Globally, the burden of gallstone disease is a major public health issue due to its complications which include cholecystitis, cholangitis and pancreatitis [1]. Among different populations, the prevalence of gallstone disease varies. In Western Europe ranges from 5.9% - 21.9% whilst in American adults the prevalence is 10%. In Asia a prevalence rate of 3.2% - 15.6% has been reported [2]. Over ninety percent of patients with gallstones have no symptoms and after 10-year follow-up, only approximately twenty percent of patients will become symptomatic [3]. In 2006, a study in the USA found that more than seven hundred thousand cholecystectomies were performed at an annual cost of 6.5 billion dollars [1]. The West has seen an increased prevalence of the disease, and in 2004, there were 1,092 gallstone-related mortalities reported in the USA, although the mortality is relatively low at 0.6% [4].

Gallstone disease has been considered to be a relatively rare disease in Sub-Saharan Africa [5,6], however, there is a steady shift towards a Westernized diet and an increase in urbanization, hence resulting in an increase in the incidence of gallstone disease in this part of the world [5]. In African countries, the prevalence rates reported are 5.2% and 5.9% in Ethiopia and Ghana, respectively [7,8]. A recent study found a high prevalence of gallstones at 22% in patients having an abdominal ultrasound in Mulago Hospital, Uganda [9].

Cholesterol or pigment stones are the several etiological factors that are responsible for gallstone disease. In Africa, sickle cell disease is primarily responsible for pigment cholelithiasis and its prevalence increases with the severity of haemolysis and with increasing age [10]. The risk factors for cholesterol stones include obesity, hypertriglyceridaemia, high-calorie diet and female gender [11]. An increased risk of gallstone disease is reported in patients with type 2 diabetes [11].

Gallstone-related complications tend to occur in 20%-40% of gallstone patients [12]. Laparoscopic or open cholecystectomy is the treatment of choice with nearly seven hundred thousand cholecystectomies performed in the USA [2]. In Sub-Saharan African countries an increase in gallstone disease has been reported and hence the number of cholecystectomies has increased significantly in the last decade [13].

In Uganda, there is a paucity of literature evaluating the epidemiology of gallstone disease. Studies have found that the overall prevalence of gallstones in our population is twenty-two percent and that laparoscopic cholecystectomy is responsible for twenty-one percent of the total number of laparoscopic surgeries [9,14]. There is a high frequency of SCD which is the main risk factor for gallstone disease in Sub-Saharan Africa. The prevalence of SCD in Uganda was found to be 13.3% with eight districts recording a prevalence of greater than 20% [15]. Studies from Senegal, West Africa, have shown a prevalence of 10% with SCD [16] and 9.4% of SCD patients present with gallstones [16].

In Sub-Saharan Africa, the prevalence of metabolic factors such as diabetes, hypercholesterolaemia and obesity is increasing [17,18]. With the increasing prevalence of obesity, Western-type diet and metabolic risk factors for gallstone disease and an ageing population, it is crucial to know the profile of these patients [19]. Prevention of cholelithiasis can be done by recognizing modifiable risk factors. Understanding the profile of gallstone disease patients will facilitate better treatment options and may reduce the complications of this condition.

Compared to males, females have better health-seeking behaviour and hence tend to have an ultrasound performed during the assessment of their health [20]. Compared to men more women tend to develop cholesterol gallstones. The reason may be due to ovarian hormones. Preliminary findings from studies have shown that in pregnancy the gallbladder function and biliary lipid composition may be abnormal [21,22]. Pregnancy has been found to be a major risk factor for the formation of gallstones with the risk increasing proportionately with the number of pregnancies [22]. Oestrogen has been found to increase the secretion of cholesterol in the bile [22] and hence this may be the reason for more pregnant patients presenting with gallstones.

The prevalence of gallstones in Uganda was found to be 22% [9]. Therefore the prevalence in Uganda is higher than that found in Ethiopia (5.2%) and Ghana (5.9%) [7,8]. The reason for this difference in prevalence may be due to dietary differences, genetic differences as well as differences in physical activity with Ugandans carrying out less physical exercise [23]. This is lower than the 72.2% prevalence found in British adults, the 60.9% prevalence over 5 years in Nigerians, and the 70% prevalence found in Pima Indians [5,24]. The reason for these differences in prevalence may be due to differences in population-based studies compared to single-centre hospital-based studies.

Factors Linked to Gallstone Disease in Uganda

A history of weight loss was found to be associated with a greater risk (OR: 1.2) of having gallstone disease [9]. This is in keeping with findings from other studies which have shown that dieting is a risk factor for gallstone disease [25]. Patients having a previous history of biliary symptoms were more likely to have gallstones (OR: 2.9) [9]. A high frequency of Ugandan patients present with epigastric pain and are subsequently found to have gallstones. In our setting many patients are initially treated for peptic ulcer disease and eventually gallstones are diagnosed on ultrasound imaging.

A history of alcohol consumption has been found to have a higher risk of having gallstone disease in a study involving participants from Uganda however this was not found to be statistically significant [9]. Women using hormone contraceptives have also been found to be three times at greater risk of developing gallstones. Ugandan women tend to use hormonal contraceptives for family planning according to the Uganda Demographic Health Survey. Several studies have shown that compared to males, females have a greater risk of gallstone disease which may be attributed to hormone contraceptive use, parity and female sex hormones. In the first year postpartum, a major non-obstetric cause of hospitalization is gallstone disease [26].

In Uganda, pregnancy and parity have not been found to be significant contributing factors for gallstone disease due to the small sample sizes for the studies conducted to date [9]. Another reason is that pregnant women are more likely to receive their ultrasound in the antenatal unit rather than the radiology department [9]. These findings from Uganda are consistent with those of other studies which showed that pregnancy and parity are not risk factors for gallstone disease [27,28].

Gallstone Disease in Patients with Sickle Cell Anaemia from Sub-Saharan Africa

In SCD patients, there is an increased catabolism of haemoglobin and hence patients who have severe disease have an increased risk of gallstone formation. Patients with severe forms of sickle cell anaemia may not survive into adulthood. The concentrations of unconjugated and conjugated bilirubin in the serum may not reflect the concentrations of these substances in the gallbladder hence it may not be used as an indicator of pigment gallstone production [29].

There is an excessive liver secretion of unconjugated bilirubin into the bile in patients with SCD due to haemolytic anaemia. Bilirubin saturation and eventual precipitation may be due to bilirubin in bile presenting in substantial amounts [29]. The plain abdominal X-ray may show only ~10% of all gallstones in the general population [29]. The presence of >4% calcium dry weight indicates radio-opaqueness [30]. The pigment stones are formed by polymerization of insoluble unconjugated bilirubin [30,32,33].

Gallstones formed in patients with SCD are of the pigment type and are either calcium bilirubinate or bilirubin [31,34]. Since the presence of >4% calcium by dry weight in gallstones is needed for radio-opaqueness, a plain abdominal X-ray may visualize only 10% of gallstones in the general population [30]. The pigment stones in patients with sickle cell disease have little or no calcium bilirubinate and therefore would not be shown on a plain abdominal X-ray. Compared to pure pigment stones, calcium bilirubinate stones are precipitated faster and are radio-opaque stones. Calcium bilirubinate stones present at a younger age supporting the theory that in patients with chronic haemolytic anaemia, there is early precipitation of calcium bilirubinate pigment stones [35].

Until the advent of ultrasonography, all SCD patients presenting with acute abdominal pain were taught to be due to sickle cell haemolytic crises. The differentiation between acute cholecystitis and sickle cell crises may be difficult. The diagnosis can be made taking the following factors into consideration: a) in acute cholecystitis, the classical picture is a positive Murphy’s sign with pain in the right upper quadrant, while early in the disease the pain may be diffuse. b) The pain and tenderness in sickle cell crises are associated with a raised unconjugated bilirubin concentration and are usually generalized and nonspecific. c) As an ultrasound transducer passes over the gallbladder area, patients with acute cholecystitis complain of pain. Both unconjugated and total bilirubin concentrations may be normal [36]. d) Biliary colic is sudden in onset and may last for several hours in contrast to bowel colic which consists of paroxysms of pain occurring in intervals of 5-10 minutes [37].

In SCD patients it is possible that a haemolytic crisis occurs in patients with acute cholecystitis and the reverse is also true. In a sickle cell crisis, the increased production of unconjugated bilirubin may precipitate acute cholecystitis. Differentiation between sickle cell crises and acute cholecystitis may be different in these cases [36].

As the mean age of the SCD population increases, gallstone disease will become more common in this patient population. In SCD patients with an abdominal crisis, an abdominal ultrasound should be carried out in order to prevent missing episodes of acute cholecystitis [36,37].

Presentation of Patients with Gallstone Disease

The majority of patients presenting with gallstones in Uganda have been found to have epigastric pain. A study reported that epigastric pain was the commonest symptom followed by fever and jaundice respectively [9]. Several studies have shown that the majority of gallstone patients remain asymptomatic and that after 10 years of follow-up, 20% of these become symptomatic [3]. In Uganda, the high number of symptomatic patients registered may be due to the fact that the studies conducted to date are not population-based studies but hospital-based studies [9]. A study has shown that it is difficult to distinguish between asymptomatic and symptomatic gallstones in a population [25].

In patients presenting for a routine abdominal ultrasound, the prevalence of gallstone disease is high in Uganda. At the presentation for an abdominal ultrasound scan, the majority of patients with gallstone disease had symptoms. A significant risk factor for gallstone disease is a history of oral contraceptive use. The hormonal contraceptive use as a risk factor for gallstone disease should be investigated through further studies in the Ugandan population. Women using these contraceptives, especially with co-morbidities such as SCD should be informed of the high risk and given alternative treatments. In patients with SCD having a sickle cell crisis, an abdominal ultrasound should be carried out in order to prevent missing episodes of acute cholecystitis. In Uganda, a screening programme using abdominal ultrasound should be implemented in the population to estimate the burden of gallstone disease and for the early detection and management of the disease.

Ethical Approval

As per international standards and university standards, ethical approval has been collected and preserved by the author.

Acknowledgements

The author wishes to thank clinical staff in the Department of Surgery of Masaka Regional Referral Hospital for their contribution in data collection and their contribution towards the clinical management of gallstone patients operated by the author. The author also wishes to extend his warm thanks to the nursing staff, medical officers, and anesthesiologists who worked with him in the surgery theatres of Masaka Regional Referral Hospital.

Conflict of Interest

Author has declared that no competing interests exist.

Funding

The author declares that he received no funding to write this manuscript and assumes full responsibility for the contents of this article.

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