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1.
BMC Gastroenterol ; 24(1): 49, 2024 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-38273255

RESUMO

BACKGROUND & AIM: To evaluate the risk of early hepatocellular carcinoma (HCC) in chronic hepatitis C patients treated with direct-acting antivirals (DAAs) in Hong Kong, as it has not been studied before in this locality. METHODS: Three hundred thirty-three consecutive chronic hepatitis C patients treated with DAAs from two hospitals over the past 6 years were identified. Kaplan-Meier method was used to calculate cumulative HCC incidence. Cox regression was used to identify factors associated with HCC development. RESULTS: During a median follow-up of 23.4 months after DAA started, 15 (5.4%, 95% CI 3.3-8.7%) out of 279 total included patients developed HCC. The overall sustained virological response (SVR) rate was 98.9%. The 1-year cumulative incidence for de-novo HCC and HCC recurrence were 0.8 and 30.9%, respectively (log-rank test p < 0.001). The 1-year cumulative HCC incidence for patients without and with cirrhosis were 0.7 and 5.1%, respectively (log-rank test p = 0.036). Univariate analysis showed that significant factors associated with HCC after DAA were: history of treated HCC, cirrhosis, evidence of portal hypertension, higher AFP at the start or end of DAA therapy, higher bilirubin, lower platelets, lower albumin, and older age. From receiver operating characteristic curve analysis, the optimal cut-off level of AFP for predicting HCC was 10.5 ng/mL at the start and 5.6 ng/mL at the end of DAA therapy. CONCLUSIONS: The risk of early HCC recurrence remains high despite achieving SVR following DAA therapy, whereas the risk of early de-novo HCC occurence is low. AFP levels, both at the start and end of DAA therapy, can be useful in stratifying risks of HCC development.


Assuntos
Carcinoma Hepatocelular , Hepatite C Crônica , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/epidemiologia , Carcinoma Hepatocelular/etiologia , Carcinoma Hepatocelular/patologia , Antivirais/uso terapêutico , Hepatite C Crônica/complicações , Hepatite C Crônica/tratamento farmacológico , Hepatite C Crônica/epidemiologia , Neoplasias Hepáticas/epidemiologia , Neoplasias Hepáticas/etiologia , Neoplasias Hepáticas/patologia , alfa-Fetoproteínas/análise , Hong Kong/epidemiologia , Cirrose Hepática/complicações , Fibrose , Resposta Viral Sustentada
2.
J Infect Chemother ; 30(3): 271-275, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37944697

RESUMO

In hemato-oncological patients, COVID-19 can present as a persistent infection with ongoing symptoms and viral replication over a prolonged period of time. Data are scarce on the preferred treatment options for these patients. We describe our experience with a five-day course of dual anti-viral treatment with remdesivir and nirmatrelvir/ritonavir for hemato-oncological immunocompromised patients with persistent COVID-19. Fifteen patients with a history of lymphoma, CLL, and MM were included. Eight were male, median age was 74. All patients had an immediate clinical and virological response. In 73 % of patients, PCR for SARS-CoV-2 became negative at the end of treatment and the rest had an increase in PCR cycle threshold (CT) values, with a median increase of 6 cycles. After a follow-up of three months, 60 % of patients remained in full clinical and virological remission. None required invasive mechanical ventilation or died. The side effects we observed, neutropenia, lactatemia and elevated transaminases, were mild and almost all transient in nature. We conclude that dual anti-viral treatment appears to be a valid treatment option for persistent COVID-19.


Assuntos
COVID-19 , Humanos , Masculino , Idoso , Feminino , COVID-19/complicações , SARS-CoV-2 , Prognóstico , Fatores de Tempo , Antivirais/efeitos adversos
3.
Clin Immunol ; 257: 109831, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37931868

RESUMO

IFNß (recombinant interferon Beta) has been widely used for the treatment of Multiple sclerosis for the last four decades. Despite the human origin of the IFNß sequence, IFNß is immunogenic, and unwanted immune responses in IFNß-treated patients may compromise its efficacy and safety in the clinic. In this study, we applied the DeFT (De-immunization of Functional Therapeutics) approach to producing functional, de-immunized versions of IFNß-1a. Two de-immunized versions of IFNß-1a were produced in CHO cells and designated as IFNß-1a(VAR1) and IFNß-1a(VAR2). First, the secondary and tertiary protein structures were analyzed by circular dichroism spectroscopy. Then, the variants were also tested for functionality. While IFNß-1a(VAR2) showed similar in vitro antiviral activity to the original protein, IFNß-1a(VAR1) exhibited 40% more biological potency. Finally, in vivo assays using HLA-DR transgenic mice revealed that the de-immunized variants showed a markedly reduced immunogenicity when compared to the originator.


Assuntos
Esclerose Múltipla , Animais , Camundongos , Cricetinae , Humanos , Esclerose Múltipla/tratamento farmacológico , Interferon beta , Interferon beta-1a/uso terapêutico , Cricetulus , Recidiva Local de Neoplasia , Adjuvantes Imunológicos
4.
J Invertebr Pathol ; 190: 107753, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35358596

RESUMO

Viruses are obligate intracellular parasites relying on host cells to obtain biosynthetic precursors and energy to successfully infect the host. The metabolic profile of the host cell is known to be altered in response to viral infection to satisfy the resources demanded during viral replication. Previous data of ours showed that white spot syndrome virus (WSSV) elicited in a crustacean host (Procambarus clarkii) a rapid and long-lasting release of crustacean hyperglycemic hormone (CHH), a well-known carbohydrate-regulating and stress response-mediating endocrine hormone. Therefore, the WSSV-enhanced release of CHH could be responsible at least in part for the metabolic alterations in the WSSV-challenged host. To investigate the possible metabolic roles of CHH in the host-parasite interaction, we studied whether silencing CHH gene expression could inhibit WSSV propagation in tissues and reduce the mortality of the WSSV-infected animals. Data presented in this study showed that CHH gene silencing indeed resists the WSSV infection. Injection of CHH dsRNA at the dosage of 140 µg/g BW caused significant decreases of viral copy number in tissues of WSSV-infected host, particularly showing a pronounced effect in the endodermal tissues (including hepatopancreas and gastrolith disk). Furthermore, results from the cumulative mortality showed that the treatment of CHH dsRNA delayed death from WSSV. Injection of CHH dsRNA at the dosages of 70, 17, and 10 µg/ g BW significantly extended the mean survival time. Together, this study concludes that the silencing of the CHH gene does have an inhibitory effect on the replication of the white spot syndrome virus and can assist the host to mitigate the invasion of WSSV, through attenuating CHH-mediated stress responses.


Assuntos
Penaeidae , Viroses , Vírus da Síndrome da Mancha Branca 1 , Animais , Astacoidea , Hepatopâncreas , RNA de Cadeia Dupla/metabolismo , Replicação Viral , Vírus da Síndrome da Mancha Branca 1/genética
5.
J Infect Dis ; 224(12 Suppl 2): S387-S397, 2021 09 30.
Artigo em Inglês | MEDLINE | ID: mdl-34590140

RESUMO

Michiaki Takahashi developed the live attenuated varicella vaccine in 1974 . This was the first, and is still the only, herpesvirus vaccine. Early studies showed promise, but the vaccine was rigorously tested on immunosuppressed patients because of their high risk of fatal varicella; vaccination proved to be lifesaving. Subsequently, the vaccine was found to be safe and effective in healthy children. Eventually, varicella vaccine became a component of measles mumps rubella vaccine, 2 doses of which are administered in the USA to ~90% of children. The incidence of varicella has dropped dramatically in the USA since vaccine-licensure in 1995. Varicella vaccine is also associated with a decreased incidence of zoster and is protective for susceptible adults. Today, immunocompromised individuals are protected against varicella due to vaccine-induced herd immunity. Latent infection with varicella zoster virus occurs after vaccination; however, the vaccine strain is impaired for its ability to reactivate.


Assuntos
Vacina contra Varicela/administração & dosagem , Varicela/prevenção & controle , Vacina contra Herpes Zoster/administração & dosagem , Herpes Zoster/prevenção & controle , Herpesvirus Humano 3/efeitos dos fármacos , Vacinas Atenuadas/administração & dosagem , Antígenos Virais , Herpesvirus Humano 3/imunologia , Humanos , Incidência , Vacina contra Sarampo-Caxumba-Rubéola , Estados Unidos/epidemiologia , Vacinação , Vacinas Combinadas
6.
Intern Med J ; 51(4): 533-539, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31994285

RESUMO

BACKGROUND: Current guidelines suggest using transient elastography (TE) or aspartate aminotransferase to platelet ratio index (APRI) score <1 to exclude cirrhosis prior to commencing treatment for hepatitis C virus (HCV). Recently, fibrosis-4 (FIB-4) <0.93 has been shown to have a high negative predictive value (NPV) for the presence of cirrhosis. AIMS: To assess FIB-4 and APRI in a cohort of HCV patients and to validate FIB-4 <0.93 in populations of HCV-infected individuals with differing cirrhosis prevalence, including secondary care, primary care and prisons. METHODS: From our treatment database, we identified patients with complete data (n = 793). We calculated FIB-4 and APRI and correlated this with the presence of cirrhosis, determined by TE. We analysed the performance of FIB-4 and APRI using area under the receiver operating curve analysis. We calculated sensitivity, specificity, positive predictive value, NPV and number of patients misclassified using published cut-offs in populations with varying cirrhosis prevalence. RESULTS: FIB-4 was superior to APRI for the diagnosis of cirrhosis (area under the receiver operating curve 0.868 vs 0.802). In secondary care (cirrhosis prevalence 32%), APRI <1 had a NPV of 80% and misclassified 14% of patients. FIB-4 <0.93 had a NPV of 97% and misclassified 1%. In primary care and prison (cirrhosis prevalence 13% and 8%), the NPV for APRI <1 was 93% and 96%, respectively, but 5% of patients with cirrhosis were misclassified. FIB-4 <0.93 had excellent NPV in both primary care (97%) and prisoners (100%). CONCLUSIONS: FIB-4 <0.93 is highly efficient at ruling out cirrhosis in HCV patients and allows TE to be appropriately avoided, thereby streamlining treatment algorithms.


Assuntos
Hepatite C , Cirrose Hepática , Aspartato Aminotransferases , Austrália/epidemiologia , Biomarcadores , Fibrose , Humanos , Cirrose Hepática/diagnóstico , Cirrose Hepática/epidemiologia , Curva ROC , Índice de Gravidade de Doença
7.
Ophthalmic Physiol Opt ; 41(5): 961-970, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34382704

RESUMO

PURPOSE: To report anti-viral therapy and outcomes for patients with herpes simplex keratitis (HSK) in a quaternary centre in Sydney, Australia. METHODS: A retrospective case review of patients who received anti-viral medications for any form of HSK was conducted. Cases were identified from pathology results, pharmacy records and hospital coding data from 2012 to 2013. Clinical details including initial anti-viral treatment and outcome were collated from the medical records. Outcome was determined from when initial anti-viral treatment was stopped or changed, and classified as either clinically resolved, partially resolved or worsened for therapeutic indication; or as either success or failure for prophylaxis. RESULTS: Anti-viral therapy was given for therapeutic and prophylactic indications at presentation in 252 (85%) and 44 patients (15%), respectively. Topical aciclovir five times daily and valaciclovir in doses ranging from 500 mg to 1 g, one to three times daily were the preferred anti-viral therapies. One hundred and fourteen patients (n = 114/296, 38.5%) also received topical corticosteroids. An outcome was determined for 210/296 (71%) patients. For therapeutic indication, half of the patients (90/174) partially resolved within 8 days, with best outcomes achieved for endothelial HSK (8/11, 73%) and keratouveitis (21/36, 58%). Adverse events, observed in 20% (35/174) of patients, included corneal perforation (n = 8) and secondary bacterial keratitis (n = 6). Prophylaxis with antiviral therapy was successful in two-thirds of patients after 6 months. CONCLUSIONS: Clinical and visual outcomes varied with the type of HSK and prescribed therapies. Diverse initial anti-viral therapies were identified; standardising them may improve outcomes.


Assuntos
Ceratite Herpética , Aciclovir/uso terapêutico , Antivirais/uso terapêutico , Austrália/epidemiologia , Humanos , Ceratite Herpética/diagnóstico , Ceratite Herpética/tratamento farmacológico , Ceratite Herpética/epidemiologia , Estudos Retrospectivos
8.
Cell Mol Life Sci ; 76(3): 405-419, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30327839

RESUMO

Herpes simplex virus type-1 (HSV-1) is a ubiquitous pathogen that infects a large majority of the human population worldwide. It is also a leading cause of infection-related blindness in the developed world. HSV-1 infection of the cornea begins with viral entry into resident cells via a multistep process that involves interaction of viral glycoproteins and host cell surface receptors. Once inside, HSV-1 infection induces a chronic immune-inflammatory response resulting in corneal scarring, thinning and neovascularization. This leads to development of various ocular diseases such as herpes stromal keratitis, resulting in visual impairment and eventual blindness. HSV-1 can also invade the central nervous system and lead to encephalitis, a relatively common cause of sporadic fetal encephalitis worldwide. In this review, we discuss the pathological processes activated by corneal HSV-1 infection and existing antiviral therapies as well as novel therapeutic options currently under development.


Assuntos
Córnea/fisiopatologia , Córnea/virologia , Doenças da Córnea/patologia , Herpes Simples/patologia , Herpesvirus Humano 1 , Antivirais/uso terapêutico , Córnea/química , Doenças da Córnea/tratamento farmacológico , Doenças da Córnea/virologia , Glicoproteínas/metabolismo , Herpes Simples/tratamento farmacológico , Herpesvirus Humano 1/metabolismo , Interações Hospedeiro-Patógeno , Humanos , Modelos Biológicos , Receptores de Superfície Celular/metabolismo
9.
Int J Mol Sci ; 21(17)2020 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-32899231

RESUMO

The coronavirus disease of 2019 (COVID-19) or severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is a global pandemic with increasing incidence and mortality rates. Recent evidence based on the cytokine profiles of severe COVID-19 cases suggests an overstimulation of macrophages and monocytes associated with reduced T-cell abundance (lymphopenia) in patients infected with SARS-CoV-2. The SARS-CoV-2 open reading frame 3 a (ORF3a) protein was found to bind to the human HMOX1 protein at a high confidence through high-throughput screening experiments. The HMOX1 pathway can inhibit platelet aggregation, and can have anti-thrombotic and anti-inflammatory properties, amongst others, all of which are critical medical conditions observed in COVID-19 patients. Here, we review the potential of modulating the HMOX1-ORF3a nexus to regulate the innate immune response for therapeutic benefits in COVID-19 patients. We also review other potential treatment strategies and suggest novel synthetic and natural compounds that may have the potential for future development in clinic.


Assuntos
Infecções por Coronavirus/metabolismo , Heme Oxigenase-1/metabolismo , Pneumonia Viral/metabolismo , Proteínas Virais Reguladoras e Acessórias/metabolismo , Animais , Antivirais/uso terapêutico , COVID-19 , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/virologia , Heme Oxigenase-1/genética , Humanos , Pandemias , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/virologia , Ligação Proteica , Proteínas Viroporinas
10.
Liver Int ; 39(10): 1837-1844, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31173468

RESUMO

BACKGROUND & AIM: Chronic infections with hepatitis B or C (HBV and HCV) are associated with adverse clinical outcomes and patient-reported outcomes (PROs). The aim is to compare PRO scores in patients with chronic HBV and HCV without advanced liver disease before and after suppression/clearance of their infection. METHODS: Patients with HCV and HBV infection prior to initiation of antiviral treatment and after viral suppression/eradication completed PRO questionnaires. RESULTS: We included 132 patients with HBV and 132 matched patients with HCV. Baseline PRO scores were significantly higher in patients with HBV in the domains of Physical Functioning, Role Physical, Bodily Pain, Social Functioning, and Role Emotional of SF-36, SF-6D utility, Emotional and Fatigue domains of CLDQ, Presenteeism and total Work Productivity Impairment of WPAI:SHP in comparison to patients with HCV by 5.8%-13.2% of a PRO score range (all P < 0.05). After viral suppression (HBV DNA < 20 IU/mL after 48 weeks of treatment for HBV) or eradication (SVR-12 for HCV), only Physical Functioning and Role Physical scores remained higher in HBV by 6.7%-9.9%, while other PRO scores became similar between HBV and HCV groups (P > 0.05). The most prominent improvement of PROs in HCV was noted in Vitality, Emotional, Fatigue and Worry domains. In addition, General Health, Worry and Work Productivity scores were the most improved in HBV. CONCLUSIONS: Prior to treatment, PRO scores were lower in patients with HCV in comparison to HBV. After successful treatment, both groups of patients experienced improvement in some PRO domains confirming the positive impact of treatment.


Assuntos
Antivirais/uso terapêutico , Hepatite B Crônica/tratamento farmacológico , Hepatite C Crônica/tratamento farmacológico , Medidas de Resultados Relatados pelo Paciente , Adulto , Quimioterapia Combinada , Feminino , Hepatite B Crônica/virologia , Hepatite C Crônica/virologia , Humanos , Internacionalidade , Cirrose Hepática/prevenção & controle , Masculino , Pessoa de Meia-Idade , Pteridinas/uso terapêutico , Qualidade de Vida , Sofosbuvir/uso terapêutico , Inquéritos e Questionários , Resultado do Tratamento , Carga Viral , Replicação Viral
11.
Cell Mol Life Sci ; 75(21): 3895-3905, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30097692

RESUMO

Chronic hepatitis B, C and D virus (HBV, HCV and HDV) infections are a major cause of liver disease and cancer worldwide. Despite employing distinct replication strategies, the three viruses are exclusively hepatotropic, and therefore depend on hepatocyte-specific host factors. The sodium taurocholate co-transporting polypeptide (NTCP), a transmembrane protein highly expressed in human hepatocytes that mediates the transport of bile acids, plays a key role in HBV and HDV entry into hepatocytes. Recently, NTCP has been shown to modulate HCV infection of hepatocytes by regulating innate antiviral immune responses in the liver. Here, we review the current knowledge of the functional role and the molecular and cellular biology of NTCP in the life cycle of the three major hepatotropic viruses, highlight the impact of NTCP as an antiviral target and discuss future avenues of research.


Assuntos
Hepacivirus/genética , Vírus da Hepatite B/genética , Vírus Delta da Hepatite/genética , Transportadores de Ânions Orgânicos Dependentes de Sódio/genética , Simportadores/genética , Hepacivirus/patogenicidade , Hepatite B/genética , Hepatite B/virologia , Vírus da Hepatite B/patogenicidade , Hepatite C/genética , Hepatite C/virologia , Hepatite D/genética , Hepatite D/virologia , Vírus Delta da Hepatite/patogenicidade , Hepatócitos/patologia , Humanos , Estágios do Ciclo de Vida/genética , Internalização do Vírus
12.
RNA Biol ; 15(3): 327-337, 2018 03 04.
Artigo em Inglês | MEDLINE | ID: mdl-29431588

RESUMO

Aptamers are high affinity single-stranded nucleic acid or protein ligands which exhibit specificity and avidity comparable to, or exceeding that of antibodies and can be generated against most targets. The functionality of aptamers is based on their unique tertiary structure, complexity and their ability to attain unique binding pockets by folding. Aptamers are selected in vitro by a process called Systematic Evolution of Ligands by Exponential enrichment (SELEX). The Kd values for the selected aptamer are often in the picomolar to low nanomolar range. Stable and nontoxic aptamers could be selected for a wide range of ligands including small molecules to large proteins. Aptamers have shown tremendous potential and have found multipurpose application in the field of therapeutic, diagnostic, biosensor and bio-imaging. While their mechanism of action can be similar to that of monoclonal antibodies, aptamers provide additional advantages in terms of production cost, simpler regulatory approval and lower immunogenicity as they are synthesized chemically. Human immunodeficiency virus (HIV) is the primary cause of acquired immune deficiency syndrome (AIDS), which causes significant morbidity and mortality with a significant consequent decrease in the quality of patient's lives. While cART has led to good viral control, people living with HIV now suffer from non-HIV comorbidities due to viral protein expression that cannot be controlled by cART. Hence pathophysiological mechanisms that govern these comorbidities with a focus on therapies that neutralize these HIV effects gained increased attention. Recent advances in HIV/AIDS research have identified several molecular targets and for the development of therapeutic and diagnostic using aptamers against HIV/AIDS. This review presents recent advances in aptamers technology for potential application in HIV diagnostics and therapeutics towards improving the quality of life of people living with HIV.


Assuntos
Aptâmeros de Nucleotídeos/farmacologia , Infecções por HIV/diagnóstico , Infecções por HIV/tratamento farmacológico , Aptâmeros de Nucleotídeos/uso terapêutico , HIV/efeitos dos fármacos , HIV/metabolismo , Humanos , Qualidade de Vida , Técnica de Seleção de Aptâmeros , Proteínas Virais/antagonistas & inibidores
13.
Klin Lab Diagn ; 63(1): 51-54, 2018.
Artigo em Russo | MEDLINE | ID: mdl-30550092

RESUMO

The purpose of study is the clinical laboratory characteristic of acquired acute cytomegalovirus infection in nonimmunocompromised adult patients. The sampling included 75 patients with acquired acute cytomegalovirus infection admitted to the specialized clinical infection hospital of the Minzdrav of the Krasnodar kraii. The verifcation of diagnosis was implemented using serological tests and polymerase chain reaction. It is demonstrated that males of younger age are most often infected with acute cytomegalovirus infection in the Krasnodar kraii. The disease takes its course in a generalized form. In clinical picture symptoms of intoxication (long-term temperature increasing, weakness), hepatomegaly with increasing of activity of hepatic enzymes, splenomegaly, monolymphocytosis prevail. In most of patients, manifestation of affection of upper respiratory tracts are observed and less frequently - community-acquired pneumonia. The alteration of immune status of patients in dynamics of disease was typical for acute faze of viral infection process with transition to a latent one. At the same time, certain percentage of patients preserved inhibition of neutrophil chain of immunity during re-convalescent period, hence developing menace of bacterial complications. The complex treatment with inclusion of etiotropic anti-viral pharmaceutical Gancyclovir with duration of 8,4±0,4 days resulted in normalization of fever, relief of organic affections and also disappearance of viral DNA from blood. The rate of wrong preliminary diagnoses (85.3%) at referral of patient to hospital testifes complicacy of clinical diagnostic of acute cytomegalovirus infection, conditioned by absence of pathognomonic symptoms under this disease. The last circumstance determines expediency of inclusion into algorithm of examination of patients with unidentifed genesis of fever, hepatosplenomegaly, lymphadenopathy, monolymphocytosis, increasing of activity of hepatic enzymes the analysis of antibodies to antigens of cytomegalovirus (IgM CMV, IgG CMV, avidity of IgG CMV) using enzyme-linked immunosorbent assay and also detection of DNA CMV in blood and urine using polymerase chain reaction technique. The alterations of immune status during re-convalescent period observed in one third of patients determine necessity of their dispensary observation.


Assuntos
Infecções por Citomegalovirus , Citomegalovirus , Adulto , Anticorpos Antivirais , DNA Viral , Ensaio de Imunoadsorção Enzimática , Humanos , Imunoglobulina G , Imunoglobulina M , Masculino
14.
Zhonghua Gan Zang Bing Za Zhi ; 25(11): 819-826, 2017 Nov 20.
Artigo em Chinês | MEDLINE | ID: mdl-29325275

RESUMO

Objective: To investigate the methods for qualitative pathological assessment of dynamic changes in liver fibrosis/cirrhosis after antiviral therapy in patients with chronic hepatitis B (CHB), since antiviral therapy can partially reverse liver fibrosis and cirrhosis caused by hepatitis B and semi-quantitative, rather than qualitative, pathological assessment is often used for the research on liver fibrosis regression. Methods: Previously untreated CHB patients with liver fibrosis and cirrhosis were enrolled, and liver biopsy was performed before treatment and at 78 weeks after the antiviral therapy based on entecavir. The follow-up assessment was performed once every half a year. Based on the proportion of different types of fibrous septum, we put forward the new qualitative criteria called P-I-R classification (predominantly progressive, predominantly regressive, and indeterminate) for evaluating dynamic changes in liver fibrosis. This classification or Ishak fibrosis stage was used to evaluate the change in liver fibrosis after treatment and Ishak liver inflammation score was used to evaluate the change in liver inflammation after treatment. Results: A total of 112 CHB patients who underwent liver biopsy before and after treatment were enrolled, and among these patients, 71 with an Ishak stage of ≥3 and qualified results of live biopsy were included in the final analysis. Based on the P-I-R classification, 58% (41/71) were classified as predominantly progressive, 29% (21/71) were classified as indeterminate, and 13% (9/71) were classified as predominantly regressive; there were no significant differences between the three groups in alanine aminotransferase, aspartate aminotransferase, albumin, HBeAg positive rate, HBV DNA, and liver stiffness (P < 0.05). After treatment, the proportion of predominantly progressive, indeterminate, or predominantly regressive patients changed to 11% (8/71), 11% (8/71), and 78% (55/71), respectively. Among the 35 patients who had no change in Ishak stage after treatment, 72% (25/35) were classified as predominantly regressive and had certain reductions in the Laennec score, percentage of collagen area, and liver stiffness. Conclusion: This new P-I-R classification can be used to assess the dynamic changes in liver fibrosis after antiviral therapy in CHB patients.


Assuntos
Hepatite B Crônica/patologia , Cirrose Hepática/patologia , Fígado/patologia , Alanina Transaminase/sangue , Antivirais/uso terapêutico , Hepatite B Crônica/complicações , Hepatite B Crônica/tratamento farmacológico , Humanos , Cirrose Hepática/tratamento farmacológico
15.
J Viral Hepat ; 22(6): 515-23, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25288051

RESUMO

Pregnancy is a para-physiologic condition, which usually evolves without any complications in the majority of women, even if in some circumstances moderate or severe clinical problems can also occur. Among complications occurring during the second and the third trimester very important are those considered as concurrent to pregnancy such as hyperemesis gravidarum, intrahepatic cholestasis of pregnancy, HELLP syndrome and acute fatty liver of pregnancy. The liver diseases concurrent to pregnancy typically occur at specific times during the gestation and they may lead to significant maternal and foetal morbidity and mortality. Commonly, delivery of the foetus, even preterm, usually terminates the progression of these disorders. All chronic liver diseases, such as chronic viral hepatitis, autoimmune hepatitis, Wilson's disease, and cirrhosis of different aetiologies may cause liver damage, independently from pregnancy. In this review we will also comment the clinical implications of pregnancies occurring in women who received a orthotopic liver transplantation (OLT) Therefore, the management of immunosuppressive therapy before and after the delivery in women who received liver transplant is becoming a relevant clinical issue. Finally, we will focus on acute and chronic viral hepatitis occurring during pregnancy, on management of advanced liver disease and we will review the literature on the challenging issue regarding pregnancy and OLT.


Assuntos
Hepatite Viral Humana/diagnóstico , Hepatite Viral Humana/terapia , Complicações Infecciosas na Gravidez , Doença Aguda , Doença Crônica , Gerenciamento Clínico , Feminino , Hepatite Viral Humana/complicações , Hepatite Viral Humana/patologia , Hepatite Viral Humana/virologia , Humanos , Transplante de Fígado , Gravidez
16.
Liver Int ; 35 Suppl 1: 71-7, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25529090

RESUMO

Chronic hepatitis C virus (HCV) causes chronic liver injury and can lead to cirrhosis and hepatocellular carcinoma (HCC). HCV can also interact with the immune system to cause several HCV related disorders including essential mixed cryoglobulinemia, vasculitis, dermatitis, glomerulonephritis and lymphoma. A strong association between HCV and diabetes mellitus also exists. These extrahepatic features may lead to increased fatigue and a reduced quality of life. It is now possible to cure most patients with chronic HCV using oral antiviral therapy. Many of these HCV-related disorders and symptoms can be cured when HCV is eradicated. However, some patients may have irreversible injury to extrahepatic sites, cirrhosis that cannot resolve, an increased risk for HCC, persistent fatigue and a reduced quality of life, despite achieving sustained virological response.


Assuntos
Antivirais/uso terapêutico , Carcinoma Hepatocelular/etiologia , Doença Hepática Terminal/etiologia , Hepatite C Crônica/complicações , Hepatite C Crônica/tratamento farmacológico , Hepatite C Crônica/epidemiologia , Neoplasias Hepáticas/etiologia , Crioglobulinemia/etiologia , Dermatite/etiologia , Glomerulonefrite/etiologia , Hepatite C Crônica/imunologia , Humanos , Linfoma/etiologia , Qualidade de Vida , Fatores de Risco , Vasculite/etiologia
17.
Biochem Biophys Res Commun ; 446(3): 736-40, 2014 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-24525121

RESUMO

Oxidative stress and dysregulated cholesterol metabolism are characteristic features of chronic hepatitis C virus infection (CHC). Therefore, we analyzed serum oxysterol profiles in CHC patients and examined the significance of oxysterols in CHC. The concentrations of 7α-hydroxycholesterol, 4ß-hydroxycholesterol and 25-hydroxycholesterol as determined by LC-ESI-MS/MS were significantly elevated by +236%, +29% and +44%, respectively, in CHC patients compared with controls. Moreover, the elevated levels were significantly decreased by anti-viral therapy using PEGylated-interferon and ribavirin for 3 months. In contrast, 24S-hydroxycholesterol, 27-hydroxycholesterol and 7α-hydroxy-4-cholesten-3-one concentrations were not affected by CHC or anti-viral treatment. These results suggest that some oxysterols that are elevated in CHC are produced by cholesterol autoxidation due to oxidative stress or inflammation in the liver. Oxysterols may represent novel targets for the inhibition of disease progression and the prevention of hepatocarcinogenesis in CHC patients.


Assuntos
Hepatite C Crônica/sangue , Hepatite C Crônica/tratamento farmacológico , Hidroxicolesteróis/sangue , Antivirais/uso terapêutico , Estudos de Casos e Controles , Feminino , Humanos , Interferon alfa-2 , Interferon-alfa/uso terapêutico , Masculino , Pessoa de Meia-Idade , Estresse Oxidativo , Polietilenoglicóis/uso terapêutico , Proteínas Recombinantes/uso terapêutico , Ribavirina/uso terapêutico , Espectrometria de Massas por Ionização por Electrospray/métodos , Espectrometria de Massas em Tandem/métodos
19.
Front Vet Sci ; 11: 1377207, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38988986

RESUMO

Introduction: Feline Infectious Peritonitis (FIP) has historically been a fatal coronavirus disease in cats. In recent years, the therapeutic agent GS-441524, developed by Gilead Sciences, was found to be a successful treatment for FIP in most patients in clinical trials. However, this particular drug has remained stalled in the therapeutic pipeline, leaving patients and cat owners without a licensed medication. In the meantime, online social media platforms began to emerge, connecting cat owners with a community of citizen non-veterinary professionals sourcing unlicensed GS-441524. Methods: This study prospectively followed participants (N = 141) that successfully completed 12 weeks of treatment, capturing their treatment experiences with self-administered GS-441524-like medication. A one-time survey was administered to enrolled participants with mixed format of questions (open-ended and multiple-choice) asking about treatment administration techniques, observed side effects of GS-441524, accrued cost, veterinarian involvement, impact on the cat-human bond, and social media usage. Results: Our results show cat owners experienced a shift in treatment modality from injectable GS-441524 to pill formulation across the treatment period. The average total cost of medication has decreased since 2021 to approximately USD 3100, and participants reported the human-animal bond being affected negatively. Additionally, there was an increased trend in veterinarian awareness of GS-441524-like therapeutics and monitoring of clients undergoing treatment. Social media usage was reported as being important at the beginning of treatment to establish treatment administration but lessened by the end of treatment. Discussion: This study is the first detailed, prospective account of owner experiences with unlicensed GS-441524, raising an important discussion surrounding citizen veterinary medicine.

20.
Ther Deliv ; 15(3): 211-232, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38410933

RESUMO

Hepatitis B virus (HBV) & hepatitis C virus (HCV) infection is a substantial reason for morbidity and mortality around the world. Chronic hepatitis B (CHB) infection is connected with an enhanced risk of liver cirrhosis, liver decompensation and hepatocellular carcinoma (HCC). Conventional therapy do face certain challenges, for example, poor tolerability and the growth of active resistance. Thus, novel treatment procedures are essential to accomplish the initiation of strong and stable antiviral immune reactions of the individuals. This review explores the current nanotechnology-based carriers for drug and vaccine delivery to treat HBV and HCV.


Hepatitis infections are a major health problem that affects lots of people across the globe. Without treatment, it can seriously harm the liver and might even lead to a type of liver cancer. The treatments we currently have can sometimes cause side effects or the virus can learn how to fight back against them. This means we need new and better ways to treat it. In our article, we talk about how Hepatitis B and C affects the body and how our natural defenses try to protect us. We then dive into a kind of science called nanotechnology, which uses tiny particles to help deliver medicine or vaccines in a better way. This new method could help medications be better at treating Hepatitis B and C.


Assuntos
Carcinoma Hepatocelular , Hepatite B Crônica , Hepatite B , Hepatite C , Neoplasias Hepáticas , Humanos , Hepatite B/tratamento farmacológico , Hepatite B/prevenção & controle , Hepatite B Crônica/tratamento farmacológico , Hepatite C/tratamento farmacológico , Antivirais/uso terapêutico
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