Results of a Prospective Study of Acute Liver Failure at 17 Tertiary Care Centers in the United States

  1. George Ostapowicz, MD;
  2. Robert J. Fontana, MD;
  3. Frank V. Schiødt, MD;
  4. Anne Larson, MD;
  5. Timothy J. Davern, MD;
  6. Steven H.B. Han, MD;
  7. Timothy M. McCashland, MD;
  8. A. Obaid Shakil, MD;
  9. J. Eileen Hay, MD;
  10. Linda Hynan, PhD;
  11. Jeffrey S. Crippin, MD;
  12. Andres T. Blei, MD;
  13. Grace Samuel, MS;
  14. Joan Reisch, PhD;
  15. William M. Lee, MD; and
  16. the U.S. Acute Liver Failure Study Group*
  1. From Gold Coast Hospital, Southport, Australia; University of Michigan, Ann Arbor, Michigan; University of Texas Southwestern Medical Center and Baylor University Medical Center, Dallas, Texas; University of Washington, Seattle, Washington; University of California at San Francisco, San Francisco, and University of California, Los Angeles, Los Angeles, California; University of Nebraska, Omaha, Nebraska; University of Pittsburgh, Pittsburgh, Pennsylvania; Mayo Clinic, Rochester, Minnesota; and Northwestern University, Chicago, Illinois.

    Abstract

    Background: Because acute liver failure is rare, related data have been sparse. Studies have suggested that viral hepatitis is the most common underlying cause of this condition.

    Objective: To describe the clinical features, presumed causes, and short-term outcomes of acute liver failure.

    Design: Prospective cohort study.

    Setting: 17 tertiary care centers participating in the U.S. Acute Liver Failure Study Group.

    Patients: 308 consecutive patients with acute liver failure, admitted over a 41-month period.

    Measurements: Detailed clinical and laboratory data collected during hospitalization, including outcome 3 weeks after study admission.

    Results: 73% of patients were women; median age was 38 years. Acetaminophen overdose was the most common apparent cause of acute liver failure, accounting for 39% of cases. Idiosyncratic drug reactions were the presumptive cause in 13% of cases, viral hepatitis A and B combined were implicated in 12% of cases, and 17% of cases were of indeterminate cause. Overall patient survival at 3 weeks was 67%. Twenty-nine percent of patients had liver transplantation, and 43% survived without transplantation. Short-term transplant-free survival varied greatly, from 68% for patients with acetaminophen-related liver failure to 25% and 17% for those with other drug reactions and liver failure of indeterminate cause, respectively. Coma grade at admission appeared to be associated with outcome, but age and symptom duration did not.

    Conclusions: Acetaminophen overdose and idiosyncratic drug reactions have replaced viral hepatitis as the most frequent apparent causes of acute liver failure. Apparent cause and coma grade at admission were associated with outcome. Although transplantation may improve patient survival, it was unavailable or unnecessary for most patients.

    * For members of the U.S. Acute Liver Failure Study Group, see Appendix.

    Article and Author Information

    • Acknowledgment: The authors thank the site coordinators and nurses for their support.

    • Grant Support: By the National Institutes of Health (RO3 DK52827, RO1 DK58369) and the U.S. Food and Drug Administration Orphan Products Program (FD-R-001661). Dr. Schiødt was supported by a Schering Research Fellowship from the American Association for the Study of Liver Diseases.

    • Potential Financial Conflicts of Interest:Consultancies: W.M. Lee.

    • Requests for Single Reprints: William M. Lee, MD, Division of Digestive and Liver Diseases, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390-9151.

    • Current Author Addresses: Dr. Ostapowicz: Department of Medicine, Gold Coast Hospital, 108 Nerang Street, Southport, QLD 4215, Australia.

    • Dr. Fontana: 1500 East Medical Center Drive, 3912 Taubman Center, Ann Arbor, MI 48109-0362.

    • Drs. Schiødt and Lee and Ms. Samuel: Division of Digestive and Liver Diseases, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390-9151.

    • Dr. Larson: Hepatology/GI/Transplant Services, University of Washington, Room EE-425, Box 356174, 1959 NE Pacific Street, Seattle, WA 98195-6174.

    • Dr. Davern: Department of Medicine, Gastroenterology, University of California, San Francisco, 513 Parnassus Avenue, Room S-357, San Francisco, CA 94143.

    • Dr. Han: Division of Digestive Diseases, University of California, Los Angeles, 10945 Le Conte Avenue, 2114 PVUB, Los Angeles, CA 900595-6949.

    • Dr. McCashland: 983285 Nebraska Medical Center, Omaha, NE 68198-3285.

    • Dr. Shakil: Center for Liver Diseases, Falk Medical Building, 3rd Floor, 3601 Fifth Avenue, Pittsburgh, PA 15213.

    • Dr. Hay: Mayo Clinic, 200 First Street SW, Rochester, MN 55905.

    • Drs. Hynan and Reisch: Academic Computing Department, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390-9151.

    • Dr. Crippin: Division of Gastroenterology, Washington University School of Medicine, 660 South Euclid Avenue, Campus Box 8124, St. Louis, MO 63110-1093.

    • Dr. Blei: Northwestern University Medical School, 303 East Chicago Avenue, Searle 10-573, Chicago, IL 60611.

    • Author Contributions: Conception and design: G. Ostapowicz, F.V. Schiødt, A. Larson, T.J. Davern, A.O. Shakil, A.T. Blei, G. Samuel, J. Reisch, W.M. Lee.

    • Analysis and interpretation of the data: G. Ostapowicz, R.J. Fontana, F.V. Schiødt, L. Hynan, W.M. Lee.

    • Drafting of the article: G. Ostapowicz, R.J. Fontana, F.V. Schiødt, W.M. Lee.

    • Critical revision of the article for important intellectual content: G. Ostapowicz, R.J. Fontana, F.V. Schiødt, A. Larson, T.J. Davern, T.M. McCashland, J.S. Crippin, A.T. Blei, W.M. Lee.

    • Final approval of the article: G. Ostapowicz, F.V. Schiødt, A. Larson, T.J. Davern, T.M. McCashland, A.O. Shakil, L. Hynan, J.S. Crippin, A.T. Blei, G. Samuel, W.M. Lee.

    • Provision of study materials or patients: G. Ostapowicz, R.J. Fontana, F.V. Schiødt, A. Larson, T.J. Davern, T.M. McCashland, A.O. Shakil, J.S. Crippin, G. Samuel.

    • Statistical expertise: L. Hynan, J. Reisch.

    • Obtaining of funding: J. Reisch, W.M. Lee.

    • Administrative, technical, or logistic support: G. Samuel, J. Reisch, W.M. Lee.

    • Collection and assembly of data: G. Ostapowicz, R.J. Fontana, F.V. Schiødt, A. Larson, T.J. Davern, S.H.B. Han, T.M. McCashland, W.M. Lee.

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    1. Ann Intern Med December 17, 2002 vol. 137 no. 12 947-954
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