Autoimmune acute liver failure: Proposed clinical and histological criteria


  • Potential conflict of interest: Dr. Norman is an employee of INOVA Diagnostics. Dr. Fontana serves on the speaker's bureau of Roche, BMS, and Gilead. Dr. Fontana consults for Vertex, GSK, and Abott. Dr. Lee consults for Eli Lilly, Gilead, and Novartis. Dr. Lee receives grants from BMS, Globeimmune, Vertex, SPRI, and Siemons.

  • Members and institutions participating in the Acute Liver Failure Study Group: W.M. Lee, M.D. (Principal Investigator), Anne Larson, M.D., Corron Sanders, Ph.D., Linda Hynan, Ph.D., University of Texas Southwestern, Dallas, TX; Iris Liu, M.D., University of Washington, Seattle, WA; Timothy Davern, M.D., University of California, San Francisco, CA; Paul Martin, M.D., Mount Sinai School of Medicine, New York, NY; Timothy McCashland, M.D., University of Nebraska, Omaha, NE; J. Eileen Hay, M.D., Mayo Clinic, Rochester, MN; Natalie Murray, M.D., Baylor University Medical Center, Fort Worth, TX; A. Obaid S. Shaikh, M.D., University of Pittsburgh, Pittsburgh, PA; Andres Blei, M.D., Northwestern University, Chicago, IL; Atif Zaman, M.D., University of Oregon, Portland, OR; Steven Han, M.D., University of California, Los Angeles, CA; Robert Fontana, M.D., University of Michigan, Ann Arbor, MI; Brendan McGuire, M.D., University of Alabama, Birmingham, AL; Ray Chung, M.D., Massachusetts General Hospital, Boston, MA; Alastair Smith, M.B., Ch.B., Duke University Medical Center, Durham, NC; Michael Schilsky, M.D., Cornell/Columbia University, New York, NY; Adrian Reuben, M.B.B.S., Medical University of South Carolina, Charleston, SC; Santiago Munoz, M.D., Albert Einstein Medical Center, Philadelphia, PA; Rajender Reddy, M.D., University of Pennsylvania, Philadelphia, PA; R. Todd Stravitz, M.D., Virginia Commonwealth University, Richmond, VA; Lorenzo Rossaro, M.D., University of California at Davis, Sacramento, CA; Raj Satyanarayana, M.D., Mayo Clinic, Jacksonville, FL; and Tarek Hassanein, M.D., University of California, San Diego, CA.


Identifying autoimmune hepatitis as the etiology of acute liver failure (ALF) is potentially important, because administering corticosteroids might avoid the need for liver transplantation. However, clinical and histological criteria of autoimmune ALF (AI-ALF) have not been defined. Liver sections (biopsies and explants) from a 72-patient subset of the ALF Study Group Registry with indeterminate ALF were reviewed by a pathologist blinded to all clinical data and were diagnosed with probable AI-ALF based on four features suggestive of an autoi mmune pathogenesis: distinctive patterns of massive hepatic necrosis (present in 42% of sections), presence of lymphoid follicles (32%), a plasma cell–enriched inflammatory infiltrate (63%), and central perivenulitis (65%). Forty-two sections (58%) were considered probable for AI-ALF; this group demonstrated higher serum globulins (3.7 ± 0.2 g/dL versus 3.0 ± 0.2 g/dL; P = 0.037) and a higher prevalence of antinuclear and/or anti–smooth muscle antibodies (73% versus 48%; P = 0.034) compared to those without histology suggestive of probable AI-ALF. Thirty patients concordant for autoantibodies and probable AI-ALF upon histological analysis were more likely to have the classical autoimmune hepatitis phenotype (female predominance [72% versus 48%; P < 0.05], higher globulins [3.9 ± 0.2 g/dL versus 3.0 ± 0.2 g/dL; P < 0.005], and higher incidence of chronic hepatitis in long-term follow-up [67% versus 17%, P = 0.019]) compared to the population without concordant AI-ALF histology and autoantibodies. Conclusion: Patients with indeterminate ALF often have features of autoimmune disease by histological analysis, serological testing, and clinical recurrence during follow-up. In contrast to classical autoimmune hepatitis, histological features of AI-ALF predominate in the centrilobular zone. (HEPATOLOGY 2011;53:517-526)