دورية أكاديمية

Podoplanin-positive dilated lymphatic vessels in duodenum associates with three-month mortality in patients with cirrhosis.

التفاصيل البيبلوغرافية
العنوان: Podoplanin-positive dilated lymphatic vessels in duodenum associates with three-month mortality in patients with cirrhosis.
المؤلفون: Juneja, Pinky, Sharma, Aarti, Shasthry, S. M., Kumar, Guresh, Tripathi, Dinesh M., Rajan, V., Rastogi, Archana, Sarin, Shiv K., Kaur, Savneet
المصدر: Frontiers in Physiology; 2023, p1-10, 10p
مصطلحات موضوعية: CIRRHOSIS of the liver, DUODENUM, GENE expression, REFERENCE values, MORTALITY
مستخلص: Dilated and dysfunctional gut lymphatic vessels (LVs) have been reported in experimental cirrhosis. Here, we studied LVs in duodenal (D2)-biopsies of liver cirrhosis patients and investigated the prognostic role of a LV marker, podoplanin (PDPN), in predicting the mortality of patientswith cirrhosis. A prospective, single-center cohort study was performed in liver cirrhosis patients (n = 31) and matched healthy controls (n = 9). D2-biopsies were obtained during endoscopy procedure, immunostained with PDPN, and scored based on 1) intensity and 2) density of positively-stained LVs per high power field. Gut and systemic inflammation were estimated by quantifying duodenal CD3+ intraepithelial lymphocytes (IELs), CD68+ macrophages, and serum TNF-α and IL-6 levels, respectively. Gut permeability and inflammation as assessed by quantifying gene expression of TJP1, OCLN, TNF-α, and IL-6 in D2-biopsies. Gene expression of LV markers, PDPN (8-fold), and LYVE1 (3-fold)was enhanced in D2-biopsies of cirrhosis patients compared to control (p < 0.0001). The mean PDPN score in decompensated cirrhosis patients (6.91 ± 1.26, p < 0.0001) was significantly increased as compared to those with compensated (3.25 ± 1.60). PDPN score positively and significantly correlated with the number of IELs (r = 0.33), serum TNF-α (r = 0.35), and IL-6 (r = 0.48) levels, while inversely correlated with TJP1 expression (r = -0.46, p < 0.05 each). In Cox regression, the PDPN score was a significant and independent 3-month-mortality predictor in patients (HR: 5.61; 1.08-29.109; p = 0.04). The area under the curve for the PDPN score was 84.2, and cutoff value for predicting mortality was =6.5 with 100% sensitivity and 75% specificity. Collectively, dilated LVs with high PDPN expression in D2-biopsies is a characteristic feature of patients with decompensated cirrhosis. PDPNscore correlateswith enhanced gut and systemic inflammation and also associates with 3-month mortality in cirrhosis. [ABSTRACT FROM AUTHOR]
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قاعدة البيانات: Complementary Index
الوصف
تدمد:1664042X
DOI:10.3389/fphys.2023.1045983