As our understanding of pathophysiology improves, frequently this results in reclassification of diseases.  Perhaps the best example in pediatric hepatology is gestational alloimune liver disease/congenital alloimmune hepatitis, formerly called neonatal hemochromatosis  (see previous post).  Hepatic ciliopathies are less commonly discussed and thus far have not resulted in abandoning previous nomenclature. These hepatic ciliopathies are related to fibrocystic disease proteins which localize to the primary cilia.  Ductal plate malformation is the main pathology that underlies the liver disease in ciliopathies.  The characteristics of one of these disorders, congenital hepatic fibrosis (CHF) in autosomal dominant polycystic kidney diseae (PKD) involving 19 patients is described in this month’s JPGN (JPGN 2012: 54: 83-89).  Portal hypertension was the main manifestation.  “Hepatocellular function was preserved and liver enzymes were largely normal.”  In patients with AD-PKD-CHF, this was  due to PKD1 mutations with probable contributions from modifier genes.  One interesting finding was that in the identified families, the parents who were affected by polycystic kidney disease did not have CHF.

Although this study demonstrates that CHF and portal hypertension can occur with AD-PKD, CHF and portal hypertension are a characteristic finding with AR-PKD.  With AD-PKD, the liver cysts originate from biliary microhamartomas (von Meyenburg complexes) and are not in continuity with the biliary tree.  In contrast, patients with AR-PKD have cystic dilatations of the biliary system; this combination is called Caroli syndrome.  Due to these differences, unlike AR-PKD, AD-PKD does not typically result in portal hypertension.

Additional references on congenital hepatic fibrosis:

• -Hepatology 2010; 52: 2223. Review. Medical/Surgical & Tx options.
• -Am J Med Genet C Semin Med Genet 2009; 151C: 296-406.  Liver disease and kidney disease in ciliopathies.
• -NEJM 2008; 359: 1477.  Review of autosomal dominant polycystic kidney disease.  ~80% develop liver cysts.
• -NEJM 2007; 356: 1560. Nice pic of resected liver with polycystic liver disease in 51 year old.
• -J Pediatr 2006; 149: 159. Review and NIH protocol for enrolling patients. Clinical GI issues: recurrent cholangitis, portal htn, cholelithiasis, and cholangiocarcinoma.
• -Pediatr Transplantation 2005; 9: 634-9.
• -Hepatology 2004; 40: 774-82.
• -Surg Endosc 2005; 19: 130-32.
• -Gastorenterol Clin N Am; 2003; 32: 857-75. “Heritable disorders of the bile ducts”