Reproductive Health and Liver Disease

Patient Guideline Summary

Publication Date: September 18, 2020

Last Updated: March 3, 2023

Objective

This patient summary means to discuss key recommendations from the American Association for the Study of Liver Diseases (AASLD) for reproductive health and liver disease. It is limited to adults 18 years of age and older and should not be used as a reference for children.

Overview

This patient summary focuses on the reproductive health of patients with liver disease.

Pregnancy Planning

Blood tests for liver disease should be included in pregnancy and pregnancy planning.

Adolescents have an increased risk of unplanned pregnancy. Long-acting reversible contraceptives have advantages in this population.

Pregnant adolescents with chronic liver disease require increased psychosocial support from pediatric and adult hepatologists, patient support (e.g., social workers), and maternal-fetal medicine specialists.

Estrogen-containing agents should be avoided in patients with decompensated cirrhosis, Budd-Chiari syndrome (BCS), hepatocellular adenomas, and transplant recipients with graft failure.

Patients using agents other than long-acting reversible contraceptives are encouraged to combine these with a barrier method given their higher failure rates.

Note: This is particularly important for women taking teratogenic medications, such as mycophenolic acid (MPA) products.

All forms of emergency contraception may be used in the setting of chronic liver disease.

Sexual dysfunction

When identified, referral to a specialist may be needed.

Assisted Reproduction

For patients with cirrhosis, the degree of hepatic decompensation is important when considering assisted reproduction.

For liver transplant recipients, the stability of graft function should be assessed.

Menopause, Andropause, and Hormone Therapy

Menopausal hormone therapy should not be used in women with decompensated liver function, BCS, or hepatocellular adenomas.

Testosterone replacement may be used in hypogonadal men with chronic liver disease.

Abdominal Imaging

Abdominal Ultrasound (US) without contrast is the preferred imaging modality throughout pregnancy.
Magnetic resonance imaging (MRI) and magnetic resonance cholangiopancreatography MRCP without gadolinium is preferred over computed tomography (CT) imaging.
Note: Gadolinium is contraindicated in pregnancy.
Abdominal CT without contrast is generally safe, but the cumulative ionizing radiation exposure should be as low as possible.
Use of iodinated contrast is recommended only if essential.
Breastfeeding is safe after iodinated or gadolinium contrast.

Acute Viral Hepatitis

Acute viral hepatitis in pregnancy warrants close monitoring for maternal and fetal complications, especially for acute hepatitis E virus (HEV) and herpes simplex virus (HSV) infections.

Management is supportive, and the use of specific antiviral therapy should be guided by the safety of the drugs in pregnancy.

A high index of suspicion is needed to identify HSV hepatitis, and intravenous acyclovir should be initiated while awaiting diagnostic studies. Acyclovir is safe in pregnancy and lactation.

Hepatitis B Virus (HBV)

All pregnant women should be tested for hepatitis B, informed of the increased risk of mother-to-child transmission (MTCT) with invasive pregnancy procedures such as amniocentesis, referred for specialist care if positive, and treated according to test results.

Breastfeeding is not contraindicated, even in women who continue on antiviral therapy.

Hepatitis C Virus (HCV)

Women and their sexual partners should be tested for HCV before and during each pregnancy. Those testing positive should be evaluated for antiviral therapy after completion of pregnancy and breastfeeding.

Preconception antiviral therapy should be prioritized to eliminate the risk of MTCT during pregnancy.

If ribavirin is used, highly effective contraception is required during and for at least 6 months following last use.

HCV-infected women requiring invasive pregnancy procedures, such as amniocentesis, should be informed of the possible risk of MTCT.

To reduce MTCT in HCV-infected women, prolonged rupture of membranes, invasive fetal monitoring, and episiotomies should be avoided.

Breastfeeding is not recommended during antiviral therapy. In addition, caution is needed if nipples bleed.

Wilson Disease (WD)

Preconception counseling should include genetic counseling and discussion of medication safety in pregnancy.

The use of zinc is safe in pregnancy, but other treatments may require contraception.
Note: Chelating agents should be continued during pregnancy due to the high risk of a spontaneous abortion if withdrawn. Dose reductions in the second and third trimesters are required.

Close monitoring of copper balance is necessary.

Breastfeeding is associated with infant risks, and there is a risk of copper deficiency in the infant.

Autoimmune Hepatitis

Delaying conception until the liver disease is well controlled on stable doses of immunosuppressants for at least 1 year is suggested. Other drugs must be reviewed for risks during pregnancy.

Liver test monitoring during each trimester is suggested.

Breastfeeding is not contraindicated.

Primary Biliary Cholangitis (PBC) and Primary Sclerosing Cholangitis (PSC)

These diseases can cause significant itching, which should prompt testing and treatment with care to avoid risks of certain treatments during pregnancy.

Non-Alcoholic Fatty Liver Disease

Evaluation for symptoms associated with polycystic ovary syndrome is recommended.

Preconception counseling should include a review of maternal and fetal risks associated with obesity and diabetes and the benefits of optimizing weight and metabolic comorbidities before conception.

Optimal gestational (during pregnancy) weight gain through a healthy diet and appropriate exercise should be emphasized.

Monitoring of liver tests should continue.

Breastfeeding is encouraged, and extended duration is associated with improved long-term outcomes in both mothers and children.

Alcohol-Associated Liver Disease (ALD)

Pregnant women should be screened for alcohol use and referred for management when appropriate.

For women with ALD, counseling should include delaying conception until abstinence is achieved.

Medication used to treat alcohol use disorder during pregnancy should be individualized, with careful weighing of the risks of alcohol use versus those of medication exposure.

Benign Hepatic Lesions

Reproductive-aged women with hepatocellular adenomas (HCAs) should be counseled about the possibility of adenoma growth and rupture in pregnancy.

Ultrasound (US) monitoring of HCAs during each trimester of pregnancy and up to 3 months postpartum is reasonable.

For HCAs greater than 5 cm in diameter, prophylactic treatment with embolization or resection should be considered before conception to reduce the risk of rupture during pregnancy.

Hepatic hemangiomas, regardless of size, do not require monitoring during pregnancy, but new onset of symptoms should prompt investigation.

Focal nodular hyperplasia, regardless of size, does not require monitoring.

Budd-Chiari Syndrome (BCS)

Doppler US is the imaging modality of choice for diagnosing BCS.

Low-molecular-weight heparin is the anticoagulant of choice during pregnancy and lactation in women with BCS.

Vitamin K antagonists are contraindicated during pregnancy but acceptable during breastfeeding.

Gallstone Disease

US is the imaging modality of choice for suspected gallstone disease in pregnancy.
Initial management of gallstone disease in pregnancy is supportive, although endoscopic retrograde cholangiopancreatography (ERCP) (imaging the gall bladder and pancreas with contrast injected through an endoscope) and laparoscopic cholecystectomy (removal of the gall bladder through an endoscope) can be considered, ideally in the second trimester. [endoscope: a long, flexible telescope with attached surgical instruments inserted through the mouth].
Note: To minimize radiation to the fetus during ERCP, lead shields will be placed on the pelvis and lower abdomen.

Cirrhosis

All women with cirrhosis should be counseled on the risk of worsening liver disease during pregnancy.

Portal Hypertension (PHT)

Prepregnancy endoscopic screening for gastroesophageal varices (GEV) (enlarged veins between the esophagus and stomach that can bleed) is recommended. Endoscopic procedures require a preoperative consultation with maternal-fetal medicine (MFM) specialists to coordinate fetal monitoring and maternal sedation.

In women with cirrhosis, screening in the early second trimester is indicated if not performed within 1 year before conception or if there is ongoing liver injury, or if decompensation occurs.

Meperidine, midazolam, propofol, and fentanyl may be used in pregnancy, with efforts to minimize the duration of anesthesia.

GEV should be treated either to prevent or to stop bleeding.

The mode of delivery should be guided only by obstetric indications.

Hyperemesis Gravidarum

Treatment of hyperemesis gravidarum is supportive with rehydration, correction of chemical abnormalities, thiamine supplements, and anti-emetic therapy.

Persistent liver chemistry abnormalities, despite symptom resolution, should prompt investigation for another cause.

Intrahepatic Cholestasis (ICP)

ICP causes pruritus (itching) and related laboratory abnormalities in the second or third trimester.

Women with ICP should be tested for HCV, if not previously done.

Pruritus management is multifaceted. It usually resolves within days or weeks.

Hypertensive Diseases of Pregnancy

In women with preeclampsia, delivery by 37 weeks is advised, with close monitoring for the development of eclampsia and hemolysis (blood cells breaking up), elevated liver enzymes, and low platelets (HELLP) syndrome.

When HELLP syndrome or eclampsia is suspected, urgent delivery is recommended after maternal stabilization.

Abdominal imaging should be performed in suspected HELLP to rule out hepatic hemorrhage, infarct, or rupture.

HELLP complicated by hepatic rupture or ALF should prompt transfer to a transplant center for evaluation.

Acute Fatty Liver of Pregnancy (AFLP)

When AFLP is suspected, urgent delivery is recommended after maternal stabilization.

Abdominal imaging should be performed in AFLP to rule out hepatic hemorrhage, infarct (loss of blood supply due to a plugged artery), or rupture. The presence of hepatic rupture or acute fatty liver (AFL) should prompt transfer to a transplant center for evaluation.

All newborns of mothers with AFLP should be screened at birth for related birth defects. Referral to genetic counseling is indicated for affected families.

Transplant Recipients

Mycophenolic acid products must not be used during pregnancy and lactation. Contraceptive agents with low failure rates should be used.

Pregnancy should be delayed until at least 1 year after transplant and with greater than or equal to 6 months of stable graft function.

Some transplant drugs are acceptable for use in pregnancy and lactation. Some are not.

More frequent monitoring of graft function during pregnancy and in the postpartum period is recommended.

The mode of delivery should be guided only by obstetric indications.

Abbreviations

6-MP: 6-mercaptopurine
AASLD: American Association For The Study Of Liver Diseases
AFL: Acute Fatthy Liver
AFLP: Acute Fatty Liver Of Pregnancy
ALD: Alcohol-Associated Liver Disease
BCS: Budd-Chiari Syndrome
CT: Computed Tomography
ERCP: Endoscopic Retrograde Cholangiopancreatography
GEV: Gastroesophageal Varices
HBV: Hepatitis B Virus
HCAS: Hepatocellular Adenomas
HCV: Hepatitis C Virus
HELLP: Hemolysis, Elevated Liver Enzymes, Low Platelets Syndrome
HEV: Hepatitis E Virus
HSV: Herpes Simplex Virus
ICP: Intrahepatic Cholestasis
MFM: Maternal-fetal Medicine
MPA: Mycophenolic Acid
MRCP: Magnetic Resonance Cholangiopancreatography
MRI: Magnetic Resonance Imaging
MTCT: Mother-to-child Transmission
NAFLD: Non-alcoholic Fatty Liver Disease
PBC: Primary Biliary Cholangitis
PHT: Portal Hypertension
PSC: Primary Sclerosing Cholangitis
US: Ultrasound
WD: Wilson Disease

Source Citation

Sarkar M, Brady CW, Fleckenstein J, Forde KA, Khungar V, Molleston JP, Afshar Y, Terrault NA. Reproductive Health and Liver Disease: Practice Guidance by the American Association for the Study of Liver Diseases. Hepatology. 2020 Sep 18. doi: 10.1002/hep.31559. Epub ahead of print. PMID: 32946672.

Disclaimer

The information in this patient summary should not be used as a substitute for professional medical care or advice. Contact a health care provider if you have questions about your health.