El comportamiento del factor de necrosis tumoral alfa e interleucina 6 en lesiones de vías biliares postcolecistectomía / Tumor necrosis factor-alpha and interleukin-6 levels among patients suffering a bile duct injury during cholecystectomy

Background: During cholecystectomy, the bile duct may be injured. When this complication occurs, Kupffer cells are activated and produce tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL6) to phagocyte toxic products Aim: To measure serum levels of TNF-α and IL-6 among patients that suffered a bile duct injury after a cholecystectomy. Patients and Methods: Serum levels of TNF-α and IL-6 were measured prior to the bile-enteric derivation and after one year of follow up, in 31 patients that had a complete bile duct obstruction after open or laparoscopic cholecystectomy and in 5 healthy controls. Results: At baseline TNF-α levels in healthy subjects and patients with bile duct injury were 0 and 43.9 ± 2.9 ng/mL, respectively (p < 0.01). At one year of follow up, TNF-á became undetectable among patients. At baseline, the values for IL-6 among healthy controls and patients were 3.0 ± 2.0 and 72.0 ± 94.7 pg/mL respectively, (p < 0,004). After one year of follow up, IL-6 levels decreased to 6.4 ± 0.3 pg/mL among patients. Conclusions: TNF-α and IL-6 levels were elevated before bile-enteric derivation among patients with bile duct injury and became normal one year later.

[Tumor necrosis factor-alpha and interleukin-6 levels among patients suffering a bile duct injury during cholecystectomy]. / El comportamiento del factor de necrosis tumoral alfa e interleucina 6 en lesiones de vías biliares postcolecistectomía.

BACKGROUND: During cholecystectomy, the bile duct may be injured. When this complication occurs, Kupffer cells are activated and produce tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL6) to phagocyte toxic products AIM: To measure serum levels of TNF-α and IL-6 among patients that suffered a bile duct injury after a cholecystectomy. PATIENTS AND METHODS: Serum levels of TNF-α and IL-6 were measured prior to the bile-enteric derivation and after one year of follow up, in 31 patients that had a complete bile duct obstruction after open or laparoscopic cholecystectomy and in 5 healthy controls. RESULTS: At baseline TNF-α levels in healthy subjects and patients with bile duct injury were 0 and 43.9 ± 2.9 ng/mL, respectively (p < 0.01). At one year of follow up, TNF-á became undetectable among patients. At baseline, the values for IL-6 among healthy controls and patients were 3.0 ± 2.0 and 72.0 ± 94.7 pg/mL respectively, (p < 0,004). After one year of follow up, IL-6 levels decreased to 6.4 ± 0.3 pg/mL among patients. CONCLUSIONS: TNF-α and IL-6 levels were elevated before bile-enteric derivation among patients with bile duct injury and became normal one year later.

Liver fibrosis secondary to bile duct injury: correlation of Smad7 with TGF-beta and extracellular matrix proteins.

BACKGROUND: Liver fibrosis is the result of continuous liver injury stemming from different etiological factors. Bile duct injury induces an altered expression of TGF-beta, which has an important role in liver fibrosis because this cytokine induces the expression of target genes such as collagens, PAI-1, TIMPs, and others that lead to extracellular matrix deposition. Smad7 is the principal inhibitor that regulates the target gene transcription of the TGF-beta signaling. The aim of the study was to determine whether Smad7 mRNA expression correlates with the gene expression of TGF-beta, Col I, Col III, Col IV, or PAI-1 in liver fibrosis secondary to bile duct injury (BDI). RESULTS: Serum TGF-beta concentration was higher in BDI patients (39 296 pg/ml) than in liver donors (9008 pg/ml). Morphometric analysis of liver sections showed 41.85% of tissue contained fibrotic deposits in BDI patients. mRNA expression of Smad7, Col I, and PAI-1 was also significantly higher (P < 0.05) in patients with BDI than in controls. Smad7 mRNA expression correlated significantly with TGF-beta concentration, Col I and Col III expression, and the amount of fibrosis. CONCLUSION: We found augmented serum concentration of TGF-beta and an increase in the percentage of fibrotic tissue in the liver of BDI patients. Contrary to expected results, the 6-fold increase in Smad7 expression did not inhibit the expression of TGF-beta, collagens, and PAI-1. We also observed greater expression of Col I and Col III mRNA in BDI patients and significant correlations between their expression and TGF-beta concentration and Smad7 mRNA expression.

[Histological evaluation of hepatic fibrosis in patients with post surgical bile duct injury]. / Evaluación histológica de la fibrosis hepática en pacientes con lesión posquirúrgica de vías biliares.

BACKGROUND: Bile duct injuries after cholecystectomy can produce fibrous and collagen deposit tissue. Our objective was to evaluate the liver fibrosis measured in histological tissue in patients with bile duct injury after cholecystectomy. METHODS: Three normal liver biopsies and 21 from patients with bile duct injuries were studied. Group I: with three normal liver biopsies. Group II: with external abdominal fistula alone in six patients. Group III with complete bile duct obstruction in 15 patients. The surgical biliary enteric reconstructions were performed 8 weeks after bile duct injury in all cases. The fibrosis and collagen deposits were studied by Masson's trichrome and Sirius red stains and they were measured by a digital program. RESULTS: Group I showed 2 % of fibrosis tissue and 1% of collagen deposit and was considered as normal. Group II showed unexpected 1 fold more liver fibrosis and 9 fold more collagen deposit in extracellular matrix macromolecule (p < 0.05, Anova) against group I. Patients in group III, had fibrous tissue increase 43 folds more and 14 collagen folds more (p < 0.0001, Bonferroni's post hoc) versus group I. CONCLUSIONS: The patients in groups II and III showed liver fibrosis, being this more important in group III.