Natalie Bzowej

Bio: Natalie Bzowej is an academic researcher from Ochsner Medical Center. The author has contributed to research in topics: Hepatitis B & Telbivudine. The author has an hindex of 32, co-authored 76 publications receiving 10291 citations. Previous affiliations of Natalie Bzowej include Harvard University & California Pacific Medical Center.

Telaprevir for Previously Untreated Chronic Hepatitis C Virus Infection

Abstract: A B S T R AC T Background In phase 2 trials, telaprevir, a hepatitis C virus (HCV) genotype 1 protease inhibitor, in combination with peginterferon–ribavirin, as compared with peginterferon–ribavirin alone, has shown improved efficacy, with potential for shortening the duration of treatment in a majority of patients. Methods In this international, phase 3, randomized, double-blind, placebo-controlled trial, we assigned 1088 patients with HCV genotype 1 infection who had not received previous treatment for the infection to one of three groups: a group receiving telaprevir combined with peginterferon alfa-2a and ribavirin for 12 weeks (T12PR group), followed by peginterferon–ribavirin alone for 12 weeks if HCV RNA was undetectable at weeks 4 and 12 or for 36 weeks if HCV RNA was detectable at either time point; a group receiving telaprevir with peginterferon–ribavirin for 8 weeks and placebo with peginterferon–ribavirin for 4 weeks (T8PR group), followed by 12 or 36 weeks of peginterferon–ribavirin on the basis of the same HCV RNA criteria; or a group receiving placebo with peginterferon–ribavirin for 12 weeks, followed by 36 weeks of peginterferon–ribavirin (PR group). The primary end point was the proportion of patients who had undetectable plasma HCV RNA 24 weeks after the last planned dose of study treatment (sustained virologic response). Results Significantly more patients in the T12PR or T8PR group than in the PR group had a sustained virologic response (75% and 69%, respectively, vs. 44%; P<0.001 for the comparison of the T12PR or T8PR group with the PR group). A total of 58% of the patients treated with telaprevir were eligible to receive 24 weeks of total treatment. Anemia, gastrointestinal side effects, and skin rashes occurred at a higher incidence among patients receiving telaprevir than among those receiving peginterferon–ribavirin alone. The overall rate of discontinuation of the treatment regimen owing to adverse events was 10% in the T12PR and T8PR groups and 7% in the PR group. Conclusions Telaprevir with peginterferon–ribavirin, as compared with peginterferon–ribavirin alone, was associated with significantly improved rates of sustained virologic response in patients with HCV genotype 1 infection who had not received previous treatment, with only 24 weeks of therapy administered in the majority of patients. (Funded by Vertex Pharmaceuticals and Tibotec; ADVANCE ClinicalTrials.gov number, NCT00627926.)

Telbivudine versus lamivudine in patients with chronic hepatitis B.

Abstract: Background Reducing hepatitis B virus (HBV) replication to minimal levels is emerging as a key therapeutic goal for chronic hepatitis B. Methods In this double-blind, phase 3 trial, 1370 patients with chronic hepatitis B were randomly assigned to receive 600 mg of telbivudine or 100 mg of lamivudine once daily. The primary efficacy end point was noninferiority of telbivudine to lamivudine for therapeutic response (i.e., a reduction in serum HBV DNA levels to fewer than 5 log10 copies per milliliter, along with loss of hepatitis B e antigen [HBeAg] or normalization of alanine aminotransferase levels). Secondary efficacy measures included histologic response, changes in serum HBV DNA levels, and HBeAg responses. Results At week 52, a significantly higher proportion of HBeAg-positive patients receiving telbivudine than of those receiving lamivudine had a therapeutic response (75.3% vs. 67.0%, P=0.005) or a histologic response (64.7% vs. 56.3%, P=0.01); telbivudine also was not inferior to lamivudine for thes...

Sofosbuvir and velpatasvir for HCV in patients with decompensated cirrhosis

Abstract: BackgroundAs the population that is infected with the hepatitis C virus (HCV) ages, the number of patients with decompensated cirrhosis is expected to increase. MethodsWe conducted a phase 3, open-label study involving both previously treated and previously untreated patients infected with HCV genotypes 1 through 6 who had decompensated cirrhosis (classified as Child–Pugh–Turcotte class B). Patients were randomly assigned in a 1:1:1 ratio to receive the nucleotide polymerase inhibitor sofosbuvir and the NS5A inhibitor velpatasvir once daily for 12 weeks, sofosbuvir–velpatasvir plus ribavirin for 12 weeks, or sofosbuvir–velpatasvir for 24 weeks. The primary end point was a sustained virologic response at 12 weeks after the end of therapy. ResultsOf the 267 patients who received treatment, 78% had HCV genotype 1, 4% genotype 2, 15% genotype 3, 3% genotype 4, and less than 1% genotype 6; no patients had genotype 5. Overall rates of sustained virologic response were 83% (95% confidence interval [CI], 74 to 90...

Cellular and molecular mechanisms of fibrosis.

Abstract: Fibrosis is defined by the overgrowth, hardening, and/or scarring of various tissues and is attributed to excess deposition of extracellular matrix components including collagen. Fibrosis is the end result of chronic inflammatory reactions induced by a variety of stimuli including persistent infections, autoimmune reactions, allergic responses, chemical insults, radiation, and tissue injury. Although current treatments for fibrotic diseases such as idiopathic pulmonary fibrosis, liver cirrhosis, systemic sclerosis, progressive kidney disease, and cardiovascular fibrosis typically target the inflammatory response, there is accumulating evidence that the mechanisms driving fibrogenesis are distinct from those regulating inflammation. In fact, some studies have suggested that ongoing inflammation is needed to reverse established and progressive fibrosis. The key cellular mediator of fibrosis is the myofibroblast, which when activated serves as the primary collagen-producing cell. Myofibroblasts are generated from a variety of sources including resident mesenchymal cells, epithelial and endothelial cells in processes termed epithelial/endothelial-mesenchymal (EMT/EndMT) transition, as well as from circulating fibroblast-like cells called fibrocytes that are derived from bone-marrow stem cells. Myofibroblasts are activated by a variety of mechanisms, including paracrine signals derived from lymphocytes and macrophages, autocrine factors secreted by myofibroblasts, and pathogen-associated molecular patterns (PAMPS) produced by pathogenic organisms that interact with pattern recognition receptors (i.e. TLRs) on fibroblasts. Cytokines (IL-13, IL-21, TGF-beta1), chemokines (MCP-1, MIP-1beta), angiogenic factors (VEGF), growth factors (PDGF), peroxisome proliferator-activated receptors (PPARs), acute phase proteins (SAP), caspases, and components of the renin-angiotensin-aldosterone system (ANG II) have been identified as important regulators of fibrosis and are being investigated as potential targets of antifibrotic drugs. This review explores our current understanding of the cellular and molecular mechanisms of fibrogenesis.