Hidden Burden: Liver and Gastrointestinal Involvement in Chronic Granulomatous Disease

Chronic granulomatous disease (CGD) is a primary immunodeficiency characterized by defective reactive oxygen species production, leading to recurrent infections, chronic inflammation, and immune dysregulation. Hepatic and gastrointestinal (GI) involvement are major contributors to disease-related morbidity. To evaluate hepatic and GI involvement in patients with CGD and to assess their associations with clinical features and outcomes. This retrospective single-center cohort study included 80 patients diagnosed with CGD between 1984 and 2025. Demographic, clinical, laboratory, genetic, and outcome data were analyzed. Hepatic and GI involvement were defined based on clinical, radiological, endoscopic, and histopathological findings. The cohort was predominantly male (63.8%), with a median age at diagnosis of 3.5 years and a high rate of parental consanguinity (62.5%). Hepatic involvement was identified in 52.5% of patients, most commonly hepatomegaly (42.5%), followed by hepatic abscesses (15%) and steatosis (11.3%). Gastrointestinal involvement was documented in 10% of patients, with inflammatory bowel disease (IBD) occurring in 8.8%, typically presenting with diarrhea, rectal bleeding, and abdominal pain. Growth failure (42.2% of children) and chronic diarrhea (21.3%) were also common clinical features. During follow-up, 17 patients (21.3%) died. Mortality was numerically higher among patients with hepatic involvement than among those without (26.2% vs. 15.8%), although the difference was not statistically significant. In exploratory multivariable Cox regression analysis, elevated alanine aminotransferase (ALT) levels at diagnosis were associated with mortality (HR 4.78, p = 0.020), whereas no independent predictors of hepatic or gastrointestinal involvement were identified. CGD is a complex disorder characterized by both susceptibility to infection and immune dysregulation. Hepatic and GI manifestations represent important components of the disease spectrum. Elevated ALT levels at the time of CGD diagnosis were associated with mortality in exploratory multivariable analysis, suggesting that baseline liver function assessment at diagnosis, together with longitudinal monitoring, may provide prognostic information, although this finding requires confirmation in larger prospective studies.