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Liver disorders in pregnancy -
03-19-2006, 11:27 PM
During normal pregnancy the various liver function tests can often show a mildly cholestatic change, with the alkaline phosphatase levels being almost double (this can persist for a few weeks after delivery too). The majority of this alk.phos however comes from the placenta. (Other markers such as serum bilirubin, aminotransferases, GTT and INR all remain within normal range during pregnancy.)
Abnormal LFTs may also occasionally be associated with other non-hepatic complications of pregnancy- notably hyperemesis gravidarum.
It can sometimes thus be difficult to distinguish the abnormal liver from the normal liver in pregnancy, especially when some of the stigmata of chronic liver disease- such as palmar erythema and spider naevi can be found on clinical examination of the pregnant woman. These signs however are due to the increasing levels of oestrogen (normal in pregnancy) rather than any liver pathology.
Despite these biochemical tests being altererd liver function and metabolism is hardly affected. The size of the liver does not normally increase either. In fact as the uterus increases in size the liver is pushed superiorly- a palpable liver therefore suggests significant hepatomegaly.
Although not a common complication of pregnancy, primary liver disease can occur and it is very important to recognise, especially since some conditions such as fatty liver can very quickly progress, becoming fatal to mother and fetus.
Liver diseases occuring in pregnancy can include liver diseases common to non-pregnant patients or liver diseases which occur only in pregnancy i.e. are a direct result of the pregnancy.
Of the liver diseases that can affect any young woman viral hepatitis is the most common cause of jaundice and abnormal LFTs in pregnant women. Titres for hep A, B and C should therefore be checked as should cytomegalovirus and toxoplasmosis in a pregnant woman presenting in such a way.
Gallstones and their complications such as acute cholecystitis have an increased incidence during pregnancy (95% of patients with acute cholecystitis have gallstones). This is because oestrogen (which itself is increased in pregnancy) raises serum cholesterol resulting in increased bile salt production which, combined with the effect of progesterone (reduces gall bladder emptying) increases risk of gall stones.
Asymptomatic gallstones do not require treatment and should the patient develop cholecystitis management should be as conservative as possible.
Liver Diseases Unique to Pregnancy
The liver diseases unique to pregnancy are:
1.) Acute fatty liver of pregnancy
2) Pregnancy toxaemies and HELLP syndrome
3) Obstetric cholestasis
Acute fatty liver of pregnancy
In acute fatty liver of pregnancy the liver becomes infiltrated with fatty deposits which can rapidly lead to hepatic failure and even death. Though very rare it has a mortality rate of 18% (maternal) and 23% (fetal).
Its peak presentation is during the third trimester and can be associated with pre-eclampsia, eclampsia, male fetus, nulliparity and twins.
It can often present rather non-specifically- with nausea and vomiting +/- abdo pain followed by jaundice- which can rapidly progress to hepatic failure. There may be proteinuria and hypertension.
Sometimes the mother presents with fulminant hepatic failure, in which case prognosis for both mother and baby is poor.
Investigations
-show a mildly raised aminotransferase with a raised alkaline phosphatase and bilirubin.
- urate is very high
- often severe hypoglycaemia
-biopsy of the liver will reveal micrscopic droplets of fat within the hepatocytes.
Management:
- supportive: coagulopathy, hypoglycaemia and fluid imbalances corrected
-fetus monitored or
-prompt delivery of the baby (definitive treatment) usually by caesarian: this can be life-saving in this condition.
There is a risk of post partum haemorrhage following delivery and the liver dysfunction may persist for sometime after delivery. Sometimes a liver transplant is necessary. However, if the patient recovers, there is no long-term impairment of the liver.
Pregnancy toxaemias and HELLP syndrome:
These are associated with severe pre-eclampsia and eclampsia (though can arise in the absence of hypertension and proteinuria). Abdominal tenderness with abnormal liver biochemistry often suggests liver involvment in these cases. The secondary effects of the metabolic, inflammatory and endothelial alterations that occur in pre-eclampsia can cause hepatocellular necrosis. Very rarely it can cause subcapsular haematoma and even hepatic rupture (1:45,000).
HELLP syndrome, believed to be a variant pre-eclampsia affecting 4-12% of those with pre-eclampsia/eclampsia describes a combination of haematological and hepatic disturbances. It stands for:
H = haemolysis
E L= elevated liver enzymes (especially transaminases)
L P = low platelets
It may present with epigastric pain, nausea and vomiting and right upper quadrant tenderness.
Numerous other disturbances including acute renal failure and D.I.C may be present.
Investigations
-a raised aspartate transaminase followed by a raised lactic dehydrogenase.
-Burr cells and polychromasia- consistent with haemolysis may be visible on a blood film.
Management
-stabilising coagulation
- possibly considering the need to deliver the baby.
The latter is usually only considered in moderate to severe cases- whereas milder cases may be managed more conservatively with close monitoring of both mother and fetus.
Obstetric cholestasis:
This is caused by an exaggerated response of the liver to the increased levels of oestrogen that occur in pregnancy resulting in cholestasis. The reason why this occurs is unknown but there is believed to be a genetic predisposition (positive family history in 50% of cases). The women generally feel well- except for the uncontrollable itching and dont complain of nausea, vomiting or abdominal pain. Pale stool and dark urine may be present
It usually presents after 30 weeks gestation with an insidious onset of pruritis affecting the limbs and trunk and is often severe. In half of these patients jaundice develops.
Investigations:
- serum total bile acid concentration: increases early in the disease and is the optimum marker of the condition
-transaminases may be increased- only moderately
-serum alkaline phosphatase and cholesterol rise
- ultrasound is normal
When investigating a mother with cholestasis it is important to exclude other causes of jaundice and pruritis including viral hepatitis, primary biliary cirrhosis (which may present for the first time during pregnancy) and biliary tract disease.
Though the condition has no serious long-term risks to the mother it can increase the risk of preterm labour and decrease fetal survival (increases risk of intrauterine fetal death). As a result the fetus is monitored closely and treatment is supportive with bile-salt binding agents.
Delivery at 37-38 weeks is appropriate in this condition.
Symptoms of the condition usually disappear a couple of weeks after delivery but there is a significant risk of reoccurence in subsequent pregnancies and with the use of combined oral contraceptive pill-COCP (or any oestrogen):the COCP is thus contraindicated.
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