Liver Diasease in Pregnancy

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Transcript of Liver Diasease in Pregnancy

  • Liver Diseasein Pregnancy

    Arjmand R. Mufti, MD, MRCP, Nancy Reau, MD*

    ferase (ALT), aspartate aminotransferase (AST) and g-glutamyl transferase (GGT)levels are within the normal range or marginally reduced secondary to hemodilu-tion.46 In contrast, serum alkaline phosphatase (ALP) increases markedly duringthe third trimester and levels can be 4 times more than the normal prepregnancyvalues. This situation is mainly the result of the production of a placental isoenzyme,

    Department of Medicine, Section of Gastroenterology, Hepatology and Nutrition, University oficago, IL 60637, USAClin Liver Dis 16 (2012) 247269Chicago Medical Center, 5841 South Maryland Avenue, MC 4076, Ch* Corresponding author.E-mail address: nreau@medicine.bsd.uchicago.eduChanges in the liver biochemical profile are normal in pregnancy. However, up to 3%to 5% of all pregnancies are complicated by liver dysfunction.1 It is important that liverdisease during pregnancy is recognized because early diagnosis may improvematernal and fetal outcomes, with resultant decreased morbidity and mortality. Liverdiseases that occur in pregnancy can be broadly divided into 3 different groups: liverdiseases that are unique to pregnancy, liver diseases that are not unique to pregnancybut can be revealed or exacerbated by pregnancy, and liver diseases that are unre-lated to but occur coincidentally during pregnancy (Box 1).


    Pregnancy is a time of great metabolic and physiologic changes, and it is essential thatany changes in liver function tests are interpreted in this context (Table 1). Duringpregnancy, the body undergoes adaptive changes in physiology, which affect allorgan systems including the liver. The plasma volume increases by approximately50%, there is an increase in venous pressure, and although the absolute hepatic bloodflow remains unchanged, the liver receives a lower percentage of the cardiac output.2

    There is also a decrease in the blood pressure and systemic vascular resistance, andthese changes mimic the physiologic changes that occur in patients with decompen-sated chronic liver disease. In addition, serum estrogen and progesterone levels areincreased.3 The resulting hyperestrogenemia is believed to be the cause of spidertelengectasias and palmar erythema, signs that are usually seen in chronic liverdisease, but are normal during pregnancy and usually resolve after delivery.The traditional tests of liver function are also affected. Serum alanine aminotrans-


    Liver disease Pregnancy Liver biochemical profiledoi:10.1016/j.cld.2012.03.011 liver.theclinics.com1089-3261/12/$ see front matter 2012 Elsevier Inc. All rights reserved.

  • Box 1

    Classification of liver diseases in pregnancy

    Diseases unique to pregnancy

    Hyperemesis gravidarum (HG)

    Intrahepatic cholestasis of pregnancy (ICP)

    Acute fatty liver of pregnancy (AFLP)

    Preeclampsia and eclampsia

    HELLP syndrome

    Preexisting underlying liver disease

    Hepatitis B and C

    Autoimmune hepatitis

    Wilson disease

    Primary sclerosing cholangitis (PSC)

    Primary biliary cirrhosis (PBC)


    Liver diseases coincident with pregnancy

    Viral hepatitis

    Budd-Chiari syndrome


    Drug-induced hepatotoxicity

    Liver transplantation


    Table 1Biochemical changes in liver tests during a normal pregnancy

    Test Alterations Seen

    Total bilirubin No change or slightly decreased

    AST No change or slightly decreased

    ALT No change or slightly decreased

    Alkaline phosphatase Increased 2-fold to 4-fold

    Albumin Decreased

    Fibrinogen Increased by 50%

    Factors V, VII, and VIII Increased

    Globulins Increased a and b globulin; Decrease ing globulin

    Partial thromboplastin and activated partialthromboplastin time

    No change

    a-Fetoprotein Increased (especially with twins)

    Platelets No change

    Cholesterol and triglycerides Increased

    Ceruloplasmin Increased

    Hemoglobin Decreased from second trimester

    White cell count Increased

    248 Mufti & Reau

  • but there is also an increase in production of the bone isoenzyme.46 In pregnantpatients, total and unconjugated bilirubin concentrations may be slightly decreasedduring all 3 trimesters and conjugated bilirubin levels are mildly reduced during thesecond and third trimesters.4 There is no difference in the total bile acid concen-trations in the pregnant and nonpregnant populations but there is decreased motilityof the gallbladder, resulting in increased lithogenicity of the bile.4 An increase inplasma volume as well as decreased synthesis results in a decrease in serumalbumin levels in the first trimester and this becomes more marked as the preg-nancy progresses. In contrast, serum triglyceride and cholesterol levels increaseby 50% and 200%, respectively, secondary to increased production.7 There isalso an increase in the hepatic synthesis of factors V, VII, VIII, and fibrinogen butthere is no change in the range for prothrombin time and activated partial throm-boplastin time (APTT). Therefore increased levels of ALT, AST, and serum bilirubinlevels should be considered pathologic and further evaluation should beundertaken.


    Of course, all modes of evaluation for abnormal liver function should be safe for the

    Table 2Diagnostic techniques used in pregnancy

    Liver Disease in Pregnancy 249DiagnosticMethod Safety Profile

    Ultrasonography Considered safe during pregnancy, with no known adverse effectsfrom in utero exposure

    Magneticresonance imaging

    Considered safe during pregnancy, but avoid gadolinium in thefirst trimester because it crosses the placenta and fetal effectsare unknown

    Radiograph exposure Up to 2 weeks gestation: exposure to high-dose ionizingradiation (>0.10 Gy) may be lethal

    216 weeks: threshold for radiation is 0.10 Gy815 weeks: highest risk for mental retardation and microcephalyrelated to abnormalities in neuronal development

    >16 weeks: threshold for radiation is 0.500.70 GyLow risk of teratogenicity after 25 weeks

    Contrast agents Should be avoided unless risk to the fetus is justified

    Liver biopsy Rarely required but both the ultrasound-guided percutaneousfetus and the mother. Ultrasonography remains the safest method to visualize the liverduring pregnancy. If further testing is required, according to the American College ofObstetricians and Gynecologists guidelines for diagnostic imaging in pregnancy,exposure to a single diagnostic procedure does not result in harmful fetal effects,and exposure to less than 0.05 Gy is not associated with fetal abnormalities or abor-tion.8,9 Nevertheless, the utmost care should be exercised when deciding how toproceed. The embryo and the fetus are particularly sensitive to ionizing radiation,and exposure to increased exposure can be teratogenic, mutagenic, or carcinogenicin nature.8,9 Table 2 outlines the different diagnostic techniques that can be used toinvestigate abnormal liver tests and their related adverse effects.route and transjugular approaches are safe


    Several liver diseases occur only during pregnancy and usually resolve only afterdelivery. Most liver dysfunction that is seen in pregnancy is caused by diseases thatfall into this category.


    Nausea and vomiting are common in pregnancy and affects up to 80% of women inthe first trimester.10 HG occurs in 0.3% to 2.0% of pregnant women11 and is definedas persistent vomiting early in pregnancy that is associated with weight loss of 5% ormore of prepregnancy body weight, dehydration, and ketosis.12 It is a diagnosis ofexclusion, and other causes of nausea and vomiting must be ruled out.13 Hospitaliza-tion is usually required for intravenous fluid therapy and symptoms start early in thefirst trimester of pregnancy, typically between 4 and 10 weeks gestation and mostcases resolve by 20 weeks.14 However, in approximately 10% of patients, symptomspersist throughout pregnancy and resolve only after delivery.15,16 The underlyingcauses of HG are poorly understood, but genetic predisposition, abnormal gastricmotility, hormonal factors, immunologic factors, and changes in the autonomicnervous system are postulated to be involved.1720 Risk factors include obesity, pre-existing diabetes, molar pregnancy, multiple pregnancies, and psychiatric illness. It isalso associated with a biochemical thyrotoxicosis in 60% of cases (increased free tri-iodothyronine [T3] and thyroxine [T4] and suppressed thyroid-stimulating hormone inthe absence of clinical hyperthyroidism) and this is believed to be caused by increasedhuman chorionic gonadotrophin levels, which increase thyroid-stimulating activityduring pregnancy.21,22

    Liver involvement is seen in 50% to 60% of cases23 and a mild increase in amino-transferase levels is the most common biochemical abnormalities seen with ALT levelsusually exceeding AST levels.24 However, more striking derangements are also seen;AST and ALT levels more than 20-times the upper limit of normal have also beenreported.24,25 Jaundice is uncommon and if abnormal chemistries persist, othercauses of liver disease such as viral hepatitis or drug-related liver injury should beexcluded. A liver biopsy should be performed only if the diagnosis of HG is in doubtand histology is usually normal or shows bland cholestasis and steatosis.26,27 Treat-ment is usually supportive and includes intravenous rehydration and nutritionalsupport. Patients should avoid triggers that aggravate nausea, and eat small, frequent,high-carbohydrate, low-fat meals. No medications are currently approved by the USFood and Drug Administration (FDA) for HG, but