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Elena BUZZETTI
Professore Associato
Dipartimento di Scienze Mediche e Chirurgiche Materno-Infantili e dell'Adulto
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Pubblicazioni
2023
- Antihypertensive treatment changes and related clinical outcomes in older hospitalized patients
[Articolo su rivista]
Cicco, S.; D'Abbondanza, M.; Proietti, M.; Zaccone, V.; Pes, C.; Caradio, F.; Mattioli, M.; Piano, S.; Marra, A. M.; Nobili, A.; Mannucci, P. M.; Pietrangelo, A.; Sesti, G.; Buzzetti, E.; Salzano, A.; Cimellaro, A.; Mannucci, P. M.; Nobili, A.; Sesti, G.; Pietrangelo, A.; Perticone, F.; Violi, F.; Corazza, G. R.; Corrao, S.; Marengoni, A.; Salerno, F.; Cesari, M.; Tettamanti, M.; Pasina, L.; Franchi, C.; Franchi, C.; Novella, A.; Tettamanti, M.; Miglio, G.; Tettamanti, M.; Galbussera, A. A.; Ardoino, I.; Novella, A.; Prisco, D.; Silvestri, E.; Emmi, G.; Bettiol, A.; Mattioli, I.; Biolo, G.; Zanetti, M.; Bartelloni, G.; Zaccari, M.; Chiuch, M.; Vanoli, M.; Grignani, G.; Pulixi, E. A.; Pirro, M.; Lupattelli, G.; Bianconi, V.; Alcidi, R.; Giotta, A.; Mannarino, M. R.; Girelli, D.; Busti, F.; Marchi, G.; Barbagallo, M.; Dominguez, L.; Beneduce, V.; Cacioppo, F.; Corrao, S.; Natoli, G.; Mularo, S.; Raspanti, M.; Argano, C.; Cavallaro, F.; Zoli, M.; Matacena, M. L.; Orio, G.; Magnolfi, E.; Serafini, G.; Simili, A.; Brunori, M.; Lazzari, I.; Simili, A.; Cappellini, M. D.; Fabio, G.; De Amicis, M. M.; De Luca, G.; Scaramellini, N.; Di Stefano, V.; Leoni, S.; Seghezzi, S.; Di Mauro, A. D.; Maira, D.; Mancarella, M.; Lucchi, T.; Rossi, P. D.; Clerici, M.; Leoni, S.; Di Mauro, A. D.; Bonini, G.; Conti, F.; Prolo, S.; Fabrizi, M.; Martelengo, M.; Vigani, G.; Di Sabatino, A.; Miceli, E.; Lenti, M. V.; Pisati, M.; Pitotti, L.; Padula, D.; Antoci, V.; Cambie, G.; Pontremoli, R.; Beccati, V.; Nobili, G.; Leoncini, G.; Alberto, J.; Cattaneo, F.; Anastasio, L.; Sofia, L.; Carbone, M.; Cipollone, F.; Guagnano, M. T.; Rossi, I.; Valeriani, E.; D'Ardes, D.; Esposito, L.; Sestili, S.; Angelucci, E.; Mancuso, G.; Calipari, D.; Bartone, M.; Delitala, G.; Berria, M.; Delitala, A.; Muscaritoli, M.; Molfino, A.; Petrillo, E.; Giorgi, A.; Gracin, C.; Imbimbo, G.; Zuccala, G.; D'Aurizio, G.; Romanelli, G.; Marengoni, A.; Volpini, A.; Lucente, D.; Manzoni, F.; Pirozzi, A.; Zucchelli, A.; Picardi, A.; Gentilucci, U. V.; Gallo, P.; Dell'Unto, C.; Bellelli, G.; Corsi, M.; Antonucci, C.; Sidoli, C.; Principato, G.; Bonfanti, A.; Szabo, H.; Mazzola, P.; Piazzoli, A.; Corsi, M.; Arturi, F.; Succurro, E.; Tassone, B.; Giofre, F.; Serra, M. G.; Bleve, M. A.; Brucato, A.; De Falco, T.; Negro, E.; Brenna, M.; Trotta, L.; Squintani, G. L.; Randi, M. L.; Fabris, F.; Bertozzi, I.; Bogoni, G.; Rabuini, M. V.; Prandini, T.; Ratti, F.; Zurlo, C.; Cerruti, L.; Cosi, E.; Manfredini, R.; Fabbian, F.; Boari, B.; De Giorgi, A.; Tiseo, R.; Paolisso, G.; Rizzo, M. R.; Catalano, C.; Di Meo, I.; Borghi, C.; Strocchi, E.; Ianniello, E.; Soldati, M.; Schiavone, S.; Bragagni, A.; Leoni, F. G.; De Sando, V.; Scarduelli, S.; Cammarosano, M.; Pareo, I.; Sabba, C.; Vella, F. S.; Suppressa, P.; De Vincenzo, G. M.; Comitangelo, A.; Amoruso, E.; Custodero, C.; Re, G.; Schilardi, A.; Loparco, F.; Fenoglio, L.; Falcetta, A.; Giraudo, A. V.; D'Aniano, S.; Fracanzani, A. L.; Tiraboschi, S.; Cespiati, A.; Oberti, G.; Sigon, G.; Cinque, F.; Peyvandi, F.; Rossio, R.; Colombo, G.; Agosti, P.; Pagliaro, E.; Semproni, E.; Ciro, C.; Monzani, V.; Savojardo, V.; Ceriani, G.; Folli, C.; Salerno, F.; Pallini, G.; Montecucco, F.; Ottonello, L.; Caserza, L.; Vischi, G.; Kassem, S.; Liberale, L.; Liberato, N. L.; Tognin, T.; Purrello, F.; Di Pino, A.; Piro, S.; Rozzini, R.; Falanga, L.; Pisciotta, M. S.; Bellucci, F. B.; Buffelli, S.; Ferrandina, C.; Mazzeo, F.; Spazzini, E.; Cono, G.; Cesaroni, G.; Montrucchio, G.; Peasso, P.; Favale, E.; Poletto, C.; Margaria, C.; Sanino, M.; Violi, F.; Perri, L.; Guasti, L.; Rotunno, F.; Castiglioni, L.; Maresca, A.; Squizzato, A.; Campiotti, L.; Grossi, A.; Diprizio, R. D.; Dentali, F.; Bertolotti, M.; Mussi, C.; Lancellotti, G.; Libbra, M. V.; Galassi, M.; Grassi, Y.; Greco, A.; Bigi, E.; Pellegrini, E.; Orlandi, L.; Dondi, G.; Carulli, L.; Sciacqua, A.; Perticone, M.; Battaglia, R.; Maio, R.; Scozzafava, A.; Condoleo, V.; Falbo, T.; Colangelo, L.; Filice, M.; Clausi, E
abstract
Background: Hypertension management in older patients represents a challenge, particularly when hospitalized. Objective: The objective of this study is to investigate the determinants and related outcomes of antihypertensive drug prescription in a cohort of older hospitalized patients. Methods: A total of 5671 patients from REPOSI (a prospective multicentre observational register of older Italian in-patients from internal medicine or geriatric wards) were considered; 4377 (77.2%) were hypertensive. Minimum treatment (MT) for hypertension was defined according to the 2018 ESC guidelines [an angiotensin-converting-enzyme-inhibitor (ACE-I) or an angiotensin-receptor-blocker (ARB) with a calcium-channel-blocker (CCB) and/or a thiazide diuretic; if >80 years old, an ACE-I or ARB or CCB or thiazide diuretic]. Determinants of MT discontinuation at discharge were assessed. Study outcomes were any cause rehospitalization/all cause death, all-cause death, cardiovascular (CV) hospitalization/death, CV death, non-CV death, evaluated according to the presence of MT at discharge. Results: Hypertensive patients were older than normotensives, with a more impaired functional status, higher burden of comorbidity and polypharmacy. A total of 2233 patients were on MT at admission, 1766 were on MT at discharge. Discontinuation of MT was associated with the presence of comorbidities (lower odds for diabetes, higher odds for chronic kidney disease and dementia). An adjusted multivariable logistic regression analysis showed that MT for hypertension at discharge was associated with lower risk of all-cause death, all-cause death/hospitalization, CV death, CV death/hospitalization and non-CV death. Conclusions: Guidelines-suggested MT for hypertension at discharge is associated with a lower risk of adverse clinical outcomes. Nevertheless, changes in antihypertensive treatment still occur in a significant proportion of older hospitalized patients.
2023
- Clinical application of NGS in the diagnosis of iron overload disorders or hyperferritinemia of genetic origin
[Abstract in Rivista]
Ricci, A.; Bergamini, E.; Scarlini, S.; Buzzetti, E.; Caleffi, A.; Rabacchi, C.; Ventura, P.; Artuso, L.; Tenedini, E.; Tagliafico, E.; Pietrangelo, A.; Corradini, E.
abstract
2023
- CREB-H is a stress-regulator of hepcidin gene expression during early postnatal development
[Articolo su rivista]
Vecchi, C.; Montosi, G.; Garuti, C.; Canali, S.; Sabelli, M.; Bergamini, E.; Ricci, A.; Buzzetti, E.; Corradini, E.; Pietrangelo, A.
abstract
Hepcidin, the hepatic iron hormone, is the central regulator of iron homeostasis. Cyclic AMP-Responsive Element-Binding protein 3-like 3 (CREB3L3/CREB-H) is a liver homeostatic regulator of essential nutrients (i.e. glucose and lipids) and has been previously involved in hepcidin response to pathologic stress signals. Here, we asked whether CREB-H has also a physiologic role in iron homeostasis through hepcidin. To this end, we analyzed hepcidin gene expression and regulation in the liver of wild type and Creb3l3 knockout mice during early postnatal development, as a model of "physiologic" stressful condition. The effect of iron challenge in vivo and BMP6 stimulation in vitro have been also addressed. In addition, we investigated the BMP signaling pathway and hepcidin promoter activity following CREB3L3 silencing and hepcidin promoter mutation in HepG2 cells. Creb3l3 knockout suckling and young-adult mice showed a prominent serum and hepatic iron accumulation, respectively, due to impaired hepcidin mRNA expression which progressively returned to normal level in adult mice. Interestingly, upon iron challenge, while the upstream BMP/SMAD signaling pathway controlling hepcidin was equally responsive in both strains, hepcidin gene expression was impaired in knockout mice and more iron accumulated in the liver. Accordingly, hepcidin gene response to BMP6 was blunted in primary CREB-H knockout hepatocytes and in HepG2 cells transfected with CREB-H siRNA or carrying a hepcidin promoter mutated in the CREB-H binding site. In conclusion, CREB-H has a role in maintaining the homeostatic balance of iron traffic through hepcidin during the critical postnatal period and in response to iron challenge.Key messagesCREB-H KO mice develop liver iron overload shortly after weaning that normalizes in adulthood.CHEB-H is involved in hepcidin gene response to oral iron in vivo.CREB-H loss hampers hepcidin promoter response to BMP6.CREB-H is a key stress-sensor controlling hepcidin gene transcription in physiologic and pathophysiologic states.
2023
- Labile plasma iron and echocardiographic parameters are associated to cardiac events in beta-thalassemic patients
[Articolo su rivista]
Ferrara, F; Coppi, F; Riva, R; Ventura, P; Ricci, A; Mattioli, Av; Talarico, M; Garuti, C; Bevini, M; Rochira, V; Buzzetti, E; Pietrangelo, A; Corradini, E
abstract
Background and aim: Notwithstanding the improvement in therapies, patients
affected by thalassemia major (TM) and intermedia (TI) are still at
high risk of cardiac complications. This study aimed at evaluating the incidence
and predictive factors for developing cardiac events in adult β-TM
and TI patients.
Population andmethods: Data on diagnosis and clinical historywere
collected retrospectively; prospective data on new-onset cardiac failure
and arrhythmias, echocardiographic parameters, biochemical variables
including non-transferrin-bound iron (NTBI) and labile plasma iron (LPI),
magnetic resonance imaging (MRI) T2* measurement of hepatic and cardiac
iron deposits, and iron chelation therapy were recorded during a 6
year follow-up.
Results: Thirty-seven patients, 29 TM and 8 TI, were included. At
baseline, 8 TM patients and 1 TI patient had previously experienced a
cardiac event (mainly heart failure). All patients were on chelation therapy
and only 3 TM patients had mild-to-severe cardiac siderosis. During
follow-up, 11 patients (29.7%) experienced a new cardiac event. The occurrence
of cardiac events was correlated to high LPI levels (OR 12.0,
95% CI 1.56-92.3, p 0.017), low mean pre-transfusion hemoglobin (OR
0.21, 95% C.I. 0.051-0.761, p 0.21), and echocardiographic parameters
suggestive of myocardial hypertrophy. Multivariate analysis disclosed
high LPI and left ventricle mass index (LVMI) as independent variables
significantly associated with cardiac events. Cardiac iron deposits measured
by MRI T2* failed to predict cardiac events.
Conclusion: LPI, Hb levels, and echocardiographic parameters assessing
cardiac remodeling are associated to cardiac events in adult TM
and TI patients. LPI might represent both a prognostic marker and a
potential target for novel treatment strategies. Further studies are warranted to confirm our findings on larger populations
2022
- Comparison of point-shear wave elastography (ElastPQ) and transient elastography (FibroScan) for liver fibrosis staging in patients with non-alcoholic fatty liver disease
[Articolo su rivista]
Roccarina, D.; Iogna Prat, L.; Pallini, G.; Guerrero Misas, M.; Buzzetti, E.; Saffioti, F.; Arico, F. M.; Mantovani, A.; Koutli, E.; Goyale, A.; Rosselli, M.; Luong, T. V.; Pinzani, M.; Tsochatzis, E. A.
abstract
Background and Aims: ElastPQ is a point shear wave elastography technique used to non-invasively assess liver fibrosis. We compared liver stiffness measurements (LSM) by ElastPQ and fibroscan transient elastography (F-TE) in a cohort of patients with non-alcoholic fatty liver disease (NAFLD). We further evaluated the performance of ElastPQ in a subgroup of patients with available liver histology. Materials and Methods: We included patients with NAFLD who presented in a dedicated multidisciplinary clinic. Anthropometric parameters, blood tests and elastography measurements were obtained using F-TE and ElastPQ as part of routine clinical care. Results: We enrolled 671 patients with NAFLD, mean age 55.8 ± 13 years, body mass index (BMI) 31.5 ± 5.7 kg/m2, 56.6% males, 41% diabetes, 53.7% hypertension, 68% dyslipidaemia. ElastPQ showed an excellent correlation with F-TE (Spearman's r = 0.80, p <.001), which was better for mild/moderate stages of fibrosis. Independent predictors of a >2 kPa discrepancy between the two techniques were a larger waist circumference and F-TE ≥10 kPa. In the subgroup of 159 patients with available histology, ElastPQ showed similar diagnostic accuracy with F-TE in staging liver fibrosis (ElastPQ area under the curves 0.84, 0.83, 0.86 and 0.95, for F ≥ 1, F ≥ 2, F ≥ 3 and F = 4 respectively). Optimal cut-off values of ElastPQ for individual fibrosis stages were lower than those of F-TE. Conclusions: ElastPQ shows an excellent correlation with F-TE in patients with NAFLD, which was better for lower LSM. The optimal cut-off values of ElastPQ are lower than those of F-TE for individual stages of fibrosis. ElastPQ has similar diagnostic accuracy to F-TE for all stages of fibrosis.
2022
- Iron in Porphyrias: Friend or Foe?
[Articolo su rivista]
Buzzetti, Elena; Ventura, Paolo; Corradini, Elena
abstract
Iron is a trace element that is important for many vital processes, including oxygen
transport, oxidative metabolism, cellular proliferation, and catalytic reactions. Iron supports these
functions mainly as part of the heme molecule. Heme synthesis is an eight-step process which, when
defective at the level of one of the eight enzymes involved, can cause the development of a group
of diseases, either inherited or acquired, called porphyrias. Despite the strict link between iron and
heme, the role of iron in the different types of porphyrias, particularly as a risk factor for disease
development/progression or as a potential therapeutic target or molecule, is still being debated, since
contrasting results have emerged from clinical observations, in vitro studies and animal models. In
this review we aim to deepen such aspects by drawing attention to the current evidence on the role of
iron in porphyrias and its potential implication. Testing for iron status and its metabolic pathways
through blood tests, imaging techniques or genetic studies on patients affected by porphyrias can
provide additional diagnostic and prognostic value to the clinical care, leading to a more tailored and
effective management.
2022
- Iron Metabolism in the Disorders of Heme Biosynthesis
[Articolo su rivista]
Ricci, Andrea; Di Betto, Giada; Bergamini, Elisa; Buzzetti, Elena; Corradini, Elena; Ventura, Paolo
abstract
Given its remarkable property to easily switch between different oxidative states, iron is
essential in countless cellular functions which involve redox reactions. At the same time, uncon-
trolled interactions between iron and its surrounding milieu may be damaging to cells and tissues.
Heme—the iron-chelated form of protoporphyrin IX—is a macrocyclic tetrapyrrole and a coordina-
tion complex for diatomic gases, accurately engineered by evolution to exploit the catalytic, oxygen-
binding, and oxidoreductive properties of iron while minimizing its damaging effects on tissues.
The majority of the body production of heme is ultimately incorporated into hemoglobin within
mature erythrocytes; thus, regulation of heme biosynthesis by iron is central in erythropoiesis.
Additionally, heme is a cofactor in several metabolic pathways, which can be modulated by iron-
dependent signals as well. Impairment in some steps of the pathway of heme biosynthesis is the main
pathogenetic mechanism of two groups of diseases collectively known as porphyrias and congenital
sideroblastic anemias. In porphyrias, according to the specific enzyme involved, heme precursors
accumulate up to the enzyme stop in disease-specific patterns and organs. Therefore, different por-
phyrias manifest themselves under strikingly different clinical pictures. In congenital sideroblastic
anemias, instead, an altered utilization of mitochondrial iron by erythroid precursors leads to mito-
chondrial iron overload and an accumulation of ring sideroblasts in the bone marrow. In line with
the complexity of the processes involved, the role of iron in these conditions is then multifarious.
This review aims to summarise the most important lines of evidence concerning the interplay be-
tween iron and heme metabolism, as well as the clinical and experimental aspects of the role of iron
in inherited conditions of altered heme biosynthesis.
2022
- The SIMI Gender ‘5 Ws’ Rule for the integration of sex and gender-related variables in clinical studies towards internal medicine equitable research
[Articolo su rivista]
Raparelli, V.; Santilli, F.; Marra, A. M.; Romiti, G. F.; Succurro, E.; Licata, A.; Buzzetti, E.; Piano, S.; Masala, M.; Suppressa, P.; Becattini, C.; Muiesan, M. L.; Russo, G.; Cogliati, C.; Proietti, M.; Basili, S.
abstract
Biological sex and sociocultural gender matter when it comes to health and diseases. They have been both proposed as the undeniable gateways towards a personalized approach in care delivery. The Gender Working Group of the Italian Society of Internal Medicine (SIMI) was funded in 2019 with the aim of promoting good practice in the integration of sex and gender domains in clinical studies. Starting from a narrative literature review and based on regular meetings which led to a shared virtual discussion during the national SIMI congress in 2021, the members of the WG provided a core operational framework to be applied by internal medicine (IM) specialists to understand and implement their daily activity as researchers and clinicians. The SIMI Gender '5 Ws' Rule for clinical studies has been conceptualized as follows: Who (Clinical Internal Medicine Scientists and Practitioners), What (Gender-related Variables-Gender Core Dataset), Where (Clinical Studies/Translational Research), When (Every Time It Makes Sense) and Why (Explanatory Power of Gender and Opportunities). In particular, the gender core dataset was identified by the following domains (variables to collect accordingly): relations (marital status, social support, discrimination); roles (occupation, caregiver status, household responsibility, primary earner, household dimension); institutionalized gender (education level, personal income, living in rural vs urban areas); and gender identity (validated questionnaires on personality traits). The SIMI Gender '5 Ws' Rule is a simple and easy conceptual framework that will guide IM for the design and analysis of clinical studies.
2021
- Ceruloplasmin gene variants are associated with hyperferritinemia and increased liver iron in patients with {NAFLD}
[Articolo su rivista]
Corradini, Elena; Buzzetti, Elena; Dongiovanni, Paola; Scarlini, Stefania; Caleffi, Angela; Pelusi, Serena; Bernardis, Isabella; Ventura, Paolo; Rametta, Raffaela; Tenedini, Elena; Tagliafico, Enrico; Ludovica Fracanzani, Anna; Fargion, Silvia; Pietrangelo, Antonello; Vittorio Valenti, Luca
abstract
Non-alcoholic fatty liver disease (NAFLD) is a multifactorial disorder resulting from genetic and environmental factors. Hyperferritinemia has been associated with increased hepatic iron stores and worse outcomes in patients with NAFLD. The aim of this study was to evaluate the prevalence of variants of iron-related genes and their association with hyperferritinemia, hepatic iron stores and liver disease severity in patients with NAFLD.
2021
- Collagen proportionate area predicts long-term mortality in patients with alcoholic hepatitis
[Articolo su rivista]
Israelsen, M.; Misas, M. G.; Koutsoumourakis, A.; Hall, A.; Covelli, C.; Buzzetti, E.; Prat, L. I.; Roccarina, D.; Luong, T. V.; Quaglia, A.; Pinzani, M.; Tsochatzis, E. A.
abstract
Background and aims: There are several short-term prognostic scores for alcoholic hepatitis (AH) that combine demographical and biochemical parameters. The extent of liver fibrosis may also be relevant to the prognosis of AH with potential added value. We evaluated collagen proportionate area (CPA) as a predictor of short and long-term mortality in AH. Methods: We retrospectively included patients with biopsy-verified AH. Clinical, laboratory and outcome data were collected. CPA and five AH scores were calculated: Maddrey's DF, MELD, GAHS, ABIC, and the Lille Model. Predictors of short and long-term all-cause mortality were assessed using Cox regression analysis. Results: We included 140 patients with AH. In total, 67 (48%) patients died after a median follow-up of 66 (IQR 102) months, with 17 (12%) dying within the first 90-days. CPA was not a predictor of 90-days mortality and had no additional value to the prognostic AH scores on short-term mortality. However, CPA predicted long-term mortality independently of prognostic AH scores. Importantly, CPA and abstinence from alcohol were independent predictors of long-term mortality in patients alive 90 days after the biopsy. Conclusion: CPA predicts long-term mortality in patients with AH independently of abstinence from alcohol but has no prognostic value on short-term mortality.
2021
- Establishing Reliability Criteria for Liver ElastPQ Shear Wave Elastography (ElastPQ-SWE): Comparison between 10, 5 and 3 Measurements
[Articolo su rivista]
Roccarina, D.; Iogna Prat, L.; Buzzetti, E.; Guerrero Misas, M.; Arico, F. M.; Saffioti, F.; Rosselli, M.; Pinzani, M.; Marshall, A.; Thorburn, D.; Tsochatzis, E.
abstract
Purpose ElastPQ is a new elastography technique for non-invasive liver fibrosis staging. However, it does not have validated reliability criteria. We tested the reliability of a different number of measurements in patients with chronic liver disease and explored whether the application of quality criteria improves the diagnostic performance. Materials and Methods All patients underwent liver stiffness assessment (LSM) with ElastPQ and Fibroscan (F-TE). The mean, median, standard deviation (SD) and interquartile range (IQR) of 10, 5 and 3 measurements were retrospectively collected for each patient and compared to each other. Liver histology was available in a subset of patients. Results Overall, 400 patients met the inclusion criteria. Non-alcoholic fatty liver disease (NAFLD) was the most represented etiology (75%), followed by primary sclerosing cholangitis (PSC), primary biliary cholangitis (PBC) and autoimmune hepatitis (AIH). The correlation of medians was significantly better between 10 and 5 measurements than between 10 and 3. The difference of medians was significant only in the comparison between 10 and 3 measurements. The correlation between ElastPQ and F-TE was equally good for 10 and 5 measurements and significantly improved after an IQR/median ≤30% was applied. The diagnostic performance of ElastPQ was better with the median value of 10 and 5 measurements and improved if LSM values were obtained with IQR/M≤30%. Conclusion The median value of 5 valid LSMs suffices for the reliable estimation of liver stiffness using ElastPQ. The quality criterion of IQR/M≤30% should also be followed when using this technique.
2021
- Lifestyle modifications for nonalcohol-related fatty liver disease: a network meta-analysis
[Articolo su rivista]
Buzzetti, E.; Linden, A.; Best, L. M. J.; Madden, A. M.; Roberts, D.; Chase, T. J. G.; Freeman, S. C.; Cooper, N. J.; Sutton, A. J.; Fritche, D.; Milne, E. J.; Wright, K.; Pavlov, C. S.; Davidson, B. R.; Tsochatzis, E.; Gurusamy, K. S.
abstract
Background: The prevalence of nonalcohol-related fatty liver disease (NAFLD) varies between 19% and 33% in different populations. NAFLD decreases life expectancy and increases the risks of liver cirrhosis, hepatocellular carcinoma, and requirement for liver transplantation. There is uncertainty surrounding the relative benefits and harms of various lifestyle interventions for people with NAFLD. Objectives: To assess the comparative benefits and harms of different lifestyle interventions in the treatment of NAFLD through a network meta-analysis, and to generate rankings of the different lifestyle interventions according to their safety and efficacy. Search methods: We searched CENTRAL, MEDLINE, Embase, Science Citation Index Expanded, Conference Proceedings Citation Index - Science, World Health Organization International Clinical Trials Registry Platform, and trials registers until February 2021 to identify randomised clinical trials in people with NAFLD. Selection criteria: We included only randomised clinical trials (irrespective of language, blinding, or status) in people with NAFLD, whatever the method of diagnosis, age, and diabetic status of participants, or presence of non-alcoholic steatohepatitis (NASH). We excluded randomised clinical trials in which participants had previously undergone liver transplantation. Data collection and analysis: We planned to perform a network meta-analysis with OpenBUGS using Bayesian methods and to calculate the differences in treatments using hazard ratios (HRs), odds ratios (ORs), and rate ratios (RaRs) with 95% credible intervals (CrIs) based on an available-participant analysis, according to National Institute of Health and Care Excellence Decision Support Unit guidance. However, the data were too sparse for the clinical outcomes. We therefore performed only direct comparisons (head-to-head comparisons) with OpenBUGS using Bayesian methods. Main results: We included a total of 59 randomised clinical trials (3631 participants) in the review. All but two trials were at high risk of bias. A total of 33 different interventions, ranging from advice to supervised exercise and special diets, or a combination of these and no additional intervention were compared in these trials. The reference treatment was no active intervention. Twenty-eight trials (1942 participants) were included in one or more comparisons. The follow-up ranged from 1 month to 24 months. The remaining trials did not report any of the outcomes of interest for this review. The follow-up period in the trials that reported clinical outcomes was 2 months to 24 months. During this short follow-up period, clinical events related to NAFLD such as mortality, liver cirrhosis, liver decompensation, liver transplantation, hepatocellular carcinoma, and liver-related mortality were sparse. This is probably because of the very short follow-up periods. It takes a follow-up of 8 years to 28 years to detect differences in mortality between people with NAFLD and the general population. It is therefore unlikely that differences by clinical outcomes will be noted in trials with less than 5 years to 10 years of follow-up. In one trial, one participant developed an adverse event. There were no adverse events in any of the remaining participants in this trial, or in any of the remaining trials, which seemed to be directly related to the intervention. Authors' conclusions: The evidence indicates considerable uncertainty about the effects of the lifestyle interventions compared with no additional intervention (to general public health advice) on any of the clinical outcomes after a short follow-up period of 2 months to 24 months in people with nonalcohol-related fatty liver disease. Accordingly, high-quality randomised clinical trials with adequate follow-up are needed. We propose registry-based randomised clinical trials or cohort multiple randomised clinical trials (a study design in which multiple interventions are trialed within large longitud
2021
- Nutritional supplementation for nonalcohol-related fatty liver disease: a network meta-analysis
[Articolo su rivista]
Komolafe, O.; Buzzetti, E.; Linden, A.; Best, L. M. J.; Madden, A. M.; Roberts, D.; Chase, T. J. G.; Fritche, D.; Freeman, S. C.; Cooper, N. J.; Sutton, A. J.; Milne, E. J.; Wright, K.; Pavlov, C. S.; Davidson, B. R.; Tsochatzis, E.; Gurusamy, K. S.
abstract
Background: The prevalence of non-alcohol-related fatty liver disease (NAFLD) varies between 19% and 33% in different populations. NAFLD decreases life expectancy and increases risks of liver cirrhosis, hepatocellular carcinoma, and the requirement for liver transplantation. Uncertainty surrounds relative benefits and harms of various nutritional supplements in NAFLD. Currently no nutritional supplement is recommended for people with NAFLD. Objectives: • To assess the benefits and harms of different nutritional supplements for treatment of NAFLD through a network meta-analysis
• To generate rankings of different nutritional supplements according to their safety and efficacy. Search methods: We searched the Cochrane Central Register of Controlled Trials, MEDLINE, Embase, Science Citation Index Expanded, Conference Proceedings Citation Index-Science, the World Health Organization International Clinical Trials Registry Platform, and trials registers until February 2021 to identify randomised clinical trials in people with NAFLD. Selection criteria: We included only randomised clinical trials (irrespective of language, blinding, or status) for people with NAFLD, irrespective of method of diagnosis, age and diabetic status of participants, or presence of non-alcoholic steatohepatitis (NASH). We excluded randomised clinical trials in which participants had previously undergone liver transplantation. Data collection and analysis: We performed a network meta-analysis with OpenBUGS using Bayesian methods whenever possible and calculated differences in treatments using hazard ratios (HRs), odds ratios (ORs), and rate ratios with 95% credible intervals (CrIs) based on an available-case analysis, according to National Institute of Health and Care Excellence Decision Support Unit guidance. Main results: We included in the review a total of 202 randomised clinical trials (14,200 participants). Nineteen trials were at low risk of bias. A total of 32 different interventions were compared in these trials. A total of 115 trials (7732 participants) were included in one or more comparisons. The remaining trials did not report any of the outcomes of interest for this review. Follow-up ranged from 1 month to 28 months. The follow-up period in trials that reported clinical outcomes was 2 months to 28 months. During this follow-up period, clinical events related to NAFLD such as mortality, liver cirrhosis, liver decompensation, liver transplantation, hepatocellular carcinoma, and liver-related mortality were sparse. We did not calculate effect estimates for mortality because of sparse data (zero events for at least one of the groups in the trial). None of the trials reported that they measured overall health-related quality of life using a validated scale. The evidence is very uncertain about effects of interventions on serious adverse events (number of people or number of events). We are very uncertain about effects on adverse events of most of the supplements that we investigated, as the evidence is of very low certainty. However, people taking PUFA (polyunsaturated fatty acid) may be more likely to experience an adverse event than those not receiving an active intervention (network meta-analysis results: OR 4.44, 95% CrI 2.40 to 8.48; low-certainty evidence; 4 trials, 203 participants; direct evidence: OR 4.43, 95% CrI 2.43 to 8.42). People who take other supplements (a category that includes nutritional supplements other than vitamins, fatty acids, phospholipids, and antioxidants) had higher numbers of adverse events than those not receiving an active intervention (network meta-analysis: rate ratio 1.73, 95% CrI 1.26 to 2.41; 6 trials, 291 participants; direct evidence: rate ratio 1.72, 95% CrI 1.25 to 2.40; low-certainty evidence). Data were sparse (zero events in all groups in the trial) for liver transplantation, liver decompensation, and hepatocellular carcinoma. So, we did not perform formal
2020
- Collagen proportionate area predicts clinical outcomes in patients with alcohol-related liver disease
[Articolo su rivista]
Israelsen, M.; Guerrero Misas, M.; Koutsoumourakis, A.; Huang, Y.; Thiele, M.; Hall, A.; Rasmussen, D.; Covelli, C.; Buzzetti, E.; Prat, L. I.; Roccarina, D.; Detlefsen, S.; Luong, T. V.; Quaglia, A.; Krag, A.; Jeffrey, G.; Pinzani, M.; Tsochatzis, E. A.
abstract
Background: No prognostic tools are established for alcohol-related liver disease (ALD). Collagen proportionate area (CPA) measurement is a technique that quantifies fibrous tissue in liver biopsies using digital image analysis. Aim: To assess the predictive value of CPA on hepatic decompensation and liver-related mortality in ALD. Methods: In a multicentre cohort study, we included 386 patients with biopsy-verified ALD and with long-term follow-up. In the development cohort of 276 patients, we assessed the predictors of hepatic decompensation and liver-related death in standard and competing risk multivariable Cox regression analyses. The results were validated in an independent prospective cohort of 110 patients, where CPA was also correlated with liver stiffness measurement (LSM). Results: In the development cohort, 231 (84%) patients had early/compensated ALD (non-cirrhotic or compensated cirrhosis) and 45 (16%) had decompensated cirrhosis. In the validation cohort, all patients had early/compensated ALD. Independent predictors of liver-related mortality were higher CPA values (HR = 1.04, 95% CI 1.02-1.04) and advanced fibrosis (HR = 2.80, 95% CI 1.29-6.05) with similar results in standard and competing risk multivariable Cox regression analysis. In early/compensated ALD, CPA was the only independent predictor of hepatic decompensation and liver-related death (HR = 1.08, 95% CI 1.06-1.11). In the prospective cohort, we validated that CPA independently predicts hepatic decompensation in early/compensated ALD. The predictive power of CPA and LSM was equally strong. Conclusions: CPA predicts liver-related mortality in ALD and hepatic decompensation and/or liver-related death in early/compensated ALD. Traditional histological assessment may benefit from the addition of CPA to the evaluation of ALD.
2020
- Genetic iron overload disorders
[Articolo su rivista]
Corradini, E.; Buzzetti, E.; Pietrangelo, A.
abstract
Due to its pivotal role in orchestrating vital cellular functions and metabolic processes, iron is an essential component of the human body and a main micronutrient in the human diet. However, excess iron causes an increased production of reactive oxygen species leading to cell dysfunction or death, tissue damage and organ disease. Iron overload disorders encompass a wide spectrum of pathological conditions of hereditary or acquired origin. A number of ‘iron genes’ have been identified as being associated with hereditary iron overload syndromes, the most common of which is hemochromatosis. Although linked to at least five different genes, hemochromatosis is recognized as a unique syndromic entity based on a common pathogenetic mechanism leading to excessive entry of unneeded iron into the bloodstream. In this review, we focus on the pathophysiologic basis and clinical aspects of the most common genetic iron overload syndromes in humans.
2020
- Hyperhomocysteinemia in patients with acute porphyrias: A potentially dangerous metabolic crossroad?
[Articolo su rivista]
Ventura, P.; Corradini, E.; Di Pierro, E.; Marchini, S.; Marcacci, M.; Cuoghi, C.; Buzzetti, E.; Pietrangelo, A.
abstract
Background: Acute porphyrias (AP) are characterized by heme deficiency and induction of hepatic 5-aminolevulinate synthase (ALAS1). Hyperhomocysteinemia (HHcy) is associated with endothelial damage, neurotoxicity and increased risk for vascular diseases. Interestingly, both heme biosynthesis and sulphur amino acid metabolism require vitamin B6, (Pyridoxal-phosphate, PLP) an important cofactor of ALAS1 and of cystathionine β-synthase (CBS) and cystathionine γ-lyase (CGL) enzymes that catabolize homocysteine (Hcy). Moreover, heme itself is an important cofactor for CBS. Aim: to assess plasma Hcy status and HHcy main determinants in patients with AP. Materials and methods: A total of 46 patients with AP (31 with Acute Intermittent Porphyria,15 with Variegate Porphyria) were assessed for clinical status (symptomatic vs. asymptomatic), serum Hcy, Cysteine (Cys), Vit.B6, Vit.B12, red blood cell folates and urinary delta-aminolevulinic acid (ALA) and porphobilinogen(PBG) levels (mean of six measurements). Results: Symptomatic AP patients had significantly higher urinary ALA and PBG levels, plasma Hcy, HHcy prevalence and Hcy/Cys ratio when compared to asymptomatic carriers of AP. Even though no significant correlation was observed between ALA/PBG urinary levels and serum Hcy levels, patients with higher levels of ALA and PBG had significantly higher levels of Hcy, a higher prevalence of moderate-to severe HHcy and serum PLP levels below the 25th percentile of a reference assessment with 300 healthy Italian subjects(<45nmol/L). Conclusions: Most patients with symptomatic AP present HHcy resulting from alterations in sulphur amino acid metabolism. HHcy may represent an indirect marker of ALAS1 induction and its prevalence may be suggestive of a role of HHcy in the pathogenesis and/or comorbidities of AP.
2020
- Risk of kidney dysfunction in NAFLD
[Articolo su rivista]
Mantovani, A.; Zusi, C.; Dalbeni, A.; Grani, G.; Buzzetti, E.
abstract
Background: The timely identification of traditional and non-traditional precursors and risk factors for chronic kidney disease (CKD) (a common systemic disease defined as a decreased kidney function documented by reduced glomerular filtration rate, or markers of kidney damage, or both) is relevant in clinical practice, as CKD increases the risk of end-stage renal disease and other serious comorbidities. A possible relationship between non-alcoholic fatty liver disease (NAFLD) (which is to date the most common chronic disease worldwide) and CKD has recently gained significant attention of researchers. Methods: A systematic literature search using appropriate keywords was made in order to identify relevant articles that have investigated the association between NAFLD and CKD. Results: Several observational studies and meta-analyses have reported the existence of an independent association between NAFLD and risk of CKD in patients with and without diabetes. However, whilst the association between NAFLD and risk of prevalent CKD is strong across various patient populations, whether NAFLD is independently associated with the development and progression of CKD is still debatable. Moreover, emerging evidence now suggests a potential association between patatin-like phospholipase domain-containing protein-3 (PNPLA3) rs738409 genotype (the most important genetic variant associated to NAFLD) and decreasing kidney function, independent of NAFLD. Conclusion: Convincing evidence now indicates that CKD is increased among patients with NAFLD. For this reason, patients with NAFLD should be regularly monitored for renal function and, on the other hand, NAFLD should be considered in all patients with CKD, especially if they are obese or have type 2 diabetes.
2019
- Cardiovascular morbidity and mortality is increased post-liver transplantation even in recipients with no pre-existing risk factors
[Articolo su rivista]
De Luca, L.; Kalafateli, M.; Bianchi, S.; Alasaker, N.; Buzzetti, E.; Rodriguez-Peralvarez, M.; Thorburn, D.; O'Beirne, J.; Patch, D.; Leandro, G.; Westbrook, R.; Tsochatzis, E. A.
abstract
Background/aims: Post-liver transplant (LT) metabolic syndrome (PTMS) and cardiovascular (CVS) mortality are becoming increasingly prevalent following sustained improvements in post-LT survival. We investigated the prevalence and predictors of PTMS and CVS complications in a cohort of consecutive LT recipients. Methods: We reviewed prospectively collected data of patients (n = 928) who underwent LT (1995-2013) and survived at least 1-year post-LT or died before that due to a major CVS complication. Results: Median follow-up was 85 months (IQR = 106). The prevalence of PTMS was 22.4% and it developed de novo in 183 recipients (19.7%). A total of 187 (20.2%) patients developed at least one CVS event post-LT within a median of 49 months (IQR = 85). Overall mortality rate was 22.6% (n = 210). Causes of death were CVS events (n = 45, 21.4%), malignancies (21%), liver-related deaths (20%) and infections (6.7%). Independent predictors of major CVS events were: documented CVS disease pre-LT (Hazard Ratio (HR) = 3.330; 95% CI = 1.620-6.840), DM (HR = 1.120; 95% CI 1.030-1.220), hypertension (HR = 1.140; 95% CI 1.030-1.270), dyslipidaemia (HR = 1.140; 95% CI 1.050-1.240) and creatinine levels at 1 year (HR = 1.010; 95% CI = 1.005-1.013). Among LT recipients without pre-LT CVS disease or MS components (n = 432), 85 recipients developed ≥1 CVS events (19.7%) with independent predictors being DM (HR = 1.150; 95% CI = 1.010-1.320), creatinine levels at 1 year (HR = 1.020; 95% CI = 1.010-1.030) and hypertension (HR = 1.190; 95% CI = 1.040-1.360). Conclusions: Post-LT patients are at increased risk of CVS morbidity even in the absence of pre-existing metabolic risk factors. Renal sparing immunosuppressive protocols might reduce CVS events post-LT.
2019
- Collagen proportionate area is an independent predictor of long-term outcome in patients with non-alcoholic fatty liver disease
[Articolo su rivista]
Buzzetti, E.; Hall, A.; Ekstedt, M.; Manuguerra, R.; Guerrero Misas, M.; Covelli, C.; Leandro, G.; Luong, T.; Kechagias, S.; Manesis, E. K.; Pinzani, M.; Dhillon, A. P.; Tsochatzis, E. A.
abstract
Background: Collagen proportionate area (CPA) measurement is a technique that quantifies fibrous tissue in liver biopsies by measuring the amount of collagen deposition as a proportion of the total biopsy area. CPA predicts clinical outcomes in patients with HCV and can sub-classify cirrhosis. Aim: To test the ability of CPA to quantify fibrosis and predict clinical outcomes in patients with NAFLD. Methods: We assessed consecutive patients with biopsy-proven NAFLD from three European centres. Clinical and laboratory data were collected at baseline and at the time of the last clinical follow-up or death. CPA was performed at two different objective magnifications, whole biopsy macro and ×4 objective magnification, named standard (SM) and high (HM) magnification respectively. The correlation between CPA and liver stiffness was assessed in a sub-group of patients. Results: Of 437 patients, 32 (7.3%) decompensated and/or died from liver-related causes during a median follow-up of 103 months. CPA correlated with liver stiffness and liver fibrosis stage across the whole spectrum of fibrosis. HM CPA was significantly higher than SM CPA in stages F0-F3 but similar in cirrhosis, reflecting a higher ability to capture pericellular/perisinusoidal fibrosis at early stages. Age at baseline (HR: 1.04, 95% CI: 1.01-1.08), HM CPA (HR: 1.04 per 1% increase, 95% CI: 1.01-1.08) and presence of advanced fibrosis (HR: 15.4, 95% CI: 5.02-47.84) were independent predictors of liver-related clinical outcomes at standard and competing risk multivariate Cox-regression analysis. Conclusions: CPA accurately measures fibrosis and is an independent predictor of clinical outcomes in NAFLD; hence it merits further evaluation as a surrogate endpoint in clinical trials.
2019
- Editorial: collagen proportionate area as a prognostic indicator in NAFLD—authors’ reply
[Articolo su rivista]
Buzzetti, E.; Tsochatzis, E. A.
abstract
2019
- Evaluating the association of serum ferritin and hepatic iron with disease severity in non-alcoholic fatty liver disease
[Articolo su rivista]
Buzzetti, E.; Petta, S.; Manuguerra, R.; Luong, T. V.; Cabibi, D.; Corradini, E.; Craxi, A.; Pinzani, M.; Tsochatzis, E.; Pietrangelo, A.
abstract
Background & Aims: Hyperferritinemia, with or without increased hepatic iron, represents a common finding in non-alcoholic fatty liver disease (NAFLD). However, it is unclear whether it reflects hepatic inflammation or true iron-overload and, in case the latter is confirmed, whether this influences disease progression. We therefore explored the association between serum ferritin, degree and pattern of hepatic iron deposition and liver disease severity in patients with NAFLD. Methods: We selected 468 patients with biopsy-proven NAFLD from 2 European centres. Iron, hepatic and metabolic parameters were collected at the time of liver biopsy. Iron deposits in hepatocytes and reticuloendothelial cells were assessed and graded. Diagnosis of non-alcoholic steatohepatitis (NASH) and fibrosis staging were performed. Results: A total of 122 (26%) patients had hyperferritinemia, whereas stainable hepatic iron was found in 116 (25%) patients (38% predominantly in hepatocytes, 20% in reticuloendothelial cells and 42% in both). Subjects with stainable hepatic iron, particularly those with a mixed pattern, had higher serum ferritin and transaminases but only a mixed pattern of iron deposition was among the variables significantly associated with presence of NASH. Serum ferritin was not associated with presence of NASH, however it increased with worsening fibrosis stage (F3 compared to F0-F1), and significantly decreased in stage F4. Conclusions: A mixed pattern of hepatic iron deposition is associated with the presence of steatohepatitis, while serum ferritin increases with worsening fibrosis up to pre-cirrhotic stage. In individual NAFLD patients, serum ferritin could be evaluated as part of non-invasive diagnostic panels but not on its own.
2019
- Incidence and Recurrence of Portal Vein Thrombosis in Cirrhotic Patients
[Articolo su rivista]
Violi, F.; Corazza, G. R.; Caldwell, S. H.; Talerico, G.; Romiti, G. F.; Napoleone, L.; Perticone, F.; Bolondi, L.; Pietrangelo, A.; Vestri, A. R.; Raparelli, V.; Basili, S.; Elena, A. M.; Paola, A.; Angelo, A.; Francesco, A.; Mario, A.; Antonio, F.; Massimiliano, A.; Umberto, A.; Maurizio, A.; Milena, B.; Cristina, B.; Gaetano, B.; Michele, B.; Battista, B. G.; Ilaria, B. P.; Benedetta, B.; Giancarlo, B.; Christian, B.; Silvia, B.; Agostino, B.; Carmelo, B.; Buzzetti, E.; Irene, C.; Stefano, C.; Roberto, C.; William, C.; Federica, C.; Isabella, C.; Pietro, C.; Benedetto, C.; Domenica, C. M.; Luigi, C.; Maurizio, C.; Lara, C.; Flavio, C.; Sebastiano, C.; Claudia, C.; Maria, C. B.; Elena, C.; Salvatore, C.; Giorgio, C.; Filippo, C.; Giuseppe, C.; Chiara, C.; Valentina, C.; Felicia, D.; Gennaro, D.; Roberto, D. F.; Alfredo, D. G.; Stefano, D. V.; Wilma, D. V.; Maria, D. B.; Lisette, D. C.; Giuseppe, D.; Andrea, D.; Valentina, D. C.; Paolo, D. G.; Dario, D. M.; Giovanni, D. M.; Emilia, D.; Davide, D.; Emanuele, D. -M.; Lorenzo, F.; Alessio, F.; Vincenza, F.; Silvano, F.; Giovanni, F.; Tiziana, F.; Alessandra, F.; Pierluigi, F.; Giovanni, G.; Paolo, G.; Matteo, G.; Ruggiero, G.; Antonio, G.; Angelo, G.; Antonina, G.; Gianluigi, G.; Paolo, G.; Paolo, G.; Alessandro, G.; Davide, G.; Antonio, G.; Alessandro, G.; Paolo, G.; Daniel, H.; Angelo, I.; Luigi, I.; Pietro, I.; Antonio, I.; Giacomo, L.; Anna, L.; Livia, L. M.; Giusi, L.; Sergio, M.; Roberto, M.; Matteo, M.; Alessandra, M.; Sara, M.; Maria, M. A.; Pio, M. G.; Maristella, M.; Michela, M.; Antonio, M.; Giuseppe, M.; Ludovico, M. A.; Ignazio, M.; Olivia, M.; Giuseppe, M.; Paola, N.; Sergio, N.; Grazia, N.; Lorenzo, N.; Donatella, P.; Giuseppe, P.; Ostilio, P. V.; Daniele, P.; Paolo, P.; Francesca, P.; Maria, P.; Paola, P.; Luigi, P.; Irene, P.; Salvatore, P.; Antonio, P.; Serena, P. F.; Pietro, P.; Pasquale, P.; Miriam, P.; Antonio, P.; Daniela, P.; Licia, P.; Vincenzo, P.; Graziella, P.; Marco, P.; Giacomo, P.; Francesco, P.; Enrico, R.; Giovanni, R.; Tea, R.; Laura, R.; Mario, R.; Isabel, R. -C. K.; Giulio, R. R.; Eleonora, R.; David, S.; Francesco, S.; Aldo, S.; Andrea, S.; Giuseppe, S.; Claudia, S.; Francesca, S.; Daniela, S.; Francesca, S.; Cosima, S.; Roberto, S.; Marco, S.; Carla, S.; Gaetano, S.; Domenico, S.; Maurizio, S.; Nicolo, S.; Silvia, S.; Orietta, S.; Stasi, C.; Patrizia, S.; Gianluca, S. B.; Michela, T.; Claudio, T.; Joseph, T. E.; Tommaso, T.; Filippo, T.; Daniele, T.; Matteo, T.; Giovanni, T.; Antonella, T.; Antonino, T.; Doriana, V.; Natale, V.; Rita, V. C.; Gianluigi, V.; Paolo, V.; Umberto, V. -G.; Elia, V.; Gianpaolo, V.; Villani, R.; Ronca, V.; Giacomo, V.; Francesco, V.; Assunta, Z. M.
abstract
2019
- Letter: use of collagen proportionate area to quantify liver fibrosis and predict clinical outcomes non-alcoholic fatty liver disease—authors' reply
[Articolo su rivista]
Buzzetti, E.; Tsochatzis, E. A.
abstract
2019
- Looking for women in hepatology: Sex authorship differences in clinical practice guidelines and position statements
[Articolo su rivista]
Mantovani, A.; Nascimbeni, F.; Buzzetti, E.; Dalbeni, A.
abstract
First female authorship is slowly increasing in scientific publications, but it is still inconsistent and seems to vary across different medical disciplines and specialties. When looking at the authorship in gastroenterology and/or hepatology original papers, it was estimated that the proportion of first female authors increased from 9% in 1992 to 29% in 2012, whereas for last authors, the proportion of female authors increased from 5% in 1992 to 14% in 2012. However, clinical practice guidelines or position statements may potentially adopt different authorship rules when compared to original articles.
2019
- Safety and efficacy of sucrosomal iron in inflammatory bowel disease patients with iron deficiency anemia
[Articolo su rivista]
Abbati, G.; Incerti, F.; Boarini, C.; Bocchi, D.; Ventura, P.; Buzzetti, E.; Pietrangelo, A.
abstract
Iron deficiency anemia (IDA) is one of the most common complications of inflammatory bowel disease (IBD). We planned a prospective study to address tolerability and efficacy of sucrosomial iron, a new oral formulation of ferric pyrophosphate, in IBD patients. Thirty patients with a confirmed diagnosis of Crohn’s Disease (CD) or ulcerative colitis (UC) and mild IDA were enrolled. Patients with severe IBD were excluded. All patients underwent 12 weeks of oral treatment with 30 mg/day of sucrosomial iron. Treatment compliance and adverse events were investigated every 4 weeks. Iron status, hematological parameters and IBD activity scores were determined at baseline and at the end of treatment, as well as serum hepcidin and non-transferrin bound iron (NTBI) levels. Twenty-four (80%) patients took more than 90% of the prescribed regimen. Forty-four adverse events (AEs) were recorded, but none of them is considered certainly or probably related to the study treatment. Interestingly, only eleven gastrointestinal events were recorded in 9 (30%) patients. At the end of treatment, all iron parameters improved significantly and Hb increased in 86% of patients (from 11.67 to 12.37 g/dl, p = 0.001). Serum hepcidin showed a significant increase in 79% of patients and became positively correlated with C-reactive protein (CRP) at the end of the study, while NTBI remained below the detection threshold after iron supplementation. The IBD activity scores improved in both CD and UC. This pilot interventional study supports the therapeutic use of sucrosomial iron in IBD and paves the way for future studies in larger or more difficult IBD populations.
2019
- Serum Albumin Is Inversely Associated With Portal Vein Thrombosis in Cirrhosis
[Articolo su rivista]
Basili, Stefania; Carnevale, Roberto; Nocella, Cristina; Bartimoccia, Simona; Raparelli, Valeria; Talerico, Giovanni; Stefanini, Lucia; Romiti, Giulio F; Perticone, Francesco; Corazza, Gino R; Piscaglia, Fabio; Pietrangelo, Antonello; Violi, Francesco; and PRO-LIVER collaborators, : Ainora Maria Elena; Andreozzi, Paola; Andriulli, Angelo; Angelico, Francesco; Angelico, Mario; Figliomeni, Antonio; Anzaldi, Massimiliano; Arena, Umberto; Averna, Maurizio; Barone, Milena; Bazzini, Cristina; Bergamaschi, Gaetano; Bertoni, Michele; Bianchi Giovanni, Battista; Bianchi Paola, Ilaria; Boari, Benedetta; Bombonato, Giancarlo; Bracco, Christian; Brocco, Silvia; Buonauro, Agostino; Buttà, Carmelo; Buzzetti, Elena; Cacciola, Irene; Calabria, Stefano; Cangemi, Roberto; Capeci, William; Caradio, Federica; Carderi, Isabella; Carleo, Pietro; Caroleo, Benedetto; Carrabba Maria, Domenica; Castorani, Luigi; Cavallo, Maurizio; Cecchetto, Lara; Cesaro, Flavio; Cicco, Sebastiano; Cimini, Claudia; Colombo Barbara, Maria; Corradini, Elena; Corrao, Salvatore; Costantino, Giorgio; Costanzo, Filippo; Croce, Giuseppe; Cuoghi, Chiara; Curigliano, Valentina; D’Alitto, Felicia; D’Amico, Gennaro; De Franchis, Roberto; De Giorgi, Alfredo; De Vuono, Stefano; Debernardi Venon, Wilma; Del Ben, Maria; Del Corso, Lisette; Delitala, Giuseppe; Denegri, Andrea; Di Cesare, Valentina; Di Giosia, Paolo; Di Michele, Dario; Di Minno, Giovanni; Donnarumma, Emilia; Drenaggi, Davide; Durante-Mangoni, Emanuele; Falsetti, Lorenzo; Farcomeni, Alessio; Farinaro, Vincenza; Fasolato, Silvano; Ferrari, Giovanni; Fierro, Tiziana; Forgione, Alessandra; Frugiuele, Pierluigi; Galati, Giovanni; Gallo, Paolo; Garcovich, Matteo; Gargano, Ruggiero; Gasbarrini, Antonio; Gatta, Angelo; Giammanco, Antonina; Giannelli, Gianluigi; Giorgini, Paolo; Gobbi, Paolo; Granito, Alessandro; Grassi, Davide; Greco, Antonio; Grembiale, Alessandro; Gresele, Paolo; Hijazi, Daniel; Iacobellis, Angelo; Iamele, Luigi; Invernizzi, Pietro; Ippolito, Antonio; Laffi, Giacomo; Licata, Anna; Liguori Maria, Livia; Lorusso, Giusi; Maimone, Sergio; Manfredini, Roberto; Marcacci, Matteo; Marchese, Alessandra; Marinelli, Sara; Marra Alberto, Maria; Martino Giuseppe, Pio; Masala, Maristella; Masotti, Michela; Merla, Antonio; Miceli, Giuseppe; Montebianco Abenavoli, Ludovico; Morana, Ignazio; Morelli, Olivia; Murgia, Giuseppe; Naccarato, Paola; Neri, Sergio; Niro, Grazia; Nobili, Lorenzo; Padula, Donatella; Palasciano, Giuseppe; Palmieri Vincenzo, Ostilio; Pastori, Daniele; Pattoneri, Paolo; Perego, Francesca; Perticone, Maria; Pesce, Paola; Petramala, Luigi; Pettinari, Irene; Piano, Salvatore; Picardi, Antonio; Pignataro Francesca, Serena; Pignataro, Pietro; Pignatelli, Pasquale; Pinna, Miriam; Pinto, Antonio; Pinto, Daniela; Polimeni, Licia; Pretti, Vincenzo; Privitera, Graziella; Proietti, Marco; Pucci, Giacomo; Purrello, Francesco; Ragone, Enrico; Raimondo, Giovanni; Restuccia, Tea; Riccardi, Laura; Rizzetto, Mario; Rodríguez-Castro Kryssia, Isabel; Romanelli Roberto, Giulio; Ruscio, Eleonora; Sacerdoti, David; Salinaro, Francesco; Salvi, Aldo; Salzano, Andrea; Santangelo, Giuseppe; Santarossa, Claudia; Santilli, Francesca; Santovito, Daniela; Scarpini, Francesca; Schiavone, Cosima; Scicali, Roberto; Senzolo, Marco; Serra, Carla; Serviddio, Gaetano; Sirico, Domenico; Soresi, Maurizio; Sperduti, Nicolò; Staffolani, Silvia; Staltari, Orietta; Stasi, Cristina; Suppressa, Patrizia; Svegliati Baroni, Gianluca; Talia, Michela; Tana, Claudio; Tassone Eliezer, Joseph; Todisco, Tommaso; Toriello, Filippo; Torres, Daniele; Traversa, Matteo; Tripepi, Giovanni; Tufano, Antonella; Tuttolomondo, Antonino; Varvara, Doriana; Vazzana, Natale; Vecchio Claudia, Rita; Vendemiale, Gianluigi; Ventura, Paolo; Vespasiani-Gentilucci, Umberto; Vettore, Elia; Vidili, Gianpaolo; Villani, Rosanna; Vincenzo, Ronca; Visioli, Giacomo; Vitale, Francesco; Zocco Maria, Assunta.
abstract
We analyzed whether serum albumin is independently associated with portal vein thrombosis (PVT) in liver cirrhosis (LC) and if a biologic plausibility exists. This study was divided into three parts. In part 1 (retrospective analysis), 753 consecutive patients with LC with ultrasound-detected PVT were retrospectively analyzed. In part 2, 112 patients with LC and 56 matched controls were entered in the cross-sectional study. In part 3, 5 patients with cirrhosis were entered in the in vivo study and 4 healthy subjects (HSs) were entered in the in vitro study to explore if albumin may affect platelet activation by modulating oxidative stress. In the 753 patients with LC, the prevalence of PVT was 16.7%; logistic analysis showed that only age (odds ratio [OR], 1.024; P = 0.012) and serum albumin (OR, -0.422; P = 0.0001) significantly predicted patients with PVT. Analyzing the 112 patients with LC and controls, soluble clusters of differentiation (CD)40-ligand (P = 0.0238), soluble Nox2-derived peptide (sNox2-dp; P < 0.0001), and urinary excretion of isoprostanes (P = 0.0078) were higher in patients with LC. In LC, albumin was correlated with sCD4OL (Spearman's rank correlation coefficient [r(s)], -0.33; P < 0.001), sNox2-dp (r(s), -0.57; P < 0.0001), and urinary excretion of isoprostanes (r(s), -0.48; P < 0.0001) levels. The in vivo study showed a progressive decrease in platelet aggregation, sNox2-dp, and urinary 8-iso prostaglandin F2 alpha-III formation 2 hours and 3 days after albumin infusion. Finally, platelet aggregation, sNox2-dp, and isoprostane formation significantly decreased in platelets from HSs incubated with scalar concentrations of albumin. Conclusion: Low serum albumin in LC is associated with PVT, suggesting that albumin could be a modulator of the hemostatic system through interference with mechanisms regulating platelet activation.
2018
- Correction to: Major adverse cardiovascular events in non-valvular atrial fibrillation with chronic obstructive pulmonary disease: the ARAPACIS study (Internal and Emergency Medicine, (2018), 13, 5, (651-660), 10.1007/s11739-018-1835-9)
[Articolo su rivista]
Raparelli, Valeria; Pastori, Daniele; Pignataro, Serena Francesca; Vestri, Anna Rita; Pignatelli, Pasquale; Cangemi, Roberto; Proietti, Marco; Davì, Giovanni; Hiatt, William Robert; Lip, Gregory Yoke Hong; Corazza, Gino Roberto; Perticone, Francesco; Violi, Francesco; Basili, Stefania; Alessandri, C.; Serviddio, G.; Palange, P.; Greco, E.; Bruno, G.; Averna, M.; Giammanco, A.; Sposito, P.; De Cristofaro, R.; Carulli, L.; Di Gennaro, L.; Pellegrini, E.; Cominacini, L.; Mozzini, C.; Pasini, A. F.; Sprovieri, M.; Spagnuolo, V.; Cerqua, G.; Cerasola, G.; Mulé, G.; Barbagallo, M.; Lo Sciuto, S.; Monteverde, A.; Saitta, A.; Lo Gullo, A.; Malatino, L.; Cilia, C.; Terranova, V.; Pisano, M.; Pinto, A.; Di Raimondo, D.; Tuttolomondo, A.; Conigliaro, R.; Signorelli, S.; De Palma, D.; Galderisi, M.; Cudemo, G.; Galletti, F.; Fazio, V.; De Luca, N.; Meccariello, A.; Caputo, D.; De Donato, M. T.; Iannuzi, A.; Bresciani, A.; Giunta, R.; Utili, R.; Iorio, V.; Adinolfi, L. E.; Sellitto, C.; Iuliano, N.; Bellis, P.; Tirelli, P.; Sacerdoti, D.; Vanni, D.; Iuliano, L.; Ciacciarelli, M.; Pacelli, A.; Palazzuoli, A.; Cacciafesta, M.; Gueli, N.; Lo Iacono, C.; Brusco, S.; Verrusio, W.; Nobili, L.; Tarquinio, N.; Pellegrini, F.; Vincentelli, G. M.; Ravallese, F.; Santini, C.; Letizia, C.; Petramala, L.; Zinnamosca, L.; Minisola, S.; Cilli, M.; Colangelo, L.; Falaschi, P.; Martocchia, A.; Pastore, F.; Bertazzoni, G.; Attalla El Halabieh, E.; Paradiso, Maria Bruna; Lizzi, E. M.; Timmi, S.; Battisti, P.; Cerci, S.; Ciavolella, M.; Di Veroli, C.; Malci, F.; De Ciocchis, A.; Abate, D.; Castellino, P.; Zanoli, L.; Fidone, F.; Mannarino, E.; Pasqualini, L.; Oliverio, G.; Pende, A.; Artom, N.; Ricchio, R.; Fimognari, F. L.; Alletto, M.; Messina, S.; Sesti, G.; Arturi, F.; Succurro, E.; Fiorentino, T. V.; Pedace, E.; Scarpino, P. E.; Carullo, G.; Maio, R.; Sciacqua, A.; Frugiuele, P.; Spagnuolo, V.; Battaglia, G.; Atzori, S.; Delitala, G.; Angelucci, E.; Sestili, S.; Traisci, G.; De Feudis, L.; Di Michele, D.; Fava, A.; Balsano, C.; De Ciantis, P.; Desideri, G.; Camerota, A.; Mezzetti, M.; Gresele, P.; Vedovati, C.; Fierro, T.; Puccetti, L.; Bertolotti, M.; Mussi, C.; Boddi, M.; Savino, A.; Contri, S.; Degl’Innocenti, G.; Saller, A.; Fabris, F.; Pesavento, R.; Filippi, L.; Vedovetto, V.; Puato, M.; Fabris, F.; Treleani, M.; De Luca, E.; De Zaiacomo, F.; Giantin, V.; Semplicini, A.; Minuz, P.; Romano, S.; Fantin, F.; Manica, A.; Stockner, I.; Pattis, P.; Gutmann, B.; Catena, Chiara; Colussi, G.; Sechi, L. A.; Annoni, G.; Bruni, A. A.; Castagna, A.; Spinelli, D.; Miceli, E.; Padula, D.; Schinco, G.; Spreafico, S.; Secchi, B.; Vanoli, M.; Casella, G.; Pulixi, E. A.; Sansone, L.; Serra, M. G.; Longo, S.; Antonaci, S.; Belfiore, A.; Frualdo, M.; Palasciano, G.; Ricci, L.; Ventrella, F.; Bianco, C.; Santovito, D.; Cipollone, F.; Nicolai, S.; Salvati, F.; Rini, G. B.; Scozzari, F.; Muiesan, M. L.; Salvetti, M.; Bazza, A.; Picardi, A.; Vespasiani-Gentilucci, U.; De Vincentis, Alessia; Cosio, P.; Terzolo, M.; Madaffari, B.; Parasporo, B.; Fenoglio, L.; Bracco, C.; Melchio, R.; Gentili, T.; Salvi, A.; Nitti, C.; Gabrielli, A.; Martino, G. P.; Capucci, A.; Brambatti, M.; Sparagna, A.; Tirotta, D.; Andreozzi, P.; Ettorre, E.; Viscogliosi, G.; Servello, A.; Musumeci, M.; Delfino, M.; Giorgi, A.; Glorioso, N.; Melis, G.; Marras, G.; Matta, M.; Sacco, A.; Stellitano, E.; Scordo, A.; Russo, F.; Caruso, A. A.; Porreca, E.; Tana, M.; Ferri, C.; Cheli, P.; Portincasa, P.; Muscianisi, G.; Giordani, S.; Stanghellini, V.; Sabbà, C.; Mancuso, G.; Bartone, M.; Calipari, D.; Arcidiacono, G.; Bellanuova, I.; Ferraro, M.; Marigliano, G.; Cozzolino, D.; Lampitella, A.; Acri, V.; Galasso, D.; Mazzei, F.; Buratti, A.; Galasso, S.; Porta, M.; Brizzi, M. F.; Fattorini, A.; Sampietro, F.; D’Angelo, A.; Manfredini, R.; Pala, M.; Fabbian, F.; Moroni, C.; Valente, L.; Lopreiato, F.
abstract
In the original publication, one of the ARAPACIS collaborators Dr. “Leonardo Di Gennaro” name has been erroneously mentioned as “Leonardo De Gennaro”.
2018
- Major adverse cardiovascular events in non-valvular atrial fibrillation with chronic obstructive pulmonary disease: the ARAPACIS study
[Articolo su rivista]
Raparelli, Valeria; Pastori, Daniele; Pignataro, Serena Francesca; Vestri, Anna Rita; Pignatelli, Pasquale; Cangemi, Roberto; Proietti, Marco; Davì, Giovanni; Hiatt, William Robert; Lip, Gregory Yoke Hong; Corazza, Gino Roberto; Perticone, Francesco; Violi, Francesco; Basili, Stefania; Alessandri, C.; Serviddio, G.; Palange, P.; Greco, E.; Bruno, G.; Averna, M.; Giammanco, A.; Sposito, P.; De Cristofaro, R.; Carulli, L.; De Gennaro, L.; Pellegrini, E.; Cominacini, L.; Mozzini, C.; Pasini, A. F.; Sprovieri, M.; Spagnuolo, V.; Cerqua, G.; Cerasola, G.; Mulé, G.; Barbagallo, M.; Lo Sciuto, S.; Monteverde, A.; Saitta, A.; Lo Gullo, A.; Malatino, L.; Cilia, C.; Terranova, V.; Pisano, M.; Pinto, A.; Di Raimondo, D.; Tuttolomondo, A.; Conigliaro, R.; Signorelli, S.; De Palma, D.; Galderisi, M.; Cudemo, G.; Galletti, F.; Fazio, V.; De Luca, N.; Meccariello, A.; Caputo, D.; De Donato, M. T.; Iannuzi, A.; Bresciani, A.; Giunta, R.; Utili, R.; Iorio, V.; Adinolfi, L. E.; Sellitto, C.; Iuliano, N.; Bellis, P.; Tirelli, P.; Sacerdoti, D.; Vanni, D.; Iuliano, L.; Ciacciarelli, M.; Pacelli, A.; Palazzuoli, A.; Cacciafesta, M.; Gueli, N.; Lo Iacono, C.; Brusco, S.; Verrusio, W.; Nobili, L.; Tarquinio, N.; Pellegrini, F.; Vincentelli, G. M.; Ravallese, F.; Santini, C.; Letizia, C.; Petramala, L.; Zinnamosca, L.; Minisola, S.; Cilli, M.; Colangelo, L.; Falaschi, P.; Martocchia, A.; Pastore, F.; Bertazzoni, G.; Attalla El Halabieh, E.; Paradiso, M.; Lizzi, E. M.; Timmi, S.; Battisti, P.; Cerci, S.; Ciavolella, M.; Di Veroli, C.; Malci, F.; De Ciocchis, A.; Abate, D.; Castellino, P.; Zanoli, L.; Fidone, F.; Mannarino, E.; Pasqualini, L.; Oliverio, G.; Pende, A.; Artom, N.; Ricchio, R.; Fimognari, F. L.; Alletto, M.; Messina, S.; Sesti, G.; Arturi, F.; Succurro, E.; Fiorentino, T. V.; Pedace, E.; Scarpino, P. E.; Carullo, G.; Maio, R.; Sciacqua, A.; Frugiuele, P.; Spagnuolo, V.; Battaglia, G.; Atzori, S.; Delitala, G.; Angelucci, E.; Sestili, S.; Traisci, G.; De Feudis, L.; Di Michele, D.; Fava, A.; Balsano, C.; De Ciantis, P.; Desideri, G.; Camerota, A.; Mezzetti, M.; Gresele, P.; Vedovati, C.; Fierro, T.; Puccetti, L.; Bertolotti, M.; Mussi, C.; Boddi, M.; Savino, A.; Contri, S.; Degl’Innocenti, G.; Saller, A.; Fabris, F.; Pesavento, R.; Filippi, L.; Vedovetto, V.; Puato, M.; Fabris, F.; Treleani, M.; De Luca, E.; De Zaiacomo, F.; Giantin, V.; Semplicini, A.; Minuz, P.; Romano, S.; Fantin, F.; Manica, A.; Stockner, I.; Pattis, P.; Gutmann, B.; Catena, C.; Colussi, G.; Sechi, L. A.; Annoni, G.; Bruni, A. A.; Castagna, A.; Spinelli, D.; Miceli, E.; Padula, D.; Schinco, G.; Spreafico, S.; Secchi, B.; Vanoli, M.; Casella, G.; Pulixi, E. A.; Sansone, L.; Serra, M. G.; Longo, S.; Antonaci, S.; Belfiore, A.; Frualdo, M.; Palasciano, G.; Ricci, L.; Ventrella, F.; Bianco, C.; Santovito, D.; Cipollone, F.; Nicolai, S.; Salvati, F.; Rini, G. B.; Scozzari, F.; Muiesan, M. L.; Salvetti, M.; Bazza, A.; Picardi, A.; Vespasiani-Gentilucci, U.; De Vincentis, A.; Cosio, P.; Terzolo, M.; Madaffari, B.; Parasporo, B.; Fenoglio, L.; Bracco, C.; Melchio, R.; Gentili, T.; Salvi, A.; Nitti, C.; Gabrielli, A.; Martino, G. P.; Capucci, A.; Brambatti, M.; Sparagna, A.; Tirotta, D.; Andreozzi, P.; Ettorre, E.; Viscogliosi, G.; Servello, A.; Musumeci, M.; Delfino, M.; Giorgi, A.; Glorioso, N.; Melis, G.; Marras, G.; Matta, M.; Sacco, A.; Stellitano, E.; Scordo, A.; Russo, F.; Caruso, A. A.; Porreca, E.; Tana, M.; Ferri, C.; Cheli, P.; Portincasa, P.; Muscianisi, G.; Giordani, S.; Stanghellini, V.; Sabbà, C.; Mancuso, G.; Bartone, M.; Calipari, D.; Arcidiacono, G.; Bellanuova, I.; Ferraro, M.; Marigliano, G.; Cozzolino, D.; Lampitella, A.; Acri, V.; Galasso, D.; Mazzei, F.; Buratti, A.; Galasso, S.; Porta, M.; Brizzi, M. F.; Fattorini, A.; Sampietro, F.; D’Angelo, A.; Manfredini, R.; Pala, M.; Fabbian, F.; Moroni, C.; Valente, L.; Lopreiato, F.; Parente, F.
abstract
Chronic obstructive pulmonary disease (COPD) increases the risk of mortality in non-valvular atrial fibrillation (NVAF) patients. Data on the relationship of COPD to major cardiovascular events (MACE) in AF have not been defined. The aim of the study is to assess the predictive value of COPD on incident MACE in NVAF patients over a 3-year follow-up. In the Atrial Fibrillation Registry for Ankle-Brachial Index Prevalence Assessment-Collaborative Italian Study (ARAPACIS) cohort, we evaluate the impact of COPD on the following clinical endpoints: MACE (including vascular death, fatal/non-fatal MI and stroke/TIA), cardiovascular (CV) death and all-cause mortality. Among 2027 NVAF patients, patients with COPD (9%) are more commonly male, elderly and at higher thromboembolic risk. During a median 36.0 months follow-up, 186 patients experienced MACE: vascular death (n = 72), MI (n = 57), stroke/TIA (n = 57). All major outcomes (including stroke/TIA, MI, vascular death, and all-cause death) are centrally adjudicated. Kaplan–Meier curves show that NVAF patients with COPD are at higher risk for MACE (p < 0.001), CV death (p < 0.001) and all-cause death (p < 0.001). On Cox proportional hazard analysis, COPD is an independent predictor of MACE (Hazard ratio [HR] 1.77, 95% Confidence Intervals [CI] 1.20–2.61; p = 0.004), CV death (HR 2.73, 95% CI 1.76–4.23; p < 0.0001) and all-cause death (HR 2.16, 95% CI 1.48–3.16; p < 0.0001). COPD is an independent predictor of MACE, CV death and all-cause death during a long-term follow-up of NVAF patients.
2018
- Pharmacological interventions for acute hepatitis C infection
[Articolo su rivista]
Kalafateli, M.; Buzzetti, E.; Thorburn, D.; Davidson, B. R.; Tsochatzis, E.; Gurusamy, K. S.
abstract
Background: Hepatitis C virus (HCV) is a single-stranded RNA (ribonucleic acid) virus that has the potential to cause inflammation of the liver. The traditional definition of acute HCV infection is the first six months following infection with the virus. Another commonly used definition of acute HCV infection is the absence of HCV antibody and subsequent seroconversion (presence of HCV antibody in a person who was previously negative for HCV antibody). Approximately 40% to 95% of people with acute HCV infection develop chronic HCV infection, that is, have persistent HCV RNA in their blood. In 2010, an estimated 160 million people worldwide (2% to 3% of the world's population) had chronic HCV infection. The optimal pharmacological treatment of acute HCV remains controversial. Chronic HCV infection can damage the liver. Objectives: To assess the comparative benefits and harms of different pharmacological interventions in the treatment of acute HCV infection through a network meta-analysis and to generate rankings of the available pharmacological treatments according to their safety and efficacy. However, it was not possible to assess whether the potential effect modifiers were similar across different comparisons. Therefore, we did not perform the network meta-analysis and instead we assessed the comparative benefits and harms of different interventions versus each other or versus no intervention using standard Cochrane methodology. Search methods: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, Science Citation Index Expanded, World Health Organization International Clinical Trials Registry Platform, and randomised controlled trials registers to April 2016 to identify randomised clinical trials on pharmacological interventions for acute HCV infection. Selection criteria: We included only randomised clinical trials (irrespective of language, blinding, or publication status) in participants with acute HCV infection. We excluded trials which included previously liver transplanted participants and those with other coexisting viral diseases. We considered any of the various pharmacological interventions compared with placebo or each other. Data collection and analysis: We used standard methodological procedures expected by Cochrane. We calculated the odds ratio (OR) and rate ratio with 95% confidence intervals (CI) using both fixed-effect and random-effects models based on the available-participant analysis with Review Manager 5. We assessed risk of bias according to Cochrane, controlled risk of random errors with Trial Sequential Analysis, and assessed the quality of the evidence using GRADE. Main results: We identified 10 randomised clinical trials with 488 randomised participants that met our inclusion criteria. All the trials were at high risk of bias in one or more domains. Overall, the evidence for all the outcomes was very low quality evidence. Nine trials (467 participants) provided information for one or more outcomes. Three trials (99 participants) compared interferon-alpha versus no intervention. Three trials (90 participants) compared interferon-beta versus no intervention. One trial (21 participants) compared pegylated interferon-alpha versus no intervention, but it did not provide any data for analysis. One trial (41 participants) compared MTH-68/B vaccine versus no intervention. Two trials (237 participants) compared pegylated interferon-alpha versus pegylated interferon-alpha plus ribavirin. None of the trials compared direct-acting antivirals versus placebo or other interventions. The mean or median follow-up period in the trials ranged from six to 36 months. There was no short-term mortality (less than one year) in any group in any trial except for one trial where one participant died in the pegylated interferon-alpha plus ribavirin group (1/95: 1.1%). In the trials that reported follow-up beyond one year, there were no further deaths. The number of serious adverse events
2018
- Platelet count does not predict bleeding in cirrhotic patients: Results from the PRO-LIVER Study
[Articolo su rivista]
Basili, S. a; Raparelli V., B; Napoleone L., B; Talerico G., A; Corazza G. R., C; Perticone F., D; Sacerdoti D., E; Andriulli A., F; Licata A., G; Pietrangelo, A.; Picardi A., I; Raimondo G., J; Violi, F.; Palasciano, G.; D’Alitto, F.; Palmieri, V. O.; Santovito, D.; Di, Michele; D., Croce; G., Brocco; S., Fasolato; S., Cecchetto; L., Bombonato; G., Bertoni; M., Restuccia; T., Andreozzi; P., Liguori; M. L., Caroleo; B., Perticone; M., Staltari; O., Manfredini; De, Giorgi; A., Averna; M., Giammanco; A., Granito; A., Pettinari; I., Marinelli; S., Bolondi; L., Falsetti; L., Salvi; A., Durante-Mangoni; E., Cesaro; F., Farinaro; V., Ragone; E., Morana; I., Ippolito; A., Iacobellis; A., Niro; G., Merla; A., Maimone; S., Cacciola; I., Varvara; D., Drenaggi; D., Staffolani; S., Vespasiani-Gentilucci; U., Galati; G., Gallo; P., Davì; G., Schiavone; C., Santilli; F., Tana; C., Soresi; Bianchi, Giovanni; B., Carderi; I., Pinto; A., Tuttolomondo; A., Ferrari; G., Gresele; P., Fierro; T., Morelli; O., Laffi; G., Romanelli; R. G., Arena; U., Stasi; Gasbarrini, A.; Garcovich, M.; Zocco, M. A.; Riccardi, L.; Ainora, M. E.; Capeci, W.; Martino, Giuseppe; P., Nobili; L., Cavallo; M., Frugiuele; P., Greco; Ventura, P.; Cuoghi, C.; Marcacci, M.; Serviddio, G.; Vendemiale, G.; Villani, R.; Gargano, R.; Vidili, G.; Di, Cesare; V., Masala; M., Delitala; G., Invernizzi; P., Vincenzo; Di, Minno; G., Tufano; A., Purrello; F., Privitera; G., Forgione; A., Curigliano; V., Senzolo; M., Rodríguez-Castro; K. I., Giannelli; G., Serra; C., Neri; S., Pignataro; P., Rizzetto; M., Debernardi; V. W., Svegliati; B. G., Bergamaschi; G., Masotti; M., Costanzo; F., Antonio; F., Angelico; Del, Ben; M., Polimeni; L., Proietti; M., Cangemi; R., Romiti; G. F., Toriello; F., Sperduti; N., Santangelo; G., Visioli; G., Todisco; Vestri, Anna; R., Farcomeni; A., Corrao; S., Gobbi; Corradini, E.; Costantino, G.; Tripepi, G.; Angelico, M.; Bolondi, L.; Granito, A.; D’Amico, G.; Franchis, De; R., Gatta; A., Tassone; E. J., Anzaldi; M., Barone; M., Bazzini; C., Bianchi; P. I., Boari; B., Bracco; C., Buonauro; A., Buttà; Buzzetti, E.; Calabria, S.; Caradio, F.; Carleo, P.; Carrabba, Maria; D., Castorani; L., Cecchetto; L., Cicco; S., Cimini; C., Colombo; B., M.; De, Giorgi; De, Vuono; S., Denegri; Del, Corso; Di, Giosia; P., Donnarumma; E., Giorgini; P., Grassi; D., Grembiale; A., Hijazi; D., Iamele; L., Lorusso; G., Marchese; Marra, Alberto; M., Masala; M., Miceli; G., Montebianco; A. L., Murgia; G., Naccarato; P., Padula; D., Pattoneri; P., Perego; F., Pesce; P., Petramala; L., Piano; S., Pinto; D., Pinna; M., Pignataro; F. S., Pretti; V., Pucci; G., Salinaro; F., Salzano; A., Santarossa; C., Scarpini; F., Scicali; R., Sirico; D., Suppressa; P., Talia; M., Torres; D., Traversa; M., Vazzana; Vecchio, Claudia; R., Vettore; E., Vitale
abstract
OBJECTIVES: Thrombocytopenia is a hallmark for patients with cirrhosis and it is perceived as a risk factor for bleeding events. However, the relationship between platelet count and bleeding is still unclear. METHODS: We investigated the relationship between platelet count and major or clinical relevant nonmajor bleedings during a follow-up of ∼4 years. RESULTS: A total of 280 cirrhotic patients with different degrees of liver disease (67% males; age 64±37 years; 47% Child–Pugh B and C) were followed up for a median of 1,129 (interquartile range: 800–1,498) days yielding 953.12 patient-year of observation. The annual rate of any significant bleeding was 5.45%/year (3.57%/year and 1.89%/year for major and minor bleeding, respectively). Fifty-two (18.6%) patients experienced a major (n=34) or minor (n=18) bleeding event, predominantly from gastrointestinal origin. Platelet counts progressively decreased with the worsening of liver disease and were similar in patients with or without major or minor bleeding: a platelet count ≤50×103/μl was detected in 3 (6%) patients with and in 20 (9%) patients without any bleeding event. Conversely, prothrombin time-international normalized ratio was slightly higher in patients with overall or major bleeding. On Cox proportional hazard analysis, only a previous gastrointestinal bleeding (hazard ratio (HR): 1.96; 95% confidence interval: 1.11–3.47; P=0.020) and encephalopathy (HR: 2.05; 95% confidence interval: 1.16–3.62; P=0.013) independently predicted overall bleeding events. CONCLUSIONS: Platelet count does not predict unprovoked major or minor bleeding in cirrhotic patients.
2017
- Carotid plaque detection improves the predictve value of CHA2DS2-VASc score in patients with non-valvular atrial fibrilation: The ARAPACIS Study
[Articolo su rivista]
Basili, S.; Loffredo, L.; Pastori, D.; Proieti, M.; Farcomeni, A.; Vesti, A. R.; Pignatelli, P.; Davi, G.; Hiatt, W. R.; Lip, G. Y. H.; Corazza, G. R.; Perticone, F.; Violi, F.; Alessandri, C.; Serviddio, G.; Fascetti, S.; Palange, P.; Greco, E.; Bruno, G.; Averna, M.; Giammanco, A.; Sposito, P.; De Cristofaro, R.; De Gennaro, L.; Carulli, L.; Pellegrini, E.; Cominacini, L.; Mozzini, C.; Pasini, A. F.; Sprovieri, M.; Spagnuolo, V.; Cerqua, G.; Cerasola, G.; Mule, G.; Barbagallo, M.; Lo Sciuto, S.; Monteverde, A.; Saitta, A.; Lo Gullo, A.; Malatino, L.; Ciia, C.; Terranova, V.; Pisano, M.; Pinto, A.; Di Raimondo, D.; Tuttolomondo, A.; Conigliaro, R.; Signorelli, S.; De Palma, D.; Galderisi, M.; Cudemo, G.; Galletti, F.; Fazio, V.; De Luca, N.; Meccariello, A.; Caputo, D.; De Donato, M. T.; Iannuzi, A.; Bresciani, A.; Giunta, R.; Utili, R.; Iorio, V.; Adinolfi, L. E.; Sellitto, C.; Iuliano, N.; Bellis, P.; Tirelli, P.; Sacerdoti, D.; Vanni, D.; Iuliano, L.; Ciacciarelli, M.; Pacelli, A.; Palazzuoli, A.; Cacciafesta, M.; Gueli, N.; Lo Iacono, G.; Brusco, S.; Verrusio, W.; Nobili, L.; Tarquinio, N.; Pellegrini, F.; Vincentelli, G. M.; Ravallese, F.; Santini, C.; Letizia, C.; Petramala, L.; Zinnamosca, L.; Minisola, S.; Cilli, M.; Savoriti, C.; Colangelo, L.; Falaschi, P.; Martocchia, A.; Pastore, F.; Bertazzoni, G.; Attalla El Halabieh, E.; Paradiso, M.; Lizzi, E. M.; Timmi, S.; Battisti, P.; Cerci, S.; Ciavolella, M.; Di Veroli, C.; Malei, F.; De Ciocchis, A.; Abate, D.; Castellino, P.; Zanoli, L.; Fidone, F.; Mannarino, E. T.; Pasqualini, L.; Oliverio, G.; Pende, A.; Aitom, N.; Ricchio, R.; Fimognari, F. L.; Alletto, M.; Messina, S.; Sesti, G.; Arturi, F.; Fiorentino, T. V.; Pedace, E.; Scarpino, P. E.; Carullo, G.; Maio, R.; Sciacqua, A.; Frugiuele, P.; Spagnuolo, V.; Battaglia, G.; Atzori, S.; Delitala, G.; Angelucci, E.; Sestili, S.; Traisci, G.; De Feudis, L.; Di Michele, D.; Fava, A.; Balsano, C.; De Ciantis, P.; Desideri, G.; Camerota, A.; Mezzetti, M.; Gresele, P.; Vedovati, C.; Fierro, T.; Puccetti, L.; Bertolotti, M.; Mussi, C.; Boddi, M.; Savino, A.; Contri, S.; Degl'Innocenti, G.; Sailer, A.; Fabris, F.; Pesavento, R.; Filippi, L.; Vedovetto, V.; Puato, M.; Fabris, F.; Treleani, M.; De Luca, E.; De Zaiacomo, F.; Giantin, V.; Semplicini, A.; Minuz, P.; Romano, S.; Fantin, F.; Manica, A.; Stockner, I.; Pattis, P.; Gutmann, B.; Catena, C.; Colussi, G.; Sechi, L. A.; Annoni, G.; Bruni, A. A.; Castagna, A.; Spinelli, D.; Miceli, E.; Paduia, D.; Schinco, G.; Spreafico, S.; Secchi, B.; Vanoli, M.; Casella, G.; Pulixi, E. A.; Sansone, L.; Serra, M. G.; Longo, S.; Antonaci, S.; Belfiaore, A.; Frualdo, M.; Palasciano, G.; Ricci, L.; Ventrella, F.; Bianco, C.; Santovito, D.; Cipollone, F.; Nicolai, S.; Salvati, F.; Rini, G. B.; Scozzari, F.; Muiesan, M. L.; Salvetti, M.; Bazza, A.; Picardi, A.; Vespasiani-Gentilucci, U.; De Vincentis, A.; Cosio, P.; Terzolo, M.; Madaffari, B.; Parasporo, B.; Fenoglio, L.; Bracco, C.; Melchio, R.; Gentili, T.; Salvi, A.; Nitti, C.; Gabrielli, A.; Martino, G. P.; Capucci, A.; Brambatti, M.; Sparagna, A.; Tirotta, D.; Andreozzi, P.; Ettorre, E.; Viscogliosi, G.; Servello, A.; Musumeci, M.; Rossi Fanelli, F.; Delfino, M.; Giorgi, A.; Glorioso, N.; Melis, G.; Marras, G.; Matta, M.; Sacco, A.; Stellitano, E.; Scordo, A.; Russo, F.; Caruso, A. A.; Porreca, E.; Tana, M.; Ferri, C.; Cheli, P.; Portincasa, P.; Muscianisi, G.; Giordani, S.; Stanghellini, V.; Sabba, C.; Mancuso, G.; Bartone, M.; Calipari, D.; Arcidiacono, G.; Bellanuova, I.; Ferraro, M.; Marigliano, G.; Cozzolino, D.; Lampitella, A.; Acri, V.; Galasso, D.; Mazzei, F.; Galasso, S.; Buratti, A.; Porta, M.; Brizzi, M. F.; Fattorini, A.; Sampietro, F.; D'Angelo, A.; Manfredini, R.; Pala, M.; Fabbian, F.; Moroni, C.; Valente, L.; Lopreiato, F.; Parente, F.; Granata, M.; Moia, M.; Braham, S.; Rossi, M.; Pesce, M.; Gentile, A.; Catozzo, V.; Baciarello, G.; Cosimati, A.; Ageno, W.; Rancan, E.; Guasti, L.; Ciccaglioni, A.; Negri, S.; Polselli, M.; P
abstract
Background and aims: Vascular disease (VD), as assessed by history of myocardial infarction or peripheral artery disease or aortic plaque, increases stroke risk in atrial fibrillation (AF), and is a component of risk assessment using the CHA2DS2-VASc score. We investigated if systemic atherosclerosis as detected by ultrasound carotid plaque (CP) could improve the predictive value of the CHA2DS2-VASC score. Methods: We analysed data from the ARAPACIS study, an observational study including 2027 Ialian patents with non-valvular AF, in whom CP was detected using Doppler Ultrasonography. Results: VD was reported in 351 (17.3%) patients while CP was detected in 16.6% patents. Adding CP to the VD definition leaded to higher VD prevalence (30.9%). During a median [IQR] follow-up time of 36 months, 56 (2.8%) stroke/TIA events were recorded. Survival analysis showed that conventional VD alone did not increase the risk of stroke (Log-Rank: 0.009, p = 0.924), while addition of CP to conventional VD was significantly associated to an increased risk of stroke (LR: 5.730, p = 0.017). Cox regression analysis showed that VD + CP was independently associated with stroke (HR: 1.78, 95% CI: 1.05-3.01, p = 0.0318). Reclassification analysis showed that VD + CP allowed a significant risk reclassification when compared to VD alone in predicting stroke at 36 months (NRI: 0.192, 95% CI: 0.028-0.323, p = 0.032). Conclusions: In non-valvular AF patients the addition of ultrasound detection of carotid plaque to conventional VD significantly increases the pedictive value of CHA2DS2-VASc score for stroke.
2017
- Gender differences in liver disease and the drug-dose gender gap
[Articolo su rivista]
Buzzetti, E.; Parikh, P. M.; Gerussi, A.; Tsochatzis, E.
abstract
Although gender-based medicine is a relatively recent concept, it is now emerging as an important field of research, supported by the finding that many diseases manifest differently in men and women and therefore, might require a different treatment. Sex-related differences regarding the epidemiology, progression and treatment strategies of certain liver diseases have long been known, but most of the epidemiological and clinical trials still report results only about one sex, with consequent different rate of response and adverse reactions to treatment between men and women in clinical practice. This review reports the data found in the literature concerning the gender-related differences for the most representative hepatic diseases.
2017
- Interventions for hereditary haemochromatosis: An attempted network meta-analysis
[Articolo su rivista]
Buzzetti, E.; Kalafateli, M.; Thorburn, D.; Davidson, B. R.; Tsochatzis, E.; Gurusamy, K. S.
abstract
Background: Hereditary haemochromatosis is a genetic disorder related to proteins involved in iron transport, resulting in iron load and deposition of iron in various tissues of the body. This iron overload leads to complications including liver cirrhosis (and related complications such as liver failure and hepatocellular carcinoma), cardiac failure, cardiac arrhythmias, impotence, diabetes, arthritis, and skin pigmentation. Phlebotomy (venesection or 'blood letting') is the currently recommended treatment for hereditary haemochromatosis. The optimal treatment of hereditary haemochromatosis remains controversial. Objectives: To assess the comparative benefits and harms of different interventions in the treatment of hereditary haemochromatosis through a network meta-analysis and to generate rankings of the available treatments according to their safety and efficacy. However, we found only one comparison. Therefore, we did not perform the network meta-analysis and we assessed the comparative benefits and harms of different interventions using standard Cochrane methodology. Search methods: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, Science Citation Index Expanded, World Health Organization International Clinical Trials Registry Platform, and randomised clinical trials registers to March 2016 to identify randomised clinical trials on treatments for hereditary haemochromatosis. Selection criteria: We included only randomised clinical trials (irrespective of language, blinding, or publication status) in participants with hereditary haemochromatosis. We excluded trials which included participants who had previously undergone liver transplantation. We considered any of the various interventions compared with each other or with inactive treatment. Data collection and analysis: We used standard methodological procedures expected by Cochrane. We calculated the odds ratio (OR) and rate ratio with 95% confidence intervals (CI) using both fixed-effect and random-effects models with RevMan 5 based on available-participant analysis. We assessed risk of bias according to Cochrane, controlled risk of random errors with Trial Sequential Analysis, and assessed the quality of the evidence using GRADE. Main results: Three trials with 146 participants met the inclusion criteria of this review. Two parallel group trials with 100 participants provided information on one or more outcomes. The remaining trial was a cross-over trial, with no usable data for analysis. All the trials were at high risk of bias. Overall, all the evidence was of very low quality. All three trials compared erythrocytapheresis (removal of red cells only, instead of whole blood) versus phlebotomy. Two of the trials shared the same first author. The mean or median age in the three trials ranged from 42 to 55 years. None of the trials reported whether the included participants were symptomatic or asymptomatic or a mixture of both. Two trials were conducted in people who were haemochromatosis treatment-naive. The trial that provided most data for this review excluded people with malignancy, heart failure, and serious cardiac arrhythmias. We found no trials assessing iron-chelating agents. Only one of the trials with 38 participants reported no short-term mortality and no serious adverse events at the end of the short-term follow-up (eight months). Two trials reported the proportion of people with adverse events: 10/49 (20.4%) in the erythrocytapheresis group versus 11/51 (21.6%) in the phlebotomy group. One of these two trials provided data on adverse event rates (42.1 events per 100 participants with erythrocytapheresis versus 52.6 events per 100 participants with phlebotomy). There was no evidence of differences in the proportion of people with adverse events and the number of adverse events (serious and non-serious) between the groups (proportion of people with adverse events: OR 0.93, 95% CI 0.36 to 2.43; participants = 100; trial
2017
- Intestinal hormones, gut microbiota and non-alcoholic fatty liver disease
[Articolo su rivista]
Koukias, N.; Buzzetti, E.; Tsochatzis, E. A.
abstract
Non-alcoholic fatty liver disease (NAFLD) is the hepatic manifestation of the metabolic syndrome and has a complex pathophysiology with multiple pathways of development and progression implicated. Intestinal hormones regulate multiple biological functions and may play a role in the pathogenesis of non alcoholic fatty liver disease (NAFLD) by affecting food intake, body weight and insulin resistance. Bacterial products can affect the secretion of these hormones and thus have an effect on metabolism. Gut microbiota are normally involved in the intestinal energy harvest and their role has been increasingly been implicated in the pathogenesis of obesity and NAFLD. The intestinal hormone pathways as well as the intestinal microbiota populations are potential therapeutic targets in the management of NAFLD. We review the evidence on the associations of the intestinal hormones and gut microbiota in the development, progression and treatment of NAFLD.
2017
- Pharmacological interventions for acute hepatitis B infection: An attempted network meta-analysis
[Articolo su rivista]
Mantzoukis, K.; Rodriguez-Peralvarez, M.; Buzzetti, E.; Thorburn, D.; Davidson, B. R.; Tsochatzis, E.; Gurusamy, K. S.
abstract
Background: Infection with hepatitis B virus (HBV) can be symptomatic or asymptomatic. Apart from chronic HBV infection, the complications related to acute HBV infection are severe acute viral hepatitis and fulminant hepatitis characterised by liver failure. The optimal pharmacological treatment of acute HBV infection remains controversial. Objectives: To assess the benefits and harms of pharmacological interventions in the treatment of acute HBV infection through a network meta-analysis and to generate rankings of the available treatments according to their safety and efficacy. As it was not possible to assess whether the potential effect modifiers were similar across different comparisons, we did not perform the network meta-analysis, and instead, assessed the benefits and harms of different interventions using standard Cochrane methodological procedures. Search methods: We searched CENTRAL, MEDLINE, Embase, Science Citation Index Expanded, WHO International Clinical Trials Registry Platform, and randomised clinical trials (RCTs) registers to August 2016 to identify RCTs on pharmacological interventions for acute HBV infection. Selection criteria: RCTs, irrespective of language, blinding, or publication status in participants with acute HBV infection. We excluded trials if participants had previously undergone liver transplantation and had other coexisting viral diseases such as hepatitis C virus and HIV. We considered any of the various pharmacological interventions compared with each other or with placebo, or no intervention. Data collection and analysis: We calculated the odds ratio (OR) and rate ratio with 95% confidence intervals (CI) using both fixed-effect and random-effects models based on available-participant analysis with Review Manager 5. We assessed risk of bias, controlled risk of random errors with Trial Sequential Analysis, and assessed the quality of the evidence using GRADE. Main results: Seven trials (597 participants) met our review inclusion criteria. All trials provided information for one or more outcomes; however, five participants were excluded from analysis by study authors. All the trials were at high risk of bias. Overall, all the evidence was low or very low quality evidence because of risk of bias (downgraded one level for risk of bias), small sample size (downgraded one level for imprecision), and wide CIs (downgraded one more level for imprecision in some comparisons). Of the seven trials, six were two-armed trials, while one trial was a three-armed trial. The comparisons included hepatitis B immunoglobulin (HBIG) versus placebo (one trial; 55 participants); interferon versus placebo (two trials; 200 participants); lamivudine versus placebo or no intervention (four trials; 316 participants); lamivudine versus entecavir (one trial; 90 participants); and entecavir versus no intervention (one trial; 131 participants). One trial included only people with acute HBV with hepatic encephalopathy (i.e. people with fulminant liver failure); one trial included only people with severe acute HBV, but it did not state whether any of the people also had fulminant HBV infection; three trials excluded fulminant HBV infection; and two trials did not report the severity of acute HBV infection. The mean or median follow-up period in the trials ranged from three to 12 months in the trials that provided this information. There was no evidence of any differences in short-term mortality (less than one year) in any of the comparisons: HBIG versus placebo (OR 1.13, 95% CI 0.36 to 3.54; participants = 55; 1 trial), lamivudine versus placebo or no intervention (OR 1.29, 95% CI 0.33 to 4.99; participants = 250; 2 trials); lamivudine versus entecavir (OR 1.23, 95% CI 0.13 to 11.65; participants = 90; 1 trial), or entecavir versus no intervention (OR 1.05, 95% CI 0.12 to 9.47; participants = 131; 1 trial). The proportion of people who progressed to chronic HBV infection was higher in the lamivudine group than the placebo or
2017
- Pharmacological interventions for acute hepatitis C infection: An attempted network meta-analysis
[Articolo su rivista]
Kalafateli, M.; Buzzetti, E.; Thorburn, D.; Davidson, B. R.; Tsochatzis, E.; Gurusamy, K. S.
abstract
Background: Hepatitis C virus (HCV) is a single-stranded RNA (ribonucleic acid) virus that has the potential to cause inflammation of the liver. The traditional definition of acute HCV infection is the first six months following infection with the virus. Another commonly used definition of acute HCV infection is the absence of HCV antibody and subsequent seroconversion (presence of HCV antibody in a person who was previously negative for HCV antibody). Approximately 40% to 95% of people with acute HCV infection develop chronic HCV infection, that is, have persistent HCV RNA in their blood. In 2010, an estimated 160 million people worldwide (2% to 3% of the world's population) had chronic HCV infection. The optimal pharmacological treatment of acute HCV remains controversial. Chronic HCV infection can damage the liver. Objectives: To assess the comparative benefits and harms of different pharmacological interventions in the treatment of acute HCV infection through a network meta-analysis and to generate rankings of the available pharmacological treatments according to their safety and efficacy. However, it was not possible to assess whether the potential effect modifiers were similar across different comparisons. Therefore, we did not perform the network meta-analysis, and instead, we assessed the comparative benefits and harms of different interventions versus each other or versus no intervention using standard Cochrane methodology. Search methods: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, Science Citation Index Expanded, World Health Organization International Clinical Trials Registry Platform, and randomised controlled trials registers to April 2016 to identify randomised clinical trials on pharmacological interventions for acute HCV infection. Selection criteria: We included only randomised clinical trials (irrespective of language, blinding, or publication status) in participants with acute HCV infection. We excluded trials which included previously liver transplanted participants and those with other coexisting viral diseases. We considered any of the various pharmacological interventions compared with placebo or each other. Data collection and analysis: We used standard methodological procedures expected by Cochrane. We calculated the odds ratio (OR) and rate ratio with 95% confidence intervals (CI) using both fixed-effect and random-effects models based on the available-participant analysis with Review Manager 5. We assessed risk of bias according to Cochrane, controlled risk of random errors with Trial Sequential Analysis, and assessed the quality of the evidence using GRADE. Main results: We identified 10 randomised clinical trials with 488 randomised participants that met our inclusion criteria. All the trials were at high risk of bias in one or more domains. Overall, the evidence for all the outcomes was very low quality evidence. Nine trials (467 participants) provided information for one or more outcomes. Three trials (99 participants) compared interferon-alpha versus no intervention. Three trials (90 participants) compared interferon-beta versus no intervention. One trial (21 participants) compared pegylated interferon-alpha versus no intervention, but it did not provide any data for analysis. One trial (41 participants) compared MTH-68/B vaccine versus no intervention. Two trials (237 participants) compared pegylated interferon-alpha versus pegylated interferon-alpha plus ribavirin. None of the trials compared direct-acting antivirals versus placebo or other interventions. The mean or median follow-up period in the trials ranged from six to 36 months. There was no short-term mortality (less than one year) in any group in any trial except for one trial where one participant died in the pegylated interferon-alpha plus ribavirin group (1/95: 1.1%). In the trials that reported follow-up beyond one year, there were no further deaths. The number of serious adverse event
2017
- Pharmacological interventions for alcoholic liver disease (alcohol-related liver disease): An attempted network meta-analysis
[Articolo su rivista]
Buzzetti, E.; Kalafateli, M.; Thorburn, D.; Davidson, B. R.; Thiele, M.; Gluud, L. L.; Del Giovane, C.; Askgaard, G.; Krag, A.; Tsochatzis, E.; Gurusamy, K. S.
abstract
Background: Alcohol-related liver disease is due to excessive alcohol consumption. It includes a spectrum of liver diseases such as alcohol-related fatty liver, alcoholic hepatitis, and alcoholic cirrhosis. Mortality associated with alcoholic hepatitis is high. The optimal pharmacological treatment of alcoholic hepatitis and other alcohol-related liver disease remains controversial. Objectives: To assess the comparative benefits and harms of different pharmacological interventions in the management of alcohol-related liver disease through a network meta-analysis and to generate rankings of the available pharmacological interventions according to their safety and efficacy in order to identify potential treatments. However, even in the subgroup of participants when the potential effect modifiers appeared reasonably similar across comparisons, there was evidence of inconsistency by one or more methods of assessment of inconsistency. Therefore, we did not report the results of the network meta-analysis and reported the comparative benefits and harms of different interventions using standard Cochrane methodology. Search methods: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, Science Citation Index Expanded, World Health Organization International Clinical Trials Registry Platform and randomised controlled trials registers until February 2017 to identify randomised clinical trials on pharmacological treatments for alcohol-related liver diseases. Selection criteria: Randomised clinical trials (irrespective of language, blinding, or publication status) including participants with alcohol-related liver disease. We excluded trials that included participants who had previously undergone liver transplantation and those with co-existing chronic viral diseases. We considered any of the various pharmacological interventions compared with each other or with placebo or no intervention. Data collection and analysis: Two review authors independently identified trials and independently extracted data. We calculated the odds ratio (OR) and rate ratio with 95% confidence intervals (CIs) using both fixed-effect and random-effects models based on available-participant analysis with Review Manager. We assessed risk of bias according to Cochrane, controlled risk of random errors with Trial Sequential Analysis, and assessed the quality of the evidence using GRADE. Main results: We identified a total of 81 randomised clinical trials. All the trials were at high risk of bias, and the overall quality of the evidence was low or very low for all outcomes. Alcoholic hepatitis Fifty randomised clinical trials included 4484 participants with alcoholic hepatitis. The period of follow-up ranged from one to 12 months. Because of concerns about transitivity assumption, we did not perform the network meta-analysis. None of the active interventions showed any improvement in any of the clinical outcomes reported in the trials, which includes mortality (at various time points), cirrhosis, decompensated cirrhosis, liver transplantation. None of the trials reported health-related quality of life or incidence of hepatocellular carcinoma. Severe alcoholic hepatitis Of the trials on alcoholic hepatitis, 19 trials (2545 participants) included exclusively participants with severe alcoholic hepatitis (Maddrey Discriminat Function > 32). The period of follow-up ranged from one to 12 months. There was no alteration in the conclusions when only people with severe alcoholic hepatitis were included in the analysis. Source of funding: Eleven trials were funded by parties with vested interest in the results. Sixteen trials were funded by parties without vested interest in the results. The source of funding was not reported in 23 trials. Other alcohol-related liver diseases Thirty-one randomised clinical trials included 3695 participants with other alcohol-related liver diseases (with a wide spectrum of alcohol-related liver diseases). Th
2017
- Surrogate endpoints for clinical trials in non-alcoholic steatohepatitis
[Articolo su rivista]
Tsochatzis, Ea; Buzzetti, E; Pinzani, M
abstract
2017
- Transaminase abnormalities and adaptations of the liver lobule manifest at specific cut-offs of steatosis
[Articolo su rivista]
Hall, A.; Covelli, C.; Manuguerra, R.; Luong, T. V.; Buzzetti, E.; Tsochatzis, E.; Pinzani, M.; Dhillon, A. P.
abstract
There is little documented evidence suggesting that liver fat is responsible for liver injury in the absence of other disease processes. We investigated the relationships between liver fat, aminotransferases and hepatic architecture in liver biopsies with simple steatosis. We identified 136 biopsies with simple steatosis from the Royal Free Hospital Archives with both clinical data and sufficient material. Digital image analysis was employed to measure fat proportionate area (mFPA). Hepatocyte area (HA) and lobule radius (LR) were also measured. There were significant increases in ALT (p < 0.001) and AST (p = 0.013) with increased fat content and evidence to suggest both 5% and 20% mFPA as a cut-off for raised ALT. In liver with increased fat content there were significant increases in HA (p < 0.001). LR also increased as mFPA increased to 10% (p < 0.001), at which point the lobule ceased to expand further and was counterbalanced with a decrease in the number of hepatocytes per lobule (p = 0.029). Consequently there are mechanisms of adaption in the liver architecture to accommodate the accumulation of fat and these are accompanied by significant increases in transaminases. These results support the generally accepted cut-off of 5% fat for steatosis and indicate 20% as a threshold of more severe liver injury.
2016
- Pancreatic cancer
[Articolo su rivista]
Falconi, M.; Tamburrino, D.; Buzzetti, E.; Partelli, S.
abstract
Pancreatic cancer is the fourth leading cause of death for neoplasm in western countries. Surgery still remains the treatment of choice although almost 80% of patients are not resectable at diagnosis because of liver metastases and the 5-year overall survival of patients treated with surgery is only (20%). During the last two decades we have witnessed an overall improvement in terms of survival, mostly due to the advances in therapy and strategies for a more accurate patient selection for surgery. Specific preoperative criteria, mostly linked to the biological features of the tumour, have been proposed to better identify those patients who will benefit from surgical resection, such as duration of symptoms and serum level of CA19-9 in resectable disease. Oncological therapy plays a central role in the management of pancreatic cancer. In patients undergone surgical resection, adjuvant therapy might increase the overall survival and reduce the rate of early relapse. Patients with locally advanced pancreatic cancer can be treated with neoadjuvant treatment. Chemotherapy or chemoradiotherapy are usually used with the aim to downstage the disease but whether one specific strategy or drug is the treatment of choice is still under debate.
2016
- The multiple-hit pathogenesis of non-alcoholic fatty liver disease (NAFLD)
[Articolo su rivista]
Buzzetti, E.; Pinzani, M.; Tsochatzis, E. A.
abstract
Nonalcoholic fatty liver disease (NAFLD) is increasingly prevalent and represents a growing challenge in terms of prevention and treatment. Despite its high prevalence, only a small minority of affected patients develops inflammation and subsequently fibrosis and chronic liver disease, while most of them only exhibit simple steatosis. In this context, the full understanding of the mechanisms underlying the development of NAFLD and non-alcoholic steatohepatitis (NASH) is of extreme importance; despite advances in this field, knowledge on the pathogenesis of NAFLD is still incomplete. The ‘two-hit’ hypothesis is now obsolete, as it is inadequate to explain the several molecular and metabolic changes that take place in NAFLD. The “multiple hit” hypothesis considers multiple insults acting together on genetically predisposed subjects to induce NAFLD and provides a more accurate explanation of NAFLD pathogenesis. Such hits include insulin resistance, hormones secreted from the adipose tissue, nutritional factors, gut microbiota and genetic and epigenetic factors. In this article, we review the factors that form this hypothesis.
2015
- Frequency of left ventricular hypertrophy in non-valvular atrial fibrillation
[Articolo su rivista]
Proietti, M.; Marra, A. M.; Tassone, E. J.; de Vuono, S.; Corrao, S.; Gobbi, P.; Perticone, F.; Corazza, G. R.; Basili, S.; Lip, G. Y. H.; Violi, F.; Raparelli, V.; Alessandri, C.; Serviddio, G.; Fascetti, S.; Serra, P.; Palange, P.; Greco, E.; Bruno, G.; Averna, M.; Giammanco, A.; Sposito, P.; de Cristofaro, R.; de Gennaro, L.; Loria, P.; Pellegrini, E.; Cominacini, L.; Mozzini, C.; Sprovieri, M.; Spagnuolo, V.; Cerqua, G.; Cerasola, G.; Mule, G.; Barbagallo, M.; Lo Sciuto, S.; Monteverde, A.; Saitta, A.; Lo Gullo, A.; Malatino, L.; Cilia, C.; Licata, G.; Tuttolomondo, A.; Conigliaro, R.; Pinto, A.; Di Raimondo, D.; Signorelli, S.; Anzaldi, M.; de Palma, D.; Galderisi, M.; Cudemo, G.; Galletti, F.; Fazio, V.; de Luca, N.; Meccariello, A.; Caputo, D.; de Donato, M. T.; Iannuzi, A.; Bresciani, A.; Giunta, R.; Cimini, C.; Durante, M. E.; Agrusta, F.; Iorio, F.; Adinolfi, L. E.; Sellitto, A.; Restivo, L.; Bellis, P.; Tirelli, P.; Sacerdoti, D.; Pesce, P.; Vanni, D.; Iuliano, L.; Ciacciarelli, M.; Pacelli, A.; Palazzuoli, A.; Cacciafesta, M.; Gueli, N.; Capeci, W.; Tarquinio, N.; Pellegrini, F.; Vincentelli, G. M.; Ravallese, F.; Santini, C.; Letizia, C.; Petramala, L.; Zinnamosca, L.; Cilli, M.; Savoriti, C.; Falaschi, P.; Martocchia, A.; Stefanelli, M.; Marigliano, V.; Lo Iacono, C.; Brusco, S.; Bertazzoni, G.; Attalla El Halabieh, E.; Paradiso, M.; Lizzi, E. M.; Timmi, S.; Battisti, P.; Cerci, S.; Ciavolella, M.; Di Veroli, C.; Malci, F.; de Ciocchis, A.; Abate, D.; Castellino, P.; Curto, I.; Vecchio, C. R.; Mannarino, E.; Pasqualini, L.; Fattori, C.; Pende, A.; Denegri, A.; Artom, N.; Ricchio, R.; Fimognari, F. L.; Alletto, M.; Messina, S.; Sesti, G.; Arturi, F.; Grembiale, A.; Maio, R.; Scarpino, P. E.; Carullo, G.; Sciacqua, A.; Frugiuele, P.; Battaglia, G.; Vidili, G.; Atzori, S.; Delitala, G.; Davi, G.; Angelucci, E.; Sestili, S.; Traisci, G.; de Feudis, L.; Di Michele, D.; Fava, A.; Balsano, C.; de Ciantis, P.; Desideri, G.; Camerota, A.; Migliacci, R.; Porciello, G.; Mezzetti, M.; Gresele, P.; Vedovati, C.; Fierro, T.; Puccetti, L.; Scarpini, F.; Bertolotti, M.; Mussi, C.; Boddi, M.; Savino, A.; Contri, S.; Saller, A.; Fabris, F.; Pesavento, R.; Filippi, L.; Vedovetto, V.; Puato, M.; Treleani, M.; de Luca, E.; de Zaiacomo, F.; Giantin, V.; Semplicini, A.; Minuz, P.; Calabria, S.; Romano, S.; Fantin, F.; Manica, A.; Stockner, I.; Pattis, P.; Gutmann, B.; Catena, C.; Colussi, G.; Annoni, G.; Bruni, A. A.; Castagna, A.; Spinelli, D.; Miceli, E.; Padula, D.; Schinco, G.; Spreafico, S.; Secchi, B.; Vanoli, M.; Casella, G.; Serra, M. G.; Longo, S.; Antonaci, S.; Belfiore, A.; Ricci, L.; Ventrella, F.; Iamele, L.; Bianco, C.; Santovito, D.; Cipollone, F.; Nicolai, S.; Salvati, F.; Rini, G. B.; Scozzari, F.; Muiesan, M. L.; Salvetti, M.; Bazza, A.; Picardi, A.; de Vincentis, A.; Cosio, P.; Terzolo, M.; Madaffari, B.; Parasporo, B.; Fenoglio, L.; Bracco, C.; Melchio, R.; Gentili, T.; Salvi, A.; Nitti, C.; Falsetti, L.; Gabrielli, A.; Paglione, I.; Capucci, A.; Brambatti, M.; Sparagna, A.; Tirotta, D.; Andreozzi, P.; Ettorre, E.; Viscogliosi, G.; Rossi, F. F.; Delfino, M.; Glorioso, N.; Melis, G.; Marras, G.; Matta, M.; Sacco, A.; Stellitano, E.; Scordo, A.; Russo, F.; Caruso, A. A.; Porreca, E.; Santilli, F.; Tana, M.; Ferri, C.; Grassi, D.; Cheli, P.; Portincasa, P.; Muscianisi, G.; Giordani, S.; Stanghellini, V.; Sabba, C.; Suppressa, P.; Mancuso, G.; Bartone, M.; Calipari, D.; Arcidiacono, G.; Bellanuova, I.; Ferraro, M.; Scalzo, A.; Marigliano, G.; Cozzolino, D.; Lampitella, A.; Acri, V.; Galasso, D.; Mazzei, F.; Galasso, S.; Buratti, A.; Porta, M.; Brizzi, M. F.; Fattorini, A.; Sampietro, F.; D'Angelo, A.; Pala, M.; Fabbian, F.; Manfredini, R.; Moroni, C.; Valente, L.; Lopreiato, F.; Parente, F.; Granata, M.; Moia, M.; Braham, S.; Rossi, M.; Pesce, M.; Gentile, A.; Catozzo, V.; Di Napoli, M.; Baciarello, G.; Rancan, E.; Ageno, W.; Guasti, L.; Ciccaglioni, A.; Negri, S.; Polselli, M.; Abbate, R.; Marcucci, R.; Cangemi, R.; Pi
abstract
Left ventricular hypertrophy (LVH) is significantly related to adverse clinical outcomes in patients at high risk of cardiovascular events. In patients with atrial fibrillation (AF), data on LVH, that is, prevalence and determinants, are inconsistent mainly because of different definitions and heterogeneity of study populations. We determined echocardiographic-based LVH prevalence and clinical factors independently associated with its development in a prospective cohort of patients with non-valvular (NV) AF. From the "Atrial Fibrillation Registry for Ankle-brachial Index Prevalence Assessment: Collaborative Italian Study" (ARAPACIS) population, 1,184 patients with NVAF (mean age 72 ± 11 years; 56% men) with complete data to define LVH were selected. ARAPACIS is a multicenter, observational, prospective, longitudinal on-going study designed to estimate prevalence of peripheral artery disease in patients with NVAF. We found a high prevalence of LVH (52%) in patients with NVAF. Compared to those without LVH, patients with AF with LVH were older and had a higher prevalence of hypertension, diabetes, and previous myocardial infarction (MI). A higher prevalence of ankle-brachial index ≤0.90 was seen in patients with LVH (22 vs 17%, p = 0.0392). Patients with LVH were at significantly higher thromboembolic risk, with CHA2DS2-VASc ≥2 seen in 93% of LVH and in 73% of patients without LVH (p <0.05). Women with LVH had a higher prevalence of concentric hypertrophy than men (46% vs 29%, p = 0.0003). Logistic regression analysis demonstrated that female gender (odds ratio [OR] 2.80, p <0.0001), age (OR 1.03 per year, p <0.001), hypertension (OR 2.30, p <0.001), diabetes (OR 1.62, p = 0.004), and previous MI (OR 1.96, p = 0.001) were independently associated with LVH. In conclusion, patients with NVAF have a high prevalence of LVH, which is related to female gender, older age, hypertension, and previous MI. These patients are at high thromboembolic risk and deserve a holistic approach to cardiovascular prevention.
2015
- Noninvasive assessment of fibrosis in patients with nonalcoholic fatty liver disease
[Articolo su rivista]
Buzzetti, E.; Lombardi, R.; De Luca, L.; Tsochatzis, E. A.
abstract
Nonalcoholic fatty liver disease (NAFLD) is prevalent in 20-25% of the general population and is associated with metabolic risk factors such as obesity, diabetes mellitus, and dyslipidemia. Histologically, NAFLD ranges from simple steatosis to nonalcoholic steatohepatitis (NASH), fbrosis, and cirrhosis. As NASH develops in only 10-15% of patients with NAFLD, it is not practical to biopsy all patients who present with NAFLD. Noninvasive fbrosis tests have been extensively developed recently and ofer alternatives for staging fbrosis. Despite their increasing use, such tests cannot adequately differentiate simple steatosis from NASH. At present, such tests can be used as first line tests to rule out patients without advanced fbrosis and thus prevent unnecessary secondary care refferrals in a significant number of patients. In this review we present the evidence for the use of noninvasive fbrosis tests in patients with NAFLD.
2015
- Non-invasive assessment of liver fibrosis in patients with alcoholic liver disease
[Articolo su rivista]
Lombardi, R.; Buzzetti, E.; Roccarina, D.; Tsochatzis, E. A.
abstract
Alcoholic liver disease (ALD) consists of a broad spectrum of disorders, ranging from simple steatosis to alcoholic steatohepatitis and cirrhosis. Fatty liver develops in more than 90% of heavy drinkers, however only 30%-35% of them develop more advanced forms of ALD. Therefore, even if the current gold standard for the assessment of the stage of alcohol-related liver injury is histology, liver biopsy is not reasonable in all patients who present with ALD. Currently, although several non-invasive fibrosis markers have been suggested as alternatives to liver biopsy in patients with ALD, none has been sufficiently validated. As described in other liver disease, the diagnostic accuracy of such tests in ALD is acceptable for the diagnosis of significant fibrosis or cirrhosis but not for lesser fibrosis stages. Existing data suggest that the use of noninvasive tests could be tailored to first tier screening of patients at risk, in order to diagnose early patients with progressive liver disease and offer targeted interventions for the prevention of decompensation. We review these tests and critically appraise the existing evidence.
2013
- Oxidative stress management in elite athletes
[Articolo su rivista]
Lamberti, I.; Buzzetti, E.; Cristani, A.
abstract
It is well known that strenuous exercise training can induce an overproduction of reactive oxygen species with subsequent impairment of cellular macromolecules and metabolism, leading to cellular dysfunction. In elite athletes, reactive oxygen species can add to other injurious factors for muscle tissue; therefore special precautions are required to avoid an increase in injury risk.