Living donor liver transplantation using a graft from a donor with Dubin-Johnson syndrome.

DJS is an autosomal recessive disorder that causes an increase in conjugated bilirubin without elevation of liver enzymes. Most patients are asymptomatic and have normal life spans, but to the best of our knowledge, their livers have never been reported to be grafts in liver transplantation. Herein, we report an infant patient with MMA that received a partial liver graft from his mother, who had DJS. A biliary anastomosis stricture was noted five months after transplantation and was successfully treated with radiological interventions. Otherwise, the patient's liver functions were normal, and a liver biopsy showed a pathognomonic picture of DJS nine months after the transplantation. The patient was followed for one yr, and the results were satisfactory for an increase in oral intake and protein uptake, no recurrence of metabolic stroke and there was a gradual catch-up with regard to physical development despite having a persistently abnormal profile of amino acid analysis. From the experience of our case, we suggest that a liver from a donor with DJS can be used as a graft for liver transplantation, although long-term follow-up is mandatory to examine the grafted liver under the use of immunosuppressive medications.

Dubin-Johnson syndrome--a clinicopathologic study of twenty cases.

Dubin-Johnson syndrome (DJS) is a rare benign chronic disorder of bilirubin metabolism, characterized by conjugated hyperbilirubinemia, darkly pigmented liver and presence of abnormal pigment in hepatic parenchymal cells. This is a retrospective study of twenty cases of DJS highlighting their major clinical and pathological findings. Liver biopsies were available in all the cases, obtained during a fourteen-year period (January 1991 to March 2005). The patients' age ranged from 7-63 years (median 21 years). These twenty cases comprised 13 males and 7 females. Major clinical manifestations were recurrent or persistent jaundice, abdominal pain and fever. Duration of illness ranged from 9 months to 58 years (median 10 years). All of them had conjugated hyberbilirubinemia and total serum bilirubin levels ranged between 1.4-13 mg/dl (mean 4.4 mg/dl). Liver biopsies revealed presence of coarse granular brown pigment in the cytoplasm of hepatocytes more concentrated in the pericanalicular region and more prominent in centrilobular hepatocytes. Associated findings were presence of hepatitis B virus related chronic hepatitis (1), history of tubercular lymphadenitis (1), chronic cholecystitis in (2), coronary heart disease (1) and exacerbation during pregnancy (1).

[Constitutional hyperbilirubinemia and mixed bilirubin. Clinical and functional study]. / Iperbilirubinemie costituzionali a bilirubina mista. Studio clinico e funzionale.

Three cases of non-haemolytic constitutional icterus with prevalently conjugated bilirubin have been studied: one case of Dubin-Johnson syndrome and two cases of Rotor's syndrome. Confirmation was obtained for the differences between the two syndromes from the physiopathological (by means of the BSF load test and determination of urinary excretion of porphyrin) and morphological (macroscopic, histological, ultrastructural) viewpoints. The following were carried out in all cases: a load curve with crystalline bilirubin, study of the course of the curve and application of compartmental analysis to the curve. Findings underlie the hypothesis that Rotor's syndrome contains an uptake defect and an accumulation change on the part of the liver cell of organic anions and that it is therefore possible to suggest some identity between Rotor's syndrome and the so-called "Hepatic storage disease".

[Dubin-Johnson syndrome: molecular basis and pathogenesis]. / Le syndrome de Dubin-Johnson: bases moleculaires et pathogenie.

The Dubin-Johnson syndrome (DJS) is an autosomal recessive liver disorder characterized by a chronic conjugated hyperbilirubinemia a dark greenish appearance of liver tissue, a double peaked sulfobromophthalein clearance curve, and a characteristic lysosomal accumulation of black pigment "melanine-like" in the hepatocytes. Laboratory datas indicated an increased urinary excretion of coproporphrin isomer I and leukotriene metabolites. In an effort to understand the morphological pattern and the pathogenesis of this disease we reviewed four cases of DJS.

Neonatal Dubin-Johnson syndrome: long-term follow-up and MRP2 mutations study.

Neonatal Dubin-Johnson syndrome (DJS) is rarely diagnosed and mutational analysis of multidrug-resistance-associated protein 2 (MRP2) in such patients had not been reported. We aimed to investigate the possible correlations between genotype and phenotype of patients with DJS. Four cases of DJS, two diagnosed during the neonatal period and two diagnosed at adolescence, were followed for 5-20 y. Mutational analysis in the MRP2/ABCC2 gene was performed in all four cases. Biphasic pattern of jaundice attack was observed in one patient who was followed for 20 y, with jaundice subsiding before 1 y of age and recurring at adolescence. Six novel mutations in four patients were found, including deletions (2748del136, 3615del229, and Del3399-3400), and missense mutations (L441M and E1352Q) and nonsense mutation (Y1275X). The immunohistochemical staining in liver tissues from two patients with neonatal onset showed negative staining for MRP2. Reviewing previously reported cases, all patients diagnosed as DJS before 10 y of age have mutations involving one of the two ATP-binding cassettes (ABC) of the MRP2. This study suggests that long-term follow-up is indicated for neonatal DJS because of possible recurrence and/or second attacks of jaundice in later life, and that disruption of functionally important ABC domains in MRP2 may be related to the earlier onset of the disease.

The effect of phenobarbital on patients with Dubin-Johnson syndrome.

11 patients with jaundice of Dubin-Johnson type were treated for 2 weeks with phenobarbital. Serum bilirubin diminished and hepatic clearance of sulfobromophthalein was variably enhanced; other measures of hepatic function were not significantly changed during therapy.

Hepatobiliary function studies on Dubin-Johnson syndrome using 99mTc-pyridoxyl-methyl-tryptophan (PMT).

Hepatobiliary studies on five patients with Dubin-Johnson syndrome were performed using 99mTc-PMT. Time-activity curves of the liver of the patients showed delayed excretion and that plasma elimination in the patients was prolonged compared to that of normal subjects.

Genes for jaundice.

The inheritable causes of jaundice comprise a large group of conditions of varying frequency, from Gilbert's syndrome which is relatively common, to the very rare Crigle-Najjar syndrome. Although these conditions have been well characterized clinically and in some cases biochemically, the underlying molecular defects were unknown because of a lack of knowledge about the process of bile secretion by hepatocytes. The recent cloning of several transporters for bile acids and other organic anions has enabled a greater understanding of this process and allowed correlation of the malfunction of these genes with specific disease processes. This new knowledge will provide for precision in diagnosis, allow antenatal testing and provide opportunities for gene therapy for some of the more serious disorders.