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New Insights Into the Causal Pathway

Maxia Dong, MD, PhD; Shanta R. Dube, MPH; Vincent J. Felitti, MD; Wayne H. Giles, MD, MS; Robert F. Anda, MD, MS

Arch Intern Med. 2003;163:1949-1956.

Objective  To examine the relationship of adverse childhood experiences (ACEs), including abuse, neglect, and forms of household dysfunction, to the risk of liver disease by assessing the role of risk behaviors, such as substance abuse and high-risk sexual activity, as mediators of the ACEs–liver disease relationship.

Methods  Retrospective cohort study data were collected from 17 337 adult health plan members through a survey. Logistic regression adjusted for age, sex, race, and education was used to estimate the strength of the ACEs–liver disease relationship and the impact of the mediators in this relationship.

Results  Each of 10 ACEs increased the risk of liver disease 1.2 to 1.6 times (P<.001). The number of ACEs (ACE score) had a graded relationship to liver disease (P<.001). Compared with persons with no ACEs, the adjusted odds ratio of ever having liver disease among persons with 6 or more ACEs was 2.6 (P<.001). The ACE score also had a strong graded relationship to risk behaviors for liver disease. The strength of the ACEs–liver disease association was reduced 38% to 50% by adjustment for these risk behaviors, suggesting they are mediators of this relationship.

Conclusions  The ACE score showed a graded relationship to the risk of liver disease that appears to be mediated substantially by behaviors that increase the risk of viral and alcohol-induced liver disease. Understanding the effect of ACEs on the risk of liver disease and development of these behaviors provides insight into causal pathways, which may prove useful in the prevention of liver disease.

From the Division of Adult and Community Health, National Center for Chronic Disease Prevention and Health Promotion, Centers for Disease Control and Prevention, Atlanta, Ga (Drs Dong, Giles, and Anda and Ms Dube); and the Department of Preventive Medicine, Southern California Permanente Medical Group (Kaiser Permanente), San Diego (Dr Felitti). The authors have no relevant financial interest in this article.

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