Hepatitis C virus in the new era:Perspectives in epidemiology,prevention,diagnostics and predictors of response to therapy

Despite the great successes achieved in the fields of virology and diagnostics,several difficulties affect improvements in hepatitis C virus(HCV)infection control and eradication in the new era.New HCV infections still occur,especially in some of the poorest regions of the world,where HCV is endemic and long-term sequelae have a growing economic and health burden.An HCV vaccine is still no available,despite years of researches and discoveries about the natural history of infection and host-virus interactions:several HCV vaccine candidates have been developed in the last years,targeting different HCV antigens or using alternative delivery systems,but viral variability and adaption ability constitute major challenges for vaccine development.Many new antiviral drugs for HCV therapy are in preclinical or early clinical development,but different limitations affect treatment validity.Treatment predictors are important tools,as they provide some guidance for the management of therapy in patients with chronic HCV infection:in particular,the role of host genomics in HCV infection outcomes in the new era of direct-acting antivirals may evolve for new therapeutic targets,representing a chance for modulated and personalized treatment management,when also very potent therapies will be available.In the present review we discuss the most recent data about HCV epidemiology,the new perspectives for the prevention of HCV infection and the most recent evidence regarding HCV diagnosis,therapy and predictors of response to it.

Deep brain stimulation for obsessive-compulsive disorder:A systematic review of worldwide experience after 20 years

BACKGROUND Twenty years after its first use in a patient with obsessive-compulsive disorder(OCD),the results confirm that deep brain stimulation(DBS)is a promising therapy for patients with severe and resistant forms of the disorder.Nevertheless,many unknowns remain,including the optimal anatomical targets,the best stimulation parameters,the long-term(LT)effects of the therapy,and the clinical or biological factors associated with response.This systematic review of the articles published to date on DBS for OCD assesses the short and LT efficacy of the therapy and seeks to identify predictors of response.AIM To summarize the existing knowledge on the efficacy and tolerability of DBS in treatment-resistant OCD.METHODS A comprehensive search was conducted in the PubMed,Cochrane,Scopus,and ClinicalTrials.gov databases from inception to December 31,2020,using the following strategy:“(Obsessive-compulsive disorder OR OCD)AND(deep brain stimulation OR DBS).”Clinical trials and observational studies published in English and evaluating the effectiveness of DBS for OCD in humans were included and screened for relevant information using a standardized collection tool.The inclusion criteria were as follows:a main diagnosis of OCD,DBS conducted for therapeutic purposes and variation in symptoms of OCD measured by the Yale-Brown Obsessive-Compulsive scale(Y-BOCS)as primary outcome.Data were analyzed with descriptive statistics.RESULTS Forty articles identified by the search strategy met the eligibility criteria.Applying a follow-up threshold of 36 mo,29 studies(with 230 patients)provided information on short-term(ST)response to DBS in,while 11(with 155 patients)reported results on LT response.Mean follow-up period was 18.5±8.0 mo for the ST studies and 63.7±20.7 mo for the LT studies.Overall,the percentage of reduction in Y-BOCS scores was similar in ST(47.4%)and LT responses(47.2%)to DBS,but more patients in the LT reports met the criteria for response(defined as a reduction in Y-BOCS scores>35%:ST,60.6%vs LT,70.7%).According to the results,the response in the first year predicts the extent to which an OCD patient will benefit from DBS,since the maximum symptom reduction was achieved in most responders in the first 12-14 mo after implantation.Reports indicate a consistent tendency for this early improvement to be maintained to the mid-term for most patients;but it is still controversial whether this improvement persists,increases or decreases in the long term.Three different patterns of LT response emerged from the analysis:49.5% of patients had good and sustained response to DBS,26.6% were non responders,and 22.5% were partial responders,who might improve at some point but experience relapses during follow-up.A significant improvement in depressive symptoms and global functionality was observed in most studies,usually(although not always)in parallel with an improvement in obsessive symptoms.Most adverse effects of DBS were mild and transient and improved after adjusting stimulation parameters;however,some severe adverse events including intracranial hemorrhages and infections were also described.Hypomania was the most frequently reported psychiatric side effect.The relationship between DBS and suicide risk is still controversial and requires further study.Finally,to date,no clear clinical or biological predictors of response can be established,probably because of the differences between studies in terms of the neuroanatomical targets and stimulation protocols assessed.CONCLUSION The present review confirms that DBS is a promising therapy for patients with severe resistant OCD,providing both ST and LT evidence of efficacy.