Cholelithiasis After Sleeve Gastrectomy and Effectiveness of Ursodeoxycholic Acid Treatment

Abstract

Aim:

Few adverse effects may occur after bariatric surgery, one being the formation of gallstones. The aim of this study is to determine the incidence of cholelithiasis after laparoscopic sleeve gastrectomy (LSG) and whether ursodeoxycholic acid (UDCA) treatment reduces gallstone formation.

Materials and Methods:

Gall bladders of all patients planned for LSG were preoperatively checked by ultrasonography (USG). Patients who had no documented gallbladder pathology before LSG and who had USG at 12th month and 2 years follow-up after LSG were included in the study. The incidences of newly developed cholelithiasis, cholecystectomy, and endoscopic retrograde cholangiopancreatography (ERCP) requirement in patients who did not receive any UDCA treatment (pre-2015 protocol, n = 128) was compared with the corresponding numbers in patients who regularly used 500 mg/day oral UDCA for 6 months after the LSG (post-2015 protocol, n = 152).

Results:

Between January 2012 and October 2018, 717 LSGs were performed in two centers and after exclusions, 280 patients were eligible for evaluation. Sixty-four of 280 (23%) patients developed cholelithiasis after LSG and cholecystectomy was performed in 24 patients (8.6%) for symptomatic cholelithiasis. In the non-UDCA group, 48 patients developed cholelithiasis (n = 48/128, 37.5%) compared with 16 patients in the UDCA group (n = 16/152, 10.5%) (P < .001). Compared with 5 patients in the UDCA group, 19 patients underwent cholecystectomy (39.6%) in the non-UDCA group due to symptomatic cholelithiasis (P = .55) and 5 of these patients also required an ERCP. No ERCP became necessary in the UDCA group (P = .2).

Conclusions:

An almost fourfold decrease in the rate of new gall stone formation with 500 mg daily UDCA treatment was impressive and may suggest routine UDCA treatment after LSG. Given the rate of exclusions and follow-up differences among the groups, certainly, randomized trials, with less exclusion are needed to provide conclusive evidence.

Introduction

Bariatric surgery is currently the best-proven treatment for obesity.¹ Worldwide, the obese population is rapidly increasing, and more and more patients are being operated every year.² However, some undesirable effects may occur after bariatric operations such as increased risk for gallstone formation and related complications. It has been known for many years that formation of gallstones is associated with rapid weight loss.³ The oversaturation of bile along with increased cholesterol and other factors are thought to be the reasons for gallstone formation.⁴ Slow and inadequate emptying of the gallbladder may be another factor.⁵ Although varying between studies, the incidence of cholelithiasis after bariatric surgery can be as high as 30%.^6–12

The aim of this study was to determine whether postoperative ursodeoxycholic acid (UDCA) treatment has a protective effect against gallstone formation after laparoscopic sleeve gastrectomy (LSG). The rate of new stone formation, cholecystectomy requirement, and relevant complications in UDCA-treated group is compared with the corresponding figures in the non-UDCA group.

Materials and Methods

All patients underwent an abdominal ultrasonography (USG) before surgery and all data were prospectively recorded. Starting from January 2015, 2 weeks after the LSG, all patients were routinely prescribed 500 mg/day, per-oral, UDCA for 6 months. All patients were followed up at 3rd, 6th, and 12th months after LSG and annually thereafter during which laboratory tests and clinical assessment was done. Abdominal USG was repeated yearly.

Inclusion criteria

Patients who underwent LSG and completed 2 years follow-up in two centers were the subjects.

Exclusion criteria

Patients having biliary stone/sludge before LSG and those having had a previous cholecystectomy were excluded. Furthermore, patients who interrupted the UDCA treatment even for a short period or followed an irregular medication course were also excluded.

Follow-up

Non-UDCA patients (operated before 2015) compared with UDCA group (operated after 2015) were followed longer. Because of the sequential nature of the groupings, only the first 2 years' outcome results were evaluated in both groups.

The rates of new biliary stone formation, symptomatic cholelithiasis requiring cholecystectomy or endoscopic retrograde cholangiopancreatography (ERCP) during the first 2 years after LSG in UDCA treatment group was compared with the corresponding data in the non-UDCA group.

Statistical analysis was performed using SPSS (version 21, SPSS, Inc., Chicago, IL). Standard deviation and mean values were used for the variables with normal distribution and median values were used for the variables that were not normally distributed. Chi-square or Fisher's exact tests were used for categorical variables, whereas for continuous variables, independent-samples t-test or Mann–Whitney U test were performed. P < .05 were considered statistically significant. The study was approved by the institutional ethics committee.

Results

Between January 2012 and October 2018, 717 patients (56.8% female) with a mean age of 38.2 ± 11.4 years and median body mass index (BMI) of 42.5 (29.8–74.2) kg/m² had undergone LSG. A total of 126 patients were excluded from the study (63 [8.8%] had a history of cholecystectomy, 48 [6.7%] underwent cholecystectomy concomitantly with LSG and 15 [2.1%] had asymptomatic gallstones). Moreover, 311 patients were further excluded because of lack of compliance with the UDCA treatment protocol (n = 305) or missing data (n = 6). After all exclusions, a total of 280 patients were evaluated; 128 were not administered UDCA, whereas the remaining 152 received UDCA treatment. The demographics of both groups are shown in Table 1.

Table 1.

Patients' Characteristics

	Without UDCA (n = 128)	With UDCA (n = 152)	P
Men/women	47/81	62/90	.48
Age (years)	38 ± 11.6	39.8 ± 10.6	.23
Preoperative BMI (kg/m²)	43.3 (33–67)	40.95 (32–66)	<.01
Excess weight loss at 1 year (%)	88.35 ± 21.3	93.6 ± 22.06	.04
Gall stone development (within 2 years post-LSG)	48 (37.5%)	16 (10.5%)	<.01
Cholecystectomy (within 2 years post-LSG)	19	5	.55
ERCP requirement (within 2 years post-LSG)	5	0	.2

Values are means ± SD, median (min–max) or number of subjects.

BMI, body mass index; ERCP, endoscopic retrograde cholangiopancreatography; LSG, laparoscopic sleeve gastrectomy; SD, standard deviation; UDCA, ursodeoxycholic acid.

Overall, 64 of 280 (23%) developed cholelithiasis after LSG. Cholecystectomy was performed in 24 patients (8.6%) for symptomatic cholelithiasis. Among the 152 UDCA-treated patients, 16 developed cholelithiasis (10.5%), whereas this number was 48 in the 128 untreated patients (37.5%, P < .01). The cholecystectomy rate was 31.6% (n = 5/16) and 39.6% (n = 19/48) in the UDCA treatment and non-UDCA groups, respectively (P = .55). In the non-UDCA group, 5 patients underwent an ERCP in addition to cholecystectomy, whereas no ERCPs were required in the UDCA treatment group (P = .2) (Table 1).

No allergic reactions or serious side effects such as hepatotoxicity due to use of UDCA was documented.

Discussion

There is still debate about the prevention of gallstone formation and the treatment of cholelithiasis after LSG. Indeed, the incidence of developing cholelithiasis after LSG reported in previous studies varies widely. In a large cohort of 361 patients, the incidence of post-LSG cholelithiasis was 7.5%.¹³ Many other studies report this rate at ∼6%.^14–16 Based on these numbers, some authors do not recommend post-LSG UDCA treatment or even regular sonographic follow-up.^13,14,17 In contrast, there are also studies to report high incidence rates of cholelithiasis after LSG.^12,18 Nevertheless, in our study, the incidence of cholelithiasis was almost 40% in the untreated group.

Present retrospective analysis showed that 500 mg/day per oral UDCA treatment for 6 months after LSG effectively reduced gallstone formation during the first 2 years after surgery. Few studies in the literature reported that UDCA treatment prevents gallstone formation after LSG. In a randomized study conducted in the United States, the incidence of gallstone formation in patients who were treated with 500 mg/day UDCA for 6 months was found to be 9%, compared with 40% in the untreated group.¹⁹ In another large retrospective study conducted in Egypt, it was found that 6 months of UDCA treatment after LSG decreased the incidence of stone formation from 5% to 0%.²⁰ In our study, the daily use of 500 mg of UDCA for 6 months postoperatively reduced gallstone formation from 37.5% to 10.5%, almost fourfolds.

Two studies have reported a 7.5% and 0.9%^13,21 the rate of cholecystectomy due to symptomatic gallstones after LSG, and this rate was 8.6% in our overall patient population. Five patients in the no-treatment group required an ERCP and cholecystectomy was done due to symptomatic gallstone formation in 39.6%. One of these patients was operated for acute cholecystitis elsewhere and had an iatrogenic biliary injury requiring reconstruction.

Whether asymptomatic gallstones detected before LSG require cholecystectomy in the same surgical session is a matter of controversy. There are many studies indicating that very few of the asymptomatic gallstones become symptomatic after LSG and, therefore, agreeably, cholecystectomy is unnecessary during the LSG.^14,22

There are several limitations of our study. First issue was the problem of medication incompliance seen in the majority of patients after LSG. Therefore, despite the close monitorization of the patients, the number of patients who regularly used 500 mg UDCA for 6 months was limited to 152 making the number of exclusions excessive. The slight difference between the two groups in terms of preoperative BMIs (Table 1) is probably due to these exclusions. Second important problem is that this study is not a randomized trial and the follow-up duration in non-UDCA group is considerably longer than the UDCA group. However, such bias is avoided as only 2 years follow-up results for all patients in both groups is taken into consideration.

In conclusion, our results showed that, after LSG, with 500 mg/day UDCA treatment, the incidence of new gallstone formation may be reduced. Further randomized trials with less exclusion are clearly needed to provide conclusive evidence and to establish precise guidelines on the issue.

Footnotes

Disclosure Statement

No competing financial interests exist.

Funding Information

No funding was received.

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