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 Table of Contents  
ORIGINAL ARTICLE
Year : 2020  |  Volume : 1  |  Issue : 1  |  Page : 25-32

Sonographic assessment of the prevalence of gall bladder abnormalities in children with sickle cell disease in Kano, Nigeria


1 Department of Radiology, Bayero University Kano/Aminu Kano Teaching Hospital, Kano, Nigeria
2 Department of Radiology, Federal Medical Center, Katsina, Nigeria

Date of Submission20-May-2020
Date of Decision01-Jun-2020
Date of Acceptance22-Jun-2020
Date of Web Publication25-Sep-2020

Correspondence Address:
Dr. Mohammed Kabir Saleh
Department of Radiology, Bayero University Kano/Aminu Kano Teaching Hospital, Kano
Nigeria
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/JRMT.JRMT_6_20

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  Abstract 


Background: The gall bladder is one of the abdominal organs that are frequently affected in sickle cell disease. This results from chronic hemolysis with its accelerated bilirubin turnover, which leads to a high incidence of gall bladder diseases. Ultrasonography is a cost-effective and noninvasive modality that permits a quick evaluation of the gall bladder in patients with sickle cell anemia. Objectives: The aim of this study was to evaluate changes in gall bladder in children with sickle cell anemia using ultrasonography. Materials and Methods: This prospective study was conducted in the department of radiology, Aminu Kano Teaching Hospital, Kano (AKTH). One hundred children with sickle cell anemia and age and sex-cross-matched 100 healthy controls aged 15 years and below were recruited for this study, (in accordance with what is obtainable at AKTH, Kano). The examination was performed using an ultrasound machine equipped with a 3.5 MHz curvilinear ultrasound transducer. The gall bladder changes that were assessed include cholelithiasis, cholecystitis, biliary sludge, and volume. Results: From the 100 children scanned, there were 68 (68%) males and 32 (32%) females in each of the study groups, with an age range of 2–15 years. The mean age of the cases and controls was 9.63 ± 3.79 years and 8.49 ± 3.39 years, respectively (P = 0.024). Among the patients; 19 (19%) had cholecystitis, 9 (9%) had gallstones and 8 (8%) had biliary sludge, with no detectable abnormality in the controls. Conclusion: The ultrasonographic prevalence of gallbladder abnormality is higher in patients with sickle cell anemia when compared to normal healthy controls showing increased prevalence with age.

Keywords: Gallstones, prevalence, sickle cell anemia, ultrasonography


How to cite this article:
Saleh MK, El-Habeeb AM, Isyaku K. Sonographic assessment of the prevalence of gall bladder abnormalities in children with sickle cell disease in Kano, Nigeria. J Radiat Med Trop 2020;1:25-32

How to cite this URL:
Saleh MK, El-Habeeb AM, Isyaku K. Sonographic assessment of the prevalence of gall bladder abnormalities in children with sickle cell disease in Kano, Nigeria. J Radiat Med Trop [serial online] 2020 [cited 2023 Mar 26];1:25-32. Available from: http://www.jrmt.org/text.asp?2020/1/1/25/296116




  Introduction Top


Sickle cell disease (SCD) is an inherited disease caused by the production of abnormal hemoglobin chains within the red blood cell, as a result of the substitution of glutamic acid with valine at position 6 of the beta chain.[1] This causes rigidity and sickling of the red blood cell, leading to vascular occlusion and ischemia in multiple organs.[2],[3] The disease is inherited as an autosomal recessive characteristic and manifests in persons who are homozygous for the gene.[2] The mutant hemoglobins HbS, HbC, and HbE are also associated with the sickling disorder in man.[4]

This disease is believed to have originated in malaria endemic West Africa, where it has the highest prevalence, but it is also present in Americans of African, Indian, and Eastern Mediterranean ancestry.[5]

Estimates suggest that 250,000 children are born annually with SCD worldwide, and thus, it is among the most important epidemiological genetic diseases in the world.[6] The prevalence of sickle cell trait in sub-Sahara Africa is as high as 30%,[7] and it is the most common hemoglobinopathy seen in Nigeria with a prevalence of 3% in the newborn population.[8]

In Nigeria, the sickle cell gene is also widely distributed. HbS is believed to be common in the northern part of Nigeria, while HbC is distributed mainly in the Southern and Eastern parts.[4]

The gall bladder is one of the abdominal organs that are frequently affected in SCD patients.[2],[9] Chronic hemolysis, with its accelerated bilirubin turnover, leads to a high incidence of pigment gallstones.[10],[11] It is also well known that the majority of SCD patients with biliary sludge eventually develop gall stone.[12]

Real-time ultrasonography is a standard screening procedure and the first-line imaging modality of choice in the assessment of the biliary tract.[5] It is a well-established first-line imaging modality that is highly sensitive and specific in the assessment of the gallbladder wall and luminal content. The inherent strengths of ultrasound, namely the absence of ionizing radiation, the dynamic test that is well tolerated, the ability to get a clinical history, and elicit useful clinical signs significantly add to the power of this imaging modality.[13] There is no risk associated with repeated investigations and it can be freely used for follow-up studies, making it an ideal means of investigating the hepatobiliary axis.[14]

The aim of this study is to assess the sonographic prevalence of gallbladder abnormalities in children with SCD and compare the result to those of normal healthy controls in Kano North-Western Nigeria.


  Materials and Methods Top


This was a cross-sectional, hospital-based prospective study carried out at the Radiology Department of Aminu Kano Teaching Hospital (AKTH), Kano State in Northern Nigeria over 1 year period involving SCD patients and age-matched controls aged 15 years and below who met the inclusion criteria.

Children with SCD aged 15 years and below attending the sickle cell clinic or admitted into the Pediatric Medical Ward were recruited for the research, after fulfilling the inclusion criteria. Apparently, healthy age-matched controls were also recruited from amongst children at the pediatric outpatient clinic. SCD was ruled out for controls and confirmed for subjects using hemoglobin electrophoresis.

Ethical approval to carry out the research was obtained from the Ethics and Research committee of AKTH, Kano. Informed written consent was obtained from the parents, caregivers, and older children as the case may be that are involved in the study.

Patients' anonymity was protected by removing all identification markers from the images. Patients and controls were scanned in the presence of their parents or guardians.

Inclusion criteria for the SCD are those who are 15-year-old and below and those with laboratory evidence of Hb SS genotype. The subjects excluded from the study include those above 15 years old, those with presence of other systemic or metabolic diseases, for example, thalassemia, diabetes, hypertension, renal diseases e.t.c. those with evidence of malnutrition (body weight <70% of the expected) and those with evidence of anatomical anomaly of the gallbladder; determined by its abnormal shape or position.

The control group include apparently healthy asymptomatic non sickle cell children aged 15 years and below.Those excluded as subjects were children >15 years of age, patients with SCD, subjects with abnormalities affecting the gall bladder, for example, ectopia or agenesis (this will be known by nonvisualization of the gall bladder on ultrasound) and subjects with clinically documented heart, liver, or kidney failure or malnutrition.

Data collection instruments

Ultrasound imaging machine (Mindray Digital Ultrasound Imaging System (Model DP-8800Plus 2012; Shenzhen Mindray Biomed electronics, China) was used to assess the gall bladder in the SCD group and controls.

Ultrasound technique

The procedure was explained to each patient (for older patients), parents and/or caregivers (for younger patients). Biodata, including age and sex, were recorded for each patient.

Each patient was examined in supine and right anterior oblique positions. Adequate coupling gel was applied over the right hypochondriac region and a 3.5 MHz curved array transducer was used for scanning. The older patients were asked to fast overnight before the study (6 h), while patients 7 years and below were required to fast for 4 h before the examination. This is to ensure adequate gallbladder distension and hence its maximum visualization.

With the patient in the supine position, the transducer was placed in the right hypochondrial area in the midclavicular line and the gallbladder was located at the inferior aspect of the liver by following the right costal margin or the main lobar fissure. It was angled cephalad in both transverse and longitudinal planes to obtain the full view of the gallbladder. Sonographic landmarks of the gallbladder were determined as the main, lobar fissure and an echogenic line leading from the bifurcation of the right portal vein to the gallbladder [Figure 1].
Figure 1: Longitudinal ultrasound scan of the right hypochondrium showing the site of measurement of gallbladder length (white line) and wall thickness in mm (white arrow heads). Key: GB - Gallbladder, PV - Portal vein, CD - Cystic duct

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It was also re-scanned in the left lateral decubitus or erect positions because stones may be missed if only supine scans are used. In each individual position, the gallbladder was assessed in the longitudinal planes and sometimes magnified to obtain a maximum gallbladder view. The measurement of gallbladder volume and wall thickness was conducted on each patient.

To obtain the gallbladder volume, the maximal gallbladder outline was visualized (on longitudinal (long-axis) and transverse (short-axis) views, and the length was measured on arrested respiration. The greatest length in cm (L) [Figure 1], greatest transverse width in cm (W), and anteroposterior in cm (H) dimensions [Figure 2] were rounded to two decimal points. Gallbladder volume in cm3 was then calculated from the ellipsoid formular;[15] thus:
Figure 2: Transverse ultrasound scan of the right hypochondrium showing sites of measurement of gallbladder width (calipers C-D) and antero-posterior dimension (calipers A-B) (cm). Key: AA - Abdominal aorta, RKD - Right kidney

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Volume of gallbladder (V) = Length (L) cm × Width (W) cm × anteroposterior dimension (H) cm × π/6

V = L × W × H × 0.52 (cm3).

Gallbladder wall thickness was measured by using the on-screen cursor on a frozen sonogram, where the measurement was taken from the anterior wall between the lumen and the liver parenchyma in millimeters as indicated by the two white arrowheads in [Figure 1]. To increase the accuracy, three repeated measurements were obtained by the same observer to reduce intra-observer variability.


  Results Top


A total of 200 patients comprising 100 children with SCD and 100 asymptomatic patients were examined. This includes 136 males and 64 females who were both matched for age and sex. Included subject-control ratio is 1:1.

The age of the patients ranged between 2 and 15 years in both the SCD patients and controls. The mean and standard deviation of the ages were 9.63 ± 3.79 years in the sickle cell group and 8.49 ± 3.39 in the control group. The difference in age between the control and study groups showed no statistical significance (P = 0.024) [Table 1]. Majority of patients belonged to the age range of 12–13 [Figure 3].
Table 1: The mean and standard deviation of the ages of the subjects

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Figure 3: Bar chart showing age distribution of the subject

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There were 18 cases of cholecystitis in the sickle cell patients made up of 8% of the total study group. Eleven of them were male, whereas 7 were female. The age range was 3–15 years with a mean age of 9.61 years [Table 2], [Table 3], [Table 4]. Cholecystitis was most prevalent in the 11–15 years age range (20%), while it is least prevalent in the 1–5 years age range 15% [Table 3].
Table 2: The abnormal findings in the gallbladder

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Table 3: The prevalence of gallbladder abnormalities by age grouping in sickle cell disease

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Table 4: Sex distribution and age ranges of the gallbladder findings in sickle cell disease patients

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The mean total gallbladder volume and standard deviation in the sickle cell patients are 10.15 ± 6.21 cm3. The mean gallbladder volume and standard deviation in males with sickle cell are 10.87 ± 6.91 cm3, while that of the females is 8.62 ± 4.09 cm3. The differences between the mean gallbladder volume in both sexes showed positive statistical significance with a P = 0.003 [Table 5].
Table 5: The gallbladder volume measurement in sickle cell anemia children

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Of the 100 children with SCD studied 9 of them had gall stones [Figure 4], which accounted for 9% of the study population, with gall stones occurring in 5 males and 4 females, respectively. The age range where gallstone was found was 9–15 years with the mean age being 13.22 years. The majority of the gall stones were found in the age range 11–15 years, representing 7%, while the remaining 2% was found in the age range 6–10 years. No gall stone was found in the age range of 1–5 years [Table 2], [Table 3], [Table 4].
Figure 4: Longitudinal section of the gall bladder with multiple hyperechoic structures of varying sizes showing acoustic shadowing

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Biliary sludge [Figure 5] was present in eight patients (8%) [Table 2] and it was most prevalent in the 11–15 year age range, which constituted 6% of the sludge present. Two percent of biliary sludge was found in the 1–5 age range, while it was absent in the 6–10 years age range [Table 3]. Biliary sludge was present in 5 male and 3 female patients, respectively; the age range where biliary sludge was found was 4–15 years with a mean age of 10.75 years [Table 4].
Figure 5: Longitudinal section of the gall bladder with echogenic debris seen layered in it dependent part

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There were 9%, 8%, and 18% of gall stone, biliary sludge, and cholecystitis, respectively, present in the sickle cell patient made up of a total of 37% of abnormal gall bladder findings in these subjects, while no abnormality was detected in the controls group [Table 6]. The mean and standard deviation of the gall stone, biliary sludge, and cholecystitis of the patients with SCD were 1.90 ± 0.302, 1.91 ± 0.0288, 1.73 ± 0.446; while the corresponding values for the control group were 2.00 ± 0.000, 2.00 ± 0.000, 2.00 ± 0.00, respectively, with P values of 0.000 which was statistically significant [Table 7].
Table 6: Comparison of gallbladder findings in cases and controls

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Table 7: Comparison of ultrasonographic measurements between cases and controls

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The mean and standard deviation of the gallbladder volume in both SCD patients and control were 10.146 ± 6.214 and 13.454 ± 5.869, respectively, the P = 0.0861, which was statistically insignificant.

Significant positive correlate was noted between age and gallbladder sonographic findings such as cholecystitis, biliary sludge, and gall stone in the patients with SCD. While negative correlate was noted between sex and cholecystitis, cholelithiasis, and biliary sludge with the Pearson correlation coefficient and P values as shown in [Table 8].
Table 8: Pearson's correlation coefficients between age, sex, and sonographic gallbladder findings in the study (sickle cell disease) group

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  Discussion Top


In this study, the gallbladder was examined in 100 children with SCD, and equal number of age-matched healthy control children using ultrasound scan. Findings in the sickle cell anemia patients included gall stones [Figure 4], wall thickness, and biliary sludge [Figure 5]. The mean age and standard deviation in the SCD group were (9.63 ± 3.79 years, age range 2–15 years), while in the control group (8.49 ± 3.39 year, age range 2–15 years). The lack of significant difference between the above two groups [Table 1] might have been due to the fact that the study participants were matched for age. This was similar to the mean age of 7.96 years used by Nzeh and Adedoyin[16] in Ilorin, Nigeria. The mean age and standard deviation of the SCD children and controls were higher than the study of Ma'aji et al.[15] on the transabdominal ultrasonographic findings in children with sickle cell anemia in Sokoto, North-western Nigeria, where the mean age was 6.1 ± 4.3 years. This may be due to the small size of the sample used in the latter study; however, it was lower than that of Agholor et al.[5] (15.24 ± 10.58 years) in Benin city Nigeria and Balci et al.[1] 19.7 ± 8.5 in Turkey. Because Agholor et al. and Balci et al. studies were in the older age group; 10 months to 51 years of age and 3–46 years, while the present study was conducted in subjects 2–15 years old. It is also much less than that of Oguntoye et al.[17] 27.6 ± 7.607 for cases and 28.0 ± 5.073 for the controls in Ile-Ife, Nigeria, because Oguntoye et al.'s study was conducted in much older age group, with age range 18–45 years. These variations were likely due to differences in age of the study groups with some of the other studies done in much younger subjects while others done in older subjects as well as the sample size of the study population. There was a higher prevalence of SCD in males than females in this study, which was in agreement with the research carried out in Sokoto, Nigeria, by Ma'aji et al.[15] being in the same region as the present study and Kaushal et al.[1] in Bopal, India.

There were 19 subjects having thickened gall bladder wall, which also happened to be the most common abnormality, out of this 11 were male subjects while 8 were female. The age range is 3–15 years, with a mean of 9.61 years. This is similar to a study in Ilorin[16] where 13 cases of gall bladder wall thickening was noted and it was also the most common finding, with the age range of 4–16 years with a mean of 9.54 years. The prevalence of cholecystitis is higher in this study compared to the studies in Sokoto[15] where it was present in seven patients making 9.7%, the age range was 1–15 years and Sudan where only two patients out of 90 presented with cholecystitis making 2.2% with age range of 6 months to 16 years. This difference may be due to the smaller sample size in the latter two studies as well as differences in geographical location with regards to Sudan. In a study carried out in Congo[18] among 190 patients with age range 3–24 years, cholecystitis was found in 48 patients (25.3%) this was much higher than our findings in this study. This may be because the Congolese study involved much older patients, with about 2/3 of their patients being 15 years and above.

The range of the gallbladder volume in the SCD patients was 2.42–33.40 cm3 with a mean gallbladder volume and standard deviation of 10.15 ± 6.21 cm3 [Table 5], the mean gallbladder volume and standard deviation in the male and female children with SCD were 10.87 ± 6.91 cm3 and 8.62 ± 4.09 cm3, respectively, with a P = 0.003 which was statistically significant. The range of the gallbladder volume in the study carried out in Ile-Ife was 3.96–50.16 cm3 with a mean gallbladder volume of 21.87 ± 10.52 cm3 which implied that the gallbladder volumes, as well as the mean volumes, are larger than in our study. This is because the study in Ile-Ife was conducted in older patients with an age range of 18–45 years. The result obtained from our study are similar to that obtained from a study in South Korea carried out in children who were without SCD where the range for the gallbladder volume was 0.3–42 cm3 while the mean gallbladder volume with standard deviation was 8.0 ± 6.1 cm3. This implied that there was no significant difference in the gallbladder volume in children with SCD and that of normal healthy controls.

The prevalence of biliary sludge in this study was 8% and is similar to that of the study carried out in Ilorin[16] where 7.5% prevalence was observed. The age range (4–15 years) of the patients with biliary sludge found in this study was similar (5–16) to the study done in Ilorin.[16] The similarities might be because both studies were conducted within the same age group. However, the prevalence of biliary sludge in this study was higher than that of the studies in Sokoto[15] with 2.8%, Benin city[19] with 1%, Ghana[20] with 1.27%, Sudan[21] with 1.1%, Congo[18] with 2.1% and Turkey[2] 3.6%. These variations were likely due to differences in age of the study groups with some of the other studies done in much older subjects as well as the sample size of the study population and also the difference in geographical location. Biliary sludge is thought to precedes the stone phase, and sludge may disappear without forming stones.[20] In a study in Saudi Arabia[2] performed in 305 children with sickle cell anemia, 50 (16.4%) had biliary sludge and in a follow-up study of these patients with biliary sludge, the majority (65.7%) developed gallstones.

Cholelithiasis is a common complication of sickle cell anemia, the chronic hemolysis of sickle cell anemia predisposes patients to cholelithiasis. The worldwide prevalence of cholelithiasis by ultrasound examination has been reported to be 11%–55% in SCA patients.[3],[18] The prevalence is low in most parts of Africa compared to the Western nations and it varies with age, gender, and method of examination.[18] The prevalence rate of cholelithiasis in Nigerian patients with sickle cell anemia is 4.3%–25% compared to 0.18%–0.8% in the general population.[22] In the present study of 100 patients, 9 were found to have gall stones making the prevalence to be 9% which was similar to a study in Nigeria[22] where the prevalence of gall stones in children was 7.7% and it was also similar to two previous studies in Sudan[21],[23] where the prevalence of gall stones was 11.1% and 11.5%, respectively, as well as the study in Egypt[24] which showed the prevalence of 7.1% and Jamaica[25] with 13% prevalence. The reason for the similarities in the prevalence of gall stones in these studies; might be due to the fact that they were conducted in patients with similar age group as the present study. The prevalence of gall stones in our present study is, however, higher than that of the following studies conducted within the same age group; Sokoto[15] with 5.6%, Ilorin[16] with 4.2% and Benin City[19] with 5%. This might be due to the difference in sample size as the study in Sokoto was done in 71 patients, while the present study involved 100 patients. The differences between the prevalence of gall stone in SCD in this study and that of the studies in Ilorin and Benin City may be related to the higher mean atmospheric temperature in the North-West (40°C–45°C) as compared to the Southern part of the Country (35°C–40°C).[26] These differences in temperature may predispose to dehydration and thereby increases the concentration of bile, which could increase the incidence of gallbladder stones in the patients from the North of Nigeria.[27] Other studies showed higher prevalence than the present study; Zaria[27] 28.4%, Benin City[5] 16%, Sudan[21] 27%, Congo[18] 58.4%, Turkey[2] 30.4%, United Kingdom[28] 58%, Jaimaica[11] 52.7%, and Brazil[29] 45%. The higher prevalence noted in these studies may be due to the fact that they were carried out in older patients; some of the sample sizes in these studies are also larger than that of the present study and also difference in the geographical location may also be a contributory factor. The youngest age in which gall stone was found in this study was 9 years. This is similar to that of the study in Ilorin[16] with 10 years, but other studies showed the presence of gall stone in much younger age group; 2 years in Benin City,[5] 3 years in Saudi Arabia[3] and 5½ years in Nigeria.[22]

There was a significant positive correlation between age and gallstone, biliary sludge, and cholecystitis with Pearson's correlation coefficients (r = 0.254, 0.049, and 0.161, respectively) and P values (P < 0.001) [Table 8]. This is supported by the increase in the prevalence of gall stones (1–5 years = 0, 6–10 years = 2 [6.7%], 11–15 = 7 [14%]); biliary sludge (1–5 year = 2 [10%], 6–10 years = 0 [0%], 11–15 years = 6 [12%]) and cholecystitis (1–5 years = 3 [15%], 6–10 years = 6 [16.7%], 11–15 years = 10 [20%]) in this study. Similar result was also obtained from the study in Egypt,[24] which showed a statistically significant correlation between increasing age and gall stones and biliary sludge formation (P < 0.041). Similarly, studies done in Brazil[30] and the United States[31] also revealed a statistically significant association between the patients' age and gallstone formation (P < 0.001). A study in Jamaica[11] carried out in patients with SCD also showed that gall stones are age-dependent: 15% under 10 years, 22% between 10 and 14 years of age and 36% between 15 and 18 years of age, with a reported prevalence of 50% by age 22 years. The prevalence of cholelithiasis in a study in Benin City[13] also correlated significantly with age P = 0.003. The increasing prevalence of gallstones with age may be attributed to the chronic hemolysis and frequent use of antibiotics such as the quinolones for the treatment of infections in older sickle cell patients.[27]

There was no significant positive correlation between sex and gallstone, biliary sludge, and cholecystitis in this study with Pearson's correlation coefficients; r = 0.129, 0.009, 0.162, and P = 0.202, 0.107, 0.109 for gall stones, biliary sludge, and cholecystitis, respectively [Table 8]. This is also similar to the studies in Benin City[5] and Jamaica[11] where there was no significant positive correlation between the prevalence of cholelithiasis and gender. The lack of correlation between gender and the gallbladder abnormalities may be because patients in this study were young patients where there was little effect of female sex hormones, no parity, and patients are not on oral contraceptives, which may increase the risk of gallbladder disease.[32]

There was a significant statistical difference in the prevalence of gallstones, biliary sludge, and cholecystitis between the patients and controls P < 0.001. This is also similar to the study in Ile-Ife[17] where there was a statistically significant difference in the prevalence of gallstones between the cases and controls (P < 0.001), but the Ile-Ife study differed from the present study in showing no statistically significant difference in the prevalence of cholecystitis and biliary sludge between the patients and controls with P = 0.639 and 0.307, respectively. In this study, none of the controls had gallstones, biliary sludge, or cholecystitis, while in the study from Ile-Ife, one control was discovered to have gallstone and another one having biliary sludge. This may be due to the fact that the controls used in the study from Ile-Ife[17] were much older than the controls in our present study since age was said to be one of the determining factors for the increase in the prevalence of gallbladder abnormality.[11],[25] However, both our study and the one in Ile-Ife showed no statistically significant difference in the volume of gallbladder between the patients and controls with P = 0.0861 and 0.664, respectively. No gallstone was seen in the controls of the Zaria[27] study, which was also in agreement with our study; there was also the significant statistical difference in the prevalence of gallstones between the patients and controls in the Zaria study which was also in agreement with the present study.


  Conclusion Top


This study has shown the usefulness of ultrasonography in evaluating the gallbladder in normal and sickle cell patients. It showed that there was an increased prevalence of gallbladder abnormalities in sickle cell patients when compared with normal healthy controls; the most common abnormality in this study was cholecystitis. The prevalence of gallbladder abnormalities (gallstones, biliary sludge, and cholecystitis) increases with age, while gender did not affect the prevalence of gallbladder abnormalities.

Acknowledgment

We would to acknowledge Matron Bilkisu Jibrin for the appropriate booking of the patients for the ultrasound examination. We also wish to acknowledge the patience and cooperation of the patients, controls, and their parents throughout data collection.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
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