Atresia

Early differentiation of extrahepatic biliary atresia from intrahepatic cholestasis is important. Hepatobiliary scintigraphy is an excellent noninvasive investigation for ruling out extrahepatic biliary atresia. This study aimed at identifying the role of ursodeoxycholic acid (UDCA), a choleretic agent, in conjunction with hepatobiliary scintigraphy in differentiating extrahepatic biliary atresia from neonatal hepatitis.. Fifty-one infants (42 male, 9 female) aged 0.3-5.5 mo (mean, 2.9 mo) presenting with neonatal jaundice underwent 99mTc-mebrofenin hepatobiliary scintigraphy. For patients who did not show any excretion of tracer into the intestine till 24 h, the study was repeated after oral administration of UDCA (20 mg/kg every 12 h) for 48-72 h. Ultrasonography and, if required, liver biopsy and intraoperative cholangiography were used with clinical data such as stool color and serologic and other etiologic investigations to form a final diagnosis.. Of 51 patients, 19 showed biliary excretion in the first study, ruling out extrahepatic biliary atresia. Neonatal hepatitis was the final diagnosis in these. Of the remaining 32 patients, 12 nonexcretors converted to excretors after UDCA treatment, whereas 20 still showed no biliary drainage. Four nonexcretors on scintigraphy had a final diagnosis of neonatal hepatitis with galactosemia; the remaining 16 had extrahepatic biliary atresia. The specificity of hepatobiliary scintigraphy in ruling out extrahepatic biliary atresia improved from 54.3% to 88.6% (P < 0.001) after UDCA treatment. None of the patients experienced any ill effects from UDCA administration.. Pretreatment with UDCA significantly improves the specificity of hepatobiliary scintigraphy in ruling out extrahepatic biliary atresia as a cause of prolonged neonatal jaundice.

Topics: Administration, Oral; Aniline Compounds; Biliary Atresia; Biliary Tract; Cholagogues and Choleretics; Diagnosis, Differential; Glycine; Humans; Imino Acids; Infant; Infant, Newborn; Jaundice, Neonatal; Liver; Organotechnetium Compounds; Radiopharmaceuticals; Reproducibility of Results; Tomography, Emission-Computed; Ursodeoxycholic Acid

The aim of this paper is to identify extrahepatic biliary atresia (EHBA) as the cause of cholestasis in neonates with prolonged jaundice and thus accelerate the decision for surgical intervention, which is critical for prognosis.. We retrospectively studied 21 infants (13 girls, 8 boys) aged 2-16 weeks who have undergone( 99m)Tc-mebrofenin iminodiacetate ((99m)Tc-BrIDA) scintigraphy. They were referred because of direct hyperbilirubinemia and jaundice persisting beyond the 2nd postnatal week. They had received phenobarbitone premedication prior to scintigraphy. Dynamic images for 30 min and then static images (if required) at 1, 2 and 24 h postinjection were acquired. Images were evaluated visually and semiquantitatively, by calculating the liver-to-heart (L/H) ratio. Age, L/H ratios, and serum gamma glutamyl transpeptidase (gamma-GT) levels were compared (Mann-Whitney U test) between infants with EHBA (Group A) and infants without (Group B). The L/H ratios were correlated with age in each group and with gamma-GT in the entire population.. A total of 7/21 infants were classified in Group A and 14/21 in Group B. The L/H ratios were significantly lower in Group A. The correlation between L/H ratio and age was negative in EHBA and positive in non-atretic infants. The gamma-GT levels were inversely correlated with the L/H ratios in the entire population, being significantly higher in Group A.. In long-standing neonatal direct hyperbilirubinemia, (99m)Tc-BrIDA scintigraphy and the L/H ratio index seem to give useful information in the differential diagnosis of EHBA, especially when associated with markedly elevated serum gamma-GT levels.

Topics: Aniline Compounds; Biliary Atresia; Biliary Tract; Cholestasis, Extrahepatic; Diagnosis, Differential; Female; Glycine; Humans; Hyperbilirubinemia, Neonatal; Imino Acids; Infant; Infant, Newborn; Jaundice, Neonatal; Liver; Male; Organotechnetium Compounds; Radionuclide Imaging; Radiopharmaceuticals; Reproducibility of Results; Sensitivity and Specificity

Kasai portoenterostomy (KP) is regarded as first-line treatment for biliary atresia, although its postoperative course is often unpredictable. Hepatobiliary scintigraphy using technetium-labeled iminodiacetic acid derivatives offers a dynamic, objective assessment both of parenchymal liver function and restored biliary excretion. The value of postoperative radionuclide scans was assessed prospectively in a large population of post-KP infants.. Radionuclide scans consisted of an intravenous dose of 20 MBq of 99mTc mebrofenin iminodiacetic acid and subsequent gamma camera imaging. Four scan variables were evaluated: the hepatic extraction fraction (HEF; ie, initial liver uptake divided by the peak vascular uptake), the half-life of tracer excretion (TEX), the shape of the excretion curve, and the presence of activity in the Roux loop at 4 hours postinjection. All infants had type 3 biliary atresia with a median age at KP of 59 days (24-120 days). To assess predictive value, outcome (clearance of jaundice and need for transplant) was assessed at 6 months (for 1-week scan) and 2 years (for 6-month scan).. Eighty-seven infants underwent a radionuclide scan at 1 week post-KP. The median HEF was 34% (10%-90%). No relationship could be identified between HEF (P = .2) or excretion curve shape (P = .9) and outcome (at 6 months), and there were too few examples of a measurable TEX to allow meaningful comparison. The only predictive element at this time point was Roux loop activity (positive predictive value, 79%; negative predictive value, 53%; for "good" isotope bowel activity). Forty-four infants completed a second scan at 6 months. Median HEF increased from a baseline of 37% (11%-90%) to 64% (8%-100%) (P < .0001), although there was no significant intercorrelation (P = .12). The most predictive variables (of outcome at 2 years) were curve shape (positive predictive value, = 95%, negative predictive value, 82%) and TEX, and the least predictive was now Roux loop activity.. Early (at 7 days) hepatic scintigraphy is not predictive of poor outcome in general, although Roux loop activity does indicate later success. Later hepatic scintigraphy (at 6 months) allows a detailed assessment of dynamic liver function with biliary excretion variables predictive of outcome in the medium term.

Topics: Adrenal Cortex Hormones; Aniline Compounds; Antibiotic Prophylaxis; Aspartate Aminotransferases; Biliary Atresia; Biliary Tract; Bilirubin; Combined Modality Therapy; Female; Follow-Up Studies; Glycine; Half-Life; Humans; Imino Acids; Infant; Infant, Newborn; Liver; Liver Transplantation; Male; Organotechnetium Compounds; Portoenterostomy, Hepatic; Postoperative Period; Predictive Value of Tests; Prognosis; Prospective Studies; Radionuclide Imaging; Radiopharmaceuticals; Randomized Controlled Trials as Topic; Time Factors; Treatment Outcome

Hepatic technetium-99m-mebrofenin iminodiacetate (99mTc-mebrofenin IDA) scans and serum gamma-glutamyl transpeptidase (GGTP) have high sensitivity for extrahepatic biliary atresia (EHBA). This study was based on the hypothesis that the interpretation of results of 99mTc-mebrofenin IDA scans and serum GGTP levels in series would result in a reduction of the false positivity observed with these tests individually. The aetiology of neonatal cholestasis in 132 study patients was: 25% (33/132) EHBA, 45.5% (60/132) neonatal hepatitis (NH) with an identifiable cause and 19.7% (26/132) idiopathic NH. Of the various clinical, biochemical and imaging parameters that were significantly different between patient groups, sensitivity for EHBA was: serum GGTP > or = 150 IU l(-1) (100%), 99mTc-mebrofenin IDA scans (100%), pale stools (82.8%) and total serum bilirubin > or = 12 mg dl(-1) (66%). However, specificity ranged from 48.5 to 79%. Of the 63 patients who had non-excreting IDA scans, operative cholangiograms could be avoided on the basis of a specific aetiological diagnosis of NH, made concurrently, in only 9 infants. The rest (54) underwent operative cholangiograms; 21 (39%) of these had patent biliary trees and therefore underwent the procedure unnecessarily. If serum GGTP (< 150 IU l(-1)) had been used as a screen after IDA scanning in these 54 patients, operative cholangiograms could have been avoided in another 12 patients and thereafter only 9/42 (21%) of the operative cholangiograms would have been considered unnecessary.. A diagnostic algorithm is proposed wherein serum GGTP level (at a cut-off level that maintains 100% sensitivity for EHBA) is used in series with non-excreting 99mTc-mebrofenin IDA scans (for patients with no specific aetiological label). This strategy reduces the false positivity of individual tests.

Topics: Algorithms; Aniline Compounds; Biliary Atresia; Cholestasis, Extrahepatic; Diagnosis, Differential; Female; gamma-Glutamyltransferase; Glycine; Hepatitis; Humans; Imino Acids; Infant; Infant, Newborn; Male; Organotechnetium Compounds; Radionuclide Imaging; Radiopharmaceuticals; Sensitivity and Specificity; Technetium

The prognosis of infants with prolonged neonatal jaundice is dependent on early diagnosis because of the need for prompt surgical management of biliary atresia.. To evaluate the usefulness of 99 mTcm-trimethylbromo-iminodiacetic acid (TBIDA, mebrofenin) in the investigation of infantile jaundice.. A retrospective study was undertaken of 58 patients with unexplained prolonged neonatal jaundice. Sixty-eight scans were reviewed.. Mebrofenin scintigraphy confirmed the presence of a choledochal cyst in three of the four cases with that diagnosis. There were no false negative results in the nine patients with extrahepatic biliary atresia (EHBA). Three further infants had an incorrect histological diagnosis of EHBA. A gall bladder was identified by US in each case and in one of these, scintigraphy showed gut excretion. In the 16 patients with no gut excretion by 24 h, the final diagnoses were intrahepatic cholestasis (n = 7), Alagille's syndrome (n = 3), neonatal hepatitis (n = 3), alpha-1-antitrypsin deficiency (n = 2) and juvenile xanthogranuloma (n = 1). Seven infants had repeat scintigraphy after the administration of ursodeoxycholic acid (URSO). This changed five non-excretors with hepatitis into excretors. Two infants with hepatitis continued to show non-excretion after URSO, but a gallbladder was identified by US in both.. Mebrofenin scintigraphy is accurate in confirming the presence of a choledochal cyst and in refuting the diagnosis of EHBA. While histology and scintigraphy are each 100 % sensitive for the diagnosis of EHBA, neither, individually, is accurate and the investigation of prolonged neonatal jaundice requires a multi-modality imaging strategy.

Topics: Aniline Compounds; Biliary Atresia; Choledochal Cyst; Glycine; Hepatitis; Humans; Imino Acids; Infant, Newborn; Jaundice, Neonatal; Liver; Organotechnetium Compounds; Radionuclide Imaging; Radiopharmaceuticals; Retrospective Studies

A compartmental model describing the extraction and disposition of 99mTc-acetanilidoiminodiacetic acid (IDA) compounds by the liver has been applied to 5 adult patients admitted for cholecystitis investigations and 29 jaundiced infants the majority of whom were clinically differentiable into neonatal hepatitic and biliary atretic groups.. In each case kinetic rate constants were calculated to describe hepatocyte extraction of 99mTc-IDA structural analogs from blood pool (k21) and subsequent elimination (k3) of this compound into biliary tract. Also modeled was the reverse-binding constant (k12) describing the return of such radiotracer to the systemic circulation and the blood fraction (f) which accounted for the composite vasculature forming a matrix in the liver.. It was shown that these indices could be used to determine accurate compartmental mean residence times (MRT(c)s) for each patient by correlation with values obtained by deconvolutional analysis and independent measurement of leading edge parenchymal transit times. For the adult patients the following indices, typical of good hepatocyte function, were derived: k21 = 0.933 +/- 0.488 min-1, k12 = 0.0277 +/- 0.0340 min-1, k3 = 0.1610 +/- 0.0531 min-1, f = 0.3519 +/- 0.3048 and MRTc = 11.19 +/- 3.13 min. Analysis of the pediatric group revealed no significant differences in their respective MRT(c)s. However, significant differences in the extraction (p < 0.01) and excretion (p < 0.001) coefficients were prominent.. This method can be applied to provide accurate and meaningful intercompartmental rate parameters and MRT(c)s for adults, nonobstructed and obstructed infants.

Topics: Aged; Aniline Compounds; Biliary Atresia; Cholecystitis; Glycine; Hepatitis; Humans; Imino Acids; Infant; Infant, Newborn; Jaundice, Neonatal; Liver; Models, Biological; Models, Theoretical; Organotechnetium Compounds; Radionuclide Imaging; Technetium Tc 99m Disofenin

Technetium-99m mebrofenin hepatobillary excretory patterns were assessed in 36 infants with hyperbilirubinemia. Phenobarbital was administered to 22 patients before imaging. Final diagnoses included: intrahepatic cholestasis (14 patients), neonatal hepatitis (nine patients), biliary atresia (eight patients), alpha-1-antitrypsin deficiency (two patients), Alagille's syndrome (two patients), and cystic fibrosis (one patient). No patient with biliary atresia showed bowel activity by 24 hours. Of the 28 infants without biliary atresia, 23 (82%) had bowel activity visualized by 6-8 hours and 26 (90%) had bowel activity by 24 hours. Two had no bowel activity at 24 hours: one had cystic fibrosis and one had neonatal hepatitis. Of the 26 patients with bowel visualization, the time to visualize bowel did not differ between patient groups with and without phenobarbital induction. All of the patients with hepatitis, including those with marked dysfunction, showed good hepatic uptake. Mebrofenin scintigraphy is an important imaging technique in the diagnostic evaluation of infants with hyperbilrubinemia. In addition to biliary atresia, intrahepatic cholestasis due to cystic fibrosis and severe neonatal hepatitis may also cause bowel nonvisualization up to 24 hours. The results of this study suggest phenobarbital induction may not be needed when Tc-99m mebrofenin scintigraphy is used for the assessment of infantile jaundice.

Topics: Aniline Compounds; Biliary Atresia; Cholestasis, Intrahepatic; Female; Glycine; Hepatitis; Humans; Imino Acids; Infant; Infant, Newborn; Jaundice, Neonatal; Liver; Male; Organotechnetium Compounds; Phenobarbital; Radionuclide Imaging; Time Factors; Ultrasonography