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  • Liver Disease in Pregnancy Preethi Reddy, MD

    Assistant Professor of Medicine University of Texas Health Science Center at Houston

    Memorial Hermann- Texas Medical Center

  • Liver in Pregnancy

    Normal physiology of pregnancy

    Liver Diseases:


    Coincidental to pregnancy

    Chronic liver disease in pregnancy

  • Normal Physiology of Pregnancy

    Hyperdynamic, pro-coagulant Physical Exam:

    Spider angioma Palmar erythema

    Normal ALT, AST, GGT, bilirubin, INR/protime alkaline phosphatase

    placenta, fetal bone AFP

    fetal liver fibrinogen, factors II, V, VII, X, XII Hemoglobin, albumin, urea

  • Biochemical Changes in Normal Pregnancy

    Test Change Trimester

    ALT --

    AST --

    Alkaline phosphatase third

    GGT --

    Total bilirubin --

    Albumin second

    Urea second

    Hemoglobin second

    Fibrinogen, factors II, V, VII, X, XII second

    Olans et al. Liver Disease in Pregnancy 2003.

  • Abnormal in Pregnancy Jaundice Hepatomegaly Splenomegaly Abdominal pain Murphys sign Diffuse excoriations Hypertension Orthostatic hypotension Peripheral edema Neurologic findings (asterixis, hyperreflexia) Ecchymosis, petechiae

  • Diagnostic Tests History and physical exam are key

    Routine blood chemistry and blood count

    Serum bile acid level- ICP

    Uric acid- AFLP, pre-eclampsia

    DIC panel- AFLP

    Amylase, lipase- abdominal pain

    Viral hepatitis serologies

    Avoid sedative medications and radiation

    Ultrasound is safe and helpful

    MRI is safe

    Gadolinium should not be used

    Liver biopsy is RARELY needed

  • Differentials for Elevated LFTs

    1st Trimester 2nd Trimester 3rd Trimester

    Hyperemesis gravidarum Cholelithiasis Viral hepatitis Drug-induced hepatitis Uncommon: ICP

    ICP Cholelithiasis Viral hepatitis Drug-induced hepatitis Uncommon: Pre-eclampsia/eclampsia HELLP syndrome

    ICP Pre-eclampsia/eclampsia HELLP syndrome AFLP Hepatic rupture Cholelithiasis Viral Hepatitis Drug-induced hepatitis

    Olans et al. Liver Disease in Pregnancy 2003.

  • Pregnancy-associated Liver Diseases

    Hyperemesis Gravidarum

    Intrahepatic Cholestasis of Pregnancy (ICP)

    Overlap Syndromes:


    HELLP (hemolysis, elevated liver tests, low platelets)

    Acute Fatty Liver of Pregnancy (AFLP)

  • Hyperemesis Gravidarum

    Most common in the 1st trimester Intractable nausea and vomiting

    Dehydration, electrolyte abnormalities, weight loss of 5%, nutritional deficiencies

    Risk factors: history of HG, hyperthyroidism, DM, overweight, multiple gestations, primiparity, age

  • ICP Reversible intrahepatic cholestasis

    Late 2nd/ 3rd trimester

    Resolves 4-6 weeks post-delivery

    Intense pruritus (palms/soles whole body), jaundice (10-25%)

    Risk factors: personal or family history of ICP, prior cholestatic hepatitis (OCPs/estrogen), progesterone use in pregnancy, advanced maternal age, multiple gestations, underlying HCV

    Etiology: genetic, hormonal, environmental

    Gene variants of hepatocanalicular transport proteins Increased sex hormone production in pregnancy

    Impaired hepatic clearance of bile acids from portal blood

    Sensitivity to estrogens

    Selenium deficiency? Friedman et al. Handbook of Liver Disease 2011. Glantz et al. Hepatol 2004. Ambros-Rudolph et al. JAMA 2007.

  • ICP Elevated aminotransferases

    Up to 4X ULN

    serum bile acid levels ( > 11 mol/L)

    10-100X ULN

    Vitamin K deficiency (malabsorption)

    US to rule out cholelithiasis

    Liver biopsy: cholestasis, mild hepatocellular necrosis


    Ursodeoxycholic acid (UDCA) 10-15 mg/kg body weight, cool environment, emollients

    Early delivery

    Typically good maternal outcome

    Fetus: Increased risk of preterm delivery, meconium staining of amniotic fluid, fetal distress/loss

    Better outcome with lower bile acid levels (

  • Pre-eclampsia/Eclampsia

    Late 2nd/ 3rd trimester (>20 weeks)

    Previously normotensive

    Hypertension (SBP >140, DBP >90), proteinuria (>300 mg/24h), edema

    Seizures, coma (eclampsia)

    Hepatic, renal, CNS, hematologic and fetal placental involvement

    Risk factors: history of pre-eclampsia/eclampsia, young and advanced maternal age, multiple gestations, obesity, insulin resistance, infection, inadequate prenatal care

    Unknown etiology

  • Pre-eclampsia/Eclampsia

    Elevated aminotransferases (5-100X ULN)

    Eclampsia (90%)

    Severe pre-eclampsia (50%)

    Pre-eclampsia (24%)

    Mild increase in total bilirubin ( 5 mg/dL)

    Thrombocytopenia, MAHA


    Anti-hypertensives, bed-rest, magnesium sulfate

    Delivery if eclampsia (or late pre-eclampsia)

    Maternal and fetal outcome depends on severity

    Death commonly from cerebral involvement

    risk of hepatic rupture and HELLP

    Resolution of abnormal LFTs post-delivery

    Friedman et al. Handbook of Liver Disease 2011.

  • HELLP Syndrome

    Hemolysis, elevated liver tests, low platelets 3rd trimester Postpartum (15-25%, usually within 2 days) Risk factors: personal history, advanced maternal age, Caucasian,

    multiparity Epigastric pain, nausea, vomiting, H/A, hypertension, visual

    changes, weight gain, edema, jaundice MAHA, LDH, indirect bilirubin, haptoglobin, schistocytes aminotransferases (mild- 100 x ULN) Thrombocytopenia (

  • HELLP Syndrome


    Anti-hypertensives, seizure prophylaxis

    Fetal monitoring

    Early delivery

    Maternal/fetal distress

    Severe thrombocytopenia

    Corticosteroids to improve fetal lung maturity (

  • AFLP Rare Microvesicular steatosis of the liver liver failure 3rd trimester May occur immediately post-partum Etiology:

    Nutritional factors Changes in lipoprotein synthesis Mitochondrial urea cycle enzyme deficiencies Defects in maternal mitochondrial fatty acid beta-oxidation

    Fetal LCHAD deficiency (longchain 3-hydroxyacyl coenzyme A dehydrogenase)

    Fetal homozygosity/maternal heterozygosity LCHAD:

    component of MTP (mitochondrial trifunctional protein) catalyzes -oxidation of long-chain fatty acids (LCFA)

    Friedman et al. Handbook of Liver Disease 2011.

  • AFLP: LCHAD Deficiency

    fetal LCFA

    {Maternal circulation}

    Heterozygosity of mother/reduced ability to oxidize


    Fatty infiltration

    Progressive liver failure



    Hepatic encephalopathy

    Renal failure

    Hepatic carnitine palmitoyl transferase I deficiency

  • AFLP aminotransferases (< 500 U/L) Mild to moderate AP and bilirubin Hyperuricemia Fatty infiltration on imaging Liver biopsy with Oil-Red-O stain Swansea Criteria (6 or more):

    Abdominal pain Vomiting Polyuria/polydipsia Hepatic encephalopathy Hyperbilirubinemia Leukocytosis Ascites/ fatty infiltration of the liver on US Transaminemia Coagulopathy Elevated ammonia Renal dysfunction Microvesicular steatosis

    Kingham et al. Gut 2010.

  • AFLP


    Emergent delivery

    Liver transplant if acute liver failure

    Plasma exchange

    Improving outcomes with supportive care

    Mostly good maternal outcome

    Screen for fatty acid oxidation defect for those affected

  • Pre-eclampsia/eclampsia



    (severe thrombocytopenia)


    intraparenchymal hemorrhage

    Subcapsular hematoma


    3rd trimester Sudden onset

    abdominal pain, N/V, distension

    Hypovolemic shock US, CT, MRI Prompt delivery Surgical or IR

    intervention High maternal and

    fetal mortality

  • Coincidental to Pregnancy

    Autoimmune Hepatitis (AIH)

    Drug-Induced Hepatitis

    Viral Hepatitis A-E, Herpes Simplex Virus


    Budd-Chiari Syndrome

  • Viral Hepatitis A-E

    Only hepatitis E course is affected by pregnancy Jaundice is more common Acute liver failure Increased maternal and fetal mortality Vertical transmission in 30% Check HEV IgM Supportive care

    Vertical transmission in uncommon with hepatitis A and D HAV immunoglobulin Control hepatitis B to prevent transmission of hepatitis D

    HCV: Higher rate of vertical transmission if significant or HIV co-infection (35%) Breastfeeding is safe

    Friedman et al. Handbook of Liver Disease 2011. Aggarwal et al. J Gastoenterol Hepatol 2009.

  • Hepatitis B Perinatal transmission is most likely to occur at delivery

    C-section not indicated

    Who to treat?

    HBsAg + mothers with HBV DNA PCR >200,000 IU/Ml

    No data on when to stop therapy

    Monitor for flares if therapy is discontinued

    Pregnancy Class B: telbivudine, tenofovir (preferred)

    Infants of all HBsAg+ mothers: HBIG and initiation of HBV vaccination series within 12 hours of birth

    Reduced rate of vertical transmission (> 90% to

  • Herpes Simplex Hepatitis (HSV)

    Disseminated HSV


    Late 2nd/ 3rd trimester

    Presentation: fever, nausea, vomiting, cutaneous lesions, abdominal pain, thrombocytop