1,721,242 research outputs found
Ledipasvir/Sofosbuvir administration achieves very high rate of viral clearance in patients with HCV genotype 1 infection without cirrhosis, regardless of ribavirin co-administration or length of treatment
No full textTREATING CHRONIC HEPATITIS B: TODAY AND TOMORROW
No full textThree hundred and fifty million people worldwide are estimated to be chronically infected with hepatitis B virus. 15-40% of these subjects will develop cirrhosis, liver failure or hepatocellular carcinoma during their life. The treatment of chronic hepatitis B has improved dramatically over the last decade thanks to the advent of nucleoside/nucleotide analogues and the use of pegylated interferons. However, these agents have increased the complexity of the management of hepatitis B. Five drugs have been approved for chronic hepatitis B treatment: standard interferon-alpha 2b, pegylated interferon-alpha 2a, lamivudine, adefovir dipivoxil, and entecavir. A definite course of standard or pegylated interferon is administered to induce hepatitis B virus clearance. Unfortunately, these agents are not effective in all patients and are associated with not negligible side effects. Nucleoside or nucleotide analogues that inhibit hepatitis B virus polymerase induce on-treatment suppression of viral replication but patients tend to relapse after cessation of treatment. Consequently, these analogues, which are well tolerated, should be used for prolonged periods, even indefinitely. However, prolonged treatment is associated with a high rate of resistance. The following anti-hepatitis B virus drugs are currently undergoing clinical testing: telbivudine, emtricitabine, tenofovir disoproxil fumarate, clevudine and thymosin-+/-1. Here we will examine the mechanism of action, efficacy, safety, tolerability and emergence of resistance of agents used to treat chronic hepatitis B. We shall also examine the potential of drugs now being tested and of combination treatment
Surrogate endpoints and non-inferiority trials in chronic viral hepatitis.
No full textThe Authors comment on paper by Garattini S, Bertelè V. Ethics in clinical research. J Hepatol 2009;51:792–797 and particularly on their statement that ‘‘Quality of life, morbidity and mortality should always be the primary hard end-points for evaluating new drugs”. The authors believe that this rule should be applied with caution in the field of chronic viral hepatitis because of the slow progression of this disease and the availability of surrogate virological end-points. In fact a trial, comparing the effects of different drugs in the setting of HBV-related or HCV-related chronic hepatitis with survival as end-point, would be considered poorly ethical. Indeed, it would take several decades to demonstrate the superiority of one drug over another, and patients would be deprived of the best treatment strategy for a prolonged period. Obviously, toxicity and adverse events must be carefully monitored in trials with a surrogate endpoint. Moreover, the authors think that availability of multiple non-inferior drugs would give the physician a better opportunity to ‘‘customize” treatment for individual patients. Lastly, new non-inferior drugs with lower costs than previous drugs would be welcome.
In non-inferior trials, it is important that the margin of noninferiority is based on clinical grounds. In fact, using a wide margin of non-inferiority, a clearly inferior treatment would be considered non-inferior. In other words, a wide non-inferiority
margin does not allow us to translate into the clinical setting
what is ‘‘non-inferior” from a statistical point of view
Efficacy and tolerability of switching to a dual therapy with darunavir/ritonavir plus raltegravir in HIV-infected patients with HIV-1 RNA ≤50 cp/mL
No full textWhat is the role of the new β-lactam/β-lactamase inhibitors ceftolozane/tazobactam and ceftazidime/avibactam?
No full textOmbitasvir: a potent pan-genotypic inhibitor of NS5A for the treatment of hepatitis C virus infection.
No full textHepatitis C virus (HCV) chronically infects about 150,000,000 people worldwide and is a relevant cause of liver cirrhosis, hepatocellular carcinoma and death. Antiviral treatment is rapidly moving from interferon (IFN)-based therapy to IFN-free approaches. This review focuses on the mechanism of action, pharmacokinetics, efficacy, tolerability, safety and resistance of ombitasvir, which is an inhibitor of the HCV nonstructural protein 5A. The pharmacokinetics of ombitasvir enables its once daily administration. In vivo, in combinations with other oral direct acting antivirals, ombitasvir achieves very high rates of sustained virological response (about 95\%) in patients with HCV genotype 1 infection with a good tolerability. Resistance profiling revealed a low barrier to resistance when given as monotherapy. However, coadministration of ombitasvir and other antivirals enhances its barrier to resistance. In conclusion, ombitasvir is a good drug to be used in IFN-free combinations for the treatment of chronic hepatitis C
Current concepts and future strategies in the antimicrobial therapy of emerging Gram-positive spontaneous bacterial peritonitis
No full textIncidence of cerebral venous thrombosis and COVID-19 vaccination: possible causal effect or just chance?
No full textVertical transmission of hepatitis B virus: challenges and solutions
No full textIvan Gentile, Guglielmo BorgiaDepartment of Clinical Medicine and Surgery, University of Naples “Federico II”, Naples, ItalyAbstract: More than 240 million people worldwide are chronically infected with hepatitis B virus (HBV). Mother-to-child transmission remains the most important mechanism of infection in countries with a high prevalence of HBV. Universal screening of all pregnant women, at-birth prophylaxis with specific anti-HBV immune globulin, as well as HBV vaccination for newborns of infected mothers are effective in reducing the risk of vertical transmission. However, in cases of a high viral load and hepatitis B e antigen positivity, there is a residual risk of HBV transmission to the newborn despite prophylaxis. This review focuses on the above-indicated strategies and on the efficacy and safety of antiviral drugs administered during the third trimester of pregnancy.Keywords: immune globulin, prophylaxis, telbuvidine, tenofovir, vaccine, viral loa
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