Question 30.2

A 30-year-old female who is 34 weeks pregnant (G1PO) has presented with nausea and vomiting for 3 days with right upper quadrant pain. On examination she is confused, jaundiced with a blood pressure of 120/70 mmHg.

The following are results from a venous blood sample taken on admission:

Parameter	Patient Value	Normal Adult Range
Sodium	138 mmol/L	135 - 145
Potassium	3.8 mmol/L	3.5 - 5.0
Urea	15.0 mmol/L*	3.0 - 8.0
Creatinine	245 µmol/L*	45 - 90
Albumin	30 q/L*	33 - 40
Glucose	2.5 mmol/L*	3.0 - 7.8
Bilirubin (total)	142 umol/L*	< 20
Alkaline phosphatase	293 U/L*	30 - 110
Aspartate aminotransferase	99 U/L*	< 31
Alanine aminotransferase	88 U/L*	< 34
y-Glutamyl transferase	67 U/L*	< 40
Lactate dehydrogenase	180 U/L	110 - 250
Uric acid	0.72 mmol/L*	0.15 - 0.50
Activated partial thromboplastin time	45 sec*	36 - 38
International normalised ratio	2.8*	0.9 - 1.3
Platelets	123 x 109/L*	150 - 450

List three likely differential diagnoses for the above clinical picture. (30% marks)

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College answer

Acute fatty liver of pregnancy (AFLP):
HELLP (Haemolysis, elevated liver enzymes and low platelets) Syndrome:
Pre-eclampsia with hepatic involvement
Viral hepatitis – commonest cause of jaundice in pregnancy
ALT and AST would be expected to be greatly elevated (>500 – 1000 U/L) and DIC is rare
Intrahepatic Cholestasis of Pregnancy

Additional Examiners‟'Comments:
Many candidates did not complete part 2.

Discussion

The abnormalities are:

Confusion
RUQ pain
Renal failure
Hypoglycaemia
Raised bilirubin
Raised LFTs - no specific pattern
Raised urate
Coagulopathy (both APTT and INR)
Thrombocytopenia, which is mild

Thus, this is pre-eclampsia, or something along the spectrum between pre-eclampsia and HELLP syndrome. A distant third possibility is TTP-HUS, but the LDH is within the normal range, which means that there is probably no haemolysis.

Thus, the differentials might include

Pre-eclampsia
HELLP
TTP/HUS
Acute fatty liver of pregnancy

Such things are usually best described in the form of a table. Good articles inform the discussion, most notably the article by Guntupalli et al from the 2005 special pregnancy issue of Critical Care Medicine.

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	Proteinuria, hypertension, oedema, visual disturbance, etc. See the local chapter.	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	read all about the difficulties of making the diagnosis of sepsis in pregnancy

References

Oh's Intensive Care manual:

Chapter 64 (pp. 684) General obstetric emergencies by Winnie TP Wan and Tony Gin

Chapter 65 (pp. 692) Severe pre-existing disease in pregnancy by Jeremy P Campbell and Steve M Yentis

Pandey, Chandra Kant, et al. "Acute liver failure in pregnancy: Challenges and management." Indian journal of anaesthesia 59.3 (2015): 144.

Sahai, Shweta, and Ravi Kiran. "Acute liver failure in pregnancy: Causative and prognostic factors." Saudi journal of gastroenterology: official journal of the Saudi Gastroenterology Association 21.1 (2015): 30.

Guntupalli, Saketh R., and Jay Steingrub. "Hepatic disease and pregnancy: an overview of diagnosis and management." Critical care medicine 33.10 (2005): S332-S339.

Aggarwal, Neelam, et al. "Pregnancy and cirrhosis of the liver." Australian and New Zealand journal of obstetrics and gynaecology 39.4 (1999): 503-506.

Horowitz, Rivka S., et al. "Placental transfer of N-acetylcysteine following human maternal acetaminophen toxicity." Journal of Toxicology: Clinical Toxicology 35.5 (1997): 447-451.

Outlaw, William M., Jamal A. Ibdah, and Kenneth L. Koch. "Hyperemesis Gravidarum and Maternal Liver Disease." (2000).

Munazza, Bibi, et al. "Liver function tests in preeclampsia." J Ayub Med Coll Abbottabad 23.4 (2011): 3-5.

Manas, Kenneth J., et al. "Hepatic hemorrhage without rupture in preeclampsia." New England Journal of Medicine 312.7 (1985): 424-426.

Kang, Yun Dan. "Portal Vein Thrombosis during Pregnancy." Korean Journal of Perinatology 26.3 (2015): 245-249.

Casey, Brian M., and Susan M. Cox. "Cholecystitis in pregnancy." Infectious diseases in obstetrics and gynecology 4.5 (1996): 303-309.

McMinn, Johnny R., and James N. George. "Evaluation of women with clinically suspected thrombotic thrombocytopenic purpura‐hemolytic uremic syndrome during pregnancy." Journal of clinical apheresis 16.4 (2001): 202-209.

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