Study Identifies High Rate of Gallstones Among Patients with Sickle Cell


Excessive hemolysis and genetic factors may be associated with cholelithiasis.

sickle cell disease

A new meta-analysis reported a high rate of gallbladder stones in patients with sickle cell disease.

Gallbladder stones, or cholelithiasis, has been reported in patients with sickle cell disease, and their complications may be responsible for increased levels of morbidity. Nevertheless, there is little evidence of the true prevalence of cholelithiasis in these patients.

As such, a team led by Sagad O O Mohamed, of the Department of Paediatrics and Child Health at the University of Khartoum in Sudan, conducted a systematic database search of studies that assessed the frequency and risk factors of cholelithiasis among patients living with sickle cell disease.

The Meta-Analysis

Mohamed’s team identified a total of 34 studies to include in their analysis. The studies were extracted from MEDLINE (PubMed), Google Scholar, ScienceDirect, WHO Virtual health library, Cochrane Library databases, and System for Information on Gray Literature in Europe (SIGLE), and represented research as early 1977 and as recent as 2020.

Case reports, editorials, reviews, abstracts, and studies that lacked sufficient data were excluded from the team’s analysis.

Once filtered and amassed, the included studies underwent quality assessment according to the Newcastle-Ottawa Scale. Data was then extracted, and independent reviewers resolved any disparities that arose.

The final analysis included a total of 6771 patients.

The Results

The overall prevalence of cholelithiasis among patients was 25.3% (95% CI; 19.4–32.3). Prevalence was higher among adults (44.1%) than among children (14.9%; X2 = 200.4, P < 0.001).

Meta-regression analysis revealed the studies’ publication years had no effect on the heterogeneity among studies. Even more, they did not have any moderating effects on cholelithiasis prevalence (P = .679).

The occurrence of gallstones was significantly associated with lower total Hb level (SMD = -0.45; 95% CI, -0.73 to -0.32), lower Hb F level (SMD = -0.85; 95% CI, -1.38 to -0.27), higher total serum bilirubin level (SMD = 1.15; 95% CI, 0.74–1.55), and higher reticulocytes count (SMD = 0.44; 95% CI, 0.12–0.75).

Additionally, UDP-glucuronosyltransferase 1A1 enzyme (UGT 1A1) polymorphism was the most common genetic factor associated with a higher risk of cholelithiasis in these patients. This was especially notable in the homozygosity for seven thymine-adenine (TA) repeats.

One study from the Netherlands, led by Landburg et al. (2007), quantified the relationship between rates of cholelithiasis in sickle cell disease and plasma concentration of asymmetric dimethylarginine.


“It is notable that all the identified associated factors with cholelithiasis in this review are correlates of excessive hemolysis,” Mohamed and colleagues wrote.

With this observation, and the identification of potentially linked genetic factors, they indicated that patients with any or more risks for cholelithiasis should be prioritized for elective cholecystectomy, if performed.

They further indicated that outcomes related to cholelithiasis should be addressed in future research.

“A more inclusive consideration of the existing evidence will raise healthcare providers’ awareness of the associated factors with cholelithiasis to ensure effective management for SCD patients,” the investigators concluded.

The study, “Correlates of gallbladder stones among patients with sickle cell disease: A meta-analysis,” was published online in the Journal of Gastroenterology and Hepatology.

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