Conformational anti‐cytochrome P4502E1 (CYP2E1) auto‐antibodies contribute to necro‐inflammatory injury in chronic hepatitis C

Summary. Circulating auto‐antibodies against cytochrome P4502E1 (CYP2E1) have been observed in a significant fraction of patients with chronic hepatitis C (CHC). This study investigated the clinical significance of these auto‐antibodies in relation to their antigen specificity. The presence of anti‐CYP2E1 IgG was investigated in 137 consecutive patients with biopsy‐proven CHC. Anti‐CYP2E1 IgG above control threshold levels was detected in 52 (38%) subjects. By combined immunoprecipitation and western blotting, we observed that among anti‐CYP2E1 IgG‐positive sera, 23 (44%) were unreactive towards denaturated CYP2E1, indicating a prevalent recognition of conformational CYP2E1 antigens. Conformational anti‐CYP2E1 auto‐antibodies were unrelated to circulating gamma‐globulins, alcohol intake or infection by specific HCV genotypes. The presence of anti‐CYP2E1 auto‐antibodies was associated with an 11‐fold (OR 10.9 95%CI 1.4–86.6 P = 0.008) increased prevalence of necro‐inflammatory grading ≥4 (Ishack’s criteria) and 4‐fold (OR 4.0; 95%CI 1.3‐11‐7: P = 0.014) increased prevalence of fibrosis staging ≥2, respectively. Multivariate analysis confirmed conformational anti‐CYP2E1 IgG (P = 0.005) and age (P = 0.033) as independent predictors of necro‐inflammatory grading ≥4. The development of anti‐CYP2E1 auto‐antibodies targeting conformational CYP2E1 epitopes is associated with more severe liver damage in CHC.