Cholecystohepatic shunt pathway reduces secondary bile acid accumulation to enhance natural killer T cell-mediated anti-hepatocellular carcinoma immunity.
J Gastroenterol Hepatol
; 39(8): 1684-1694, 2024 Aug.
Article
em En
| MEDLINE
| ID: mdl-38747068
ABSTRACT
BACKGROUND AND AIM:
The impact of cholecystectomy, which blocks the cholecystohepatic shunt pathway (CHSP), on the prognosis of patients with hepatocellular carcinoma (HCC) is unclear. Hepatic secondary bile acids (BAs) inhibit natural killer T (NKT) cell-mediated immunity against HCC, and the regulation of homeostasis of hepatic secondary BAs is controlled by the CHSP. However, the influence of CHSP on NKT cell-mediated immunity against HCC remains unclear.METHODS:
The clinical data of hospitalized patients undergoing HCC resection were collected. Meanwhile, an in situ HCC mouse model was established, and the CHSP was augmented using oleanolic acid (OA).RESULTS:
After 11 propensity score matching, Cox regression analysis revealed that cholecystectomy was an independent risk factor for HCC recurrence after hepatectomy (P = 0.027, hazard ratio 1.599, 95% confidence interval 1.055-2.422). Experimentally, when OA enhanced CHSP, a significant decrease was observed in the accumulation of secondary BAs in the livers of mice. Additionally, a significant increase was observed in the levels of C-X-C ligand 16 and interferon γ in the serum and tumor tissues. Further, the percentage of C-X-C receptor 6 (+) NKT cells in the tumor tissues increased significantly, and the growth of liver tumors was inhibited.CONCLUSIONS:
This clinical study revealed that cholecystectomy promoted the recurrence after radical hepatectomy in patients with HCC. Preserving the normal-functioning gallbladder as much as possible during surgery may be beneficial to the patient's prognosis. Further investigation into the mechanism revealed that CHSP enhanced NKT cell-mediated immunity against HCC by reducing the hepatic accumulation of secondary BAs.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Ácidos e Sais Biliares
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Carcinoma Hepatocelular
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Células T Matadoras Naturais
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Neoplasias Hepáticas
Limite:
Aged
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Animals
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
J Gastroenterol Hepatol
Assunto da revista:
GASTROENTEROLOGIA
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
China