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Myocarditis
Published in Mary N. Sheppard, Practical Cardiovascular Pathology, 2022
Hepatitis C virus (HCV) is seen more frequently in patients with myocarditis and DCM especially in Japan. The fact that worldwide more than 70 million patients are chronically infected with HCV illustrates the possible clinical impact arising if cardiomyopathies were induced or aggravated by HCV. A novel path has been opened by the recent development of interferon-free, highly efficient and well tolerable anti-HCV regimens. The new direct-acting antiviral (DAA) agents are highly virus-specific and lack unspecific side effects upon cardiac function which have always confounded the interpretation of interferon treatment data.
Hepatic disorders in pregnancy
Published in Hung N. Winn, Frank A. Chervenak, Roberto Romero, Clinical Maternal-Fetal Medicine Online, 2021
Ghassan M. Hammoud, Jamal A. Ibdah
The currently recommended therapy of chronic HCV infection in nonpregnant patients is the combination of a pegylated interferon-alfa and ribavirin. This regimen has been shown to be effective in 40% to 70% of patients (30–32). In mid 2011, two new direct-acting antiviral agents have been approved in combination with pegylated interferon and ribavirin for hepatitis C therapy in non-pregnant genotype 1 patients. HCV treatment success is measured by sustained virologic response (SVR) (defined as undetectable HCV RNA by a sensitive assay 6 months following discontinuation of treatment). Interferon is classified by the FDA as a category C drug while ribavirin is a category X product, indicating that its use is contraindicated in women who are pregnant. Interferon monotherapy is far less effective than combined therapy with ribavirin and is associated with low SVR rates, and hence the risk of HCV therapy outweighs its benefit during pregnancy.
Adverse Reactions to Antibiotics in the Critical Care Unit
Published in Cheston B. Cunha, Burke A. Cunha, Infectious Diseases and Antimicrobial Stewardship in Critical Care Medicine, 2020
Diane M. Parente, Cheston B. Cunha, Michael Lorenzo
The “To Err Is Human” report published in 1999 shed light on the alarming frequency of avoidable medical errors, and since its publication, significant efforts have been undertaken to improve the safety of patient care by reducing medications errors [4]. While some anti-infective-associated adverse events can be the result of a medication error (e.g., acute renal failure due to a patient receiving colistin dosing based on colistin base when the intended dose was based on the salt colistimethate sodium), the unavoidable necessity of anti-infective use in the CCU represents a significant challenge in assuring patient safety, as adverse events may be present even in the most vigilant monitoring and risk mitigation strategies. For this reason, it behooves clinicians in the CCU setting to be familiar with common anti-infective adverse events and be able to recognize such events in a timely manner to avoid undue patient harm [5,6]. The following chapter includes a summary of adverse events seen with anti-infectives commonly utilized in the adult critical care arena. Discussions of adverse events secondary to anti-retrovirals and direct acting antivirals used to treat the human immunodeficiency virus and viral hepatitis are excluded. Similarly, anti-infectives that are unlikely to be used in critically ill patients (e.g., nitrofurantoin and oral cephalosporins) and those unavailable in the US market are excluded. Some of the work included in this chapter is adapted from the work of Granowitz and Brown [7].
Effectiveness of hepatitis C antiviral treatment and feasibility of hepatitis C elimination goal
Published in Postgraduate Medicine, 2023
Cristina Burgui, Ramón San Miguel, Silvia Goñi-Esarte, Regina Juanbeltz, Juan Isidro Úriz-Otano, Jesús Reparaz, Maite Sarobe, José Manuel Zozaya, Jesús Castilla
Previous treatments with interferon had limited efficacy and frequent side effects [12]. In 2011, first-generation direct-acting antivirals improved the efficacy, but still with significant adverse effects [13]. However, since 2013 highly effective and safe second-generation direct-acting antivirals (DAAs) have markedly changed the landscape of treatment of HCV infection. DAAs are combinations of two or more HCV antiviral drugs such as simeprevir, sofosbuvir, ledipasvir, daclatasvir, ombitasvir, paritaprevir, ritonavir, dasabuvir, elbasvir, grazoprevir, glecaprevir, pibrentasvir, velpatasvir and voxilaprevir, with or without ribavirin. The first clinical trials demonstrated efficacies above 90% in achieving SVR [14–22], and effectiveness estimates were even better in further observational studies [23–25].
Challenges with the discovery of RNA-based therapeutics for flaviviruses
Published in Expert Opinion on Drug Discovery, 2023
Mei-Yue Wang, Rong Zhao, Yu-Lan Wang, De-Ping Wang, Ji-Min Cao
In the last two decades of the 21st century, there have been several viral outbreaks caused by flavivirus family members, posing a great threat to public health worldwide [1]. To date, flaviviruses are still spreading worldwide, leading to the loss of human lives and economic damage. Flaviviruses are positive-sense, single-stranded RNA viruses, including Dengue virus (DENV), Zika virus (ZIKV), West Nile virus (WNV), tick-borne encephalitis virus (TBEV), and Japanese encephalitis virus (JEV). The translation of viral RNA generates a polyprotein that is cleaved into seven non-structural proteins (NS1, NS2A, NS2B, NS3, NS4A, NS4B, and NS5) and three structural proteins, namely the capsid (C), envelope (E), and pre-membrane/membrane (prM/M) proteins (Figure 1) [2–4]. The key steps in the viral life cycle, including viral entry, endocytosis or trafficking, viral uncoating, replication, transcription, translation, and viral particle assembly, represent potential therapeutic targets [5]. There are two fundamental types of antiviral therapeutics: direct-acting antivirals that target the virus itself and host-factor antivirals that target critical segments of the host cell [6].
Chronic hepatitis C: Diagnosis and treatment made easy
Published in European Journal of General Practice, 2022
Naim Abu-Freha, Binil Mathew Jacob, Ali Elhoashla, Zaid Afawi, Talab Abu-Hammad, Foad Elsana, Sergey Paz, Ohad Etzion
In the highly effective direct-acting antivirals (DAA) treatment era, the diagnosis and treatment process has become short and simple. Although in the past, various pre-treatment requirements were needed, followed by several visits to the hepatologist or gastroenterologist to establish definitive diagnosis, today the decision-making process has become less laborious. The important parts of the process include screening and linkage to treatment, meaning any patient with risk factors for HCV should be screened; if HCV antibodies are positive, then reflex testing for HCV RNA should be performed. Genotype testing is no longer needed in most countries due to the availability of pan-genotypic treatment. In most individuals, the Fib-4 calculator or APRI index can be used for fibrosis assessment and only among patients suspected to have advanced fibrosis or high Fib-4 score would any additional fibrosis assessment (fibroscan or fibrotest) be performed. After treatment with DAAs, additional HCV RNA test for 12 weeks after treatment is needed to confirm sustained viral response (SVR). Patients with advanced fibrosis, relapses or comorbidities should be treated and followed in a liver clinic. In cases of cirrhosis, hepatic carcinoma screening is required. Screening, diagnosis and treatment of HCV made easy and summarized in Figure 1.