Pregnancy is a prothrombotic state, so you must exclude Budd-Chiari syndrome. Up to 20% of cases of Budd-Chiari syndrome occur in women who are on oral contraceptives or are pregnant or 2 months postpartum.5 Right upper quadrant pain, jaundice, and ascites are the common clinical features.
Gallstones are strongly associated with higher parity in women. Pre-pregnancy obesity and high serum leptin levels are strong risk factors for pregnancy-associated gallbladder disease. Gallbladder sludge and stones are common in pregnancy and the postpartum period, and cholecystectomy is frequently done within the first year postpartum.6 Serum alkaline phosphatase is less helpful in diagnosing cholecystitis in pregnancy because of elevated levels from the placenta.
With hepatitis, Budd-Chiari syndrome, and gallstones remaining in the differential, what other investigations would you pursue to narrow the differential?
A test for hepatitis A virus immunoglobulin M (IgM) proves negative. Hepatitis B surface antigen is negative, and hepatitis B surface antibody is 11.5 mIU/L, suggesting borderline protective level of antibody. Hepatitis C virus antibody also is negative. Hepatitis E occurs in the Indian subcontinent, Africa, and the Middle East, and is therefore unlikely in this patient. Serologies for cytomegalovirus IgG and Epstein-Barr virus IgM are negative. Herpes simplex type-1 specific IgG antibody is present. These serologic results exclude viral causes of hepatitis.
Antinuclear (ANA) and antimitochondrial antibodies are negative. Antismooth muscle antibody (ASMA) is positive at a titer of 1:20. Quantitative IgG is 7.23 g/L (normal, 5.52-17.24), IgA is 1.36 g/L (0.87-3.94), and IgM is 1.19 g/L (0.44-2.47). Negative ANA, weakly positive ASMA, and normal levels of immunoglobulins in our patient do not support a diagnosis of autoimmune liver disease.
Imaging is the next step for this patient. Even during pregnancy, ultrasound and magnetic resonance imaging are safe and readily available. The diagnostic accuracy of ultrasound for detecting gallstones is 95%. When ultrasound findings are equivocal in a pregnant patient, magnetic resonance cholangiopancreatography provides an accurate evaluation of the biliary system and can substitute for endoscopic retrograde cholangiopancreatography (ERCP).7
An ultrasound examination of the patient shows a normal liver with no significant fatty infiltration. The gallbladder, however, is packed with calculi. The common hepatic duct measures 4.6 mm and the common bile duct measures 8.5 mm. The intrahepatic ducts are not dilated. Doppler ultrasound of the hepatic and portal veins demonstrates normal flow without evidence of thromboses. Absence of jaundice, ascites, and hepatic vein thrombosis on ultrasound excludes Budd-Chiari syndrome.
The diagnosis
History of sudden-onset epigastric pain, chills, and nausea in the postpartum period, no history of liver disease, and an uneventful pregnancy makes cholecystitis the most likely diagnosis for the patient.
Gallstones are common in pregnancy and more than 4% of pregnant women have incident gallbladder sludge or stones persisting to the early postpartum. Cholesterol secretion is increased in the second and third trimester of pregnancy, thus increasing the lithogenicity of the bile.8
The outcome
ERCP showed several stones in the common bile duct. We performed a papillotomy and removed 15 pale, almost white-faced, stones. Subsequent laparoscopic cholecystectomy removed a large gallbladder with multiple remaining stones. Microscopic examination of the gallbladder wall showed thickened muscularis propria and fibrosis of the subserosa, findings consistent with chronic cholecystitis.
CORRESPONDENCE
H.U. Rehman, MBBS, Clinical Associate Professor, Department of Medicine, Regina General Hospital, 1440 14th Avenue, Regina, SK, S4P 0W5, Canada; habib31@sasktel.net