Clinical, Pathologic, and Genetic Features of Neonatal Dubin-Johnson Syndrome: A Multicenter Study in Japan.

OBJECTIVE: To clarify the clinical, pathologic, and genetic features of neonatal Dubin-Johnson syndrome. STUDY DESIGN: Ten patients with neonatal Dubin-Johnson syndrome were recruited from 6 pediatric centers in Japan between September 2013 and October 2016. Clinical and laboratory course, macroscopic and microscopic liver findings, and molecular genetic findings concerning ATP-binding cassette subfamily C member 2 (ABCC2) were retrospectively and prospectively examined. RESULTS: All neonates exhibited cholestasis, evident as prolonged jaundice with or without acholic stools and elevations of serum direct bilirubin as well as γ-glutamyltransferase or total bile acids. Only 38% (3 of 8) of patients who underwent liver biopsy showed a grossly black liver or melanin-like pigment deposits in hepatocytes; their biopsies were performed in early infancy. Immunohistochemically, all liver specimens showed no expression of multidrug resistance-associated protein 2 but increased expression of the bile salt export pump protein. Homozygous or compound heterozygous pathogenic variants of ABCC2 were identified in all patients, representing 11 distinct pathogenic variants including 2 not previously reported. CONCLUSIONS: Immunohistochemical staining of the liver for multidrug resistance-associated protein 2 and molecular genetic analysis of ABCC2 are crucial for accurate diagnosis of neonatal Dubin-Johnson syndrome.

Improvement of serum bilirubin levels after venesection in a patient with Dubin-Johnson syndrome and HCV-positive chronic liver disease.

Direct-type hyperbilirubinemia in Dubin-Johnson syndrome is due to the genetic dysfunction of multidrug resistance protein 2. However, serum bilirubin levels may fluctuate as a result of acquired conditions. Iron-reduction therapy by venesection, an alternative to interferon, was performed in a 55-year-old male patient with Dubin-Johnson syndrome complicated by hepatitis C virus-positive chronic liver disease and hepatic iron overload. His pretreatment serum total bilirubin was 10.2 mg/dl, with a dominant direct fraction. The treatment induced a significant reduction in serum total bilirubin, although it remained as high as 7.9 mg/dl. A negative correlation between serum total bilirubin and cumulative bled volume suggested that venesection could suppress bilirubin production from aged erythrocytes. The hepatic iron overload was distributed in hepatocyte lysosomes with Dubin-Johnson granules; thus, it seems that iron removal from the lysosomal granules may also help to reduce serum bilirubin. In conclusion, deep jaundice in a patient with Dubin-Johnson syndrome complicated by hepatitis C virus-positive chronic liver disease and iron overload was partially improved by iron-reduction therapy.

Hepatocellular carcinoma in a case of Dubin-Johnson syndrome treated successfully with a central bilateral segmentectomy.

A 72-year-old woman with hepatocellular carcinoma and HCV cirrhosis combined with Dubin-Johnson syndrome was successfully treated by a central bilateral segmentectomy. While the preoperative serum bilirubin level is one of the established criteria for determining the indications for a hepatic resection, it is not effective for HCV cirrhosis cases associated with Dubin-Johnson syndrome. Postoperative hyperbilirubinemia may be cured without special treatment such as bilirubin absorption or plasma exchange, but such patients must be carefully observed to ensure that liver failure does not occur.

Ictericia colestásica del primer trimestre en gemelos / Cholestatic jaundice in the first months of twins

Colestasis significa reducción del flujo biliar. en el primer trimestre de vidaa, la ictericia colestásica constituye un síndrome que puede tener varias etiologías y su importancia radica en la necesidad de decidir la conducta terapeútica, especialmente la indicación de intervención quirúrgica, lo antes posible, por el riesgo de cirrosis secundaria a atresia biliar. La incidencia del síndrome es de 1:2500 nacidos vivos y aproximadmente el 50 por ciento es causado por obstrucción extrahepática. Se describen en el presentetrabajo dos csos de ictericia colestásica del primer trimestre, en gemelos atendidos en el Servicio de Pediatría del Hospital de Santa Cruz, Caja Petrolera de Salud; ambos con el diagnóstico centellográfico de atresia biliar extrahepática, el cual es descartado al realizar la cirugía y colangiografía intraoperatoria; por estudio anatomopatológico se llegó al diagnóstico de colestasis intra y extracelular

Síndrome de Dubin Johnson / Dubin-Johnson`s Syndrome

Se presentan 5 pacientes con Síndrome de Dubin-Johnson diagnósticados entre noviembre de 1975 y noviembre de 1985 en el Hospital San Juan de Dios. Se realizó análisis clínico de laboratorio, gabinete y estudios histológicos del hígado. Tres de los 5 casos eran de sexo femenino, siendo los tres primeros casos presentados, hermanos. La edad en el momento del diagnóstico osciló entre 17 y 26 años siendo el promedio 20 años. Todos los casos cursaron con hiperbilirrubinemia de predominio directo, que no pasó de 4 mg/dl. Cuatro de los 5 casos, mostraron aumento paradójico en la eliminación de la bromosulftaleína (BSP); así mismo en los cuatro que se realizó biopsia hepática, ésta reveló depósito de pigmento pardo oscuro en los hepatocitos, descrito como característico de la enfermedad. El cuadro clínico se caracterizó principalmente por ictericia y hepatomegalia leve.