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Objective: This study aimed at evaluating the effects of candesartan and ramipril on liver fibrosis in patients with chronic hepatitis C. Methods: This randomized controlled prospective study involved 64 patients with chronic hepatitis C and liver fibrosis. Participants were randomized into 3 groups: group I (control group; nâ¯=â¯21), members of which received traditional therapy only; group 2 (ramipril group; nâ¯=â¯21), members of which received traditional therapy plus 1.25 mg/d oral ramipril; and group 3 (candesartan group; nâ¯=â¯22), members of which received traditional therapy plus 8 mg/d oral candesartan. Patients were assessed at baseline and 6 months after intervention through measuring of liver stiffness (Fibro-Scan; Echosens, Paris, France); evaluation of the serum levels of hyaluronic acid and transforming growth factor beta-1; and calculation of indices of liver fibrosis, including fibrosis index based on the 4 factors and aspartate transaminase-to-platelet-ratio index. Data were analyzed using paired t test and 1-way ANOVA followed by Tukey's honest significant difference test for multiple pairwise comparisons. Results: At baseline, the 3 study groups were statistically similar in demographic and laboratory data. After treatment, the 3 study groups showed significant decrease in liver stiffness, serum levels of hyaluronic acid and transforming growth factor beta-1, and indices of liver fibrosis compared with baseline data (P < 0.001). Six months after treatment, patients taking ramipril and candesartan showed significant improvement in all measured parameters compared with the control group. Additionally, the candesartan-treated group showed significant decrease in liver stiffness, biomarkers, and indices of liver fibrosis compared with ramipril recipients. Conclusions: The administration of ramipril and candesartan in patients with chronic hepatitis C with hepatic fibrosis was well tolerated and effective in improving liver fibrosis. angiotensin II receptor 1 (AT1) antagonist candesartan maintained antifibrotic effects more effectively than ramipril and may represent a safe and effective therapeutic strategy for liver fibrosis in patients with chronic liver diseases. ClinicalTrials.gov identifier: NCT03770936. (Curr Ther Res Clin Exp. 2022; 83:XXX-XXX) © 2022 Elsevier HS Journals, Inc.
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BACKGROUND: Cholangiocarcinoma (CC) is a fatal malignancy, the incidence of which is increasing worldwide, with substantial regional variation. Current diagnostic techniques to distinguish benign from malignant biliary disease are unsatisfactory. Metabolic profiling of bile may help to differentiate benign from malignant disease. No previous studies have compared the metabolic profiles of bile from two geographically and racially distinct groups of CC patients. OBJECTIVES: This study aimed to compare metabolic profiles of bile, using in vitro proton magnetic resonance spectroscopy, from CC patients from Egypt and the UK, and from patients with CC and patients with non-malignant biliary disease. METHODS: A total of 29 bile samples, collected at cholangiography, were analysed using an 11.7-T system. Samples were from eight CC patients in either Egypt (n = 4) or the UK (n = 4) and 21 patients with benign biliary disease (choledocholithiasis [n = 8], sphincter of Oddi dysfunction [n = 8], primary sclerosing cholangitis [n = 5]). RESULTS: Bile phosphatidylcholine (PtC) was significantly reduced in CC patients. Egyptian CC patients had significantly lower biliary PtC levels compared with UK patients. Taurine- and glycine-conjugated bile acids (H-26 and H-25 protons, respectively) were significantly elevated in bile from patients with CC compared with bile from patients with benign diseases (P = 0.013 and P < 0.01, respectively). CONCLUSIONS: Biliary PtC levels potentially differentiate CC from benign biliary disease. Reduced biliary PtC in Egyptian compared with UK patients may reflect underlying carcinogenic mechanisms.
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Ácidos y Sales Biliares/metabolismo , Neoplasias de los Conductos Biliares/metabolismo , Conductos Biliares Intrahepáticos/metabolismo , Bilis/metabolismo , Biomarcadores de Tumor/metabolismo , Colangiocarcinoma/metabolismo , Fosfatidilcolinas/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias de los Conductos Biliares/diagnóstico por imagen , Conductos Biliares Intrahepáticos/diagnóstico por imagen , Colangiocarcinoma/diagnóstico por imagen , Colangiopancreatografia Retrógrada Endoscópica , Colangitis Esclerosante/metabolismo , Coledocolitiasis/metabolismo , Diagnóstico Diferencial , Egipto , Femenino , Humanos , Espectroscopía de Resonancia Magnética , Masculino , Metabolómica/métodos , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Disfunción del Esfínter de la Ampolla Hepatopancreática/metabolismo , Reino UnidoAsunto(s)
Hepatitis C/sangre , Inmunoglobulinas/sangre , Hepatopatías/sangre , Adulto , Enfermedad Crónica , Femenino , Humanos , MasculinoRESUMEN
INTRODUCTION: Obstructive jaundice is an important clinical problem. It may cause transient hemolysis and shortened erythrocyte life span as well as cytokine induction. An increase in lipid peroxidation has been noted as evidence of oxidative damage in red cells due to cholestasis. The influence of endoscopic retrograde cholangiopancreatography (ERCP), mechanical lithotrepsy and stone extraction on the antioxidative capacity of the erythrocyte and immune response is still unclear. METHODS: Superoxide dismutase (SOD), catalase (CAT) and glutathione (GSH) content of red blood cells (RBC), and serum interleukin (IL-18) were measured in 20 patients with calcular obstructive jaundice before and 4 weeks after ERCP intervention and compared with 10 matched healthy volunteers. RESULTS: A significant decrease (p<0.05) in SOD and CAT activities and glutathione concentration but a significant increase (p<0.05) in serum IL-18 were observed in cholestatic patients compared with the healthy control and were significantly correlated with variable of hepatic dysfunction (alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin, alkaline phosphatase (ALP) and gamma glutamyl transferase (GGT). After ERCP, serum IL-18 and antioxidant capacity of red blood cells were significantly improved and returned to normal concentration (p<0.05). CONCLUSIONS: In biliary obstruction, serum IL-18 is increased and antioxidative capacity is decreased, and have a direct correlation with biochemical markers of liver injury. After ERCP intervention, the altered antioxidative capacity as well as serum IL-18 was completely restored to normal.