To the Editor: I thank Whitfield and colleagues for their article about hyperemesis gravidarum and abnormal liver function in pregnancy.1 In a 15‐month prospective study in South West Wales, abnormalities of liver function were present in 3% of pregnancies.2 In managing pregnant women with hepatic dysfunction, it is important to consider uncommon causes of liver disease that may be associated with serious maternal and fetal morbidity and mortality if untreated. Addison disease is a rare but potentially life‐threatening condition that may imitate hyperemesis gravidarum in presenting with vomiting, weight loss, postural hypotension and hyponatraemia.3,4 Addison disease has also been associated with elevated hepatic transaminases in 16 published cases, reversing with glucocorticoid replacement.5 In excluding Addison disease, the physiological rise in cortisol during pregnancy must be considered using trimester‐specific reference ranges for short synacthen testing.6 In the pregnant woman with unexplained liver disease and fever, acyclovir should be administered empirically, given the absence of cutaneous vesicles in up to 80% of affected patients and the extreme maternal and fetal mortality associated with untreated herpes simplex virus hepatitis.7 Budd–Chiari syndrome should be considered with abnormal liver function in pregnancy with abdominal pain, hepatomegaly and ascites. Additionally, the use of herbal and over‐the‐counter medications should be sought in pregnant women with abnormal liver function, given the high rates of complementary and alternative medicine use in pregnancy and their potential to cause liver injury.8 Investigations need to be interpreted with regard to gestational physiological changes, as copper, ceruloplasmin, α‐1 antitrypsin and alkaline phosphatase levels rise significantly in pregnancy. Serum lipase levels are commonly elevated in hyperemesis gravidarum — levels up to ten times normal have been reported in the absence of pancreatitis.9 Antithrombin III levels may be useful to distinguish acute fatty liver of pregnancy from pre‐eclampsia with haemolysis, elevated liver enzymes and low platelets.10 Bile acid levels are not specific for intrahepatic cholestasis of pregnancy, being elevated in many hepatic disorders including non‐alcoholic fatty liver disease. Twenty per cent of women with pruritus typical of intrahepatic cholestasis of pregnancy have normal bile acids and liver function at presentation, and symptoms may precede abnormal biochemistry by up to 6 weeks.11 In addition to ondansetron and glucocorticoids, mirtazapine has been effective in the management of hyperemesis gravidarum in case reports.12
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