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1.
Emerg Microbes Infect ; 11(1): 1664-1671, 2022 Dec.
Article in English | MEDLINE | ID: covidwho-1978179

ABSTRACT

To reach the WHO target of hepatitis C virus (HCV) elimination by 2025, Taiwan started to implement free-of-charge direct-acting antiviral (DAA) treatment programme in 2017. Evaluating the progress of HCV microelimination among people living with HIV (PLWH) is a critical step to identify the barriers to HCV elimination. PLWH seeking care at a major hospital designated for HIV care in Taiwan between January 2011 and December 2021 were retrospectively included. For PLWH with HCV-seropositive or HCV seroconversion during the study period, serial HCV RNA testing was performed using archived samples to confirm the presence of HCV viremia and estimate the prevalence and incidence of HCV viremia. Overall, 4199 PLWH contributed to a total of 27,258.75 person-years of follow-up (PYFU). With the reimbursement of DAAs and improvement of access to treatments, the prevalence of HCV viremia has declined from its peak of 6.21% (95% CI, 5.39-7.12%) in 2018 to 2.09% (95% CI, 1.60-2.77%) in 2021 (decline by 66.4% [95% CI, 55.4-74.7%]); the incidence has declined from 25.94 per 1000 PYFU (95% CI, 20.44-32.47) in 2019 to 12.15% per 1000 PYFU (95% CI, 8.14-17.44) (decline by 53.2% [95% CI, 27.3-70.6%]). However, the proportion of HCV reinfections continued to increase and accounted for 82.8% of incident HCV infections in 2021. We observed significant declines of HCV viremia among PLWH with the expansion of the DAA treatment programme in Taiwan. Further improvement of the access to DAA retreatments is warranted to achieve the goal of HCV microelimination.


Subject(s)
HIV Infections , Hepatitis C, Chronic , Hepatitis C , Antiviral Agents/therapeutic use , HIV Infections/drug therapy , HIV Infections/epidemiology , Hepacivirus/genetics , Hepatitis C/drug therapy , Hepatitis C/epidemiology , Hepatitis C, Chronic/drug therapy , Humans , Retrospective Studies , Taiwan/epidemiology , Viremia/drug therapy , Viremia/epidemiology
2.
Viruses ; 14(8)2022 07 27.
Article in English | MEDLINE | ID: covidwho-1957460

ABSTRACT

Although hepatitis C virus (HCV) prevails in patients receiving methadone maintenance treatment (MMT), most do not receive anti-HCV therapy. This single-center observational study aimed to achieve HCV micro-elimination at an MMT center during the COVID-19 pandemic using a collaborative referral model, which comprised a referral-for-diagnosis stage (January 2020 to August 2020) and an on-site-diagnosis stage (September 2020 to January 2021). A multidisciplinary team was established and all MMT center patients were enrolled. HCV micro-elimination was defined as >90% of HCV-infected patients diagnosed and >80% of HCV-viremic patients treated. A total of 305 MMT patients, including 275 (90.2%) anti-HCV seropositive patients, were enrolled. Among 189 HCV-infected patients needing referral, the accumulative percentage receiving HCV RNA testing increased from 93 (49.2%) at referral-for-diagnosis stage to 168 (88.9%) at on-site-diagnosis stage. Among 138 HCV-viremic patients, the accumulative percentage receiving direct-acting antiviral (DAA) therapy increased from 77 (55.8%) at referral-for-diagnosis stage to 129 (93.5%) at on-site-diagnosis stage. We achieved an HCV RNA testing rate of 92.4% (254/275), an HCV treatment rate of 95.8% (203/212) and a sustained virological response rate of 94.1% (191/203). The collaborative referral model is highly effective in HCV RNA testing and HCV treatment uptake among MMT patients, achieving HCV micro-elimination.


Subject(s)
COVID-19 , Hepatitis C, Chronic , Hepatitis C , Antiviral Agents/therapeutic use , COVID-19/drug therapy , COVID-19/epidemiology , Hepacivirus/genetics , Hepatitis C/drug therapy , Hepatitis C/epidemiology , Hepatitis C, Chronic/drug therapy , Humans , Methadone/therapeutic use , Pandemics , RNA , Referral and Consultation
3.
Clin Microbiol Infect ; 28(4): 611.e1-611.e7, 2022 Apr.
Article in English | MEDLINE | ID: covidwho-1828108

ABSTRACT

OBJECTIVES: Chronic hepatitis C virus (HCV) infection affects the immune system. Whether elimination of HCV with direct-acting antivirals (DAA) restores immunity is unclear. We used mass cytometry to get a broad and in-depth assessment of blood cell populations of patients with chronic HCV before and after DAA therapy. METHODS: Before and 12 weeks after sustained virological response (SVR12) to DAA therapy, 22 cell populations were analysed by mass cytometry in blood collected from ten healthy control individuals and 20 HCV-infected patients with (ten patients) or without (ten patients) human immunodeficiency virus (HIV) infection. RESULTS: HCV infection altered the frequency of 14/22 (64%) blood cell populations. At baseline, the frequencies (median, interquartile range (IQR); control, HCV, HCV/HIV) of intermediate monocytes (1.2, IQR 0.47-1.46; 1.76, IQR 0.83-2.66; 0.78, IQR 0.28-1.77), non-classical monocytes (1.11, IQR 0.49-1.26; 0.9, IQR 0.18-0.99; 0.54, IQR 0.28-1.77), conventional dendritic cells type 2 (0.55, IQR 0.35-0.59; 0.31, IQR 0.16-0.38; 0.19, IQR 0.11-0.36) and CD56dim natural killer cells (8.08, IQR 5.34-9.79; 4.72, IQR 2.59-6.05) 3.61, IQR 2.98-5.07) were reduced by 35% to 65%, particularly in HCV/HIV co-infected patients. In contrast, activated double-negative T cells (0.07, IQR 0.06-0.10; 0.10, IQR 0.09-0.19; 0.19, IQR 0.12-0.25), activated CD4 T cells (0.28, IQR 0.21-0.36; 0.56, IQR 0.33-0.77; 0.40, IQR 0.22-0.53) and activated CD8 T cells (0.23, IQR 0.14-0.42; 0.74, IQR 0.30-1.65; 0.80, IQR 0.58-1.16) were increased 1.4 to 3.5 times. Upon stimulation with Toll-like receptor ligands, the expression of cytokines was up-regulated in 7/9 (78%) and 17/19 (89%) of the conditions in HCV- and HCV/HIV-infected patients, respectively. Most alterations persisted at SVR12. CONCLUSIONS: Chronic HCV and HCV/HIV infections induce profound and durable perturbations of innate and adaptive immune homeostasis.


Subject(s)
HIV Infections , Hepatitis C, Chronic , Hepatitis C , Antiviral Agents/therapeutic use , CD8-Positive T-Lymphocytes , HIV Infections/complications , HIV Infections/drug therapy , Hepacivirus , Hepatitis C/complications , Hepatitis C/drug therapy , Hepatitis C, Chronic/drug therapy , Humans
4.
J Family Med Prim Care ; 11(3): 828-832, 2022 Mar.
Article in English | MEDLINE | ID: covidwho-1753780

ABSTRACT

HIV with coexisting Hepatitis C infection has been a global health problem. HIV with Hepatitis C prevalence is significantly higher in people living with HIV. These patients being immunocompromised are at higher risk of contracting COVID-19 infection. Super added COVID-19 infection may prove to be fatal in these patients. We decided to review literature for assessing the clinical manifestations and management of these patients contracting COVID-19 infection and explore the public health measures in practice in the current scenario. Practices of safety norms against COVID-19 shall prevent associated health morbidity and mortality. Moreover, management of these patients needs to be judiciously done by Physicians as COVID-19 infection may worsen their condition. The Public Health Specialist are playing a crucial role in management of COVID-19 pandemic especially by strategy planning for surveillance, health education and preparedness for any future wave of COVID-19 infection.

5.
J Clin Exp Hepatol ; 12(3): 937-947, 2022.
Article in English | MEDLINE | ID: covidwho-1562325

ABSTRACT

Patients with chronic liver disease (CLD) with or without cirrhosis remain at risk of developing hepatic decompensation when infected with viral or bacterial pathogens. The Advisory Committee on Immunization Practices (ACIP) currently recommends vaccination in CLD against hepatitis A virus (HAV), hepatitis B virus (HBV), influenza, pneumococcus, herpes zoster, tetanus, diphtheria, pertussis, and SARS-CoV-2. Inactivated vaccines are preferred over live attenuated ones, especially in transplant recipients where live vaccines are contraindicated. As the severity of the liver disease progresses, vaccine efficacy declines, and therefore, vaccines should be ideally administered early in the disease course for optimal immune response. Despite the strong recommendations, overall vaccination coverage in CLD remains poor; however, it is encouraging to note that in recent years coverage against influenza and pneumococcus has shown some improvement. Inadequate access to healthcare, lack of information on vaccine safety, poor financial reimbursement for healthcare providers, and vaccine misinformation are often responsible for low immunization rates. This review summarizes the impact of vaccine-preventable illness in those with CLD, updated vaccine guidelines, seroconversion rates in the vaccinated, and barriers faced by healthcare professionals in immunizing those with liver disease.

6.
Viruses ; 13(11)2021 10 20.
Article in English | MEDLINE | ID: covidwho-1538529

ABSTRACT

Viruses are obligate parasites that depend on a host cell for replication and survival. Consequently, to fully understand the viral processes involved in infection and replication, it is fundamental to study them in the cellular context. Often, viral infections induce significant changes in the subcellular organization of the host cell due to the formation of viral factories, alteration of cell cytoskeleton and/or budding of newly formed particles. Accurate 3D mapping of organelle reorganization in infected cells can thus provide valuable information for both basic virus research and antiviral drug development. Among the available techniques for 3D cell imaging, cryo-soft X-ray tomography stands out for its large depth of view (allowing for 10 µm thick biological samples to be imaged without further thinning), its resolution (about 50 nm for tomographies, sufficient to detect viral particles), the minimal requirements for sample manipulation (can be used on frozen, unfixed and unstained whole cells) and the potential to be combined with other techniques (i.e., correlative fluorescence microscopy). In this review we describe the fundamentals of cryo-soft X-ray tomography, its sample requirements, its advantages and its limitations. To highlight the potential of this technique, examples of virus research performed at BL09-MISTRAL beamline in ALBA synchrotron are also presented.


Subject(s)
Tomography, X-Ray/methods , Virus Diseases/virology , Virus Physiological Phenomena , Animals , Antiviral Agents/pharmacology , Humans , Tomography, X-Ray/instrumentation , Virus Diseases/diagnostic imaging , Virus Diseases/drug therapy , Viruses/chemistry , Viruses/drug effects
7.
Front Mol Biosci ; 8: 671263, 2021.
Article in English | MEDLINE | ID: covidwho-1344278

ABSTRACT

SARS-CoV-2 belongs to the family of enveloped, single-strand RNA viruses known as Betacoronavirus in Coronaviridae, first reported late 2019 in China. It has since been circulating world-wide, causing the COVID-19 epidemic with high infectivity and fatality rates. As of the beginning of April 2021, pandemic SARS-CoV-2 has infected more than 130 million people and led to more than 2.84 million deaths. Given the severity of the epidemic, scientists from academia and industry are rushing to identify antiviral strategies to combat the disease. There are several strategies in antiviral drugs for coronaviruses including empirical testing of known antiviral drugs, large-scale phenotypic screening of compound libraries and target-based drug discovery. To date, an increasing number of drugs have been shown to have anti-coronavirus activities in vitro and in vivo, but only remdesivir and several neutralizing antibodies have been approved by the US FDA for treating COVID-19. However, remdesivir's clinical effects are controversial and new antiviral drugs are still urgently needed. We will discuss the current status of the drug discovery efforts against COVID-19 and potential future directions. With the ever-increasing movability of human population and globalization of world economy, emerging and reemerging viral infectious diseases seriously threaten public health. Particularly the past and ongoing outbreaks of coronaviruses cause respiratory, enteric, hepatic and neurological diseases in infected animals and human (Woo et al., 2009). The human coronavirus (HCoV) strains (HCoV-229E, HCoV-OC43, HCoV-NL63, and HCoV-HKU1) usually cause common cold with mild, self-limiting upper respiratory tract infections. By contrast, the emergence of three deadly human betacoronaviruses, middle east respiratory syndrome coronavirus (MERS) (Zaki et al., 2012), severe acute respiratory syndrome coronavirus (SARS-CoV) (Lee et al., 2003), the SARS-CoV-2 (Jin et al., 2020a) highlight the need to identify new treatment strategies for viral infections. SARS-CoV-2 is the etiological agent of COVID-19 disease named by World Health Organization (WHO) (Zhu N. et al., 2020). This disease manifests as either an asymptomatic infection or a mild to severe pneumonia. This pandemic disease causes extent morbidity and mortality in the whole world, especially regions out of China. Similar to SARS and MERS, the SARS CoV-2 genome encodes four structural proteins, sixteen non-structural proteins (nsp) and accessory proteins. The structural proteins include spike (S), envelope (E), membrane (M), nucleoprotein (N). The spike glycoprotein directly recognizes and engages cellular receptors during viral entry. The four non-structural proteins including papain-like protease (PLpro), 3-chymotrypsin-like protease (3CLpro), helicase, and RNA-dependent RNA polymerase (RdRp) are key enzymes involved in viral transcription and replication. The spike and the four key enzymes were considered attractive targets to develop antiviral agents (Zumla et al., 2016). The catalytic sites of the four enzymes of SARS-CoV2 share high similarities with SARS CoV and MERS in genomic sequences (Morse et al., 2020). Besides, the structures of the key drug-binding pockets are highly conserved among the three coronaviruses (Morse et al., 2020). Therefore, it follows naturally that existing anti-SARS-CoV and anti-MERS drugs targeting these enzymes can be repurposed for SARS-CoV-2. Based on previous studies in SARS-CoV and MERS-CoV, it is anticipated a number of therapeutics can be used to control or prevent emerging infectious disease COVID-19 (Li and de Clercq, 2020; Wang et al., 2020c; Ita, 2021), these include small-molecule drugs, peptides, and monoclonal antibodies. Given the urgency of the SARS-CoV-2 outbreak, here we discuss the discovery and development of new therapeutics for SARS-CoV-2 infection based on the strategies from which the new drugs are derived.

8.
Crit Rev Anal Chem ; : 1-23, 2021 Jun 17.
Article in English | MEDLINE | ID: covidwho-1276053

ABSTRACT

Human beings are in dire need of developing an efficient treatment against fierce viruses like hepatitis C virus (HCV) and Coronavirus (COVID-19). These viruses have already caused the death of over two million people all over the world. Therefore, over the last years, many direct-acting antiviral drugs (DAADs) were developed targeting nonstructural proteins of these two viruses. Among these DAADs, several drugs were found more effective and safer than the others as sofosbuvir, ledipasvir, grazoprevir, glecaprevir, voxilaprevir, velpatasvir, elbasvir, pibrentasvir and remdesivir. The last one is indicated for COVID-19, while the rest are indicated for HCV treatment. Due to the valuable impact of these DAADs, larger number of analytical methods were required to meet the needs of the clinical studies. Therefore, this review will highlight the current approaches, published in the period between 2017 to present, dealing with the determination of these drugs in two different matrices: pharmaceuticals and biological fluids with the challenges of analyzing these drugs either alone, with other drugs, in presence of interferences (pharmaceutical excipients or endogenous plasma components) or in presence of matrix impurities, degradation products and metabolites. These approaches include spectroscopic, chromatographic, capillary electrophoretic, voltametric and nuclear magnetic resonance methods that have been reported during this period. Moreover, the analytical instrumentation and methods used in determination of these DAADs will be illustrated in tabulated forms.

9.
Virusdisease ; 32(2): 279-285, 2021 Jun.
Article in English | MEDLINE | ID: covidwho-1216275

ABSTRACT

The coronavirus pandemic could be the most threatening outbreak in the twenty-first century. According to the latest records of world health organization, more than 130 millions have been infected by COVID-19, with more than 2.9 million reported deaths. Yet, there is no magic cure for treatment of COVID-19. The concept of drug repurposing has been introduced as a fast, life-saving approach for drug discovery. Drug repurposing infers investigating already approved drugs for new indications, using the available information about pathophysiology of diseases and pharmacodynamics of drugs. In a recent work, more than 3000 FDA approved drugs were tested using virtual screening as potential antiviral agents for COVID-19. In this work, the top ranked five hits from the previous docking results together with drugs of similar chemical feature and/or mechanistic destinations were further tested using AutoDock Vina. The results showed that anti-HCV combinations could be potential therapeutic regimens for COVID-19 infections. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13337-021-00691-6.

10.
Struct Chem ; 32(2): 909-913, 2021.
Article in English | MEDLINE | ID: covidwho-1081899

ABSTRACT

At the time of COVID-19 coronavirus pandemia, the Nobel Prize of Physiology or Medicine 2020 was awarded jointly to three researchers Harvey J. Alter, Charles M. Rice, and Michael Houghton for the discovery of Hepatitis C virus. Their works contributed to the isolation of the blood-borne virus, causing chronic hepatitis in 80% of infected person, resulting in cirrhosis, and in elevated risk of liver failure and hepatocellular carcinoma formation. Their results created the basis of HCV screening of blood, and blood products, achieving more than 95% cure of infected people without nearly side effects with direct-acting antiviral agents, supporting the goal of the WHO targeting the elimination of viral hepatitis by 2030.

11.
World J Hepatol ; 12(8): 485-492, 2020 Aug 27.
Article in English | MEDLINE | ID: covidwho-782299

ABSTRACT

In recent years, significant progress in the antiviral treatment of chronic hepatitis C (CHC) has been made due to the development of interferon-free therapies. Three different highly effective, oral direct-acting antiviral (DAA) regimens have been approved for use in adolescents with CHC between the ages of 12-years-old and 17-years-old in Europe. According to the current recommendations, all treatment-naïve and treatment-experienced children with CHC virus infection should be considered for DAA therapy to prevent the possible progression of hepatitis C virus-related liver disease and its complications. However, the novel coronavirus disease 2019 outbreak, which was classified as a pandemic in March 2020, is currently spreading throughout the world, resulting in a disruption of the healthcare system. This disruption is having a negative impact on the care of patients with chronic diseases, including children with CHC. Thus, several efforts have to be made by pediatric hepatologists to prioritize patient care in children with CHC. These efforts include promoting telemedicine in the outpatient setting, using local laboratory testing for follow-up visits, and engaging in the home delivery of DAAs for patients under antiviral therapy whenever possible.

12.
Med Res Rev ; 40(5): 1519-1557, 2020 09.
Article in English | MEDLINE | ID: covidwho-971

ABSTRACT

Direct-acting antiviral agents (DAAs) represent a class of drugs targeting viral proteins and have been demonstrated to be very successful in combating viral infections in clinic. However, DAAs suffer from several inherent limitations, including narrow-spectrum antiviral profiles and liability to drug resistance, and hence there are still unmet needs in the treatment of viral infections. In comparison, host targeting antivirals (HTAs) target host factors for antiviral treatment. Since host proteins are probably broadly required for various viral infections, HTAs are not only perceived, but also demonstrated to exhibit broad-spectrum antiviral activities. In addition, host proteins are not under the genetic control of viral genome, and hence HTAs possess much higher genetic barrier to drug resistance as compared with DAAs. In recent years, much progress has been made to the development of HTAs with the approval of chemokine receptor type 5 antagonist maraviroc for human immunodeficiency virus treatment and more in the pipeline for other viral infections. In this review, we summarize various host proteins as antiviral targets from a medicinal chemistry prospective. Challenges and issues associated with HTAs are also discussed.


Subject(s)
Antiviral Agents , Hepatitis C, Chronic , Antiviral Agents/pharmacology , Antiviral Agents/therapeutic use , Chemistry, Pharmaceutical , Hepatitis C, Chronic/drug therapy , Humans , Prospective Studies , Viral Proteins
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