Chapter 48 PREGNANCY AND LIVER DISEASE
Screening tests for women presenting with abnormal liver function tests (LFTs) in pregnancy should include serology for hepatitis A, B, C, Epstein-Barr virus (EBV), cytomegalovirus (CMV) and herpes simplex virus (HSV) as well as an upper abdominal ultrasound to exclude biliary disorders.
Determine the stage of pregnancy, and whether there is anything in the history to indicate a liver disorder. A pregnancy-related liver disorder should be considered in the event of any relevant past history, or history of medications or in the presence of features of pre-eclampsia.
Normal physiological changes in pregnancy are shown in Table 48.1. The mother’s blood volume increases by 40%, and her total body water increases by 20%. This is reflected in a 10%–60% fall in serum albumin and also a fall in haemoglobin. Up to 50% of women develop spider naevi and palmar erythema during pregnancy, which is thought to be due to the increasing levels of oestrogen. This reverses quickly post delivery. Serum alkaline phosphatase increases 2–4-fold in the third trimester (placental) and gamma-glutamyltranspeptidase decreases slightly. No change is observed in the aminotransferases (alanine aminotransferase and aspartate aminotransferase) or the prothrombin time. A rise in the transaminases should lead to further investigation.
|Blood test||Change during pregnancy|
|Alkaline phosphatase||Increases 2–4-fold (placenta)|
|Gamma-glutamyl transpeptidase||No change or slightly decreases|
|Aspartate aminotransferase||No change|
|Alanine aminotransferase||No change|
|Bilirubin||No change or slightly increases|
|Bile salts||No change|
|Albumin||Decreases by 10%–60%|
|Prothrombin time||No change|
Up to 3% of pregnancies are complicated by abnormal LFTs at term. The best guide in determining the cause of abnormal LFTs is the timing of the problem during pregnancy (Figure 48.1). The differential diagnoses include:
Pregnancy is associated with an increased rate of gallstone formation. Hence cholecystitis and cholelithiasis need to be excluded in any pregnant woman presenting with right upper quadrant pain, nausea and abnormal LFTs. The differential diagnosis of right upper quadrant pain (Table 48.5) in late pregnancy includes pregnancy-related liver problems, such as liver involvement in pre-eclampsia, even hepatic infarction or rupture. It should be remembered that the gravid uterus pushes up the appendix, and appendicitis in late pregnancy can present with right upper quadrant pain.
|Diagnosis||Incidence during pregnancy|
|Cholelithiasis/cholecystitis||3%–5% have biliary sludge|
|Pre-eclampsia + liver involvement||<1%|
|Acute viral hepatitis||Same as in the general population|
|Acute Budd-Chiari syndrome||Rare|
AFLP = Acute fatty liver of pregnancy; HELLP = haemolysis elevated liver enzymes and low platelet syndrome.
Hyperemesis gravidarum or extreme morning sickness is not a liver disease. However, one-quarter of women hospitalised for this condition have elevated aminotransferase levels. The condition classically occurs in the first trimester and resolves by about week 20, and is usually worse in twin pregnancies and during a first pregnancy. The LFT abnormalities improve on fluid and electrolyte management.
Cholestasis of pregnancy is the most common liver disease unique to pregnancy. The incidence is about 1/500 pregnancies (0.2%) in Australia. A higher prevalence is seen in Scandinavia and South America (14% risk in Chile). The condition is characterised by pruritus, and an increase in the serum bile acid, and is usually seen in the third trimester. Women present with an itch, without any skin lesions (apart from scratch marks). There may be a history of mothers or sisters with the same problem, and it may have occurred in previous pregnancies. The itch normally goes within days after delivery.
An itch is the only symptom; there should be no pain. Check for skin lesions as well as fasting bile acids, LFTs and an upper abdominal ultrasound (to exclude cholelithiasis). Make sure the expectant mother is not taking any drugs or herbs that could cause hepatotoxicity. Take a careful history, because any preexisting liver problem or hepatotoxic drug reaction will become more cholestatic during pregnancy. In addition, any form of cholestasis will cause an increase in serum bile acids. Rarely, thyrotoxicosis or primary biliary cirrhosis can present with an itch during pregnancy. These can be excluded by thyroid function tests and anti-mitochondrial antibody screening, respectively (especially if the problem doesn’t resolve postpartum). The hallmark of the condition is normalisation of symptoms and LFT abnormalities within a few weeks post delivery. A liver biopsy is not necessary for the diagnosis, but histology would show intracanalicular cholestasis without inflammation, or liver damage.
The pathogenesis is not understood. Membrane layers of the hepatocytes and the bile canaliculi become slightly leaky during a normal pregnancy (an effect of oestrogen), and this is more pronounced in women with a family history. Genetic deficiencies of canalicular transport proteins are associated with this condition.
Apart from a severe itch, cholestasis of pregnancy does not affect the mother (excluding the increased risk of a postpartum haemorrhage). Some women develop LFT abnormalities—the bilirubin may rise to 100 μmol/L and serum aminotransferases increase to 2–10 times the upper limit of normal—but there is no associated increased risk of liver failure. There is a 70% chance of recurrence during a subsequent pregnancy.
There is a five-fold increase in the risk of preterm labour and stillbirth. Fetal monitoring does not predict the babies at risk, as there is no problem with placental blood flow. The fetal risk is not understood; high bile acids appear toxic to the baby, and cause myometrial irritability. When the total bile acids are 40 μmol/L or greater, fetal complications can occur. Women with this condition will usually have an induced delivery at 38 weeks, to decrease the fetal risk.