Papers by gianfranco elia
Journal of Hepatology, 2017
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Journal of Hepatology, 2005
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Digestive and Liver Disease, 2003
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Clinica Chimica Acta, 2013
Manual microscopy remains the gold standard for enumeration and classification of nucleated cells... more Manual microscopy remains the gold standard for enumeration and classification of nucleated cells in peritoneal fluids, especially for diagnosing bacterial peritonitis. However, this approach carries several drawbacks, so that the use of simple and automated tests may be a viable option for initial screening of peritoneal fluids. Neutrophil gelatinase-associated lipocalin (NGAL), lactate dehydrogenase (LDH), proteins and glucose were assessed in peritoneal fluids from patients with new onset nonmalignant ascites, along with nucleated cell count and differentiation. One hundred and eleven specimens were analyzed, 26 of which (23%) with polymorphonuclear leukocyte (PMN) count≥250/μL, thus compatible with bacterial peritonitis. The median concentration of LDH and NGAL was 3.4 and 3.7-fold higher in samples with ≥250 PMN/μL. The concentration of proteins was also higher in samples with ≥250 PMN/μL, whereas that of glucose was lower. The PMN count significantly correlated with peritoneal fluid values of LDH (r=0.859), NGAL (r=0.774) and proteins (r=0.268), but not with glucose (r=-0.069). The area under ROC curve was 0.88 for LDH, 0.89 for NGAL and 0.94 for their combination (both tests positive), whereas that of proteins and glucose was 0.80 and 0.71, respectively. Sensitivities and specificities were 0.81 and 0.87 for LDH≥227 U/L, 0.96 and 0.75 for NGAL≥120 ng/mL, 0.77 and 0.95 for their combination. The agreement with PMN count was 0.86 for LDH, 0.80 for NGAL, and 0.91 for their combination. These results suggest that assessment of NGAL in peritoneal fluids, especially in combination with LDH, may be a reliable approach for screening of bacterial peritonitis in patients with new onset nonmalignant ascites.
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Journal of Hepatology
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Hepatitis Monthly, 2005
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Journal of Hepatology
BACKGROUND & AIMS Primary biliary cholangitis (PBC) is a chronic liver disease in which autoi... more BACKGROUND & AIMS Primary biliary cholangitis (PBC) is a chronic liver disease in which autoimmune destruction of the small intra-hepatic bile ducts eventually leads to cirrhosis. Many patients have inadequate response to licensed medications, motivating the search for novel therapies. Previous genome-wide association studies (GWAS) and meta-analyses (GWMA) of PBC have identified numerous risk loci for this condition, providing insight into its aetiology. We undertook the largest GWMA of PBC to date, aiming to identify additional risk loci and prioritise candidate genes for in silico drug efficacy screening. METHODS We combined new and existing genotype data for 10,516 cases and 20,772 controls from five European and two East Asian cohorts. RESULTS We identified 56 genome-wide significant loci (20 novel) including 46 in European, 13 in Asian, and 41 in combined cohorts; and a 57th genome-wide significant locus (also novel) in conditional analysis of the European cohorts. Candidate genes at newly identified loci include FCRL3, INAVA, PRDM1, IRF7, CCR6, CD226, and IL12RB1, each having key roles in immunity. Pathway analysis reiterated the likely importance of pattern recognition receptor and TNF signalling, Jak-STAT signalling, and differentiation of TH1 and TH17 cells in the pathogenesis of this disease. Drug efficacy screening identified several medications predicted to be therapeutic in PBC, some well-established in the treatment of other autoimmune disorders. CONCLUSIONS This study has identified additional risk loci for PBC, provided a hierarchy of agents that could be trialled in this condition, and emphasised the value of genetic and genomic approaches to drug discovery in complex disorders. LAY SUMMARY Primary biliary cholangitis (PBC) is a chronic liver disease that eventually leads to cirrhosis. In this study, we analysed genetic information from 10,516 people with PBC and 20,772 healthy individuals recruited in Canada, China, Italy, Japan, UK, or USA. We identified several genetic regions associated with PBC. Each of these regions contains several genes. For each region, we used diverse sources of evidence to help us choose the gene most likely to be involved in causing PBC. We used these 'candidate genes' to help us identify medications that are currently used for treatment of other conditions, which might also be useful for treatment of PBC. CLINICAL TRIAL NUMBER Not applicable.
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Journal of Hepatology
BACKGROUND & AIMS The ANSWER study reported that long-term albumin administration to patients... more BACKGROUND & AIMS The ANSWER study reported that long-term albumin administration to patients with cirrhosis and uncomplicated ascites improves survival. Such treatment led serum albumin to increase within a month, remaining stable thereafter. This post-hoc analysis aimed at determining whether on-treatment serum albumin could guide therapy. METHODS Logistic regression was used to assess the association between baseline serum albumin and mortality and determine on-treatment factors associated with mortality and predicting the achievement of a given on-treatment serum albumin level. Survival was assessed by Kaplan-Meier estimates and 2nd-order polynomial regression. Patients failing to normalise on-treatment serum albumin were compared with a subset of patients from the control arm matched by principal score. RESULTS Baseline serum albumin was closely associated with 18-month mortality in untreated patients; albumin treatment almost effaced this relationship. On-treatment serum albumin and MELD-Na at month 1 were the sole independent variables associated with mortality. 2nd-order polynomial regression revealed that survival improved in parallel with 1-month on-treatment serum albumin. Kaplan-Meier estimations showed that any value of 1-month on-treatment serum albumin (0.1 g/dL intervals) in the range 2.5-4.5 g/dL discriminated patient survival. In the normal range of serum albumin, the best discriminant value was 4.0 g/dL. Even those patients who failed to normalise serum albumin had a better survival than untreated patients. CONCLUSION Baseline serum albumin per se should not guide the decision to start albumin therapy. Contrarywise, 1-month on-treatment serum albumin is strongly associated with outcomes and could be used as a guide in order to improve the use of albumin, 4.0 g/dL being the target threshold to be pursued. However, even patients failing to normalise serum albumin take advantage from long-term albumin administration.
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Lancet (London, England), Jun 16, 2018
Evidence is scarce on the efficacy of long-term human albumin (HA) administration in patients wit... more Evidence is scarce on the efficacy of long-term human albumin (HA) administration in patients with decompensated cirrhosis. The human Albumin for the treatmeNt of aScites in patients With hEpatic ciRrhosis (ANSWER) study was designed to clarify this issue. We did an investigator-initiated multicentre randomised, parallel, open-label, pragmatic trial in 33 academic and non-academic Italian hospitals. We randomly assigned patients with cirrhosis and uncomplicated ascites who were treated with anti-aldosteronic drugs (≥200 mg/day) and furosemide (≥25 mg/day) to receive either standard medical treatment (SMT) or SMT plus HA (40 g twice weekly for 2 weeks, and then 40 g weekly) for up to 18 months. The primary endpoint was 18-month mortality, evaluated as difference of events and analysis of survival time in patients included in the modified intention-to-treat and per-protocol populations. This study is registered with EudraCT, number 2008-000625-19, and ClinicalTrials.gov, number NCT012...
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Nature communications, Jan 22, 2015
Primary biliary cirrhosis (PBC) is a classical autoimmune liver disease for which effective immun... more Primary biliary cirrhosis (PBC) is a classical autoimmune liver disease for which effective immunomodulatory therapy is lacking. Here we perform meta-analyses of discovery data sets from genome-wide association studies of European subjects (n=2,764 cases and 10,475 controls) followed by validation genotyping in an independent cohort (n=3,716 cases and 4,261 controls). We discover and validate six previously unknown risk loci for PBC (Pcombined<5 × 10(-8)) and used pathway analysis to identify JAK-STAT/IL12/IL27 signalling and cytokine-cytokine pathways, for which relevant therapies exist.
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Jaids Journal of Acquired Immune Deficiency Syndromes, 1992
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Pharmacology, 1988
The effects of indapamide (2.5 mg once a day) on urinary composition are reported in 20 patients ... more The effects of indapamide (2.5 mg once a day) on urinary composition are reported in 20 patients (10 with recurrent calcium nephrolithiasis and 10 with essential hypertension) compared with 20 controls. Indapamide was well absorbed in every patient (mean plasma level at the steady state was 111 +/- 41 ng/ml) and its antihypertensive action was more pronounced in hypertensive than in normotensive patients. It lowered calcium excretion in 18/20 patients (mean fall on the 7th day of treatment: 53%) and raised the Mg/Ca ratio in 20/20 patients (mean increase on the 7th day: 167%). The effect on Ca2+ and Mg2+ excretion was not associated with a strong diuretic effect. During intravenous calcium loading (0.375 mmol/kg body weight) 6 normal subjects after a single oral dose of indapamide excreted less calcium, suggesting a direct renal hypocalciuric action by the drug. Indapamide could represent an alternative drug to thiazide diuretics in diseases with dangerous renal calcium losses, but long-term studies are needed.
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Journal of Hepatology, 2003
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British journal of …, 1990
An epidemiological study of stone disease in a Northern Italian city was carried out by means of ... more An epidemiological study of stone disease in a Northern Italian city was carried out by means of a postal questionnaire mailed to 6000 individuals (2.5% of the entire population). It was found that the incidence of stone disease was comparable to that of industrialised Western Europe. There was a relationship between stone disease and gout and stone disease and a positive family history. The frequency of uric acid stones was high (26.5%). Stone-formers showed no alimentary differences from non-stone formers apart from the use of spices and herbs. Stone-formers used less water from public aqueducts and more uncarbonated mineral water, but only 19% of these drank at least 2 litres a day.
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…, 2002
Amalia Penna,1 Gabriele Missale,1 Vincenzo Lamonaca,1 Massimo Pilli,1 Cristina Mori,1 Paola Zanel... more Amalia Penna,1 Gabriele Missale,1 Vincenzo Lamonaca,1 Massimo Pilli,1 Cristina Mori,1 Paola Zanelli,2 Albertina Cavalli,1 Gianfranco Elia,1 and Carlo Ferrari1 ... To compare the functional features of circulating and intrahepatic hepatitis C virus (HCV)- specific CD4 T cells in ...
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Journal of …, 2002
Hepatitis B and hepatitis C viruses (HBV and HCV) are both noncytopathic and can cause acute and ... more Hepatitis B and hepatitis C viruses (HBV and HCV) are both noncytopathic and can cause acute and chronic infections of the liver. Although they share tropism for the same organ, development of chronic hepatitis is much more frequent following HCV infection, suggesting different ...
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Journal of Hepatology, 2005
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Gastroenterology
BACKGROUND & AIMS Genome-wide association studies (GWAS) in primary biliary cholangitis (PBC)... more BACKGROUND & AIMS Genome-wide association studies (GWAS) in primary biliary cholangitis (PBC) have failed to find X chromosome (chrX) variants associated with the disease. Here, we specifically explore the chrX contribution to PBC, a sexually-dimorphic complex autoimmune disease. METHODS We performed a chrX-wide association study (XWAS), including genotype data from five GWAS (from Italy, UK, Canada, China, Japan; 5,244 cases, 11,875 controls). RESULTS Single-marker association analyses found ∼100 loci displaying P<5*10-4, with the most significant being a signal within the OTUD5 gene (rs3027490, P=4.80*10-6; OR=1.39 CI=1.028-1.88; Japanese cohort). While the transethnic meta-analysis evidenced only a suggestive signal (rs2239452, mapping within the PIM2 gene; OR=1.17, 95%CI=1.09-1.26; P=9.93*10-8), the population-specific meta-analysis showed a genome-wide significant locus in East Asians pointing to the same region (rs7059064, mapping within the GRIPAP1 gene; P=6.2*10-9, OR=1.33, CI=1.21-1.46). Indeed, rs7059064 tags a unique LD block including seven genes: TIMM17B, PQBP1, PIM2, SLC35A2, OTUD5, KCND1, and GRIPAP1, as well as a super-enhancer (GH0XJ048933 within OTUD5) targeting all these genes. GH0XJ048933 is predicted to target also FOXP3, the main T regulatory cell lineage-specification factor. Consistently, OTUD5 and FOXP3 RNA levels were upregulated in PBC cases (1.75- and 1.64-fold, respectively). CONCLUSION This work represents the first comprehensive study of the chrX contribution to the genetics of an autoimmune liver disease and revealed a novel PBC-related genome-wide significant locus.
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Papers by gianfranco elia