Pediatric cholelithiasis is known to be uncommon. However, recent series documented increased detection rate of gallstones in the pediatric age group [1]. Many risk factors have been described for the development of gallstones in children as hemolytic disorders, prematurity, parenteral nutrition, chronic hepatobiliary diseases, cystic fibrosis, genetic factors, sepsis, ileal diseases, obesity, ceftriaxone use, and abdominal or cardiac surgeries [6]. Idiopathic gallstones, with no identifiable risk factors, have been reported in the literature in the range of 23.2–52.5% [2, 7, 8]. This is close to the current study where no risk factors were identified in 28.6%of cases.
Twenty to 40% of all pediatric gallstone disease can be attributed to hemolytic diseases [9]. Recent studies demonstrated hemolytic diseases in 21.6% and in 11.8% of cases [10, 11]. In the current study, hemolytic anemia was identified as a risk factor in 34.3%. G6PD deficiency was identified as a risk factor in 9 cases (25.7%); this high percentage may be explained by the high prevalence of G6PD deficiency in Egypt as reported by Abo Elella et al. in 2017 who estimated an overall prevalence of G6PD deficiency of 4.3% among Egyptian neonates [12].
Therapy with ceftriaxone was identified as a risk factor in 17.1% of cases, in agreement with literature where ceftriaxone use was responsible for 6% and 27.3% of cases of gallstones [2, 13].
Chronic biliary disease in the form of cholestasis was present in 8.6% of our cases, which is close to the results of Dooki and Norouzi (2013) and Della Corte et al (2008) studies (7.5% and 5% respectively) [2, 13]. It is known that patients with chronic cholestasis especially those with progressive familial intrahepatic cholestasis (PFIC) are prone to cholelithiasis. This is attributed to impaired bile acid secretory function and supersaturation of bile with cholesterol [14]. The three cholestatic patients in this study had normal GGT cholestasis; however, the unavailable genetic analysis in Egypt limited the ability to finally diagnose their specific conditions. These patients might have had PFIC 1 or 2.
Unlike adults, children are likely to be symptomatic [8]. Our cases showed symptomatic presentation in 62.9%, which is comparable to other studies [2, 9, 10]. On the other hand, the study of Kirsaclioglu et al. [11] showed that symptomatic patients were significantly older than asymptomatic patients, and abdominal pain was the most frequent symptom [11]. Our cases also showed abdominal pain to be the most common symptom in 51.4%.
Complications were documented in 20% of our cases, which is close to the literature, where they were reported in about 7–20% of cases [6]. While some older studies reported pancreatitis as the most common complication [15, 16], recent studies reported cholecystitis and choledocholithiasis to be more common [1, 11, 17]. Our study showed choledocholithiasis to be more common; meanwhile, none of our cases showed pancreatitis or acute cholecystitis. The relatively high complication rate seen in our study group could be explained by the nature of our hospital being a tertiary referral hospital. Severe and complicated cases are commonly referred to our institution, while uncomplicated cases can be managed conservatively in secondary referral centers.
In children, cholecystectomy is recommended for symptomatic and complicated gallstones. It is also recommended for asymptomatic gallstones with chronic hemolytic anemia and asymptomatic large sized gallstones (> 2 cm) for the risk of gallbladder carcinoma [4]. Otherwise, expectant management with periodic clinical and sonographic assessment appears more appropriate [4]. LC was done for 7 of our patients: 6 of them because of choledocholithiasis and one for symptomatic gallstone with agonizing typical right upper quadrant pain. Hajong et al. in 2013 reported 15 non-hemolytic cases of gallstones managed by LC; 80% were symptomatic, and 13.3% were asymptomatic while 6.7% had complicated gallstone in the form of pancreatitis [18]. Another study showed that primary indications for surgery in pediatric population were symptomatic cholelithiasis (53%), choledocholithiasis (28%), and biliary dyskinesia (16%) [9].
Histopathological analysis of the removed gall bladder (GB) in this study was available in 6 cases and revealed chronic cholecystitis in all of them (100%); none had papillomatosis or adenoma of GB. This is comparable to the results of Kim et al. study, who showed that, in 24 cases for whom cholecystectomy was performed, histopathology of most cases revealed chronic cholecystitis [19]. On the other side, the removed gallbladders in Della Corte et al. study revealed chronic cholecystitis in 84.6%, papillomatosis in 5.1%, adenoma in 2.6%, and normal GB in 7.7% [2].
Eighty percent of our cases were managed conservatively, with periodic clinical, laboratory and US follow-up for 8 to 34 months. None of them developed complications, while 2 cases showed complete spontaneous resolution of gallstones, and 8 cases showed resolution of symptoms and/or sonographic improvement. This may justify the conservative management for uncomplicated cases of gallstones in pediatric population, especially in infants. Jeanty et al., who performed their study on infantile cholelithiasis, observed complete resolution of stones in 25% of the cases [20], while Gokce et al. [21] reported spontaneous complete resolution in 50% of infantile cases and 19.8% in older children [1]. This was higher than the resolution rate observed in the current study.
Limitations of this study include the small sample size and the short duration of follow-up in some patients. Moreover, as the study was conducted in a tertiary care unit, many uncomplicated cases may be diagnosed and managed in other centers without referral to our unit, which may explain the higher rate of complications at presentation of our cases.
The strength of this study is that it is the first study to evaluate gallstones among infants and children in Egypt. The absence of a national screening program for G6PD deficiency and other hemolytic anemias, together with high incidence of consanguineous marriages, raises the risk of childhood gallstones in Egypt.