You are in: eMedicine Specialties > Gastroenterology > Liver Liver Disease and PregnancyArticle Last Updated: Jan 16, 2008AUTHOR AND EDITOR INFORMATIONSection 1 of 10
  Author: Praveen K Roy, MD, Assistant Professor of Medicine, Associate Director of Research, Division of Gastroenterology, Department of Internal Medicine, University of Missouri at Columbia; Chief of Gastroenterology, Harry Truman Veteran Affairs Memorial Hospital Praveen K Roy is a member of the following medical societies: American College of Gastroenterology, American Gastroenterological Association, and Canadian Association of Gastroenterology Coauthor(s): Angela G Bradley, MD, Staff Physician, Department of Internal Medicine, Mayo Clinic Scottsdale; Mohamed Othman, MD, Staff Physician, Department of Internal Medicine, University of New Mexico School of Medicine; Jack Bragg, DO, FACOI, Assistant Professor, Department of Clinical Medicine, University of Missouri School of Medicine; Gautam Dehadrai, MD, Consulting Staff, Section Chief, Department of Interventional Radiology, Veterans Affairs Medical Center, Albuquerque Editors: Ann Ouyang, MBBS, Professor, Department of Internal Medicine, Pennsylvania State University College of Medicine; Chief, Division of Gastroenterology and Hepatology, Milton S Hershey Medical Center; Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine; BS Anand, MD, Department of Internal Medicine, Division of Gastroenterology, Professor, Baylor University College of Medicine; Alex J Mechaber, MD, FACP, Assistant Dean for Medical Curriculum, Associate Professor of Medicine, Division of General Internal Medicine, University of Miami Miller School of Medicine; David Chelmow, MD, Professor of Obstetrics and Gynecology, Tufts University School of Medicine; Program Director, Tufts University Affiliated Hospitals OB/GYN Residency Program; Chair, Tufts University Health Sciences Campus Institutional Review Board Author and Editor Disclosure Synonyms and related keywords: acute fatty liver, acute fatty liver of pregnancy, AFLP, intrahepatic cholestasis, IHC, intrahepatic cholestasis of pregnancy, ICP, hemolysis and elevated liver enzymes and low platelets syndrome, HELLP syndrome, hepatic rupture, portal hypertension, viral hepatitis, Budd-Chiari syndrome, BCS INTRODUCTIONSection 2 of 10
  Liver disease that occurs during pregnancy can present a challenge for health care providers. Certain liver diseases are uniquely associated with pregnancy, whereas others are unrelated. The liver diseases unique to pregnancy are discussed in this article. ACUTE FATTY LIVERSection 3 of 10
The prevalence of acute fatty liver of pregnancy (AFLP) is 1 per 7000-16,000 pregnancies. The condition manifests in the second half of pregnancy, usually close to term, but may also develop in the postpartum period. Typically, diagnosis is made based on an incidental finding of abnormal liver enzyme levels. Symptoms Symptoms include nausea, vomiting, lethargy, abdominal pain, jaundice, bleeding, and mental status changes. Transient polyuria and polydipsia may also occur. Acute renal failure occurs in 60% of patients. Diagnosis Serum aminotransferase levels are usually only moderately elevated (typically <500 U/L). Mild neutrophilia, as well as hyperglycemia and elevated ammonia levels, may be noted. Treatment The primary treatment is prompt delivery of the fetus with supportive measures to stabilize the mother. Prognosis The maternal mortality rate is low, and the prognosis is good. Risk factors Acute fatty liver can recur in subsequent pregnancies. The incidence of acute fatty liver of pregnancy is increased in mothers who carry a fetus deficient in the liver isoform of carnitine palmitoyltransferase (L-CPT I). Affected mothers and their newborn infants should be assessed. Studies have revealed a higher incidence of AFLP in women who (1) have a genetic mutation that affects their mitochondrial fatty acid oxidation pathway and (2) carry a fetus with a long-chain 3-hydroxyacyl-coenzyme A dehydrogenase (LCHAD) deficiency. This deficiency is associated with a higher mortality rate in affected children; therefore, affected mothers and their newborn infants should be assessed for this deficiency. INTRAHEPATIC CHOLESTASIS OF PREGNANCYSection 4 of 10
Intrahepatic cholestasis of pregnancy (ICP) is a benign disorder that occurs in the second or third trimester and resolves spontaneously after delivery. Prevalence varies among countries. Intrahepatic cholestasis of pregnancy is common in The etiology is unknown but may be multifactorial. Possible causes include genetic abnormalities, increased hormonal exposure, decreased sulfotransferase activity, and endogenous opioids. Intrahepatic cholestasis of pregnancy has been found more frequently in certain ethnic groups, suggesting that genetic factors are involved. Recurrent familial intrahepatic cholestasis of pregnancy has been described as a heritable defect of the MDR3 gene, which encodes for a canalicular phospholipid translocator involved in bile duct secretion of phospholipids. The incidence of intrahepatic cholestasis of pregnancy is highest during the third trimester, when estrogen levels peak. Formation of large amounts of sulfated progesterone metabolites results in saturation of the hepatic transport system used for biliary excretion. Symptoms Generalized pruritus is the main symptom of intrahepatic cholastasis of pregnancy. The itching may be more intense over the palms and sole but can extend to the trunk, extremities, eyelids, and, in rare cases, the oral cavity. The pruritus is worse at night. Jaundice is uncommon (10-25%); when it occurs, jaundice follows the onset of pruritus. Differential Diagnosis
Serology findings may exclude autoimmune hepatitis and viral hepatitis. In addition, the absence of anti-mitochondrial antibody excludes primary biliary cirrhosis. Patients with cholangitis and choledocholithiasis may also present with pruritus. However, the absence of fever, abdominal pain, or dilated common bile duct makes these diagnoses unlikely. The serum bilirubin level is usually lower than 6 times the upper limit of reference range and is usually conjugated. Fever is rare. Steatorrhea may be present, which may lead to deficiency of fat-soluble vitamins, especially vitamin K. Aminotransferase levels are less than 1000 U/L, which distinguishes intrahepatic cholestasis (IHC) from viral hepatitis. Alkaline phosphatase is 4 times higher than the reference range (44-147 U/L). Interestingly, gamma-glutamyl transpeptidase levels are within the reference range or only mildly elevated. Liver biopsy is rarely needed for diagnosis but reveals cholestasis with minimal hepatocellular necrosis. Treatment Medical treatment is directed at relieving maternal symptoms and improving fetal outcome. Pruritus can be controlled with antihistamines, benzodiazepines, low-dose phenobarbital, dexamethasone, S-adenosyl-L-methionine, and ursodeoxycholic acid. Fetal outcome is improved with early diagnosis and prompt treatment. Prognosis Long-term maternal outcome is good. Intense pruritus can cause severe fatigue and distress for the mother. Anorexia, nausea, vomiting, and poor weight gain can occur. The risk of postpartum cholelithiasis is increased, as is the risk of postpartum hemorrhage. The risk of fetal prematurity is increased 3-fold, and the risk of meconium-stained amniotic fluid is increased 1.5-fold. Fetal distress is also an increased risk. In addition, abnormal fetal heart patterns can occur. HEMOLYSIS, ELEVATED LIVER ENZYMES, AND LOW PLATELETS SYNDROMESection 5 of 10
The combination of hemolysis, elevated liver enzymes, and low platelets (HELLP syndrome) is a severe form of preeclampsia that can occur at any point, from the middle of the second trimester to the immediate postpartum period (usually within 2 days of delivery). HELLP syndrome occurs in 0.2-0.6% of pregnancies. Women who are white, multiparous, and older than 25 years carry an increased risk. Etiology The etiology is unknown, although abnormal vascular tone, vasospasm, and long-chain 3-hydroxyacyl-coenzyme A dehydrogenase (LCHAD) deficiency in the infant are thought to be involved. Symptoms Symptoms and signs are nonspecific and include the following:
Diagnosis In patients within the appropriate gestational period, the presence of laboratory abnormalities confirms the diagnosis. Laboratory abnormalities include the following:
Differential diagnoses
Treatment The obstetrician should guide therapy. Delivery of the fetus is indicated in the presence of maternal or fetal distress. Supportive therapy includes volume replacement, blood pressure control with antihypertensive medication (eg, hydralazine [Apresoline]), and bed rest. The benefit of prepartum or postpartum corticosteroid use remains unclear. Prognosis Maternal outcome is generally good and independent of liver involvement; however, patients are at increased risk of complications such as abruptio placentae (16%), acute renal failure (8%), subcapsular hematoma (1%), and retinal detachment (1%). The infant mortality rate is 10-60%. Infants carry an increased risk of prematurity, intrauterine growth retardation, disseminated intravascular coagulation, and thrombocytopenia. HEPATIC RUPTURESection 6 of 10
Although the exact occurrence is unknown, hepatic rupture is estimated to occur in 1 per 100,000 pregnancies. Most instances of hepatic rupture are associated with preeclampsia or eclampsia. Hepatic rupture can also occur in combination with acute fatty liver disease, HELLP syndrome, hepatocellular carcinoma, hepatic adenoma, hemangioma, and hepatic abscess. The right lobe of the liver is involved more often than the left lobe. Hepatic rupture usually occurs in the late third trimester or within 24 hours of delivery. Symptoms Symptoms include acute abdominal pain, nausea, vomiting, hypovolemic shock, and abdominal distension. Diagnosis Abdominal ultrasonography, CT scanning, MRI, and angiography can be used to confirm the diagnosis. Differential diagnosis
MRI evaluation and history of penetrating trauma can differentiate aortic dissection from diaphragmatic trauma, respectively. Infectious processes are excluded because of the insidious course of these diseases and the absence of fever and leukocytosis. Treatment Treatment consists of early recognition and prompt surgical or radiologic intervention. Prognosis Maternal and fetal mortality rates are high (50-75%). PORTAL HYPERTENSIONSection 7 of 10
Limited data have been found concerning the outcome of pregnancy in patients with liver cirrhosis. The prevalence of fetal wastage is 9.6-66%, and the spontaneous abortion rate in patients with cirrhosis is 15-20%. The spontaneous abortion rate is lower in patients with compensated liver cirrhosis. Most spontaneous abortions occur in the first trimester. Perinatal mortality is increased in patients with cirrhosis or portal hypertension, with rates ranging from 11-18%. Etiology During pregnancy, the intravascular volume increases, which is a physiologic response to the fetus's additional blood flow requirements. In response to the portal hypertension, varices develop to decompress the portal system and shunt the blood into the systemic circulation. When variceal bleeding occurs, placental perfusion decreases, which can result in ischemic events such as cerebral palsy or stroke. Therefore, obliteration of esophageal varices before conception improves fetal outcome. Symptoms Variceal hemorrhage, hepatic failure, hepatic encephalopathy, postpartum hemorrhage, rupture of splenorenal shunts, spontaneous bacterial peritonitis, and maternal death can occur in pregnant patients with portal hypertension. Variceal hemorrhage occurs in 19-45% of patients, manifesting in the second trimester or during labor. Up to 78% of patients with esophageal varices bleed during labor, and maternal mortality is increased with variceal bleeding. Postpartum hemorrhage occurs in 7-26% of patients. Differential diagnosis
Treatment A team of doctors (ie, obstetrician, hepatologist, perinatologist) should treat pregnant patients with portal hypertension. Preconception counseling should be offered, along with discussion of potential risks to the mother and fetus. Esophageal varices should be sought, and, if present, primary prophylaxis should be offered. Consider endoscopic obliteration of the varices if the patient is unable to tolerate oral beta-blockers or in the presence of medium or large esophageal varices. Patients should be screened for splenic artery aneurysms with abdominal ultrasonography and Doppler. During delivery, every attempt should be made to keep the second stage of labor short. Intravenous fluid overload should be avoided, and coagulation parameters should be monitored closely. VIRAL HEPATITISSection 8 of 10
Viral hepatitis can occur in any trimester. All hepatotropic viruses can infect the pregnant patient. Hepatitis A Hepatitis A virus infection occurs in 1 per 1000 pregnancies. The clinical course is similar to that in patients who are not pregnant. Intrauterine and perinatal transmission has been reported but is rare. Prevention with passive immune globulin is safe for both mother and fetus. Hepatitis B virus can be transmitted vertically from the mother to the child, leading to chronic infection in the child. Of perinatal transmissions, 95% occur intrapartum. The risk of transmission is 10-40% in mothers who are HBe antigen (HBeAg)–negative and 90% in mothers who are HBeAg-positive. Acute disease occurs in 2 per 1000 pregnancies. Acute disease is not severe during pregnancy. Chronic disease occurs in 5-15 per 1000 pregnancies. All pregnant patients should be tested for hepatitis B surface antigen (HBsAg) antepartum. Active and passive immunization is 85-95% effective in preventing transmission to neonates. Hepatitis C Hepatitis C virus infection does not affect the course of pregnancy unless cirrhosis is present. The risk of vertical transmission is low (<10%). Vertical transmission is more likely to occur in patients who are co-infected with human immunodeficiency virus (HIV) and in those with high maternal viral titers (>1 million copies/mL). Hepatitis D Hepatitis D virus infection occurs in conjunction with hepatitis B virus infection. Vertical transmission is rare. Control of hepatitis B virus can help prevent spread. Hepatitis E Hepatitis E virus infection is rare in the
These conditions can present with elevated aminotransferase levels. However, laboratory tests and clinical features specific to each disease can exclude these diagnoses. BUDD-CHIARI SYNDROMESection 9 of 10
Etiology In Budd-Chiari syndrome, 20% of cases are associated with pregnancy and contraceptives. Symptoms Symptoms are usually acute, and patients present with abdominal pain, hepatomegaly, and ascites. Differential Diagnosis
Fulminant hepatic failure resembles acute Budd-Chiari syndrome but progresses more rapidly. Consider Budd-Chiari in the differential diagnosis of suspected veno-occlusive disease, which is observed most commonly after hematopoietic cell transplantation. Diagnosis Ultrasonography, MRI, or liver biopsy can be used to confirm the diagnosis. The maternal mortality rate is as high as 70% in those who present with an acute onset during pregnancy. Cirrhosis and portal hypertension also have some clinical similarities to Budd-Chiari syndrome. Laboratory and clinical findings can be used to differentiate these conditions. Cirrhosis reveals stigmata of chronic liver disease and only moderately elevated aminotransferase levels. The absence of thrombosis of the hepatic vein or inferior vena cava on ultrasonographic imaging excludes Budd-Chiari syndrome. Treatment Treatment is similar to that for women who are not pregnant. REFERENCESSection 10 of 10
Liver Disease and Pregnancy excerpt Article Last Updated: Jan 16, 2008 |
