1309 BILE ACID GLUCURONIDATION IN HUMAN LIVER AND KIDNEY EXTRACTS

Abstract

and symptoms of PBC-related liver disease and histologic data were collected, as well as the presence of other autoimmune diseases, response to therapy and final outcome (death or liver transplantation). Results: HLA-DRB1*08 was significantly increased among patients with PBC, present in 8.1% compared to 2.6% in controls (OR 3.29, 95%CI: 1.75–6.19, p < 0.001) while DRB1*15 was decreased in PBC (6.5%) as compared with controls (12.8%) (OR: 0.474; 0.29–0.79, p = 0.04), as it was observed with the DRB1*07 (23.6% versus 16.0%, p = 0.054). DQB1*02 and DQB1*04 alleles were also associated with an increased risk for PBC (OR 1.68, 1.25–22.25, p = 0.005, and 2.90, 1.59–5.29, p < 0.001, respectively). By contrast the DQB1*06 led to a reduced risk of PBC (OR 0.40, 0.35–0.72). The DRB1*08, DQB1*04 haplotype was associated with the development (OR: 2.86, 1.49– 5.47, p = 0.003) whilst the DRB1*15, DQB1*06 haplotype (OR: 0.38, 0.21–066, p < 0.001) was protective for PBC. No associations were observed regarding to the UDCA response, but both pruritus (OR: 6.32, 1.99–19.99, p = 0.001) and fatigue (OR: 3.81, 1.37–10.56, p = 0.001) were more frequent in patients with the DRB1*08, DQB1*04 haplotype. Moreover, the DRB1*03-DQB1*02 haplotype was associated with poor prognosis (60% of death/transplant patients and 22% of the cases with good outcome (OR: 5.25; 95%CI:1.39–19.75, p = 0.007). No associations were observed with Sjogren’s syndrome. Conclusions: The positive association between the DRB1*08DQB1*04 haplotype in PBC confirms observations from other geographical areas. It is associated with symptoms such as pruritus and fatigue, and the DRB1*03, DQB1*02 haplotype is an indicator of bad prognosis.