an internationally acceptable grading system, which has al-A panel of recognized experts in liver transplantation ready been developed for kidney, 3 heart, 4 and lung. 5 At the pathology, hepatology, and surgery was convened for Third Banff Conference on Allograft Pathology, a group of the purpose of developing a consensus document for the specialists in liver transplantation from North America, Eugrading of acute liver allograft rejection that is scientifirope, and Asia met for this purpose. cally correct, simple, and reproducible and clinically useful. Over a period of 6 months pertinent issues were DEFINITION OF ACUTE REJECTION discussed via electronic communication media and a consensus conference was held in Banff, Canada in the In general, organ allograft rejection can be defined as, ''an summer of 1995. Based on previously published data and immunological reaction to the presence of a foreign tissue or the combined experience of the group, the panel agreed organ, which has the potential to result in graft dysfunction on a common nomenclature and a set of histopathologi-and failure.'' 2 This report is specifically concerned with acute cal criteria for the grading of acute liver allograft rejec-rejection, recently defined by the international consensus tion, and a preferred method of reporting. Adoption of document on terminology for hepatic allograft rejection 2 as, this internationally accepted, common grading system ''inflammation of the allograft, elicited by a genetic disparity by scientific journals will minimize the problems associ-between the donor and recipient, primarily affecting interlobated with the use of multiple different local systems. ular bile ducts and vascular endothelia, including portal Modifications of this working document to incorporate veins and hepatic venules and occasionally the hepatic artery chronic rejection are expected in the future. (HEPATOL-and its branches.'' 2 Early rejection, cellular rejection, nonduc-OGY 1997;25:658-663.) topenic rejection, rejection without duct loss, and reversible rejection are synonyms for acute rejection that appear in the literature, but their use is discouraged. The general clinical, The success of hepatic transplantation has resulted in its laboratory, and histopathological abnormalities listed below widespread use for treatment of many patients with endstage were derived from the international consensus document.2 liver disease; it is currently offered by more than 100 centers worldwide. One-year survival rates range from 70% to 90%; CLINICAL AND LABORATORY FINDINGSand long-term survival of 50% to 60% of patients is not unViewed from a biological perspective, any recipient's imcommon.1 Therefore, an increasing number of physicians, inmune system will likely be perturbed after transplantation, cluding pathologists, many of whom have no specific training resulting in immune activation. 2 However, viewed from a in transplantation biology, will become involved in the care clinical perspective, because of baseline immunosuppressive of organ all...

It is possible to maintain a liver in a viable condition for a minimum of 72 hr of extracorporeal perfusion. This technique has been developed primarily as a preclinical model of extracorporeal liver support with the intention of proceeding to a clinical trial in patients with fulminant liver failure. However, it also has potential applications in organ preservation or resuscitation before transplantation and in the experimental study of isolated liver physiology.

The association between Z α 1 -antitrypsin deficiency and juvenile cirrhosis is well-recognized, and there is now convincing evidence that the hepatic inclusions are the result of entangled polymers of mutant Z α 1 -antitrypsin. Four percent of the northern European Caucasian population are heterozygotes for the Z variant, but even more common is S α 1 -antitrypsin, which is found in up to 28% of southern Europeans. The S variant is known to have an increased susceptibility to polymerization, although this is marginal compared with the more conformationally unstable Z variant. There has been speculation that the two may interact to produce cirrhosis, but this has never been demonstrated experimentally. This hypothesis was raised again by the observation reported here of a mixed heterozygote for Z α 1 -antitrypsin and another conformationally unstable variant (I α 1 -antitrypsin; 39 Arg→Cys) identified in a 34-year-old man with cirrhosis related to α 1 -antitrypsin deficiency. The conformational stability of the I variant has been characterized, and we have used fluorescence resonance energy transfer to demonstrate the formation of heteropolymers between S and Z α 1 -antitrypsin. Taken together, these results indicate that not only may mixed variants form heteropolymers, but that this can causally lead to the development of cirrhosis.

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