Km. Boberg et al., The HLA-DR3,DQ2 heterozygous genotype is associated with an accelerated progression of primary sclerosing cholangitis, SC J GASTR, 36(8), 2001, pp. 886-890
Background: An improvement of prognostic models in primary sclerosing chola
ngitis (PSC) is needed. In particular, inclusion of prognostic markers that
are independent of the disease stage would be advantageous. We investigate
d whether HLA class II genes associated with PSC are also related to diseas
e progression. Methods: Tnt: study included 265 PSC patients from five Euro
pean countries with a median follow-up of 9.1 years. The end-points were de
ath (n = 38) or liver transplantation (n = 52). Thirty patients developed c
holangiocarcinoma during follow-up. Results: The DRB1*03,DQA1*0501, DQB1*02
(i.e. DR3,DQ2) heterozygous genotype was associated with an increased risk
of death or liver transplantation (hazard ratio = 1.63; 95% confidence int
erval (CI)= 1.06-2.52). The presence of a DQ6 encoding haplotype (DQB1*0603
or DQB1*0602) in DR3,DQ? negative individuals was associated with a reduce
d risk of death or liver transplantation (hazard ratio = 0.57: 95% CI = 0.3
6-0.88). There was a trend towards an increased risk of developing cholangi
ocarcinoma among DR4,DQ8 positive patients, but this did not reach signific
ance (odds ratio = 2.27; 95% CI = 0.78-6.62). Conclusion: The DR3,DQ?, hete
rozygous genotype is associated with a more rapid progression of PSC, where
as HLA-DQ6 is associated with a retarded disease progression. It is possibl
e that the DR-l,DQ8 haplotype is related to cholangiocarcinoma development.