Introduction
PSC is chronic infammatory disease of bile ducts leading to strictures of bile duct and eventually to liver cirrhosis. Chronic inflammation is associated with markedly increased risk of cholangiocancer (CCA). In addition, gall bladder abnormalities are common in patients with PSC1 such as cholecystitis, gallstones, polys and gallbladder carcinoma (GBCA). Increased fasting gallbladder volume has been reported with normal gallbladder emptying2. Due to the increased risk of GBCA3 cholecystectomy is recommended in PSC with gallbladder polyps ≥8 mm and smaller polyps growing4. However, cholecystectomy has been associated with impaired PSC outcome. A study consisting of 11 PSC patients with cholecystectomy suggested protective role of gallbladder based on MRCP changes and elevated AST levels in patients with cholecystectomy. No significant difference in serum bile acids was observed in patients with or w/o cholecystectomy5. Another small study including five PSC patients with cholecystectomy showed that cholecystectomy was associated with worse Mayo scores and an elevated FIB46. More than 50% of PSC have enlarged gallbladder which is suspected to be caused by hyperpressure in the biliary tract5. Cholecystectomy may thus eliminate this reserve function and lead to progression of bile duct strictures.
Aims & Methods
To evaluate the impact of cholecystectomy on liver enzyme levels, biliary bile acid composition, bile duct disease progression, and overall outcomes in a large PSC patient cohort, we analyzed data from 1,009 individuals enrolled in the prospective Helsinki PSC registry. Of these, 114 patients (11.3%) had undergone cholecystectomy—34 prior to and 80 following the PSC diagnosis. Patients with gallbladder cancer were excluded. Clinical and laboratory parameters were collected, along with data on disease progression based on sequential ERC examinations scored by the Helsinki ERC score7. Additionally, bile composition was analyzed in a subgroup of 157 patients receiving UDCA therapy, 32 of whom had undergone cholecystectomy.
Results
Demographics, liver function tests, and outcomes stratified by cholecystectomy, are presented in the table. We found no differences between the three groups (no cholecystectomy, cholecystectomy done prior or after PSC dg) regarding the progression of bile duct disease or its severity, liver function tests, development of biliary dysplasia or need for dilatation, Mayo- and MELD-scores. The cumulative incidence of the composite end point (= transplantation, liver related death, HCC or CCA) did not differ between groups. The molar-% of phospholipids were lower and cholic acid and deoxycholic acid (mg) elevated in bile in patients with cholecystectomy, whereas no differences were found in UDCA content.
| Variable | No cholecystectomy,
n=895 | Cholecystectomy before PSC dg,
n=34 | Cholecystectomy after PSC dg,
n=80
| P-value** |
| Men, n(%) | 537(60)
| 12(35)
| 39(49)
| 0.003 |
Age, mean (SD)
| 37(13)
| 46(12)
| 43(13)
| <0.001
|
BMI, mean(SD)
| 25.6(4.5)
| 26.5(4.2)
| 26.4(4.5)
| 0.22
|
ERC-score, mean (SD)
| 5.8(3.5)
| 6.4(3.7)
| 6.4(3.5)
| 0.16
|
| Need for dilatation | 398(44)
| 18(53)
| 42(53)
| 0.26 |
P-AST, U/l, median (IQR)
| 36(25,58)
| 37(28,52)
| 34(26,51)
| 0.83
|
P-ALP, U/l, median (IQR)
| 132(96,222)
| 130(88,191)
| 113(84,179)
| 0.082
|
Mayo Score, mean (SD)
| -0.29(0.84)
| -0.10(0.63)
| -0.10(0.78)
| 0.079
|
| Composite end point, n [Incidence (95% CI:)]* | 142 [16.4 (13.8 -19.3)]
| 6 [13.31 (4.88 - 28.97)] | 14 [14.16 (7.74 - 23.76)] | 0.66
|
* Per 1 000 person years
** Adjusted for sex and PSC age
Conclusion
In this large study investigating the impact of cholecystectomy on PSC outcomes, we found no effect on liver enzyme levels, prognostic indices, bile duct disease progression, or overall prognosis, regardless of whether the procedure was performed before or after the PSC diagnosis.
References
1. Said K, eta al. Journal of Hepatology 2008; 48:598–605
2. Said K, et al. World J Gastroenterol 2009; 15: 3498-3503
3. van Erp LW, et al. Liver Int 2020; 40:382–92.
4. Chazouilleres O et al. EASL Clinical Practice Guidelines on sclerosing cholangitis. J Hepatol 2022; 77:761–806
5. Cazzagon N, et al. JHEP Reports 2023. https://doi.org/10.1016/j.jhepr.2022.100649
6. Miyake N, et al. Cureus 17(3): e80184. DOI 10.7759/cureus.80184
7. Boyd S, et al. Endoscopy. 2016;48:432-9.