Abstract
Postcholecystectomy bile duct injuries (BDI) produce hepatic cholestasis and cause infection of the biliary tract. The biliary cells participate in secreting cytokines and in expression of immune response receptors. Toll-like receptors (TLRs) conduct signalling and activate the innate and adaptive inflammatory response. The objective was to determine the serum levels of TLR-2 and the expression of TLR-1 and TLR-2 and β-defensin in liver biopsies of postcholecystectomy BDI patients. A transverse, analytical study with 2 groups was done. One group included healthy volunteers (control group) and other included 25 postcholecystectomy BDI patients with complete biliary obstruction. Using the Enzyme-linked Immunosorbent Assay (ELISA) technique, serum levels of TLR-2 were determined, and with immunofluorescence the morphologic analysis of TLR-1 and TLR-2 and β-defensin in liver biopsies of postcholecystectomy BDI patients was performed. The average TLR-2 serum level in the control group was 0.0 pg/mL and in the BDI group, 0.023 ± 0.0045 pg/mL (P < 0.0001, bilateral Mann Whitney U). Immunofluorescence was used to determine the expression in liver biopsies, blood vessels, bile ducts, and hepatic parenchyma where 12 hepatic biopsies were positive for TLR-1 with average of 3213057.74 ± 1071019.25 μm2; and 7 biopsies were positive for β-defensin with an average of 730364.33 ± 210838.02 μm2; and 6 biopsies positive for TLR-2, obtaining an average of 3354364.24 ± 838591.06 μm2. In conclusion, TLR-1 and TLR-2 and β-defensin play an important role in the innate antimicrobial defense of the hepatobiliary system.
Highlights
Postcholecystectomy bile duct injuries (BDI) are feared complications in biliary surgery because they cause stenosis of the bile ducts with disastrous consequences, which can lead to secondary biliary cirrhosis, hepatic insufficiency and, as an ultimate consequence, cause death [1].Management of BDI is complicated, requiring experience, hepatobiliary capabilities, and a tertiary level of care [2]
It included 25 postcholecystectomy BDI patients with complete biliary obstruction who were sent to the Department of General Surgery at the Specialties Hospital of the National Occidental Medical Health Centre of the Mexican Social Security Institute as a tertiary care facility to undergo the most appropriate biliary-digestive reconstruction depending on the individual characteristics of each patient and their type of biliary lesion
Of the 25 patients included in the study who were positive for Toll-like receptors (TLRs)-2 in the Enzyme-linked Immunosorbent Assay (ELISA) test, 12 hepatic biopsies were positive for TLR-1 and the morphometric analysis of 141 random fields showed average of 3213057.74 ± 1071019.25 μm2; in the 7 biopsies positive for β-defensin, 135 random fields were measured with an average of 730364.33 ± 210838.02 μm2 and in 6 biopsies positive for TLR-2, 190 random fields were measured obtaining an average of 3354364.24 ± 838591.06 μm2. (Figure 3)
Summary
Postcholecystectomy bile duct injuries (BDI) are feared complications in biliary surgery because they cause stenosis of the bile ducts with disastrous consequences, which can lead to secondary biliary cirrhosis, hepatic insufficiency and, as an ultimate consequence, cause death [1]. The biliary epithelial cells are immunologically powerful, and when inflammation in the bile ducts exists they participate in secreting cytokines and in expression of the immune. TLRs are expressed in immune cells including the polymorphonuclear (PMN) and epithelial cells. They have an extracellular domain with regions rich in leucine, one or two regions rich in cysteine, and an intracellular domain of approximately 200 amino acids through which they carry out the transmission of signals [8]. The ligands bind to the TLR to conduct signalling and activate the innate and adaptive immune response. The TLRs that are expressed in the presenter cells of the antigen after recognizing the ligands are activated and induce molecules that participate in the presentation of antigenic peptides on the surface. The study proposed to determine the serum levels of TLR-2 and, through immunofluorescence, evaluate the expression of the TLR-1 and TLR-2 and β-defensin in liver biopsies of postcholecystectomy BDI patients
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