Environmental risk factors are associated with autoimmune hepatitis

Background Failure of immunologic homeostasis and resultant hepatocyte destruction in autoimmune hepatitis (AIH) is likely the result of environmental triggers within a permissive genetic architecture. Aims We aimed to identify risk factors associated with AIH in a well-phenotyped AIH cohort. Methods We prospectively collected environmental questionnaires from 358 AIH cases and 563 healthy controls. Response frequencies were compared using logistic regression, adjusting for age at recruitment, sex and education. Results AIH cases were more likely to ever have a urinary tract infection (UTI) (53.6% vs 33.9%, P < .001) and recurrent UTI (more than 1 per year) (23.5% vs 15.9%, P = .002) compared to controls. Female cases more frequently had ever used oral contraceptives (83.0% vs 73.7%, P = .006), fewer pregnancies (median = 1 vs 3, P < .001) and less often used hormone replacement therapy compared to controls (28.5% vs 60.1%, P < .001). Current smoking was more prevalent in cases (18.9% vs 7.4%, P = .022), yet no difference according to historical smoking behaviours was observed. Finally, cases were less likely to have history of mumps (32.4% vs 53.1%, P = .011) and rheumatic fever (1.1% vs 4.4%, P = .028), but reported higher vaccination frequency to chicken pox (38% vs 28.1%), measles (66.5% vs 39.3%), mumps (58.7% vs 34.6%), rubella (55.3% vs 32.7%), pertussis (59.8% vs 40.1%) and pneumococcus (47.2% VS 39.4%) (P < .002). Conclusions Environmental factors are important in AIH pathogenesis. Replication of these findings and prospective examination may provide new insight into AIH onset and outcomes.

Automated summary

The onset of autoimmune hepatitis (AIH) may result from the interaction of environmental triggers within a genetic background, with risk factors associated with AIH including urinary tract infections, oral contraceptive use, and immunization history.