Reproductive Health and Liver Disease

Publication Date: September 17, 2020
Last Updated: August 13, 2022

Guidance Statements

Sexual Function Across Age in Patients with Chronic Liver Disease 

Evaluation and Management of Sexual Dysfunction in Chronic Liver Disease

Sexual dysfunction is common in chronic liver disease and clinicians should routinely inquire about symptoms. When identified, referral to a specialist may be needed for evaluation and treatment.
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Pregnancy Planning in Adolescents and Adults With Liver Conditions

Adolescents have an increased risk of unplanned pregnancy. Long‐acting reversible contraceptives have advantages in this population.
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Clinicians should routinely inquire about sexual activity and pregnancy intentions in all reproductive‐aged adolescents and women with chronic liver disease or liver transplant.
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Pregnant adolescents with chronic liver disease require increased psychosocial support, necessitating close collaborations between pediatric and adult hepatologists, patient support (e.g., social workers), and maternal‐fetal medicine specialists.
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Estrogen‐containing agents should be avoided in patients with decompensated cirrhosis, BCS, hepatocellular adenomas, and transplant recipients with graft failure.
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Patients using agents other than long‐acting reversible contraceptives are encouraged to combine these with a barrier method given their higher failure rates; this is particularly important for women taking teratogenic medications, such as mycophenolic acid (MPA) products.
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All forms of emergency contraception may be used in the setting of chronic liver disease.
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Assisted Reproduction and Liver Disease

There is no absolute contraindication to assisted reproduction in women with cirrhosis or prior transplant. Preconception counseling for risk stratification is recommended.
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For patients with cirrhosis, the degree of hepatic decompensation is important when considering assisted reproduction, with caution used in Child‐Turcotte‐Pugh B or C cirrhosis.
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For liver transplant recipients, stability of graft function should be assessed when considering assisted reproduction.
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Menopause, Andropause, and Hormone Therapy

Menopausal hormone therapy should not be used in women with decompensated liver function, BCS, or hepatocellular adenomas.
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Testosterone replacement may be used in hypogonadal men with chronic liver disease.
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Evaluation of Liver Disease in Pregnancy

Initial Evaluation of a Pregnant Patient With Liver Disease

Liver Biochemistry Changes During Normal Pregnancy
Elevation in aminotransferases, bilirubin, or bile acids in pregnancy is abnormal and requires investigation.
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Abdominal Imaging in Pregnancy
Abdominal US without contrast is the preferred imaging modality throughout pregnancy. Limited Doppler study of hepatic vasculature can be used, but exposure time should be minimized.
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MRI/MRCP without gadolinium is preferred over CT imaging. Gadolinium is contraindicated in pregnancy.
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Abdominal CT without contrast is generally safe, but the cumulative ionizing radiation exposure should be as low as possible and less than 50 mGy.
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Use of iodinated contrast is recommended only if essential.
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There are insufficient data to recommend use of elastography during pregnancy.
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Breastfeeding is safe after iodinated or gadolinium contrast.
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Management of Chronic Liver Diseases During Pregnancy and Lactation

Hepatitis B

All pregnant women should be tested for HBsAg. Women newly identified as HBsAg‐positive should be linked with a clinician knowledgeable in the long‐term management of HBV.
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HBsAg‐positive pregnant women:
Should be informed of the increased risk of MTCT with invasive pregnancy procedures, such as amniocentesis.
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Require quantification of HBV DNA in the second trimester, and if maternal HBV DNA is greater than 200,000 IU/mL, antiviral therapy should be started between gestational weeks 28 and 32, to reduce the risk of MTCT. Antiviral therapy can be stopped at delivery or up to 3 months postpartum.
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If antiviral therapy is required, TDF is preferred. There are insufficient safety data to recommend entecavir or tenofovir AF.
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Monitoring of ALT and HBV DNA for 6 months postpartum or after cessation of antivirals is recommended.
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Breastfeeding is not contraindicated, even in women who continue on antiviral therapy.
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Hepatitis C

Pregnant women should be tested for HCV during each pregnancy, and those testing positive should be evaluated for antiviral therapy after completion of pregnancy and breastfeeding.
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Preconception antiviral therapy should be prioritized for HCV‐infected women of childbearing age, to eliminate the risk of MTCT during pregnancy.
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For women or men whose HCV therapy includes ribavirin, highly effective contraception is required, and conception should be deferred for at least 6 months following last ribavirin use.
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There are insufficient safety data on DAAs to recommend their use in pregnancy as a means of reducing MTCT.
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HCV‐infected women requiring invasive pregnancy procedures, such as amniocentesis, should be informed of the possible risk of MTCT.
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To reduce MTCT in HCV‐infected women, prolonged rupture of membranes, invasive fetal monitoring, and episiotomies should be avoided.
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Monitoring for ALT flares in HCV‐infected women is not required during pregnancy and postpartum.
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Breastfeeding is not contraindicated in HCV‐infected women, but not recommended during antiviral therapy. In addition, caution is needed if skin breakdown occurs with associated bleeding of nipples.
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Wilson Disease

In women with WD:
  • Preconception counseling should include genetic counseling and discussion of medication safety in pregnancy.
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  • Use of zinc is safe in pregnancy and delaying conception until the patient is on zinc monotherapy should be encouraged.
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  • Chelating agents should be continued during pregnancy due to the high risk of spontaneous abortion if withdrawn. Dose reductions in the second and third trimesters are required.
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  • Breastfeeding is associated with infant risks, as all WD drugs are excreted in breast milk, and there is risk for copper deficiency in the infant.
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Autoimmune Hepatitis

In women with AIH:
  • Preconception counseling should include discussion of medication safety in pregnancy and potential for disease exacerbation, including decompensation. Delaying conception until liver disease is well controlled on stable doses of immunosuppressants for at least 1 year is suggested.
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  • Counseling regarding the potential risks of azathioprine and 6‐mercaptopurine (6‐MP) is recommended, although these drugs are considered safe in pregnancy and lactation.
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  • Prednisone and budesonide are considered low risk in pregnancy and lactation.
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  • MPA products are contraindicated in pregnancy and lactation.
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Chronic Cholestatic Liver Diseases

Primary Biliary Cholangitis and Primary Sclerosing Cholangitis
In women with PBC and PSC:
  • Measurement of total serum bile acids may be considered in the first trimester to aid in excluding ICP in the setting of new‐onset or worsening pruritus during pregnancy.
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  • UDCA is safe in pregnancy and lactation, although no data support a therapeutic benefit in primary sclerosing cholangitis.
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  • Obeticholic acid and fibrate use cannot be recommended in pregnancy or lactation in women with PBC due to lack of safety data.
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  • Clinically significant pruritus typically requires a multifaceted approach with cholestyramine (4‐16 g daily, divided dose and separated from other medications by at least 2 hours), rifampin (300‐600 mg daily), SAMe (1,000‐1,200 mg daily), and antihistamines considered, although evidence is low.
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  • Vitamin K deficiency related to cholestasis should be corrected, and regular monitoring of PT is recommended.
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Nonalcoholic Fatty Liver Disease

In reproductive‐aged patients with NAFLD:
  • Evaluation for symptoms associated with polycystic ovary syndrome is recommended.
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  • Preconception counseling should include review of maternal and fetal risks associated with obesity and diabetes and the benefits of optimizing weight and metabolic comorbidities before conception.
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In pregnant patients with NAFLD:
Breastfeeding is encouraged, and longer duration of lactation is associated with lower rates of future NAFLD among offspring and reduced maternal metabolic complications, including NAFLD.
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Alcohol‐Associated Liver Disease

Pregnant women should be screened for alcohol use and referred for management when appropriate.
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For women with ALD, counseling should include delaying of conception until abstinence is achieved.
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Medication use to treat alcohol use disorder during pregnancy should be individualized, with careful weighing of the risks of alcohol use versus those of medication exposure.
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Liver Conditions Requiring Special Management in Pregnancy

Benign Hepatic Lesions in Pregnancy

Hepatocellular Adenomas
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  • US monitoring of HCAs during each trimester of pregnancy and up to 3 months postpartum is reasonable.
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  • Pregnancy in women with HCAs less than 5 cm in diameter is not contraindicated.
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  • 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.
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Hepatic Hemangiomas
Hepatic hemangiomas, regardless of size, do not require monitoring during pregnancy, but new onset of symptoms should prompt investigation.
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Focal Nodular Hyperplasia
Focal nodular hyperplasia, regardless of size, does not require monitoring.

Budd‐Chiari Syndrome

Doppler US is the imaging modality of choice for diagnosing BCS.
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Treatment of acute BCS is the same as in nonpregnant patients with the exception of more limited choices of anticoagulation and insufficient safety data to endorse thrombolytic therapy in pregnancy.
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Low‐molecular‐weight heparin is the anticoagulant of choice during pregnancy and lactation in women with BCS.
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Vitamin K antagonists are contraindicated during pregnancy but acceptable during breastfeeding.
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Gallstone Disease in Pregnancy

US is the imaging modality of choice for suspected gallstone disease in pregnancy.
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Initial management of gallstone disease in pregnancy is supportive, although ERCP and laparoscopic cholecystectomy can be considered, ideally in the second trimester.
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If ERCP is required, fetal radiation should be minimized by reducing fluoroscopy time and shielding the fetus with lead shields placed on the pelvis and lower abdomen.
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Acute Viral Hepatitis

Acute viral hepatitis in pregnancy warrants closer monitoring for maternal and fetal complications, especially for acute hepattis E virus (HEV) and herpes simplex virus (HSV) infections.
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Management is supportive, and use of specific antiviral therapy should be guided by safety of the drugs in pregnancy.
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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.
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Pregnancy in the Patient With Cirrhosis

Management of  portal hypertension (PHT) in Pregnancy

Endoscopic procedures require preoperative consultation with maternal-fetal medicine specialist (MFM) specialists to coordinate fetal monitoring and maternal sedation.
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In women with cirrhosis, prepregnancy endoscopic variceal screening is recommended. Screening in the early second trimester is indicated if not performed within 1 year before conception or if there is ongoing liver injury or decompensation occurs.
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Meperidine, midazolam, propofol, and fentanyl may be used in pregnancy, with efforts to minimize the duration of anesthesia.
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For pregnant women with small GEV, primary prophylaxis using NSBBs should be considered.
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For pregnant women with medium or large GEV, primary prophylaxis using band ligation or NSBBs is recommended. Propranolol is the preferred NSBB.
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For pregnant women with acute variceal hemorrhage, standard therapy with octreotide or somatostatin, proton pump inhibitors, antibiotic therapy with cephalosporins, and endoscopy are recommended. Terlipressin should be avoided.
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Mode of delivery should be guided only by obstetric indications.
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Liver Diseases Unique to Pregnancy and Their Management

Hyperemesis Gravidarum

Treatment of hyperemesis gravidarum is supportive with rehydration, correction of electrolyte abnormalities, thiamine supplementation, and anti‐emetic therapy.
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Liver chemistry abnormalities typically resolve with hydration and resolution of vomiting. Persistent liver chemistry abnormalities, despite symptom resolution, should prompt investigation for another etiology.
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Intrahepatic Cholestasis of Pregnancy

Pruritus presenting in the second or third trimester plus total bile acids >10 μmol/L without other causes of pruritus is diagnostic for ICP. Elevation of AST and ALT are frequent but not required for the diagnosis.
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Women with ICP should be tested for HCV, if not previously performed.
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Pruritus management is multifaceted and includes UDCA (10‐15 mg/kg) as first‐line therapy. For refractory symptoms, antihistamines, cholestyramine, rifampin, and SAMe may be considered, although the evidence is scant.
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UDCA is safe in pregnancy and reduces serum bile acid levels, although data supporting a benefit in reducing fetal risks, including IUFD, are lacking.
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Vitamin K should be supplemented when PT is prolonged. More frequent monitoring of PT may be considered for women on cholestyramine.
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Women with persistent symptoms or elevated liver tests or total bile acids postpartum should be evaluated for other causes of chronic liver diseases, including genetic variants associated with cholestasis.
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Hypertensive Diseases of Pregnancy

In women with preeclampsia, delivery by 37 weeks is advised, with close monitoring for the development of eclampsia and HELLP syndrome.
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When HELLP syndrome or eclampsia are suspected, expeditious delivery is recommended after maternal stabilization.
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Abdominal imaging should be performed in suspected HELLP to rule out hepatic hemorrhage, infarct, or rupture.
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HELLP complicated by hepatic rupture or ALF should prompt transfer to a transplant center for evaluation.
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Acute Fatty Liver of Pregnancy

When AFLP is suspected, expeditious delivery is recommended after maternal stabilization.
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Diagnosis of AFLP can be made on clinical and laboratory parameters, and liver biopsy is rarely required.
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Abdominal imaging should be performed in AFLP to rule out hepatic hemorrhage, infarct or rupture, and presence of hepatic rupture or ALF should prompt transfer to a transplant center for evaluation.
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All newborns of mothers with AFLP should be screened at birth for long‐chain 3‐hydroxyacyl‐CoA dehydrogenase deficiency or other fatty acid oxidation defects; referral to genetic counseling is indicated for affected families.
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Reproductive Health and Pregnancy in Transplant Recipients

Mycophenolic acid products are contraindicated in pregnancy and lactation, and contraceptive agents with low failure rates should be used.
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Pregnancy should be delayed until at least 1 year after transplant and with greater than or equal to 6 months of stable graft function.
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CNIs, azathioprine/6‐MP, and corticosteroids are acceptable for use in pregnancy and lactation.
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mTORs are not recommended in pregnancy or lactation due to lack of safety data.
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CNI trough levels should be obtained every 2‐4 weeks during pregnancy, with dosing guided by levels and liver tests.
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More frequent monitoring of graft function during pregnancy and in the postpartum period is recommended.
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Mode of delivery should be guided only by obstetric indications.
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Recommendation Grading

Overview

Title

Reproductive Health and Liver Disease

Authoring Organization

American Association for the Study of Liver Diseases

Publication Month/Year

September 17, 2020

Last Updated Month/Year

August 30, 2024

Supplemental Implementation Tools

Document Type

Guideline

External Publication Status

Published

Country of Publication

US

Document Objectives

This first Practice Guidance on Reproductive Health from the American Association for the Study of Liver Diseases (AASLD) is intended to be a comprehensive reference on adolescents and adults with chronic liver disease. The Guidance specifically (1) addresses management of reproductive health in women and men from puberty to senescence and (2) summarizes the natural history, risk factors, evaluation, and optimal management of liver diseases during pregnancy and after birth.

Inclusion Criteria

Female, Male, Adolescent, Adult

Health Care Settings

Ambulatory

Intended Users

Nurse, nurse practitioner, physician, physician assistant

Scope

Assessment and screening, Management

Diseases/Conditions (MeSH)

D008107 - Liver Diseases, D060728 - Reproductive Health, D016031 - Liver Transplantation

Keywords

Reproductive Health, liver 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.