Hepatitis and cholestasis in a middle-aged woman.

Abstract

mal in size and echogenicity. Ascites and splenomegaly wereThe patient is a 42-year-old female who presented to a local absent. A hepatitis panel and immunoserological tests re-hospital in September of 1994 with a history of scleral icterus. vealed the following: hepatitis A virus antibody /:anti-She first noticed this in July but did not seek medical advice nuclear antibody (ANA), /1:2,560; hepatitis B surface anti-at that time. The jaundice progressed, and she developed gener- gen 0:AMA, /1:320; hepatitis B surface antibody 0:ASMA,alized weakness and malaise that increased over several weeks. /1:20; hepatitis B core antibody /:Anti-liver/kidney micro-The patient eventually became homebound because of her fa- somal antibody, /1:40; hepatitis B e antigen 0:immunoglob-tigue. Her other complaints were decreased appetite and pro- ulin G, 2,050 mg/dL (normal range, 725-1,475 mg/dL); hepati-gressive swelling of the lower extremities. When she was seen tis B e antibody 0:immunoglobulin A (IgA), 511 mg/dLby a local physician in mid September, her laboratory data (normal range, 86-360 mg/dL); and hepatitis C virus antibodyrevealed an alanine transaminase of 360 U/L, aspartate trans- 0:IgM, 356 mg/dL (normal range, 79-463 mg/dL).aminaseof1215 U/L(normalranges,5to 40U/L),totalbilirubin The presence of circulating antibody to pyruvate dehydro-of 17.5 mg/dL (normal range, .2 to 1.5 mg/dL), and an alkaline genase subunit 2 was detected by both an ELISA and West-phosphatase of 285 U/L (normal range, 38 to 126 U/L). Her ern blot reactivities (kindly performed by Dr. Michael Manns,physician recommended prednisone therapy at a dose of 40 mg Hannover, Germany).daily. She was referred to the Ochsner Clinic (New Orleans, The patient underwent liver biopsy in October, 1994, whichLA) on October 15, 1994, approximately 3 weeks after initiating will be described below.immunosuppressive therapy. She was initially maintained on 40 mg of prednisone andHer past medical history was significant for vaginal bleed- 600 mg of ursodeoxycholic acid daily was added. Her livering in November of 1993, which required transfusions and a tests improved and 50 mg of azathioprine daily was initiatedhysterectomy. She had no other risk factors for liver disease. 2 months later enabling reduction of the prednisone dose toShe also had a history of hypothyroidism for approximately 30 mg per day. At that time, serum cholesterol had risen to1 year and was on thyroid replacement therapy. Her family 332 mg/dL, and she was started on insulin therapy becausehistory was significant for diabetes and hypothyroidism. ofnewonsethyperglycemia. Twomonthslater,hercorticoste-When seen at the Ochsner Clinic, she was noted to be jaun- roid dose was reduced to 25 mg and azathioprine was in-diced and there was palmar erythema with no other visible creased to 75 mg. During this time, her liver tests were stead-evidence of chronic liver disease. The liver edge was palpable ily improving (Fig. 1A and B). Five months after startingjust below the costal margin with a span of 10 cm. The spleen treatment, her azathioprine dose was further increased towas not palpable and there was no evidence of ascites. The 100 mg and 2 months later the prednisone dose was reducedpatient had 1/pedal edema in her lower extremities. to 10 mg per day. Over the next 5 months her prednisoneLaboratory data were as follows: alanine transaminase, dose was further reduced to 2.5 mg and azathioprine dose244 U/L (normal range, 5-40 U/L); aspartate transaminase, was increased to 150 mg. One year after initial diagnosis the834 U/L (normal range, 5-40 U/L); total bilirubin, 18.2 mg/ azathioprine was increased to 175 mg (approximately 2 mg/dL (normal range, 1-1.0 mg/dL); alkaline phosphatase, 347 kg) and she was maintained on 2.5 mg of prednisone, but theU/L(normal range,45-130 U/L);gamma glutamyltranspepti- azathioprine dose had to be reduced because of neutropenia.dase, 316 U/L (normal range, 8-55 U/L); albumin, 2.6 gm/dL She had a repeat liver biopsy performed in October of 1995,(normal range, 3.5-5.5 gm/dL); alpha 1 Antitrypsin, 305 mg/ which is described below. One month later, her liver functiondL (normal range, 190-350 mg/dL); hemoglobin, 9.9 gm/dL tests continued to show improvement with an aspartate(normal range, 14-18 gm/dL); white blood count, 5.9 110