Rare fatal complications of acute fatty liver of pregnancy

Background

Acute fatty liver of pregnancy (AFLP) and the syndrome of haemolysis, elevated liver enzyme levels, and low platelet count (HELLP) are rare but major disorders of the third trimester of pregnancy and are maybe related to pre-eclampsia. Mortality of 9-24% has been reported and complications include pulmonary oedema, adult respiratory distress syndrome, abruptio placentae, disseminated intravascular coagulation, ruptured liver haematomas, and acute renal failure increasing mortality to 50-90%. Multi-organ failure may result requiring full intensive care support. Perinatal mortality is equally high, ranging from 79 to 367 per 1000 live births, and neonatal complications correlate with the severity of maternal disease. Most presentations of AFLP and HFLLP require monitoring and supportive care, however, early recognition of rarely associated complications and their appropriate treatment is of paramount importance to the survival of the mother and child.

Case reports

We report five patients referred to the Liver Intensive Care Unit (LITU) with mild AFLP in 3 years. Their disease progressed rapidly to acute hepatic failure with associated multi-organ failure (1 ± 2 days post admission to LITU) Patients (age 26.4 ± 5.2 years) presented in the third trimester of pregnancy (33 ± 3 weeks) with proteinuria, hypertension (systolic 186 ± 27.1, diastolic 103 ± 10.1 mmHg), and deranged liver function consistent with AFLP and evidence in four patients of HELLP syndrome. Maternal deterioration and foetal distress required emergency cacsarean section. Following uncomplicated caesarean section, reduced conscious level (Grade I-II encephalopathy) was associated with severe hypovolaemic shock (systolic 60 ± 5 diastolic 40 ± 7 mmHg). Haematological investigations demonstrated a fall in haemoglobin (8.6 ± 1.4 g/dl), worsening thromhocytopaenia (platelets 42 ± 20 × 10⁹/l), rising coagulopathy (prothromhin time 23.2 ± 5.6 s), and disseminated intravascular coagulopathy. Biochemical investigations revealed, metabolic acidosis (pH 7.09 ± 0.15), hyperlactataemia (l0.16 ± 4.5 mmol/l), severe transaminitis (AST 4050 ± 599 iu/l), increasing total bilirubin (194 ± 75 μmol/l) and oligo-anuric renal failure (creatinine 3.53 ± 1.56 μmol/l). Patients were resuscitated, intubated and mechanically ventilated. Intra-cranial transducers were inserted to monitor intracranial pressure. Vaso-active agents were used to maintain haemodynamic stability and continues venous-venous haemofiltration initiated. Intravenous N-acetylcysteine, antibiotics and anti-fungals were commenced. Ultrasound, helical computer tomography and angiography confirmed extensive subcapsular haematomas suggestive of liver rupture in three patients, massive hepatic necrosis in the fourth patient and abnormal aorto-portal shunting suggestive of veno-occlusive disease in the fifth patient. Patients were listed for liver transplantation.

Of the five patient one did not survive long enough for transplantation, however, the others successfully received liver transplants (7.4 ± 6 days post caesarean section). Unfortunately patient two developed hepatic artery thrombosis and was re-transplanted, but died soon after.

The other three patients remain alive and well. Patients have been investigated for pro-thrombotic disorders, evidence of which is not present.

Conclusion

We describe potentially fatal complications in five patients initially presenting with mild AFLP and or HELLP associated with pre-eclampsia with a mortality of greater than 90%. These rare complications include hepatic rupture, hepatic infarction and necrosis and veno-occlusive disease. Clinical suspicion must be high if there is evidence of hypotension, altered conscious state, metabolic acidosis. hyperlactataemia and deranged liver function. The early recognition of the changing clinical parameters of disease, multidisciplinary support, and specialist intensive care is required for the survival of this rate group of patients and their children.