Circulating metabolites are associated with persistent elevations of ALT in patients with chronic hepatitis B with complete viral suppression.

Hepatitis B virus (HBV) can be completely suppressed after antiviral treatment; however, some patients with chronic hepatitis B (CHB) exhibit elevated alanine aminotransferase (ALT) levels and sustained disease progression. This study provides novel insights into the mechanism and potential predictive biomarkers of persistently elevated ALT (PeALT) in patients with CHB after complete viral inhibition. Patients having CHB with undetectable HBV DNA at least 12 months after antiviral treatment were enrolled from a prospective, observational cohort. Patients with PeALT and persistently normal ALT (PnALT) were matched 1:1 using propensity score matching. Correlations between plasma metabolites and the risk of elevated ALT were examined using multivariate logistic regression. A mouse model of carbon tetrachloride-induced liver injury was established to validate the effect of key differential metabolites on liver injury. Of the 1238 patients with CHB who achieved complete viral suppression, 40 (3.23%) had PeALT levels during follow-up (median follow-up: 2.42 years). Additionally, 40 patients with PnALT levels were matched as controls. Ser-Phe-Ala, Lys-Ala-Leu-Glu, 3-methylhippuric acid, 3-methylxanthine, and 7-methylxanthine were identified as critical differential metabolites between the two groups and independently associated with PeALT risk. Ser-Phe-Ala and Lys-Ala-Leu-Glu levels could be used to discriminate patients with PeALT from those with PnALT. Furthermore, N-acetyl- l-methionine (NALM) demonstrated the strongest negative correlation with ALT levels. NALM supplementation alleviated liver injury and hepatic necrosis induced by carbon tetrachloride in mice. Changes in circulating metabolites may contribute to PeALT levels in patients with CHB who have achieved complete viral suppression after antiviral treatment.

COVID-19 Drug Treatments Are Prone to Sequestration in Extracorporeal Membrane Oxygenation Circuits: An Ex Vivo Extracorporeal Membrane Oxygenation Study.

Drug treatments for coronavirus disease 2019 (COVID-19) dramatically improve patient outcomes, and although extracorporeal membrane oxygenation (ECMO) has significant use in these patients, it is unknown whether ECMO affects drug dosing. We used an ex vivo adult ECMO model to measure ECMO circuit effects on concentrations of specific COVID-19 drug treatments. Three identical ECMO circuits used in adult patients were set up. Circuits were primed with fresh human blood (temperature and pH maintained within normal limits). Three polystyrene jars with 75 ml fresh human blood were used as controls. Remdesivir, GS-441524, nafamostat, and tocilizumab were injected in the circuit and control jars at therapeutic concentrations. Samples were taken from circuit and control jars at predefined time points over 6 h and drug concentrations were measured using validated assays. Relative to baseline, mean (± standard deviation [SD]) study drug recoveries in both controls and circuits at 6 h were significantly lower for remdesivir (32.2% [±2.7] and 12.4% [±2.1], p < 0.001), nafamostat (21.4% [±5.0] and 0.0% [±0.0], p = 0.018). Reduced concentrations of COVID-19 drug treatments in ECMO circuits is a clinical concern. Remdesivir and nafamostat may need dose adjustments. Clinical pharmacokinetic studies are suggested to guide optimized COVID-19 drug treatment dosing during ECMO.

Lymphocyte counts predict optimal timing of chemotherapy reinitiation after antivirus treatment for herpes zoster in children with leukemia.

Herpes zoster (HZ) is rare in healthy children, but more prevalent in those with leukemia. Optimal timing of chemotherapy reinitiation after HZ treatment is challenging because chemotherapy suppresses immunity and increases risk of HZ relapse. We aimed to optimize the timing of chemotherapy reinitiation after HZ therapy in children with leukemia. The study included 31 children with acute leukemia and HZ infection. General information, clinical symptoms, laboratory test results, duration of HZ treatment, and prognosis were compared with those of children with leukemia alone. Correlation analysis was performed for 20 children who restarted chemotherapy after HZ treatment. Of 31 children with leukemia and HZ, 67.74% had lesions at multiple sites. The median time from chemotherapy initiation to HZ onset was 14.1 (1.5-29.5) months. Among 27 children included in the follow-up, there was one case of HZ relapse. After excluding children who did not continue chemotherapy after HZ treatment, the median interval between completion of HZ therapy and chemotherapy reinitiation in the remaining 20 children was 8.00 (- 3 to 27) days. Lymphocyte counts (LY#) on restarting chemotherapy correlated inversely with HZ lesion healing time (p < 0.05). LY# at the time of HZ onset were lower than those pre- and post-onset, and lower than those in the control group (p < 0.05). In conclusion, children with leukemia have a good HZ prognosis, but an increased risk of HZ recurrence. LY# at the time of chemotherapy reinitiation may be a useful indicator for selecting the optimal interval between antiviral therapy completion and chemotherapy reinitiation.

Evaluation of the Effect of Favipiravir on QT Intervals in COVID-19 Patients with and without Diabetes Mellitus.

OBJECTIVE: To evaluate the effect of favipiravir administered to diabetic and non-diabetic COVID-19 patients on the QT/QTc interval. STUDY DESIGN: Analytical study. Place and Duration of the Study: Republic of Turkey, Ministry of Health, State Hospital, Corlu, Tekirdag, Turkiye, from March to September 2021. METHODOLOGY: Electrocardiogram (ECG) analysis was performed on all participants (n=180) divided into four groups. Group 1 included only healthy volunteers. Group 2 included only cases diagnosed with T2DM. Group 3 included only severe acute respiratory syndrome coronavirus-2 (SARS-Cov-2) cases. Group 4 included cases diagnosed with both SARS and T2DM. Favipiravir was administered only to the cases in Group 3 and Group 4. In the cases that were administered favipiravir, the QT/QTc interval was calculated and recorded at different time intervals on the first and fifth days of the therapy. The difference between groups was determined by Tukeye's test after ANOVA. Pearson's correlation test was used to determine whether there was a linear relationship between two numericals. The alpha significance value was determined to be <0.05 in all statistical analyses. RESULTS: When all groups were compared, it was seen that both QT and QTc values ​​increased in Groups 3 and 4, which were administered favipiravir (p <0.05). Favipiravir may cause an increased risk of ventricular and atrial arrhythmias. CONCLUSION: Favipiravir may cause QT interval prolongation, particularly in SARS-Cov-2 patients diagnosed with T2DM. KEY WORDS: COVID-19, Drug-induced long QT syndrome, Intra-infarct haemorrhage; Favipiravir, Type 2 diabetes mellitus.

[The use of immunoglobulins and monoclonal antibodies against COVID-19].

INTRODUCTION: When a new disease occurs, one of the most affordable remedies is drugs containing specific antibodies to this infectious agent. The use of such drugs is aimed at reducing the amount of the pathogen in the macroorganism and the associated reduction in the severity of the symptoms of the disease or recovery. The purpose of this review is to analyze the experience of using immunoglobulins and monoclonal antibodies in the treatment of COVID-19 patients during the pandemic. RESULTS AND CONCLUSION: The two main groups of medical protective agents that block the penetration of the SARS-CoV-2 virus into permissive cells are drugs obtained from blood plasma of convalescents (immunoglobulin) and human monoclonal antibodies. The first group of drugs in the treatment of COVID-19 includes blood plasma of convalescents, which can be successfully used for emergency prevention. The main disadvantage of using blood plasma convalescents is the difficulty of standardization due to the different content of specific antibodies in donors. Another disadvantage is the undesirable side effects in recipients that occur after plasma administration. An alternative approach to COVID-19 therapy is the use of humanized and genetically engineered human monoclonal antibodies against certain epitopes of the SARS-CoV-2 virus. For example, monoclonal antibodies against receptor-binding domain of the S-protein, which prevents the virus from entering permissive cells and interrupts the development of infection. The advantages of these drugs are their safety, high specific activity, and the possibility of standardization. However, the complexity of their production and high cost make them inaccessible for mass use in practical medicine.

Nirmatrelvir/ritonavir or Molnupiravir for treatment of non-hospitalized patients with COVID-19 at risk of disease progression.

BACKGROUND: In randomized controlled trials, Nirmatrelvir/ritonavir (NMV/r) and Molnupiravir (MPV) reduced the risk of severe/fatal COVID-19 disease. Real-world data are limited, particularly studies directly comparing the two agents. METHODS: Using the VA National COVID-19 database, we identified previously uninfected, non-hospitalized individuals with COVID-19 with ≥1 risk factor for disease progression who were prescribed either NMV/r or MPV within 3 days of a positive test. We used inverse probability of treatment weights (IPTW) to account for providers' preferences for a specific treatment. Absolute risk difference (ARD) with 95% confidence intervals were determined for those treated with NMV/r vs. MPV. The primary outcome was hospitalization or death within 30 days of treatment prescription using the IPTW approach. Analyses were repeated using propensity-score matched groups. RESULTS: Between January 1 and November 30, 2022, 9,180 individuals were eligible for inclusion (6,592 prescribed NMV/r; 2,454 prescribed MPV). The ARD for hospitalization/death for NMV/r vs MPV was -0.25 (95% CI -0.79 to 0.28). There was no statistically significant difference in ARD among strata by age, race, comorbidities, or symptoms at baseline. Kaplan-Meier curves did not demonstrate a difference between the two groups (p-value = 0.6). Analysis of the propensity-score matched cohort yielded similar results (ARD for NMV/r vs. MPV -0.9, 95% CI -2.02 to 0.23). Additional analyses showed no difference for development of severe/critical/fatal disease by treatment group. CONCLUSION: We found no significant difference in short term risk of hospitalization or death among at-risk individuals with COVID-19 treated with either NMV/r or MPV.

Host factors of SARS-CoV-2 in infection, pathogenesis, and long-term effects.

SARS-CoV-2 is the causative virus of the devastating COVID-19 pandemic that results in an unparalleled global health and economic crisis. Despite unprecedented scientific efforts and therapeutic interventions, the fight against COVID-19 continues as the rapid emergence of different SARS-CoV-2 variants of concern and the increasing challenge of long COVID-19, raising a vast demand to understand the pathomechanisms of COVID-19 and its long-term sequelae and develop therapeutic strategies beyond the virus per se. Notably, in addition to the virus itself, the replication cycle of SARS-CoV-2 and clinical severity of COVID-19 is also governed by host factors. In this review, we therefore comprehensively overview the replication cycle and pathogenesis of SARS-CoV-2 from the perspective of host factors and host-virus interactions. We sequentially outline the pathological implications of molecular interactions between host factors and SARS-CoV-2 in multi-organ and multi-system long COVID-19, and summarize current therapeutic strategies and agents targeting host factors for treating these diseases. This knowledge would be key for the identification of new pathophysiological aspects and mechanisms, and the development of actionable therapeutic targets and strategies for tackling COVID-19 and its sequelae.

Intralesional acyclovir versus intralesional Hepatitis-B vaccine in treatment of resistant plantar warts: a randomized controlled trial.

Treating plantar warts is still a challenging problem with a long list of diverse treatment options that none of them seems to be definitive. To evaluate the effectiveness of intralesional acyclovir versus intralesional Hepatitis-B vaccine (HBV) in treatment of multiple resistant plantar warts. Forty-eight patients with resistant plantar warts completed the study with no dropouts. They were randomized into 3 groups; group(A) receiving intralesional HBV, group (B) receiving intralesional acyclovir and group (C) receiving intralesional saline as a control group over 5 biweekly sessions or until wart clearance. Clinical outcome was assessed through sequential digital lesion photographing upon each visit. Treatment related adverse reactions were recorded. 43.8%, 37.5% & 18.7% of Groups A, B &C respectively showed a complete response. pain was obvious in 100% and 56.3% of cases receiving intralesional acyclovir and HBV respectively. Up to the 6 month follow up period, none of the complete responders in all groups returned with a recurrence. Both acyclovir and HBV showed comparable efficacy and seem to be promising options for treating plantar warts being safe, affordable, and theoretically safe in immunocompromised cases.

Early initiation of combined therapy in severely immunocompromised patients with COVID-19: a retrospective cohort study.

This single-centre retrospective cohort study reports on the results of a descriptive (non-comparative) retrospective cohort study of early initiation of antivirals and combined monoclonal antibody therapy (mAbs) in 48 severely immunocompromised patients with COVID-19. The study assessed the outcomes and the duration of viral shedding. The patients started early combined therapy (ECT) a median of 2 days (interquartile range [IQR]: 1-3 days) after the diagnosis of SARS-CoV-2 infection. Except for 1 patient who died due COVID-19-related respiratory failure, patients had their first negative nasopharyngeal swab result after a median of 11 days (IQR: 6-17 days) after starting combined therapy. There were no reports of severe side effects. During a follow-up period of 512 days (interquartile range [IQR]: 413-575 days), 6 patients (12.5%) died and 16 (33.3%) were admitted to hospital. Moreover, 12 patients (25%) were diagnosed with SARS-CoV-2 reinfection a median of 245 days (IQR: 138-401 days) after starting combined treatment. No relapses were reported. Although there was no comparison group, these results compare favourably with the outcomes of severely immunocompromised patients with COVID-19 reported in the literature.

Nirsevimab Effectiveness Against Cases of Respiratory Syncytial Virus Bronchiolitis Hospitalised in Paediatric Intensive Care Units in France, September 2023-January 2024.

In September 2023, France was one of the first countries that started a national immunisation campaign with nirsevimab, a new monoclonal antibody against respiratory syncytial virus (RSV). Using data from a network of paediatric intensive care units (PICUs), we aimed to estimate nirsevimab effectiveness against severe cases of RSV bronchiolitis in France. We conducted a case-control study based on the test-negative design and included 288 infants reported by 20 PICUs. We estimated nirsevimab effectiveness at 75.9% (48.5-88.7) in the main analysis and 80.6% (61.6-90.3) and 80.4% (61.7-89.9) in two sensitivity analyses. These real-world estimates confirmed the efficacy observed in clinical studies.

[Results of a randomized double-blind multicenter clinical trial of the efficacy and safety of riamilovir in the treatment of COVID-19].

AIM: To evaluate the efficacy and safety of riamilovir in the treatment of COVID-19 in adults. MATERIALS AND METHODS: The study included 180 patients with a laboratory-confirmed diagnosis of COVID-19 which fully meet the criteria for inclusion, non-inclusion and exclusion, signed a voluntary informed consent to participate in a clinical trial. RESULTS: The efficacy, good tolerability and safety of the drug riamilovir in the treatment of COVID-19 have been established. CONCLUSION: As a result of a multicenter randomized double-blind clinical trial, the effectiveness of the drug riamilovir for therapeutic use in patients with COVID-19 according to the 1250 mg/day scheme (250 mg capsules 5 times per day) for 10 days was established. The drug riamilovir in a daily dose of 1250 mg for 10 days does not differ in safety from placebo.

[Chronic hepatitis B in rheumatic diseases: issues of screening and reactivation of infection: A review].

Patients with rheumatic diseases infected with hepatitis B virus (HBV) are difficult to manage not only due to the presence of risk factors for the development and rapid progression of liver cirrhosis, but also due to the likelihood of reactivation of this infection. Despite the successes achieved in the fight against HBV, the virus cannot be completely defeated due to the presence of hidden forms of the disease, escaping the field of vision of a rheumatologist and an infectionist. Based on the results of the analysis of current publications, the paper presents the rationale for a complete immunological screening of patients with rheumatic diseases when prescribing antirheumatic therapy. The issues of the role of COVID-19 in the exacerbation of chronic viral hepatitis B, antiviral prevention and monitoring are discussed, the classification of antirheumatic drugs according to the risk of HBV reactivation is presented.

Safety and effectiveness of remdesivir in hospitalized patients with COVID-19 and severe renal impairment: experience at a large medical center.

BACKGROUND: Literature on the safety of remdesivir in hospitalized COVID-19 patients with severe renal impairment is limited. We aimed to investigate the safety and effectiveness of remdesivir in this population. METHODS: We conducted a retrospective cohort study of adult hospitalized COVID-19 patients who received remdesivir between April 2022 and October 2022. Outcomes were compared between estimated glomerular filtration rate (eGFR) <30 mL/min/1.73 m2 and ≥30 mL/min/1.73 m2 groups. The primary safety outcomes were acute kidney injury (AKI) and bradycardia, while the primary effectiveness outcomes included mortality in COVID-19-dedicated wards and hospital mortality. Secondary outcomes included laboratory changes, disease progression, and recovery time. RESULTS: A total of 1,343 patients were recruited, with 307 (22.9%) in the eGFR <30 group and 1,036 (77.1%) in the eGFR ≥30 group. Patients with an eGFR <30 had higher risks of AKI (adjusted hazard ratio [aHR] 2.92, 95% CI 1.93-4.44) and hospital mortality (aHR 1.47, 95% CI 1.06-2.05) but had comparable risks of bradycardia (aHR 1.15, 95% CI 0.85-1.56) and mortality in dedicated wards (aHR 1.43, 95% CI 0.90-2.28) than patients with an eGFR ≥30. Risk of disease progression was higher in the eGFR <30 group (adjusted odds ratio 1.62, 95% CI 1.16-2.26). No difference between the two groups in laboratory changes and recovery time. CONCLUSIONS: Hospitalized COVID-19 patients receiving remdesivir with severe renal impairment had an increased risk of AKI, hospital mortality, and COVID-19 disease progression compared to patients without severe renal impairment.

Clinical characteristics and outcomes of patients with Herpes Simplex Encephalitis in Vietnam: a retrospective study.

BACKGROUND: Herpes simplex encephalitis (HSE) is an important central nervous infection with severe neurological sequelae. The aim of this study was to describe clinical characteristic and outcomes of patients with HSE in Vietnam. METHODS: This was a retrospective study of 66 patients with herpes simplex encephalitis who admitted to the National Hospital for Tropical Diseases, Hanoi, Vietnam from 2018 to 2021. The detection of herpes simplex virus (HSV) in cerebrospinal fluid was made by the real-time PCR assay. We reported the clinical manifestation on admission and evaluated clinical outcomes at the hospital discharge by modified Rankin Scale (mRS). Multivariate logistic regression analysis was used to analyze the independent risk factors of severe outcomes. RESULTS: Of the 66 patients with laboratory confirmed HSE, the median age was 53 years (IQR 38-60) and 44 patients (69.7%) were male. The most common manifestations included fever (100%), followed by the consciousness disorder (95.5%). Other neurological manifestation were seizures (36.4%), memory disorders (31.8%), language disorders (19.7%) and behavioral disorders (13.6%). Conventional magnetic resonance imaging (MRI) showed 93.8% patients with temporal lobe lesions, followed by abnormalities in insula (50%), frontal lobe (34.4%) and 48.4% of patients had bilateral lesions. At discharge, 19 patients (28.8%) completely recovered, 15 patients (22.7%) had mild sequelae, 28 patients (42.4%) had moderate to severe sequelae. Severe neurological sequelae were memory disorders (55.8%), movement disorders (53.5%), language disorders (30.2%). Multivariate logistic regression analysis showed that Glasgow score decrement at admission, seizures, and time duration from onset of symptoms to the start of Acyclovir treatment > 4 days were independent factors associated with severe outcomes in HSE patients. CONCLUSION: Glasgow score decrement, seizures and delay treatment with Acyclovir were associated with the poor outcome of patients with HSE.

Managing and treating COVID-19 in patients with hematological malignancies: a narrative review and expert insights.

Patients with hematologic malignancies (HMs) are at a significantly higher risk of contracting COVID-19 and experiencing severe outcomes compared to individuals without HMs. This heightened risk is influenced by various factors, including the underlying malignancy, immunosuppressive treatments, and patient-related factors. Notably, immunosuppressive regimens commonly used for HM treatment can lead to the depletion of B cells and T cells, which is associated with increased COVID-19-related complications and mortality in these patients. As the pandemic transitions into an endemic state, it remains crucial to acknowledge and address the ongoing risk for individuals with HMs. In this review, we aim to summarize the current evidence to enhance our understanding of the impact of HMs on COVID-19 risks and outcomes, identify particularly vulnerable individuals, and emphasize the need for specialized clinical attention and management. Furthermore, the impaired immune response to COVID-19 vaccination observed in these patients underscores the importance of implementing additional mitigation strategies. This may include targeted prophylaxis and treatment with antivirals and monoclonal antibodies as indicated. To provide practical guidance and considerations, we present two illustrative cases to highlight the real-life challenges faced by physicians caring for patients with HMs, emphasizing the need for individualized management based on disease severity, type, and the unique circumstances of each patient.

Clinical effectiveness of nirmatrelvir plus ritonavir on the short- and long-term outcome in high-risk children with COVID-19.

This study investigated the clinical effectiveness of nirmatrelvir plus ritonavir (NMV-r) on short-term outcome and the risk of postacute sequelae of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (PASC) among pediatric patients with coronavirus disease 2019 (COVID-19). This retrospective cohort study used the TriNetX research network to identify pediatric patients between 12 and 18 years with COVID-19 between January 1, 2022 and August 31, 2023. The propensity score matching (PSM) method was used to match patients receiving NMV-r (NMV-r group) with those who did not receive NMV-r (control group). Two cohorts comprising 633 patients each (NMV-r and control groups), with balanced baseline characteristics, were identified using the PSM method. During the initial 30 days, the NMV-r group showed a lower incidence of all-cause hospitalization, mortality, or ED visits (hazard ratio [HR] = 0.546, 95% confidence interval [CI]: 0.372-0.799, p = 0.002). Additionally, the NMV-r group had a significantly lower risk of all-cause hospitalization compared with the control group (HR = 0.463, 95% CI: 0.269-0.798), with no deaths occurring in either group. In the 30-180-day follow-up period, the NMV-r group exhibited a non-significantly lower incidence of post-acute sequelae of SARS-CoV-2 infection (PASC), encompassing symptoms such as fatigue, cardiopulmonary symptoms, pain, cognitive impairments, headache, dizziness, sleep disorders, anxiety, and depression, compared to the control group. This study underscores the potential effectiveness of NMV-r in treating high-risk pediatric patients with COVID-19, demonstrating significant reductions in short-term adverse outcomes such as emergency department visits, hospitalization, or mortality within the initial 30-day period. Additionally, NMV-r shows promise in potentially preventing the development of PASC.

Expanded Access Programme for the use of tecovirimat for the treatment of monkeypox infection: A study protocol for an Expanded Access Programme.

BACKGROUND: Monkeypox is a viral zoonotic disease commonly reported in humans in parts of Central and West Africa. This protocol is for an Expanded Access Programme (EAP) to be implemented in the Central African Republic, where Clade I monkeypox virus diseases is primarily responsible for most monkeypox infections. The objective of the programme is to provide patients with confirmed monkeypox with access to tecovirimat, a novel antiviral targeting orthopoxviruses, and collect data on clinical and virological outcomes of patients to inform future research. METHODS: The study will be conducted at participating hospitals in the Central African Republic. All patients who provide informed consent to enrol in the programme will receive tecovirimat. Patients will remain in hospital for the duration of treatment. Data on clinical signs and symptoms will be collected every day while the patient is hospitalised. Blood, throat and lesion samples will be collected at baseline and then on days 4, 8, 14 and 28. Patient outcomes will be assessed on Day 14 -end of treatment-and at Day 28. Adverse event and serious adverse event data will be collected from the point of consent until Day 28. DISCUSSION: This EAP is the first protocolised treatment programme in Clade I MPXV. The data generated under this protocol aims to describe the use of tecovirimat for Clade I disease in a monkeypox endemic region of Central Africa. It is hoped that this data can inform the definition of outcome measures used in future research and contribute to the academic literature around the use of tecovirimat for the treatment of monkeypox. The EAP also aims to bolster research capacity in the region in order for robust randomised controlled trials to take place for monkeypox and other diseases. TRIAL REGISTRATION: {2a & 2b}: ISRCTN43307947.

Predicting drug-Protein interaction with deep learning framework for molecular graphs and sequences: Potential candidates against SAR-CoV-2.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused the COVID-19 disease, which represents a new life-threatening disaster. Regarding viral infection, many therapeutics have been investigated to alleviate the epidemiology such as vaccines and receptor decoys. However, the continuous mutating coronavirus, especially the variants of Delta and Omicron, are tended to invalidate the therapeutic biological product. Thus, it is necessary to develop molecular entities as broad-spectrum antiviral drugs. Coronavirus replication is controlled by the viral 3-chymotrypsin-like cysteine protease (3CLpro) enzyme, which is required for the virus's life cycle. In the cases of severe acute respiratory syndrome coronavirus (SARS-CoV) and middle east respiratory syndrome coronavirus (MERS-CoV), 3CLpro has been shown to be a promising therapeutic development target. Here we proposed an attention-based deep learning framework for molecular graphs and sequences, training from the BindingDB 3CLpro dataset (114,555 compounds). After construction of such model, we conducted large-scale screening the in vivo/vitro dataset (276,003 compounds) from Zinc Database and visualize the candidate compounds with attention score. geometric-based affinity prediction was employed for validation. Finally, we established a 3CLpro-specific deep learning framework, namely GraphDPI-3CL (AUROC: 0.958) achieved superior performance beyond the existing state of the art model and discovered 10 molecules with a high binding affinity of 3CLpro and superior binding mode.

Sustained virological response in chronic hepatitis C patients by direct-acting antiviral treatment significantly reduces liver stiffness over 24 weeks posttreatment.

To investigate whether direct-acting antiviral (DAA) treatment affected liver fibrosis testing, including transient elastography (TE), aspartate aminotransferase-to-platelet ratio index (APRI), and Fibrosis-4 (FIB-4) index, after establishing a sustained virological response for 24 weeks. This prospective cohort study was conducted between October 1, 2019, and September 30, 2020, at Rajavithi Hospital, Bangkok, Thailand. All the patients had significant liver fibrosis (TE ≥ 7.0 kPa) at baseline and completed 12 weeks of DAA therapy. After achieving SVR, liver stiffness measurements were repeated for at least 24 weeks. The primary outcome was a > 30% improvement in TE score at the end of the study compared to baseline. A multivariate logistic regression model was used to identify the parameters associated with the primary outcome. Temporal changes in APRI and FIB-4 indices from baseline to 24 weeks posttreatment were also examined. A total of 110 chronic HCV patients were included in our cohort, of which 57 (52.3%) achieved the primary outcome. The median TE decreased from 15.05 (8.76-23.68) kPa at pretreatment to 9.60 (6.50-14.40) kPa at 24 weeks posttreatment (P < .001). Those who had a baseline TE ≥ 9.5 kPa had higher odds of meeting the primary outcome, and this remained significant after adjusting for age, sex, baseline body mass index, underlying diabetes mellitus, HCV genotype 3, baseline laboratory levels, and treatment regimens (OR 3.04; 95% CI 1.22-7.60, P = .017). Similar to TE, the median APRI and FIB-4 index displayed a considerable reduction from baseline to 24 weeks after successful therapy. Modern DAA treatment has been associated with considerable improvement in liver stiffness measured by TE in chronic HCV patients who achieve SVR, with roughly 52% of patients experiencing a reduction of > 30% in TE over 24 weeks posttreatment compared to baseline. This probably indicates early fibrosis regression, although the effect of resolution of inflammation after treatment completion cannot be ruled out.

[Research progress on novel antiviral therapeutic drugs for chronic hepatitis B].

The ideal goal of hepatitis B treatment is to achieve a functional cure, and the persistent cccDNA in the liver is a barrier to functional cure. Currently, antiviral drugs represented by pegylated interferon-α and nucleos (t) ide analogues cannot eliminate cccDNA, which is difficult to achieve functional cure. With the deepening of the exploration of various mechanisms and drug targets, significant progress has been made in the research and development of several novel drugs targeting the hepatitis B virus's life cycle and immune system, offering hope for a functional cure. This article presents an overview of the new progress in clinical research on antiviral therapy for chronic hepatitis B based on the literature published in recent years and international conference materials.