Impaired gallbladder motility and delayed orocecal transit contribute to pigment gallstone and biliary sludge formation in β -thalassemia major adults

AIM: Gallbladder and gastrointestinal motility defects exist in gallstones patients and to a lesser extent in pigment gallstone patients. To investigated the role of gallbladder and gastrointestinal motility disorders in pigment gallstone formation in β -thalassemia major. METHODS: Twenty-three patients with β -thalassemia major (16 females; age range 18-37 years) and 70 controls (47 females, age range 18-40 years) were studied for gallbladder and gastric emptying (functional ultrasonography), orocecal transit (OCTT, H2-breath test), autonomic dysfunction (sweat-spot, cardiorespiratory reflex tests), bowel habits, gastrointestinal symptoms and quality of life (all with questionnaires). Gallbladder content (ultrasonography) was examined before and during 8-12 mo follow-up. RESULTS: Gallstones and/or biliary sludge were found in 13 (56%) patients. β -thalassemia major patients had increased fasting (38.0 ± 4.8 mL vs 20.3 ± 0.7 mL, P = 0.0001) and residual (7.9 ± 1.3 mL vs 5.1 ± 0.3 mL, P = 0.002) volume and slightly slower emptying (24.9 ± 1.7 min vs 20.1 ± 0.7 min, P = 0.04) of the gallbladder, together with longer OCTT (132.2 ± 7.8 min vs 99.7 ± 2.3 min, P = 0.00003) than controls. No differences in gastric emptying and bowel habits were found. Also, patients had higher dyspepsia (score: 6.7 ± 1.2 vs 4.9 ± 0.2, P = 0.027), greater appetite (P = 0.000004) and lower health perception (P = 0.00002) than controls. Autonomic dysfunction was diagnosed in 52% of patients (positive tests: 76.2% and 66.7% for parasympathetic and sympathetic involvement, respectively). Patients developing sludge during follow-up (38%, 2 with prior stones) had increased fasting and residual gallbladder volume. CONCLUSION: Adult β -thalassemia major patients have gallbladder dysmotility associated with delayed small intestinal transit and autonomic dysfunction. These abnormalities apparently contribute together with haemolytic hyperbilirubinemia to the pathogenesis of pigment gallstones/ sludge in β -thalassemia major.