Higher Household Dysfunction in Adverse Childhood Experiences Score & Low Household Income Associate With Increased Risk of Cirrhosis in Adulthood

Introduction: Adverse childhood experiences (ACEs) have been linked to development of chronic liver disease later in life. This link was driven by increased risk behaviors for viral and alcoholic liver disease (ALD). With the rise of non-alcoholic steatohepatitis (NASH) and its different underlying risks, we aimed to update characterizations of the association between ACEs and cirrhosis. Methods: We conducted a cross-sectional analysis of participants (pts) enrolled in the Southern Liver Health Study, a multi-site study investigating associations between environmental exposures and liver cancer. We included 2 cohorts of pts: diagnosis of cirrhosis and healthy controls aged 40-75 years enrolled from 1/1/2022–1/31/2023. History of ACEs was collected via a validated survey with scores ranging from 0-8. Demographic data was obtained for all pts and chart review of cirrhosis pts enrolled at Duke was performed for additional medical history. We used adjusted multivariable logistic regression models to test the association between ACEs and cirrhosis. Results: 461 pts were included in the final analyses (cirrhosis, n = 187; control, n = 274). More pts with cirrhosis were older (median: 61 vs 58.5 yrs), male (46% vs 28%), and non-Hispanic White (79% vs 61%) (Table 1). Both cohorts reported a median of 1 ACE while more cirrhosis pts reported ≥4 ACEs than controls (20% vs 15%). NASH was the most common etiology of cirrhosis (49%). Cirrhosis significantly associated with history of ≥1 ACE in the household dysfunction domain but not with total ACE score or history of ACEs in the childhood abuse domain. There was a significant interaction between number of ACEs and household income (HHI) on the odds of cirrhosis, such that in pts with a HHI of < $50,000/yr, pts with ≥4 ACEs had 3 times the odds of cirrhosis than pts with 0-3 ACEs. Conclusion: Reporting ≥1 ACE related to household dysfunction associated with 78% higher odds of cirrhosis in adulthood. High total ACE score and low HHI also significantly associated with cirrhosis. While we did not find an association between total ACE score and cirrhosis, we found that certain ACEs impacted risk for cirrhosis more than others. Income and other household factors also likely play a role. The high prevalence of NASH cirrhosis and different risk behaviors may explain these findings, but larger studies are needed. Future efforts should focus on how ACEs differently impact cirrhosis risk by etiology in order to develop preventative strategies. Table 1. - Demographic information and ACE scores of participants with and without cirrhosis CirrhosisN = 187N (%) ControlN = 274N (%) P-value Age (years) 0.006 Median (IQR) 61.0 (55.0-67.0) 58.5 (50.0-66.0) Sex < 0.001 Male 86 (46.0) 77 (28.3) Female 101 (54.0) 195 (71.7) Missing 0 2 Race/Ethnicity < 0.001 White, non-Hispanic 141 (78.8) 167 (61.2) Black/African American, non-Hispanic 26 (14.5) 95 (34.8) Other 12 (6.7) 11 (4.0) Missing 8 1 Highest Level of Education 0.010 High school or less 40 (22.1) 42 (15.4) Trade or some college 37 (20.4) 37 (13.6) Associate or Bachelor degree 65 (35.9) 103 (37.7) Graduate or professional degree 39 (21.5) 91 (33.3) Missing 6 1 Marital Status 0.059 Single, divorced, widowed 65 (34.8) 123 (44.9) Married or living with partner 114 (61.0) 145 (52.9) Unknown 8 (4.3) 6 (2.2) Annual Household Income 0.498 Less than $50,000 68 (36.4) 98 (35.8) $50,000 - $100,000 49 (26.2) 68 (24.8) Greater than $100,000 46 (24.6) 82 (29.9) Unknown 24 (12.8) 26 (9.5) Diabetes < 0.001 Yes 71 (39.4) 49 (18.0) No 109 (60.6) 223 (82.0) Missing 7 2 Alcohol Use < 0.001 Current drinker 23 (12.9) 139 (52.3) Former drinker 88 (49.2) 50 (18.8) Never drinker 68 (38.0) 77 (29.0) Missing 8 8 Enrolling Institution < 0.001 Duke University 97 (51.9) 41 (15.0) North Carolina State University 3 (1.6) 146 (53.3) University of North Carolina 9 (4.8) 32 (11.7) Emory University 78 (41.7) 55 (20.1) Cirrhosis Etiology* NASH 45 (49.5) Alcohol 22 (24.2) HBV/HCV 9 (9.9) Cryptogenic 5 (5.5) Other 10 (11.0) Missing 96 MELD Score* Median (IQR) 10.1 (7.0-14.0) Missing 112 CirrhosisN = 187N (%) ControlN = 274N (%) aOR† (95% CI) Total ACE Score 0 54 (28.9) 89 (32.5) (ref) 1 42 (22.5) 63 (23.0) 0.73 (0.34, 1.57) 2-3 53 (28.3) 80 (29.2) 1.58 (0.77, 3.25) ≥4 38 (20.3) 42 (15.3) 1.67 (0.73, 3.82) Childhood Abuse No 98 (52.4) 150 (54.7) (ref) Yes 89 (47.6) 124 (45.3) 1.09 (0.63, 1.88) Childhood Household Dysfunction No 71 (38.0) 120 (43.8) (ref) Yes 116 (62.0) 154 (56.2) 1.78 (1.01, 3.12) *includes Duke data only. † aOR was adjusted for age, sex, enrolling institution, diabetes, and alcohol use. Abbreviations: IQR = interquartile range; BMI = body mass index; NASH = non-alcoholic steatohepatitis; HBV = hepatitis B virus; HCV = hepatitis C virus; MELD = model for end-stage liver disease; ACE = adverse childhood experience; aOR = adjusted odds ratio; CI = confidence interval.