Elevated serum alkaline phosphatase • generalized pruritus • Dx?

DISCUSSION

PBC, historically known as primary biliary cirrhosis, is a chronic, likely immune-mediated, cholestatic liver disease characterized by the progressive inflammatory destruction of intrahepatic bile ducts. The disease has a female to male predominance of 10:1, with age of diagnosis most often between 40 and 50 years, although about a quarter of female patients present during their reproductive years.^1,2

PBC in pregnant women

During pregnancy, the profound physiologic changes and adaptations in the endocrine, metabolic, and immune systems that are necessary for normal fetal development can affect the maternal hepatobiliary system. In patients with prior autoimmune liver disease, the liver is known to adapt itself to these physiologic changes by entering a state of immune tolerance. This is induced by relative hypercortisolism, a shift from predominantly cell-mediated immunity to humoral immunity, and inhibition of T-cell activation. These changes can result in remission of autoimmune disease activity during pregnancy and postpartum flaring when these protective mechanisms are lost (although neither remission nor postpartum flaring occurred in this patient’s case).^1-3

While a well-compensated state is associated with better fetal and maternal outcomes than a decompensated condition, cirrhosis is not a contraindication to pregnancy. Vaginal delivery is generally safe for patients with PBC, and studies have reported no childbirth complications or adverse maternal outcomes.^1,3,4

The approved treatment for PBC, ursodeoxycholic acid (UDCA), was classified as a category B agent according to the Food and Drug Administration’s now defunct classification system for drugs used during pregnancy and lactation. It’s considered to be the treatment of choice for intrahepatic cholestasis of pregnancy, but there are no recommendations for its use in pregnant patients with PBC. Several studies have observed no significant teratogenic effect in babies whose mothers were treated with UDCA for PBC during pregnancy.^1-4 Postpartum, 60% to 70% of PBC patients have been reported to exhibit biochemical disease activity,^1,3 and in one case, a liver transplant was required due to liver failure.⁵

Look for AMA, elevated ALP

The diagnosis of the disease in this case was made by the detection of AMA, which has a specificity of 98% for PBC. However, isolated instances of the presence of AMA are not uncommon; they have been documented in up to 64% of healthy individuals.⁶ In addition, while one would expect to see a 2- to 4-fold rise in ALP levels during pregnancy (due to placental isoenzyme production),^2,7 our patient’s serum ALP level was much higher, suggesting probable cholestatic liver disease such as PBC. The diagnosis in this case was confirmed by liver biopsy.

Our patient was started on UDCA 13 to 15 mg/kg/d. She remained clinically stable at subsequent follow-ups.

THE TAKEAWAY

Typically seen in middle-aged women, PBC can be detected by the presence of AMA and elevated ALP levels. Pregnant patients with chronic liver disease, including PBC, should be followed by a hepatologist and a high-risk obstetrician. They should be carefully monitored and frequently reassessed throughout the pregnancy, delivery, and postpartum period, even though studies have documented favorable outcomes for both mother and baby.^1,3,4