Liver disease in pregnancy

Table 1 Features of pregnancy-associated liver diseases

Disease	Timing of occurrence	Clinical features	Histology
Hyperemesis gravidarum	First trimester	Nausea, vomiting, weight loss, nutritional deficiency	No distinct histopathology, may see normal tissue or hepatocyte necrosis, bile plugs, steatosis
Preeclampsia/eclampsia	Second/third trimester	Hypertension, edema, proteinuria, neurological deficits (headaches, seizures, coma)	Periportal hemorrhage, necrosis, fibrin deposits, may see microvesicular fat
Syndrome of hemolysis, elevated liver tests, and low platelets (HELLP)	Third trimester	Abdominal pain, nausea, vomiting, edema, hypertension, proteinuria	Necrosis, periportal hemorrhage, fibrin deposits
Acute fatty liver of pregnancy (AFLP)	Third trimester	Nausea, vomiting, abdominal pain, fatigue, jaundice	Microvesicular fat
Intrahepatic cholestasis of pregnancy (ICP)	Second/third trimester	Pruritus, jaundice, fatigue, abdominal pain, steatorrhea	Centrilobular cholestasis, no inflammation

Table 2 Safety of drugs used in pregnancy-associated liver diseases

Drug	FDA pregnancy category	Comments
Antiemetics
Promethazine	C	Possible respiratory depression if drug is administered near time of delivery
Metoclopramide	B	Available evidence suggests safe use during pregnancy
Ondansetron	B	Additional studies are needed to determine safety to the fetus, particularly during the first trimester
Prochlorperazine	C	There are isolated reports of congenital anomalies; however, some included exposures to other drugs. Jaundice, extrapyramidal signs, hyper-/hyporeflexes have been noted in newborns
Antihypertensives
ACE inhibitors	C/D	First trimester exposure to ACE inhibitors may cause major congenital malformations
		Second and third trimester use of an ACE inhibitor is associated with oligohydramnios and anuria, hypotension, renal failure, skull hypoplasia, and death in the fetus/neonate
Beta blockers	C/D	Fetal bradycardia, hypotension, risk of intrauterine growth retardation
Calcium channel blockers	C	Teratogenic and embryotoxic effects have been demonstrated in small animals. There are no adequate and well-controlled studies in pregnant women
Anticoagulation
Aspirin	C (1st/2nd trimesters) D (3rd trimester)	Adverse effects in the fetus include intrauterine growth retardation, salicylate intoxication, bleeding abnormalities, and neonatal acidosis. Use of aspirin close to delivery may cause premature closure of the ductus arteriosus. Data have shown low-dose aspirin (60-150 mg/day) may be safe in pregnancy
Enoxaparin	B	No adequate and well-controlled studies using enoxaparin. Postmarketing reports include congenital abnormalities and also fetal death
Heparin	C	Does not cross the placenta
Intrahepatic cholestasis
Ursodeoxycholic acid	B	Relatively low risk
S-adenosyl-L-methionine	Not evaluated by FDA	Relatively low risk
Cholestyramine	C	Cholestyramine is not absorbed systemically, but may interfere with vitamin absorption

United States Food and Drug Administration (FDA) pregnancy categories: Category A: Well-controlled studies failed to show a risk to the fetus in the first trimester of pregnancy (and there is no evidence of risk in the second or third trimesters). Category B: Animal reproduction studies failed to show a risk to the fetus, and there are no adequate studies in pregnant women. Category C: Animal reproduction studies have shown an adverse effect on the fetus. There are no adequate studies in humans, but potential benefits may warrant use of the drug in pregnant women despite potential risks. Category D: There is evidence of human fetal risk based on data from investigational or marketing experience or studies in humans. However, the potential benefits may warrant use of the drug in pregnant women despite potential risks. Category X: Data have demonstrated fetal abnormalities in animals and humans, and/or there is positive evidence of human fetal risk based on data from investigational or marketing experience. The risks of the use of the drug in pregnant women outweigh potential benefits.