Meconium ileus is the presenting clinical manifestation of cystic fibrosis in 10 to 20% of cases.

Of
infants with meconium ileus, 80 to 90% have cystic fibrosis.
About 50% of cases are complicated by malrotation, intestinal atresia, or perforation. The distended
loops of small bowel may twist to form a volvulus in utero. If the intestine loses its vascular supply and
infarcts, sterile meconium peritonitis can result. The infarcted intestinal loop may be resorbed, leaving an
area or areas of intestinal atresia. Infants with meconium ileus are also at increased risk of
developing cholestasis.

are: Alagille syndrome,

progressive familial intrahepatic cholestasis (PFIC), alpha-

1-antitrypsin deficiency (α1-ATD), and cystic fibrosis.

Neonatal haemochromatosis, Zellweger syndrome,

Niemann–Pick disease type C, and glycogen storage disease

type IV should also be considered in the differential

diagnosis of infantile cholestasis (Tables 9.1, 9.2).

Alagille syndrome

Alagille syndrome can present with very early cholestasis of

infancy but it may also be asymptomatic for a very long time.

Liver damage may progress quickly in some patients with

portal hypertension, recurrent cholangitis, and malnutrition6.

Diagnosis of Alagille syndrome is aided by the presence of

syndromic features, including bile duct paucity on liver

histology, chronic cholestasis, cardiac murmur, vertebral

abnormalities, peculiar facies, eye findings, renal disease, and

xantomas7. Usually differential diagnosis is performed in early

infancy when biliary atresia must be excluded.

Typical facial features are a prominent forehead, pointed

chin, deep set eyes, moderate hypertelorism, and a saddle or

straight nose with a bulbous tip (9.1), but these features are

not very typical in early infancy. The parents may also have

the typical appearance (9.2) which may indicate the need to

diagnose this disease. Pulmonary artery stenosis is a typical

finding which may also cause a serious heart disease (9.3,

9.4). Embryotoxon posterior observed in a slit lamp is one

of the most common features of the Alagille syndrome.

Butterfly vertebrae observed in late infancy are also a

characteristic feature (9.5). Liver biopsy is helpful to

establish the diagnosis (9.6). Liver disease may slowly

progress to liver insufficiency and liver transplantation may

be needed. However, in most of the patients liver disease

remains stable for a long time.

Another neonatal liver disease presenting with typical

features and cholestasis is Zellweger’s syndrome (9.15), a

generalized peroxisomal biogenesis disorder which is

characterized by a wild spectrum of abnormalities including

in the nervous system and kidneys. Patients have

characteristic craniofacial abnormalities with wide

fontanelle, prominent forehead, anteverted nostrils, and

narrow upper lip. Hepatic involvement includes

hepatomegaly and conjugated hyperbilirubinaemia due to

abnormal bile acid synthesis. In some cases cirrhosis and

portal hypertension has been reported in the first year of life.

The administration of primary bile acids (cholic acid and

chenodeoxycholic acid) may improve liver function.

Cytolysis (ALT/GPT; AST/GOT; GGT, and LDH).

• Cholestasis (alkaline phosphatase; GGT; direct bilirubin;

bile acids, cholesterol, and 5´ nucleotidase).

• Synthetic liver function (albumin, prothrombin time, and

cholinesterase).

• Chronicity (immunoglobulin G and other immuno -

globulins).

Aminotransferases represent the integrity of liver cells. The

quotient AST/ALT is normally less than 1. When it is higher

than 1, it may mean that a more severe liver damage is present

(Table 9.4). GGT and alkaline phosphatase increase if there is

an obstruction or a damage in hepatic canaliculae (Tables 9.5,

9.6). Prothrombin time is an excellent marker of liver synthetic

function, as most coagulation factors are synthesized in the

liver. Prothrombin time is a measure of the extrinsic and

common pathway of coagulation. Prolonged prothrombin

time is a sign of an important hepatocellular dysfunction.

LDH

• ↑ in hepatic and extrahepatic damage

• Less specific

• Fraction 5: more liver specific

Alkaline phosphatase

• Synthesis in bile canaliculi membranes

• Bone, kidney and small intestine

• If there is no GGT rise, hepatopathy is not probable

Table 9.8 Causes of acute liver disease

Viral hepatitis by A, B, C, D, E, G virus

• Viral hepatitis by CMV, EBV

• Drug-induced hepatitis, alcohol

• Ischaemic hepatitis (heart failure, hypotension,

sepsis, Budd–Chiari)

• Cholangitis

• Wilson’s disease

• Autoimmune hepatitis

• Other rare infectious agents

Causes of chronic liver disease

Viral chronic liver disease

• Wilson’s disease

• α-1-antitrypsin deficiency

• Autoimmune hepatitis

• Drug/alcohol-induced hepatitis

• Nonalcoholic fatty liver disease

• Haemochromatosis

• Porphyrias

• Cystic fibrosis

• The most frequent causes of gross elevation in

transaminases in acute hypertransaminasaemia

(AST/ALT >1000) are: viral hepatitis, drug and alcoholinduced

hepatitis, and ischaemic hepatitis (heart failure,

hypotension, sepsis, Budd–Chiari) (9.25).

• In chronic hepatitis, the inversion of the quotient

AST/ALT (>1), indicates a deeper damage (mito -

chondrial) and evolution to fibrosis-cirrhosis.

• Liver transplantation is indicated if there is reduced

transaminases with increased bilirrubin and decreased

prothrombin time. These are signs of submassive liver

necrosis and consequent hepatocellular failure. Grade

III/IV encephalopathy and/or factor V <25% are clear

indications for liver transplantation.