Elastography for Hepatic Fibrosis Severity in Chronic Hepatitis B or C

AIMS: To assess the value of transient elastography for predicting significant fibrosis or cirrhosis in chronic hepatitis B or C (CHB or CHC) patients. METHODS: 75 patients (CHB: 45, CHC: 32) were included. All underwent elastography and liver biopsy concurrently. Biopsies were evaluated using Ishak's classification. Fibrosis was mild, moderate or severe/cirrhosis when scores were 0-1 (n = 30), 2-3 (n = 20), 4-6 (n = 25), respectively. RESULTS: Median liver stiffness values were higher in patients with severe fibrosis or cirrhosis than in those with moderate or mild fibrosis (14.8 vs. 6.4 vs. 5.3 kPa, p < 0.001). The diagnostic accuracy of elastography for severe fibrosis and cirrhosis was excellent [area under the receiver operating characteristic (AUROC) curve 0.938 vs. 0.948], but it was not optimal for mild fibrosis (AUROC 0.78). Values of 7.5, 9.0 and 12 kPa had a sensitivity and specificity for severe fibrosis/cirrhosis of 96, 84 and 60%, and 76, 90 and 94%, respectively. The median stiffness value in cirrhotic patients (score 5-6) was 16.6 kPa (7.7-48). No differences in accuracy of elastography between CHB or CHC patients were found. Cutoff was 12.5 kPa for cirrhosis; 10/75 patients (13%) were misclassified. CONCLUSION: Transient elastography has an excellent diagnostic accuracy for severe fibrosis and cirrhosis in CHB and CHC, but the cutoffs need further evaluation

Η σημασία της αγγειοποιητίνης-2 στο σηπτικό σύνδρομο

We aimed to investigate if angiopoietin-2 (Ang 2) participates in the septic process and what may be the role of monocytes as a site of release of Ang 2 in sepsis. Concentrations of Ang 2 were estimated in sera and in supernatants of monocytes derived from a cohort of 90 patients with septic syndrome due to ventilator-associated pneumonia (VAP). Mononuclear cells of 17 healthy volunteers were stimulated by serum of patients in the presence or absence of various intracellular pathway inhibitors. Ang 2 gene expression after stimulation was also tested. Ang 2 was higher in patients with septic shock compared to patients with sepsis, severe sepsis and controls. Ang 2 was significantly increased in non-survivors compared with survivors. Serum levels greater than 9700 pg/ml were accompanied by a 3.254 odds ratio for death (p: 0.033). Ang 2 release from monocytes of septic patients was slightly decreased after stimulation with lipopolysaccharide (LPS) of Escherichia coli O55: B5. Release of Ang 2 from healthy mononuclear cells was stimulated by serum of patients with shock but not by serum of non-shocked patients (p: 0.016). Release was decreased by LPS; increased in the presence of a TLR4 antagonist; and decreased by anti-TNF antibody. RNA transcripts of PBMCs after stimulation with serum of patients with septic shock were higher than those after LPS stimulation. It is concluded that Ang 2 is increased in serum in the event of septic shock and that its increase is related to unfavorable outcome. It seems that a circulating factor may exist in the serum of patients with septic shock that stimulates gene expression and subsequent release of Ang 2 from monocytes. TLR4 and TNFα modulate release of Ang 2.Σκοπός της παρούσης μελέτης είναι να διερευνήσει τη συμμετοχή της Αng 2 στη σηπτική διεργασία και το ρόλο των μονοκυττάρων, ως τόπο παραγωγής της στη σήψη. Η συγκέντρωση της Ang 2 εκτιμήθηκε στον ορό και στα υπερκείμενα των μονοκυττάρων 90 ασθενών με πνευμονία του αναπνευστήρα. Μονοκύτταρα 17 υγιών εθελοντών ενεργοποιήθηκαν με ορό σηπτικών ασθενών με την παρουσία ή την απουσία ποικίλων ανασταλτών ενδοκυττάριων οδών. Επιπλέον εκτιμήθηκε η γονιδιακή έκφραση της Αng 2 μετά την ενεργοποίηση των κυττάρων. Τα επίπεδα της Αng 2 ήταν υψηλότερα στον ορό των ασθενών με σηπτική καταπληξία σε σχέση με αυτά των ασθενών με απλή ή σοβαρή σήψη και των υγιών εθελοντών. Επίπεδα ορού υψηλότερα από 9700 pg/ml συνοδεύονταν από 3. 254 φορές μεγαλύτερο κίνδυνο για θάνατο (p=0.033). Η παραγωγή Αng 2 από τα μονοκύτταρα σηπτικών ασθενών ήταν ελαφρώς μειωμένη μετά την ενεργοπίηση με ενδοτοξίνη LPS από E.coli Ο55: Β5. Η απελευθέρωση Αng 2 από τα μονοκύτταρα υγιών ενεργοποιήθηκε με τον ορό ασθενών με σηπτική καταπληξία, αλλά όχι με τον ορό μη σηπτικών ασθενών (p=0.016). Η απελευθέρωση μειώθηκε με την προσθήκη ενδοτοξίνης LPS, αυξήθηκε με την παρουσία ανταγωνιστή TLR4 και μειώθηκε με αντίσωμα anti-TNF. Τα αντίγραφα RNA των PBMCs μετά την ενεργοποίηση με ορό ασθενών με σηπτική καταπληξία ήταν υψηλότερα από εκείνα μετά την ενεργοποίηση με LPS. Συμπεραίνεται ότι η Αng 2 αυξάνεται στον ορό ασθενών με σηπτική καταπληξία και η αύξηση αυτή σχετίζεται με κακή πρόγνωση. Φαίνεται ότι ένας παράγοντας μπορεί να κυκλοφορεί στον ορό ασθενών με σηπτική καταπληξία που ενεργοποιεί την έκφραση του γονιδίου και επομένως την παραγωγή Αng 2 από τα μονοκύτταρα. Οι TLR4 και TNFα τροποποιούν αυτήν την παραγωγή της Αng 2

Sarcoid-like granulomatosis in patients treated with anti-TNF alpha factors. A case report and review of the literature

This report describes a 56-year-old woman who developed granulomatous lesions consistent with sarcoidosis during adalimumab therapy for rheumatoid arthritis. Cervical and axillary lymphadenopathy developed approximately 21 months after adalimumab administration. Non-caseating epithelioid cell granulomas consistent with sarcoidosis were detected both in an axillary lymph node specimen and in the bone marrow. Diseases showing similar histologic changes, especially tuberculosis, were excluded, and a diagnosis of sarcoidosis was made. Adalimumab was discontinued, and recovery was observed. The current case is, to our knowledge, the first to describe adalimumab-induced non-caseating granulomas in lymph nodes and bone marrow without pulmonary involvement in a patient treated for rheumatoid arthritis

Oleuropein: A novel immunomodulator conferring prolonged survival in experimental sepsis by Pseudomonas aeruginosa

Oleuropein, a novel immunomodulator derived from olive tree, was assessed in vitro and in experimental sepsis by Pseudomonas aeruginosa. After addition in monocyte and neutrophil cultures, malondialdehyde, TNF-alpha, IL-6, and bacterial counts were estimated in supernatants. Acute pyelonephritis was induced in 70 rabbits after inoculation of pathogen in the renal pelvis. Intravenous therapy was administered in four groups postchallenge by one multidrug-resistant isolate (A, controls; B, oleuropein; C, amikacin; D, both agents) and in three groups postchallenge by one susceptible isolate (E, controls; F, oleuropein; G, amikacin). Survival was recorded; bacterial growth in blood and organs was counted; endotoxins (LPS), malondialdehyde, total antioxidant status, and TNF-alpha in serum were estimated. TNF-alpha and IL-6 of cell supernatants were not increased compared with controls when triggered by LPS and P. aeruginosa. Counts of multidrug-resistant P. aeruginosa were decreased in monocyte supernatants. Median survival of groups A, B, C, D, E, F, and G were 3.00, 6.00, 2.00, 10.00, 1.00, 5.00, and 1.00 days, respectively. Bacteria in blood were lower at 48 h in groups B and D compared with A and in groups F and G compared with E. Total antioxidant status decreased steadily overtime in groups A, C, D, and G, but not in groups B and F. TNF-alpha of groups B, C, and D was lower than A at 48 h. Tissue bacteria decreased in group F compared with E. Oleuropein prolonged survival in experimental sepsis probably by promoting phagocytosis or inhibiting biosynthesis of proinflammatory cytokines

Clinical and epidemiological characteristics of hepatitis C virus-infected people who inject drugs: a Greek descriptive analysis

Background It is estimated that 17,000 people who inject drugs (PWID) in Greece have hepatitis C virus (HCV) viremia. The aim of our study was to explore the characteristics of the HCV-infected, direct acting antiviral (DAA)-naive PWID. Methods This is a retrospective analysis of PWID with HCV infection. We selected data from six liver clinics during the period from 1st May 2014 to 31st May 2017 in order to record the characteristics of infected PWID. Results We included 800 PWID with HCV infection (78.5% male, mean age 42 +/- 10 years) who had not received DAAs before 1st June 2017. One third of the patients had comorbidities (diabetes mellitus, arterial hypertension and psychological disorders); 70% were smokers, 27% alcohol users, 67% unemployed, 29% married, and 34% had education &gt;12 years; 65% were attending addiction programs; 57% were receiving methadone and 36% buprenorphine. Sporadic or systemic drug use was reported by 37% while 1.4% and 2.9% had HIV and HBV coinfection, respectively. The genotype distribution was 20.5%, 4.6%, 3.3%, 61% and 10% for genotypes 1a, 1b, 2, 3 and 4, respectively. Mean (+/- SD) liver stiffness was 9 +/- 7 kPa and 21% of the patients had cirrhosis. Half of the patients were in the F0-F1 stage of liver disease, defined as stiffness &lt;= 7 kPa. Conclusions Our real-life data suggest that HCV genotype 3 remains the predominant genotype among PWID. One third of PWID had comorbidities and one-fifth cirrhosis. Half of PWID had early-stage liver disease and remained without access to DAAs according to the Greek prioritization criteria