Liver disease in Pregnancy

Discuss liver disease in pregnancy?

Abnormal liver tests occur in 3%-5% of pregnancies. The potential causes are:

  • Liver disease coincidental to Pregnancy (viral hepatitis, autoimmune hepatitis etc)
  • Underlying Chronic Liver Disease
  • Diseases Unique to Pregnancy

Most liver dysfunction in pregnancy is pregnancy-related and is due to one of the following 5 liver diseases:

  • Hyperemesis gravidarum (HG)
  • Intrahepatic cholestasis of pregnancy (ICP)
  • Preeclampsia,
  • HELLP syndrome
  • Acute fatty liver of pregnancy (AFLP).

Each of them has a characteristic timing: HG occurs in the first trimester, ICP in the second half of pregnancy, and the other 3 in the third trimester.

Discuss Hyperemesis Gravidarum (HG)?

HG is intractable vomiting in the 1st trimester of pregnancy (typically 4-10 weeks).
Liver dysfunction occurs in 50% patients with aminotransferases up to 20-fold elevation and with occasional jaundice.
Exclude other causes of raised aminotransferases
Treatment is supportive.

Discuss Intrahepatic Cholestasis of Pregnancy (ICP)?

  • ICP is defined as pruritus and elevated bile acid (BA) levels which appear in the second half of pregnancy (typically 25-32 weeks) and disappear after delivery, typically to recur in subsequent pregnancies.
  • The most specific and sensitive marker of ICP is serum BA levels of greater than 10 umol/L; however the test is not routinely available.
  • Aminotransferases levels are elevated and may reach values greater than 1000 IU/l; bilirubin is usually less than 100umol/l.
  • Alkaline phosphatase will be elevated though diagnostically unhelpful in pregnancy (due to placental isoenzyme); mildly elevated levels of GGT are found in fewer than 30% cases. This is unusual as in most other forms of cholestatic liver disease; GGT levels parallel other cholestatic markers.
  • Management
    • Ursodeoxycholic acid (10-15mg/kg) is the treatment of choice for relief of pruritus with improvement in liver tests and with no adverse maternal or foetal effects.
    • The main risk in ICP is to the foetus and necessitates referral to a high-risk obstetrician. Foetal monitoring for chronic placental insufficiency is essential. Foetal complications in ICP are placental insufficiency, premature labour, and sudden foetal death, probably due to elevated foetal levels of BA.
    • Adverse foetal outcome can be prevented only by delivery as soon as the foetal lungs are mature.
  • ICP resolves with foetal delivery to recur in 45%-70% of subsequent pregnancies
  • and occasionally with oral contraceptives.

Discuss Preeclampsia?

  • Preeclampsia is the triad of hypertension, edema, and proteinuria in the third trimester.
  • Liver involvement indicates severe preeclampsia with significant perinatal morbidity and mortality
  • Aminotransferases are variable from mild to 10-fold to 20-fold elevations; bilirubin is usually less than 100umol/l.
  • Its only significance is that hepatic involvement in pre eclampsia indicates severe disease with need for immediate delivery to avoid eclampsia, hepatic rupture, or necrosis.

Discuss HELLP Syndrome?

  • HELLP syndrome is a triad of haemolysis (H) with a microangiopathic blood smear, elevated liver enzymes (EL), and a low platelet count (LP). The syndrome probably represents a severe form of preeclampsia, however this is controversial and 15 to 20 percent of affected patients do not have antecedent hypertension or proteinuria.
  • Most patients present between 27 and 36 weeks’ gestation, but 25% in postpartum period. The most common clinical presentation is abdominal pain and tenderness. Many patients also have nausea, vomiting, and malaise. Hypertension and proteinuria are present in approximately 85 percent of cases. Jaundice is uncommon
  • Diagnosis requires the presence of all 3 laboratory criteria: (1) haemolysis (elevated indirect bilirubin, LDH>600U/L, abnormal blood smear, (2) elevated aminotransferases (AST >70U/L), and (3) thrombocytopenia (<150,000)
  • Aminotransferase elevation is variable, from mild to 10- fold to 20-fold, and bilirubin is usually less than 100umol/l.
  • Delivery is the only definitive therapy.
  • Most patients have rapid, early resolution of HELLP after delivery with normalization of platelets by 5 days.
  • The outcome for mothers with HELLP syndrome is generally good, but serious complications such as abruptio placentae, acute renal failure, subcapsular liver hematoma, and retinal detachment may occur.
  • The risk of recurrence in future pregnancies appears to be increased.

Discuss Acute Fatty Liver of Pregnancy (AFLP)

  • AFLP is a sudden catastrophic illness characterised by microvesicular fatty infiltration, occurring almost exclusively in the third trimester from 28 to 40 weeks, rarely in late second trimester.
  • The presentation can vary from asymptomatic to fulminant liver failure. The most frequent symptoms are nausea, vomiting, anorexia, abdominal pain and jaundice. About 50% of patients with AFLP have preeclampsia, and there is some overlap with the HELLP syndrome.
  • In AFLP, aminotransferases vary from near-normal to 1000; bilirubin is usually also elevated. Severely affected patients also have coagulopathy with or without DIC, metabolic acidosis, renal dysfunction, hypoglycaemia and high ammonia.
  • The main differential diagnosis of AFLP is HELLP. It may be impossible to differentiate them. However, evidence of hepatic insufficiency such as hypoglycaemia or encephalopathy is suggestive of AFLP.
  • Early recognition and diagnosis of AFLP with immediate termination of pregnancy and intensive supportive care is essential for both maternal and foetal survival. There are no reports of recovery before delivery.
  • Most patients improve rapidly after delivery. However, AFLP still carries significant perinatal (9-23%) and maternal mortality (7-18%)
  • AFLP can recur in subsequent pregnancies


  1. Hay JE. Liver Disease in Pregnancy. Hepatology. 2008 Mar; 47(3):1067-76. (Archived copy at Webcite)

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