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Semin Liver Dis 2002; 22(4): 395-406
DOI: 10.1055/s-2002-35710
DIAGNOSTIC PROBLEMS IN HEPATOLOGY

Copyright © 2002 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York, NY 10001, USA. Tel.: +1(212) 584-4662

A 38-Year-Old African-American Woman with an Unusually Rapid Progression of ``Primary Biliary Cirrhosis'': A Missed Opportunity!

Dirk J. van Leeuwen1 , Gagan Sood1 , Dino Ferrante1 , Audrey J. Lazenby2 , Marty J. Sellers3
  • 1Division of Gastroenterology and Hepatology, University of Alabama at Birmingham Liver Center, Birmingham, Alabama
  • 2Department of Pathology, University of Alabama at Birmingham Liver Center, Birmingham, Alabama
  • 3Department of Surgery (Transplantation), University of Alabama at Birmingham Liver Center, Birmingham, Alabama
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Publikationsdatum:
25. November 2002 (online)

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ABSTRACT

The case discussed is of a 38-year-old African-American woman who developed upper abdominal symptoms and liver test abnormalities. She underwent cholecystectomy for presumed gallstone disease. This was followed by a worsening of her condition, with the development of jaundice in the next 2 weeks. Results of reevaluation included transaminases around 1000 IU/L with minimal elevation of alkaline phosphatase (ALP), an antimitochondrial antibody (AMA) titer of 1:320, and an elevated immunoglobulin M (IgM). The antinuclear antibodies (ANA) level was positive, but titers were not obtained. There was no suggestion of bile duct obstruction. Liver biopsy findings were believed to be consistent with primary biliary cirrhosis (PBC). She was therefore started on, but failed treatment with, ursodeoxycholic acid. She was transferred to a transplant center 8 weeks later after a brief episode of encephalopathy and hypoglycemia. The clinical findings were consistent with subfulminant hepatic failure secondary to autoimmune hepatitis (AIH) with an ANA titer of 1:1280, an anti-smooth muscle antibody (SMA) titer of 1:40, and an elevated IgG. Review of the biopsy showed panlobular inflammation and bridging necrosis consistent with severe AIH. On imaging, she had ascites and a nodular appearance of the liver. An immediate drop in transaminases followed corticosteroid therapy, but her disease was already irreversible, and she underwent successful liver transplantation. The explanted liver was shrunken and noncirrhotic with massive hepatocellular collapse and contained multiple regenerating nodules, explaining the ultrasonographic appearances. The inflammatory component had greatly diminished compared with the earlier biopsy. The case illustrates the importance of knowledge of the natural course of a specific disease and the careful interpretation of clinical data, including autoimmune markers. PBC would rarely cause liver failure in a young woman; it is not a rapidly progressive disease. The original clinical diagnosis was unduly swayed by a positive AMA, which can be seen in up to 20% of patients with AIH. Markedly elevated transaminases with minimal elevation of ALP and positive ANA in a young woman should have pointed toward AIH at an earlier stage. The academic discussion of AMA-positive AIH versus PBC/AIH overlap syndrome remains intriguing, but prompt institution of aggressive immunosuppressive therapy aimed at the AIH component should not be deferred. In retrospect, an opportunity was missed.

KEYWORDS

Acute hepatitis - autoimmune hepatitis - primary biliary cirrhosis - subfulminant liver failure - antimitochondrial antibody - liver transplantation - overlap syndrome - variant syndrome - liver regeneration - liver biopsy - immunosuppression

REFERENCES

  • 1 Holt C, Csete M, Martin P. Hepatotoxicity of anaesthetics and other central nervous system drugs.  Gastroenterol Clin North Am . 1995;  24 853-874
    PubMedGoogle Scholar
  • 2 Gitlin N, Serio K M. Ischemic hepatitis: widening horizons.  Am J Gastroenterol . 1992;  87 831-836
    PubMedGoogle Scholar
  • 3 Isogai M, Hachisuka K, Yamaguchi A. Etiology and pathogenesis of marked elevation of serum transaminases in patients with acute gallstone disease.  HPB Surg . 1991;  4 95-107
    PubMedGoogle Scholar
  • 4 Harrison H B, Middleton II M H, Crosby J H, Dasher Jr N M. Fulminant hepatic failure: an unusual presentation of metastatic liver disease.  Gastroenterology . 1981;  80 820-25
    PubMedGoogle Scholar
  • 5 Colby T V, LaBrecque D R. Lymphoreticular malignancy presenting as fulminant hepatic disease.  Gastroenterology . 1982;  80 820-825
    PubMedGoogle Scholar
  • 6 Bass N M, Burroughs A K, Scheuer P J. Chronic intrahepatic cholestasis due to sarcoidosis.  Gut . 1982;  23 417-423
    PubMedGoogle Scholar
  • 7 Murphy J R, Sjogren M H, Kikendall J W, Peura D A, Goodman Z. Small bile duct abnormalities in sarcoidosis.  J Clin Gastroenterol . 1990;  12 555-561
    CrossrefPubMedGoogle Scholar
  • 8 Matteoni C A, Younossi Z M, Gramlich T. Nonalcoholic fatty liver disease: a spectrum of clinical and pathological severity.  Gastroenterology . 1999;  116 1413-1419
    CrossrefPubMedGoogle Scholar
  • 9 Kaplan M. Primary biliary cirrhosis.  N Engl J Med . 1996;  335 1570-1580
    CrossrefPubMedGoogle Scholar
  • 10 Wiesner R H. Liver transplantation for PBC and primary sclerosing cholangitis: predicting outcome with natural history models.  Mayo Clin Proc . 1998;  73 575-588
    PubMedGoogle Scholar
  • 11 Christensen E, Gunson B, Neuberger J. Optimal timing of liver transplantation for patients with primary biliary cirrhosis: use of prognostic modeling.  J Hepatol . 1999;  30 285-292
    CrossrefPubMedGoogle Scholar
  • 12 Loose A W, Meyer um Buschenfelde H, Franz B. Characterization of the overlap syndrome of primary biliary cirrhosis (PBC) and autoimmune hepatitis: evidence for it being a hepatitic form of PBC in genetically susceptible individuals.  Hepatology . 1999;  29 1078-1084
    CrossrefPubMedGoogle Scholar
  • 13 Chazouilleres O, Wendum D, Serfaty L. Primary biliary cirrhosis-autoimmune hepatitis overlap syndrome: clinical features and response to therapy.  Hepatology . 1998;  28 296-301
    CrossrefPubMedGoogle Scholar
  • 14 Czaja A J. The variant forms of autoimmune hepatitis.  Ann Intern Med . 1996;  125 588-598
    PubMedGoogle Scholar
  • 15 Nikias G A, Batts K P, Czaja A J. The nature and prognostic implications of autoimmune hepatitis with acute presentation.  J Hepatol . 1994;  21 866-871
    CrossrefPubMedGoogle Scholar
  • 16 Maggiore G, Porta G, Bernard O. Autoimmune hepatitis with initial presentation as acute hepatic failure in young children.  J Pediatr Gastroenterol Nutr . 1990;  116 97-106
    PubMedGoogle Scholar
  • 17 Obermayer-Straub P, Strassburg C P, Manns M P. Autoimmune hepatitis.  J Hepatol . 2000;  32(Suppl 1) 181-197
    PubMedGoogle Scholar
  • 18 Autoimmune hepatitis: the investigational and clinical challenges. AASLD Clinical Research Single Topic Conference. Abstracts of presentations. September 16-18, 1999; Atlanta, Georgia
    Google Scholar
  • 19 McFarlane I G. The relationship between autoimmune markers and different clinical syndromes in autoimmune hepatitis.  Gut . 1998;  42 599-602
    PubMedGoogle Scholar
  • 20 Gregorio G, Portmann B, Reid F. Autoimmune hepatitis in childhood: a 20-year experience.  Hepatology . 1997;  25 541-547
    CrossrefPubMedGoogle Scholar
  • 21 Johnson P J, McFarlane I G. Meeting report. International Autoimmune Hepatitis Group.  Hepatology . 1993;  18 998-1005
    CrossrefPubMedGoogle Scholar
  • 22 Alvarez F, Berg P A, Bianchi F B. International Autoimmune Hepatitis Study Group report: review of criteria for diagnosis of autoimmune hepatitis.  J Hepatol . 1999;  3 929-938
    PubMedGoogle Scholar
  • 23 Herzog D, Rasquin-Weber A M, Debray D, Alvarez F. Subfulminant hepatic failure in autoimmune hepatitis type 1: an unusual form of presentation.  J Hepatol . 1997;  27 578-582
    CrossrefPubMedGoogle Scholar
  • 24 Bernuau J, Rueff B, Benhamou J P. Fulminant and subfulminant liver failure: definitions and causes.  Semin Liver Dis . 1986;  6 97-106
    Artikel in Thieme ConnectPubMedGoogle Scholar
  • 25 Waldenstrom J. Leber, Blutproteine und Nahrungseiweiss.  Dtsch Z Verdau Stoffwechselkr . 1950;  2 113-119
    PubMedGoogle Scholar
  • 26 Mackay I R, Taft L T, Cowling D C. Lupoid hepatitis.  Lancet . 1956;  ii 123-126
    PubMedGoogle Scholar
  • 27 MacKay I R. Treatment of chronic active hepatitis and other liver disease with corticosteroid agents.  Med J Aust . 1987;  146 370-374
    PubMedGoogle Scholar
  • 28 Maddrey W C. Drug-induced chronic active hepatitis. In: Krawitt EL, Wiesner RH, eds. Autoimmune Liver Diseases New York: Raven Press 1991: 219-232
    Google Scholar
  • 29 Shukla M, van Leeuwen J D. Drug-induced vs.  autoimmune hepatitis? Don't delay steroids. AGC National Fellow's Forum, April 1996; Scottsdale Arizona/American College of Gastroenterology, October 1996, Abst .
    PubMedGoogle Scholar
  • 30 Lam K C, Yuen P, ColbourneMJ, ChangJ, S o. Deleterious effect of prednisolone in HBsA positive chronic active hepatitis.  N Engl J Med . 1981;  304 380
    PubMedGoogle Scholar
  • 31 Czaja A, Manns M P, McFarlane I G, Hoofnagle J H. Autoimmune hepatitis: the investigational and clinical challenges.  Hepatology . 2000;  31 1194-1200
    CrossrefPubMedGoogle Scholar
  • 32 Zauli D, Cassani F, Bianchi F B. Cytoskeletal antigens. In: McFarlane IG, Williams R, eds. Molecular Basis of Autoimmune Hepatitis Austin, TX: RG Landes 1996: 45-58
    Google Scholar
  • 33 Walker J G, Doniach D, Roitt I M. Serological tests in the diagnosis of primary biliary cirrhosis.  Lancet . 1965;  1 827-831
    PubMedGoogle Scholar
  • 34 Doniach D, Roitt I M, Walker J G, Sherlock S. Tissue antibodies in primary biliary cirrhosis, active chronic lupoid hepatitis, cryptogenic cirrhosis and other liver diseases and their clinical implications.  Clin Exp Immunol . 1966;  3 237-262
    PubMedGoogle Scholar
  • 35 Rubin E, Schaffner F, Popper H. Primary biliary cirrhosis: chronic nonsuppurative destructive cholangitis.  Am J Pathol . 1965;  46 387-407
    PubMedGoogle Scholar
  • 36 Scheuer P J. Primary biliary cirrhosis.  Proc R Soc Med . 1967;  60 1257-1260
    PubMedGoogle Scholar
  • 37 Berg P A, Klein R. Autoantibody patterns in primary biliary cirrhosis. In: Krawitt EL, Wiesner RH, eds. Autoimmune Liver Diseases New York: Raven Press 1991: 123-142
    Google Scholar
  • 38 Kenny R P, Czaja A J, Ludwig J, Dickson E R. Frequency and significance of antimitochondrial antibodies in severe chronic active hepatitis.  Dig Dis Sci . 1986;  31 705-711
    CrossrefPubMedGoogle Scholar
  • 39 Ben-Ari Z, Dhillon A P, Sherlock S. Autoimmune cholangiopathy: part of spectrum of autoimmune chronic active hepatitis.  Hepatology . 1993;  18 10-15
    CrossrefPubMedGoogle Scholar
  • 40 Goodman Z, McNally P R, Davis D R, Ishak K O. Autoimmune cholangitis: a variant of primary biliary cirrhosis.  Dig Dis Sci . 1995;  40 1232-1242
    PubMedGoogle Scholar
  • 41 Heathcote J E. Autoimmune cholangitis.  Clin Liver Dis . 1998;  2 303-311
    PubMedGoogle Scholar
  • 42 Goulis J, Leandro G, Burroughs A K. Randomised controlled trials of ursodeoxycholic acid therapy for primary biliary cirrhosis: a meta analysis.  Lancet . 1999;  354 1053-1060
    CrossrefPubMedGoogle Scholar
  • 43 Leuschner M, Maier K P, Schlichting J. Oral budesonide and ursodeoxycholic acid for treatment of primary biliary cirrhosis: results of a prospective double-blind trial.  Gastroenterology . 1999;  117 918-925
    CrossrefPubMedGoogle Scholar
  • 44 Angulo P, Jorgensen R A, Keach J C. Oral budesonide in the treatment of patients with primary biliary cirrhosis with a suboptimal response to ursodeoxycholic acid.  Hepatology . 2000;  31 318-323
    CrossrefPubMedGoogle Scholar
  • 45 Kurktschiev D, Subat S, Adler D, Schentke K U. Immunomodulating effect of ursodeoxycholic acid therapy in patients with primary biliary cirrhosis.  J Hepatol . 1993;  18 373-377
    CrossrefPubMedGoogle Scholar
  • 46 O'Grady J G, Alexander G JM, Hallyar K M, Williams R. Early indicators of prognosis in fulminant hepatic failure.  Gastroenterology . 1989;  97 437-445
    PubMedGoogle Scholar
  • 47 Neuberger J, Portmann B, Calne R, Williams R. Recurrence of autoimmune chronic active hepatitis following orthotopic liver grafting.  Transplantation . 1984;  37 363-365
    PubMedGoogle Scholar
  • 48 Sanchez-Urdazpal L, Czaja A J, van Hoek B. Prognostic features and role of liver transplantation in severe corticosteroid-treated autoimmune chronic hepatitis.  Hepatology . 1992;  15 215-221
    PubMedGoogle Scholar
  • 49 Milkiewicz P, Hubscher S G, Skiba G. Recurrence of autoimmune hepatitis after liver transplantation.  Transplantation . 1999;  68 253-256
    CrossrefPubMedGoogle Scholar
  • 50 Trouillot T E, Shrestha R, Kam I. Successful withdrawal of prednisone after adult liver transplantation for autoimmune hepatitis.  Liver Transpl Surg . 1999;  5 375-380
    CrossrefPubMedGoogle Scholar
  • 51 Jones D E, James O F, Portmann B. Development of autoimmune hepatitis following liver transplantation for primary biliary cirrhosis.  Hepatology . 1999;  30 53-57
    CrossrefPubMedGoogle Scholar