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DOI: 10.1055/s-2005-916327
Copyright © 2005 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York, NY 10001, USA.
Liver Failure in an Antimitochondrial Antibody-Positive Patient with Sarcoidosis: Primary Biliary Cirrhosis or Hepatic Sarcoidosis?
Publication History
Publication Date:
06 September 2005 (online)
CASE REPORT
A 63-year-old white male with a history of chronic liver disease presented for evaluation for liver transplantation in March of 1993. He had been working as a schoolteacher and described exposure to chalk dust. He was born in the United States, lived primarily in the New York area, and had no significant travel history. The patient never smoked or used illicit drugs, and was allergic to penicillin.
His prior medical history was noteworthy for episodes of severe abdominal pain and jaundice, ascribed to hepatitis, in his 20s, followed by recurrent biliary colic starting in 1980. An oral cholecystogram revealed multiple large radiolucent calculi. Subsequently, the patient underwent emergency cholecystectomy for perforated cholecystitis in 1982. He received a blood transfusion and had postoperative jaundice. His liver function tests (LFTs) never completely normalized and he started having intermittent pruritus; viral hepatitis markers were negative. Several endoscopic retrograde cholangiopancreatography procedures, including papillotomy, were performed over the following years; they showed normal pancreatic and common bile duct. In one instance, a small calculus was removed. The pruritus and abnormal LFTs persisted, with some fluctuation. A liver and spleen nuclear scan (with technetium) performed in 1986 was unremarkable. It was followed by a liver biopsy (now unavailable), which detected fibrosis, granulomas, and inflammation attributed at that time to prior extrahepatic obstruction. The same year, antimitochondrial antibodies (AMAs) and elevated immunoglobulin M levels were detected. In light of these findings, the liver biopsy specimen was reinterpreted as consistent with primary biliary cirrhosis. The patient was started on colchicine without significant improvement in his LFTs.
By the end of 1986, the patient complained of a persistent cough with occasional production of green sputum. An initial chest X-ray was unremarkable. The respiratory symptoms continued and repeat chest X-ray in May of 1987 demonstrated bilateral interstitial infiltrates with a slightly nodular appearance, affecting all lung fields. Spirometry demonstrated normal lung volumes and diffusing capacity, with a mild reduction in flow rates at low lung volumes, which suggested small airway disease. A bronchoscopy with bronchoalveolar lavage did not detect endobronchial lesions; a smear for Pneumocystis was negative. A gallium scan revealed diffuse radiotracer uptake in the lungs consistent with an active infectious or interstitial process. Ultimately, an open lung biopsy revealed many well formed non-necrotizing granulomas (Fig. [1]); special stains were negative for acid-fast organisms and fungi. Although nonspecific, the findings were considered to be consistent with sarcoidosis. A Kveim test for sarcoidosis was negative.[1] The liver biopsy from 1986 was re-reviewed again and now interpreted as being more consistent with sarcoidosis than primary biliary cirrhosis. This re-interpretation was primarily based on the presence of lung granulomas and the relative rarity of primary biliary cirrhosis in men compared with women (1:9, respectively). The patient was started on prednisone and his respiratory symptoms and liver function tests both improved.
Figure 1 Lung biopsy showing coalescent noncaseating epithelioid granulomas with multinucleated giant cells consistent with sarcoidosis (hematoxylin and eosin stain, original magnification × 100.)
A then routine follow up liver biopsy performed in 1988 showed multiple, focally confluent non-necrotizing epithelioid granulomas involving a few portal areas, fibrosis, mild diffuse lymphoid infiltrates associated with ductular proliferation, and slight neutrophilic infiltrates (Fig. [2]). The granulomas were described as being histologically identical to those in the lung. Additionally, several features of the granulomas were specifically noted to be unusual for primary biliary cirrhosis, such as their high prevalence and confluence in some areas. The following year (1989), the patient was diagnosed with papillary carcinoma of the thyroid. Lastly, the case for hepatic sarcoidosis as the cause of his liver disease was further supported by the detection of identical non-caseating granulomas in non-cancerous areas of his resected thyroid lobe (Fig. [3]).
Figure 2 Needle liver biopsy showing multiple noncaseating epithelioid granulomas that are partly hyalinized. The granulomas are found in portal and lobular areas (periodic acid-Schiff stain, original magnification × 200).
Figure 3 Thyroid resection showing multiple coalescent noncaseating epithelioid granulomas, some of which are partly hyalinized. Other sections from the thyroid not shown here have typical histology of papillary thyroid carcinoma (hematoxylin and eosin stain, original magnification × 100).
Between 1989 and 1993, his liver enzymes remained somewhat elevated despite steroid treatment. Interestingly, while on steroids during this period his AMA titer was normal, which has not been noted in primary biliary cirrhosis patients receiving steroids. In early 1993, he developed thrombocytopenia and was noted to have enlarged esophageal varices, consistent with portal hypertension. It was at this point that he was referred for liver transplantation evaluation.