Liver disease in pregnancy Flashcards

1
Q

Define

A

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

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2
Q

Aetiology

A

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.

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3
Q

Risk factors

A
  • 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
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4
Q

Signs and Symptoms

A

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
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5
Q

Investigations

A

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
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6
Q

Management

A

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

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7
Q

Complications

A

Premature birth

PPH (due to low vitamin K)

o Intrauterine death (intracranial haemorrhage)

Meconium passage

o Severe liver impairment

Foetal distress

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8
Q

PACES

A

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

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9
Q

Define acute fatty liver

A

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
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10
Q

Risk factors

A

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

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11
Q

Signs and Symptoms

A

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

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12
Q

Investigations

A

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
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13
Q

Management/ Complications of fatty liver

A

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

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