Prevalence of Gastrointestinal (GI), Hepatic, and Infectious Manifestations in Patients with Common Variable Immunodeficiency (CVID)

Abstract

RationaleCommon variable immunodeficiency (CVID) is the most common, symptomatic, primary immunodeficiency in adults. Gastrointestinal (GI) and hepatic manifestations in CVID remain poorly delineated. We assessed the prevalence of GI, hepatic, and infectious manifestations among patients with CVID and correlated the findings with immunophenotype. MethodsWe conducted a retrospective cohort study of CVID patients at our large, academic center. We evaluated baseline patient characteristics, GI, hepatic, and infectious manifestations of 319 CVID patients. Laboratory studies and immunologic profiles of the patients were evaluated. Results: 291/319 CVID patients (91%) had documented GI or hepatic manifestations. The most common GI symptoms were diarrhea (n = 153), vomiting/dysphagia (n = 146), abdominal pain (n = 117), and weight loss/malabsorption/protein wasting (n = 43). Autoimmune/inflammatory GI disease was reported in 72/319 (23%) of patients. 135/238 (57%) of patients had abnormal liver biochemistries at some point [ALT: 63/135 (47%), AST: 78/135 (58%), Alkaline phosphatase: 76/135 (56%)]. Chronic inflammatory hepatitis was identified in 43/319 (13%); including autoimmune hepatitis (n = 32), transaminitis hepatitis (n = 6), infectious hepatitis (n = 6). Other hepatic conditions were portal hypertension (n = 30), liver cirrhosis (n = 18), and nonalcoholic fatty liver disease (n = 15). 23/319 (7%) had undergone transient elastography, 42/319 (13%) had undergone liver biopsy, of which 22/42 (52%) had a diagnosis of nodular regenerative hyperplasia. The most common GI infections were H. pylori (n = 22), C. difficile (n = 18), Giardia (n = 8). Low absolute CD3+ cells were associated with autoimmune hepatitis [OR 2.91; 95%CI (1.07–7.87); P = 0.03], portal hypertension [OR 5.14; 95%CI (1.86–14.17); P = 0.002], autoimmune/inflammatory GI disease [OR 2.69; 95%CI (1.13–6.41); P = 0.02], and IBD [OR 5.09; 95%CI (1.07–24.20); P = 0.04]. Low absolute CD4+ cells were associated with portal hypertension [OR 5.11; 95%CI (1.87–13.93); P = 0.001], autoimmune/inflammatory GI disease [OR 3.47; 95%CI (1.49–8.12); P = 0.004], and autoimmune gastroenteropathy [OR 3.78; 95%CI (1.44–9.92); P = 0.007]. Low absolute CD19+ cells were associated with autoimmune gastroenteropathy [OR 3.66; 95%CI (1.16–11.6); P = 0.02]. Low switched memory B-cells (IgM-IgD-CD27+CD19+) were associated with autoimmune gastroenteropathy [OR 5.07; 95%CI (1.35–19.04); P = 0.01], and portal hypertension [OR 5.89; 95%CI (1.13–28.16); P = 0.02]. Conclusions: CVID patients had a high prevalence of GI, hepatic, and infectious manifestations, which was associated with more severe immunophenotypes.