BACKGROUND & AIMS:

It is widely believed that autoimmune hepatitis accumulates in families, but the degree of familial clustering has not been clarified. We conducted a population-based study on the family occurrence of autoimmune hepatitis.

METHODS:

Through Danish nationwide registries we identified 8,582 first-degree and 9,230 second-degree relatives of index patients diagnosed with autoimmune hepatitis in 1994-2015; and 64 co-twins of index patients diagnosed with autoimmune hepatitis in 1977-2011. For first- and second-degree relatives we calculated the sex- and age-adjusted standardized incidence ratio of autoimmune hepatitis relative to the general population, and we calculated the cumulative risk, i.e. the cumulative incidence, of developing autoimmune hepatitis from the time of the index patient's diagnosis. For co-twins, we estimated the standardized incidence ratio and the concordance rate of autoimmune hepatitis.

RESULTS:

In first-degree relatives, there were six incident autoimmune hepatitis diagnoses during 64,020 years of follow-up: the standardized incidence ratio was 4.9 (95% CI 1.8-10.7), and the 10-year cumulative risk was 0.10% (95% CI 0.04-0.23). In the second-degree relatives, there were no incident autoimmune hepatitis diagnoses (expected number assuming incidence rate as in the Danish general population = 0.8). In the co-twins, there was one incident autoimmune hepatitis diagnosis during 1,112 years of follow-up, and the standardized incidence ratio was 53.9 (95% CI 1.4-300.4). The probandwise concordance rate, a measure of heritability, was higher in monozygotic than in dizygotic twins (8.7% [95% CI 1.1-28.0] vs. 0%).

CONCLUSIONS:

This nationwide study indicates that only first-degree relatives of index patients with autoimmune hepatitis are at increased risk of autoimmune hepatitis from the time of the index patient's diagnosis, but the absolute risk is very low.

LAY SUMMARY:

Autoimmune hepatitis is a chronic liver disease caused by a dysfunctional immune system. It is widely believed that autoimmune hepatitis accumulates in families. We studied the family members of patients with autoimmune hepatitis from the entire Danish population. We found that autoimmune hepatitis does accumulate in families, but the risk of autoimmune hepatitis in the family members is very low.