Acute fatty liver of pregnancy is an uncommon (estimated 1 in 22,000 births in the UK) but serious complication of predominantly primiparous women, especially those with multiple pregnancy and possibly low body mass index (BMI). The condition was first reported in the literature in 1934, and traditionally the mortality for both mother and fetus has been reported to be as high as 85%, secondary to multi-organ failure. Current figures estimate maternal mortality to be about 10-20%, the improvement being attributed to earlier diagnosis and delivery. The median gestation at diagnosis is 36 weeks.
In some cases, the condition may be associated with long-chain-3-hydroxyacyl-CoA dehydrogenase (LCHAD) deficiency; this is an enzyme that catalyses a reaction in the oxidation of fatty acids, and its deficiency allows a build-up of fatty acids. Both parents have 50% of normal LCHAD activity and the fetus has no LCHAD activity, with the fetal liver dysfunction apparently causing fatty liver disease in the mother. Other enzyme deficiencies have also been correlated with acute fatty liver, so deficiency of LCHAD does not account for all the cases.
Symptoms usually present in the third trimester and tend to be non-specific: malaise, nausea and vomiting (which may be severe), headache and diffuse right upper quadrant or epigastric pain. Liver function may deteriorate rapidly, leading to acute liver failure. There is overlap between acute fatty liver and pre-eclampsia, and it has been suggested that acute fatty liver is a manifestation of pre-eclampsia, as is the HELLP (haemolysis, elevated liver enzymes and low platelet count) syndrome (see Chapter 85). It is often difficult to differentiate between HELLP and acute fatty liver.
The only treatment for acute fatty liver of pregnancy is delivery of the fetus regardless of gestational age; expectant management is not appropriate. As with pre-eclampsia, there may be a time lag of several days between delivery and clinical improvement.
Recovery is usually complete, with no evidence of chronic liver disease. Recurrence in subsequent pregnancies is said to be uncommon, although there have not been a large number of documented pregnancies in survivors of acute fatty liver. In cases associated with LCHAD deficiency, the risk of acute fatty liver is 25% in each pregnancy.
Problems and special considerations
The differential diagnoses at initial presentation include pre-eclampsia, acute viral hepatitis, drug-induced hepatitis, cholestasis of pregnancy and biliary tract disease. Pruritus is uncommon in acute fatty liver and is highly suggestive of cholestasis (see Chapter 83).
The mother is usually, but not invariably, jaundiced. Although she may complain of abdominal pain, it is unusual to find marked liver tenderness on examination, and this finding is suggestive of viral hepatitis or HELLP syndrome. If presentation occurs late, all the stigmata of acute liver failure may be present, including hepatic encephalopathy, disseminated intravascular coagulation (DIC) and renal failure. The prognosis is poor if the disease presents in this advanced state.
The Swansea criteria may be used to diagnose acute fatty liver, in which six or more of the following are present in the absence of another cause: vomiting; abdominal pain; polydipsia/polyuria; encephalopathy; elevated bilirubin; elevated transaminases; elevated ammonia; hypoglycaemia; renal impairment; coagulopathy; elevated urate; leucocytosis; ascites or bright liver echo texture on ultrasound; and microvesicular steatosis on liver biopsy.
Management options
Acute fatty liver of pregnancy is uncommon but has a high maternal and fetal mortality if the diagnosis is delayed. A high index of clinical suspicion is needed for the non-specifically unwell mother with pre-eclampsia, especially if there is any indication that she may be jaundiced.
Once the diagnosis is confirmed, the mother should be stabilised as necessary and the baby delivered. Medical support is likely to include administration of glucose, blood, clotting factors and platelets. Hypertension associated with pre-eclampsia should be controlled. Careful fluid balance is required, as acute kidney injury and propensity towards pulmonary oedema may be present. Increased likelihood of postpartum haemorrhage should be anticipated.
Regional analgesia and anaesthesia are contraindicated in the presence of any coagulopathy. If regional analgesia is contraindicated, analgesia for labour can be provided by using cautious doses of opioid drugs, preferably by using intravenous patient-controlled analgesia (PCA). Elimination of opioid drugs is likely to be prolonged, and remifentanil PCA may be advantageous. Adjuvant sedative drugs such as promazine and promethazine should not be given. General anaesthesia may adversely affect hepatic encephalopathy. Because of impaired metabolism, atracurium is the preferred neuromuscular blocking drug for general anaesthesia.
Operative delivery is not indicated unless the obstetrician considers that successful vaginal delivery is unlikely to be achieved. If operative delivery is needed, persistent bleeding from surgical sites should be anticipated and prophylactic wound drains are advisable. Close observation is essential following delivery, and intensive care management including multi-organ support may be required. Transfer to a specialist liver unit may be necessary. Mildly affected mothers should have a low-protein diet and scrupulous fluid and electrolyte management until clinical and laboratory findings return to normal.
Key points
• Acute fatty liver of pregnancy potentially has a very high mortality unless diagnosed and treated promptly.
• Some cases are caused by long-chain-3-hydroxyacyl-CoA dehydrogenase (LCHAD) deficiency and have an increased risk of recurrence.
• Delivery of the fetus is the only definitive treatment.
• Acute liver failure and multi-organ derangement can occur rapidly. Regional analgesia and anaesthesia are usually contraindicated because of abnormal clotting studies.
• Pre-eclampsia frequently coexists with acute fatty liver, and it is possible that acute fatty liver is a variant of pre-eclampsia.
Further reading
Kia L, Rinella ME. Interpretation and management of hepatic abnormalities in pregnancy. Clin Gastroenterol Hepatol 2013; 11: 1392-8.
Knight M, Nelson-Piercy C, Kurinczuk JJ, Spark P, Brocklehurst P; UK Obstetric Surveillance System. A prospective national study of acute fatty liver of pregnancy in the UK. Gut 2008; 57: 951-6.
Rajasri AG, Srestha R, Mitchell J. Acute fatty liver of pregnancy: an overview. J Obstet Gynaecol 2007; 27: 237-40.
Tran TT, Ahn J, Reau NS. ACG clinical guideline: liver disease and pregnancy. Am J Gastroenterol 2016; 111: 176-94.