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Table of Contents
ORIGINAL ARTICLE
Year : 2022  |  Volume : 27  |  Issue : 2  |  Page : 190-196

The prevalence of cholelithiasis and variations in gallbladder volume among sickle cell anemia patients seen in a Nigerian tertiary health care institution


Department of Radiology, University of Benin Teaching Hospital (UBTH)/University of Benin (UNIBEN), Benin City, Edo State, Nigeria

Date of Submission03-Apr-2021
Date of Decision02-May-2021
Date of Acceptance11-Jun-2021
Date of Web Publication3-Mar-2022

Correspondence Address:
Osaigbovo Emmanuel Ighodaro
Department of Radiology, University of Benin Teaching Hospital (UBTH), University of Benin (UNIBEN), 1154, Main Gate, P.M.B, Benin-Ore Road, Benin City, Edo State.
Nigeria
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ijmh.IJMH_11_21

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  Abstract 

Background: Sickle cell disease (SCD) is an autosomal recessive blood disorder characterized by multiple-organ involvement including the gallbladder. Subjects with SCD are prone to developing pigment gallstones due to chronic red blood cell hemolysis, increased bilirubin levels, cholecystitis, and biliary sludge.Ultrasonography is a noninvasive, readily available, and permits a fast evaluation of the gallbladder. It is useful in establishing the various patterns of gallbladder disease and volume abnormalities. Objectives: The objectives of this study were to sonographically evaluate cholelithiasis and gallbladder volume in patients with SCD and correlate the findings with age and gender. A comparison of the above parameters in sickle cell patients was also made with apparently healthy controls. Materials and Methods: This was a prospective study of 150 patients with SCD and an equal number of apparently healthy control subjects in Benin City. Each subject was sonographically evaluated for possible gallbladder stones and its volume using a 3–5 MHz curvilinear array transducer with a SonoaceX4 ultrasound machine (Medison, Seoul, South Korea). Result: The prevalence of cholelithiasis among subjects with SCD in this study was 10%. Patients with SCD had a significantly higher mean gallbladder volume (34.50 ± 20.43 cm3) compared with apparently healthy control subjects (20.39 ± 10.71 cm3; P = 0.000). Conclusion: The prevalence of cholelithiasis in SCD was shown to increase with age. There was a positive linear correlation between the incidence of cholelithiasis and gallbladder volume with age of the patient.

Keywords: Gallbladder volume, sickle cell disease, ultrasonography cholelithiasis


How to cite this article:
Ighodaro OE. The prevalence of cholelithiasis and variations in gallbladder volume among sickle cell anemia patients seen in a Nigerian tertiary health care institution. Int J Med Health Dev 2022;27:190-6

How to cite this URL:
Ighodaro OE. The prevalence of cholelithiasis and variations in gallbladder volume among sickle cell anemia patients seen in a Nigerian tertiary health care institution. Int J Med Health Dev [serial online] 2022 [cited 2022 May 24];27:190-6. Available from: https://www.ijmhdev.com/text.asp?2022/27/2/190/339020




  Introduction Top


Sickle cell disease (SCD) is a genetically inherited autosomal recessive abnormality in which valine replaces glutamic acid in the sixth position of the β-chain in the hemoglobin molecule. The consequence is the formation of hemoglobin S (Hb S). Subjects who are homozygous for Hb S are said to have SCD.[1] Other rare forms of SCD include Hb SC, Hb AC, and β thalassemia.[2] SCD is believed to have originated in malaria-endemic West Africa where it has the highest prevalence. Nigeria has one of the largest endemic populations of adults and children with SCD in the world. A quarter of all Nigerians have the sickle cell trait and approximately 150,000 children are born each year with the disorder in Nigeria.[3],[4]

SCD has recently been recognized as a problem of major public health significance by the World Health Organization. Although more than 70% of the sufferers live in Africa, expenditure on the related care and research in the continent is negligible.[5] Mustapher et al.[6] studied the prevalence of SCD in Kano metropolis and found out that it was 11.87% for Hb SS, 40.33% for Hb AS, 0.22% for Hb SC, and 1.51% for Hb AC. The prevalence of SCD in Benin was studied by Odunvbun et al.[7] and estimated at 2.8% for Hb SS and 0.2% for Hb SC.

SCD is characterized by the typical clinical picture of chronic hemolytic anemia and vaso-occlusive crises, which are precipitated by a variety of factors, such as dehydration, extent of deoxygenated Hb, pH, and temperature.[8] Malaria is a major precipitating factor in Nigeria; hence, the practice of giving malaria prophylactic drugs to patients with SCD attending clinics is rife.[8] Patients with SCD are known to present with a variety of abdominal problems such as hepatomegaly, splenomegaly, autosplenectomy, gallbladder disease, and renal changes.[9] A high prevalence of gallbladder disease has been reported in patients with SCD; however, relatively few data exist on the prevalence of gallbladder disease in Africans with SCD.[10]

The gallbladder is one of the organs affected in sickle cell anemia and the patterns of gallbladder disease reported include gallbladder stones, gallbladder wall thickening, hydrops of the gallbladder, and biliary sludge. Gallbladder involvement can present as abdominal crisis that may mimic vascular crisis. This was noted by Suell et al.[11] in a study where they recommended elective cholecystectomy in sickle cell patients with gallbladder stones before symptoms or complications arise as this improves overall survival rate. Hence, it is important to know the prevalence of gallbladder stones in patients with sickle cell anemia in our locality as this will help in the management of the condition and reduce morbidity and mortality.

Gallbladder imaging primarily involves real-time ultrasonography and computed tomography.[12] Oral cholecystography was the gold standard until the 1970s but it is now rarely used in clinical practice. Although the gallbladder is readily imaged using magnetic resonance imaging (MRI), this modality currently has a limited role in assessing the gallbladder due to high cost and relative unavailability.

At present, real-time ultrasonography is the dominant screening method for gallbladder evaluation. It has the advantage that it is relatively simple, available, reliable, nonionizing, and has high sensitivity in assessing gallbladder dimensions and function.[13]


  Materials and Methods Top


Study design

This was a prospective comparative sonographic study of the prevalence of cholelithiasis and gallbladder volume abnormalities in sickle cell anemia patients with age-matched controls. It was carried out in the ultrasound unit of the Department of Radiology, University of Benin Teaching Hospital (UBTH), Benin City. Edo State.

Ethical clearance for this study was obtained from the Ethics and Research Committee of the University of Benin Teaching Hospital. The study was conducted among patients with SCD not in crisis, and without a history of cholecystectomy, attending the Sickle cell Clinic at the Consultant Outpatient Department (COPD) of the hospital. The control group comprised of same age- and sex-matched subjects who have normal genotypes. Both were evaluated after obtaining consent from them or their parents/guardians in the case of children.

All sonograms were performed using a 3.5 MHz or 5.0 MHz curvilinear array transducer of a SonoaceX4 ultrasound machine (Medison, Seoul, South Korea). Subjects were examined at least 4 h before meal or just before the next meal in the case of children to avoid post-prandial effect and ensure better imaging of the gallbladder. The biometric parameters such as age, sex, height, and weight were recorded. The ultrasound examination was performed with the subjects lying in the supine position on the examination couch, longitudinal, and transverse scan were obtained, using the electronic calipers, the maximum length (L) of the gallbladder measured across its central longitudinal axis were recorded in centimeters. A transverse scan was also taken; measurements of the maximum width (W), and height or anteroposterior dimension (H) were also obtained and recorded in centimeters, as shown in [Figure 1]A and [B]. Any mobile echogenic focus casting distal acoustic shadow within the anechoic bile in the gallbladder lumen was regarded as a calculus as shown in [Figure 2].
Figure 1: Scatter plot (regression graph) for gallbladder volume against age in male and female sicklers

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Figure 2: Scatter plot (regression graph) for gallbladder volume against body surface area in male and female sicklers

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For each subject, the gallbladder volume in cubic centimeters was calculated using the following ellipsoid formula:[14],[15]



where L represents the length, W is the width, and H is the height or anteroposterior dimension of the gallbladder. The constant has a value of 0.532, where is a constant (22/7).

Data analysis

Data were analyzed using the Statistical Package for Social Sciences (SPSS Window Version 16.0, Chicago, IL, USA). Nonparametric data were summarized using median and the range of values for continuous variables, whereas category variables were reported as frequencies and percentages. Independent samples Mann–Whitney U test was used to compare median differences between the groups, whereas chi-square test was used to assess the relationship between the categorical variables. Spearman correlation analysis was used to evaluate the relationship between gallbladder volume and age according to gender. Results were presented with the aid of tables and scatter diagrams.

The statistical level of significance was set at P < 0.05.


  Results Top


A total of 150 subjects with SCD and 150 apparently age- and sex-matched healthy subjects were sonographically studied. The age range of subjects was between 2 and 45 years, with a median age of 13.00 years and 13.00 years for both sicklers and control subjects, respectively. Approximately 71 (47.3%) male and 79 (52.7%) female sickle cell subjects were investigated compared with 72(48%) male and 78 (52%) female apparently healthy subjects. Gallstones were seen in 15 of the 150 sickle cell subjects with a prevalence of 10%. There was no case of gallstones in the apparently healthy control subjects. This was statistically significant (P = 0.000; [Table 1]). Sickle cell subjects had a median gallbladder volume of (34.60 cm3). This was significantly higher compared with apparently healthy control subjects who had a median gallbladder volume of (21.91 cm3). Fasting gallbladder volume ranged from 0.72–112.30 cm3 and 0.09–35.30 cm3 for sickle cell and control subjects, respectively (P = 0.000; [Table 1]). The highest number of cases with gallstones (7 or 14.3%) was seen in sicklers in the 13–23 years age group, women were more affected (male:female ratio of 3:4), whereas those in the 2–12 years age group had the least cases (3 or 4.2%); [Table 2]. The median gallbladder volume was significantly higher in sicklers who had calculi (68.01 cm3) than in sicklers without calculi (32.07 cm3) (P = 0.000; [Table 1]). Sicklers with calculi also had a higher median age (18years) in comparison with those without calculi (12 years) (P = 0.006; [Table 1]). These two observations were statistically significant. The body mass index (BMI) was significantly higher in sicklers who had calculi 24.52 compared to those without calculi 20.26. (P = 0.018; [Table 1]). Male sickle cell subjects had marginally higher median fasting gallbladder volume 19.42 cm3 compared to 17.99 cm3 in the female sickle cell subjects [Table 3] and [Figure 3]. However, differences in median gallbladder volume across the different age groups were not statistically significant between the genders. Female sicklers showed a slightly stronger positive correlation between gallbladder volume and age (r = 0.785, P = 0.000) compared to their male counterparts (r = 0.743, P = 0.000), whereas normal male subjects showed slightly stronger positive correlation between gallbladder volume and age compared to their female counterparts (r = 0.874, P = 0.000 for age).
Table 1: General data of the studied population showing the median age, weight, height, presence of gallstone and gallbladder volume in Sicklers and controls

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Table 2: Prevalence of cholelithiasis in 150 sickle cell disease patients with age

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Table 3: Comparison of gallbladder volume between male and female sicklers among the different age groups

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Figure 3: Scatter plot (regression graph) for gallbladder volume against age in male and female controls

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  Discussion Top


SCD is a genetically inherited autosomal recessive abnormality in which valine replaces glutamic acid in the sixth position of the β-chain in the Hb molecule. The consequence is the formation of Hb S.[1] It is believed to have originated in malaria-endemic West Africa where it has the highest prevalence.[3] Nigeria has one of the largest endemic populations of adults and children with SCD in the world.[4] SCD remains a disease of utmost importance in the Nigerian environment. Affectation of the gallbladder resulting in gallstone formation, gallbladder hydrops, sludge, and gallbladder wall thickening has been documented in the literature.[11]Assessment of the gallbladder volume is important in medical practice, as most diseases of the biliary system tend to affect it in SCD. Ultrasound has a high sensitivity and specificity in identifying pathologies of the gallbladder, including gallstones.[16]

The higher prevalence of gallstones in male sicklers seen in this study is similar to the work of Darko et al.,[17] but they are at variance with other studies done by Agholor et al.[18] and Billa et al.[19] where a higher prevalence in female sickle cell subjects was documented. These differences may be due to a smaller sample size (90 subjects) in the study done by Billa et al.

In Europe, North and South America, gallstones are common with prevalence rates in ultrasound surveys surpassing 20% in most studies.[20] The prevalence of cholelithiasis is substantially lower in Africa compared to Jamaica, Europe, or North America.[21] The 10% prevalence in this study was corroborated by other African studies: Nzeh et al.[21] (4.2%), Akinyanju et al.[22] (9%), Darko et al.[17] (4%), Agholor et al.[18] (16%). The low prevalence rate in Africans was attributed to difference in dietary habits in our environment which includes a high-fiber and low-cholesterol diet compared to that of the Western world. However, Caroli-Bosc et al.[23] in France reported a prevalence of 13.9%. The slight variation in prevalence rate recorded was probably due to the predominantly adult age group (subjects over 30 years of age) and larger sample size (528 subjects) compared to our study of predominantly pediatric age group and a smaller sample size of 150 sickle cell subjects.

Contrary to the low prevalence of cholelithiasis in this study, Durosinmi et al.[24] found a relatively higher prevalence of cholelithiasis in a sonographic study performed on 157 fasting Nigerian subjects with SCD. This difference was probably due to the predominantly adult age group recruited in their study which ranged from 9 to 60 years (mean 34.5 years), in contrast to this study with a predominant pediatric age group. The authors postulated that the adults were probably exposed to dietary and/or lifestyle factors that could influence formation of gallstones. Durosinmi et al.[24] showed gallstones in 38 subjects (24.2%) compared with 15 subjects (10%) in the current study. The youngest age at which cholelithiasis was detected in this study was 9 years; this is similar to studies done by Nzeh et al.[21] and Akinyanju et al.[22] They reported that the youngest age at which cholelithiasis was detected was 9 and 10 years, respectively. However, in the study done by Agholor et al.,[18] cholelithiasis was detected at 2 years of age. The authors postulated that this early detection in the study done by Agholo et al. was probably due to early referral to the hospital of the subjects recruited in their study.

Cholelithiasis has been reported to occur more commonly in patients older than 10 years and it is directly related to the severity of the SCD and the intensity of the hemolysis.[18] In this study, the highest number of cases with calculi (7 or 14.3%) was seen in sicklers in the 13–23 years age group, and women were more affected than men, whereas those in the 2–12 years age group showed the least percentage occurrence (3, 4.2%). This finding is similar to the observations of Agholor et al.;[18] they documented that the highest number of cases with calculi in sicklers was in the 21–30 years age group. Also, women were more affected than men. The lowest figures were in the 1–10 years of age group. The prevalence of cholelithiasis increased with age in this study. This finding is also in keeping with those of Billa et al.,[19] Akamaguna et al.[25] Olokoba et al.,[26] Gumiero et al.[27] and Agholor et al.[18] However, this study found that men were slightly more affected than women; in most studies, women had higher gallstone prevalence rates than men and more frequently required gallbladder surgery.[20]

In this study, the measured mean longitudinal length, height, and width of the gallbladder were obtained and used to calculate the gallbladder volume using the ellipsoid formula as proposed by Dodds et al.[14] This formula was used in this study because it has been proven satisfactorily to approximate gallbladder volume for clinical or investigative studies, especially in an ellipsoid-shaped gallbladder. From this study, fasting gallbladder volume was significantly higher in sickle cell anemia subjects than control group. This finding was probably due to the hepatobiliary system being overworked from high turnover rate of red blood cell hemolysis. The finding is similar to that of Ngige et al.[28] in Lagos, Nigeria, and Shing et al.[29] in Tokyo, Japan. They documented higher fasting gallbladder volumes in sickle cell subjects compared to control. There was a positive correlation between fasting gallbladder volume and age this was also observed by Jeong-Hyun et al.[30] in their study.

Gallbladder volume can reflect clinical, therapeutic implications, physiological, functional status, and possibly pathophysiological mechanisms of gallstone disease.[28] Studies of gallbladder function indicate that those with cholelithiasis have larger fasting and post-prandial gallbladder volumes suggesting that stasis and incomplete emptying may contribute to sludge and gallstone formation. As observed in this study, there was a positive linear relationship between gallbladder volume and presence of gallstones, this relationship was also shown in the study done by Olokoba et al.[26] and Caroli-Bosc et al.[23]

The median gallbladder volume was significantly higher in sicklers who had calculi than in sicklers without calculi thus presupposing that large gallbladder volume is a risk factor for calculus formation in SCD. This observation is corroborated by findings in the study by Olokoba et al.[26]

The prevalence of cholelithiasis is high in sickle cell patients and increases with age. This increase is due to the longer survival of these patients from improved medical care as well as the regular use of ultrasonography in detecting them. This was shown in this study where sicklers with calculi had a higher median age in comparison with those without calculi. This is similar to the study by Billa et al. In this study, the BMI was significantly higher in sicklers who had calculi compared to sicklers without calculi. This may be due to the relationship between weight, cholesterol, and gallstone formation.


  Conclusion Top


The prevalence of cholelithiasis among sickle cell anemia subjects in this study was 10%. The prevalence increased with age. There was a positive linear correlation between the incidence of cholelithiasis and age. Gallbladder volume increased with age and with the presence of gallstones.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
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    Figures

  [Figure 1], [Figure 2], [Figure 3]
 
 
    Tables

  [Table 1], [Table 2], [Table 3]



 

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