Year : 2010 | Volume
: 53 | Issue : 2 | Page : 334--336
PFIC type III in infant presenting as acute liver cell failure
Syed Ahmed Zaki1, Preeti Shanbag1, Anjali Amarapurkar2,
1 Department of Pediatrics, Lokmanya Tilak Municipal Medical College and General Hospital, Mumbai-400 022, India
2 Department of Pathology, TN Medical College and BYL Nair Hospital, Mumbai Central, Mumbai 400 008, India
Syed Ahmed Zaki
Room no. 509, new RMO quarters, LTMG hospital, Sion, Mumbai-400 022
An eight-month-old female, delivered to consanguineous parents, presented with acute liver cell failure. Her investigations showed progressive cholestatic jaundice, high liver enzymes and high gamma-glutamyl transferase. Hepatitis and inborn errors of metabolism were excluded. The liver biopsy showed a prominent parenchymal bile stasis without features of bile obstruction or paucity of bile ducts. These findings wee suggestive of Byler disease or progressive familial intra hepatic cholestasis type III (PFIC III) which begins in infancy and usually progresses to cirrhosis and hepatic failure in the first few years of life.
|How to cite this article:|
Zaki SA, Shanbag P, Amarapurkar A. PFIC type III in infant presenting as acute liver cell failure.Indian J Pathol Microbiol 2010;53:334-336
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Zaki SA, Shanbag P, Amarapurkar A. PFIC type III in infant presenting as acute liver cell failure. Indian J Pathol Microbiol [serial online] 2010 [cited 2020 Oct 24 ];53:334-336
Available from: https://www.ijpmonline.org/text.asp?2010/53/2/334/64326
Progressive familial intrahepatic cholestasis (PFIC) or Byler disease is an autosomal recessive inherited condition characterized by inability to drain bile from the liver even though the large bile ducts are open (i.e. cholestasis). It is a very rare cause of chronic liver disease in children and usually begins in infants less than six months of age. However some may present in later childhood. , We present a case of PFIC type III in an infant who presented an acute liver cell failure and was managed successfully.
An eight-month-old female infant presented with a history of itching all over body and yellowish discoloration of eyes and urine since two months. She had one episode of generalized tonic clonic convulsion associated with fever lasting for 15 minutes on the day of admission. This was followed by lethargy and drowsiness. She had no history of blood transfusion or hospital admission in the past. Her stools were yellowish in color. There was no other significant history. Her birth history was normal without any postnatal complication. Her parents were first-degree cousins without any family history of a similar condition. She was immunized up-to-date and weaning was started at the age of 5 months. She had a normal developmental history. On physical examination, the child was pale and deeply jaundiced, with multiple scratch marks all over her body. She had boils on her scalp which had ruptured and were bleeding continuously for two days. The pulse rate was 160/min and peripheral pulses were weak. Her respiratory rate was 32/min and blood pressure was 70/40mm Hg in the right upper arm in the supine position. Her weight was 7.2 kg and height 71cm, both below the 25th centile. She had signs of rickets in form of wrist flare and chest beading. There was no clubbing or cyanosis. Her liver was enlarged with a span of nine cm in the mid-clavicular line. It was non-tender and firm in consistency. The spleen was not palpable and there was no ascites. The infant was drowsy and had brisk deep tendon reflexes in the lower limbs with bilateral flexor plantars. There were no meningeal signs. Other systemic examination was normal.
Laboratory evaluation showed the following values: hemoglobin 3.2 g/dL; lukocyte count 28,800/mm 3 ; platelet count 450,000/mm 3 . Her liver function tests and coagulation profile on admission was deranged [Table 1]. Serum calcium was 8.6 mg/dL and random blood glucose 106 mg/dL. Her renal function tests, serum ammonia and serum electrolytes were normal. She was started on intravenous fluids with 10% dextrose, pressor support with dopamine and intravenous ceftriaxone and amikacin. In view of low hemoglobin and altered coagulation profile she was given packed red cell and fresh frozen plasma transfusions. She recovered gradually over a period of one week. A repeat coagulation profile was within normal limits. [Table 1]
Serum cholesterol and triglycerides levels were normal. Blood pyruvate, lactate and alpha 1-antitrypsin levels and serum chromatography for amino-acids were also normal. Her gamma-glutamyl transferase (GGT) was 230 IU/l (normal: 11-50) which was high. No organic acids or reducing substances were detected in the urine. Infectious screen for hepatitis A, B, C, and TORCH (Toxoplasmosis, Rubella, Cytomegalovirus, and Herpes) infections were all negative. Thyroid function tests were normal. Abdominal ultrasound showed slightly increased echogenicity of the enlarged liver. Hepatobiliary scan was not suggestive of extra hepatic biliary atresia with mild retention of tracer in the liver favoring intrahepatic cholestasis of the non-obstructive type.
Liver biopsy showed features of cholestatic liver disease with portal areas of normal size and intact limiting plates. Interlobular ducts were unremarkable with evidence of porto-portal bridging fibrosis (stage 3 fibrosis). There was prominent parenchymal bile stasis but no features of bile obstruction, paucity of bile ducts or storage disease. There was feathery change and rossetoid arrangement of hepatocytes. [Figure 1] and [Figure 2]. The above findings, along with the clinical and laboratory data, were suggestive of PFIC type III.
Ursodeoxycholic acid (20 mg/kg daily), cholestyramine, vitamins A, D, E, K and skin moisturizing lotions were started and the patient was discharged after one month. Parents were counseled on the need for liver transplantation and importance of antenatal testing in any future pregnancy. Her skin changes and pruritis had subsided on follow-up after two months.
The common differential diagnoses for such a presentation are extra hepatic biliary obstruction, metabolic disorders or an infective pathology. Alpha-1-antitrypsin deficiency was excluded immunocytochemically. Viral infections were not considered as giant cells were scarce and there were no cytoplasmic or nuclear inclusions. Benign recurrent intra hepatic cholestasis was not considered because of both clinical and histopathological features. Severe pruritis and jaundice were characteristic of cholestasis in our patient. Ultrasonography and hepatobiliary scan excluded extra hepatic cause for cholestasis in our patient. Intrahepatic cholestasis is further divided into two types on histopathological examination of liver biopsy: one with morphologic changes of intrahepatic bile ducts and the other without any changes. Our patient had no evidence of morphological changes of bile ducts on liver biopsy.
In addition to PFIC, there are many other causes of intra hepatic cholestasis without morphologic changes of intrahepatic bile ducts: hypothyroidism, peroxisomal disorders, Niemann-Pick disease, alpha-1-antitrypsin deficiency, cystic fibrosis, galactosemia, and tyrosinemia.  Clinical and laboratory findings of this case including liver biopsy were not consistent with these disorders. Thus clinical presentation, consanguinity, high GGT levels and histopathological examination of liver biopsy was suggestive of PFIC type III, although genetic analysis could not be performed due to financial constraints.
PFIC is caused by defects in several genes that produce proteins needed for bile formation and the "transportation" or flow of bile throughout the body.  A defect leads to blockage of bile in the liver or bile ducts, damaging liver cells and causing a dangerous buildup of waste in the blood stream. Decreased bile flow also prevents the body from being able to properly absorb fats and vitamins. Common symptoms of PFIC include, severe itching caused by the buildup of bile salts in the body, disproportionate jaundice, poor weight gain (due to a lack of bile needed to digest and absorb fat) and poor growth. ,
PFIC has autosomal recessive inheritance with three different genes dividing the disease into three types; types PFIC-1 and PFIC-2 have low to normal gamma-glutamyl-transferase (GGT) levels while type PFIC-3 has high-GGT levels and is the most severe type leading to early cirrhosis. , In most cases, progressive familial intrahepatic cholestasis leads to cirrhosis and liver failure.
Medical treatment is usually supportive and includes dietary modification, use of agents to treat cholestasis and pruritis, supplementation with fat-soluble vitamins. Common agents used for treatment of pruritis and cholestasis include ursodeoxycholic acid (a naturally-occurring bile acid) and cholestyramine which is a bile acid sequestrant, that binds bile in the gastrointestinal tract to prevent its reabsorption.  Some patients may respond to medical therapy, although surgical treatment is usually necessary for survival. Surgical treatment in children with progressive familial intrahepatic cholestasis includes liver transplantation and partial external biliary diversion (PEBD).
Partial external biliary diversion may be used as the first choice of treatment for patients who have not yet developed cirrhosis and who are unresponsive to all medical therapy, especially older patients. Liver transplantation is considered if partial external biliary diversion is ineffective or if the patient has liver cirrhosis. Survival rates after liver transplantation are excellent. 
We would like to thank Dr. Sandhya Kamath, dean of our institution, for permission to publish this manuscript.
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