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ALTERATIONS IN AMA AND ANA DURING UDCA THERAPY OF PBC
C Soulellis, A Szilagyi, C Holcroft, N Hilzenrat
Division of Gastroenterology, SMBD Jewish General Hospital, McGill university, Montreal, Quebec
AIMS: We evaluated AMA disappearance or emergence of ANA during UDCA therapy and their relevance for long term outcome in PBC.
METHODS: Over 135 mo. (47-312), 22 (allAMA+, 15 with biopsies, 1M, µ age 63.8(42-84)) patients were observed. Age, dose and start time of UDCA, concomitant autoimmune disease(s) were recorded. Mayo Index scores(MIs) suggested good prognosis. Initial ANAs were negative. AMA disappearance and/or ANA emergence times were recorded. Initial bilirubin, albumin, ALP, GGT, ALT were compared with those at the time of marker change. The AMA and ANA were measured by indirect fluorescence assay(IFA). Statistical analysis was by paired and unpaired student t test.
RESULTS: Of 22 patients, 17 received UDCA ( 850mg/d, range 500-1250) from diagnosis, 5 began UDCA after 12-144mo. Follow-up MIs 2-6 yrs after therapy were unchanged. None died and none decompensated during observation.14 patients lost AMA, 14-84 mo after UDCA therapy. They had significantly lower ALP and higher albumin at time of switch (AMA lost, µ 111.8±12.8SE, vs 198.28±18,p=0.04 and 40.6±7.6 vs 39.8±2.1, p=0.046). 21 had ANA measured, 10 developed ANA (5-168mo after therapy) and 11 didn’t. There were no significant differences in age or dose of UDCA. In these 2 ANA (+/–) groups, 6 lost AMA in the ANA+ and 8 in the ANA– group(NS).Frequency of autoimmune diseases were similar(ANA+, 6/10, ANA– 4/11, NS) Initial bilirubin was higher in ANA+ than in ANA– group (µ1 2.8±8.4SE vs 7.3±2.6, p=0.055). At appearance, bilirubin decreased in the ANA+ group and albumin increased(NS). In the ANA– group bilirubin inreased and albumin did not change at the time of AMA disappearance (NS). Other measured liver tests improved with time in both groups.
CONCLUSIONS: Overall 63% lost AMA and 47.6% developed ANA+ during UDCA therapy.We speculate that subtle increase in albumin in those losing AMA may represent a more substantial therapeutic response. Our data suggest during UDCA treatment, ANA or AMA have little bearing on prognosis when overall prognosticators are favourable.