Long-term effects of cholecystectomy on bile acid metabolism

doi:10.1016/0270-9139(95)90406-9

Hepatology

Volume 21, Issue 1, January 1995, Pages 41-45

https://doi.org/10.1016/0270-9139(95)90406-9 Get rights and content

Abstract

Comparative studies between different patient groups have suggested that cholecystectomy enhances bacterial dehydroxylation of the primary bile acid cholic acid (CA) to the secondary bile acid deoxycholic acid (DCA). DCA may exert a cocarcinogenic effect on the colonic mucosa. In a short-term follow-up study on nine female patients we found no alterations of the CA or DCA pools after cholecystectomy. However, in the long term, cholecystectomy could promote changes of the intestinal bacterial flora and thereby lead to enhanced conversion of CA to DCA, causing an expansion of the DCA pool size and a reduction of the CA pool size. To test this hypothesis, pool sizes, fractional turnover rates (FTR), and synthesis or input rates of CA, chenodeoxycholic acid (CDCA) and DCA were determined in 12 female patients before and again 5 to 8 years after cholecystectomy. In the long term, pool size and synthesis rate of CA had not changed and DCA pool size had expanded by only 7.5% (not significant [NS]). DCA input increased by 32% (NS) but was balanced by an increase in FTR of 36%. Pool size (−17%) and synthesis rate (−5%) of CDCA were not significantly diminished. Overall, the sizes of the total bile acid pool (−6%, NS; 50 ± 8 vs. 53 ± 13 μmol/kg) and the pool fractions of CA (44.7 ± 10.3% vs. 42.8 ± 7.6%) and DCA (25.5 ± 14.1% vs. 23.6 ± 9.3%) remained similar. In conclusion, cholecystectomy causes no changes in bile acid pool composition and thus has no adverse effects on bile acid metabolism in the long term.

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Previous cholecystectomy is common in patients with short bowel syndrome (SBS). An intact gallbladder is beneficial in preventing cirrhosis in SBS patients, but the nutritional consequences of cholecystectomy are largely unknown. Our aim was to evaluate the effect of pre-SBS cholecystectomy on need for chronic parenteral nutrition (PN).
We reviewed 485 adults with SBS: 267 underwent cholecystectomy prior to SBS and 218 patients had an intact gallbladder. Demographic data, intestinal anatomy, and nutritional outcome were compared.
Pre-SBS cholecystectomy patients were more likely to have had postoperative SBS and BMI >35. Intestinal remnant length and anatomy type and performance of surgical rehabilitation procedures within the first year were similar.
Overall, there was no significant difference in the need for PN > 1year between the two groups. There was also no significant difference in the need for PN > 1year in any specific subgroup of intestinal remnant length or intestinal anatomy.
Cholecystectomy performed prior to the development of SBS does not influence the nutritional prognosis of SBS, regardless of the intestinal remnant length and anatomy type.
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In fact, FGF15/19 regulates energy expenditure and insulin sensitivity in diabetic mice due to the activation of adipose tissue thermogenesis.55,56 Another in vitro studies have demonstrated the inhibitory effect of FGF-19 on the synthesis of hepatic fatty acids, as well as the decrease in FGF19 serum levels after cholecystectomy can alter metabolic regulation, favoring the accumulation of triglycerides in the liver.57 It was found that a lower serum level of FGF19 was associated with an increased risk of NAFLD.58
Hepatic steatosis and gallstone disease are highly prevalent in the general population; the shared risk factors are age, ethnicity, obesity, insulin resistance, metabolic syndrome, atherosclerosis, risk of cardiovascular disease, and mortality. The presence of insulin resistance is the critical element in this association because it represents a crucial link between metabolic syndrome and non-alcoholic fatty liver disease, as well as a higher susceptibility to gallstone formation.
An exhaustive search engine investigation of gallstone disease, cholecystectomy, and liver steatosis latest literature was made.
Clinical studies and systematic reviews suggest an association between gallstone disease, cholecystectomy, and hepatic steatosis.
The bidirectional relationship between liver steatosis and gallstone disease and cholecystectomy is summarized in the role of insulin resistance, lipid metabolism, bile acids signaling pathways regulated by transcription factors expression, and to the gallbladder physiological role; however, more epidemiological and experimental studies should be complemented.
Cholecystectomy is an independent factor of enhanced insulin release and impaired insulin sensitivity
2020, Diabetes Research and Clinical Practice
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Cholecystectomy is the best and most cost-effective treatment for gallstone disease, which explains why it is one of the most common operations performed worldwide. This procedure has long been regarded as safe with no deleterious effects on health [1,2]. However, recent studies indicate that cholecystectomy could be a risk factor for several components of metabolic syndrome, including dyslipidemia, hypertension, and insulin resistance (IR) [3–5].
Cholecystectomy is a risk factor for insulin resistance and diabetes, but the association between cholecystectomy and insulin release/sensitivity remains obscure. We investigated the association between cholecystectomy and the factors related to glycemia and glucose tolerance.
A cross-sectional study was conducted in 2011 with 10,027 participants aged $\geq$ 40 in Nanjing, China. After applying exclusion criteria, 8,030 participants were divided into three groups: 1, without gallbladder disease (n = 6783); 2, with gallbladder disease but without cholecystectomy (n = 857); and 3, with cholecystectomy (n = 390).
Various indexes of blood glucose and insulin level after the oral glucose tolerance test (OGTT) were assessed. The association between gallbladder disease or cholecystectomy and diabetes was evaluated with logistic regression models. Group 3 had a higher prevalence of newly diagnosed diabetes by OGTT criteria compared with groups 2 and 1, respectively (20.5% vs. 12.4% vs. 10.6%, P < 0.001). The adjusted odds ratio and 95% confidence interval of diabetes associated with cholecystectomy were 1.546 (1.168, 2.046) (P = 0.002). Pattern 2, which was characterized by a lasting late insulin response, was more frequent in group 3 compared with groups 2 and 1, respectively (61.0% vs. 54.3% vs.48.3%, P < 0.001). After adjusting for confounding factors, a higher total insulin release and lower Matsuda insulin sensitivity index (P < 0.001) were found in group 3 compared with the other two groups.
Cholecystectomized subjects demonstrated a higher prevalence of diabetes characterized by lower peripheral insulin sensitivity and higher total insulin release.
Relationship between remote cholecystectomy and incident Clostridioides difficile infection
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Cholecystectomy (CCY) is associated with increased faecal levels of secondary bile acids. Secondary bile acids confer resistance to Clostridioides difficile infection (CDI, formerly Clostridium difficile infection) in animal studies. This study tested the hypothesis that CCY confers protection against CDI by increasing gut levels of secondary bile acids.
This was a retrospective case–control study. Adults hospitalized between January 2010 and June 2017 at our institution were included. CDI cases were defined as a positive stool PCR followed by anti-CDI treatment and were matched 1:1:1 with two control groups (those who tested negative for CDI and those who were not tested for CDI) by sex, age group, body mass index (BMI), and exposure to antibiotics. CCY was defined as a history of CCY at least 6 months prior to the index C. difficile test or the index admission date in the untested controls. Conditional logistic regression modelling was used to estimate the relationship between remote CCY and risk for CDI.
The final study population was 7077 (2359 CDI cases, 2359 matched controls without CDI, and 2359 matched controls not tested for CDI). Rates of remote CCY did not differ among the three groups (14.4% vs. 15.5% vs. 14.2%) and this result was unchanged after adjusting for additional clinical factors (adjusted OR 0.90, 95% CI 0.76–1.06 comparing CDI cases vs. matched controls without CDI; adjusted OR 1.04, 95% CI 0.78–1.39 comparing CDI cases vs. matched controls not tested for CDI).
There was no association between remote CCY and risk for CDI.
Anatomy of rodent and human livers: What are the differences?
2019, Biochimica et Biophysica Acta - Molecular Basis of Disease
Citation Excerpt :
In humans, cholecystectomy is frequently performed, because 10–15% of the adult western population has bile stones and 1–4% become symptomatic within a year, especially when middle aged [50]. Humans [51] and mice [52–54] do quite well after cholecystectomy. The intervention decreases the bile acid pool, but because secretion rates of bile acids and cholesterol, and the enterohepatic recirculation rate are increased, in particular during fasting, digestion and absorption remain relatively unaffected ([53–56]; for a recent review, see [40]).
The size of the liver of terrestrial mammals obeys the allometric scaling law over a weight range of >3 ∗ 10⁶. Since scaling reflects adaptive changes in size or scale among otherwise similar animals, we can expect to observe more similarities than differences between rodent and human livers. Obvious differences, such as the presence (rodents) or absence (humans) of lobation and the presence (mice, humans) or absence (rats) of a gallbladder, suggest qualitative differences between the livers of these species. After review, however, we conclude that these dissimilarities represent relatively small quantitative differences. The microarchitecture of the liver is very similar among mammalian species and best represented by the lobular concept, with the biggest difference present in the degree of connective tissue development in the portal tracts. Although larger mammals have larger lobules, increasing size of the liver is mainly accomplished by increasing the number of lobules. The increasing role of the hepatic artery in lobular perfusion of larger species is, perhaps, the most important and least known difference between small and large livers, because it profoundly affects not only interventions like liver transplantations, but also calculations of liver function.
A High-Fat, High-Cholesterol Diet Promotes Intestinal Inflammation by Exacerbating Gut Microbiome Dysbiosis and Bile Acid Disorders in Cholecystectomy
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^☆: This work was supported by grant no. Be 890/2–3 (to F. Berr) from the Deutsche Forschungsgemeinschaft, Bonn, Germany.

^☆☆: A preliminary report of this study was presented at Digestive Disease Week (American Gastroenterological Association/American Association for the Study of Liver Diseases) in Boston, MA, May 1993, and was published in abstract form (Gastroenterology 1993; 104: A931).

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Other clinical studyLong-term effects of cholecystectomy on bile acid metabolism☆,☆☆

Abstract

Gastroenterology

Gastroenterology

Lancet

Lancet

Gastroenterology

Gastroenterology

Gastroenterology

Am J Clin Nutr

J Lipid Res

J Lipid Res

Gastroenterology

Eur J Clin Invest

J Clin Invest

A prospective analysis of 1518 laparoscopic cholecystectomies

N Engl J Med

Gallbladder stones: management

Lancet

Cholecystectomy and carcinoma of the colon

Z Krebsforsch

Cholecystectomy and cancer of the large bowel

Br J Surg

Increased risk of colorectal cancer after cholecystectomy

Ann Surg

Adenomas of the large intestine after cholecystectomy

Gut

The relationship between cholecystectomy and colon cancer: an Iowa study

J Surg Oncol

Do colon and rectum exhibit an opposite cancer risk trend versus cholecystectomy?

Cholecystectomy and right colon cancer in Puerto Rico

Cancer

Other clinical study
Long-term effects of cholecystectomy on bile acid metabolism☆,☆☆