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Abstract Background The impact of viral subtype on the rate of sustained virological response (SVR) to antiviral therapy in patients chronically infected with hepatitis C genotype 1 subtype 1a and 1b has not been extensively investigated. The aim of this study is to determine whether the HCV genotype 1 subtypes 1a and 1b respond differently to treatment with PEGylated interferon (PEG-IFN) plus ribavirin. Methods For 48 weeks, 388 “naïve”genotype 1 patients were treated weekly with PEG-IFN α-2a or PEG-INF α-2b combined with daily ribavirin (1000–1200 mg/day). The numbers of patients in whom HCV-RNA was undetectable were compared after 4 (rapid virological response, RVR), 12 (early virological response, EVR), and 48 (end treatment virological response, ETR) weeks of treatment as well as 24 weeks after the last treatment (sustained virological response, SVR). Results The rate of SVR was higher in subtype 1a patients than subtype 1b patients (55% vs. 43%; p 10 IU/ml (OR: 3.2; 95% CI: 2.7 to 6.9) and fibrosis score < S3 (OR: 3.8; 95% CI:3.2 to 7.4), were all independent predictors of SVR. Conclusion Dual antiviral therapy is more effective against HCV subtype 1a than against subtype 1b and this difference is independent of other factors that may favour viral clearance. Trial registration ClinicalTrials.gov Identifier: NCT01342003

Abstract Background In patients with chronic hepatitis C virus (HCV) genotype 2 or 3, 24 weeks' treatment with pegylated interferon alfa (PEG-IFN-alpha) and ribavirin induces a sustained virological response (SVR) in almost 80% of cases. Evidence suggests that a similar response rate may be obtained with shorter treatment periods, especially in patients with a rapid virological response (RVR). The aim of this study was to compare the efficacy of 12 or 24 weeks of treatment in patients with chronic HCV genotype 2 or 3 and to identify patients suitable for 12 weeks treatment. Methods Two hundred and ten patients received PEG-IFN-alpha-2a (180 ug/week) and ribavirin (800-1200 mg/day) for 4 weeks. Patients with a RVR (HCV RNA not detectable) were randomized (1:1) to either 12 (group A1) or 24 (group A2) weeks of combination therapy. Patients without a RVR continued with 24-weeks' combination therapy (group B). HCV RNA was monitored at weeks 4, 8, 12, and 24, and at week 24 post-treatment. Results At study end, end of treatment response (ETR) was observed in 62 (86%) patients of group A1 and in 55 (77%) patients of group A2 (p < 0.05) Relapse rate was 3% each in groups A1 and A2, and 6% in group B. Among patients with a HCVRNA test 24 weeks after the end of treatment, SVR was observed in 60 (83%) of group A1 patients and in 53 (75%) of group A2 patients. Rapid virological response, low baseline HCV RNA levels, elevated alanine aminotransferase levels and low fibrosis score, were the strongest covariates associated with SVR, independent of HCV genotype. No baseline characteristic was associated with relapse. Conclusion In HCV patients with genotype 2 or 3, 12-week combination therapy is as efficacious as 24-week therapy and several independent covariates were predictive of SVR. Trial registration Trial number ISRCTN29259563

Abstract Background Right-sided endocarditis occurs predominantly in intravenous drug users, in patients with pacemaker or central venous lines and in patients with congenital heart disease. The vast majority of cases involve the tricuspid valve. Eustachian valve endocarditis is an uncommon disease with similar signs and symptoms of the tricuspid valve endocarditis. A series of only 16 cases of eustachian valve endocarditis are reported in the literature. Case Presentation We present a case of a 25-year old woman with intravenous drug abuse who had a staphylococcus aureus tricuspid valve endocarditis associated to eustachian valve endocarditis. Transthoracic echocardiography, as first line examination, showed the vegetations on tricuspid and eustachian valve. Conclusion Our case describe an unusual location of right side endocarditis in a intravenous drug abuser. In our case, in accord with other cases described in the literature, transthoracic echocardiography disclosed eustachian valve endocarditis. Antimicrobial management is not altered by the recognition of eustachian valve endocarditis. Antibiotic treatment and duration of eustachian endocarditis depends on the isolated organism and is similar to antibiotic therapy used in native valve endocarditis.

Summary: Risk of hepatocellular carcinoma (HCC) in hepatitis C virus cirrhotic patients treated with direct‐acting antiviral agents (DAA) is still debating. We investigated it in a large cohort. The cohort comprised 1045 cirrhotic patients who completed treatment with DAA, with a median follow‐up of 17.3 months after end of treatment (EOT), including 943 patients without history of HCC and 102 previously treated for HCC. The majority were men (59.9%), with compensated cirrhosis (88.8%), genotype 1b (44.7%). Univariate, multivariate analysis and Kaplan‐Meier curves were performed to detect predictors of HCC in patients with and without reduction in alpha‐fetoprotein (AFP) during treatment. SVR12 was 95.6%. HCC developed in 95 (9.9%), including 54 of 943 (5.7%) occurrent and 41 of 102 (39%) recurrent tumours. De novo were more often unifocal (P = 0.01) and curable (P = 0.03). AFP decreased from 16.1 ± 36.2 mg/dL (baseline) to 11.4 ± 55 mg/dL (EOT). At univariate analysis, predictors were a previous HCC, older age, higher model for end‐stage liver disease, prolonged INR, lower platelets, baseline and EOT AFP, virological failure and no reduction in AFP during treatment. Kaplan‐Meier curves showed lower incidence of HCC in patients showing any reduction in AFP (P = 0.001). Those with AFP <6 ng/mL had the lowest risk (P = 0.0002). At logistic regression, platelets (P = 0.009, OR 0.99 CI: 0.99‐1.00), previous HCC (P < 0.000 01, OR: 10.76, 95% CI: 5.89‐19.34) and no reduction in AFP during treatment (P = 0.0005, OR: 2.98, CI: 1.60‐5.54) were independent predictors of HCC. In conclusion, risk of HCC after DAA treatment remains substantial. It is higher among patients with previous HCC, low platelets and without reduction in AFP during treatment. [ABSTRACT FROM AUTHOR]

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 <65 years and 97.7% (130/133) of those ≥65 years. Diabetes was the most common comorbidity in patients ≥65 years compared to younger patients (26.3% vs 12.4% P<.003). The most common adverse event ( AE) in elderly patients was a grade 2 anaemia (35.3% vs 19.9% P<.004). Conclusions Sofosbuvir/simeprevir plus a daily flat dose of RBV 800 mg for 12 weeks was highly effective and safe in genotype 1 elderly patients with compensated cirrhosis. [ABSTRACT FROM AUTHOR]

Background & Aims Despite the excellent efficacy of direct-acting antivirals ( DAA) reported in clinical trials, virological failures can occur, often associated with the development of resistance-associated substitutions ( RASs). This study aimed to characterize the presence of clinically relevant RASs to all classes in real-life DAA failures. Methods Of the 200 virological failures that were analyzed in 197 DAA-treated patients, 89 with pegylated-interferon+ribavirin (Peg IFN+ RBV) and 111 without ( HCV-1a/1b/1g/2/3/4=58/83/1/6/24/25; 56.8% treatment experienced; 65.5% cirrhotic) were observed. Sanger sequencing of NS3/ NS5A/ NS5B was performed by home-made protocols, at failure (N=200) and whenever possible at baseline (N=70). Results The majority of the virological failures were relapsers (57.0%), 22.5% breakthroughs, 20.5% non-responders. RAS prevalence varied according to IFN/ RBV use, DAA class, failure type and HCV genotype/subtype. It was 73.0% in IFN group vs 49.5% in IFN free, with the highest prevalence of NS5A- RASs (96.1%), compared to NS3- RASs (75.9% with IFN, 70.5% without) and NS5B- RASs (66.6% with IFN, 20.4% without, in sofosbuvir failures). In the IFN-free group, RASs were higher in breakthrough/non-responders than in relapsers (90.5% vs 40.0%, P<.001). Interestingly, 57.1% of DAA IFN-free non-responders had a misclassified genotype, and 3/4 sofosbuvir breakthroughs showed the major- RAS-S282T, while RAS-L159F was frequently found in sofosbuvir relapsers (18.2%). Notably, 9.0% of patients showed also extra target RASs, and 47.4% of patients treated with ≥2 DAA classes showed multiclass resistance, including 11/11 NS3+ NS5A failures. Furthermore, 20.0% of patients had baseline- RASs, which were always confirmed at failure. Conclusions In our failure setting, RAS prevalence was remarkably high in all genes, with a partial exception for NS5B, whose limited resistance is still higher than previously reported. This multiclass resistance advocates for HCV resistance testing at failure, in all three genes for the best second-line therapeutic tailoring. [ABSTRACT FROM AUTHOR]

Rituximab is a chimeric anti-CD20 monoclonal antibody that is a widely used for the treatment of B cells non-Hodgkin lymphoma. The use of chemotherapy regimens containing rituximab in HCV-positive patients with non-Hodgkin lymphoma has been associated with liver dysfunction, but no cases of cholestatic hepatitis C were described. To our knowledge, this is the first case of cholestatic hepatitis C in an HCV-positive patient with diffuse large B-cell lymphoma describes in the literature. We discuss the pathogenetic mechanisms underlying this severe form of hepatitis and describe its evolution after antiviral treatment. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: In patients with chronic hepatitis C virus (HCV) genotype 2 or 3, 24 weeks' treatment with pegylated interferon alfa (PEG-IFN-alpha) and ribavirin induces a sustained virological response (SVR) in almost 80% of cases. Evidence suggests that a similar response rate may be obtained with shorter treatment periods, especially in patients with a rapid virological response (RVR). The aim of this study was to compare the efficacy of 12 or 24 weeks of treatment in patients with chronic HCV genotype 2 or 3 and to identify patients suitable for 12 weeks treatment. Methods: Two hundred and ten patients received PEG-IFN-alpha-2a (180 ug/week) and ribavirin (800-1200 mg/day) for 4 weeks. Patients with a RVR (HCV RNA not detectable) were randomized (1:1) to either 12 (group A1) or 24 (group A2) weeks of combination therapy. Patients without a RVR continued with 24-weeks' combination therapy (group B). HCV RNA was monitored at weeks 4, 8, 12, and 24, and at week 24 post-treatment. Results: At study end, end of treatment response (ETR) was observed in 62 (86%) patients of group A1 and in 55 (77%) patients of group A2 (p < 0.05) Relapse rate was 3% each in groups A1 and A2, and 6% in group B. Among patients with a HCVRNA test 24 weeks after the end of treatment, SVR was observed in 60 (83%) of group A1 patients and in 53 (75%) of group A2 patients. Rapid virological response, low baseline HCV RNA levels, elevated alanine aminotransferase levels and low fibrosis score, were the strongest covariates associated with SVR, independent of HCV genotype. No baseline characteristic was associated with relapse. Conclusion: In HCV patients with genotype 2 or 3, 12-week combination therapy is as efficacious as 24-week therapy and several independent covariates were predictive of SVR. [ABSTRACT FROM AUTHOR]

Abstracts: Objectives:The aim of this study was to assess the therapeutic effectiveness of adefovir dipivoxil (ADV), administered in combination with lamivudine (LAM) or as monotherapy, and the rate of resistance to ADV, in hepatitis B e antigen (HBeAg)-negative adult patients with chronic hepatitis B virus (HBV) infection and clinical or virologic resistance to LAM. Furthermore, we evaluated in these selected patients the clinical co-variates associated with a sustained virologic response. Methods:Data from adult outpatients aged >18 years with chronic HBV infection and clinical or virologic resistance to LAM were used in this retrospective, multicenter, nonrandomized, open-label study. Patients were selected if they received ADV 10 mg PO QD + LAM 100 mg QD PO or ADV 10 mg PO QD as monotherapy for 24 to 32 months between June 2003 and July 2006. End points were the proportions of patients who achieved virologic response (undetectable HBV-DNA [<3.3 log10 copies/mL]) and biochemical response (normalization [<40 IU/L] of alanine aminotransferase [ALT]), and the proportions in whom resistance to ADV (rebound serum HBV-DNA >1 log10 copies/mL compared with on-treatment nadir, as confirmed on molecular analysis) was found. HBV-DNA and ALT levels were checked every month during the first 3 months of treatment and every 3 months thereafter until 28 months. Data from each center were stored in a centralized database and analyzed by a blinded independent investigator. Results:Data from 70 patients were included (48 men, 22 women; median age, 51 years; ADV + LAM, 36 patients; ADV monotherapy, 34). The median duration of the pharmacologic treatment in the 2 groups of patients was 28 months (range, 24–32 months). By month 3, virologic response was achieved in 30 patients (83%) in the ADV + LAM group and in 26 patients (76%) in the ADV monotherapy group. At 12 months, virologic response was achieved in 5 additional patients in the ADV + LAM group and 2 additional patients in the ADV monotherapy group. Biochemical response was found to be time dependent: in the 2 groups, the rates of biochemical response were, respectively, 56% and 54% at month 3, 80% and 71% at month 6, and 96% and 79% at month 12, persisting up to the end of the study period. The rates of clinical resistance to ADV were 3% with ADV + LAM and 18% with ADV monotherapy (with a 6% rate of resistance due to rtA181 mutation in the monotherapy group). Logistic regression analysis found that pre-treatment levels of HBV-DNA <5 log10 copies/mL, ALT levels >150 IU/L, an inflammation score >7, and a fibrosis score <2 were the strongest covariates independently associated with a sustained virologic response in both groups of patients. No adverse events were reported in any of the patients. Conclusion:ADV, administered in combination with LAM or as monotherapy, appeared to be effective in this small, selected group of HBeAg-negative patients with clinical or virologic resistance to LAM, especially in those with low pretreatment HBV-DNA levels, high ALT levels, and low fibrosis scores. [Copyright &y& Elsevier]

The article discusses a study on the relation of epicardial fat tissue and alanine aminotransferase (ALT) in patients with increased visceral fat. It notes that increased visceral adipose tissue (VAT) is a risk factor for an unfavorable cardio-metabolic profile and fatty liver. Based on the results, human immunodeficiency virus (HIV)-infected patients with metabolic syndrome (MS) showed higher magnetic resonance imaging (MRI)-VAT, waist circumference and epicardial fat thickness.

Background: Right-sided endocarditis occurs predominantly in intravenous drug users, in patients with pacemaker or central venous lines and in patients with congenital heart disease. The vast majority of cases involve the tricuspid valve. Eustachian valve endocarditis is an uncommon disease with similar signs and symptoms of the tricuspid valve endocarditis. A series of only 16 cases of eustachian valve endocarditis are reported in the literature. Case Presentation: We present a case of a 25-year old woman with intravenous drug abuse who had a staphylococcus aureus tricuspid valve endocarditis associated to eustachian valve endocarditis. Transthoracic echocardiography, as first line examination, showed the vegetations on tricuspid and eustachian valve. Conclusion: Our case describe an unusual location of right side endocarditis in a intravenous drug abuser. In our case, in accord with other cases described in the literature, transthoracic echocardiography disclosed eustachian valve endocarditis. Antimicrobial management is not altered by the recognition of eustachian valve endocarditis. Antibiotic treatment and duration of eustachian endocarditis depends on the isolated organism and is similar to antibiotic therapy used in native valve endocarditis. [ABSTRACT FROM AUTHOR]

Previous cases of pulmonary hypertension (PH) in human immunodeficiency virus (HIV) infection have been reported in the literature. The role of HIV in PH is still debatable. The purpose of this report was to analyze whether HIV plays a direct or indirect role in PH pathogenesis. Between February and November 1997, 56 HIV-infected patients with cardiac symptoms and signs were studied by serial color Doppler echocardiography. In four patients (7.1%), PH not related to other well-known associated conditions, was disclosed. In spite of a low serum HIV RNA viral load and a high-efficacy antiretroviral therapy, including a protease inhibitor in two patients, PH developed and worsened. It could be hypothesized that in some patients with an individual immunogenetic predisposition, a high secretion of cytokines and endothelin-1 stimulated by an unidentified pathogen different from HIV could lead to PH. Antiretroviral therapy seems not to prevent or reduce right ventricle pressure gradient in PH. [ABSTRACT FROM AUTHOR]

Patients infected with human immunodeficiency virus (HIV) are at increased risk for subclinical atherosclerosis. Whether increased cardiac adiposity may be related to HIV subclinical atherosclerosis is still unexplored. The objective of this study was to evaluate whether echocardiographically determined subepicardial adipose tissue, an index of cardiac adiposity, is related to carotid intima-media thickness (IMT), an index of subclinical atherosclerosis, in HIV-infected patients receiving highly active antiretroviral therapy. Echocardiographic epicardial fat thickness and ultrasonographic IMT were measured in 103 consecutive HIV-infected Caucasian subjects receiving highly active antiretroviral therapy. Echocardiographic subepicardial adipose tissue showed an excellent correlation with IMT (r = 0.92, p <0.01). Multiple regression analysis showed that IMT was best predicted by epicardial fat thickness (r2 = 0.81, p <0.01). In conclusion, this study suggests, for the first time, that epicardial adipose tissue, an index of cardiac adiposity, may be significantly related to subclinical atherosclerosis in HIV-infected patients. [Copyright &y& Elsevier]

Describes cases of Aspergillus endocarditis in injection drug users (IDU). Risk factors associated with the acquisition of invasive aspergillosis; Percentage of infections in IDU attributed to fungal infections; Association of Aspergillus endocarditis with HIV infection.