Progressive Familial Intrahepatic Cholestasis type 1 


Dr.Ghaniya KC ,Dr.Sreya drSindhu ,Dr Sathyajith A , Dr.Sajitha Nair ,Dr Bhanu Vikraman Pillai Dr.C.Jayakumar 

Fifty five day old male child 1.7kg first born out of a non consanguineous parentage from Maldives, born at 34 weeks with bilateral CTEV came to AIMS for evaluation of progressive jaundice, pale yellow stools and dark colored urine noticed since day 5 of life.
No H/o mucocutaneous bleed/altered sensorium / seizure
PAST HISTORY
Mother was on treatment for hypothyroidism . She had GDM also and was on metformin.
Delivered emergency LSCS due to absent felal movement and meconium stained liquor was resuscitated with Bag and Mask Ventilation .
Mother’s blood group : O positive 
Ba’s blood group : A negative 

Hyperbilirubinemia was noted on day 2→started on phototherapy
Day 5 report say that ba had→ Conjugated hyperbilirubinemia
At 1 month → mother noticed increased yellowish discolouration of face and body along with irritability. Evaluation at a local hospital showed increased conjugated hyperbilirubinemia : 
TSB -15 mg/dL DSB-10.5 mg/dL

CLINICAL EXAM: –
Afebrile, jaundiced, stool pale yellow, urine dark yellow
Umblical Hernia 1cm x1cm and ba was on Ponsetti cast for bilateral CTEV 

P/A : mild distension+, liver palpable 3cm Below right costal margin , firmish, non tender. Span of 7 cm . Spleen tip palpable. No ascites 

INVESTIGATIONS
-TC – 11.33 KU/ml N-23.4 % L-57.7 % 
Hb-6.7 g/dL.Plt 580 Ku/ml
Bili 10.99, Direct 7.11, 
SGOT – 333, SGPT-135
ALP-763, GGT: 55 Normal, 
AFP: 106686
PT/INR : 16.8 /14.7/1.15
-USG Abdomen: Gallbladder : Physiologically distended.Wall thickness is normal.No Hepatosplenomegaly.
-Blood cultures Sterile
– Urine culture: Sterile
– Perpheral smear : microcytic hypochromic anemia
– IgM TORCH- Negative
– HIDA – normal progression
– G6PD assay – normal
– Blood Galactose level – Normal
– Urinary Succinyl acetone – normal 
⁃ HPLC – normal
⁃ ECHO – normal
⁃ Liver biopsy – shows cannalicular cholestasis with duct paucity.
Possibility of PFIC 1 to be considered in view of the almost bland canalicular cholestasis, duct paucity and normal GGT.
⁃ WES & microarray results – awaited

DIFFERENTIAL DIAGNOSIS 
⁃ Biliary atresia 
⁃ Alagille syndrome Choledochal cyst
⁃ Gallstones, biliary sludge, or 
inspissated bile
⁃ Neonatal sclerosing cholangitis
⁃ PFIC
⁃ α1-Antitrypsin 
⁃ Tyrosinemia 
⁃ Galactosemia 
⁃ Hypothyroidism
Child was discharged with Vit ADEK and iron drops

MANAGEMENT:
Both medical and surgical interventions. 
Medical : 1)Phenobarbital3to 5mg /kg has long been used in the treatment of newborn hyperbilirubinemia through its ability to induce CYP enzymes. 
As it cause neuronal apotoposis this is not a good drug at all Irrespective off its choleretic property 
In case of biliary atresia valuable five days is lost if we prime with phenobarbitone for Five days

2)ursodeoxycholic acid (UDCA) 15mg /kg 

3)cholestyramine —> treat pruritis associated with PFIC – 240 mg/kg/24 hr

4)Rifampicin —> work via FXR related mechanisms to upregulate specific detoxification enzymes. 

Surgery – Biliary diversion procedures either external or internal
Newer methods 
Partial internal biliary drainage procedures 
ileal pass procedures.

Liver transplant is still the best treatment option for patients with PFIC and is now being considered a first-line option in many centers, even in patients without evidence of end-stage liver disease.

PROGNOSIS: 
Most patients with PFIC will develop end-stage liver disease with significant fibrosis adulthood. Given the progressive nature of this condition, if patients do not undergo a liver transplant, there is high morbidity and mortality associated with it.

Take Home Message : Possibility of PFIC should always be considered in an infant presenting with severe pallor and jaundice

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