Tumor necrosis factor-α serum levels in healthy smokers and nonsmokers

Florin Petrescu1, Sebastian Cosmin Voican1, Isabela Silosi21Department of Internal Medicine, University of Medicine and Pharmacy of Craiova, Craiova, Romania; 2Department of Immunology, University of Medicine and Pharmacy of Craiova, Craiova, RomaniaBackground: Tobacco smoking is the most important risk factor for chronic obstructive pulmonary disease (COPD) development. Inhaled cigarette smoke can induce tumor necrosis factor-a (TNF-a) production by alveolar macrophages, which in turn may enhance the production of metalloproteinases (MMPs). MMPs have been involved in mediating airway inflammation and lung destruction.Objectives: We aimed to measure the TNF-a serum levels in healthy heavy smokers and healthy nonsmokers to determine the dose-response relationship based on the cigarette smoke exposure.Subjects and methods: We included in our study 43 healthy heavy smokers and 19 healthy nonsmokers (the control group). The smokers group was classified as less than one pack, one pack, and more than one pack per day. A clinical and paraclinical evaluation was performed in both groups, without any evidence of infection or COPD. The serum levels of TNF-a were assessed by ELISA.Results: The TNF-a serum levels were significantly higher for the group of smokers compared to the group of nonsmokers (P < 0.004). We also noticed an increased TNF-a concentration in the serum of smokers with more than one pack per day compared with those with less than one pack per day (P < 0.03). There was a positive correlation between the serum level of TNF-a and tobacco smoke exposure.Conclusions: The high levels of TNF-a in the serum of smokers suggest an imbalance between the proinflammatory and anti-inflammatory factors as a result of tobacco smoke exposure. The concentration of TNF-a is elevated in the serum of healthy heavy smokers in a cigarette dose-dependent manner. We speculate that the serum level of TNF-a might be a useful biomarker for the selection of heavy smokers with a high risk of developing smoke induced pulmonary diseases.Keywords: tobacco smoking, inflammation, chronic obstructive pulmonary disease, metalloproteinase

Computed tomography assessment of postoperative gastric vascular supply and staple-line leak development after sleeve gastrectomy

Background: Residual arterial supply of the gastric tube after sleeve gastrectomy (SG) can be damaged by surgery, which can reduce gastric tube perfusion and could promote postoperative leakage. Objective: To compare the postoperative vascularization of the gastric tube using early computed tomography (CT) scanning after SG in patients with or without postoperative staple-line leak. Setting: University hospital. Methods: A retrospective analysis of a prospective database was performed in consecutive patients undergoing SG. Patients who presented with a staple-line leak were matched (1:3) with a control group of patients who underwent surgery without postoperative morbidity during the same period. Gastric tube vascularization was studied on a postoperative day 2 CT scan in both groups of patients. Results: During the study period, 1826 patients underwent SG, including 42 patients (2.3%) who presented with a staple-line leak. Those 42 patients were successfully matched to 126 control patients. Global identification of residual gastric arterial supply in early postoperative CT scans was similar in patients with or without staple-line leak after SG. However, residual vascular supply of the gastroesophageal junction (i.e., terminal and anterior cardiotuberosity branches of the left gastric artery or left inferior phrenic artery) was more frequently interrupted by the staple line in the group of patients who developed a gastric leak. Conclusion: This study suggests a correlation between interruption of the main arteries supplying the gastroesophageal junction by the staple line on early postoperative CT scans and the development of gastric leak after SG. These results support the vascular theory as one of the causes of leak after SG

The Osteopontin Level in Liver, Adipose Tissue and Serum Is Correlated with Fibrosis in Patients with Alcoholic Liver Disease

<div><h3>Background</h3><p>Osteopontin (OPN) plays an important role in the progression of chronic liver diseases. We aimed to quantify the liver, adipose tissue and serum levels of OPN in heavy alcohol drinkers and to compare them with the histological severity of hepatic inflammation and fibrosis.</p> <h3>Methodology/Principal Findings</h3><p>OPN was evaluated in the serum of a retrospective and prospective group of 109 and 95 heavy alcohol drinkers, respectively, in the liver of 34 patients from the retrospective group, and in the liver and adipose tissue from an additional group of 38 heavy alcohol drinkers. Serum levels of OPN increased slightly with hepatic inflammation and progressively with the severity of hepatic fibrosis. Hepatic OPN expression correlated with hepatic inflammation, fibrosis, TGFβ expression, neutrophils accumulation and with the serum OPN level. Interestingly, adipose tissue OPN expression also correlated with hepatic fibrosis even after 7 days of alcohol abstinence. The elevated serum OPN level was an independent risk factor in estimating significant (F≥2) fibrosis in a model combining alkaline phosphatase, albumin, hemoglobin, OPN and FibroMeter® levels. OPN had an area under the receiving operator curve that estimated significant fibrosis of 0.89 and 0.88 in the retrospective and prospective groups, respectively. OPN, Hyaluronate (AUROC: 0.88), total Cytokeratin 18 (AUROC: 0.83) and FibroMeter® (AUROC: 0.90) estimated significance to the same extent in the retrospective group. Finally, the serum OPN levels also correlated with hepatic fibrosis and estimated significant (F≥2) fibrosis in 86 patients with chronic hepatitis C, which suggested that its elevated level could be a general response to chronic liver injury.</p> <h3>Conclusion/Significance</h3><p>OPN increased in the liver, adipose tissue and serum with liver fibrosis in alcoholic patients. Further, OPN is a new relevant biomarker for significant liver fibrosis. OPN could thus be an important actor in the pathogenesis of this chronic liver disease.</p> </div

Intrahepatic cholestasis: suggested future investigations

International audienc

Multikinase inhibitor-induced liver injury in patients with cancer: A review for clinicians

International audienceBACKGROUND: Multikinase inhibitors (MKI) are targeted molecular agents that have revolutionized cancer management. However, there is a paucity of data concerning MKI-related liver injury risk and clinical guidelines for the management of liver toxicity in patients receiving MKI for cancer are scarce. DESIGN: We conducted a PubMed search of articles in English published from January 2000 to December 2018 related to hepatotoxicity of the 29 FDA-approved MKIs at doses used in clinical practice. The search terms were the international non-proprietary name of each agent cross-referenced with «hepatotoxicity», «hepatitis», «hepatic adverse event», or «liver failure», and «phase II clinical trial», «phase III clinical trial», or «case report». RESULTS: Following this search, 140 relevant studies and 99 case reports were considered. Although asymptomatic elevation of aminotransferase levels has been frequently observed in MKI clinical trials, clinically significant hepatotoxicity is a rare event. In most cases, the interval between treatment initiation and the onset of liver injury is between one week and two months. Liver toxicity is often hepatocellular and less frequently mixed. Life-threatening MKI-induced hepatic injury has been described, involving fulminant liver failure or death. Starting from existing data, a description of MKI-related liver events, grading of hepatotoxicity risk, and recommendations for management are also given for various MKI molecules. CONCLUSION: All MKIs can potentially cause liver injury, which is sometimes irreversible. As there is still no strategy available to prevent MKI-related hepatotoxicity, early detection remains crucial. The surveillance of liver function during treatment may help in the early detection of hepatotoxicity. Furthermore, the exclusion of potential causes of hepatic injury is essential to avoid unnecessary MKI withdrawal

Evolution of liver function tests in the 3 cases of antidepressant-induced liver injury.

<p>Evolution of liver function tests in the 3 cases of antidepressant-induced liver injury.</p

Characteristics of patients with normal and abnormal LFT.

<p>Characteristics of patients with normal and abnormal LFT.</p

Description of the 3 cases of antidepressant-induced liver injury.

<p>Description of the 3 cases of antidepressant-induced liver injury.</p

Un modèle pour identifier les buveurs excessifs à haut risque de progression de la maladie du foie

International audienceBACKGROUND & AIMS:Alcohol-related liver disease (ALD) causes chronic liver disease. We investigated how information on patients' drinking history and amount, stage of liver disease, and demographic feature can be used to determine risk of disease progression.METHODS:We collected data from 2334 heavy drinkers (50 g/day or more) with persistently abnormal results from liver tests who had been admitted to a hepato-gastroenterology unit in France from January 1982 through December 1997; patients with a recorded duration of alcohol abuse were assigned to the development cohort (n=1599; 75% men) or the validation cohort (n=735; 75% men), based on presence of a liver biopsy. We collected data from both cohorts on patient history and disease stage at the time of hospitalization. For the development cohort, severity of the disease was scored by the METAVIR (due to the availability of liver histology reports); in the validation cohort only the presence of liver complications was assessed. We developed a model of ALD progression and occurrence of liver complications (hepatocellular carcinoma and/or liver decompensation) in association with exposure to alcohol, age at the onset of heavy drinking, amount of alcohol intake, sex and body mass index. The model was fitted to the development cohort and then evaluated in the validation cohort. We then tested the ability of the model to predict disease progression for any patient profile (baseline evaluation). Patients with a 5-y weighted risk of liver complications greater than 5% were considered at high risk for disease progression.RESULTS:Model results are given for the following patient profiles: men and women, 40 y old, who started drinking at an age of 25 y, drank 150 g/day, and had a body mass index of 22 kg/m2 according to the disease severity at baseline evaluation. For men with baseline F0-F2 fibrosis, the model estimated the probabilities of normal liver, steatosis, or steatohepatitis at baseline to be 31.8%, 61.5% and 6.7%, respectively. The 5-y weighted risk of liver complications was 1.9%, ranging from 0.2% for men with normal liver at baseline evaluation to 10.3% for patients with steatohepatitis at baseline. For women with baseline F0-F2 fibrosis, probabilities of normal liver, steatosis, or steatohepatitis at baseline were 25.1%, 66.5% and 8.4%, respectively; the 5-y weighted risk of liver complications was 3.2%, ranging from 0.5% for women with normal liver at baseline to 14.7% for patients with steatohepatitis at baseline. Based on the model, men with F3-F4 fibrosis at baseline have a 24.5% 5-y weighted risk of complications (ranging from 20.2% to 34.5%) and women have a 30.1% 5-y weighted risk of complications (ranging from 24.7% to 41.0%).CONCLUSIONS:We developed a Markov model that integrates data on level and duration of alcohol use to identify patients at high risk of liver disease progression. This model might be used to adapt patient care pathways