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The long-term changes of liver stiffness (LS) in patients who achieve viral clearance after direct-acting anti-HCV therapy remain undefined. We conducted a multicenter prospective study to investigate this aspect. Patients with HCV infection treated with DAAs were enrolled from six Italian centers; they underwent clinical, biochemical, ultrasound, and transient elastography evaluations before treatment (T0), 12 weeks (SVR12), and 24 months (T24) after the end of therapy. Among the 516 consecutive patients enrolled, 301 had cirrhosis. LS significantly decreased from T0 to SVR (14.3 kPa vs 11.1 kPa, p=0.002), with a progressive reduction until T24 (8.7 kPa, p

People who use drugs are a key population in global HCV control. We evaluated the efficacy of an innovative model to eliminate HCV infection in a high-risk population of PWUD in a service for substance use disorder (SUD). Between January 2018 and December 2018, we conducted a prospective, interventional, before and after study, based on audits performed by Infectious Diseases physicians in a SUD facility in Piedimonte Matese, in southern Italy, to improve the knowledge about HCV infection; a shared protocol for screening and linkage to care of patients was implemented. The pre-intervention period was defined as January-December 2017 and the post-intervention period as January-December 2018. The subjects followed up at SUD facility in the pre-intervention and post-intervention periods were 318 and 275, respectively. Compared with the pre-intervention period, the number of anti-HCV–positive subjects tested for HCV RNA was higher in the post-intervention period (91% vs 27%, P&nbsp

OBJECTIVE An important prognostic factor in any form of infection seems to be glucose control in patients with type 2 diabetes. There is no information about the effects of tight glycemic control on coronavirus disease 2019 (COVID-19) outcomes in patients with hyperglycemia. Therefore, we examined the effects of optimal glycemic control in patients with hyperglycemia affected by COVID-19. RESEARCH DESIGN AND METHODS Fifty-nine patients with COVID-19 hospitalized with moderate disease were evaluated. On the basis of admission glycemia >7.77 mmol/L, patients were divided into hyperglycemic and normoglycemic groups. Interleukin 6 (IL-6) and D-dimer levels were evaluated at admission and weekly during hospitalization. The composite end point was severe disease, admission to an intensive care unit, use of mechanical ventilation, or death. RESULTS Thirty-four (57.6%) patients were normoglycemic and 25 (42.4%) were hyperglycemic. In the hyperglycemic group, 7 (28%) and 18 (72%) patients were diagnosed with diabetes already before admission, and 10 (40%) and 15 (60%) were treated without and with insulin infusion, respectively. The mean of glycemia during hospitalization was 10.65 ± 0.84 mmol/L in the no insulin infusion group and 7.69 ± 1.85 mmol/L in the insulin infusion group. At baseline, IL-6 and D-dimer levels were significantly higher in the hyperglycemic group than in the normoglycemic group (P < 0.001). Even though all patients were on standard treatment for COVID-19 infection, IL-6 and D-dimer levels persisted higher in patients with hyperglycemia during hospitalization. In a risk-adjusted Cox regression analysis, both patients with hyperglycemia and patients with diabetes had a higher risk of severe disease than those without diabetes and with normoglycemia. Cox regression analysis evidenced that patients with hyperglycemia treated with insulin infusion had a lower risk of severe disease than patients without insulin infusion. CONCLUSIONS Insulin infusion may be an effective method for achieving glycemic targets and improving outcomes in patients with COVID-19.

In Italy, HDV infection endemicity has greatly decreased overtime. Migratory flow may change this scenario as migrants often come from high HDV endemicity areas. Here, we studied characteristics of HDV infection in Italy, particularly addressed to the birth area of subjects. Chronic HBsAg carriers consecutively referring to 9 units in Italy prospectively enrolled for a six-month period in 2019 were tested for anti-HDV by ELISA. Multiple logistic regression analysis was performed to identify anti-HDV positivity independent predictors. A total of 894 HBsAg-positive subjects were enrolled. Of them, 786 (87.9%) were tested for anti-HDV. Anti-HDV overall prevalence was 9.9% (6.4% in Italian natives and 26.4% in non-natives; P&nbsp

Patients with type 2 diabetes (T2D) are characterized by blunted immune responses, which are affected by glycaemic control. Whether glycaemic control influences the response to COVID-19 vaccines and the incidence of SARS-CoV-2 breakthrough infections is unknown. Here we show that poor glycaemic control, assessed as mean HbA1c in the post-vaccination period, is associated with lower immune responses and an increased incidence of SARS-CoV-2 breakthrough infections in T2D patients vaccinated with mRNA-BNT162b2. We report data from a prospective observational study enroling healthcare and educator workers with T2D receiving the mRNA-BNT162b2 vaccine in Campania (Italy) and followed for one year (5 visits, follow-up 346 ± 49 days) after one full vaccination cycle. Considering the 494 subjects completing the study, patients with good glycaemic control (HbA1c one-year mean < 7%) show a higher virus-neutralizing antibody capacity and a better CD4 + T/cytokine response, compared with those with poor control (HbA1c one-year mean ≥ 7%). The one-year mean of HbA1c is linearly associated with the incidence of breakthrough infections (Beta = 0.068; 95% confidence interval [CI], 0.032-0.103; p p = 0.008). Among other factors, only smoking (HR = 0.290, CI 0.146-0.576 for non-smokers; p p

SARS-CoV-2 is still a health problem worldwide despite the availability of vaccines. Therefore, there is a need for effective and safe antiviral. SARS-CoV-2 and HCV necessitate RNA-dependent RNA polymerase (RdRp) for replication; therefore, it has been hypothesized that RdRp inhibitors used to treat HCV may be effective treating SARS-CoV-2. Accordingly, we evaluated the effect of the sofosbuvir/velpatasvir (SOF/VEL) combination in early SARS-CoV-2 infection. A multicenter case–control study was conducted, enrolling 120 patients with mild or moderate COVID-19, of whom 30, HCV coinfected or not, received SOF/VEL tablets (400/100 mg) once daily for 9 days within a median of 6 days from the beginning of infection and 90 controls were treated with standard care. The primary endpoint was the effect on viral clearance, and the secondary endpoint was the improvement of clinical outcomes. Nasal swabs for SARS-CoV-2 by PCR were performed every 5–7 days. Between 5–14 days after starting SOF/VEL treatment, SAS-CoV-2 clearance was observed in 83% of patients, while spontaneous clearance in the control was 13% (p

Background Cardiovascular disease (CVD) is a major cause of morbidity and mortality after liver transplantation, mostly in patients transplanted for nonalcoholic steatohepatitis, obesity and diabetes. Few data exist on cardiovascular diseases among patients transplanted for viral hepatitis. Objective Our aim is to clarify the cardiovascular risk and subclinical vascular damage among liver transplant recipients for chronic viral hepatitis (i.e. hepatits C virus, hepatis B virus and hepatitis D virus infection). Methods Adult patients (age ≥ 18 years) with orthotopic liver transplants (OLT) due to viral hepatitis who signed informed consent, and were admitted for a routine follow-up between June 2019 and September 2020 at the Infectious Disease outpatient clinic of the University of Campania Luigi Vanvitelli, Naples, Italy, were prospectively enrolled. An estimation of cardiovascular risk was assessed using three main risk charts, echocolor-Doppler of epiaortic vessels was performed to assess subclinical Intima-Media changes. Results A total of 161 patients were evaluated; of these 15 were excluded because not affected by viral hepatitis. 146 patients were considered. 83 patients (56.8%) were considered at high cardiovascular risk according to Framingham, 54 patients (36.9%) to American Heart Association Arteriosclerotic Cardiovascular Disease (ASCVD) score and 19 (13.0%) to Heart Score. Only 8 patients (5.4%) showed a normal carotid ultrasound, while 52 patients (35.6%) had a carotid artery Intima-Media Thickness (IMT) and 86 (58.9%) an atherosclerotic plaque. Conclusions Liver transplant recipients for virus-related associated liver disease are, in light of the high percentage of carotid lesions, at high risk of CVD. Risk charts compared to subclinical carotid lesions which represent damage already established and a real localization of the disease, seem to underestimate the cardiovascular risk. A chronic inflammatory status, could play a key role. It’s important to raise the awareness of cardiovascular risk in liver transplant patients to prevent cardiovascular diseases and improve the timing of early diagnosis of premature vascular lesions.

Background: In the present study we evaluated the efficacy of an innovative model of HCV micro-elimination in a hospital setting in an area of high HCV prevalence.Patients and metods: Between January and December 2019, a prospective, interventional study for a program of HCV case-finding and linkage-to-care was performed in S. Anna and S. Sebastiano hospital of Caserta, in Campania, a region in southern Italy. All adult patients who were admitted to the Caserta hospital in the study period and resulted positive for anti-HCV were included in the study. The outcomes evaluated were the number of subjects resulting HCV-RNA-positive, those linked-to-care and treated with a DAA and the subjects whose anti-HCV-status was unknown.Results: In the study period, 14,396 subjects, admitted to the hospital for different reasons, were tested for anti-HCV: 529 (3.7%) subjects resulted positive for anti-HCV. Of the 529 anti-HCV-positive subjects, 10 died during hospitalization and 243 were already treated with a DAA. The remaining 276 subjects were contacted and agreed to be evaluated. Of these 276 subjects, 68 patients resulted HCV- RNA-negative and 194 HCV-RNA-positive and 180 of these were treated with a DAA according to the international guidelines.Discussion: A simple, rapid, inexpensive model of HCV micro-elimination in the hospital setting allowed us to find anti-HCV-positive subjects with unknown anti-HCV status or not linked to a clinical center. (c) 2022 The Author(s). Published by Elsevier Ltd on behalf of King Saud Bin Abdulaziz University for Health Sciences. CC_BY_NC_ND_4.0

Tocilizumab (TCZ) is used for treating moderate-to-severe Covid-19 pneumonia by targeting interleukin-6 receptors (IL-6Rs) and reducing cytokine release. Yet, in spite of this therapy, patients with vs. patients without diabetes have an adverse disease course. In fact, glucose homoeostasis has influenced the outcomes of diabetes patients with infectious diseases. Of the 475 Covid-19-positive patients admitted to infectious disease departments (University of Bologna, University Vanvitelli of Napoli, San Sebastiano Caserta Hospital) in Italy since 1 March 2020, 31 (39.7%) hyperglycaemic and 47 (60.3%) normoglycaemic patients (blood glucose levels >= 140 mg/dL) were retrospectively evaluated at admission and during their hospital stay. Of note, 20 (64%) hyperglycaemic and 11 (23.4%) normoglycaemic patients had diabetes (P < 0.01). At admission, hyperglycaemic vs. normoglycaemic patients had fivefold higher IL-6 levels, which persisted even after TCZ administration (P < 0.05). Intriguingly, in a risk-adjusted Cox regression analysis, TCZ in hyperglycaemic patients failed to attenuate risk of severe outcomes as it did in normoglycaemic patients (P < 0.009). Also, in hyperglycaemic patients, higher IL-6 plasma levels reduced the effects of TCZ, while adding IL-6 levels to the Cox regression model led to loss of significance (P < 0.07) of its effects. Moreover, there was evidence that optimal Covid-19 infection management with TCZ is not achieved during hyperglycaemia in both diabetic and non-diabetic patients. These data may be of interest to currently ongoing clinical trials of TCZ effects in Covid-19 patients and of optimal control of glycaemia in this patient subset. Crown Copyright (C) 2020 Published by Elsevier Masson SAS. All rights reserved.

INTRODUCTION: In people living with HIV (PLWH), immune activation and inflammation levels are high even when viral suppression is maintained, potentially contributing to several comorbidities, and hampering the immune response to infections such as the recent SARS-CoV-2 disease 2019 (COVID-19). AREAS COVERED: Immune activation and inflammation play a role in SARS-CoV-2 infection. Severe COVID-19 patients may experience cytokine release syndrome (CRS), leading to alveolar damage, pulmonary fibrinolysis, dysregulated coagulation, and pulmonary injury. Into the systemic circulation, cytokines in excess might leak out of pulmonary circulation, causing systemic symptoms and possibly a multiple-organ dysfunction syndrome. Preexisting comorbidities are also linked to worse COVID-19 outcome: studies suggest that diabetes and hypertension are linked to higher mortality rates. Such comorbidities are more frequent in PLWH, but it is unclear if they have worse outcomes in the case of COVID-19. The literature was searched in PubMed/MEDLINE and EMBASE, and manually in COVID-19 resources. EXPERT OPINION: A body of evidence shows that HIV and SARS-CoV-2 are able to activate inflammatory pathways, acute in the case of SARS-CoV-2, chronic in the case of HIV, while the comorbidities seem to represent, in the first case, a contributory cause, in the second an effect of the virus-induced damage.

Background: Second generation direct acting antivirals (DAAs) drastically changed the landscape of chronic HCV (CHCV). Aim of this paper was to assess the effectiveness of DAAs, also looking at the demographic characteristics of subjects enrolled. Research design and methods: Ambispective multi-center real-life study conducted among patients with CHCV treated with DAAs in Campania Region (Southern Italy). Patient were enrolled in two cohorts according to time of enrolment. Results: 1,479 patients were enrolled. Patients aged ≥60 years were 74.7% in the historic cohort (953 patients) and 70.2% in the prospective cohort (526 patients. Patients aged ≥ 60 years showed a higher prevalence of genotype 1b (p

INTRODUCTION: We assessed the performance of direct-acting antivirals (DAAs) in hepatitis C virus (HCV)-infected people who use drugs (PWUDs) in terms of sustained virological response (SVR) and adherence rates in comparison to a location-matched cohort of non-PWUD HCV patients. METHODS: All consecutive HCV RNA-positive PWUDs were enrolled between 2015 and 2019. All subjects underwent DAA treatment according to international guidelines and then followed, at least, up to 12 weeks after the end of treatment (SVR12). The SVR and adherence to treatment was compared with that of non-PWUD HCV patients observed at hepatological units of the CLEO platform. Intention-to-treat analysis was performed. RESULTS: A total of 1,786 PWUDs who were followed up were available for assessment. Most PWUDs (85.4%) were managed inside the specialized outpatient addiction clinics (SerDs). The overall SVR rate was 95.4%. The SerDs group achieved an SVR rate of 96.2% compared with 91.6% of the non-SerDs group (P < 0.001). Comparison with the non-SerDs group and the control HCV group showed a significant difference in the dropout rate (0.6% in the SerDs group versus 2.8% in the non-SerDs group and 1.2% in the control group; P < 0.001). At multivariate analysis, factors independently associated with SVR were use of the most recent regimens (elbasvir/grazoprevir, glecaprevir/pibrentasvir, and sofosbuvir/ velpatasvir; odds ratio: 3.126; P 5 0.000) and belonging to the SerDs group (odds ratio: 2.356; P 5 0.002). DISCUSSION: The performance of DAAs in PWUD is excellent, if 2 conditions are met: (i) that the latest generation drugs are used and (ii) that the patients are managed within the SerDs.

Purpose: The aim of this study was to evaluate the effects of antiviral therapy on liver stiffness measurement (LSM). Methods: Two hundred HBV patients were enrolled from four hospital centers in southern Italy; median age was 50.7 (25–75) males were 68%; 171 patients underwent to liver biopsy and 200 patients had LSM at baseline and 189 at the end of follow-up. One hundred and forty-nine patients were treated with nucleos(t)ide analogs, while 51 patients were untreated. The cutoffs of the LSM, related to the fibrosis stages, were as follows: non-advanced fibrosis ≤ 8.1 kPa and advanced fibrosis ≥ 8.2 Kpa. Results: At baseline, the median value of LSM was 14.1 kPa for advanced fibrosis/cirrhosis and 6.9 kPa for non-advanced fibrosis. LSM was performed at 24 months from the start of therapy. The treated patients (68% received Entecavir and 32% Tenofovir) showed a decrease in liver stiffness measurement of 1.5 kPa (p < 0.001) in non-advanced fibrosis and of 6 kPa (p < 0.001) in advanced fibrosis/cirrhosis. In the patients not undergoing antiviral treatment, no statistically significant change of the LSM was observed (p = 0.26). A logistic binary regression model showed that the only independent factor associated with a significant change in the LSM was the liver stiffness value at baseline (odd ratio 2.855; 95% CI 1.456–5.788; (p = 0.007). Conclusion: Long-term antiviral therapy induced a significant reduction of liver stiffness measurement and this result may be related to the reduction of liver fibrosis. © 2018, Springer-Verlag GmbH Germany, part of Springer Nature.

Context: The Global Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) pandemic has resulted in explosive patterns of transmission in most countries. Nasopharyngeal swabs were the specimen’s collection tools recommended for the diagnosis of SARS-CoV-2 infection, and for monitoring infection outbreaks in communities. Our objective was to report the quality and efficacy of unsupervised self-collected mid turbinate “dry FLOQSwabs” (MT FLOQSwabs) (56380CS01, Copan). There were 111 specimens collected for the study: 36 by health care personnel, from themselves, to verify the quality and efficacy of mid-turbinate swabs, 75 to compare and assess the diagnostic performance, among health care personnel, of nasopharyngeal swabs and self-collected mid-turbinate FLOQSwabs. A collection of 51 specimens was enrolled to define the efficacy of the Testami program (validation). Our analyses demonstrate that self-collected mid-turbinate dry swabs ensure an accuracy of 97.3%, as compared to the standard nasopharyngeal swabs collected by health care workers. Furthermore, the mid-turbinate FLOQSwabs can be stored without medium for six days at room temperature without affecting the molecular diagnosis of the SARS-CoV-2 virus infection. Self-collection of diagnostic specimens at home could offer an avenue to increase testing availability for SARS-CoV-2 infection without asking people to travel to a clinic or a laboratory, thus reducing people’s exposure to infection. Our findings demonstrate that unsupervised self-collection swabs, transported dry, are sensitive, practical and easy-to-use tools and should be considered for diagnosis of SARS-COV-2 and coronavirus disease 2019 (COVID-19) surveillance.

BACKGROUND Coronavirus disease 2019 (COVID‐19) is the cause of a pandemic disease, with severe acute respiratory syndrome by binding target epithelial lung cells through angiotensin‐converting enzyme 2 in humans. Thus, patients with hypertension with COVID‐19 could have worse prognosis. Indeed, angiotensin‐converting enzyme inhibitors and/or angiotensin receptor blockers may interfere with angiotensin‐converting enzyme 2 expression/activity. Thus, patients with hypertension undergoing angiotensin‐converting enzyme inhibitor and/or angiotensin receptor blockers drug therapy may be at a higher risk of contracting a serious COVID‐19 infection and should be monitored. Moreover, in the present study we investigated the effects of angiotensin‐converting enzyme inhibitor versus angiotensin receptor blockers versus calcium channel blockers on clinical outcomes as mechanical ventilation, intensive care unit admissions, heart injury, and death in 62 patients with hypertension hospitalized for COVID‐19 infection. METHODS AND RESULTS The multicenter study was prospectively conducted at Department of Infectious Diseases of Sant'Anna Hospital of Caserta, and of University of Campania "Luigi Vanvitelli" of Naples, at Department of Advanced Surgical and Medical Sciences of University of Campania "Luigi Vanvitelli," Naples, and at General Medical Assistance Unit "FIMG," Naples, Italy. Lowest values of left ventricle ejection fraction predicted deaths (1.142, 1.008–1.294, P CONCLUSIONS Anti‐hypertensive drugs didn't affect the prognosis in patients with COVID‐19. Consequently, tailored anti‐inflammatory and immune therapies in addition to chronic antihypertensive therapy, could prevent a worse prognosis, as well as improve the clinical outcomes in patients with hypertension with COVID‐19 infection.

BackgroundHypertension is the most frequent co-morbidity in patients with covid-19 infection, and we might speculate that a specific blood group could play a key role in the clinical outcome of hypertensive patients with covid-19.MethodsIn this prospective study, we compared 0 vs. non-0 blood group in hypertensive patients with covid-19 infection. In these patients, we evaluated inflammatory and thrombotic status, cardiac injury, and death events.ResultsPatients in non-0 (n = 92) vs. 0 blood group (n = 72) had significantly different values of activated pro-thrombin time, D-dimer, and thrombotic indexes as Von Willebrand factor and Factor VIII (p p ConclusionsTaken together, our data indicate that non-0 covid-19 hypertensive patients have significantly higher values of pro-thrombotic indexes, as well as higher rate of cardiac injury and deaths compared to 0 patients. Moreover, AB0 blood type influences worse prognosis in hypertensive patients with covid-19 infection.

Background & Aims The proportion of HCV-infected patients over age 65 years in Western countries is increasing. This growth and the advent of new antiviral therapy bring into the question the real-world efficacy and safety of the combination of sofosbuvir (SOF) and simeprevir (SMV) plus a flat dose of 800 mg/d ribavirin (RBV) in elderly patients with cirrhosis compared to younger patients. Methods Retrospective observational multicentre real-life investigation study of SOF/SMV/RBV for a duration of 12 weeks in HCV genotype 1-infected patients with cirrhosis. Results Of the 270 patients enrolled in this study, with compensated cirrhosis, 133 (49.2%) were ≥65 years of age. Sustained virological response at 12 weeks (SVR12) was achieved by 94.2% (129/137) of those aged

Background and Aims: Tenofovir disoproxil fumarate (TDF) is recommended for chronic hepatitis B (CHB) treatment, but it may induce kidney dysfunction whose management is not yet known. This Italian, multicentre, retrospective study aimed to assess the efficacy and safety of switching to entecavir (ETV) patients who developed TDF-associated glomerular and/or tubular dysfunction. Methods: A total of 103 TDF-treated patients were included as follows: age 64years, 83% male, 49% cirrhotics, 98% with undetectable HBV DNA, 47% with previous lamivudine resistance (LMV-R) and 71% previously treated with adefovir. Twenty-nine (28%) were switched to ETV because estimated glomerular filtration rate (eGFR MDRD ) was

Background This real-world clinical setting study characterized the virological patterns in genotype-1 patients failing interferon (IFN)-free regimens and evaluated the efficacy of re-treatment. Methods A total of 73 consecutive patients failing IFN-free regimens were enrolled (17 genotype-1a and 56 −1b). At failure Sanger sequencing of NS3, NS5A and NS5B regions was performed by home-made protocols. Results In patients having failed an NS3 inhibitor, the prevalence of NS3-RASs was higher in the 10 with genotype-1a than in the 24 with genotype-1b (80% versus 41.6%). In patients treated with an NS5A inhibitor, the prevalence of NS5A-RASs was very high in the 14 with genotype-1a and the 27 with genotype-1b (78.6% and 92.5%, respectively). In patients having failed sofosbuvir, the prevalence of NS5B-RASs was more frequently identified in the 45 with genotype-1b than in the 10 with genotype-1a (37.7% versus 10%). The prevalence of NS5B-RASs in patients having failed dasabuvir was high in both genotypes, 66.6% in the 6 with genotype-1a and 45.5% in the 11 with genotype-1b. The 6 patients re-treated with genotype-1a less frequently (50%) showed sustained virological response (SVR) than the 18 with genotype-1b (88.8%; P=0.07). SVR was more frequent in the 21 patients with an effective second-line direct-acting antiviral (DAA) regimen than the 3 without (90.4% versus 0%; PConclusions The prevalence of RASs was high in our real-world population. NS3, NS5A and NS5B sequencing seems mandatory in the choice of DAA re-treatment.

BACKGROUND AND AIMS It is paramount to identify predictors of treatment failure with direct antiviral agents in 'field-practice' patients, including people who inject drugs (PWID). Data on the efficacy of glecaprevir/pibrentasvir (GLE/PIB) in a field-practice scenario are scant. The multicentre MISTRAL study enrolled 1177 patients, including PWID, to assess real-life efficacy and safety of GLE/PIB and to identify the predictive factors for this treatment. METHODS This was a prospective, longitudinal study. The outcome variable was the rate of sustained virological response (SVR) at week 12. RESULTS A total of 123 patients (10%) were infected from hepatitis C virus (HCV) 3. METAVIR fibrosis score was F4 in 104 subjects (9%); 118 patients (10%) were PWID. Overall, 1163/1177 (99%) patients achieved SVR. The baseline clinical factors discriminating between treatment success and treatment failure were age at treatment (P = 0.031) and creatinine level (P = 0.034). SVR rates were not influenced by gender, substance abuse, previous treatment, treatment duration, fibrosis or chronic kidney disease stage. Compared with non-substance users, the 118 PWID exhibited a significantly different genotype pattern distribution (χ2

Background/Aims Patients with genotype 3 hepatitis C virus (G3-HCV) cirrhosis are very difficult to treat compared to patients with other HCV genotypes. The optimal treatment duration and drug regimen associated with ribavirin (RBV) remain unclear. To evaluate the efficacy and safety of daclatasvir (DCV)/sofosbuvir (SOF) plus a flat dose of 800 mg RBV (flat dose) compared to DCV/SOF without RBV or DCV/SOF plus an RBV dose based on body weight (weight-based) in G3-HCV patients with compensated or decompensated cirrhosis. Methods We analyzed data for 233 G3 cirrhotic patients. Of these, 70 (30%), 87(37%) and 76 (33%) received SOF/DCV, SOF/DCV/RBV flat dose, and SOF/DCV/RBV weight-based dose, respectively. Treatment duration was 24 weeks. Sustained virological response (SVR) was evaluated at week 12 posttreatment (SVR12). Results Overall, SVR12 was achieved in 220 out of 233 patients (94.4%). The SVR12 rate was lower in the DCV/SOF group than in the DCV/SOF/RBV flat-dose group and the DCV/SOF/RBV weight-based group (87.1% vs 97.7% and 97.4%, respectively, p=0.007). A higher incidence of anemia occurred in the DCV/SOF/RBV weight-based group compared to those in the other two groups (p

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 65years. 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 (25/150/100mg) and twice-daily dasabuvir (250mg) plus Ribavirin (RBV) (OBV/PTV/r + DSV + RBV) for 12 (GT1b) or 24 (GT1a) weeks. Endpoints were to evaluate safety and efficacy, the latter defined as HCV RNA negative 12weeks after the end of treatment (SVR12). Results: Patients who suffered any adverse event (AE) were 74/240 (30.8%); 13/240 (5.4%) discontinued the treatment. A multivariate analysis found albumin < 3.5g/dL (OR 2.04: 95% CI 1.0–4.2, p < 0.05) and hypertension (OR 4.6: 95% CI 2.3–9.2, p < 0.001) as variables independently associated with AE occurrence. The SVR12 was 95% (228/240). Multivariate analysis identified baseline bilirubin < 2mg/dL (OR 4.9: 95% CI 1.17–20.71, p = 0.029) as the only variable independently associated with SVR12. Conclusion: Our findings suggest that OBV/PTV/r + DSV + RBV is safe and effective in real-life use in patients with compensated cirrhosis, HCV-GT1 infection, and age over 65.

The effectiveness of a 12-week course of sofosbuvir-ledipasvir in treatment-experienced HCV genotype 1b-infected patients with cirrhosis is still under debate. Our primary endpoint was to compare the sustained virological response at post-treatment week 12 (SVR12) of sofosbuvir-ledipasvir in combination with ribavirin for 12 weeks, and sofosbuvir-ledipasvir alone for 24 weeks. This was a prospective observational study that enrolled 424 (195 naive, 229 experienced; 164 treated for 12 weeks with Ribavirin and 260 with sofosbuvir-ledipasvir alone for 24 weeks) consecutive HCV genotype 1b-infected patients with cirrhosis. The SVR12 rates were 93.9% and 99.2% in patients treated for 12 and 24 weeks, respectively (p=0.002). The baseline characteristics of patients treated for 12 weeks were significantly different from those treated for 24 weeks as regards their younger age (p=0.002), prevalence of Child-Pugh class A (p=0.002), lower MELD scores (p=0.001) and smaller number of non-responders (p=0.04). The shorter treatment was significantly associated with a lower SVR12 in univariate and multivariate analysis (p=0.007 and p=0.008, respectively). The SVR rate was unaffected by age, gender, BMI, Child-Pugh class, MELD score or previous antiviral treatment. Patients receiving ribavirin experienced more episodes of ascites and headache but less recurrence of hepatocellular carcinoma (HCC), and were prescribed more diuretics and cardiopulmonary drugs. No patient discontinued treatment. The therapeutic regimen of sofosbuvir-ledipasvir plus ribavirin administered for 12 weeks was less effective than sofosbuvir-ledipasvir alone given for 24 weeks. At odds with European guidelines, the recommended 12-week treatment with sofosbuvir-ledipasvir alone might be suboptimal for this setting of patients. This article is protected by copyright. All rights reserved.

To identify early predictors of a severe or fulminant course in patients with acute viral hepatitis B (AVH-B).138 patients with symptomatic acute hepatitis B observed from 1999 to 2012 were enrolled. For each patient, the demographics, risk factors for the acquisition of HBV infection, clinical, biochemical and virological data (HBV DNA, HBV DNA sequences) were recorded and analyzed. The HBV mutants in the polymerase region were sought in 110 (87\%) patients by direct sequencing, and the rtM204V/I mutations also by an allele-specific polymerase chain reaction.AVH-B was severe in 13 (9.4\%) of the 138 patients enrolled, fulminant in 6 (4.3\%) and with a normal clinical course in 119. The 19 patients with severe or fulminant AVH-B more frequently than the 119 with a normal course stated intravenous drug use (63.2\% vs. 36.1\%, p=0.04) and were HBV-DNA negative (31.6\% vs. 11.8\%, p = 0.03) and anti-HCV positive (57.9\% vs. 19.3\%, p=0.0008); the prevalences of different HBV genotypes and of the rtM204V/I mutant were similar in these three forms of AVH-B. A multivariate logistic regression analysis identified a pre-existing HCV chronic infection as the only factor independently associated with a severe or fulminant clinical course of AHV-B (O.R.: 4.89, C.I. 95\%: 1.5-15.94, p=0.01).A pre-existing HCV chronic infection was identified as the only factor independently associated with a severe clinical presentation of acute hepatitis B, an association most probably due to the combination of the liver lesions caused by acute hepatitis B and the pre-existing histological abnormalities related to HCV chronic infection This article is protected by copyright. All rights reserved.

Background To investigate the association between inosine triphosphatase (ITPase) activity and the degree of anaemia occurring during direct-acting antiviral (DAA)/ribavirin (RBV)-based therapy in patients with cirrhosis. Methods In a multicentre, prospective study 227 patients with HCV-related cirrhosis treated with DAA and RBV were enrolled. All patients were screened for the rs1127354 and rs7270101 ITPA single nucleotide polymorphisms using direct sequencing. Results 150 (66.1%) patients had normal (100%) ITPase activity, 48 (21.1%) had moderate (60%) activity and 29 (12.8%) minimal (≤30%) activity. The ITPase activity significantly influenced the haemoglobin concentration: at day 15 it was -1.248 (sd ±0.978) in the 150 patients with an ITPase activity of 100% and -0.616 (±0.862) in the 77 patients with an ITPase activity less than 100% ( P Conclusions This study suggests that the polymorphisms in the ITPA gene influence the severity of anaemia during the first month of a DAA/RBV-based treatment in HCV-related cirrhosis.

Background Sustained virological response (SVR12) rates at 12 weeks after treatment for HCV-infected patients with decompensated cirrhosis are used when referring to those with moderate functional impairment, while few data are available for those with more severe impairment. The use of the cirrhosis staging system proposed by D’Amico might provide new insights on timing for antiviral therapy. Methods We investigated efficacy (SVR12), safety, and post-treatment variations in clinical and laboratory parameters in 2612 patients with advanced fibrosis (n = 575) or cirrhosis (n = 2037). Cirrhosis was in the compensated phase (without/with varices) or had previously been in the decompensated stage. Different direct-acting antiviral (DAA) regimens were administered in accordance with scientific guidelines. Results The SVR12 rate was 97.6% in patients with advanced fibrosis. For patients with cirrhosis, the rate was 96.5% in stage 1, 95.1% in stage 2, 100% in stage 3, 95.7% in stage 4, and 93.6% in stage 5. These rates were independent of gender, age, HCV genotype, and treatment schedule. Positive changes in biochemical parameters and CPT classes following therapy were evident in compensated and previously decompensated patients. Conclusion Our findings support the use of DAAs in patients with advanced cirrhosis (stages 3–5) who are at greatest risk and have the most to gain from therapy.

Background and rationale of the study. Effect of Long-term nucleoside/nucleotide (NUC) on hepatocellular carcinoma (HCC) incidence in a population of HBeAg-negative genotype D patients has not been adequately studied in real-life cohorts. Our aim was to evaluate the impact of liver fibrosis and other variables on HCC incidence in this population of patients. Of 745 patients with chronic hepatitis B (CHB), 306 HBeAg-negative genotype D were selected and included in this study. All patients received treatment with NUC for at least 18 months. Patients with CHB or compensated cirrhosis were included. Patients with HCC diagnosed before or during the first 18 months of NUC therapy were excluded. Results. HCC was diagnosed in 2 CHB patients (1.0%) and 23 cirrhosis patients (20%) (OR = 24.41, 95% CI 5.40 < OR < 153.2; p < 0.0001). Multivariate analysis revealed that HCC risk was independently associated with age ≥ 60 years (OR = 6.45, 95% CI 1.22 to 34.0; p = 0.02) and liver cirrhosis (OR = 12.1, 95% CI 1.39 to 106.2; p = 0.02), but not with virological response (VR), and previous resistance to NUC, or rescue therapy. Multivariate analysis in cirrhosis patients revealed that only age ≥ 60 years was an independent risk factor associated with HCC (p = 0.003). Conclusions. Liver cirrhosis and age ≥ 60 years are the stronger risk factors for HCC in genotype D HBeAgnegative patients. Previous resistance to NUC in patients that achieved a VR after rescue therapy was not a predictive factor regarding HCC. VR does not appear to significantly reduce the overall incidence of HCC when a patient has already progressed to liver cirrhosis.

The aims of the study were to evaluate the long-term efficacy and tolerability of different doses of interferon-alpha (IFN alpha) and different durations of treatment in chronic hepatitis C by comparing 3 or 6 mega units (MUs) three times weekly given for either 12 or 24 months, and the possibility of obtaining a response in non-responder patients by increasing the dose or by administering IFN daily. A total of 504 patients with non-cirrhotic chronic hepatitis C enrolled in a multicentre study were consecutively assigned to receive either 3 (255 patients) or 6 MU (249 patients) of lymphoblastoid IFN alpha 3 times a week (tiw). At the 12th month of therapy, patients with normal aminotransferase (AMT) in both groups were either given IFN for an additional 12 months with an unmodified or halved dose, or else discontinued therapy. For patients with unmodified AMT levels after 6 months of therapy, the IFN dose was doubled in the 3-MU group, while it was administered at 3 MU daily in the 6-MU group. When no improvement was achieved, therapy was discontinued; otherwise it was prolonged until the 18th month. Patients were followed up for 12 months after discontinuing IFN. Of the 255 patients enrolled at 3 MU, therapy was stopped during the first 6 months in 36 patients (14.1%) because of side effects, and in 24 (9.4%) because of lack of cooperation. Of the remaining 195 patients at the 6th month of therapy, 119 (61%) had normal and 76 (39%) unmodified AMT levels; 14 of the 76 normalized AMT after doubling the dose of IFN, but only 5 (6.6%) had a sustained response. Of the 119 patients with normal AMT, 40 discontinued IFN at the 12th month (schedule A), 39 remained at 3 MU tiw (schedule B) and 40 were given a dose of 1.5 MU tiw (schedule C) for an additional 12 months. At the end of follow-up, 23/40 (57.5%) patients in schedule A, 31/39 (79.5%) on schedule B and 29/40 (72.5%) on schedule C still had normal AMT (A vs. B p = 0.04). In an intention-to-treat analysis, the sustained response rate for patients enrolled at 3 MUs, including the 5 initial non-responders, was 34.5%. Of the 249 patients enrolled at 6 MU, therapy was discontinued during the first 6 months for 39 (15.7%) because of side effects, and for 27 (10.8%) because of lack of cooperation. Of the remaining 183 patients at the 6th month of therapy, 110 (60%) had normal and 73 (40%) unmodified AMT levels. Of the 73 patients, 55 accepted the daily regimen and 8 of them (14.5%) showed a sustained response. Of the 110 patients with normal AMT, 32 (29.1%), despite normalization of AMT, spontaneously discontinued IFN or reduced the dose because of a poor quality of life, while 78 continued with 6 MU until the 12th month, when therapy was discontinued for 28 (schedule A1); 24 patients were given an unmodified dose (schedule B1) and 26 a halved dose (schedule C1) for an additional 12 months. At the end of follow-up, 18/28 (64.3%) patients on schedule A1, 19/24 (79.2%) on schedule B1 and 19/26 (73.1%) on C1 still had normal AMT (p = NS). In an intention-to-treat evaluation, the sustained response rate for patients enrolled at 6 MU, including the 8 from the daily treatment, was 25.7% (64/249). HCV viraemia was undetectable 1 year after discontinuation of IFN in 72.6% of patients with a sustained response. Sustained response was observed in 36.4% of patients with minimal, 46.6% of those with mild, and 33.3% with moderate or severe histological activity (p = NS). The rate of sustained response was lower in patients with genotype 1b (23.6%) than in those with genotype 2a (67.8%, p = 0.002) or genotype 3 (50%, p = 0.03), irrespective of the histological activity. In conclusion, 6 MU IFN alpha are no more effective than 3 MU in inducing a sustained response in treatments of both 12 and 24 months. A 24-month treatment is more effective than a 12-month treatment in maintaining a biochemical response after discontinuation of IFN. In terms of efficacy, compliance and cost, 3 MU for 24 months app

Aims: To detect HBV rtM204V/I lamivudine-resistant strains in serum of patients with acute hepatitis B and to assess their biological and clinical significance. Methods: Eighty HBV DNA-positive patients with symptomatic acute hepatitis B observed from 1999 to 2010 were enrolled. A plasma sample obtained at the first observation was tested for HBV mutants in the polymerase region by direct sequencing; the antiviral drug-resistant rtM204V/I mutations, the most frequent HBV mutants in Italy, were also sought by the more sensitive allele-specific polymerase chain reaction (PCR). Results: No HBV mutation associated with resistance to nucleos(t)ide analogues was identified by direct sequencing, whereas allele-specific PCR identified HBV strains carrying the substitution rtM204V/I in 11 (13.7%) patients. Compared with those with the HBV wild strain, patients with rtM204V/I more frequently showed severe acute hepatitis B (36.4% vs 8.7%; p

Objective To correlate lipid metabolism and autonomic dysfunction with anxious-depressive spectrum and eating disorders. To propose the lipid index (LI) as a new possible biomarker. Methods 95 patients and 60 controls were enrolled from the University Psychiatry Unit of Catania and from general practitioners (GPs). The patients were divided into four pathological groups: Anxiety, Depression, Anxious-Depressive Disorder and Eating Disorders [Diagnostic and Statistical Manual of Mental Disorders Fourth Edition Text Revision (DSM-IV-TR) official/appendix criteria]. The levels of the cholesterol, triglycerides and apolipoproteins A and B were determined. The LI, for each subject, was obtained through a mathematical operation on the values of the cholesterol and triglycerides levels compared with the maximum cut-off of the general population. The autonomic functioning was tested with Ewing battery tests. Particularly, the correlation between heart rate variability (HRV) and lipid metabolism has been investigated. Results Pathological and control groups, compared among each other, presented some peculiarities in the lipid metabolism and the autonomic dysfunction scores. In addition, a statistically significant correlation has been found between HRV and lipid metabolism. Conclusions Lipid metabolism and autonomic functioning seem to be related to the discussed psychiatric disorders. LI, in addition, could represent a new possible biomarker to be considered.

Background & Aims: It was recently demonstrated that none of the hepatitis B e antigen (HBeAg)-negative patients without any serum hepatitis B surface antigen (HBsAg) decline and with = 2 log HBV DNA decline at week 12. SR was defined as HBV DNA

To explore changes in molecular epidemiology of acute viral hepatitis B (AVH-B), hepatitis B virus (HBV) genotypes were determined by direct sequencing of the Pre-S-S region in 123 consecutive patients, with AVH-B observed in Naples or its surroundings in the last decade (group AVH-B) and in 123 HBV chronic carriers [chronic carrier of HBV (CC-B) group] from the same areas, who had been hepatitis B surface antigen-positive for more than 10 years. Genotype D was less frequently detected in patients with AVH-B than in those in the CC-B group (76.4%vs 97.5%, P < 0.0001). In the AVH-B group, intravenous drug addiction (IVDA) was the prevalent risk factor (55.3%) for acquiring HBV in the 94 patients with HBV genotype D, but it was rarely recorded (6.9%) in the 29 patients with genotypes non-D (P < 0.0001); unsafe sexual intercourse was prevalent in patients with genotype non-D (72.3%) and less frequent in those with genotype D (28.8%, P < 0.005). In the AVH-B group, the prevalence of non-D genotypes increased during the observation period from 11.1% in 1999-2003 to 41.1% in 2004-2008 (P < 0.0005), paralleling the increase in the prevalence of patients with unsafe sexual intercourse; similarly, the progressive decrease in IVDA paralleled the decrease in the prevalence of genotype D (from 88.3% in 1999-2003 to 11.7% in 2004-2008). The prevalence of HBV non-D genotypes recorded in the last 10 years in AVH-B in this area shows a progressive increase, most probably because of recent changes in HBV epidemiology, namely, the HBV mass vaccination campaign and increased immigration from areas with high HBV endemicity. © 2009 Blackwell Publishing Ltd.

Background: The gold standard for the diagnosis of acute hepatitis C (AHC) is seroconversion to anti-HCV/HCV-RNA positivity, an occurrence frequently missed in clinical practice. Objectives: This study aims to diagnose AHC by the combined use of the HCV Avidity Index (HCV-AI) and HCV-IgM titre. Study design: We enrolled 45 patients with AHC diagnosed by seroconversion to anti-HCV/HCV-RNA positivity and 36 with exacerbation of chronic hepatitis C (e-CHC) diagnosed at least 1 year earlier. HCV-IgM titres were determined by a commercial enzyme-linked immunosorbent assay (ELISA) and HCV-AI by an ELISA for detection of HCV IgG with a partial modification. For each test, specific cut-off values at four selected checking points were established during the observation (20 days from the onset of symptoms): for the HCV-IgM assay, the highest value in e-CHC +5% and for HCV-AI assay, the lowest value in e-CHC -5%. Results: Around 90% of patients with AHC or e-CHC were correctly diagnosed at all checking points by combining the results of both tests. This practice afforded an improvement in sensitivity for the diagnosis of AHC, with the highest values at first and third checking points (92.3% and 92.6%, respectively) and an improvement in negative predictive value (NPV), with the highest value at first checking point (92.6%). Conclusions: The diagnosis of AHC, made by seroconversion to anti-HCV/HCV-RNA positivity, was confirmed in more than 90% of patients by combining the results of IgG Avidity Index (IgG-AI) and HCV-IgM obtained in a single serum sample. © 2009 Elsevier B.V. All rights reserved.

The impact of hepatitis B virus (HBV) superinfection in hepatitis C virus (HCV) chronic carriers was evaluated in a long-term follow-up study on 29 chronic anti-HCV carriers with acute hepatitis B (AVH-B) (Case group BC) and 29 anti-HCV negative patients with AVH-B (Control group B), pair-matched for age (±5 years), sex, and risk factors for the acquisition of HBV infection. Patients in Case group BC and those in Control group B showed similar initial HBV viral load and a similar trend of becoming negative for HBV-DNA. AVH-B showed a severe course more frequently in Case group BC than in Control group B (34.5% versus 6.9%, P < 0.05). Of the 28 patients in Case group BC alive at the end of the acute illness (one death from liver failure), 24 were followed up for 2-6 years, median 5 years: 22 patients became HBsAg-negative and two progressed to HBsAg-positive chronic hepatitis. HCV-RNA was undetectable in all patients during AVH-B; in the 24 patients with a long-term follow-up, HCV-RNA was detected in seven (29.2%) after 1 year, in 14 (58.3%) after 2 years, and in 18 (75%) after 3-6 years. The six patients who eradicated chronic HCV infection, compared with 18 showing reactivation of HCV replication, had higher values of aspartate aminotransferase and alanine aminotransferase and a higher prevalence of cases with severe AVH-B (83.3% versus 22.2%, P < 0.05). Conclusions: Although it can be life-threatening, HBV superinfection in HCV chronic carriers may lead to clearance of chronic HCV infection, especially in patients with severe AVH-B. Copyright © 2009 by the American Association for the Study of Liver Diseases.

The diagnosis of acute hepatitis C (AHC) is based on seroconversion to positive anti-HCV, which is usually not clinically possible.To determine if avidity of anti-HCV IgG can be used for the diagnosis of AHC infection.We enrolled 40 consecutive patients with AHC, 16 drug addicts (IVDA) with exacerbation of chronic hepatitis C (IVDA e-CHC group), 21 non-IVDA with exacerbation of chronic hepatitis C (IVDA-free e-CHC group) and 40 with chronic hepatitis C (CHC group). HCV avidity index (HCV-AI) was determined by ELISA on sera pre-diluted 1:10 with 1M guanidine.On admission, HCV-AI values were significantly lower in the AHC group (mean+/-S.D.: 0.50+/-0.30) than in IVDA-free e-CHC group (0.97+/-0.08, p0.0001), IVDA e-CHC group (0.90+/-0.29, p0.0001) or CHC group (1.06+/-0.20, p0.0001). An HCV-AI lower than 0.7 obtained within the 8th day of illness distinguished patients with AHC infection from the IVDA-free e-CHC cases. An increase in HCV-AI was observed in 24 (72.7%) of 33 in AHC group, in none of 13 in IVDA-free e-CHC group and in 3 (27.3%) of 11 in IVDA e-CHC group.HCV-AI is useful in identifying AHC infection in patients observed within the 8th day from the onset of symptoms.

Objectives: The use of antiarrhythmic drugs after ablation is a controversial issue when evaluating the efficacy of atrial fibrillation (AF) ablation. This study compares in a prospective and randomized fashion the impact of an antiarrhythmic drug in preventing AF recurrence after AF ablation. Methods: From February 2004 to May 2005, 107 consecutive patients (mean age 57 ± 10 years, 69 men), with paroxysmal (60%) or persistent (40%) drug refractory AF, were randomly assigned to ablation alone (Group A, 53 patients) or combined with the best antiarrhythmic therapy, preferably amiodarone (Group B, 54 patients). All patients underwent cavo-tricuspid and left inferior pulmonary vein (PV)-mitral isthmus ablation plus circumferential PV ablation, using a guided electro-anatomical approach. Standard electrocardiograms (ECG), and ambulatory and transtelephonic ECG monitoring were used to assess AF recurrences. Recurrences during the first month after ablation were excluded from this analysis. Results: At 12 months of follow-up, no significant difference was observed in the rates of AF recurrences between Group A (18/53 patients, 34%) and Group B (16/54 patients, 30%). The percentage of patients with ≥1 asymptomatic AF episode was higher in Group B than in Group A (10/16 patients, 63%, vs 5/18 patients, 28%, P = 0.04). Conclusions: Continuing antiarrhythmic drug therapy in patients who undergo catheter ablation for AF did not lower the rate of AF recurrences. Antiarrhythmic drugs increased the proportion of patients with asymptomatic AF episodes.

In 2001, 6,999 anti-HCV positive subjects referred to 79 Italian hospital in a 6 months enrollment period were evaluated. Of them, 5,632 (80.5%) tested anti-HCV positive alone, 1,163 (16.6%) reported also an excessive alcohol intake, and 204 (2.9%) were also HBsAg positive. Normal biochemistry was observed in 7.8% of cases, chronic hepatitis in 67.9% of cases, liver cirrhosis in 18.9% of cases, and hepatocellular carcinoma in 3.6% cases. HCV positive subjects with excessive alcohol intake were statistically significantly younger, of male sex, and having more severe liver disease than those without excessive alcohol intake. Adjusting for the confounding effect of age and sex by multiple logistic regression analysis, HCV positive chronic hepatitis cases drinking more than four alcoholic drinks daily were 2.2-fold (CI 95% = 1.3-4.0) more likely to progress to liver cirrhosis than teetotallers. These findings indicate that nearly a quarter of HCV positive subjects referred to hospitals in Italy have a severe liver disease causing a remarkable impact on the national health system. Excessive alcohol intake in HCV chronic hepatitis cases increases the risk of progression to liver cirrhosis.

The flecainide infusion test has been proposed to screen candidates for hybrid pharmacological and ablation therapy. We report the long-term follow-up of 154 consecutive patients with paroxysmal or persistent atrial fibrillation (AF) who developed atrial flutter (AFL) during flecainide infusion (IC AFL), treated with inferior vena cava-tricuspid annulus isthmus catheter ablation and oral flecainide (hybrid therapy). Over a mean of 54.1 +/- 13.1 months 82 patients (53%) remained free of AF and AFL. Flecainide was discontinued because of adverse effects in 6 patients (4%). A history of persistent AF, and the documentation of >/=1 spontaneous AFL episode before the flecainide test were independent predictors of successful hybrid therapy. In patients with paroxysmal AF without documented spontaneous AFL, the long-term efficacy of hybrid therapy was 38.5% (P = 0.03). The flecainide infusion test reliably detects candidates for hybrid therapy. The efficacy of this therapy is maintained over the long-term with a high patient compliance.

Background/Aims We investigated whether serial determination of IgM to HCV core protein (HCV IgM) may be useful to identify acute hepatitis C (AHC) and to distinguish this disease from reactivation of chronic hepatitis C (r-CHC). Methods We enrolled 35 consecutive patients with AHC identified by seroconversion to anti-HCV and 31 consecutive patients who had been anti-HCV positive for at least six months at the time of reactivation. Titres of HCV IgM were calculated as Index values by a commercially available enzyme immunoassay. Results During the early phase of the illness we observed a wide variation in the HCV IgM Index values in all patients in the AHC group and consistent values in all cases in the r-CHC group. The HCV viral load determined soon after the onset of symptoms was of no use in identifying AHC.Twenty-three patients in the AHC group were observed as outpatients for 6-30 months; of these, 10 became plasma HCV-RNA negative within the third month of observation, but three showed a subsequent reactivation of HCV infection. Conclusions Our data indicate that the detection of high and variable titres of HCV IgM in the early phase of the illness may identify acute hepatitis C and allow early antiviral treatment.

From January 1999 to today 5 patients have been treated with self-expanding enteral stents for low intestinal occlusion in our General and Emergency Surgery Department. The patients' ages ranged from 75 to 90 years. Their general clinical condition was precarious and the emergency surgical treatment necessary was at very high risk. After a brief period of clinical monitoring the patients were submitted to a colonoscopy which revealed a tight neoplastic stenosis in the lowest portion of the colon. Self-expanding enteral stents measuring 9 by 20 mm were implanted in 4/5 patients, while, in the fifth patient, in view of the extent of the cancer, an oesophageal enteral stent measuring 12 by 23-28 mm was used. Over the following 24 hours we observed canalization and consequent disocclusion of the colorectum. It was thus possible to readjust the altered metabolic parameters, improve the respiratory and circulatory compliance and begin the study and the staging of the malignancy. Only two patients in acceptable general condition were submitted to radical surgery, while the other three were referred to our oncological radiotherapy centre. On the basis of this preliminary study we believe that in given clinical conditions and in a situation of emergency the use of self-expanding enteral stents, when indicated, is the only therapeutic measure capable of avoiding surgery carrying a very high risk and of creating the basis for appropriate, in-depth study of the cancer. In addition, it enables a better balance to be restored in the patient's general condition.

To study in HBsAg chronic carriers the expression of liver hsa-miR-125a-5p and its correlation with liver HBV-DNA values and clinical presentation, 27 consecutive Caucasian, HBsAg/anti-HBe/HBV-DNA-positive patients who were naive to nucleos(t)ide analogues and interferon therapy and had no marker of HCV, HDV or HIV infection and no history of alcohol intake were enrolled. For each patient, liver HBV DNA and liver hsa-miR-125a-5p were quantified by real-time PCR in relation to β-globin DNA or RNU6B, respectively. Liver fibrosis and necroinflammation were graded by applying Ishak's scoring system. Liver hsa-miR-125a-5p was detected in all patients enrolled and a correlation between its concentration and liver HBV DNA was demonstrated (p103 IU/ml (p6 (p = 0.02) and those with fibrosis score >2 (p2 (p = 0.02) than in patients with a lower load. By multivariate logistic regression analysis, liver hsa-miR-125a-5p was identified as an independent predictor of disease progression: O.R. = 4.21, C.I. 95% = 1.08-16.43, p6; O.R. = 3.12, C.I. 95% = 1.17-8.27, p2. In conclusion, in HBsAg/anti-HBe-positive patients, the liver hsa-miR-125a-5p level correlated with liver and plasma HBV-DNA values and was associated to a more severe disease progression. © 2013 Coppola et al. To study in HBsAg chronic carriers the expression of liver hsa-miR-125a-5p and its correlation with liver HBV-DNA values and clinical presentation, 27 consecutive Caucasian, HBsAg/anti-HBe/HBV-DNA-positive patients who were naive to nucleos(t)ide analogues and interferon therapy and had no marker of HCV, HDV or HIV infection and no history of alcohol intake were enrolled. For each patient, liver HBV DNA and liver hsa-miR-125a-5p were quantified by real-time PCR in relation to β-globin DNA or RNU6B, respectively. Liver fibrosis and necroinflammation were graded by applying Ishak's scoring system. Liver hsa-miR-125a-5p was detected in all patients enrolled and a correlation between its concentration and liver HBV DNA was demonstrated (p103 IU/ml (p6 (p = 0.02) and those with fibrosis score >2 (p2 (p = 0.02) than in patients with a lower load. By multivariate logistic regression analysis, liver hsa-miR-125a-5p was identified as an independent predictor of disease progression: O.R. = 4.21, C.I. 95% = 1.08-16.43, p6; O.R. = 3.12, C.I. 95% = 1.17-8.27, p2. In conclusion, in HBsAg/anti-HBe-positive patients, the liver hsa-miR-125a-5p level correlated with liver and plasma HBV-DNA values and was associated to a more severe disease progression. © 2013 Coppola et al.