Liver disease in pregnancy

• ALT increased by up to 15 times normal
• Bilirubin increased by up to 15 times normal
• Bile acids usually normal

• ALT increased by up to 30 times normal
• Bilirubin increased by up to 10 times normal
• Bile acids usually normal

• ALT increased by up to 5 times
• Bilirubin usually normal
• Bile acids usually normal

• ALT increased by up to 8 times
• Bilirubin usually normal
• Bile acids increased by up to 15 times

• If patient is actively bleeding
• To facilitate surgery
• To facilitate insertion of invasive lines

• Same as you would for severe pre-eclampsia
• Supportive ABC management
• Correct the correctables (clotting, anaemia, platelets, sugar, electrolytes)
• Deliver the foetus

History

Symptom onset, duration and severity

• Abdominal discomfort
• Itching
• Dark urine
• Pale stools
• Fatigue
• Recent drugs, travel or other illness
• Family history of liver problems

Examination

• Stigmata of chronic liver disease
• Ascites
• Jaundice
• Right upper quadrant pain

• Use the Swansea criteria

You need at least six of:

• Vomiting
• Abdominal pain
• Ascites
• Polydipsia/polyuria
• Elevated transaminases
• Encephalopathy
• Leucocytosis
• Hyperammonaemia
• Hyperbilirubinaemia
• Renal dysfunction
• Coagulopathy
• Hypoglycaemia
• Microvesicular steatosis on biopsy (probably not gonna use this one much in a DGH labour ward)

There also needs to be no other decent explanation for the patient's symptoms.

• ABCDE assessment to begin with, as always
• HDU or ICU environment on Labour ward
• IV access
• Cautious IV fluid resuscitation as required - risk of ARDS and peripartum cardiomyopathy
• Correct hypoglycaemia
• Correct coagulopathy - use TEG/ROTEM if possible
• Deliver the foetus - general anaesthesia if coagulopathic
• Expect renal and hepatic function to get worse over next 48 hours
• May require intubation for encephalopathy or respiratory failure
• May require renal replacement therapy - if refractory acidosis, fluid overload, hyperkalaemia or symptomatic uraemia

Platelets generally remain fairly steady in AFLP, compared to HELLP where they can drop precipitously.

• Commonest cause of liver dysfunction and jaundice during pregnancy worldwide
• Can be Hepatitis A, B, C, D, E, G, HSV, CMV, EBV
• Most of the time it's Hep E to blame
• Vertical transmission to the foetus is possible
• It can also be reduced through immunisation (for Hep B)
• Presentation is similar to non-obstetric patients, however HSV hepatitis appears to be more severe in pregnancy
• Obstetric complications include intrauterine growth restriction, premature rupture of membranes and delivery and increased perinatal mortality

• Usually gets better during the relatively immunosuppressed period of pregnancy
• Immunosuppressive medication should be continued
• Tacrolimus, ciclosporin and azathioprine are all safe
• Mycophenolate is teratogenic

• Cirrhosis in pregnancy brings a high mortality of around 10%
• Pregnancy makes portal hypertension worse
• This makes varices worse
• C-section is advised as straining during labour increases risk of rupture

There's also the additional complications to consider such as ascites, decompensation and encephalopathy, as well as a raised mortality overall.

• You can essentially treat a woman with a liver transplant as you would any other parturient
• Assuming their liver function and coagulation are normal
• They should keep their immunosuppression going throughout pregnancy
• They're at higher risk of PET, gestational diabetes and pre-term delivery

• The hepatic vein is obstructed, most of the time by thrombosis
• This leads to hepatomegaly and ascites
• There may also be right upper quadrant pain
• There is increased risk of early foetal loss

• Drugs can cause liver injury
• Methyldopa
• Paracetamol
• Retrovirals
• Hormones
• Psychotropics
• Carbamazepine

• Yes if the disease is relatively mild and crucially stable
• The risks and benefits, as always, need thorough discussion with the mother
• Avoid in a haemodynamically unstable coagulopathic emergencies with dubious ability to provide fully informed consent

This can be broken down into those conditions that are directly related to the pregnancy, and those that can happen at any time.

Pregnancy related

• Acute fatty liver of pregnancy
• HELLP syndrome
• Obstetric cholestasis
• Pre-eclampsia with liver dysfunction

Not pregnancy related

• Hepatitis - viral, autoimmune, drug induced
• Budd-Chiari syndrome
• Acute on chronic liver disease - alcohol, drugs, autoimmune

• HELLP syndrome (haemolysis, elevated liver enzymes, low platelets)
• Acute fatty liver of pregnancy
• Intrahepatic cholestasis of pregnancy
• Pre-eclampsia with hepatic dysfunction

The first two are the most common causes of intensive care admission for liver failure.

• Rapid onset severe liver injury
• With impaired synthetic function (coagulopathy)
• And hepatic encephalopathy
• In a patient without pre-existing chronic liver disease or cirrhosis

• A lactate of more than 2.8
• Encephalopathy

This signifies an impaired ability of the liver to clear lactate, and severe end organ dysfunction.

• Grade 1 = mild confusion, slurred speech
• Grade 2 = lethargy, moderately confused
• Grade 3 = sleepy but rousable
• Grade 4 = coma

• Progressive fat accumulation within hepatocytes during third trimester
• Eventually leads to liver dysfunction and multiple organ failure
• Historically associated with 85% maternal and foetal mortality
• Current maternal mortality estimated at 10 to 20%
• Perinatal mortality remains around 20 to 30%
• Presumed to be due to dysfunctional fatty acid metabolism
• Incidence is approximately 1 in 7,000 to 20,000 pregnancies

• Clinical diagnosis of exclusion

Swansea criteria (6 of the following needed)

• Vomiting
• Polydipsia or polyuria
• Abdominal pain
• Encephalopathy
• Bilirubinaemia
• Hypoglycaemia
• Raised urate
• Raised WCC
• Raised transaminase count
• Ascites
• Coagulopathy
• Renal failure
• Microvesicular steatosis seen on biopsy

Liver function tests

• Transaminases elevated 3–10x in AFLP
• Raised alkaline phosphatase
• Hyperbilirubinaemia is more marked than in HELLP

Urea and electrolytes

• Hyperuricaemia often disproportionate to other pre-eclampsia signs, helping to differentiate from pre-eclampsia

Other parameters may also be raised

• Amylase
• Lipase
• Ammonia

Full blood count

• Haemolysis
• Thrombocytopaenia

Others

• Coagulation studies
• Blood sugar

Imaging

• Ultrasound
• MRI

Biopsy

• Definitive diagnosis but invasive and high risk if coagulopathic
• Microvesicular steatosis
• Fibrin deposits
• Haemorrhage

• Multiparity
• Diabetes
• Pre-eclampsia
• Cholestasis
• Family history
• Low BMI <20
• Male baby
• Long chain acetyl CoA dehydrogenase deficiency

• Impaired excretion of bile acids leads to uncomfortable pruritus
• Vitamin K malabsorption can affect coagulation
• It can herald more severe liver disease, so needs close monitoring

This is generally accepted as the time interval between jaundice and encephalopathy.

• Hyperacute - <7 days - high cerebral oedema risk but relatively good prognosis
• Acute - 8 - 28 days - moderate risk and prognosis
• Subacute - 5 - 12 weeks - low oedema risk but poor prognosis

Hyperacute is usually caused by paracetamol, hepatitis or ischaemia.

Acute is usually caused by drug reactions or viral hepatitis (A and B).

Subacute is caused by autoimmune disease, Wilson's disease, Budd-Chiari, malignancy or Hep B and C

• Alcohol excess
• Ascites
• Platelets <160
• Spider Naevi
• ALT/AST ratio <0.7
• INR >1

• Pulmonary oedema
• Eclampsia
• Subcapsular liver rupture
• Intracranial haemorrhage
• Cerebral oedema
• Hypertensive encephalopathy