Anti-parietal cell autoantibodies (PCA) as serological marker of recurrent primary biliary cirrhosis after liver transplantation

Liver transplantation (OLT) for primary biliary cirrhosis (PBC) is characterized by disease recurrence of up to one third of patients. The diagnosis of recurrence requires a cholestatic profile and a typical histology representing a challenge for transplant hepatologists. Antimitochondrial antibodies (AMA) establish the initial diagnosis, persist after OLT, and are thus of limited value for the diagnosis of recurrence. Aim of this analysis was to identify serological parameters associated with recurrent PBC.

OLT performed between 1992 and 2006 at Hannover Medical School were evaluated retrospectively including histology before and after OLT, autoimmune serological parameters (AMA, anti PHD-E2, ANA, PCA, SLA, LKM), immunosuppressive therapy, and outcome. Recurrent PBC was based on the presence of epitheloid granulomas, florid bile duct lesions, bile duct injury, and lymphoid aggregates in liver specimens, and biochemical cholestasis.

Between 1983 and 2006 72 patients (68 female, 4 male) underwent OLT with histologically confirmed PBC. AMA were posive in 68 (94%), and negative in 4 (6%) patients. Median follow up was 123 months. 5 patients died because of sepsis or cholestatic liver failure, 2 patients required re-transplantation because of bile duct necrosis and thrombosis of the hepatic artery. AMA persisted in 55 (76%) patients. Anti-PDH-E2 directed AMA (26/66 (39%) before, 27/64 (42%) after OLT) ANA (17/72 before, 21/72 after OLT), and anti-parietal cell antibodies (PCA) (28/68 (41%) before, 34/72 (47%) after OLT) were detectable. Liver biopsies were obtained in 34 patients post OLT upon clinical suspicion, and recurrent PBC was diagnosed in 20/72 (28%) after a mean of 66 months (range 13–161). Anti-PCA were detected in 100% of patients with recurrence before and following transplantation, 15/28 (54%) of patients with anti-PCA before OLT developed recurrence during follow-up. There was no difference of immunosuppressive regimens.

AMA have a high specificity for PBC and serve as serological confirmation of the diagnosis. Additional autoantibodies such as ANA and anti-PCA are detectable in a subgroup of PBC patients but to date have limited diagnostic relevance. Although unspecific for the diagnosis of PBC, anti-PCA were detectable in 100% of patients with recurrent PBC before and after OLT. 54% of patients with anti-PCA before OLT developed recurrent PBC suggesting a diagnostic role of anti-PCA as a simple and cost effective marker of recurrence.