You are called to the Emergency Department to review a nulliparous 28 year old woman. She is currently 35 weeks pregnant, and has presented with 72 hours of nausea  and vomiting accompanied by epigastric and right upper quadrant pain. On examination she was jaundiced, confused and had a blood pressure of 120/70. Laboratory results from a venous blood taken on arrival are shown below:

Venous Blood

Value

Reference range

Na+

138

135 -145 mmol/L

K+

3.8

3.2-4.5 mmol/L

Urea

15

3.0-8.0 mmol/L

Creatinine

245

50-100 micromol/L

Albumin

30

33-40g/L

Glucose

2.5

3.0-7.8mmol/L

Bilirubin (total)

142

<20micromol/L

ALP

293

32-156 U/L

AST

99

<31U/L

ALT

88

<34U/L

GGT

67

<38U/L

LDH

180

110-250U/L

Uric acid

0.72

0.15-0.5 mmol/L

APTT

45

36-38 sec

INR

2.8

<1.2

Platelets

123

150-450x109/L

List 3 likely differential diagnoses for the above history and laboratory data

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College Answer

List 3 likely differential diagnoses for the above history and laboratory data

A number of differentials are possible however in the third trimester in a nulliparous woman the three main considerations are:
•    Acute fatty liver of pregnancy ( AFLP):
•    HELLP (Haemolysis, elevated liver enzymes and low platelets) Syndrome:
•    Pre eclampsia with hepatic involvement.

Other considerations are: (these are not the cause of severe hepatic failure in pregnancy and so will attract fewer marks if mentioned without the first three)
•    Intrahepatic Cholestasis of Pregnancy:
•    Viral hepatitis: The commonest cause of jaundice in pregnancy. May occur at any time. The ALT and AST would be expected to be greatly elevated (>500-
1000U/L). DIC is rare.

Discussion

Yes, the model answer lists at least 5 differentials, but the question asked for only "3 likely differential diagnoses".

Thus, one would be forced to mention the following:

  • HELLP (but LDH is not elevated)
  • Acute fatty liver of pregnancy
  • HUS-TTP (the renal function is wildly deranged)

Elaboration upon these syndromes is carried out in the discussion of Question 6 from the first paper of 2010.

In too mich detail, here are the causes of acute liver failure in pregnancy:

Acute Liver Failure in Pregnancy
Cause Diagnostic features Notes and management options
Causes of liver failure which are unrelated to pregnancy
Drug-induced hepatitis
  • Paracetamol level
  • N-acetylcysteine crosses the placenta and has a protective effect in the foetus (Horowitz et al, 1997)
Shock, haemorrhage
  • Ultrasound: structurally normal liver
  • The LFT derangement which follows resuscitation for severe postpartum haemorrhage
  • Should improve after the shock state has resolved
Decompensation of pre-existing liver disease
  • Ultrasound: cirrhosis
  • Risk of preterm delivery and peripartum complications is increased (Aggarwal et al, 1999)
  • Normal management of the cirrhotic patient applies
Causes of liver failure which are exacerbated by pregnancy
Viral hepatitis
  • Hep B and C serology
  • Most common cause of LFT derangement in pregnancy
  • B and C are the most common
  • usually, BP is normal (in contrast with HELLP)
  • Ribavirin is contraindicated (a teratogen)
  • Other antiviral drugs may still be useful to decrease the viral load preior to delivery (to protect the baby from vertical transmission)
Portal vein thrombosis
  • Ultrasound: portal vein occlusion on Doppler
  • Due to hypercoagulable state of pregnancy
  • Heparin infusion is the standard of care 
  • Generally, TIPS procedure is too technically difficult in pregnancy - but that is another option
Hepatic venous thrombosis
  • Ultrasound: hepatic vein occlusion on Doppler
Cholecystitis
  • Ultrasound: thickened gall bladder wall, stones
  • LFTs: cholestatic picture
  • Conservative antibiotic therapy is best
  • Non-emergency surgery has better outcomes, i.e. it pays to delay until the acute flare has passed (Casey et al, 1996)
Pregnancy-related causes of liver failure
Hyperemesis gravidarum
  • LFTs: "transaminitis"
  • Unlike the others, this is a feature mainly of the first trimester
  • It is associated with raised transaminases, as opposed to liver failure per se - synthetic function is preserved (Outlaw et al, 2000)
  • Antiemetics and supportive care are the only options
Intrahepatic cholestasis of pregnancy (icterus gravidarum)
  • History of jaundice and pruritis
  • LFTs: cholestatic picture
  • Ultrasound: gall bladder looks normal
  • Pruritis is usually the patient's greatest concern. Can be managed with ursodeoxycholic acid.
  • Resolves rapidly with delivery
  • Will occur again in the next pregnancy in 60%
Pre-eclampsia
  • LFT derangement is due to fibrin deposition and endothelial dysfunction in the sinusoids.
  • Typically, this is also not "liver failure" but rather an LFt derangement of unclear significance (Munazza et al, 2013)
  • Standard therapy applies: antihypertensives, magnesium sulfate, and urgent delivery
HELLP
  • Thrombocytopenia
  • Low haptoglobin
  • Raised LDH,
  • Uncojugated bilirubin
  • Blood film features of haemolysis
  • See the local chapter.
  • Delivery is the treatment
  • Some authors recommend corticosteroids (Guntupalli et al, 2005) but only as a means of helping foetal lung maturation
  • Thrombocytopenia and LFT derangement will continue for up to 48 hours postpartum
  • Standard therapy applies: antihypertensives, magnesium sulfate, urgent delivery, correction of coagulopathy
Acute fatty liver of pregnancy
  • Presents with abdominal pain, vomiting, hypoglycaemia, coagulopathy
  • Characteristic ultrasound findings of the liver parenchyma
  • 18% maternal mortality, 2% foetal mortality (Guntupalli et al, 2005)
  • Liver failure is present, not just LFT derangement
  • Delivery fixes everything, as in HELLP
  • Fulminant liver failure may be present by then, and liver transplant may be the only option
Acute hepatic rupture
  • Ultrasound: haematoma
  • Haemodynamic instability and haemorrhagic shock
  • Abdominal pain (RUQ)
  • Haemoperitoneum
  • Maternal mortality is around 30% (Manas et al, 1985
  • If it has not ruptured (i.e. only a subcapsular haematoma) then conservative management and urgent dleivery are probably safe
  • Surgical packing and/or angioembolisation may be the only options
Other causes of febrile jaundiced coma with thrombocytopenia
TTP/HUS
  • Pentad: thrombocytopenia, microangiopathic haemolytic anemia, neurologic abnormalities, renal failure, and fever. See local chapter.
  • Low ADAMTS-13 levels are found. 
  • The SAQs often give a picture which could be consistent with TTP. It actually does occur often in pregnancy and the postpartum period (McMinn et al, 2001)
  • "How is this not HELLP?" one might ask. Well:
    • HELLP is never in the first trimester
    • HELLP always resolves following delivery
  • I.e. if after delivery the abnormalities persist, plasmapheresis becomes a serious option.
Sepsis with DIC
  • Bacteraemia
  • Haemodynamic instability, hypotension
  • blood film (for HELLP, TTP, HUS)
  • Septic screen (for sepsis)
  • Quantitiative D-dimer (for DIC)
  • formal LFTs (for HELLP)
  • ADAMTS13 (for TTP)
  • Urinary protein (for pre-eclampsia)
  • Ammonia level (for encephalopathy of acute fatty liver of pregnancy)
  • Liver ultrasound (for fatty liver of pregnancy, as well as to exclude liver rupture)