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Diseases

Pregnancy and Liver Disease

The hormones estrogens (estradiol) and progesterone increase progressively during the course of a normal pregnancy. These hormones have effects on major liver functions. Some liver function tests may, accordingly, get altered even in a normal pregnancy. Approximately 3% of pregnant women are affected by some form of liver disease during pregnancy. Pregnancy-related liver diseases can lead to disastrous consequences for both mother and child sometimes.

    Pregnancy related liver diseases are trimester specific

    Hyperemesis Gravidarum (HG)

    • Affects nearly 3% of pregnant women, usually primigravida or first time pregnancy
    • Symptoms include nausea and intractable vomiting resulting in dehydration, metabolic disturbance causing an increase in ketone bodies (ketosis)s, and loss of more than 5% of body weight
    • Symptoms start before the 9th week of pregnancy and disappear by the 20th week
    • HG is not a true liver disease, but abnormal liver tests (increase in the liver enzyme serum aminotransferases) are seen in 50% of women
    • Risk factors include more than one fetus, obesity, pre-existing diabetes, or psychiatric illness
    • Abdominal ultrasound will show a normal liver without biliary obstruction; multiple births
    • Severe symptoms may need hospitalization for intravenous (IV) fluid replacement, correction of electrolyte abnormalities, medications to control nausea and the use of vitamin supplements; severe cases will need IV nutrition

    Intrahepatic Cholestasis of Pregnancy (ICP)

    • Most common pregnancy-related liver disease
    • Causes reduction or blocking of bile flow (cholestasis), reversing spontaneously within 6 weeks of delivery
    • Usually occurs during the late second and third trimester
    • Risk factors are maternal age >35 years, multiple births, history of oral contraceptive use, history of fertility treatment in women, and history of ICP during previous pregnancies
    • The main symptom of ICP is itching of palms and soles of the feet that is worse at night. Pruritus often develops after 25 weeks of gestation, with 80% of cases occurring after the 30th week Jaundice may develop 1 to 4 weeks once itching starts, with dark urine and pale feces in some women
    • Total bile acids concentration and liver enzymes are monitored
    • Risk of preterm labor, stillbirth, if serum bile acids is more than 40 μmol serum
    • Persistent abnormal laboratory findings beyond 8 weeks after delivery needs exclusion of liver disease
    • Treatment is with ursodeoxycholic acid (UDCA) at a dose of 300 mg twice a day or 15 mg/kg per day and is safe in the third trimester

    Acute Fatty Liver of Pregnancy

    • Rare but serious condition usually occurring in the third trimester
    • In the absence of signs of pre-existing liver disease, most women recover completely during the first month after delivery
    • Risk factors include multiple pregnancies, high blood pressure (pre-eclampsia), multiple pregnancies
    • Symptoms include nausea, vomiting, abdominal pain, headache, and malaise
    • Can rapidly progress to acute liver failure and its complications
    • Abnormal liver values include high levels of aminotransferase, bilirubin

    Pre-eclampsia, Eclampsia, and HELLP Syndrome

    Pre-eclampsia is defined by high blood pressure after the 20th week of pregnancy (BP) ≥140/90 mmHg and proteinuria of >300 mg/day, kidney, liver and other systemic other dysfunction of the mother) When fits (seizures) are present, it is known as eclampsia

    • HELLP (Hemolysis, elevated liver enzymes, and low platelets)syndrome is a variant of severe preeclampsia that occurs in up to 12% of patients with preeclampsia
    • Risk factors are advanced maternal age and multiple pregnancies
    • Elevated liver aminotransferases and low platelet counts
    • Can develop after delivery (postpartum period) within the first 48 h, usually in patients who had proteinuria and hypertension prior to delivery should be monitored
    • HELLP has similar symptoms to acute fatty liver and must be differentiated early
    • The only definitive treatment is delivery of the fetus and stabilization of the maternal clinical condition
    • Laboratory abnormalities often return to normal levels within 2 weeks of delivery

     

    Pre-existing diseases of the liver and pregnancy

    Cirrhosis and Portal Hypertension

    • If decompensated cirrhosis is present, pregnancy rarely occurs
    • When pregnancy occurs, the risk is very high for spontaneous abortion, prematurity, and newborn death
    • Portal hypertension (PH) is increased pressure in the portal vein, worsens during the second trimester and the in the second stage of labor causing bleeding from upper gut
    • Liver decompensation occurs with symptoms of jaundice, confusion, clotting disorder, and swelling of abdomen ( ascites)
    • Bleeding from the gut during pregnancy should be treated by endoscopic ligation therapy to stabilize the mother

    Chronic Hepatitis B and C

    Chronic hepatitis B may lead to liver cirrhosis and hepatocellular carcinoma.

    • All pregnant women should be screened for hepatitis B virus (HBV) and hepatitis B surface antigen (HBsAg) in the first trimester
    • High risk for developing chronic liver infection
    • In pregnant women with chronic HBV infection and high viral load, therapy with nucleoside analogs (NAs) is recommended, to be initiated in later half of second trimester and in third trimester of pregnancy to prevent infecting the newborn
    • Vaccination should be administered to all newborns from HBV-positive mothers within 12–24 h after delivery. If during delivery, mother is having high viral load, then the infant has to receive Anti HBs immunoglobulin immediately after delivery to prevent infection with hepatitis B.
    • All infants should be tested for anti-HBsAg and HBsAg 9-18 months after delivery
    • Breast feeding is not a contraindication for hepatitis B positive mothers

    Chronic hepatitis C virus (HCV) does not worsen maternal liver disease or other adverse complications in the mother and child

    • All pregnant women with risk factors for HCV should be screened with anti-HCV antibody There may be an increased risk for preterm birth
    • Transmission from the mother’s HCV is low (about 3–5%)

    Autoimmune Liver Hepatitis (AIH)

    • The course is highly variable and depends on the timing of the pregnancy and clinical guidance and preparation of the mother before the pregnancy
    • The live birth rate (LBR) is about 73%, but lower if complicated by cirrhosis
    • Disease activity flares up in about 33% of pregnancies, mostly after delivery
    • Pregnancy occurring during remission is most favorable
    • Poor disease control carries the risk of poor outcome
    • Azathioprine is safe to use during pregnancy and lactation

    Role of Liver Transplantation (LT) and Pregnancy

    • Fertility is restored in most women with LT after the first year, but delaying pregnancy for 1 or 2 years following LT is advocated
    • Walcott and colleagues reported successful pregnancy in 1978 post liver transplant
    • Monitoring is to be done for maternal and graft risk and fetal growth by liver specialists and obstetricians
    • Optimal immunosuppression is continued; steroids, azathioprine, and the calcineurin inhibitor (CNI) tacrolimus are safe
    • Coexisting preeclampsia/eclampsia, gestational diabetes (7%), and bacterial infections lead to poor outcomes