Progressive Familial Intrahepatic Cholestasis Type 3: A Case Report and Literature Review

Case Report

J Pediatr & Child Health Care. 2017; 2(1): 1014.

Progressive Familial Intrahepatic Cholestasis Type 3: A Case Report and Literature Review

Azami MA¹*, Lahbali O¹, Lamalmi N¹, Oukabli M² and Bouzidi AA²

¹Department of pathology, Child Hospital in Rabat, Mohammed V University, Morocco

²Department of pathology, Mohamed V Military Hospital, Mohammed V University, Morocco

*Corresponding author: Mohamed Amine Azami, Department of Pathology, Child Hospital in Rabat, Mohammed V University in Rabat, Morocco

Received: May 05, 2017; Accepted: June 02, 2017; Published: June 09, 2017


Progressive Familial Intrahepatic Cholestasis (PFIC) is a group of rare disorders which are caused by defect in bile secretion and present with intrahepatic cholestasis, usually in infancy and childhood.

Based on clinical presentation, laboratory findings, liver histology and genetic defect, these are broadly divided into three types: PFIC type 1(Byler’s disease), PFIC type 2 and PFIC type 3.

The main clinical presentation is in the form of cholestatic jaundice and pruritus. Serum Gamma Glutamyl Transpeptidase (GGT) is normal in patients with PFIC1/2 while it is raised in patients with PFIC3.

PFIC can progress rapidly and cause cirrhosis during infancy or may progress relatively slowly with minimal scarring well into adolescence. Few patients have survived into the third decade of life without treatment.

In PFIC3, clinical signs of cholestasis are noted within the first year of life in about one third of patients and rarely in the neonatal period, in contrast to PFIC1 and 2.

We report in this paper a case of a 45-days old boy presented early in the infantile period with deep jaundice, his investigations showed progressive cholestatic jaundice, high liver enzymes and high GGT. Hepatitis and metabolic errors were excluded. The liver biopsy showed a prominent parenchymal bile stasis without features of bile obstruction or an evidence of paucity of bile ducts. These findings are going with the diagnosis Progressive Familial Intrahepatic Cholestasis (PFIC3).

Keywords: PFIC3; Liver disease; Cholestasis; MDR3 deficiency


Progressive Familial Intrahepatic Cholestasis type 3 (PFIC3) is an autosomal recessive disorder of cholestasis of hepatocellular origin. The onset of PFIC3 is typically in infancy or in childhood.

PFIC3 has been ascribed to a defect in MDR3 (class III multidrug resistance p-glycoprotein) or ABCB4 gene, and the current preferred terminology is MDR3 deficiency [1].

Children with PFIC3 often present in the first year of life with clinical signs of cholestasis that leads to progressive liver disease and cirrhosis. PFIC3 patients have elevated serum Gamma Glutamyl Transferase activity (GGT) that differentiates them from those with PFIC 1 and 2.

Liver histology shows hepatocellular damage, inflammatory infiltration of the portal tract and fibrosis. In advanced disease, extensive fibrosis and biliary cirrhosis are seen [2].

We recently encountered a new presentation of this rare entity and share our experience in its diagnosis and treatment with progression of disease.

Case Report

45-days-old boy is a product of a full term normal delivery with birth weight of 2800 grams, pregnancy was uneventful, and his post-natal period passed without problems. His symptoms started at the first month of life when the parent noticed that he has yellow discoloration of skin and sclera which was becoming deeper by time then he started to have severe itching to his skin. His parents are first degree cousins but no family history of similar condition. On physical examination the child was deeply jaundiced with multiple scratch marks all over his body. His weight was 3.8 kg, his height was 59cm with moderate hepatosplenomegaly. There was no ascites, and no other signs of chronic liver disease or rickets. The results of his investigations showed a normal CBC, urea, creatinine and electrolytes. Total bilirubin was 19.2 gm with a direct of 7.7 gm. His liver enzymes, alkaline phosphatase 552, AST: 509, ALT: 231, Gama Glutamyl Transpeptidase (GGT):541 IU/l (normal:7-32). Prothrombin time was 14 seconds (control=14seconds) and partial thromboplastin time was 30seconds (control 32 seconds), albumin, cholesterol and triglycerides levels were normal. Infectious screen for hepatitis A, B, C, and TORCH infections were all negative. TSH and T4 are normal. Abdominal ultrasound showed slightly increased echogenicity of the enlarged liver. Liver biopsy showed prominent parenchymal bile stasis and partially distorted architecture but no features of bile obstruction or paucity of bile ducts (Figure1 and Figure 2). The patient is on medical treatment including fat soluble vitamins (A,D,E,K) and phenobarbitone without proper response and he is still having severe pruritis and deterioration of liver function so he will be referred for surgical treatment.

Citation: Azami MA, Lahbali O, Lamalmi N, Oukabli M and Bouzidi AA. Progressive Familial Intrahepatic Cholestasis Type 3: A Case Report and Literature Review. J Pediatr & Child Health Care. 2017; 2(1): 1014.