Liver Disease and Reproductive Health

Liver Disease and Reproductive Health

Summary of CME Lecture by Nancy Reau, MD

1. Main Clinical Topics Discussed

• Liver diseases unique to pregnancy (intrahepatic cholestasis of pregnancy [ICP], preeclampsia/HELLP spectrum)
• Chronic liver disease and its impact on reproductive health and fertility
• Normal physiologic hepatic changes in pregnancy and their diagnostic implications
• Contraception and fertility considerations in women with cirrhosis or advanced liver disease

2. Key Learning Points, Guidelines, and Recommendations

Guiding Documents

• AASLD Guidelines (2021) and EASL Guidelines (2023) are the two primary reference documents
• Both emphasize that pregnancy-induced liver disease must be distinguished from first presentation of chronic liver disease or coincidental acute hepatic conditions

Fertility and Reproductive Health in Liver Disease

• Advanced liver disease disrupts the hypothalamic-pituitary axis, causing altered estrogen metabolism, anovulation, and amenorrhea
• Fertility impairment scales with disease severity:

- ~25% of all women with advanced liver disease experience amenorrhea

- ~75% of women awaiting liver transplantation are amenorrhic

• Pregnancy can still occur even in decompensated cirrhosis — contraception counseling is essential
• Women with well-compensated cirrhosis often have normal estrogen metabolism and reproductive function
• Men with liver disease may experience erectile dysfunction, azoospermia, testicular atrophy, and feminization

Normal Lab Changes in Pregnancy

• Unchanged regardless of trimester: ALT, AST, GGT, bilirubin
• Increases: Alkaline phosphatase (placental origin), AFP
• Decreases: Albumin (dilutional)
• ⚠️ AFP is not a valid HCC screening tool during pregnancy
• Any abnormality in transaminases or bilirubin warrants further evaluation

3. Intrahepatic Cholestasis of Pregnancy (ICP)

Epidemiology and Diagnosis

• Most common pregnancy-specific liver disease
• 80% occur after 30 weeks gestation
• Risk factors: genetic predisposition, fertility treatments, hepatitis C, multiple gestations
• Pruritus precedes jaundice; jaundice alone is not the primary presenting feature
• Diagnostic test: fasting bile acids — ICP confirmed at >10 µmol/L

Outcome-Relevant Thresholds

• Adverse fetal outcomes begin at bile acids >40 µmol/L
• Stillbirth risk increases significantly at bile acids >100 µmol/L
• ALT/AST may be strikingly elevated (into the thousands) but do not correlate with fetal outcomes
• ⚠️ Draw bile acids in a non-fasting state — fasting levels may underestimate peak values and miss high-risk cases

Management

• Weekly bile acid monitoring after 32 weeks
• Ursodeoxycholic acid (UDCA): weight-based dosing initiated when bile acids approach 40 µmol/L

- Most effective in the 40–100 µmol/L range

- A meta-analysis of ~7,000 women confirmed UDCA reduces preterm birth but does not significantly reduce stillbirth

- Does not consistently relieve pruritus

• Pruritus management: antihistamines, cholestyramine; rifampin reduces bile acids in ~one-third of UDCA non-responders and relieves itching
• SAMe: Cochrane analysis did not support efficacy; occasional use persists
• Delivery timing: Previously standardized at 37 weeks; now more individualized based on bile acid levels per EASL 2023 — bile acids <100 µmol/L may allow extension toward 40 weeks
• Bile acids >100 µmol/L → prompt delivery indicated
• Investigational: IBAT inhibitor (maralixibat/volixibat class) — a small abstract (n=4) demonstrated bile