Real life experiences in HCV management in 2018
Introduction: Hepatitis C virus (HCV) infection is a major cause of chronic liver disease, with approximately 71 million chronically infected individuals worldwide. Treatment of chronic hepatitis C has considerably improved in the last few years thanks to the introduction of direct-acting antivirals able to achieve sustained virological response in more than 95% of patients. Successful anti-HCV treatment can halt liver disease progression and solve the HCV-related extra-hepatic manifestations, eventually reducing liver-related and overall mortality. Areas covered: With the aim to respond to unmet needs in patient’s identification, universal access to antiviral therapy and treatment optimiza…
Transient elastography (TE) as a tool to evaluate acute liver damage: A prospective, multicentric cohort study
Italian association for the study of the liver position statement on SARS-CoV2 vaccination.
The vaccination campaign against Sars-CoV-2 commenced in Italy at the end of December 2020. The first ones to receive the immunization against the virus were the health workers and the residents of nursing homes, following which the vaccine would be available for the entire population, beginning with the most vulnerable individuals. SARS-CoV2 vaccines have been demonstrated to be safe for the general population, although no data for patients with liver diseases or those having undergone liver transplantation are available so far. The present position statement AISF is an attempt to suggest, based on the published data on the impact of Sars-Cov-2 infection in patients with chronic liver dise…
AISF position paper on liver disease and pregnancy.
Abstract The relationship between liver disease and pregnancy is of great clinical impact. Severe liver disease in pregnancy is rare; however, pregnancy-related liver disease is the most frequent cause of liver dysfunction during pregnancy and represents a severe threat to foetal and maternal survival. A rapid differential diagnosis between liver disease related or unrelated to pregnancy is required in women who present with liver dysfunction during pregnancy. This report summarizes the recommendation of an expert panel established by the Italian Association for the Study of the Liver (AISF) on the management of liver disease during pregnancy. The article provides an overview of liver disea…
Safety and efficacy of ombitasvir/paritaprevir/ritonavir/dasabuvir plus ribavirin in patients over 65 years with HCV genotype 1 cirrhosis
Purpose: To analyse safety and efficacy of treatment based on ombitasvir/paritaprevir/ritonavir/dasabuvir plus ribavirin in the sub-group of GT1 patients older than 65 years. Methods: We collected data extracted from the ABACUS compassionate-use nationwide Italian programme, in patients with cirrhosis due to hepatitis C virus (HCV) Genotype-1 (GT1) or 4 and at high risk of decompensation. GT1-HCV-infected patients received once-daily ombitasvir/paritaprevir, with the pharmacokinetic enhancer ritonavir (25/150/100 mg) and twice-daily dasabuvir (250 mg) plus Ribavirin (RBV) (OBV/PTV/r + DSV + RBV) for 12 (GT1b) or 24 (GT1a) weeks. Endpoints were to evaluate safety and efficacy, the latter def…
Predicting in-hospital mortality from Coronavirus Disease 2019: A simple validated app for clinical use
Backgrounds Validated tools for predicting individual in-hospital mortality of COVID-19 are lacking. We aimed to develop and to validate a simple clinical prediction rule for early identification of in-hospital mortality of patients with COVID-19. Methods and findings We enrolled 2191 consecutive hospitalized patients with COVID-19 from three Italian dedicated units (derivation cohort: 1810 consecutive patients from Bergamo and Pavia units; validation cohort: 381 consecutive patients from Rome unit). The outcome was in-hospital mortality. Fine and Gray competing risks multivariate model (with discharge as a competing event) was used to develop a prediction rule for in-hospital mortality. D…
Liver stiffness measurement by transient elastography predicts early recovery from acute hepatitis
We read with interest the lead article by Castera and Pinzani,1 particularly the comment regarding the role of transient elastography (TE) in the context of acute hepatitis (AH). The assumption that liver stiffness is determined exclusively by hepatic fibrosis has been challenged by evidence that patients with AH can have high values of liver stiffness measurement (LSM) by TE.2 AH is a suitable model for studying the kinetics of LSM, since inflammation and necrosis increase rapidly and sometimes massively, but may revert with equal speed. We evaluated 92 consecutive patients (mean age 41.8±16.3 years, 71.7% males) with symptomatic AH to assess how LSM was influenced by aetiology, and whethe…
Dynamic angiopoietin-2 assessment predicts survival and chronic course in hospitalized patients with COVID-19
Key Points Three-day change in angiopoietin-2 levels predicts COVID-19 in-hospital mortality, whereas the 10-day trend is associated with chronic lung disability. Angiopoietin-2 may play an important pathogenic role in patients with COVID-19, and it could be a target for new treatments.
Update of the statements on biology and clinical impact of occult hepatitis B virus infection
In October 2018 a large number of international experts with complementary expertise came together in Taormina to participate in a workshop on occult hepatitis B virus infection (OBI). The objectives of the workshop were to review the existing knowledge on OBI, to identify issues that require further investigation, to highlight both existing controversies and newly emerging perspectives, and ultimately to update the statements previously agreed in 2008. This paper represents the output from the workshop.
Changes over time in risk factors for cardiovascular disease and use of lipid-lowering drugs in HIV-infected individuals and impact on myocardial infarction.
Background. Because of the known relationship between exposure to combination antiretroviral therapy and cardiovascular disease (CVD), it has become increasingly important to intervene against risk of CVD in human immunodeficiency virus (HIV)-infected patients. We evaluated changes in risk factors for CVD and the use of lipid-lowering therapy in HIV-infected individuals and assessed the impact of any changes on the incidence of myocardial infarction. Methods. The Data Collection on Adverse Events of Anti-HIV Drugs Study is a collaboration of 11 cohorts of HIV-infected patients that included follow-up for 33,389 HIV-infected patients from December 1999 through February 2006. Results. The pro…
Portal Hypertension and Ascites: Patient-and Population-centered Clinical Practice Guidelines by the Italian Association for the Study of the Liver (AISF)
Abstract Portal hypertension and ascites are two crucial events in the natural history of liver cirrhosis, whose appearance marks a downward shift in the prognosis of the disease. Over the years, several international and national societies have issued clinical practice guidelines for the diagnosis and management of portal hypertension and ascites. The present document addresses the needs of an updated guidance on the clinical management of these conditions. Accordingly, the AISF Governing Board appointed a multi-disciplinary committee of experts for drafting an update of the most recent EASL Clinical Practice Guidelines. The aim of this work was to adapt the EASL recommendations to nationa…
Personalized cost-effectiveness of boceprevir-based triple therapy for untreated patients with genotype 1 chronic hepatitis C
Abstract Background We assessed the cost-effectiveness of boceprevir-based triple therapy compared to peginterferon alpha and ribavirin dual therapy in untreated patients with genotype 1 chronic hepatitis C; patients were discriminated according to the combination of baseline plus on-treatment predictors of boceprevir-based triple therapy. Methods Cost-effectiveness analysis performed according to data from the available published literature. The target population was composed of untreated Caucasian patients, aged 50 years, with genotype 1 chronic hepatitis C, and these were evaluated over a lifetime horizon by Markov model. The study was carried out from the perspective of the Italian Nati…
Competing-risk analysis of coronavirus disease 2019 in-hospital mortality in a Northern Italian centre from SMAtteo COvid19 REgistry (SMACORE).
AbstractAn accurate prediction of the clinical outcomes of European patients requiring hospitalisation for Coronavirus Disease 2019 (COVID-19) is lacking. The aim of the study is to identify predictors of in-hospital mortality and discharge in a cohort of Lombardy patients with COVID-19. All consecutive hospitalised patients from February 21st to March 30th, 2020, with confirmed COVID-19 from the IRCCS Policlinico San Matteo, Pavia, Lombardy, Italy, were included. In-hospital mortality and discharge were evaluated by competing risk analysis. The Fine and Gray model was fitted in order to estimate the effect of covariates on the cumulative incidence functions (CIFs) for in-hospital mortality…
Robust Adaptive Modulation and Coding (AMC) selection in LTE systems using reinforcement learning
Adaptive Modulation and Coding (AMC) in LTE networks is commonly employed to improve system throughput by ensuring more reliable transmissions. Most of existing AMC methods select the modulation and coding scheme (MCS) using pre-computed mappings between MCS indexes and channel quality indicator (CQI) feedbacks that are periodically sent by the receivers. However, the effectiveness of this approach heavily depends on the assumed channel model. In addition CQI feedback delays may cause throughput losses. In this paper we design a new AMC scheme that exploits a reinforcement learning algorithm to adjust at run-time the MCS selection rules based on the knowledge of the effect of previous AMC d…
Offloading through Opportunistic Networks with Dynamic Content Requests
Offloading is gaining momentum as a technique to overcome the cellular capacity crunch due to the surge of mobile data traffic demand. Multiple offloading techniques are currently under investigation, from modifications inside the cellular network architecture, to integration of multiple wireless broadband infrastructures, to exploiting direct communications between mobile devices. In this paper we focus on the latter type of offloading, and specifically on offloading through opportunistic networks. As opposed to most of the literature looking at this type of offloading, in this paper we consider the case where requests for content are non-synchronised, i.e. users request content at random …
Treatment of Hepatitis C virus infection in Italy: A consensus report from an expert panel
Abstract Hepatitis C virus (HCV) infection remains one of the main causes of chronic liver disease worldwide. The advent of direct-acting antivirals (DAAs) has significantly improved the course of patients with chronic HCV infection (CHC), due to the ability of these drugs to achieve high rates of sustained virological response (SVR). These exceedingly high rates of SVR and the excellent safety data have been confirmed in real life practice. Evolving guidelines have been issued by national and international scientific societies in accordance with the progression of clinical knowledge and the availability of new DAAs. These recommendations, however, may not be applied universally because of …
West Nile Disease (WND) in Sicily
WND is an emerging vector-borne zoonosis caused by an RNA virus included in the Japanese encephalitis group within the Flavivirus genus. In Italy, after the first appearance in Tuscany in 1998, West Nile Virus (WNV) has been continuously circulating since 2008. A National Surveillance Program consisting of monitoring horses, “sentinel poultries”, wild bird mortality and mosquitoes is active in the entire national territory since 2002. Authors describe the outbreaks which occurred in Sicily in 2010 and 2011. Case study: Between September-October 2010, seven horses from the western part of the island, in the Trapani province, showed neurological symptoms. In October 2011, another two horses s…
Use of hydroxychloroquine in hospitalised COVID-19 patients is associated with reduced mortality: Findings from the observational multicentre Italian CORIST study.
Abstract Background Hydroxychloroquine (HCQ) was proposed as potential treatment for COVID-19. Objective We set-up a multicenter Italian collaboration to investigate the relationship between HCQ therapy and COVID-19 in-hospital mortality. Methods In a retrospective observational study, 3,451 unselected patients hospitalized in 33 clinical centers in Italy, from February 19, 2020 to May 23, 2020, with laboratory-confirmed SARS-CoV-2 infection, were analyzed. The primary end-point in a time-to event analysis was in-hospital death, comparing patients who received HCQ with patients who did not. We used multivariable Cox proportional-hazards regression models with inverse probability for treatme…
Common cardiovascular risk factors and in-hospital mortality in 3,894 patients with COVID-19: survival analysis and machine learning-based findings from the multicentre Italian CORIST Study.
Background and aims There is poor knowledge on characteristics, comorbidities and laboratory measures associated with risk for adverse outcomes and in-hospital mortality in European Countries. We aimed at identifying baseline characteristics predisposing COVID-19 patients to in-hospital death. Methods and results Retrospective observational study on 3894 patients with SARS-CoV-2 infection hospitalized from February 19th to May 23rd, 2020 and recruited in 30 clinical centres distributed throughout Italy. Machine learning (random forest)-based and Cox survival analysis. 61.7% of participants were men (median age 67 years), followed up for a median of 13 days. In-hospital mortality exhibited a…
Treatment of chronic hepatitis B: update of the recommendations from the 2007 Italian Workshop
Abstract The Italian recommendations for the therapy of hepatitis B virus (HBV)-related disease were issued in 2008. Subsequently in 2008 the nucleotide analogue (NA) Tenofovir was approved for antiviral treatment. The introduction of this important new drug has called for the current guidelines update, which includes some additional revisions: (a) the indication for therapy is extended to mild liver fibrosis and the indication for treatment is graded as “possible”, “optional” or “mandatory” according to the fibrosis stage; (b) two different treatment strategies are described: first line definite duration treatment with interferon, long-term treatment of indefinite duration with NA; (c) the…
Lopinavir/ritonavir and darunavir/cobicistat in hospitalized covid-19 patients: Findings from the multicenter italian corist study
Background: Protease inhibitors have been considered as possible therapeutic agents for COVID-19 patients.Objectives: To describe the association between lopinavir/ritonavir (LPV/r) or darunavir/cobicistat (DRV/c) use and in-hospital mortality in COVID-19 patients.Study Design: Multicenter observational study of COVID-19 patients admitted in 33 Italian hospitals. Medications, preexisting conditions, clinical measures, and outcomes were extracted from medical records. Patients were retrospectively divided in three groups, according to use of LPV/r, DRV/c or none of them. Primary outcome in a time-to event analysis was death. We used Cox proportional-hazards models with inverse probability of…
Cost-effectiveness of sofosbuvir-based triple therapy for untreated patients with genotype 1 chronic hepatitis C
We assessed the cost-effectiveness of sofosbuvir (SOF)-based triple therapy (TT) compared with boceprevir (BOC)- and telaprevir (TVR)-based TT in untreated genotype 1 (G1) chronic hepatitis C (CHC) patients discriminated according to IL28B genotype, severity of liver fibrosis, and G1 subtype. The available published literature provided the data source. The target population was made up of untreated Caucasian patients, aged 50 years, with G1CHC and these were evaluated over a lifetime horizon by Markov model. The study was carried out from the perspective of the Italian National Health Service. Outcomes included discounted costs (in euros at 2013 value), life-years gained (LYG), quality-adju…
AISF position paper on HCV in immunocompromised patients.
Abstract This report summarizes the clinical features and the indications for treating HCV infection in immunocompromised and transplanted patients in the Direct Acting Antiviral drugs era.
Cost-effectiveness of boceprevir or telaprevir for untreated patients with genotype 1 chronic hepatitis C.
BACKGROUND AND AIMS: Randomized controlled trials (RCTs) show that triple therapy (TT) with peginterferon alfa, ribavirin and boceprevir (BOC) or telaprevir (TVR) is more effective than peginterferon-ribavirin dual therapy (DT) in the treatment of previously untreated patients with genotype 1 (G1) chronic hepatitis C (CHC). We assess the cost-effectiveness of TT compared to DT in the treatment of untreated patients with G1 CHC. METHODS: We created a Markov Decision Model to evaluate, in an untreated Caucasian patients aged 50 years, weight 70 kg, with G1 CHC and Metavir F2 liver fibrosis score, for a time horizon of twenty years, the cost-effectiveness of the following 5 competing strategie…
Management of infections in cirrhotic patients: Report of a Consensus Conference
a b s t r a c t The statements produced by the consensus conference on infection in end-stage liver disease promoted by the Italian Association for the Study of the Liver, are here reported. The topics of epidemiology, risk factors, diagnosis, prophylaxis, and treatment of infections in patient with compensated and decompensated liver cirrhosis were reviewed by a scientific board of experts who proposed 26 statements that were graded according to level of evidence and strength of recommen- dation, and approved by an independent jury. Each topic was explored focusing on the more relevant clinical questions. By systematic literature search of available evidence, comparison and discussion of e…
Correlation between FIB4, liver stiffness and metabolic parameters in patients with HIV and hepatitis C virus co-infection.
Assessment of liver fibrosis is crucial in HIV/HCV coinfected patients, in whom metabolic disturbances are frequent. Aims of this study were to analyse the association of two non-invasive liver fibrosis evaluation methods, liver stiffness measurement and FIB4, and their correlation with metabolic parameters.This was a single centre cross-sectional study. All patients underwent biochemical and virological assessment, FIB4 score, HOMA and transient elastography.Seventy-five patients were evaluated. Liver stiffness values positively correlated with FIB4 (R = 0.62; p0.0001). By ROC curve analysis the optimal cut-off for liver stiffness to identify high FIB4 was calculated as 10.1 kPa. The area …
Cost-effectiveness of sorafenib treatment in field practice for patients with hepatocellular carcinoma
The purpose was to assess the cost-effectiveness of sorafenib in the treatment of hepatocellular carcinoma (HCC) patients incorporating current prices and the results of the recent published field practice SOraFenib Italian Assessment (SOFIA) study. We created a Markov Decision Model to evaluate, in a hypothetical cohort of Caucasian male patients, aged 67 years with Barcelona Clinic Liver Cancer (BCLC) C HCC, or BCLC B HCC who were unfit or failed to respond to locoregional therapies, well compensated cirrhosis, and with performance status 0-1 according to Eastern Cooperative Oncology Group (ECOG), the cost-effectiveness of the following strategies: (1) full or dose-adjusted sorafenib for …
Clinical features and comorbidity pattern of HCV infected migrants compared to native patients in care in Italy: A real-life evaluation of the PITER cohort
Background: Direct-acting antivirals are highly effective for the treatment of hepatitis C virus (HCV) infection, regardless race/ethnicity. We aimed to evaluate demographic, virological and clinical data of HCV-infected migrants vs. natives consecutively enrolled in the PITER cohort. Methods: Migrants were defined by country of birth and nationality that was different from Italy. Mann-Whitney U test, Chi-squared test and multiple logistic regression were used. Results: Of 10,669 enrolled patients, 301 (2.8%) were migrants: median age 47 vs. 62 years, (p < 0.001), females 56.5% vs. 45.3%, (p < 0.001), HBsAg positivity 3.8% vs. 1.4%, (p < 0.05). Genotype 1b was prevalent in both gro…
Cost-effectiveness of sofosbuvir-based triple therapy for untreated patients with genotype 1 chronic hepatitis C
We assessed the cost-effectiveness of sofosbuvir (SOF)-based triple therapy (TT) compared with boceprevir (BOC)- and telaprevir (TVR)-based TT in untreated genotype 1 (G1) chronic hepatitis C (CHC) patients discriminated according to IL28B genotype, severity of liver fibrosis, and G1 subtype. The available published literature provided the data source. The target population was made up of untreated Caucasian patients, aged 50 years, with G1CHC and these were evaluated over a lifetime horizon by Markov model. The study was carried out from the perspective of the Italian National Health Service. Outcomes included discounted costs (in euros at 2013 value), life-years gained (LYG), quality-adju…
Nutritional parameters associated with prognosis in non-critically ill hospitalized covid-19 patients: the nutri-covid19 study
Background & aims: To investigate the association between the parameters used in nutritional screening assessment (body mass index [BMI], unintentional weight loss [WL] and reduced food intake) and clinical outcomes in non-critically ill, hospitalized coronavirus disease 2019 (COVID-19) patients. Methods: This was a prospective multicenter real-life study carried out during the first pandemic wave in 11 Italian Hospitals. In total, 1391 patients were included. The primary end-point was a composite of in-hospital mortality or admission to ICU, whichever came first. The key secondary end-point was in-hospital mortality. Results: Multivariable models were based on 1183 patients with comple…
Disentangling the Association of Hydroxychloroquine Treatment with Mortality in Covid-19 Hospitalized Patients through Hierarchical Clustering
The efficacy of hydroxychloroquine (HCQ) in treating SARS-CoV-2 infection is harshly debated, with observational and experimental studies reporting contrasting results. To clarify the role of HCQ in Covid-19 patients, we carried out a retrospective observational study of 4,396 unselected patients hospitalized for Covid-19 in Italy (February–May 2020). Patients’ characteristics were collected at entry, including age, sex, obesity, smoking status, blood parameters, history of diabetes, cancer, cardiovascular and chronic pulmonary diseases, and medications in use. These were used to identify subtypes of patients with similar characteristics through hierarchical clustering based on Gower distan…
Triple therapy with first-generation Protease Inhibitors for patients with genotype 1 chronic hepatitis C: Recommendations of the Italian Association for the Study of the Liver (AISF)
AbstractThe first-generation Protease Inhibitors Boceprevir and Telaprevir administered in triple therapy regimens with Peg-interferon alpha and Ribavirin have been proven effective in increasing the rate of Sustained Virological Response in both naive and treatment-experienced patients with chronic genotype-1 hepatitis C. However, at the individual level, the therapeutic advantage of triple therapy is highly variable and results from the combination of multiple factors related to the characteristics of patient, viral status and liver disease.The recommendations presented are promoted by the Italian Association for the Study of the Liver, with the aim to help the physician in the decision-m…
Cost effectiveness of boceprevir or telaprevir for previously treated patients with genotype 1 chronic hepatitis C.
Background & Aims Randomised controlled trials (RCTs) show that triple therapy (TT) with peginterferon alfa, ribavirin, and boceprevir (BOC) or telaprevir (TVR) is more effective than peginterferon-ribavirin dual therapy (DT) in the treatment of genotype 1 (G1) chronic hepatitis C (CHC) patients with previous relapse (RR), partial response (PAR), and null-response (NR). We assess the cost-effectiveness of TT compared to no therapy in the treatment of patients previously treated with G1 CHC. Methods The available published literature provided the data source. The target population was made up of previously treated Caucasian patients with G1 CHC and these were evaluated over a lifetime horizo…
Analysis of MAC-level throughput in LTE systems with link rate adaptation and HARQ protocols
LTE is rapidly gaining momentum for building future 4G cellular systems, and real operational networks are under deployment worldwide. To achieve high throughput performance, in addition to an advanced physical layer design LTE exploits a combination of sophisticated mechanisms at the radio resource management layer. Clearly, this makes difficult to develop analytical tools to accurately assess and optimise the user perceived throughput under realistic channel assumptions. Thus, most existing studies focus only on link-layer throughput or consider individual mechanisms in isolation. The main contribution of this paper is a unified modelling framework of the MAC-level downlink throughput of …
Ombitasvir, paritaprevir, and ritonavir, with or without dasabuvir, plus ribavirin for patients with hepatitis C virus genotype 1 or 4 infection with cirrhosis (ABACUS): a prospective observational study
Summary Background We ran a compassionate use nationwide programme (ABACUS) to provide access to ombitasvir, paritaprevir, and ritonavir, with dasabuvir, plus ribavirin for hepatitis C virus (HCV) genotype 1 infection and ombitasvir, paritaprevir, and ritonavir, plus ribavirin for HCV genotype 4 infection in patients with cirrhosis at high risk of decompensation while approval of these regimens was pending in Italy. Methods In this prospective observational study, we collected data from a compassionate use nationwide programme from March 17, 2014, to May 28, 2015. Patients with HCV genotype 1 infection and cirrhosis at high risk of decompensation were given coformulated ombitasvir (25 mg), …