Importance of liver biopsy findings in immunosuppression management: Biopsy monitoring and working criteria for patients with operational tolerance


  • Banff Working Group on Liver Allograft Pathology,

  • Anthony Demetris M.D.

    Corresponding author
    1. University of Pittsburgh Medical Center, 3459 5th Avenue, UPMC Montefiore E741, Pittsburgh, PA 15213
    • University of Pittsburgh Medical Center, 3459 5th Avenue, UPMC Montefiore E741, Pittsburgh, PA 15213
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    • Telephone: 412-647-2067; FAX: 412-624-6666

  • The Banff Working Group on Liver Allograft Pathology is a multidisciplinary group comprising pathologists, hepatologists, transplant surgeons, immunologists, and tissue typing experts devoted to the study of various aspects of liver allograft structural integrity, (dys)function, and histopathology. Most importantly, this group strives to develop recommendations for standardized diagnostic histopathological and testing criteria for causes of liver allograft injury/dysfunction, and these recommendations are updated as needed. The group relies on a combination of evidence-based literature reviews and critiques, multidisciplinary experience–based expertise, directed studies, discussions, and consensus building (which occurs during intense biennial working-session international meetings and Internet-based discussions). The members of the group include the following: Oyedele Adeyi (Toronto General Hospital), Graeme Alexander (University of Cambridge), Leonardo Baiocchi (University of Rome Tor Vergata), Manjula Balasubramanian (Albert Einstein Medical Center), Ibrahim Batal (Brigham and Women's Hospital), Chris O. C. Bellamy (Edinburgh Royal Infirmary), Atul Bhan (Harvard Medical School, Massachusetts General Hospital), Nancy Bridges (National Institute of Allergy and Infectious Diseases), John Bucuvalas (Cincinnati Children's Hospital Medical Center), Frederic Charlotte (Pitié-Salpêtrière Hospital), Bob Colvin (Harvard Medical School, Massachusetts General Hospital), Albert Czaja (Mayo Clinic College of Medicine), Anthony Demetris (chairman; University of Pittsburgh Medical Center), Michael DeVera (Loma Linda University), Magda S. El-Monayeri (Wadi El Neel Hospital), Sandy Feng (University of California San Francisco Medical Center), Linda Ferrell (University of California San Francisco Medical Center), Maria Isabel Fiel (Mount Sinai School of Medicine), Paulo Fontes (University of Pittsburgh Medical Center), John Fung (Cleveland Clinic Foundation), Hironori Haga (Kyoto University Hospital), John Hart (University of Chicago Medical Center), Eva Honsova (Institute for Clinical and Experimental Medicine), Stefan Hubscher (cochairman; University of Birmingham), Ismail Wesam (Bani Sweif University), Tomoo Itoh (Hokkaido University Hospital), Nirag Jhala (University of Alabama at Birmingham), Patricia Jungmann (Federal University of Pernambuco), Urmila Khettry (Lahey Clinic Medical Center), Takaaki Koshiba (Kyoto University), Charles Lassman (David Geffen School of Medicine, University of California Los Angeles), Jan Lerut (Saint Luc University Hospital), Saverio Ligato (Hartford Hospital), John Lunz (University of Pittsburgh Medical Center), George Mazariegos (University of Pittsburgh Medical Center), Geoff McCaughan (University of Sydney, Royal Prince Alfred Hospital), Sandra A. McClelland (University of Pittsburgh Medical Center), Marta I. Minervini (University of Pittsburgh), Joseph Misdraji (Massachusetts General Hospital), Thalachallour Mohanakumar (Washington University in St. Louis), Johan Molne (Sahlgrenska University Hospital), Alexandru Musat (University of Wisconsin School of Medicine and Public Health), Michael Nalesnik (University of Pittsburgh), Imad Nasser (Harvard Medical School, Beth Israel Deaconess Medical Center), Desley Neil (University Hospitals Birmingham), James Neuberger (University Hospitals Birmingham), Orit Pappo (Hadassah Medical Center), Lydia Petrovic (University Hospital, University of Southern California), Parmjeet Randhawa (University of Pittsburgh), Finn P. Reinholt (University of Oslo and Rikshospitalet, Oslo University Hospital), Erin Rubin (University of Pittsburgh), Phil Ruiz (University of Miami School of Medicine), Ozgul Sagol (Dokuz Eylül University), Alberto Sanchez Fueyo (Liver Transplant Unit, Hospital Clinic of Barcelona), Eizaburo Sasatomi (University of Pittsburgh), Thomas Schiano (Mount Sinai Medical Center), Mylene Sebagh (Paul Brousse Hospital), Avi Shaked (Hospital of the University of Pennsylvania), Francis Edward Sharkey (University of Texas Health Science Center in San Antonio), Tomokazu Shimizu (Tokyo Women's Medical University), Banu Sis (University of Alberta Hospital), Maxwell Smith (Mayo Clinic Arizona), Aurelio Sonzogni (University of Pittsburgh Medical Center in Palermo), Nadia Tchao (University of California San Francisco), Swan Thung (Mount Sinai Medical Center), Giuseppe Tisone (University of Rome), Athanassios Tsamandas (University of Patras School of Medicine), Annika Wernerson (Karolinska University Hospital), Tong Wu (Tulane University School of Medicine), and Funda Yilmaz (University of Ege).


Obstacles to morbidity-free long-term survival after liver transplantation (LT) include complications of immunosuppression (IS), recurrence of the original disease and malignancies, and unexplained chronic hepatitis and graft fibrosis. Many programs attempt to minimize chronic exposure to IS by reducing dosages and stopping steroids. A few programs have successfully weaned a highly select group of recipients from all IS without apparent adverse consequences, but long-term follow-up is limited. Patients subjected to adjustments in IS are usually followed by serial liver chemistry tests, which are relatively insensitive methods for detecting allograft damage. Protocol biopsy has largely been abandoned for hepatitis C virus–negative recipients, at least in part because of the inability to integrate routine histopathological findings into a rational clinical management algorithm. Recognizing a need to more precisely categorize and determine the clinical significance of findings in long-term biopsy samples, the Banff Working Group on Liver Allograft Pathology has reviewed the literature, pooled the experience of its members, and proposed working definitions for biopsy changes that (1) are conducive to lowering IS and are compatible with operational tolerance (OT) and (2) raise concern for closer follow-up and perhaps increased IS during or after IS weaning. The establishment of guidelines should help us to standardize analyses of the effects of various treatments and/or weaning protocols and more rigorously categorize patients who are assumed to show OT. Long-term follow-up using standardized criteria will help us to determine the consequences of lowering IS and to define and determine the incidence and robustness of OT in liver allografts. Liver Transpl 18:1154–1170, 2012. © 2012 AASLD.