What are the implications of hypertransaminasemia during the first trimester of pregnancy?

From the Guidelines

Elevated liver enzymes in the first trimester of pregnancy, such as hypertransaminasemia, require prompt evaluation and management to prevent potential complications, as approximately 50% of cases of hyperemesis gravidarum are associated with abnormal liver enzymes 1. The first step in managing hypertransaminasemia during the first trimester is to repeat the liver function tests and conduct a comprehensive panel, including bilirubin, alkaline phosphatase, and coagulation studies, as well as a complete blood count, renal function tests, and screening for viral hepatitis.

• Key considerations in the evaluation of hypertransaminasemia include:
  • The severity of the elevation, with significant increases (typically more than 2-3 times the upper limit of normal) warranting close monitoring and potential intervention
  • The presence of symptoms such as persistent vomiting, weight loss, and dehydration, which may indicate hyperemesis gravidarum
  • The need for abdominal ultrasound to evaluate liver structure
• Treatment approaches may vary depending on the underlying cause, but may include:
  • Rehydration and correction of electrolyte abnormalities
  • Nutrition and thiamine supplementation to prevent Wernicke’s encephalopathy
  • Anti-emetic therapy with agents such as ondansetron, which have a favorable pregnancy safety profile 1
• It is essential to note that while elevated liver enzymes can be concerning, many women with mild to moderate elevations have uncomplicated pregnancies, and early detection, thorough evaluation, and appropriate management can help ensure the best outcomes for both mother and fetus.
• In cases of severe elevation without a clear cause, hospitalization for close monitoring and supportive care may be necessary, highlighting the importance of prompt and thorough evaluation of hypertransaminasemia in the first trimester of pregnancy.

From the Research

Implications of Hypertransaminasemia During the First Trimester of Pregnancy

• Hypertransaminasemia, or elevated liver enzymes, during the first trimester of pregnancy has been associated with various adverse outcomes, including gestational diabetes and preeclampsia 2.
• A study found that asymptomatic elevated alanine aminotransferase (ALT) values measured in the first trimester can predict a macrosomic fetus 3.
• Elevated liver enzymes in early pregnancy may be indicative of underlying metabolic syndrome or non-alcoholic fatty liver disease (NAFLD), which can increase the risk of adverse pregnancy outcomes 3, 2.
• The relationship between elevated liver enzymes and adverse outcomes is not fully understood, and further research is needed to determine the clinical significance of hypertransaminasemia in pregnancy 4, 5.

Clinical Significance and Management

• Elevated liver enzymes during pregnancy can be caused by various factors, including hyperemesis gravidarum, pre-eclampsia, viral hepatitis, and HELLP syndrome 6.
• A study suggested that elevated liver enzymes up to 3-4 times the upper normal limit during the first two trimesters can be safely observed with careful history taking and hepatitis viral antigen tests 6.
• However, abnormal liver function tests in the third trimester may be associated with a shorter duration of pregnancy and should be managed carefully 6.
• The American College of Obstetricians and Gynecologists' criteria for severe features of preeclampsia include elevated liver enzymes, but the threshold used to define severe liver enzyme elevation has a direct impact on neonatal outcomes 4.

Association with Adverse Outcomes

• Elevated liver enzymes have been associated with an increased risk of adverse neonatal outcomes, including preterm birth and low birth weight 4, 5.
• A study found that patients with preeclampsia with severe features and elevated liver enzymes had a higher risk of adverse neonatal outcomes, but this association was driven by earlier gestational age at delivery 4.
• Another study found that markedly elevated liver enzymes in pregnancy were associated with a higher risk of adverse maternal and fetal outcomes, but no adverse outcomes occurred in pregnancies where no cause was identified for the elevated liver enzymes 5.