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

Obstacles to morbidity free long-term survival after liver transplantation (LT) include complications of immunosuppression (IS), recurrence of 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 all IS without apparent adverse consequences in a highly selected group of recipients, but long-term follow-up is limited. Patients subjected to adjustments of IS are usually followed by serial liver chemistry tests, which are a relatively insensitive method of detecting allograft damage. Protocol biopsies have largely been abandoned for HCV-negative recipients, at least in part, because of an inability to integrate routine histopathologic findings into a rational clinical management algorithm. Recognizing a need to more precisely categorize and determine the clinical significance of findings in long-term biopsies, the Banff Working Group on Liver Allograft Pathology have reviewed literature, pooled experience, and are proposing working definitions for biopsy changes that would: 1) be conducive to lowering IS and compatible with operational tolerance (OT); and 2) raise concern for closer follow-up and perhaps increased IS during or after weaning of IS. Establishment of guidelines should help standardize analyses of the effects of various treatment and/or weaning protocols and more rigorously categorize patients that are assumed to show OT. Long term follow-up using standardized criteria will help to determine the consequences of lowering IS and define and determine the incidence and robustness of OT in liver allografts. Liver Transpl, 2012. © 2012 AASLD.