Management Issues of Liver Disease in Pregnancy
Arjmand Mufti, MD, MRCP
Fellow, Department of Gastroenterology, University of Chicago Medical Center, IL
Nancy Reau, MD
Associate Professor of Medicine, Center for Liver Disease, University of Chicago Medical Center, IL
Liver dysfunction occurs in approximately 3 percent of all pregnancies, and early recognition can improve maternal and fetal outcomes.1 However, during pregnancy, women undergo many hormonal and physiological changes with associated alterations of routine liver function tests. These variations represent the “new normal” of pregnancy and it is essential to be aware of them in order to appropriately triage patients for further investigation (see table one). It is also broadly true that liver diseases that are unique to pregnancy generally tend to be trimester specific, and the occurrence of liver abnormalities in relation to gestational age can give a clue about the etiology of liver dysfunction. We keep three broad categories of disorders in mind when evaluating pregnant patients with liver disease, namely:
- Liver diseases that were present before pregnancy.
- Liver diseases that are unique to pregnancy.
- Liver diseases that are coincidental to pregnancy (see table two).
The initial clue that liver dysfunction may be present is patient-reported nausea, vomiting, pruritus and upper abdominal pain. This should result in basic laboratory testing. Any increase in alanine aminotransferase (ALT), aspartate aminotransferase (AST) and serum bilirubin levels should be considered pathologic, and further evaluation needs to be carried out. We advocate a comprehensive diagnostic approach for all patients who are referred to us (see table three). After going through this general schema for initial evaluation, specific patterns in liver function tests can be allied to clinical course and gestational age to try and arrive at a diagnosis.
Pre-existing liver disease
In patients with known liver disease, it is paramount to have a candid pre-pregnancy discussion about the risks of complications in the mother, especially in individuals with established portal hypertension. In the pregnant patient, each pre-existing liver disease is managed differently. However, all pregnant patients are screened for hepatitis B and all babies born to hepatitis B surface antigen positive mothers receive the hepatitis B immunoglobulin and first dose of the hepatitis B vaccine within 12 hours of birth. Patients with hepatitis C are generally monitored closely, but there is no role for treatment during pregnancy. Patients with autoimmune hepatitis who are on azathioprine prior to pregnancy are generally kept on it. In carefully selected patients, therapy may be discontinued. However, as pregnancy represents a relatively immunosuppressed state, patients with either hepatitis B or autoimmune hepatitis may have a flare in the post-partum phase. Therefore, patients with hepatitis B are monitored closely for three to six months after delivery, and if discontinued, therapy for autoimmune hepatitis should be reinstituted prior to delivery. Additionally, anyone with suspected portal hypertension should have an upper endoscopy in the second trimester to look for esophageal varices.
Pregnancy-related liver disease
Liver diseases unique to pregnancy are always part of the differential diagnosis in patients with abnormal liver function tests; history, clinical course and biochemical testing help to differentiate between them (see table two). With the exception of hyperemesis gravidarum, they usually present in the second and third trimester. Obtaining the correct diagnosis is important because delivery is the primary treatment. High AST and ALT levels may be seen in all of these disorders and they can recur during subsequent pregnancies.2
Hyperemesis gravidarum is defined by persistent vomiting, dehydration and weight loss in the first trimester. It usually resolves by week 20, but can be present throughout pregnancy. Intrahepatic cholestasis of pregnancy is associated with severe pruritus and high bile acid levels. Pre-eclampsia is characterized by hypertension and proteinuria, whilst hemolytic anemia with low platelets are markers of HELLP syndrome (Hemolysis, Elevated Liver enzymes, Low Platelet counts). Acute fatty liver of pregnancy can present in many different ways, including with coagulopathy, renal failure and jaundice. The differential diagnoses include HELLP syndrome and acute viral hepatitis.
Diseases coincident to pregnancy
Acute viral hepatitis can occur throughout pregnancy and accounts for up to 40 percent of jaundice seen in pregnant patients. It usually tends to have the same disease course as in the non-pregnant population. The exceptions are hepatitis E and herpes simplex infections, which have significant mortality and morbidity. We have a low threshold to test for them, as early diagnosis is associated with improved outcomes.3 Gallstones are more common in pregnancy, especially during the second and third trimesters and should always be considered, especially in the presence of any abdominal pain. Drug-induced hepatotoxicity may occur at any time during the pregnancy and a detailed history of all prescription and nonprescription medications should always be obtained.
All management decisions must account for the health of both the mother and fetus. This is especially true when treating chronic diseases such as autoimmune hepatitis or hepatitis B where therapy can impact both the mother and fetus. Ultrasonography is safe and is first line for imaging. MRI without contrast can also be employed as it does not use ionizing radiation. A liver biopsy is rarely necessary for diagnosis during pregnancy and we only obtain one if the etiology of liver dysfunction is unclear and the biopsy result has the potential to alter clinical management.
In summation, when we are confronted with a pregnant patient with liver dysfunction, we employ a comprehensive approach to evaluation and look for clinical and biochemical patterns that will allow us to make an accurate and rapid diagnosis.
Dr. Mufti had no conflicts to disclose.
Dr. Reau is a consultant for and serves on the advisory board of Abbott Laboratories, Johnson & Johnson and Vertex Pharmaceuticals. She is also president of the American Liver Foundation, and a member of AASLD’s public policy committee.
1. Ch’ng CL, Morgan M, Hainsworth I, Kingham JG. Prospective study of liver dysfunction in pregnancy in Southwest Wales. Gut 2002;51:876-80.
2. Bacq Y. Liver diseases unique to pregnancy: a 2010 update. Clin Res Hepatol Gastroenterol 2011;35:182-93.
3. Aggarwal R, Jameel S. Hepatitis E. Hepatology 2011;54:2218-26.1. Shan L, Molberg O, Parrot I, et al. Structural basis for gluten intolerance in coeliac sprue. Science 2002;297:2275-2279.