Resistencia a los inhibidores de la integrasa en niños con el virus de la inmunodeficiencia humana por transmisión vertical: primeros casos en Uruguay / Resistance to integrase inhibitors in children with vertically-transmitted human immunodeficiency virus: First cases in Uruguay

La resistencia a los antirretrovirales (ARV) es un problema de salud pública. Con el uso de inhibidores de la integrasa (INSTI) en pediatría, también comienzan a aparecer resistencias. El objetivo de esta comunicación es describir 3 casos con resistencia a los INSTI. Se describen 3 pacientes pediátricos con transmisión vertical del virus de la inmunodeficiencia humana (VIH). Iniciaron ARV de lactantes y preescolares, con mala adherencia al tratamiento, cursaron con diferentes planes secundarios a comorbilidades asociadas y fallas virológicas por resistencia. Los 3 casos clínicos describen la rápida aparición de resistencia frente a la falla virológica y el compromiso de los INSTI. La adherencia debe ser supervisada para detectar precozmente el aumento de la viremia. La falla virológica en un paciente tratado con raltegravir obliga a un rápido cambio de esquema ARV, ya que continuar utilizándolo podría favorecer nuevas mutaciones y resistencia a los INSTI de segunda generación.

Antiretroviral (ARV) drug resistance is a public health issue. Resistance has also been observed in the case of integrase strand transfer inhibitors (INSTIs) used in pediatrics. The objective of this article is to describe 3 cases of INSTI resistance. These are the cases of 3 children with vertically-transmitted human immunodeficiency virus (HIV). They were started on ARVs as infants and preschoolers, with poor treatment adherence, and had different management plans due to associated comorbidities and virological failure due to resistance. In the 3 cases, resistance developed rapidly as a result of virological failure and INSTI involvement. Treatment adherence should be monitored so that any increase in viremia can be detected early. Virological failure in a patient treated with raltegravir forces to a rapid change in ARV therapy because its continued use may favor new mutations and resistance to second-generation INSTIs.

An antimicrobial activity of oil extracted from Saara hardwickii / Atividade antimicrobiana do óleo extraído de Saara hardwickii

Present research work represents antiviral and antibacterial value of body fat of Saara hardwickii commonly called as spiny tailed lizard. Oil was extracted from body fats located in the ventral region of this animal using hydrocarbons e.g., n-hexane, methanol, butanol and ethyl acetate as a solvent. The antibacterial activity of lizard oil was tested against standard as well as multi-resistant lines ofEscherichia coli, Styphalococcus aureus, Pseudomonas aeruginosa and Proteus vulgaris alone and with antibiotic ampicillin. For antibacterial potential, Ethyl acetate and Butanol solvent extract showed best zone of inhibition (7mm) with P. aeruginosa and S. aureus respectively. For antiviral potential, Butanol and Methanol extract showed best HA (Hemagglutination) titer of 04 with NDV and IBV viral strain respectively. It is concluded that lizard oil has antimicrobial potential against different pathogens strains (virus, bacteria).

O presente trabalho de pesquisa apresenta a importância antiviral e antibacteriana da gordura corporal de Saara hardwickii, comumente chamado de lagarto de cauda espinhosa. O óleo foi extraído de gorduras corporais localizadas na região ventral desse animal usando hidrocarbonetos, por exemplo, n-hexano, metanol, butanol e acetato de etila, como solvente. A atividade antibacteriana do óleo do lagarto foi testada em linhagens padrão e multirresistentes de Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa e Proteus vulgaris, de forma isolada e com antibiótico ampicilina. Para o potencial antibacteriano, acetato de etila e extrato de butanol apresentaram melhor zona de inibição (7 mm) com P. aeruginosa e S. aureus, respectivamente. Para o potencial antiviral, o extrato de butanol e o extrato de metanol apresentaram melhor título de hemaglutinação de 4 com as cepas virais NDV e IBV, respectivamente. Conclui-se que o óleo do lagarto possui potencial antimicrobiano contra diferentes cepas de patógenos (vírus e bactérias).

An antimicrobial activity of oil extracted from Saara hardwickii

Abstract Present research work represents antiviral and antibacterial value of body fat of Saara hardwickii commonly called as spiny tailed lizard. Oil was extracted from body fats located in the ventral region of this animal using hydrocarbons e.g., n-hexane, methanol, butanol and ethyl acetate as a solvent. The antibacterial activity of lizard oil was tested against standard as well as multi-resistant lines ofEscherichia coli, Styphalococcus aureus, Pseudomonas aeruginosa and Proteus vulgaris alone and with antibiotic ampicillin. For antibacterial potential, Ethyl acetate and Butanol solvent extract showed best zone of inhibition (7mm) with P. aeruginosa and S. aureus respectively. For antiviral potential, Butanol and Methanol extract showed best HA (Hemagglutination) titer of 04 with NDV and IBV viral strain respectively. It is concluded that lizard oil has antimicrobial potential against different pathogens strains (virus, bacteria).

Resumo O presente trabalho de pesquisa apresenta a importância antiviral e antibacteriana da gordura corporal de Saara hardwickii, comumente chamado de lagarto de cauda espinhosa. O óleo foi extraído de gorduras corporais localizadas na região ventral desse animal usando hidrocarbonetos, por exemplo, n-hexano, metanol, butanol e acetato de etila, como solvente. A atividade antibacteriana do óleo do lagarto foi testada em linhagens padrão e multirresistentes de Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa e Proteus vulgaris, de forma isolada e com antibiótico ampicilina. Para o potencial antibacteriano, acetato de etila e extrato de butanol apresentaram melhor zona de inibição (7 mm) com P. aeruginosa e S. aureus, respectivamente. Para o potencial antiviral, o extrato de butanol e o extrato de metanol apresentaram melhor título de hemaglutinação de 4 com as cepas virais NDV e IBV, respectivamente. Conclui-se que o óleo do lagarto possui potencial antimicrobiano contra diferentes cepas de patógenos (vírus e bactérias).

Recent advances in small-molecule inhibitors targeting influenza virus RNA-dependent RNA polymerase / 药学学报

Influenza virus causes serious threat to human life and health. Due to the inherent high variability of influenza virus, clinically resistant mutant strains of currently approved anti-influenza virus drugs have emerged. Therefore, it is urgent to develop antiviral drugs with new targets or mechanisms of action. RNA-dependent RNA polymerase is directly responsible for viral RNA transcription and replication, and plays key roles in the viral life cycle, which is considered an important target of anti-influenza drug design. From the point of view of medicinal chemistry, this review summarizes current advances in diverse small-molecule inhibitors targeting influenza virus RNA-dependent RNA polymerase, hoping to provide valuable reference for development of novel antiviral drugs.

Exantema en enfermedad por virus de inmunodeficiencia humana, ¿manifestación de infección o reacción alérgica?

Paciente varón que presentó exantema maculopapular, no pruriginoso, sin afectación palmoplantar, luego de recibir tratamiento con trimetoprim/sulfametoxazol por siete días debido a sintomatología gastrointestinal. Tras realizar historia clínica completa y con pruebas de cuarta generación se confirmó infección por VIH. Al quinto día de tratamiento antirretroviral presentó nuevas lesiones eritematosas con descamación gruesa, pruriginosas, edema facial y eosinofilia. Se realizó una biopsia de piel que reportó una dermatitis liquenoide, con espongiosis, degeneración vacuolar de la capa basal, queratinocitos necróticos e infiltrado de eosinófilos, características que favorecen la reacción por drogas. El tratamiento consistió en interrumpir la terapia combinada, uso de corticoides sistémicos, antihistamínicos y ya que, no se trató de un cuadro severo, se reinició el tratamiento antirretroviral sin complicaciones.

A male patient presented with a maculopapular, non-pruritic rash, without palmoplantar involvement, after receiving treatment with trimethoprim/sulfamethoxazole for seven days due to gastrointestinal symptoms. After taking a complete medical history and using fourth-generation tests confirmed HIV infection. On the fifth day of antiretroviral treatment, he presented new erythematous lesions with thick, pruritic scaling, facial edema and eosinophilia. A skin biopsy reported lichenoid dermatitis, with spongiosis, vacuolar degeneration of the basal layer, necrotic keratinocytes and eosinophil infiltrate, characteristics that favor drug reaction. The treatment consisted of interrupting the combined therapy, using systemic corticosteroids, antihistamines and since it was not a severe condition, antiretroviral treatment restarted without complications.

Ethnopharmacological Characteristics of Pycnanthus angolensis (Welw.) Warb. (Myristicaceae), a Plant Used in the Traditional Treatment of Viral and Parasitic Diseases

Background: Pycnanthus angolensis (Welw.) Warb. (Myristicaceae) is a medicinal plant used in traditional Ivorian medicine. A recent ethnobotanical survey has discovered Pycnanthus angolensis in the traditional treatment of viral and parasitic diseases. Aim: The present study aims to highlight the distinctive ethnopharmacological characteristics of Pycnanthus angolensis. Methods: The aim was to identify some groups of chemical compounds by thin layer chromatography, to assay some minerals and finally to characterise the specific anatomical and micrographic features of the plant. Results: Terpenes and sterols, saponosides, flavonoids and tannins are the main phytocompounds revealed. Magnesium with 621.3 mg/100 g dry matter is the most abundant mineral. Anatomical sections and plant powder revealed starch grains, calcium oxalate crystals, secretory pockets and tector hairs that are responsible for the formation of various biological substances in the plant. Conclusion: These results add to the data on Pycnanthus angolensis, a taxon much used in traditional Ivorian medicine for the treatment of antiparasitic and antiviral diseases.

A Mouthwash with Cetylpyridinium Chlorideis reducing salivary SARS-CoV-2 viral load in +COVID-19 / Un enjuague con Cloruro de Cetilpiridinio redujo la carga salival del virus SARSCoV-2 en pacientes con Covid-19

Aim: The aim of this randomised, double-blind, placebo-controlled pilot clinical trial is to evaluate the capacity of a mouthwash to reduce SARS-CoV-2 viral load in the saliva of patients with COVID-19. Methods: Twenty-three symptomatic SARS-CoV-2-positive outpatients were selected andrandomised into two groups and registered at NTC 04563689. Both groups rinsed and gargled for one minute with either distilled water (Placebo) or with 0.05% Cetylpyridinium chloride (CPC) plus 0.12% Chlorhexidine (CHX) mouthwash (PERIOAID Intensive Care). Saliva samples were collected before the use of placebo or mouthwash and after 15 minutes and 1 and 2 hours of either of the above treatment. A saliva sample was also taken five days after regular use of placebo or mouthwash twice daily. The virus was detected by qRT-PCR. Results: A great heterogeneity in the viral load values was observed at baseline in both groups for nasopharyngeal and saliva samples. Most of the patients who used the mouthwash (8/12) had a significant decrease in baseline viral load after 15 min (greater than 99% reduction). This inhibitory effect was maintained for up to two hours in 10 of the 12 patients. At five days, SARS-CoV-2 RNA was detectedin only 1 patient from the mouthwash group and in 5 from the placebo group. Conclusions: This study points out that a CPC mouthwash can reduce the viral load in saliva of COVID-positive patients. This finding may be important in transmission control of SARS-CoV-2. Nevertheless, the clinical relevance of CPC mouthwash-reduction on SARS-CoV-2 shedding in saliva requires further study.

Objetivo: El objetivo de este ensayo clínico piloto aleatorizado, doble ciego y controlado con placebo es evaluar la capacidad de un enjuague bucal para reducir la carga viral del SARS-CoV-2 en la saliva de pacientes con COVID-19. Materiales y métodos:Veintitrés pacientes ambulatorios positivos para SARS-CoV-2 sintomáticos fueron seleccionados y aleatorizados en dos grupos y registrados en el NTC 04563689. Ambos grupos se enjuagaron y hicieron gárgaras durante un minuto con agua destilada (placebo) o con cloruro decetilpiridinio al 0 ,05 % (CPC). ) más enjuague bucal con Clorhexidina (CHX) al 0,12% (PERIOAID Intensive Care). Se recolectaron muestras de saliva antes del uso de placebo o enjuague bucal y después de 15 minutos y 1 y 2 horas de cualquiera de los tratamientos anteriores. También se tomó una muestra de saliva cinco días después del uso regular de placebo o enjuague bucal dos veces al día. El virus fue detectado por qRT-PCR. Resultados:Se demostró una gran heterogeneidad en los valores de carga viral al inicio del estudio en grupos ambos para muestras de nasofaringe y saliva. La mayoría de los pacientes que usaron el enjuague bucal (8/12) tuvieron una disminución significativa en la carga viral inicial después de 15 minutos (reducción superior al 99 %). Este efecto inhibidor se mantuvo hasta dos horas en 10 de los 12 pacientes. A los cinco días, se detectó ARN del SARS-CoV-2 en solo 1 paciente del grupo de enjuague bucal y en 5 del grupo de placebo. Conclusiones:Este señala que un enjuague bucal CPC puedereducir la carga viral en saliva de pacientes COVID positivos. Este hallazgo puede ser importante en el control de la transmisión del SARS-CoV-2. Sin embargo, la relevancia clínica de la reducción del enjuague bucal con CPC en la excreción de SARS-CoV-2 en la saliva requiere más estudios.

Hepatic pathological characteristics and factors influencing alanine transaminase value below twice the upper limit of normal in patients with chronic hepatitis B / 中华肝脏病杂志

Objective: To analyze the hepatic pathological characteristics and factors influencing an alanine transaminase value below twice the upper limit of normal in patients with chronic hepatitis B (CHB) and further explore the optimal ALT threshold strategy for initiating antiviral therapy. Methods: Clinical data of treatment-naïve CHB patients who underwent liver biopsies from January 2010 to December 2019 were retrospectively collected. Multiple regression models were used to explore the ALT levels and significant risk of hepatic histological changes (≥G2/S2). Receiver operating characteristic curve was used to evaluate the value of different models in diagnosing liver tissue inflammation≥G2 or fibrosis ≥ S2. Results: A total of 447 eligible CHB patients, with a median age of 38.0 years and 72.9% males, were included. During ALT normalization, there was significant liver inflammation (≥G2) and fibrosis (≥S2) in 66.9% and 53.0% of patients, respectively. With an ALT rise of 1-2×ULN, the proportions of liver inflammation≥G2 and fibrosis≥S2 were 81.2% and 60.0%, respectively. After adjusting for confounding factors, higher ALT levels (> 29 U/L) were found to be associated with significant liver inflammation (OR: 2.30, 95% CI: 1.11 ~ 4.77) and fibrosis (OR: 1.84, 95% CI: 1.10 ~ 3.09). After the measurement of glutamyltransferase-platelet ratio (GPR), the proportion of CHB patients with≥G2/S2 was significantly reduced under different treatment thresholds of ALT standards, and in particular, the erroneous evaluation of liver fibrosis≥S2 was significantly improved (33.5% to 57.5%). Conclusion: More than half of CHB patients have a normal ALT or one within 2 × ULN, regardless of whether or not there is apparent inflammation and fibrosis. GPR can significantly improve the precise assessment of different conditions of treatment thresholds for the ALT value in CHB patients.

In vitro inhibition of carnosic acid against influenza A virus infections / 药学学报

Carnosic acid (CA) is the main phenolic diterpenoid active ingredient in plants such as rosemary and sage, and has antiviral, antioxidant, anti-inflammatory effects and so on, however, its antiviral activity against influenza virus infections was not reported. In this study, antiviral activities against influenza A virus infections of three main bioactive ingredients from rosemary, including rosmarinic acid, CA and ursolic acid, were evaluated using virus titer titration assay, and CA showed remarkable inhibition on influenza H5N1 replication in A549 cells. The antiviral activity of CA was further confirmed and its mechanism of action was investigated using the indirect immunofluorescence assay (IFA), Western blot and real-time fluorescence quantification polymerase chain reaction (qRT-PCR). The results showed that the 50% effective concentration (EC50) of CA against influenza H5N1 in A549 cells and MDCK cells were 4.30 and 3.64 μmol·L-1, respectively. Meanwhile, CA also showed inhibition on influenza virus 2009panH1N1 (EC50: 10.1 μmol·L-1) and H3N2 (EC50: 12.8 μmol·L-1) replications in A549 cells. Mechanistic studies showed that antiviral activity of CA is related to its induction of heme oxygenase-1 (HO-1) in A549 cells and suppression on production of reactive oxygen in H5N1-infected cells.

Status of clinical research in HCV-negative recipients undergoing kidney transplantation from HCV-positive renal allografts / 器官移植

Antiviral therapy for chronic hepatitis C virus (HCV) infection has entered the era of direct antiviral agent (DAA), and up to 95% of patients could be clinically cured. Under this circumstance, HCV infection has gradually changed from relative contraindication to surgical indication for kidney transplantation. However, at present, the number of kidney transplantation from HCV-infected donors or recipients has been rarely reported in China. The short-term follow-up data of HCV-negative recipients undergoing kidney transplantation from HCV-positive renal allografts in other countries have confirmed that DAA yields high cure rate and safety in the treatment of HCV infection, and recipients could obtain favorable short-term survival and allograft outcome. However, the long-term safety of HCV-infected kidney transplantation remains to be validated by clinical trials with large sample size and long-term follow-up. In this article, the virological clearance, allograft outcome and safety of DAA use in HCV-negative recipients undergoing kidney transplantation from HCV-positive renal allografts under the intervention of DAA were investigated, aiming to evaluate clinical safety and efficacy of this pattern of kidney transplantation and deepen the understanding of safe use of HCV-positive organs.

Predictive factors for functional cure after sequential therapy with nucleos(t)ide analogues and pegylated interferon alfa-2b in treatment of chronic hepatitis B / 临床肝胆病杂志

Objective To investigate the independent predictive factors for functional cure after long-term nucleos(t)ide analogue (NUC) antiviral therapy followed by pegylated interferon α-2b therapy in chronic hepatitis B (CHB) patients. Methods A total of 162 CHB patients who were admitted to several hospitals in Qingdao, China, from 2018 to 2021 were enrolled as subjects, and all patients received pegylated interferon α-2b for at least 48 weeks after NUC therapy for one year or longer. According to whether HBsAg clearance was achieved at week 48 of pegylated interferon α-2b treatment, the patients were divided into functional cure group with 79 patients and non-cure group with 83 patients, and related clinical indices were compared between the two groups. The two-independent-samples t test and the Mann-Whitney U rank sum test were used for comparison of continuous data between two groups, and the chi-square test was used for comparison of categorical data between two groups. The Spearman correlation analysis was performed, and the univariate and multivariate logistic regression analyses were used to investigate the independent predictive factors for functional cure. The receiver operating characteristic (ROC) curve was plotted for related variables, and the area under the ROC curve (AUC) was used to evaluate the prediction accuracy of the variables. Results Compared with the non-cure group, the functional cure group had a significantly lower HBsAg level at baseline [21.63 (3.33-157.60) IU/mL vs 794.70 (336.10-1 185.34) IU/mL, Z =-8.869, P 1000 IU/mL (0 vs 8.4%, χ 2 =5.073, P =0.024), a significantly lower level of total bilirubin at baseline [12.60 (10.12-15.93) μmol/L vs 15.50 (11.80-24.10) μmol/L, Z =-3.611, P 2×upper limit of normal (16.5% vs 4.8%, χ 2 =5.835, P =0.016). The multivariate logistic regression analysis showed that baseline HBsAg (odds ratio [ OR ]=0.996, 95% confidence interval [ CI ]: 0.995-0.997, P < 0.001), HBsAg at week 12 of pegylated interferon α-2b treatment ( OR =0.990, 95% CI : 0.986-0.994, P < 0.001), HBsAg at week 24 of pegylated interferon α-2b treatment ( OR =0.983, 95% CI : 0.975-0.991, P < 0.001), and baseline total bilirubin ( OR =0.885, 95% CI : 0.826-0.949, P =0.001) were independent predictive factors for functional cure. The ROC curve of baseline HBsAg showed an AUC of 0.904 and the optimal cut-off value of 118.24 IU/mL; the ROC curve of HBsAg at week 12 of pegylated interferon α-2b treatment showed an AUC of 0.948 and the optimal cut-off value of 73.74 IU/mL; the ROC curve of HBsAg at week 24 of pegylated interferon α-2b treatment showed an AUC of 0.975 and the optimal cut-off value of 11.01 IU/mL; the ROC curve of baseline total bilirubin showed an AUC of 0.664 and the optimal cut-off value of 19.9 μmol/L. Conclusion Baseline HBsAg, HBsAg at week 12 of pegylated interferon α-2b treatment, HBsAg at week 24 of pegylated interferon α-2b, and baseline total bilirubin are independent predictive factors for functional cure at week 48 of pegylated interferon α-2b treatment in CHB patients receiving sequential therapy with NUC and pegylated interferon α-2b.

The host-targeting compound peruvoside has a broad-spectrum antiviral activity against positive-sense RNA viruses

Positive-sense RNA viruses modify intracellular calcium stores, endoplasmic reticulum and Golgi apparatus (Golgi) to generate membranous replication organelles known as viral factories. Viral factories provide a conducive and substantial enclave for essential virus replication via concentrating necessary cellular factors and viral proteins in proximity. Here, we identified the vital role of a broad-spectrum antiviral, peruvoside in limiting the formation of viral factories. Mechanistically, we revealed the pleiotropic cellular effect of Src and PLC kinase signaling via cyclin-dependent kinase 1 signaling leads to Golgi-specific brefeldin A-resistance guanine nucleotide exchange factor 1 (GBF1) phosphorylation and Golgi vesiculation by peruvoside treatment. The ramification of GBF1 phosphorylation fosters GBF1 deprivation consequentially activating downstream antiviral signaling by dampening viral factories formation. Further investigation showed signaling of ERK1/2 pathway via cyclin-dependent kinase 1 activation leading to GBF1 phosphorylation at Threonine 1337 (T1337). We also showed 100% of protection in peruvoside-treated mouse model with a significant reduction in viral titre and without measurable cytotoxicity in serum. These findings highlight the importance of dissecting the broad-spectrum antiviral therapeutics mechanism and pave the way for consideration of peruvoside, host-directed antivirals for positive-sense RNA virus-mediated disease, in the interim where no vaccine is available.

Tea tree oil, a vibrant source of neuroprotection via neuroinflammation inhibition: a critical insight into repurposing Melaleuca alternifolia by unfolding its characteristics / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Over the past few decades, complementary and alternative treatments have become increasingly popular worldwide. The purported therapeutic characteristics of natural products have come under increased scrutiny both in vitro and in vivo as part of efforts to legitimize their usage. One such product is tea tree oil (TTO), a volatile essential oil primarily obtained from the native Australian plant, Melaleuca alternifolia, which has diverse traditional and industrial applications such as topical preparations for the treatment of skin infections. Its anti-inflammatory-linked immunomodulatory actions have also been reported. This systematic review focuses on the anti-inflammatory effects of TTO and its main components that have shown strong immunomodulatory potential. An extensive literature search was performed electronically for data curation on worldwide accepted scientific databases, such as Web of Science, Google Scholar, PubMed, ScienceDirect, Scopus, and esteemed publishers such as Elsevier, Springer, Frontiers, and Taylor & Francis. Considering that the majority of pharmacological studies were conducted on crude oils only, the extracted data were critically analyzed to gain further insight into the prospects of TTO being used as a neuroprotective agent by drug formulation or dietary supplement. In addition, the active constituents contributing to the activity of TTO have not been well justified, and the core mechanisms need to be unveiled especially for anti-inflammatory and immunomodulatory effects leading to neuroprotection. Therefore, this review attempts to correlate the anti-inflammatory and immunomodulatory activity of TTO with its neuroprotective mechanisms.

Research progress on the nucleoside/nucleotide-loaded nanomedicines / 浙江大学学报·医学版

Nucleoside drugs play an essential role in treating major diseases such as tumor and viral infections, and have been widely applied in clinics. However, the effectiveness and application of nucleoside drugs are significantly limited by their intrinsic properties such as low bioavailability, lack of targeting ability, and inability to enter the cells. Nanocarriers can improve the physiological properties of nucleoside drugs by improving drug delivery efficiency and availability, maintaining drug efficacy and system stability, adjusting the binding ability of the carrier and drug molecules, as well as modifying specific molecules to achieve active targeting. Starting from the design strategy of nucleoside drug nanodelivery systems, the design and therapeutic effect of these nanomedicines are described in this review, and the future development directions of nucleoside/nucleotide-loaded nanomedicines are also discussed.

Diagnostic value of novel hepatic fibrosis markers in assessing cirrhosis in patients with chronic hepatitis C / 中华肝脏病杂志

Objective: To investigate the efficacy of chitinase-3-like protein 1 (CHI3L1) and Golgi protein 73 (GP73) in the diagnosis of cirrhosis and the dynamic changes of CHI3L1 and GP73 after HCV clearance in patients with chronic hepatitis C (CHC) treated with direct-acting antiviral drugs (DAAs). The comparison of continuous variables of normal distribution were statistically analyzed by ANOVA and t-test. The comparison of continuous variables of non-normal distribution were statistically analyzed by rank sum test. The categorical variables were statistically analyzed by Fisher's exact test and χ(2) test. Correlation analysis was performed using Spearman correlation analysis. Methods: Data of 105 patients with CHC diagnosed from January 2017 to December 2019 were collected. The receiver operating characteristic curve (ROC curve) was plotted to study the efficacy of serum CHI3L1 and GP73 for the diagnosis of cirrhosis. Friedman test was used to compare CHI3L1 and GP73 change characteristics. Results: The areas under the ROC curve for CHI3L1 and GP73 in the diagnosis of cirrhosis at baseline were 0.939 and 0.839, respectively. Serum levels of CHI3L1 and GP73 in the DAAs group decreased significantly at the end of treatment compared with baseline [123.79 (60.25, 178.80) ng/ml vs. 118.20 (47.68, 151.36) ng/ml, P = 0.001; 105.73 (85.05, 130.69) ng/ml vs. 95.52 (69.52, 118.97) ng/ml, P = 0.001]. Serum CHI3L1 and GP73 in the pegylated interferon combined with ribavirin (PR) group were significantly lower at the end of 24 weeks of treatment than the baseline [89.15 (39.15, 149.74) ng/ml vs. 69.98 (20.52, 71.96) ng/ml, P < 0.05; 85.07 (60.07, 121) ng/ml vs. 54.17 (29.17, 78.65) ng/ml, P < 0.05]. Conclusion: CHI3L1 and GP73 are sensitive serological markers that can be used to monitor the fibrosis prognosis in CHC patients during treatment and after obtaining a sustained virological response. Serum CHI3L1 and GP73 levels in the DAAs group decreased earlier than those in the PR group, and the serum CHI3L1 levels in the untreated group increased compared with the baseline at about two years of follow-up.

Study on the related factors of antiviral treatment in previously reported hepatitis C patients based on the Andersen model / 中华肝脏病杂志

Objective: To understand the basic characteristics of previously reported patients with hepatitis C and analyze the related factors affecting their antiviral treatment. Methods: A convenient sampling method was adopted. Patients who had been previously diagnosed with hepatitis C in the Wenshan Prefecture of Yunnan Province and Xuzhou City of Jiangsu Province were contacted by telephone for an interview study. The Andersen health service utilization behavior model and related literature were used to design the research framework for antiviral treatment in previously reported hepatitis C patients. A step-by-step multivariate regression analysis was used in previously reported hepatitis C patients treated with antiviral therapy. Results: A total of 483 hepatitis C patients, aged 51.73 ± 12.06 years, were investigated. The proportion of male, agricultural occupants who were registered permanent residents, farmers and migrant workers was 65.24%, 67.49%, and 58.18%, respectively. Han ethnicity (70.81%), married (77.02%), and junior high school and below educational level (82.61%) were the main ones. Multivariate logistic regression analysis results showed that married patients with hepatitis C (OR = 3.19, 95% CI: 1.93-5.25, compared with unmarried, divorced, and widowed patients) with high school education or above (OR = 2.54, 95% CI: 1.54-4.20, compared with patients with junior high school education or below) were more likely to receive antiviral treatment in the predisposition module. Patients with severe self-perceived hepatitis C in the need factor module (compared with patients with mild self-perceived disease, OR = 3.36, 95% CI: 2.09-5.40) were more likely to receive treatment. In the competency module, the family's per capita monthly income was more than 1,000 yuan (compared with patients with per capita monthly income below 1,000 yuan, OR = 1.59, 95% CI: 1.02-2.47), and the patients had a high level of awareness of hepatitis C knowledge (compared with patients with a low level of knowledge, OR = 1.54, 95% CI: 1.01-2.35), and the family members who knew the patient's infection status (compared with patients with an unknown infection status, OR = 4.59, 95% CI: 2.24-9.39) were more likely to receive antiviral treatment. Conclusion: Different income, educational, and marital statuses are related to antiviral treatment behavior in hepatitis C patients. Family support of hepatitis C patients receiving hepatitis C-related knowledge and their families knowing the infection status is more important in promoting the antiviral treatment of patients, suggesting that in the future, we should further strengthen the hepatitis C knowledge of hepatitis C patients, especially the family support of hepatitis C patients' families in treatment.

Caracterización de pacientes con hepatitis C que recibieron tratamiento con drogas antivirales de acción directa

Introducción: La hepatitis C constituye un problema de salud pública mundial por su prevalencia y progresión a la cronicidad. El tratamiento de la hepatitis C con drogas antivirales de acción directa ha revolucionado la práctica de la hepatología clínica por la posibilidad de curar a la mayoría de los pacientes con tratamientos cortos y sin efectos adversos significativos. Objetivo: Caracterizar los pacientes con hepatitis C que recibieron tratamiento con drogas antivirales de acción directa en la provincia Camagüey. Métodos: Se realizó un estudio observacional descriptivo, transversal y retrospectivo en la provincia Camagüey durante el período del 4 de enero del año 2021 al 28 de marzo del año 2022. El universo de estudio estuvo constituido por 405 pacientes con diagnóstico de hepatitis C en la provincia. La muestra por 110 pacientes que hicieron tratamiento con ribavirina e interferón pegilado y no resolvieron pues sus cargas siguió detectables. Resultados: Se observó un predominio de los pacientes con hepatitis C en el grupo de edad de 55-59 años, sexo masculino, con 1 a 3 años de diagnosticada la enfermedad. No todos terminaron el tratamiento debido a la ocurrencia de fallecimientos. Los que cumplieron con el uso de las drogas antivirales de acción directa sofosbuvir y daclatasvir durante las 12 semanas, en su gran mayoría sus cargas virales resultaron no detectables fundamentalmente en población, no así en los hemodializados aunque estos disminuyeron sus cifras con relación a las que tenían antes de iniciar el tratamiento. Conclusiones: El tratamiento resultó ser efectivo.

Introduction: Hepatitis C constitutes a global public health problem due to its prevalence and progression to chronicity. The treatment of hepatitis C with direct-acting antiviral drugs has revolutionized the practice of clinical hepatology due to the possibility of curing the majority of patients with short treatments and without significant side effects. Objective: To characterize patients with hepatitis C who received treatment with direct-acting antiviral drugs in Camagüey province. Methods: A descriptive, cross-sectional and retrospective observational study was carried out in the Camagüey province during the period from January 4th, 2021 to March 28th, 2022. The universe of study consisted of 405 patients diagnosed with hepatitis C in the province. The sample was made up of 110 patients who underwent treatment with ribavirin and pegylated interferon and did not resolve as their charges continued to be detectable. Results: A predominance of patients with hepatitis C was observed in the age group of 55-59 years, male, with 1 to 3 years of diagnosis of the disease. Not all patients completed treatment due to the occurrence of deaths. Those who complied with the use of the direct-acting antiviral drugs sofosbuvir and daclatasvir during the 12 weeks, the vast majority of their viral loads were not detectable, mainly in the population, not so in the hemodialysis patients, although their figures decreased in relation to those who they had before starting treatment. Conclusions: The treatment turned out to be effective.

Effectiveness of wearing masks during the COVID-19 outbreak in cohort and case-control studies: a systematic review and meta-analysis / Eficácia do uso de máscaras durante o surto de COVID-19 em estudos de coorte e caso-controle: uma revisão sistemática e meta-análise

ABSTRACT Objective: To evaluate the efficacy of wearing a mask to prevent COVID-19 infection. Methods: This was a systematic review and meta-analysis of cohort and case-control studies, considering the best level of evidence available. Electronic databases (MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, and Clinical Trials.gov) were searched to identify studies that evaluated the effectiveness of wearing masks compared with that of not wearing them during the COVID-19 pandemic. Risk of bias and quality of evidence were assessed using the Cochrane risk of bias tool and the Grading of Recommendations Assessment, Development, and Evaluation. Results: Of the 1,028 studies identified, 9 met the inclusion criteria (2 cohort studies and 7 case-control studies) and were included in the analysis. The meta-analysis using cohort studies alone showed statistically significant differences, wearing a cloth mask decreased by 21% [RD = −0.21 (95% CI, −0.34 to −0.07); I2 = 0%; p = 0,002] the risk of COVID-19 infection, but the quality of evidence was low. Regarding case-control studies, wearing a surgical mask reduced the chance of COVID-19 infection [OR = 0.51 (95% CI, 0.37-0.70); I2 = 47%; p = 0.0001], as did wearing an N95 respirator mask [OR = 0.31 (95% CI, 0.20-0.49); I2 = 0%; p = 0.00001], both with low quality of evidence. Conclusions: In this systematic review with meta-analysis, we showed the effectiveness of wearing masks in the prevention of SARS-CoV-2 infection regardless of the type of mask (disposable surgical mask, common masks, including cloth masks, or N95 respirators), although the studies evaluated presented with low quality of evidence and important biases.

RESUMO Objetivo: Avaliar a eficácia do uso de máscaras na prevenção da infecção por COVID-19. Métodos: Revisão sistemática e meta-análise de estudos de coorte e caso-controle, considerando o melhor nível de evidência disponível. Bancos de dados eletrônicos (MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials e ClinicalTrials.gov) foram pesquisados para identificar estudos que avaliassem a eficácia do uso de máscaras em comparação com ausência de seu uso durante a pandemia de COVID-19. O risco de viés e a qualidade da evidência foram avaliados usando a ferramenta Cochrane risk of bias e Grading of Recommendations Assessment, Development, and Evaluation. Resultados: Dos 1.028 estudos identificados, 9 preencheram os critérios de inclusão (2 estudos de coorte e 7 estudos de caso-controle) e foram incluídos na análise. A meta-análise usando apenas estudos de coorte mostrou diferenças estatisticamente significativas: o uso de máscara de tecido diminuiu 21% [(risk difference = −0,21 (IC 95%: −0,34 a −0,07); I2 = 0%; p = 0,002] o risco de infecção por COVID-19, mas a qualidade da evidência foi baixa. Em relação aos estudos caso-controle, o uso de máscara cirúrgica reduziu a chance de infecção por COVID-19 [OR = 0,51 (IC 95%: 0,37-0,70); I2 = 47%; p = 0,0001], assim como o uso de máscara respiratória N95 [OR = 0,31 (IC 95%: 0,20-0,49); I2 = 0%; p = 0,00001], ambos com baixa qualidade de evidência. Conclusões: Nesta revisão sistemática com meta-análise, demonstramos a eficácia do uso de máscaras na prevenção da infecção por SARS-CoV-2 independentemente do tipo de máscara (máscara cirúrgica descartável, máscaras comuns, incluindo máscaras de tecido, ou respiradores N95), embora os estudos avaliados apresentassem evidências de baixa qualidade e vieses importantes.

Real-world effectiveness and safety of direct-acting antivirals for the treatment of hepatitis C virus in kidney and liver transplant recipients: experience of a large transplant center in Brazil

ABSTRACT Direct-acting antivirals are the gold-standard treatment for chronic HCV infections, but few studies have investigated their use on kidney and liver transplant recipients. We conducted a real-world study to evaluate the rates of sustained virological response with direct-acting antivirals in kidney and liver transplant recipients. Moreover, it also aimed to evaluate direct-acting antivirals (DAAs) interference with immunosuppressant levels and to describe the frequency of adverse events. As part of this retrospective observational cohort, we included adult patients that had undergone a kidney transplant (KT) or liver transplant (LT) at our center, had a chronic HCV infection, and were treated with DAAs from June 2016 to December 2021. A total of 165 patients were included in the analysis, divided in 108 KT and 57 LT recipients. HCV genotype 1 was more frequent in KT (58.4%), and genotype 3 was more prevalent in LT (57.9%) patients. Sustained virological response was achieved in 89.6% of patients. Adverse effects were reported by 36% of patients. There were significant interactions with immunosuppressants requiring dose adjustments. A total of three episodes of rejection were reported in KT recipients. In conclusion, DAA treatment resulted in high rates of SVR and was well tolerated in both kidney and liver transplant patients. Adverse events were frequent but not severe in most patients, with low treatment drop-out rates. Interactions with immunosuppressants need monitoring since dose adjustments may be required. Reporting real-life experiences is important to help build evidence for patient management in non-controlled environments.

Exploration on ALT threshold for initiating antiviral therapy in chronic HBV-infected patients based on results of 707 liver puncture cases / 中国热带医学

@#Abstract: Objective To explore the threshold of ALT for initiating antiviral therapy in HBV infected patients, and to provide a basis for initiating antiviral therapy in chronic HBV-infected patients. Methods This retrospective cohort study recruited 707 consecutive treatment-naïve chronic hepatitis B (CHB) patients undergoing diagnostic liver biopsy in the department of infectious diseases of the Affiliated Hospital of Yan′an University from October 2013 to August 2018. Liver biopsy specimens were obtained under ultrasound guidance using Menghini 16G disposable needles. The METAVIR scoring system, which is commonly used internationally, was used to divide the patients into the group with mild liver tissue injury and the group with significant liver tissue injury, and the alanine aminotransferase (ALT) levels were measured separately. Receiver operating characteristic (ROC) curve and Mann-Whitney U test were used to evaluate the diagnostic value of ALT for significant liver tissue injury under different demographic characteristics. Results Of 707 patients, 292 (41.30%) had significant liver tissue injury confirmed by liver biopsy (METAVIR ≥A2 and/or F2). When the ULN of ALT was set to NICE criteria (30 U/L for males, 19 U/L for females), AASLD criteria (35 U/L for males, 25 U/L for females) and EASL or APASL criteria (40 U/L for males and females), CHB patients with <ULN accounted for 32.38%, 35.03% and 36.07% of significant liver tissue injury, respectively. And significant liver tissue injury in CHB patients with 1-2×ULN accounted for 41.99%, 41.85% and 50.30%, respectively. The optimal ALT critical values were 33 U/L for overall patients, 25 U/L for females, 45 U/L for males, 45 U/L for ≤30 years olds, 33 U/L for>30 years olds, 22 U/L for HBeAg negative and 31 U/L for HBeAg positive patients. Conclusions The threshold of ALT for initiating antiviral therapy in chronic HBV patients should be individualized, especially should be down-regulated for the females, olders and HBeAg-negative patients.