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Thirty-eight patients with severe chronic active liver disease (CALD) were found to have a significantly higher frequency of HLA-Dw3 (68%) than 91 healthy controls (24%) (P < 0.0001). The association of CALD was statistically significantly stronger with the D locus than with the B locus of HLA. The response to treatment was significantly worse in patients with HLA-Dw3 than in patients who lacked this antigen.