Pregnancy

Liver Diseases in Pregnancy
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Pruritus is the main feature of IHCP and is present in
all patients. Pruritus can be disabling and most commonly
involves the hands and feet although it can be
generalized. Jaundice occurs 2-4 weeks after the onset
of pruritus in 10%-25% of affected women. Other
symptoms include nausea, vomiting and abdominal
pain.
Laboratory assessment shows a marked elevation of
alkaline phosphatase and serum bile acids. Serum
transaminases are typically mildly elevated. Total and
direct bilirubin levels are increased in up to one-third
of patients but total bilirubin levels are rarely greater
than 5 mg/dl. Interestingly serum level of Gamma
Glutamyl Transferase GGT is normal or slightly elevated.
Liver biopsy is usually not needed to make the diagnosis
of IHCP. Typical histologic findings include centrilobular
cholestasis, canaliculi containing bile plugs,
and bile pigment in hepatocytes. Inflammation and necrosis
are not usually observed in the portal tracts.
Therapy of IHCP is aimed at ameliorating the pruritus
in the mother and improving fetal outcome. Cholestyramine
has been used in the past for the management
of pruritus but was found to worsen fetal outcome by
increasing the risk of fetal hemorrhage due to vitamin
K deficiency and should be avoided.
Fetal hemorrhage has been
reported in association
with IHCP due to vitamin K
deficiency.
Fetal hemorrhage has been reported in association
with IHCP due to vitamin K deficiency. Thus all patients
with IHCP with prolonged cholestasis should be
monitored with prothrombin time and vitamin K deficiency
corrected.
Ursodeoxycholic acid (UDCA) (FDA Category B) has
been tested in randomized clinical trials and is considered
the treatment of choice in pregnant women with
IHCP due to its documented efficacy and safety to the
fetus after the first trimester. UDCA is a hydrophilic
bile acid that modifies the bile acid pool composition
in replacing toxic bile acids. It decreases the passage
of maternal bile acids to the fetal placental unit and
improves the function of bile acid transporters. When
given to women with severe symptoms of IHCP, at 1
gram divided into three daily doses, significant relief
from pruritus and marked reduction of serum bile acids
occured after one week of therapy. Liver test abnormalities
were also noted to be improved without
maternal or fetal toxicity. 12
Maternal outcome is favorable in IHCP although poor
weight gain due to anorexia and vomiting can occur.
The pruritus disappears within 48 hours of delivery in
most cases. Biochemical abnormalities and liver histology
resolve after several weeks. Long-term followup
studies have shown that women with IHCP are at
increased risk for gallstone related hepatobiliary disorders.
13
Fetal outcome is less benign however, with increased
risk of premature delivery, neonatal death (stillbirth),
and meconium staining of amniotic fluid. Fetal mortality
in the absence of therapy averages 11-20%. The
mechanism of fetal complications associated with
IHCP is not known although it has been proposed that
elevated serum bile acids may stimulate uterine muscle
contractions and may lead to fetal anoxia. Because
of the potential for serious fetal complications in pregnant
women with IHCP, it is recommended that aggressive
monitoring for fetal distress during the third
trimester should be done. The role of UDCA on fetal
outcome is not clearly established, and while elevated
serum bile acid levels > 40 micromol/L have been reported
in association with more severe disease and fetal
distress, babies should be delivered promptly after
lung maturity regardless of bile acid levels to avoid
fetal compromise.
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