Correlates of gallbladder stones among patients with sickle cell disease: A meta‐analysis

Abstract

Sickle cell disorders are the most common hemoglobinopathies worldwide. Clinical variability of sickle cell disease (SCD) and susceptibility to its complications have been attributed to hematologic, genetic, and other influencing factors. This review aimed to provide further summary and analyses of the prevalence and factors associated with cholelithiasis among patients with SCD. A systematic database search was conducted in MEDLINE (PubMed), ScienceDirect, Google Scholar, World Health Organization Virtual Health Library, Cochrane Library databases, and System for Information on Gray Literature in Europe (SIGLE). Pooled prevalence, odds ratio (OR), and standardized mean difference (SMD) with the corresponding 95% confidence interval (CI) were calculated using Comprehensive Meta‐Analysis Software version 3.3. A total of 34 studies that fulfilled the eligibility criteria were included in the analyses. The overall prevalence of cholelithiasis among SCD patients was 25.3% (95% CI 19.4–32.3%). The risk of developing cholelithiasis was significantly associated with lower total hemoglobin level (SMD = −0.45; P = 0.002), lower hemoglobin F (HbF) level (SMD = −0.85; P = 0.003), higher total serum bilirubin level (SMD = 1.15; P < 0.001), higher reticulocytes count (SMD = 0.44; P = 0.007), and UDP‐glucuronosyltransferase‐1A1 enzyme (UGT1A1) promoter polymorphism. This review provides a comprehensive view of the high rate of cholelithiasis and its associated factors in SCD patients.

Age‐ and sex‐specific rates of gall bladder disease in children with sickle cell disease

“…Indeed, in a recent meta-analysis studying correlates of GBD in children and adults with SCD, the largest individual study sample size was 616, and the entire pooled population from studies spanning 1997-2020 was 6,771. 28 Our study's large sample size, drawn from broad geographic regions across the United States, reduces the risk of publication selection bias and provides more of a population-level estimate of GBD than prior studies.…”

“…[9][10][11][12] Although knowledge of gallstones as a complication of SCD is decades old, prevalence estimates in children vary widely (4-43%). [13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28] Additionally, the literature disagrees about the rate that gallstones cause GBD complications in individuals with SCD, with some studies suggesting a low rate of complications 21,29 and others with a higher rate. 24,25 Notably, most of the literature about gallstones and GBD preceded the availability of disease-modifying therapies such as hydroxyurea.…”

“…While most people with gallstones remain asymptomatic, some develop gall bladder disease (GBD) with life‐threatening complications requiring emergency department care, inpatient hospitalizations, endoscopic retrograde cholangiopancreatography (ERCP), or emergency cholecystectomy (surgical gall bladder removal) 9–12 . Although knowledge of gallstones as a complication of SCD is decades old, prevalence estimates in children vary widely (4–43%) 13–28 . Additionally, the literature disagrees about the rate that gallstones cause GBD complications in individuals with SCD, with some studies suggesting a low rate of complications 21,29 and others with a higher rate 24,25 .…”

Predisposing factors for advanced liver fibrosis in patients with sickle cell disease

“…Cholelithiasis, on the other hand, was significantly more common in patients with advanced fibrosis ( p = 0.003), a fact that may reflect the increased hemolysis in this group of patients, although cirrhosis per se represents a major risk factor for the formation of gallstones 16 . Cholelithiasis incidence in both group of patients combined was 52.9%, much higher than the percentage described in literature that is about 25% 17 …”

“…16 Cholelithiasis incidence in both group of patients combined was 52.9%, much higher than the percentage described in literature that is about 25%. 17 Liver iron concentration and ferritin levels were also higher in the group with advanced fibrosis (6.44 to 4.81 mg Fe/g dry weight and 968 to 740 ng/mL respectively) indicating the importance of secondary hemochromatosis in the pathophysiology of liver fibrosis and the need for proper iron chelation therapy. Moreover, the group of patients with advanced fibrosis had a slight difference in duration of transfusion therapy (8.77 to 7.81 years, p = 0.178) and a significant difference in transfusions of PRBC per year (10.07 to 5.64, p = 0.004).…”