A 10-year-old girl of Caucasian origin was admitted to our Pediatric Hematology-Oncology Outpatient Clinic for thrombocytopenia (68 × 103/mm3) and splenomegaly. Family history was unremarkable except for the girl's mother being affected by microhematuria and asymptomatic proteinuria. The girl's past personal medical history showed asymptomatic microhematuria since age 4. Three weeks before the visit at our Clinic she had started presenting headache with an itching rubeoliform rash all over the body.
Physical examination was unremarkable except for splenomegaly (4,5 cm). The blood count showed thrombocytopenia (68 × 103/mm3) while the remaining values were within normal range (haemoglobin 13,2 g/dL, mean corpuscular volume 75,8 fL, leukocyte 4.2 × 103/mm3, with neutrophil 2.5 × 103/mm3, reticolocytes 41 × 103/mm3). Kidney and liver function test were all within normal ranges: aspartate aminotransferase 34 U/L (nv 15-40), alanine aminotransferase 24 U/L (nv 5-40), bilirubin 21,7 umol/L (nv 1,7-17), γGT 12 U/L (nv 3-22), alkaline phosphatase 177 IU/L (nv 56-247), creatinine 39 umol/L (nv 27-62).
Coagulation (PT 58%, IRN 1.42, PTT 33 sec) and haptoglobin were normal, while Coombs Test was negative.
Serological tests for hepatitis B virus, hepatitis C virus, HIV, cytomegalovirus, Epstein-Barr virus, parvovirus, Toxoplasma, Rubeovirus, Herpes Simplex virus 1-2, HHV6-7-8, Bartonella, Weil- Felix, Widal-Wright, Plasmodium Falciparum were all negative.
Peripheral blood smear and bone marrow aspirate, performed in order to exclude leukemia and metabolic diseases, were normal.
The abdominal ultrasound showed splenomegaly (17 cm) with liver and kidneys of normal size and echogenicity. A Doppler ultrasound showed a normal portal blood flow. The thorax x-Ray was normal.
Two months later, due to the persistence of the thrombocytopenia (57 × 103/mm3), in order to exclude an autoimmune disease, we evaluated antiplatelet antibodies, Antinuclear (ANA), antiDNA, anti-extractable nuclear antigen (ENA), antimitochondrial and anti parietal cell (APCA) antibodies, anti muscle antibody which all resulted negative.
Three months after the initial evaluation, physical examination, thrombocytopenia and abdominal ultrasound remained unchanged. The child persisted in good general conditions.
Six months later, due to the persistence of both the thrombocytopenia (50 × 103/mm3) and the splenomegaly, an abdominal CT scan was performed confirming the splenomegaly but showing also an ectasia of the portal vein, hepatomegaly -with the left liver lobe reaching the left posterior axillary region- with dilatation of the intrahepatic bile ducts, mainly in the right liver lobe.
Due to the results of the abdominal CT scan, the girl was admitted to the Pediatric Gastroenterology and Hepatology Unit for further investigations of a possible liver pathology. Ceruloplasmin 0,29 g/l (nv 0,22-0,6), cupremia 9,9 umol/l (nv 14-25), cupruria 0,543 umol/24 h (nv 0,047-0,55), α fetoprotein 1,3 ug/l, α1- antitrypsin 135 mg/dl were all within normal ranges. An abdomen MRI revealed reduction of the volume of the right liver lobe, hypertrophy of the lateral segment of the left liver lobe and splenomegaly (Figure 1). Cholangio-MRI revealed slight dilatation of the biliary tract of the right lobe; the hepatic duct and the choledoch were normal (Figure 2).
Hepatobiliary scintigraphy showed hepatomegaly of the left lobe, with a normal captation of the radionuclide; after the first forty-five minute there was a feeble visualization of some parts of the biliary tract and of the bowel; an elevated parenchymal activity persisted after the first hour of acquisition. After two hours from a fat meal there was an elevated bowel activity; the outflow of the left lobe was complete, while there was a persistence of the activity in the lateral portion of the right lobe. Gastroscopy revealed esophagogastric varices. The liver biopsy, performed on both the right and the left lobe, demonstrated the characteristic abnormalities of congenital hepatic fibrosis (persistence of bile ducts remnants, abnormal branching of the intrahepatic portal veins and fibrosis of the portal tracts) on both lobes; the kidney biopsy was normal.