PFIC2 is an autosomal recessive childhood disorder of bile formation in hepatocytes that is not associated with extrahepatic features.32 It is caused by impaired bile salt secretion due to defects in ABCB11 encoding the bile salt export pump protein (BSEP).58
PFIC2 accounts for about half the cases of PFIC.32 Untreated PFIC2 usually leads to progressive liver fibrosis and cirrhosis, and more rapidly than with PFIC1.32 Clinical and laboratory findings associated with PFIC2 are similar to those associated with PFIC1 but with an absence of extrahepatic symptoms. In PFIC2, gallstone formation and early elevation of serum aminotransferase activity may be observed. The development of hepatobiliary malignancies, both hepatocellular carcinoma and cholangiocarcinoma can be a serious complication of PFIC2, which is not commonly reported with PFIC1.32
PFIC2 is characterised by cholestasis with normal GGT and elevated total serum bile acids.
Diagnosis
- Liver biopsy reveals giant-cell (syncytial) hepatitis with hepatocelluar cholestasis and various degrees of lobular fibrosis32
Diagnosis is confirmed by genetic sequencing of the ABCB11 gene.32,58
Clinical, biochemical and histological features of PFIC1, PFIC2 and PFIC331
| Feature | PFIC type 1 | PFIC type 2 | PFIC type 3 |
| Age at onset | Infancy | Neonatal period-early infancy | Late infancy (30%) to early adulthood |
| End stage liver disease | First decade | Rapid, first few years | 1st to 2nd decade of life |
| Course of disease | Moderately severe | Severe | Insidious |
| Pruritus | Severe | Very severe | Moderate |
| Extrahepatic manifestations (watery diarrhoea, pancreatitis, sensorineural deafness, short stature, abnormalities in sweat chloride) | Present | Absent | Absent |
| Risk of development of liver tumours | Low | High | Mild increase |
| Risk of cholesterol stone formation | Absent | Increased | Increased |
| Serum ALT | Mild elevation | Moderate elevation | Mild elevation |
| Serum AFP | Normal | Elevated | Normal |
| Serum GGT | Normal | Normal | Elevated |
| Serum bile acids | Elevated ++ | Elevated +++ | Elevated + |
| Primary bile acids | Low (3–8 mM) | Very low ( ‹ 1 mM) | Normal |
| Phospholipids | Normal | Normal | Low |
| Liver histology | Cholestasis, mild lobular fibrosis | Cholestasis, giant cell hepatitis, hepatocellular necrosis, lobular fibrosis | Bile ductular proliferation, cholestasis, portal fibrosis |
| Electron microscopy | Granular bile | Amorphous bile | - |
31. Srivastava A. Progressive familial intrahepatic cholestasis. J Clin Exp Hepatol 2014;4:25-36.
32. Sticova E, Jirsa M, Pawłowska J. New Insights in Genetic Cholestasis: From Molecular Mechanisms to Clinical Implications. Can J Gastroenterol Hepatol 2018;2018:2313675.
58. Davit-Spraul A, Gonzales E, Baussan C, Jacquemin E. Progressive familial intrahepatic cholestasis. Orphanet J Rare Dis 2009;4:1.
