Antiviral Treatment Group Research Articles

Real-world effectiveness of early anti-SARS therapy in severely immunocompromised COVID-19 outpatients during the SARS-CoV-2 omicron variant era: a propensity score-adjusted retrospective cohort study.

The effectiveness of the early treatment for antiviral agents in SARS-CoV-2 infection is closely related to patient comorbidities. Data on effectiveness in immunocompromised patients are limited, with reports involving highly heterogeneous and not well-defined populations. We aimed to assess the effectiveness of treatment in reducing hospitalizations in a real-world cohort of severely immunocompromised COVID-19 outpatients. We conducted a multicentre, retrospective, observational cohort study of immunocompromised outpatients attended in infectious diseases departments from 1 January to 31 December 2022. Propensity score matching (PSM) multivariable logistic regression models were used to estimate the adjusted odds ratio [(aOR, 95% confidence interval (CI)] for the association between antiviral prescription and outcome (COVID-19-related hospitalization up to Day 90). We identified 746 immunocompromised outpatients with confirmed SARS-CoV-2 infection. After eligibility criteria and PSM, a total of 410 patients were analysed: 205 receiving treatment (remdesivir, sotrovimab or nirmatrelvir/ritonavir) and 205 matched controls. Fifty-two patients required at least one COVID-19-related hospitalization 8 (3.9%) versus 44 (21.5%) in the antiviral and matched control cohorts, respectively. There were 13 deaths at 90 days, of which only 4 were COVID-19-related and none in the antiviral treatment group. After adjustment for residual confounders, the use of early therapy was associated with a protective effect on the risk of hospitalization [aOR 0.13 (0.05-0.29)], as was the use of biological immunomodulators [aOR 0.27 (0.10-0.74)], whereas chronic obstructive pulmonary disease [aOR 4.65 (1.09-19.69)] and anti-CD20 use [aOR 2.76 (1.31-5.81)] increased the odds. Early antiviral treatment was associated with a reduced risk of COVID-19-related hospitalization in ambulatory severely immunocompromised COVID-19 patients.

A multicenter study on the effects of congenital cytomegalovirus infection on hearing loss

Objective: To assess the clinical features and effectiveness of antiviral therapy in newborns with sensorineural hearing loss (SNHL) caused by congenital congenital cytomegalovirus (cCMV) infection, and to speculate the risk factors for poor hearing outcomes. Methods: A multicenter prospective cohort study wasconducted, enrolling 176 newborns diagnosed with cCMV at four research centers in Zhejiang Province from March 1, 2021, to April 30, 2024. Clinical characteristics at birth were recorded and hearing was followed up. The children were divided into groups based on their condition at birth, specifically into asymptomatic, mild symptom, and moderate to severe symptom groups. Additionally, they were divided into SNHL and normal hearing groups based on the results of air conduction brainstem audiometry at birth. And they were also divided into treatment and untreated groups according to antiviral treatment. Mann Whitney U test, and chi square test were used for inter group comparison to analyze the differences in clinical features between different disease groups, and to analyze the effects of clinical features, antiviral therapy, and other factors on hearing improvement. Logistic regression analysis was employed to identify the risk factors influencing hearing outcomes. Results: Among the cohort of 176 children diagnosed infection with cCMV, 90 cases were male and 86 cases were female. Of these, 79 cases were asymptomatic, 12 cases classified as mild cCMV and 85 cases as moderate to severe cCMV. Fifty cases belonged to SNHL group, with different degrees of severity, including 30 cases of mild, 9 cases of moderate, 5 cases of severe, and 6 cases of extremely severe SNHL. Among the 121 cases in the normal hearing group, 2 cases (1.7%) exhibited late-onset hearing loss despite having normal hearing at birth. Among 81 cases (46.0%) who completed the hearing follow-up, 71 cases (87.7%) had good hearing outcomes and 10 cases (12.3%) had poor hearing outcomes. Among the 81 children, 29 cases (35.8%) had SNHL at birth. During follow-up, the hearing threshold improved in 19 cases (65.5%), remained stable in 7 cases (24.1%) and progressed in 3 cases (10.3%). A total of 26 cases in the treatment group and 55 cases in the untreated group completed the hearing follow-up assessment. The rate of hearing improvement in the treatment group was found to be higher compared to the untreated group (13 cases (50.0%) vs. 6 cases (10.9%), χ2=15.00, P<0.01), with individuals in the treatment group having a 4.58 times greater likelihood of experiencing hearing improvement (RR=4.58,95%CI 1.96-10.70, P<0.05). However, no statistically significant difference was observed in hearing outcomes between the antiviral treatment group and the untreated group (RR=0.90, 95%CI 0.57-1.41, P=0.517). Multivariate analysis further confirmed SNHL (OR=11.58, 95%CI 2.10-63.93, P=0.005) and preterm birth (OR=4.98, 95%CI 1.06-23.41, P=0.042) as independent risk factors for poor hearing outcomes. Conclusions: SNHL resulting from cCMV infection presents symptoms at birth and can be improved by antiviral therapy. Poor hearing outcomes are associated with SNHL and prematurity.

Assessment of blood viral load in asymptomatic and symptomatic cases of congenital cytomegalovirus infection.

This study aimed to retrospectively evaluate the baseline and follow-up viral loads and viral clearance times in cases followed for asymptomatic and symptomatic congenital cytomegalovirus (cCMV) infection between August 2010 and August 2022. Among 93 cases, they had asymptomatic (n: 55) and symptomatic (n: 38). The median baseline blood viral load detected in the symptomatic cCMV (ScCMV) infection (13 054 IU/mL) was significantly higher than that of asymptomatic cCMV (AcCMV) infection (4636 IU/mL) (p < 0.013). There was no difference in median viral clearance times (75 and 90 days, respectively) in baseline viremic cases in the ScCMV and AcCMV infection groups. There were no differences in median baseline blood viral load (6930 IU/mL and 14 268 IU/mL, respectively) and median viral clearance times (75 and 85 days, respectively) between the 6-week and 6-month antiviral treatment group. No correlation was found between baseline blood viral load, clinical severity, and the number of systems involved. However, in initial viremic cases, the viral load threshold for a symptomatic case was 8856 IU/mL, with 85.7% sensitivity and 54.5% specificity.

Real-World Effectiveness of Ensitrelvir in Reducing Severe Outcomes in Outpatients at High Risk for COVID-19.

This study aimed to evaluate the effectiveness of ensitrelvir, an oral antiviral, in reducing hospitalization risk in outpatients at high-risk for severe COVID-19 during the Omicron era. This was a retrospective study using a large Japanese health insurance claims database. It included high-risk outpatients for severe symptoms who received their first COVID-19 diagnosis between November 2022 and July 2023. The study included outpatients aged≥18years. The primary endpoint was all-cause hospitalization during the 4-week period from the date of outpatient diagnosis and medication, comparing the ensitrelvir group (n=5177) and the no antiviral treatment group (n=162,133). The risk ratio and risk difference were evaluated after adjusting patient background distribution by the inverse probability of treatment weight (IPTW) method. Secondary endpoints were incidence of respiratory and heart rate monitoring, oxygen therapy, ventilator use, intensive care admission, and all-cause death. The risk ratio for all-cause hospitalization between the ensitrelvir group (n=167,385) and the no antiviral treatment group (n=167,310) after IPTW adjustment was 0.629 [95% confidence interval (CI) 0.420, 0.943]. The risk difference was -0.291 [95% CI -0.494, -0.088]. The incidence of both respiratory and heart rate monitoring and oxygen therapy was lower in the ensitrelvir group. Ventilator use, intensive care admission, and all-cause death were difficult to assess because of the limited events. The incidence of all-cause hospitalization was significantly lower in the ensitrelvir group than in the no antiviral treatment group, suggesting ensitrelvir is an effective treatment in patients at risk of severe COVID-19.

#2231 The efficacy of anti-viral therapies for hepatitis B in kidney transplant recipients

Abstract Background and Aims The efficacy and long-term outcomes of anti-viral therapies used for hepatitis B treatment or prevention continue to be a challenging area in kidney transplantation practice. This study aimed to determine the effectiveness of anti-viral treatment in a hepatitis B kidney transplant cohort and its effect on long-term graft and overall survival. Method We reviewed the data of 589 patients who were followed up on at our clinic between January 1, 2002, and December 31, 2023. Recipients who were AntiHbc IgG positive and received Rituximab and HbsAg negative recipients whose donor was HbsAg positive were included in the prophylaxis group, and recipients who were HbsAg positive were included in the treatment group. Age- and gender-matched recipients who did not use anti-viral treatment constituted the control group. HBV-DNA positivity in the prophylaxis group and an increase in HBV-DNA titers in the treatment group were indicators of treatment ineffectiveness. Anti-viral treatment-related side effects were noted. Graft functions, graft, and overall survival rates were examined at the beginning of treatment and at the last visit. Results A total of 30 patients receiving anti-viral therapy (prophylaxis n = 15, treatment n = 15) were included and compared with 32 control patients. The median age of the prophylaxis group was 49 (13–60) years, the median age of the treatment group was 46 (15–63) years, and the median age of the control group was 44 (22–71) years (p = 0.846). No difference was detected between the groups in terms of gender distribution. Entecavir was used in 17 patients, tenofovir in 7, and lamivudine in 6 patients. Hepatitis B activation was not observed in any patient in the prophylaxis group. An increase in HBV-DNA level was observed in 2 of 5 patients (40%) in the treatment group, followed by lamivudine. No treatment unresponsiveness was observed with other agents. No anti-viral drug-related side effects were reported in any patient. While there was no graft loss in the anti-viral treatment groups during follow-up, overall survival was determined as 100% in the prophylaxis group, 80% in the treatment group, and 90.6% in the control group (log rank p = 0.404). No hepatitis B-related mortality was reported. The findings are summarized in Tables 1 and 2. Conclusion Kidney transplant recipients using anti-viral medications for Hepatitis B, either for treatment or prophylaxis, showed similar graft and patient survival compared to the control group. Entecavir is the most commonly used anti-viral agent. Our findings support that it is advisable to consider alternative anti-viral medications instead of lamivudine, as there is a potential risk of non-response.

Efficacy and Safety of Nirmatrelvir/Ritonavir in Severe Hospitalized Patients with COVID-19 and in Patients at High Risk for Progression to Critical Illness: A Real-World Study.

Background: Nirmatrelvir/Ritonavir is an orally administered anti-SARS-Cov-2 drug used in mild-to-moderate COVID-19 patients. Our retrospective cohort study aims to evaluate the efficacy and safety of Nirmatrelvir/Ritonavir in severe hospitalized patients with Omicron infection, as well as in patients at high risk for progression to critical illness in real-world settings. Methods: A total of 350 patients received Nirmatrelvir/Ritonavir while 350 matched controls did not. Patients with confirmed COVID-19 were administered Nirmatrelvir 300 mg and Ritonavir 100 mg orally twice a day for 5 days, with the medication initiated on the first day after admission. The primary endpoint of the study was a composite outcome of hospitalization or death from any cause within 28 days. Secondary endpoints included the occurrence of adverse events and the evaluation of serum levels of IL-6 and viral load. Results: We documented the mortality risk from any cause within 28 days, viral load, serum IL-6 levels, and adverse events. Nirmatrelvir/Ritonavir reduced the 28-day risk of all-cause mortality by 86% (P = .011, hazard ratio (HR) = 0.14, 95% confidence interval (CI) = 0.03, 0.64). At baseline, the serum level of IL-6 was significantly higher in the antiviral treatment group compared to the control group (P < .001), but no significant difference (P = .990) was found between the two groups at discharge. In CKD patients undergoing hemodialysis, no significant worsening of renal function was observed in the Nirmatrelvir/Ritonavir treatment group compared to the control group. Conclusion: Nirmatrelvir/Ritonavir may reduce the 28-day risk of all-cause mortality in critically ill patients with COVID-19 and in patients at high risk for critical disease progression.

Does Nirmatrelvir/Ritonavir Influence the Immune Response against SARS-CoV-2, Independently from Rebound?

Recurrence of coronavirus disease 19 (COVID-19) symptoms and SARS-CoV-2 viral load relapse have been reported in people treated with nirmatrelvir/ritonavir (NM/r). However, little is understood about the etiology of this phenomenon. Our aim was to investigate the relation between the host's immune response and viral rebound. We described three cases of COVID-19 rebound that occurred after treatment with nirmatrelvir/ritonavir (group A). In addition, we compared spike-specific antibody response and plasma cytokine/chemokine patterns of the rebound cases with those of (i) control patients treated with nirmatrelvir/ritonavir who did not show rebound (group B), and (ii) subjects not treated with any anti-SARS-CoV-2 drug (group C). The anti-spike antibodies and plasma cytokines/chemokines were similar in groups A and B. However, we observed a higher anti-BA.2 spike IgG response in patients without antiviral treatment (group C) [geometric mean titer 210,807, 5.1- and 8.2-fold higher compared to group A (p = 0.039) and group B (p = 0.032)]. Moreover, the patients receiving antiviral treatment (groups A-B) showed higher circulating levels of platelet-derived growth factor subunit B (PDGF-BB) and vascular endothelial growth Factors (VEGF) and lower levels of interleukin-9 (IL-9), interleukine-1 receptor antagonist (IL-1 RA), and regulated upon activation normal T cell expressed and presumably secreted chemokine (RANTES) when compared to group C. In conclusion, we observed lower anti-spike IgG levels and different cytokine patterns in nirmatrelvir/ritonavir-treated patients compared to those not treated with anti-SARS-CoV-2 drugs. This suggests that early antiviral treatment, by reducing viral load and antigen presentation, could mitigate the immune response against SARS-CoV-2. The clinical relevance of such observation should be further investigated in larger populations.

Surveillance for feline herpesvirus type 1 mutation and development of resistance in cats treated with antiviral medications.

Feline herpesvirus type 1 (FHV-1) commonly causes ocular surface disease in cats and is treated with antiviral medications targeting viral DNA polymerase (UL30/42). Herein, we describe a method to assess the FHV-1 genome for mutation development and to assess the functional impact of mutations, if present. Fourteen shelter-housed domestic cats with FHV-1 ocular surface disease were assigned to one of four treatment groups: placebo (n = 3), cidofovir 0.5% ophthalmic solution (n = 3), famciclovir oral solution (n = 5), or ganciclovir 0.15% ophthalmic solution (n = 3). Swabs were collected before (day 1) and after (day 8) 1 week of twice-daily treatments to isolate viable FHV-1. Viral DNA was extracted for sequencing using Illumina MiSeq with subsequent genomic variant detection between paired day 1 and day 8 isolates. Plaque reduction assay was performed on paired isolates demonstrating non-synonymous variants. A total of 171 synonymous and 3 non-synonymous variants were identified in day 8 isolates. No variants were detected in viral UL23, UL30, or UL42 genes. Variant totals were not statistically different in animals receiving antiviral or placebo (p = 0.4997). A day 8 isolate from each antiviral treatment group contained a single non-synonymous variant in ICP4 (transcriptional regulator). These 3 isolates demonstrated no evidence of functional antiviral resistance when IC50 was assessed. Most (10/14 pairs) day 1 and 8 viral isolate pairs from the same host animal were near-identical. While functional variants were not detected in this small sample, these techniques can be replicated to assess FHV-1 isolates suspected of having developed resistance to antiviral medications.

Comparative Efficacy of Topical Ophthalmic Ganciclovir and Oral Famciclovir in Cats with Experimental Ocular Feline Herpesvirus-1 Epithelial Infection.

Purpose: To determine the comparative efficacy of ganciclovir ophthalmic gel and famciclovir oral tablets in cats with experimentally induced ocular feline herpesvirus-1 (FHV-1) epithelial infection. Methods: A randomized, placebo-controlled trial was performed using 16 nonvaccinated, specific pathogen-free cats with experimental FHV-1 infection induced by topical ocular inoculation. Cats received topical ganciclovir 0.15% ophthalmic gel (1 drop 3 times daily, n = 6 cats), oral famciclovir (90 mg/kg twice daily, n = 6), or topical artificial tear gel (1 drop 3 times daily, n = 4) for 14 days. Cats were monitored after inoculation for 30 days. Ophthalmic examinations were performed every 2 days and ocular disease scores calculated. In vivo confocal microscopy was performed, and corneal leukocyte infiltrates quantified. Ocular samples for FHV-1 quantitative polymerase chain reaction (qPCR) and virus isolation assays were collected every 3 days. Hemograms and serum biochemistry panels were performed at intervals. Results: Clinical ocular disease scores and corneal leukocyte infiltrates were significantly lower in the ganciclovir and famciclovir groups compared with placebo, but no significant differences were detected between the antiviral treatment groups. Ocular viral loads determined by qPCR were significantly lower in the ganciclovir group compared with the placebo group, but there were no significant differences between the other study groups. Hemograms and biochemistry panels were unremarkable. Conclusion: Topical application of ganciclovir gel 3 times daily was well-tolerated and displayed similar efficacy at reducing clinical ocular disease scores and corneal inflammation as twice daily oral famciclovir treatment in cats with experimental ocular FHV-1 infection.

Hepatitis B surface antigen kinetics after discontinuation of and retreatment with oral antivirals in non-cirrhotic HBeAg-positive chronic hepatitis B.

The outcome of nucleos(t)ide analogues (NAs) discontinuation and retreatment is still uncertain. We evaluated hepatitis B surface antigen (HBsAg) kinetics after NAs discontinuation and during retreatment due to off-treatment clinical relapse among non-cirrhotic HBeAg-positive CHB patients. Four groups were studied: 129 HBeAg-positive patients from a prospective cohort who stopped NAs therapy after achieving sustained response (Group A), 39 patients who received retreatment after off-treatment clinical relapse in the discontinuation group (Group B), 214 patients who maintained treatment after achieving sustained response (Group C) and 291 patients who firstly initiated antiviral treatment (Group D). During a 5-year follow-up, the cumulative incidence of HBsAg loss was significantly higher in Group A than Group C (22.3% vs. 1.6%, p<.001). The quantitative HBsAg (qHBsAg) level at enrolment and NAs discontinuation were independently associated with HBsAg loss. Additionally, patients in Group B showed significantly greater HBsAg loss than those in the Groups C and D, with 5-year cumulative incidences of 9.0%, 1.6% (p=.040) and 0.6% (p<.001), respectively. Moreover, patients in the Group B exhibited better virologic response (100% vs. 98.8%, p<.001) and HBeAg seroconversion (92.6% vs. 69.8%, p<.001) than those in Group D at year 5. Propensity score-matched analysis also showed the similar trend of HBsAg decline. NAs discontinuation with or without subsequent retreatment resulted in a more profound reduction of HBsAg in non-cirrhotic HBeAg-positive patients, suggesting that discontinuation may be a potential cure strategy for those with sustained virological suppression.

Peginterferon Alfa-2a (40KD) Plus Lamivudine or Entecavir in Children With Immune-Tolerant Chronic Hepatitis B.

Treatment guidelines for chronic hepatitis B (CHB) do not recommend antiviral therapy for patients in the immune-tolerant phase of the disease, which generally occurs in children who acquire hepatitis B virus (HBV) vertically and may last for decades. On the basis of promising results of a pilot study, we conducted a randomized, controlled, multicenter study to evaluate the efficacy and safety of antiviral therapy in children and adolescents with immune-tolerant CHB. Fifty-nine children aged 3 to <18 years hepatitis B e antigen-positive with an HBV DNA titer >20,000 IU/mL and persistently normal alanine aminotransferase levels were randomized to 56 weeks of antiviral therapy with an oral nucleoside analogue [entecavir or lamivudine], combined with subcutaneous peginterferon alfa-2a from week 8, or 80 weeks of untreated observation. The primary efficacy outcome was hepatitis B surface antigen loss 24 weeks post-treatment in the antiviral therapy group or at the end of observation in the control group. Enrollment was terminated after the results of two similar studies showed that similar antiviral regimens were ineffective in children and adults with immune-tolerant CHB. At 24 weeks post-treatment, 1 of 26 patients in the antiviral treatment group experienced HBsAg loss (vs none of 33 patients in the control group). No serious treatment-related adverse events were reported, and no patients discontinued treatment because of adverse events. The antiviral regimen evaluated in this trial had an acceptable tolerability profile, but was ineffective in children and adolescents with immune-tolerant CHB.

Favipiravir Experience in COVID-19 Patients at a Tertiary Center Intensive Care Unit.

ObjectivesThe aim of this study was to compare intensive care unit (ICU) and overall hospital mortality in patients treated with favipiravir and lopinavir-ritonavir for COVID-19.MethodsData were collected retrospectively between March 10 and May 10, 2020, from patients’ records admitted to ICU due to COVID-19. Laboratory data, clinical characteristics, ICU and hospital mortality, ICU and hospital length of stay were compared in patients treated with favipiravir and lopinavir-ritonavir.ResultsA total of 100 patients’ data were investigated. Favipiravir was used as the treatment for 85% of patients, with the rest treated with lopinavir-ritonavir. Clinical and laboratory data of both antiviral treatment groups were similar. Length of hospital stay was 16 (9–24) days with favipiravir and 8.5 (5–12.5) days with lopinavir-ritonavir (p=0.002). Length of ICU stay for favipiravir and lopinavir-ritonavir groups were 8 (5–15) days and 4 (3–9) days, respectively (p=0.011). ICU mortality was 65.9% for the favipiravir and 80% for lopinavir-ritonavir (p=0.002). Hospital mortality for favipiravir and lopinavir-ritonavir was 67.1% and 80%, respectively (p=0.001).ConclusionThe mortality in patients treated with favipiravir was less than patients treated with lopinavir-ritonavir. Favipiravir needs more attention and trials for its effect to be confirmed.

Distinct Impacts of Pre-Operative Antiviral Treatment on Post-Operative Outcomes of HBV-related Hepatocellular Carcinoma: A Landmark Analysis.

Background: The effect of anti-viral treatment (AVT) initiated before surgery (pre-operative AVT) on HBV-related hepatocellular carcinoma (HCC) has been controversial. This study aimed to elucidate the prognostic significance of pre-operative AVT for HCC patients who received hepatectomy.Materials and Methods: A large-scale retrospective study was conducted based on a cohort consisting of 1937 HBV-related HCC patients who underwent R0 liver resection between January 2011 and December 2012. Propensity score matching (PSM) method was adopted to balance covariates and landmark survival analyses were performed to visualize effects in different phases after surgery.Results: After PSM, a total of matched 744 patients (372 in each group) were recruited. The patients in the pre-operative AVT group had lower HBV-DNA loading levels and better recurrence-free survival (RFS) than those in the non-AVT group. The 1, 3, 5-year RFS rates of two groups were 67.3%, 49.0%, and 43.1% vs. 66.7%, 41.1% and 18.5%, respectively (P<0.001). Landmark survival analyses demonstrated that pre-operative AVT could improve RFS, and the effect was beginning to show after the first 12 months. There was no significant difference of overall survival (OS) between the two groups (P=0.543), and the landmark survival analyses indicated that pre-operative AVT could improve OS and this effect was beginning to show after 36 months. Additionally, multivariate Cox regression analyses revealed that larger tumor (>5cm), esophageal and gastric varices, lymph node metastasis were independent risk factors of RFS, and larger tumor (>5cm) and ascites were independent risk factors of OS.Conclusions: Pre-operative AVT could significantly improve the RFS, and could not improve short-term OS (< 36 months) but could better long-term survival of the patients with HBV-HCC after surgery.

Role of Prophylactic Vitrectomy in Acute Retinal Necrosis in Preventing Rhegmatogenous Retinal Detachment: Systematic Review and Meta-analysis

ABSTRACT Purpose To evaluate the effects of prophylactic vitrectomy for rhegmatogenous retinal detachment (RRD) risk and visual outcome in acute retinal necrosis (ARN). Methods A systematic search of online databases was performed for articles published between 1994 June and 2020 March. The main outcomes that were assessed by a fixed effects model were RRD risk and visual outcome during a follow up period. Results A total of 7 trials involving 265 eyes (121 prophylactic vitrectomy eyes vs 144 routine antiviral treatment eyes) were analyzed in this study. RRD risk significantly decreased in the prophylactic vitrectomy group compared to the routine antiviral treatment group (P < .001, OR = 0.27, 95% CI: 0.16–0.46, I 2 = 35.3%). Significantly deteriorated visual outcome was observed in the prophylactic vitrectomy group in comparison with the routine antiviral treatment group (P < .001, WMD = 0.47, 95%CI: 0.26–0.67, I 2 = 32.2%). Conclusion This meta-analysis of retrospective cohort studies revealed that prophylactic vitrectomy could reduce the risk of RRD. The silicone oil tamponade and long-term complications may result in deteriorated visual outcome.

Changes in circulating follicular helper T cells in peripheral blood of patients with acute hepatitis C virus infection.

To investigate the changes in circulating follicular helper T cells (cTfh) in peripheral blood of patients with acute hepatitis C virus (HCV) infection and its correlation with symptom severity of the disease. A total of 105 subjects were enrolled in this study, including 35 healthy people, 35 patients with acute HCV infection and 35 acute HCV patients with antiviral therapy. Flow cytometry was used to detect the expression of molecular markers related to the surface of cTfh cells, such as CD69, HLA-DR and CD57, and ELISA was used to detect the secretion of cytokines (IL-21, IL-4) in each group. The relationship between these markers and disease was analyzed statistically. Flow cytometry analysis demonstrated that the percentage of CD69 in peripheral blood of patients with acute hepatitis C infection was (18.90%±9.29%) significantly higher than that of normal control group (5.10%±4.21%) and antiviral treatment group (11.50%±5.38%). The difference was statistically significant (P<0.05). The results of HLA-DR and CD57 were consistent with CD69. The serum levels of IL-4 and IL-21 in the acute HCV infection group were significantly higher than those in the treatment and the control groups. After antiviral treatment, IL-4 and IL-21 levels significantly decreased but remained higher than those in the control group. This showed that antiviral treatment was effective, and the difference was statistically significant (P<0.05). The ratio of cTfh in infected group was negatively correlated with HCV RNA content (r=-0.6858, P=0.0028). Antiviral immune response in patients with acute hepatitis C infection may be related to the proportion of T helper cells in peripheral blood circulation follicles. Dynamic detection of the number of T helper cells in clinical practice is conducive to identifying more effective methods to treat acute hepatitis C infection, which has important theoretical and clinical significance.

Effect of Antiviral Therapy on the Outcome of Mechanically Ventilated Patients With Herpes Simplex Virus Type 1 in BAL Fluid: A Retrospective Cohort Study

Herpes simplex virus type 1 (HSV-1) is frequently detected in the BAL fluid of patients on mechanical ventilation. The aim of the study was to investigate whether antiviral therapy is associated with improved overall survival within 30days. This was a retrospective cohort study in four ICUs between January 2011 and December 2017. All adult patients on mechanical ventilation with a respiratory tract infection with positive polymerase chain reaction testing for HSV-1 in the BAL were included. Patients already receiving antiviral agents on the day BAL was performed were excluded. We performed uni- and multivariable Cox and logistic regression modeling. Overall, 306 patients were included in the analysis. Among them, 177 patients (57.8%) received antiviral therapy (90.9%acyclovir, 6.2%ganciclovir, 2.9%both). The overall 30-day mortality rate was 42.4%(n= 75) in the antiviral treatment group and 50.4%(n= 65) in the control group. The adjusted hazard ratio (HR) for the primary outcome was 0.62 (95%CI, 0.44-0.87; P= .005), indicating better overall survival within 30days for the antiviral-treated group than for the untreated group. This benefit was also present in the subgroup of patients without immunosuppression (n= 246; adjusted HR, 0.53; 95%CI, 0.36-0.78; P= .001). Overall, the median lengths of hospital stay (31 vs24days, P= .002) and ICU stay (24 vs17days, P< .001), and the duration of mechanical ventilation (18 vs11days, P< .001), were longer for patients with therapy. No evidence for the treatment-related deterioration of renal function was observed. These data suggest that detection of HSV-1 in the BAL of patients on mechanical ventilation may be of clinical significance and that specific antiviral treatment may improve clinical outcomes. However, this needs to be proven in multicenter randomized controlled trials before implementation into the clinical routine.

Serum Hepcidin In Patients With Chronic Hepatitis C And Its Relation To Treatment With Antiviral Drugs

HCV infection has been implicated in iron accumulation in the liver and iron overload has been shown to be a potential cofactor for HCVassociated hepatocellular carcinoma progression.Hepcidin produced by hepatocytes, is a key regulator of iron metabolism. Alteration of Hepcidin expression levels has been reported in the setting of chronic HCV infection and hepatocellular carcinoma. The aim of the work is to assess the serum concentration of hepcidin in chronic hepatitis C patients and evaluate any possible association with the viral load after therapy. Ourstudy was carried on50 patients with chronic hepatitisC.Hepcidin levels were evaluated for Hepcidin before starting the antiviral therapy treatment (group A) and after 24 weeks course of antiviral therapy(group B)with a commercially available enzyme-linked immunosorbentassay kitin addition to 20 healthy volunteers with matched age and sex as control group.As regard serum Hepcidin level, there was a highly statistical significant differencebetween control and patient group.Hepcidin concentrations in patients with CHC were relatively low compared to HCV negative individuals. Highly statistical significant (p-value > 0.05) positive correlation (r = 0.67) between Hepcidin before and after treatment in patients group. In conclusion Chronic HCV infection is associated with reduced level of hepcidin. The level of hepcidin was fully reversible after antiviral therapy.Initial rise in serum hepcidin concentration might have a potential for being used as one of the indicators of patient response to therapy.

Prophylactic Antiviral Therapy Before Hepatectomy Is Beneficial to HBV-Related Hepatocellular Carcinoma Patients with Negative HBV-DNA

The purpose of this study was to explore the role of prophylactic antiviral therapy in hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) patients with negative HBV-DNA. The study included 79 HBV-related HCC patients with preoperative negative HBV-DNA who underwent hepatectomy. Patients were prospectively assigned to two groups: preoperative antiviral treatment group (n = 39) and untreated group (n = 40). Follow-up visits were performed with patients regularly once per month. The data for the two groups were analyzed including HBV activation; tumor recurrence; liver function; 1-, 2-, and 3-year survival rate; and cumulative survival time. In the antiviral group, 1 of 39 (2.56%) patients had HBV activation, while there were 8 of 40 (20%) with HBV activation in the untreated group (p < 0.05). Our findings indicate, therefore, that antiviral therapy is a protective factor for HBV activation. There was no statistically significant difference in tumor recurrence between the two groups. Tumor recurrence is related to non-antiviral status, postoperative HBV activation, level of AFP, tumor invasion, and tumor microinvasion (p < 0.05). Postoperative 1-, 2-, and 3-year cumulative overall survival rates were 92.30%, 84.61%, and 76.33%, respectively, for the antiviral groups, and 90%, 72.5%, and 54.28%, respectively, for the untreated group (p = 0.048). There was no statistically significant difference in disease-free survival between the two groups (p = 0.120). HBV can be activated after hepatectomy for HBV-related HCC patients who exhibit preoperative negative HBV-DNA. Preventative antiviral treatment for HBV- HCC patients with negative HBV-DNA undergoing hepatic resection facilitates reduction of activation of HBV.

Early antiviral therapy of abidor combined with lopinavir/ritonavir and re-combinant interferonα-2b in patients with novel coronavirus pneumonia in Zhejiang: A multicenter and prospective study

Objective@#Comparing the benefit of Abidor, lopinavir/ritonavir and recombinant interferon α-2b triple combination antiviral therapy and lopinavir/ritonavir and interferon dual combination antiviral therapy to hospitalized novel coronavirus pneumonia 2019 in Zhejiang province.@*Methods@#A multi-center prospective study was carried out to compare the effect of triple combination antiviral therapy with dual combination antiviral therapy in 15 medical institutions of Zhejiang Province. All patients were treated with recombinant interferon α-2b (5 million U, 2 times/d) aerosol inhalation. 196 patients were treated with abidol (200 mg, 3 times/d) + lopinavir / ritonavir (2 tablets, 1 time/12 h) as the triple combination antiviral treatment group. 41 patients were treated with lopinavir / ritonavir (2 tablets, 1 time/12 h) as the dual combination antiviral treatment group. The patients who received triple combination antiviral therapy were divided into three groups: within 48 hours, 3-5 days and > 5 days after the symptom onset. To explore the therapeutic effects of triple combination antiviral drugs and dual combination antiviral drugs, as well as triple combination antiviral drugs with different antiviral initiate time. SPSS17.0 software was used to analyze the data.@*Results@#The time of virus nucleic acid turning negative was (12.2 ± 4.7) days in the triple combination antiviral drug group, which was shorter than that in the dual combination antiviral drug group [(15.0 ± 5.0) days] (t = 6.159, P 5 days after the symptom onset of triple combination antiviral drug group, the time from the symptom onset to the negative of viral shedding was 13 (10,16.8), 17 (13,22) and 21 (18-24) days respectively (Z = 32.983, P < 0.01), and the time from antiviral therapy to the negative of viral shedding was (11.8±3.9) , (13.5±5.1) and (11.2±4.3) d. The differences among the three groups were statistically significant (Z=32.983 and 6.722, P<0.01 or<0.05).@*Conclusions@#The triple combination antiviral therapy of Abidor, Lopinavir/Litonavir and recombinant interferon α-2b showed shorter viral shedding time and hospitalization time compared with the dual combination antiviral therapy. The earlier the time to initiate triple antiviral treatment, the shorter the time of virus shedding.

Efficacy and safety of anti-viral therapy for Hepatitis B virus-associated glomerulonephritis: Ameta-analysis.

To assess the potency of anti-viral treatment for hepatitis B virus-associated glomerulonephritis (HBV-GN). Method: We searched for controlled clinical trials on anti-viral therapy for HBV-GN in MEDLINE, Embase, the Cochrane Library, and PubMed from inception to March 11th 2019. Seven trials, including 182 patients met the criteria for evaluating. The primary outcome measures were proteinuria and changes in the estimated glomerular filtration rate, and the secondary outcome measure was hepatitis B e-antigen clearance. A fixed or random effect model was established to analyze the data. Subgroup analyses were performed to explore the effects of clinical trial type, anti-viral drug type, age, and follow-up duration. The total remission rate of proteinuria (OR = 10.48, 95% CI: 4.60-23.89, I2 = 0%), complete remission rate of proteinuria (OR = 11.64, 95% CI: 5.17-26.21, I2 = 23%) and clearance rate of Hepatitis Be Antigen (HBeAg) were significantly higher in the anti-viral treatment group than in the control group (OR = 27.08, 95% CI: 3.71-197.88, I2 = 63%). However, antiviral therapy was not as effective regarding the eGFR (MD = 5.74, 95% CI: -4.24-15.73). In the subgroup analysis, age and drug type had significant impacts on proteinuria remission, and study type and follow-up duration only slightly affected the heterogeneity. Antiviral therapy induced remission of proteinuria and increased HBeAg clearance but failed to improve the eGFR. Pediatric patients were more sensitive to antiviral therapy than adults. IFNs seem more effective but are accompanied by more adverse reactions than NAs.