clinical appearance of disease is important not only for Whether primary biliary cirrhosis (PBC) recurs after liver transplantation but also for understanding the natliver transplantation has remained an interesting and ural history of PBC. (HEPATOLOGY 1996;24:1079-1084.) controversial issue; rejection, viral hepatitis, and drug effects all may mimic recurrent PBC histologically and biochemically. Furthermore, reliable clinical criteria for Primary biliary cirrhosis (PBC), one of the three most com-PBC recurrence are lacking. In this study, the issue of mon indications for liver transplantation in the United disease recurrence using a well-characterized mono-States, is an autoimmune liver disease characterized by proclonal antibody (MAb), C355.1, that reacts with the imgressive granulomatous destruction of intrahepatic bile munodominant mitochondrial autoantigen of PBC ducts, periportal hepatitis with piecemeal necrosis, and even-(pyruvate dehydrogenase complex [PDC-E2]) was adtual cirrhosis. The question of whether PBC recurs after dressed. When used in an immunohistochemical assay, transplantation has generated much interest and contro-C355.1 produces intense apical staining of bile duct epiversy. [4][6] The morphological features of PBC, aside from perthelium specifically in liver sections of patients with haps the near-pathognomonic florid duct lesion, can be seen PBC and may be the earliest known marker of PBC. in many other conditions that affect allografts, in particular Immunohistochemical and histological analysis of serial cellular rejection, viral hepatitis, and drug effects. Furtherliver biopsy specimens of 67 patients pre-and post-ormore, there appears to be no pathognomonic indicator, either thotopic liver transplantation (OLT), including 38 paclinical or biochemical, of disease recurrence. 7 tients with PBC and 29 non-PBC liver disease controls, Two important features of PBC are that the primary target was performed. Sections were stained with MAb C355.1 of destruction is the epithelial cells of the intrahepatic bile or the control MAb C315 and analyzed to determine ducts and that patients develop antimitochondrial antibodies whether there was a recurrence of apical reactivity in (AMAs) directed against the E2 component of pyruvate dehythe bile ducts of the posttransplantation biopsy specidrogenase (PDC-E2). We made an observation that links mens. The immunohistochemical staining was correthese two features when we reported the presence of a molelated with the histological findings and serum biochemcule in biliary epithelial cells of patients with PBC but not istries at the time of the biopsy. Our data indicate that in controls that react with a murine monoclonal antibody a significant number of patients who underwent trans-(MAb; C355.1) to PDC-E2. This increased reactivity was plantation for PBC (28 of 38) but not controls (0 of 29) observed using C355.1 but not a series of other anti-PDCdevelop a staining pattern of liver bile duct epithelium E2 murine MAbs and suggests that the increased immunorewith MAb C355.1 that is indistinguishable from the preactivity may be caused by the presence of a molecule crosstransplantation pattern. Of the 28 patients with this apireactive to PDC-E2 or possibly an aberrantly expressed or cal staining pattern, 8 were characterized histologically altered form of PDC-E2. Moreover, this unique apical stainas possible recurrent PBC, 2 as chronic rejection, 2 as ing pattern has been found recently in early or stage I PBC acute rejection, 9 as nonspecific changes, 4 as normal or before the appearance of either the costimulatory molecule near normal, and 3 had other histological changes. Only B7 or class II molecules, suggesting that it is the earliest 50% of the patients with apical C355.1 staining had liver detectable sign of the disease process. 17 enzyme levels suggestive of cholestasis. Thus, there ap-
In the current study, we attempted to identify, in liver pears to be immunohistochemical evidence that supallografts, the PBC-specific staining pattern observed with ports the concept of recurrence of PBC after OLT. The MAb C355.1. Using this data in conjunction with histological appearance of biliary epithelial abnormalities before the criteria and serum biochemistries, we further investigated the putative recurrence of PBC after transplantation.
Methods
Abbreviations: PBC, primary biliary cirrhosis; AMA, antimitochondrial antibody; PDC-Clinical Specimens. Liver explants or needle biopsy specimens E2, pyruvate dehydrogenase complex; MAb, monoclonal antibody; OLT, orthotopic liver were collected at the time of transplantation from the livers of 38 transplantation.
consecutive patients with PBC (19 from University of California San