Liver disease in pregnancy Flashcards
Define
Obstetric Cholestasis
· Obstetric cholestasis → pruritus in pregnancy, resolves on delivery, associated with abnormal liver function in the absence of other identifiable pathology à PPH (vitamin K deficient), foetal distress, meconium delivery, PTL, IVH
· Cause – likely genetic (defect in membrane phospholipid) and hormonal (oestrogen impairing sulphation) factors
· Risk factors – previous OC, FHx, ethnicity (South Asia, Chilean, Bolivian), multiple pregnancy, pruritis on COCP
o Affects ~1% of pregnancies in the 2nd half of pregnancy
Classification
MILD - Elevated bile acids > 20-40mmol/L
SEVERE- Elevated bile acids > 40mmol/L, coagulopathy
Aetiology
Aetiology
Impaired bile flow allowing bile salts to deposit into the placenta and skin
- Defect in membrane phospholipid
- Mutations occur in the canalicular phospholipid export pump (MDR3) and other canalicular bile transporters.
- MDR3 mutations are usually associated with raised g-glutamyl transferase (gGT) levels
Pathophysiology
Foetal morbidity occurs secondary to the limited ability of the foetal liver to remove the bile acids from the blood and the vasoconstricting effects of the bile acids on the human placental chorionic veins
NOTE: the vasoconstricting effects in the placental veins may cause asphyxia events associated with the condition
ICP causes a reversible impairment in bile formation- this includes impairment of vesicular transcytosis through hepatocytes.
Risk factors
- Previous history of ICP
- STRONG FAMILY HISTORY- +ve in 35% of cases as there is a strong family link
- Family studies suggest AD sex-limited inheritance
- History of Hepatitis C
- Ethnicity (S.Asian, Chilean, Bolivian)
- Multiple preg
- Pruritis on OCP
- > 35 years old
Signs and Symptoms
Presenting Symptoms
Usually in 2nd half of pregnancy- > 20 weeks (more commonly seen in the 3rd trimester)
Pruritis – of palms and soles of feet in particular
NO RASH
Sleep deprivation (as a consequence of intense pruritis)
Signs O/E
- Excoriations without rash
- Mild jaundice
Investigations
Basic observations- BP + urine
Bloods
- Look at: ALT, AST, gGT
- For transaminases, gGT and bilirubin, the upper limit of normal throughout pregnancy is 20% LOWER than the non-pregnant range
- Usually ALP and gGT are higher than rise in ALT
- Raised bile acids
- Hepatitis A-E screen
- NOTE: Increase in ALP in pregnancy is usually placental so does not reflect liver disease
- Coag screen - may be high if vit K deficient
DIAGNOSIS:
Unexplained abnormalities in LFTs (transaminases, gGT) and/or bile salts
- MUST rule out autoantibodies
Chronic active hepatitis- anti-smooth muscle antibodies
Primary biliary cirrhosis- anti-mitochondrial antibodies
- Liver USS
- CTG to monitor foetal wellbeing
Management
Conservative
- Wear loose cotton clothes
- Sit in front of a fan
- Soak in a cool bath
- Topic emollients are safe, but the efficacy is unknown
- Menthol 0.5% or 1% in aqueous cream may be relieving if emollient is not enough
- Milk thistle/ Dandelion extracts
Medical
Antihistamines e.g. chlorphenamine, dihydramine
- May provide some sedation but does not have significant impact on pruritis
1st LINE if Bilirubin > 40mmol/L- Ursodeoxycholic acid (UDCA)
- Improves pruritis and liver function
- DOES NOT improve foetal and neonatal outcomes
- MoA: this competes with other cytotoxic bile acids, reverses abnormalities of placental bile acid transport and improves the transport of bile acids from the foetal to the maternal component across trophoblastic tissue.
Vitamin K (as phytomenadione)
- If PT is NORMAL, low doses should be used
- If the PT is prolonged, 5-10mg/ daily should be given
Antenatal Monitoring
- Weekly LFTs until delivery
- Twice-weekly Doppler and CTG until delivery
- Consultant-led care
Antenatal care
- If pruritis is persistent (but NORMAL LFTs)- repeat LFTs every 1-2 weeks
- Once DIAGNOSED, measure LFTs weekly until delivery
Intrapartum
- If < 34 weeks, may be given IM betamethasone to mature foetal lungs
- Women normally offered delivery after 37+0 weeks gestation
- Induced delivery
- Common practice
- If bile acids are >50, induce at 37 wks
When BA are between 12-50, closely monitor but do NOT induce
- Caesarean section
- Continuous foetal monitoring in labour
Postnatal care
Postnatal resolution of pruritis and abnormal LFTs should be confirmed- delay LFTs for at least 10 days postnatally
LFTs usually done 2 weeks postnatally
Complications
Premature birth
PPH (due to low vitamin K)
o Intrauterine death (intracranial haemorrhage)
Meconium passage
o Severe liver impairment
Foetal distress
PACES
Obstetric cholestasis is a disorder that affects your liver during pregnancy. This causes a build-up of bile acids in your body. The main symptom is itching of the skin but there is no skin rash. The symptoms get better when your baby has been born.
It is not yet understood why it happens but hormones, genetic and environmental factors are thought to be involved
Risk factors: prev OC, FHx, Hx of liver disease and multiple preg
It can be very uncomfortable, like the itching on your palms and feet may spread to arms and legs and may disrupt your sleep as it is worse at night
The itching gets better after birth and causes no long-term health problems.
A few women with obstetric cholestasis develop jaundice (yellowing of the skin owing to liver changes). Some women feel unwell and lose their appetite. Jaundice can also cause dark urine and pale bowel movements.
Effects on baby:
More likely to pass meconium (move it’s bowels) before birth so fluid around your baby is in green/brown colour
Increased chance of premature birth
There is an increased risk of still birth which is why labour may be induced at 37 wks esp if your symp are severe or blood tests are really abnormal but the consultant will discuss this in further detail with you
The baby will be closely monitored using a CTG
You will be under the care of the obstetrician
We will continue to repeat the LFTs every 1-2 weeks
There is no cure for obstetric cholestasis except the birth of your baby. Treatment may ease symptoms for most women. None of the treatments offered affects the outcome for your baby.
Treatments include
Skin creams and ointments to relieve the itching. These are safe in pregnancy and may provide temporary relief.
Antihistamines may help you sleep at night but don’t appear to have much success in helping itching.
Ursodeoxycholic acid often known as ‘Urso’ reduces the level of bile acids in your blood and improves LFTs. It may also help reduce the itching.
Some women have found that having cool baths and wearing loose-fitting cotton clothing helps to reduce the itching.
OC can cause a problem with the way your blood clots - If your blood clotting time is prolonged, it is recommended that you take a daily dose of vitamin K to prevent complications if you start to bleed.
Should have a follow up with a HCP 6-8 wks after delivery to make sure it bing has gone away and your liver is working properly
There is a high chance that obstetric cholestasis may happen again in a future pregnancy: 45–90 in 100 women (45–90%) who have had obstetric cholestasis will develop it again in future pregnancies
If you have had obstetric cholestasis in your pregnancy, it is better to avoid the estrogen-containing contraceptive pill
Define acute fatty liver
Acute fatty liver → rare pregnancy associated disorder characterised by fatty infiltration of the liver
o Accumulation of microvesicular fat in hepatocytes, periportal sparing, small yellow liver on gross examination
o Likely mitochondrial disorder affecting fatty acid oxidation
Epidemiology
- Rare
- 1 in 7,000-15,000
DDx: HELLP
- Haemolysis
- Elevated liver enzymes
- Low platelets
Risk factors
Foetal long-chain 3-hydroxyacyl CoA dehydrogenase (LCHAD) deficiency
Previous episode of AFLP
Multiple pregnancy
Pre-eclampsia or haemolysis, or elevated liver enzymes and a low platelet count syndrome
Obesity
Male foetus
Low BMI < 20kg/m2)
Common in primigravida
Signs and Symptoms
Normally 3rd trimester, typically between 30-38 weeks or immediately following delivery
Signs O/E
- Hypoglycaemia
- Hypertension (maybe)
- Proteinuria (maybe)
- Signs of liver failure: jaundice, ascites, encephalopathy, DIC, hypoglycaemia
- AKI which can rapidly progress to multiorgan failure
DDx
HELLP
Ob cholestasis
- Differentiate from cholestasis of pregnancy by pruritis
Viral Hep
Investigations
Appropriate Investigations
- Check blood glucose- if don’t maintain blood glucose, will keep falling to hypoglycaemic state
- Urine dipstick- urine protein: creatinine ratio
Bloods
- FBC, U+Es, LFTs,
- LFTs
- Transaminases (ALT) usually > 500IU/L, may exceed 1000IU/L in some severe cases
- Total bilirubin- RAISED ≥ 40mg/L (much more than in HELLP)
- PT- prolonged
- LDH
- Uric acid - elevated
- Usually the rise in AST/ ALT > ALP, with raised WCC + potential clotting abnormalities
Liver USS- usually shows non-specific changes
Liver biopsy- confirms diagnosis (but rarely needed) à fatty infiltration
DIAGNOSIS
- Profound hypoglycaemia
- Marked hyperuricaemia
- Coagulopathy in the ABSENCE of thrombocytopaenia – liver not producing clotting factors properly
Management/ Complications of fatty liver
This is a LIFE-THREATENING EMERGENCY
Supportive care –> stabilisation then delivery
Initial/ Immediate
- PROMPT delivery of foetus regardless of gestational age
- Magnesium sulphate- in pregnancies <32 weeks of gestation, magnesium sulphate is administered until delivery
- Foetal monitoring
- Glucose replacement if needed
- Plasmapheresis for coagulopathy
Delivery
- Route of delivery depends on maternal-foetal compromise
Postnatal
- Monitoring of mother and baby
- MDT, specialist centre
Complications
- Fatal to mother and baby
- Maternal => haemorrhage (secondary to DIC), renal failure, hepatic encephalopathy, sepsis, pancreatitis
- Most foetal death is secondary to maternal decompensation and/or preterm delivery
Maternal mortality: 10-20%
Perinatal mortality: 20-30%
Prognosis
It can recur
