What are the causes and implications of elevated liver enzymes (transaminitis) in pregnancy?

From the Guidelines

Transaminitis in pregnancy should be managed with ursodeoxycholic acid 10-15 mg/kg/day for intrahepatic cholestasis, and delivery should be considered based on serum total bile acid levels, with delivery at 36 weeks or at diagnosis if after 36 weeks for levels >100 mmol/L, and at 36 or 39 weeks of gestation if diagnosed later for levels <100 mmol/L, as recommended by the Society for Maternal-Fetal Medicine 1. The approach to transaminitis in pregnancy depends on the severity of elevation and gestational age, and initial management involves comprehensive laboratory testing including liver function tests, viral hepatitis serologies, and assessment for pregnancy-specific liver disorders such as preeclampsia, HELLP syndrome, intrahepatic cholestasis of pregnancy, and acute fatty liver of pregnancy. Some key points to consider in the management of transaminitis in pregnancy include:

• Mild transaminase elevations (less than 2-3 times normal) without symptoms may be monitored with serial testing every 1-2 weeks.
• More significant elevations or those accompanied by symptoms warrant prompt referral to maternal-fetal medicine and hepatology specialists.
• Treatment is directed at the underlying cause, and certain medications like acetaminophen (up to 3000 mg/day) are generally safe for symptom management, while NSAIDs should be avoided, particularly in the third trimester.
• Regular fetal monitoring is recommended, with frequency determined by the underlying condition and severity of liver dysfunction, as suggested by the European Association for the Study of the Liver guidelines 1.
• The diagnosis of intrahepatic cholestasis of pregnancy is based on a serum bile acid level >10 mmol/L in the setting of pruritus, typically during the second or third trimester, and treatment should be offered with oral ursodeoxycholic acid in a total daily dose of 10–15 mg/kg, as recommended by the American Gastroenterological Association 1.
• The Society for Maternal-Fetal Medicine recommends delivery at 36 weeks or at diagnosis if after 36 weeks for patients with total bile acid levels of 100 mmol/L, and delivery between 36 0/7 and 39 0/7 weeks of gestation for patients with intrahepatic cholestasis of pregnancy and total bile acid levels of <100 mmol/L 1.

From the Research

Definition and Causes of Transaminitis in Pregnancy

• Transaminitis refers to the elevation of liver enzymes, such as alanine transaminase (ALT) and aspartate transaminase (AST), in the blood 2.
• The causes of transaminitis in pregnancy can be variable and difficult to differentiate, including hyperemesis gravidarum, pre-eclampsia, viral hepatitis, and HELLP syndrome 3.

Management and Outcome of Transaminitis in Pregnancy

• Elevated transaminase levels up to 3 to 4 times the upper normal limit during the first two trimesters can be safely observed with careful history taking and hepatitis viral antigen tests 3.
• However, abnormal results in the third trimester are associated with a shorter duration of pregnancy and should be managed carefully 3.
• The overall outcome of acute liver failure in pregnancy depends on the etiology, timely diagnosis, prompt management, and early referral to a center equipped to manage medical or obstetric complications 2.

Safety Considerations and Treatment Options

• Acetaminophen can be used safely in patients with liver disease, including those who are pregnant, at recommended doses 4.
• New therapies for chronic hepatitis B infection may cause transaminase elevations, but these flares can be a sign of the therapeutic effect of the treatment 5.
• The goal of treatment for chronic hepatitis B infection is to achieve a "functional cure," characterized by the absence of detectable viremia and antigenemia, normal liver function, and reversal of liver damage 5.