Page 617 - Textbook of Pathology, 6th Edition

Crigler-Najjar Syndrome NEONATAL HEPATITIS 601
Crigler-Najjar syndrome is a rare form of familial non- Neonatal hepatitis, also termed giant cell hepatitis or
haemolytic jaundice with very high unconjugated hyper- neonatal hepatocellular cholestasis, is a general term used
bilirubinaemia. There are 2 forms of this condition: type I and for the constant morphologic change seen in conjugated
type II. hyperbilirubinaemia as a result of known infectious and
metabolic causes listed in Table 21.4, or may have an
Type I Crigler-Najjar syndrome. This is inherited as an idiopathic etiology. ‘Idiopathic’ neonatal hepatitis is more
autosomal recessive disorder. There is complete absence of common and accounts for 75% of cases. Though all the cases
conjugating enzyme UDP-glucuronosyl transferase in the with either known etiologies or idiopathic type are grouped
hepatocytes and hence no conjugated bilirubin is formed. together under neonatal hepatitis, all of them are not
There is extreme elevation of unconjugated bilirubin (usually necessarily inflammatory conditions, thus belying their
more than 20 mg/dl) with high risk of developing permanent nomenclature as ‘hepatitis’. The condition usually presents
CNS damage from kernicterus. The prognosis is generally in the first week of birth with jaundice, bilirubinuria, pale
fatal, with death coming from kernicterus usually in the first stools and high serum alkaline phosphatase.
year of life.

MORPHOLOGIC FEATURES. There are no significant MORPHOLOGIC FEATURES. Irrespective of the etio-
morphologic changes except some canalicular stasis. logy, there is morphologic similarity in all these cases. The
histologic features are as under:
Type II Crigler-Najjar syndrome. This is inherited as an 1. Loss of normal lobular architecture of the liver.
autosomal dominant disease. There is deficiency of enzyme 2. Presence of prominent multinucleate giant cells
UDP-glucuronosyl transferase but not complete absence. derived from hepatocytes.
Thus, unconjugated hyperbilirubinaemia is generally mild 3. Mononuclear inflammatory cell infiltrate in the portal
to moderate (usually less than 20 mg/dl). Occurrence of tracts with some periportal fibrosis.
kernicterus is exceptional and patients respond well to 4. Haemosiderosis.
phenobarbital therapy. 5. Cholestasis in small proliferated ductules in the portal
tract and between necrotic liver cells. CHAPTER 21
MORPHOLOGIC FEATURES. There are no morphologic
changes in the liver. BILIARY ATRESIAS

Biliary atresias, also called as infantile cholangiopathies, are a
Dubin-Johnson Syndrome
group of intrauterine developmental abnormalities of the
Dubin-Johnson syndrome is autosomal recessive disorder biliary system. Though they are often classified as congenital,
characterised by predominant conjugated hyperbilirubinaemia the abnormality of development in most instances is
(usually less than 5 mg/dl) with genetic defect in canalicular extraneous infection during the intrauterine development or
excretion of conjugated bilirubin. A prolonged BSP dye shortly after birth that brings about inflammatory destruction
excretion test is diagnostic of Dubin-Johnson syndrome of the bile ducts. The condition may, therefore, have various
(page 593). grades of destruction ranging from complete absence of bile
ducts termed atresia, to reduction in their number called
MORPHOLOGIC FEATURES. Grossly, the condition paucity of bile ducts.
differs from other forms of hereditary hyperbili- Depending upon the portion of biliary system involved,
rubinaemias in producing greenish-black pigmented liver. biliary atresias may be extrahepatic or intrahepatic.
Microscopically, The hepatocytes show dark-brown, The Liver, Biliary Tract and Exocrine Pancreas
melanin-like pigment in the cytoplasm, the exact nature Extrahepatic Biliary Atresia
of which is obscure but it is neither iron nor bile. Unrelated The extrahepatic bile ducts fail to develop normally so that
viral hepatitis mobilises the hepatic pigment of Dubin- in some cases the bile ducts are absent at birth, while in others
Johnson syndrome leading to its excretion in urine but the ducts may have been formed but start undergoing
the pigment reappears after recovery from viral hepatitis.
sclerosis in the perinatal period. It is common to have
multiple defects and other congenital lesions. Extrahepatic
The disease runs a benign course and does not interfere
with life. biliary atresia is found in 1 per 10,000 livebirths. Cholestatic
jaundice appears by the first week after birth. The baby has
severe pruritus, pale stools, dark urine and elevated serum
Rotor’s Syndrome
transaminases. In some cases, the condition is correctable
This is another form of familial conjugated hyperbilirubinaemia by surgery, while in vast majority the atresia is not correc-
with mild chronic jaundice but differs from Dubin-Johnson table and in such cases hepatic portoenterostomy (Kasai
syndrome in having no brown pigment in the liver cells. The procedure) or hepatic transplantation must be considered.
disease is inherited as an autosomal recessive character. The Death is usually due to intercurrent infection, liver failure,
defect probably lies in intrahepatic storage of bilirubin but and bleeding due to vitamin K deficiency or oesophageal
the exact protein abnormality is not known. varices. Cirrhosis and ascites are late complications
Rotor’s syndrome has an excellent prognosis. appearing within 2 years of age.