Antiviral activity of bone morphogenetic proteins and activins.

Understanding the control of viral infections is of broad importance. Chronic hepatitis C virus (HCV) infection causes decreased expression of the iron hormone hepcidin, which is regulated by hepatic bone morphogenetic protein (BMP)/SMAD signalling. We found that HCV infection and the BMP/SMAD pathway are mutually antagonistic.

Corrigendum: Conformational rearrangements in the transmembrane domain of CNGA1 channels revealed by single-molecule force spectroscopy.

This corrects the article DOI: 10.1038/ncomms8093.

Acute hepatitis E virus infection in a migrant population in North East Italy: A retrospective analysis.

Objective: To study the epidemiological and clinical features of Hepatitis E Virus (HEV) infection in a migrant population.

Methods: We performed a retrospective chart review, identifying a cohort of 21 symptomatic patients of migrant origin with confirmed HEV infection admitted in the period between January 1995-November 2014.

Results: 20 (95%) patients came from South Asian countries highly endemic for HEV, all positive for HEV genotype 1.

Interferon-free antiviral treatment in B-cell lymphoproliferative disorders associated with hepatitis C virus infection.

Regression of hepatitis C virus (HCV)-associated lymphoma with interferon (IFN)-based antiviral treatment supports an etiological link between lymphoma and HCV infection. In addition, a favorable impact of antiviral treatment on overall survival of patients with HCV-related lymphoma has been reported. Data on IFN-free regimens combining direct-acting antivirals (DAAs) in HCV-associated lymphoproliferative disorders are scanty.

MAIT cells are activated during human viral infections.

Mucosal-associated invariant T (MAIT) cells are abundant in humans and recognize bacterial ligands. Here, we demonstrate that MAIT cells are also activated during human viral infections in vivo. MAIT cells activation was observed during infection with dengue virus, hepatitis C virus and influenza virus.

The Role of Rac1 in the Growth Cone Dynamics and Force Generation of DRG Neurons.

We used optical tweezers, video imaging, immunocytochemistry and a variety of inhibitors to analyze the role of Rac1 in the motility and force generation of lamellipodia and filopodia from developing growth cones of isolated Dorsal Root Ganglia neurons. When the activity of Rac1 was inhibited by the drug EHop-016, the period of lamellipodia protrusion/retraction cycles increased and the lamellipodia retrograde flow rate decreased; moreover, the axial force exerted by lamellipodia was reduced dramatically. Inhibition of Arp2/3 by a moderate amount of the drug CK-548 caused a transient retraction of lamellipodia followed by a complete recovery of their usual motility.

Conformational rearrangements in the transmembrane domain of CNGA1 channels revealed by single-molecule force spectroscopy.

Cyclic nucleotide-gated (CNG) channels are activated by binding of cyclic nucleotides. Although structural studies have identified the channel pore and selectivity filter, conformation changes associated with gating remain poorly understood. Here we combine single-molecule force spectroscopy (SMFS) with mutagenesis, bioinformatics and electrophysiology to study conformational changes associated with gating.

The role of myosin-II in force generation of DRG filopodia and lamellipodia.

Differentiating neurons process the mechanical stimulus by exerting the protrusive forces through lamellipodia and filopodia. We used optical tweezers, video imaging and immunocytochemistry to analyze the role of non-muscle myosin-II on the protrusive force exerted by lamellipodia and filopodia from developing growth cones (GCs) of isolated Dorsal Root Ganglia (DRG) neurons. When the activity of myosin-II was inhibited by 30 μM Blebbistatin protrusion/retraction cycles of lamellipodia slowed down and during retraction lamellipodia could not lift up axially as in control condition.

Acute hepatitis C: a 24-week course of pegylated interferon α-2b versus a 12-week course of pegylated interferon α-2b alone or with ribavirin.

Unlabelled: Therapy of acute hepatitis C (AHC) has not yet been standardized and several issues are still unresolved. This open, randomized, multicenter trial aimed to assess the efficacy and safety of a 24-week course of pegylated IFN (Peg-IFN) alpha-2b versus a 12-week course of Peg-IFN alpha-2b alone or with ribavirin (RBV) in AHC patients. One hundred and thirty HCV acutely infected patients who did not spontaneously resolve by week 12 after onset were consecutively enrolled and randomized to receive Peg-IFN alpha-2b monotherapy (1.

Therapy of chronic hepatitis C with PEG-IFN α-2b plus ribavirin in patients with genotype 2 or 3: 16 versus 24 weeks, clinical outcome and direct cost analyses.

Introduction: Short antiviral therapy has been proposed for patients with chronic hepatitis C, easy genotypes, low fibrosis score, low viral load at baseline, and rapid virological response (RVR). However, this approach is not completely accepted.

Objectives: The aims of this study were (a) to evaluate the sustained virological response (SVR) in noncirrhotic patients with genotype 2 or 3, achieving an RVR, randomized to receive pegylated-interferon (IFN) α-2b plus ribavirin for either 16 or 24 weeks and (b) to carry out direct cost analysis comparing patients treated for 16 versus 24 weeks.

Snail1 transcription factor is a critical mediator of hepatic stellate cell activation following hepatic injury.

Following liver injury, the wound-healing process is characterized by hepatic stellate cell (HSC) activation from the quiescent fat-storing phenotype to a highly proliferative myofibroblast-like phenotype. Snail1 is a transcription factor best known for its ability to trigger epithelial-mesenchymal transition, to influence mesoderm formation during embryonic development, and to favor cell survival. In this study, we evaluated the expression of Snail1 in experimental and human liver fibrosis and analyzed its role in the HSC transdifferentiation process.

Full-length characterization of hepatitis C virus subtype 3a reveals novel hypervariable regions under positive selection during acute infection.

Hepatitis C virus subtype 3a is a highly prevalent and globally distributed strain that is often associated with infection via injection drug use. This subtype exhibits particular phenotypic characteristics. In spite of this, detailed genetic analysis of this subtype has rarely been performed.

Insulin resistance predicts rapid virological response in non-diabetic, non-cirrhotic genotype 1 HCV patients treated with peginterferon alpha-2b plus ribavirin.

Background/aims: The rapid decline in hepatitis C virus RNA is crucial for determining the outcome of therapy in patients with genotype 1 chronic hepatitis C. However, the variables influencing the early phase of viral decay are still largely unexplored. We aimed to assess which pre-treatment variable may predict rapid virologic response (RVR) and sustained virologic response (SVR).

Impact of occult HBV infection in HIV/HCV co-infected patients: HBV-DNA detection in liver specimens and in serum samples.

Prevalence and impact of occult HBV infection in HIV positive patients is controversial. The aims of this study were to determine the prevalence of occult HBV infection and its impact on histological and virological parameters. 52 HIV/HCV (but HBsAg-negative) co-infected patients, 29 HBsAg and anti-HCV negative chronic hepatitis, and 20 HBsAg positive chronic hepatitis controls were studied.

Changing epidemiology of HCV and HBV infections in Northern Italy: a survey in the general population.

Aim: To evaluate the hepatitis B virus (HBV) and the hepatitis C virus (HCV) epidemiology in the general population of Northern Italy, a cohort of 965 subjects, all residents (including 47 immigrants), were anonymously tested for HBV and HCV infections.

Material And Methods: Serum samples were assayed for anti-HCV and anti-HBV markers by enzyme-linked immunosorbent assay and for HCV-RNA by polymerase chain reaction, and the positive cases were genotyped. HBsAg-positive cases were assayed for HBeAg/anti-HBe, whereas HBsAg negatives were tested for both anti-HBc and anti-HBs.

Lack of higher frequency of the chemokine receptor 5-delta32/delta32 genotype in hepatitis C.

Purpose: An elevated frequency of the CCR5-Delta32 mutation in German patients with hepatitis C with viremia has been reported. The aim of the present study was to verify whether this mutation occurs in an Italian population with hepatitis C and whether it is an adverse host factor indicative of severity of liver disease and response to antiviral therapy.

Study: The authors amplified 189-bp (wild-type) and 157-bp (Delta32 deletion) fragments of the CCR5 gene by polymerase chain reaction in 130 patients with chronic hepatitis C.

Onset of type 1 diabetes mellitus during peginterferon alpha-2b plus ribavirin treatment for chronic hepatitis C.

A 61-year-old man was observed to develop type 1 diabetes mellitus following a 3-month treatment with recombinant alpha-2b peginterferon combined with ribavirin for chronic hepatitis C. Serum samples, collected before the start of therapy and 2 months after the diagnosis of diabetes mellitus, revealed islet-cell antibodies at a titer of 20 and 40 JDF-U, respectively, and glutamic acid decarboxylase autoantibodies at a value of 76.5 and 196 IU/ml, respectively.

Relationship between steatosis, inflammation, and fibrosis in chronic hepatitis C: a meta-analysis of individual patient data.

Background & Aims: Steatosis is a frequent histologic finding in chronic hepatitis C (CHC), but it is unclear whether steatosis is an independent predictor for liver fibrosis. We evaluated the association between steatosis and fibrosis and their common correlates in persons with CHC and in subgroup analyses according to hepatitis C virus (HCV) genotype and body mass index.

Methods: We conducted a meta-analysis on individual data from 3068 patients with histologically confirmed CHC recruited from 10 clinical centers in Italy, Switzerland, France, Australia, and the United States.

Clinical pharmacokinetics of nelfinavir and its metabolite M8 in human immunodeficiency virus (HIV)-positive and HIV-hepatitis C virus-coinfected subjects.

In order to evaluate the potential risk of nelfinavir (NFV) accumulation in human immunodeficiency virus (HIV)-hepatitis C virus (HCV)-coinfected patients with liver disease, we investigated the concentrations of NFV and M8, the active metabolite of NFV, in plasma HIV-positive (HIV+) patients coinfected with HCV. A total of 119 HIV+ subjects were included in our study: 67 HIV+ patients, 32 HIV+ and HCV-positive (HCV+) patients without cirrhosis, and 20 HIV+ and HCV+ patients with cirrhosis. Most of the enrolled patients (chronically treated) were taking NFV at the standard dosage of 1,250 mg twice a day.

Alcohol is an important co-factor for both steatosis and fibrosis in Northern Italian patients with chronic hepatitis C.

Background/aims: Steatosis in patients with chronic hepatitis C (CHC) may be the result of both viral and host factors. To evaluate: (1) the relationship between steatosis and either host or viral factors; (2) the correlation between steatosis and fibrosis in patients with CHC.

Methods: A consecutive series of 349 patients were evaluated for steatosis.

Occult hepatitis B virus infection does not affect liver histology or response to therapy with interferon alpha and ribavirin in intravenous drug users with chronic hepatitis C.

Background: the frequency and the impact of occult HBV infection in patients with chronic hepatitis C infection is still a matter of some controversy.

Objectives: our aim was to evaluate the prevalence of occult HBV infection and assess its impact on liver biochemistry, HCV viral titre, liver histology and on outcome of therapy in patients with chronic hepatitis C.

Study Design: paired liver biopsies and serum samples were collected from 51 patients (84% IVDUS) with HBsAg negative chronic hepatitis C, and tested for HBV-DNA with nested PCR.