Acute Fatty Liver of Pregnancy Jonathan Healan and Niamh O’ Shiel Patient • 25 year old seen in Antenatal clinic 10 weeks gestation. • G2P1 (still birth 38w back in 2011) • Previous pregnancy normal until week 38, patient felt nauseous with abdominal pain and was admitted to hospital. Very unwell. • No fetal heart rate on CTG confirmed IUD • Vaginal delivery. Patient Liver enzymes  Leucocytes  Uric acid  • PMHx: Nil • FHx: Nil • Diagnosis Fatty liver of pregnancy, liver enzymes began to normalise following delivery with no lasting effect on patient. Acute Fatty Liver of Pregnancy (AFLP) • Obstetric emergency; Maternal and fetal mortality significantly raised, 18% and 23% respectively. • Usually occurs in third trimester. Microvesicular infiltration of hepatocytes. • Fortunately it is a rare condition. UK study found incidence of 5/100,000. • Gold standard of diagnosis is liver biopsy, but Swansea classification relies on signs and symptoms. These changes usually revert to normal within days to weeks following delivery without persistent hepatic injury. (Ch’ng et al.2002) Pathophysiology • Abnormality in mitochondrial β oxidation is recognised as the cause of this condition. • Long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) catalyses the third step in the β oxidation of fatty acids in mitochondria. (Joshi et al. 2010) • If fetus is deficient in LCHAD toxic metabolites can accumulate and cause damage to the mothers liver. The long chain fatty acids are deposited in the mothers liver giving rise to the characteristic appearance of steatosis histologically. (Joshi et al. 2010) Pathophysiology • It is recessive and so it is thought that under normal physiological conditions the mother has normal fatty acid oxidation • If both parents are heterozygous, the fetus can inherit both mutations and will be unable to oxidise long-chain fatty acids • The free fatty acids remain unmetabolised and are returned to the mother’s circulation • This causes strain on the mother’s liver and ‘overwhelms any diminished maternal hepatic enzymatic activity’ • (Hin Ko & Yoshida, 2004) Pathophysiology • Progressive lipid accumulation in hepatocytes • Usually fat content of liver is 5%, can go up to 19% in AFLP • Fat accumulation plus ammonia production leads to coagulopathy and hypoglycemia • Liver can be small, soft and yellow • Microvesicular fat can also infiltrate kidney, brain and bone marrow (McNulty 2004) Management • Get the baby out! • Early diagnosis, quick delivery and intensive care • Stablise mother– airway management, IV fluids, correct hypoglycemia, electrolyte and coagulation abnormalities, blood products • Once stabilised, deliver baby – vaginal birth if possible, but often c-section is necessary • Postpartum plasma exchange in severe cases (Moldenhauer, O’Brien, Barton & Sibai, 2004) Complications • Patients at high risk of bleeding due to coagulation problems – blood transfusion and fluids may be needed • Risk of hypoglycaemia – glucose infusion may be needed • Pancreatitis can develop following renal and hepatic dysfunction Prognosis • Mortality from AFLP – app 18% for mothers, 23% for fetus - deaths usually secondary to sepsis, renal failure, circulatory collapse, pancreatitis or GI bleeding • Maternal outcomes – liver function tests can continuously worsen for up to a week but then recover • Fetal outcomes – there can be fetal distress in a clinically stable mother – so fetal monitoring is essential • Recurrence of AFLP can occur in further pregnancies but is quite uncommon (Hin Ko & Yoshida, 2004) Patient • Autosomal recessive condition. Recurrence of AFLP estimated around 20% in general population. • Greater risk in primiparous women. • Surveillance of pregnancy paramount, especially in third trimester. • Deliver baby quickly if showing signs of AFLP. Hopefully at viable gestation, as delivery is only cure. GUT 2002 Prospective study of liver dysfunction in pregnancy in Southwest Wales C L Ch’ng, M Morgan, I Hainsworth,JGC Kingham • LFT abnormalities were investigated in 4377 deliveries during the 15 month study period. • Liver dysfunction was seen in 3% of deliveries during the 15 month prospective study. • Of the 3% only 5 cases of AFLP. Close medical and obstetric collaboration ensued low mortality. References • Hin Ko, H. & Yoshida, E. (2006) Acute fatty liver of pregnancy. Canadian Journal of Gastroenterology. 20: 25-30 • McNulty J. Acute fatty liver of pregnancy. In: Foley MR, Strong TH, Garite TJ, editors. Obstetric Intensive Care Manual. 2. New York: The McGraw-Hill Companies Inc; 2004. pp. 207–15. • Moldenhauer, J.S., O’Brien, J.M., Barton, J.R., & Sibai, B. (2004). Acute fatty liver of pregnancy associated with pancreatitis: a life-threatening complication. American Journal of Obstetrics and Gynaecology. 190:502-505 • Marsha F. Browning, Harvey L. Levy, Louise E. WilkinsHaug, Cecilia Larson and Vivian E. Shih. (2006) Fetal Fatty Acid Oxidation Defects and Maternal Liver Disease in Pregnancy, American college of obstetricians and gynaecologists. 1:107. • Ch’ng C, Morgan M, Hainsworth I, Kingham J. (2002) Prospective study of liver dysfunction in pregnancy in Southwest Wales. GUT. 51:876–880. • Joshi D, James A, Quaglia A, Westbrook R, Heneghan M. (2010) Liver Disease in Pregnancy. The Lancet. 375:594-605 • Willacy H. (2011) Jaundice in Pregnancy. Patient.co.uk. Available at: http://www.patient.co.uk/doctor/Jaundicein-Pregnancy.htm#ref-6