Liver disease in pregnancy (Obstetric Cholestasis/acute fatty liver of pregnancy) Flashcards
Obstetric cholestasis algorithm
OC presentation in pregnancy:
Obstetric cholestasis typically present later in pregnancy, particularly in the third trimester.
Itching (pruritis) is the main symptom, particularly affecting the palms of the hands and soles of the feet.
Other symptoms are related to cholestasis and outflow obstruction in the bile ducts:
- Fatigue
- Dark urine
- Pale, greasy stools
- Jaundice
differential diagnosis of OC:
Other causes of pruritus and deranged LFTs should be excluded, for example:
- Gallstones
- Acute fatty liver
- Autoimmune hepatitis
- Viral hepatitis
Investigations for OC:
Women presenting with pruritus should have liver function tests and bile acids checked.
Obstetric cholestasis will cause:
- Abnormal liver function tests (LFTs), mainly ALT, AST and GGT
- Raised bile acids
TOM TIP: It is normal for alkaline phosphatase (ALP) to increase in pregnancy. This is because the placenta produces ALP. A rise in ALP without other abnormal LFT results is usually due to placental production of ALP, rather than liver pathology.
- Examination – pregnant abdomen, neuro
- Obs – BP important
- Urine dip
- Bloods – FBC, LFTs, Serum Bile acid
- Virology – hepatitis, EBV, CMV
- Liver autoimmune screen
- Liver USS
management of OC:
- Ursodeoxycholic acid (oral) is the primary treatment for obstetric cholestasis. It improves LFTs, bile acids and symptoms ((rifampicin 150mg BD)
Symptoms of itching can be managed with:
- Emollients (i.e. calamine lotion) to soothe the skin
- Antihistamines (e.g. chlorphenamine) can help sleeping (but does not improve itching)
- Water-soluble (oral) vitamin K can be given if clotting (prothrombin time) is deranged. Vitamin K is a fat-soluble vitamin. Bile acids are important in the absorption of fat-soluble vitamins in the intestines. A lack of bile acids can lead to vitamin K deficiency. Vitamin K is an important part of the clotting system, and deficiency can lead to impaired clotting of blood.
- Monitor of LFTs is required during pregnancy (weekly) and after delivery (after at least ten days), to ensure the condition does not worsen and resolves after birth.
- Planned delivery after 37 weeks may be considered, particularly when the LFTs and bile acids are severely deranged. Stillbirth in obstetric cholestasis is difficult to predict, and early delivery aims to reduce the risk.
peak bile acid and recommendation
Peak Bile Acid Level
Recommendation
>100
Delivery is recommended in the 35th gestational week, with input from the obstetric medicine team and individualisation of care.
Where women have already passed this gestation, induction of labour should be arranged imminently.
BA: 40-100
38-39 weeks
BA: <40
There is a lack of evidence to support prolonged pregnancy past 40 gestational weeks, although there is no evidence that these babies are at increased perinatal risk. Therefore, women with mild disease can be supported to continue the pregnancy to 40 weeks, at which point induction of labour can be offered
OC pathophysiology:
Obstetric cholestasis is also known as intrahepatic cholestasis of pregnancy. Chole- relates to the bile and bile ducts. Stasis refers to inactivity. Obstetric cholestasis is characterised by the reduced outflow of bile acids from the liver. The condition resolves after delivery of the baby.
Obstetric cholestasis is a relatively common complication of pregnancy, occurring in around 1% of pregnant women. It usually develops later in pregnancy (i.e. after 28 weeks), and is thought to be the result of increased oestrogen and progesterone levels. There seems to be a genetic component. It is more common in women of South Asian ethnicity.
Bile acids are produced in the liver from the breakdown of cholesterol. Bile acids flow from liver to the hepatic ducts, past the gallbladder and out of the bile duct to the intestines. In obstetric cholestasis, the outflow of bile acids is reduced, causing them to build up in the blood, resulting in the classic symptoms of itching (pruritis).
Obstetric cholestasis is associated with an increased risk of stillbirth.
key questions in history for OC:
- Full history of current pregnancy – how far along? Any problems? Up to date scans? Any abnormalities seen on scans? Under care of midwife or consultant doctor
- Itching – where is itching? Hands and feet worse? How bad? Worse at night? Keeping you up at night? Itching breaking the skin? Causing bleeding?
- Any rash? Dryness?
- Any relief for itching?
- Dark stools?
- Pale urine?
- Jaundice? Yellow eyes?
- Abdominal pain?
- Eating and drinking ok?
- FRAB?
- FLAWS?
- Malaise?
- PET screen – problems with BP so far? headache? Visual disturbances? N&V? swelling or oedema?
- Gynae – brief history
- Obs – past pregnancies? Problems in past pregnancies?
- PMH and DH
- FH
- Social – living situation? Well-supported? Working? Coping ok? Stress? Smoking? ETOH? Drugs?
management of OC (PACES style):
- What is it? – ‘This is a condition where there is a problem with your liver which causes a substance called bile acids to build up in your blood and cause the symptoms you’ve been experiencing. It is quite important that we keep an eye on you to make sure baby is doing ok, because if that substance gets too high it can cause some complications.’
- What are the complications? – ‘The risks of having this high bile acid in the blood is that it can make baby do a poo inside your womb around the time of delivery, it can cause baby to be born early and in some very rare cases, it can cause baby to pass away. This is a very rare complication and we will be doing everything we can to make sure that doesn’t happen.’
- What is going to be done? – ‘Your care will now be taken over by the senior obstetricians who will follow you up. We will be doing weekly blood tests to measure your bile acid level and monitor your liver function. Unfortunately, there is no cure for this conditions but the monitoring is to reduce the risk of any complications. We can give you some creams or some anti-histamines to help with the itching and to help you sleep better. A medication called Ursodeoxycholic acid can help reduce the bile acids in your blood and help with the itching.’
- Lifestyle – ‘Some women find that wearing loose clothing and having cool or tepid baths helps improve the itchiness.’
- Delivery – ‘To reduce the risk of complications, we find that it is better to deliver your baby a bit earlier at around 37 weeks, especially if your blood tests are very abnormal. This condition can increase your chances of bleeding for too long during the delivery so we are also going to prescribe you some vitamin K every day to take from now until delivery to reduce that risk too.
presentation of AFLP:
The presentation is with vague symptoms associated with hepatitis :
- General malaise and fatigue
- Nausea and vomiting
- Jaundice
- Abdominal pain
- Anorexia (lack of appetite)
- Ascites
Bloods in AFLP (differentials):
Liver function tests will show elevated liver enzymes (ALT and AST).
Other bloods may be deranged, with:
- Raised bilirubin
- Raised WBC count
- Deranged clotting (raised prothrombin time and INR)
- Low platelets
TOM TIP: In your exams, elevated liver enzymes and low platelets should make you think of HELLP syndrome rather than acute fatty liver of pregnancy.
HELLP syndrome is much more common, but keep acute fatty liver of pregnancy in mind as a differential.
management of AFLP:
Acute fatty liver of pregnancy is an obstetric emergency and requires prompt admission and delivery of the baby. Most patients will recover after delivery.
Management also involves treatment of acute liver failure if it occurs, including consideration of liver transplant.
pathophysiology of acute fatty liver of pregnancy:
Acute fatty liver of pregnancy is a rare condition that occurs in the third trimester of pregnancy. There is a rapid accumulation of fat within the liver cells (hepatocytes), causing acute hepatitis. There is a high risk of liver failure and mortality, for both the mother and fetus.
what genetic condition is associated with AFLP:
Acute fatty liver of pregnancy results from impaired processing of fatty acids in the placenta. This is the result of a genetic condition in the fetus that impairs fatty acid metabolism. The most common cause is long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) deficiency in the fetus, which is an autosomal recessive condition. This mode of inheritance means the mother will also have one defective copy of the gene.
Th LCHAD enzyme is important in fatty acid oxidation, breaking down fatty acids to be used as fuel. The fetus and placenta are unable to break down fatty acids. These fatty acids enter the maternal circulation, and accumulate in the liver. The mother’s defective copy of the gene may also contribute to the accumulation of fatty acids. The accumulation of fatty acids in the mother’s liver leads to inflammation and liver failure.
what is Pruritis folliculitis
pruritic follicular eruption with papules and pustules affecting trunk can involve limbs
o 2nd or 3rd trimester, resolve a week after delivery
o SS: acne (considered a type of hormone-induced acne)
o M: topical steroids
