Liver disease in pregnancy

Liver Disease In Pregnancy

I. Problem/Condition.

Development of physical exam findings associated with liver disease and changes in liver biochemical profile are normal in pregnancy. These normal changes include development of spider angiomas and palmar erythema with decrease in albumin and increase in alkaline phosphatase. Although any liver disease can occur during pregnancy, several liver disorders are unique to the pregnant patient. These liver disorders include hyperemesis gravidarum, intrahepatic cholestasis of pregnancy, pre-eclampsia/eclampsia, HELLP (hemolysis, elevated liver enzymes, low platelets) syndrome, and acute fatty liver of pregnancy.

Liver diseases unique to pregnancy are estimated to complicate 3% of all pregnancies. Although rare, HELLP and acute fatty liver of pregnancy are severe diseases necessitating early recognition and intervention due to significant morbidity and accounting for 18% maternal and 23% fetal mortality.

II. Diagnostic Approach.

A. What is the differential diagnosis for this problem?

Any pregnant patient who has abnormal liver enzymes not associated with normal pregnancy such as elevation in alanine aminotransferase, aspartate aminotransferase, or bilirubin should undergo evaluation. The differential diagnoses for these pregnancy associated liver disorders include non-alcoholic steatohepatitis, acute or chronic viral hepatitis, drug or toxin mediated hepatitis, autoimmune hepatitis, Wilson’s disease, Budd-Chiari syndrome, and biliary disease.

B. Describe a diagnostic approach/method to the patient with this problem.

The first in step differentiating these liver disorders unique to pregnancy is identification of the trimester of pregnancy.

Hyperemesis gravidarum typically occurs in patients in the first or second trimester of pregnancy. Liver involvement in this illness usually manifest as elevated aminotransferases. The laboratory abnormalities resolve when the vomiting symptoms from the hyperemesis gravidarum also resolve.

Intrahepatic cholestasis of pregnancy is a reversible condition that typically occurs in the second to third trimester. The diagnostic laboratory abnormality is an elevated serum bilirubin. Pre-eclampsia and eclampsia causing elevation in aminotransferases or hepatic rupture or infarction can occur during the third trimester. Patients typically have other symptoms which classically define preeclampsia and eclampsia: hypertension and proteinuria.

HELLP and acute fatty liver of pregnancy are considered to be illnesses on a continuum with preeclampsia and eclampsia. HELLP syndrome is a variant of severe preeclampsia that occurs in up to 12% of patients with preeclampsia. However, one does not have to have preeclampsia or eclampsia to have either HELLP or acute fatty liver of pregnancy. The classic symptoms that are also associated with HELLP are evidence of hemolysis and low platelets. Unlike the other liver disorders unique to pregnancy, acute fatty liver of pregnancy is a common cause of liver failure in pregnancy and is a medical and obstetric emergency.

Patients being considered to have one of the above disorders should undergo an extensive drug and toxin history to rule out this as cause of liver enzyme abnormality. Laboratory studies should evaluate for acute or chronic viral hepatitis. Ultrasound of the liver and biliary tree with doppler evaluation should be done to evaluate for biliary disease or venous obstruction. If no etiology is defined after this initial evaluation, serologies to evaluate for autoimmune hepatitis or Wilson’s disease should be considered. Ultimately, a liver biopsy can also be considered.

1. Historical information important in the diagnosis of this problem.

The history should investigate for any exposures to new drugs, toxins, or risk factors for hepatitis such as travel, unprotected intercourse, intravenous (IV) drug use, and blood transfusions. Also, past medical history and family history review should investigate for other liver disorders that are a part of the differential diagnoses. Risk factors for the liver diseases specific to pregnancy are variable but special attention should be paid to complications noted in patient’s prior pregnancies.

2. Physical Examination maneuvers that are likely to be useful in diagnosing the cause of this problem.

N/A

3. Laboratory, radiographic and other tests that are likely to be useful in diagnosing the cause of this problem.

Laboratory workup includes an acute hepatitis viral panel as well as lab to fulfill diagnostic criteria for these unique liver disorders. A right upper quadrant ultrasound is required to rule out biliary disease or thrombosis.

C. Criteria for Diagnosing Each Diagnosis in the Method Above.

Hyperemesis Gravidarum is considered a diagnosis when pregnant patients have intractable nausea and vomiting that results in dehydration, weight loss, and ketosis. Serum aminotransferases can be raised up to 20 times the upper limits of normal without significant elevation of bilirubin. Other electrolyte abnormalities can occur secondary to vomiting and malnutrition such as hypokalemia, hypophosphatemia, hypomagnesemia. In addition, hyperthyroidism can be an associated problem in more than half of patients. There are no specific abdominal ultrasound findings. Associated fulminant hepatic failure has never been reported.

Intrahepatic cholestasis of pregnancy should be considered as a diagnosis if patients are in their second trimester of pregnancy, complaining of pruritus, and have elevated bilirubin and aminotransferases. Pruritis especially occurs at night and often involves the palms and soles. Aminotransferases may be elevated 2-10 fold. Alkaline phosphatase levels may not be helpful due to higher physiological levels in late pregnancy, however, an elevated fasting serum bile acids level (> 10 micromole/L [μmol/L]) confirms the diagnosis.

HELLP is the combination of microangiopathic hemolysis, increased liver enzymes, and low platelets. Laboratory evaluation will show thrombocytopenia and anemia with elevated LDH and low haptoglobin. Peripheral blood smear will show schistocytes. Liver enzyme abnormalities are usually a mild to moderation elevation in amiotransferases and only slight increase in bilirubin levels. The Mississippi Triple-class HELLP System further classifies the severity of the disorder as shown by the diagnostic criteria in Table 1. Class 1 is defined by severe thrombocytopenia (platelets ≤50,000/micromole [μmol]), evidence of hepatic dysfunction (AST and/or ALT ≥70 units/Liter [U/L]), and evidence suggestive of hemolysis (LDH ≥600 U/L). Class 2 requires similar criteria except thrombocytopenia is moderate (>50,000 to ≤100,000/μL). Class 3 includes patients with mild thrombocytopenia (platelets >100,000 but ≤150,000/μL), mild hepatic dysfunction (AST and/or ALT ≥40 U/L), and hemolysis (LDH ≥600 U/L).