Incidence And Predictors of Relapse After Stopping Antiviral Therapy In Pediatric Chronic Hepatitis B

Objective: The objective was to evaluate the incidence of relapse after stopping antiviral therapy and to identify the predictors of relapse. Methods: All HBsAg positive children with who had been on antivirals for at least 2 years with undetectable HBV-DNA and normal alanine-aminotransferase (ALT) on three consecutive occasions over last 12 months were included. Antivirals were stopped if liver biopsy showed histological activity index <5 and fibrosis (metavir) <3. Children were monitored for virological relapse (elevation of HBV-DNA >2000 IU/mL) and biochemical relapse (ALT levels >2 × upper limit of normal (ULN)). Those having biochemical relapse were started on pegylated interferon alpha-2b based sequential therapy. Results: Antivirals were stopped in 31 HBsAg positive children. Virological and biochemical relapse was seen in 12 (38.7%) and 5 (16.1%) children within 12 months of stopping antiviral treatment. Majority of virological relapse occurred within a month and biochemical relapses within 6 months of stopping therapy. HBeAg positive status at the time of stopping antiviral therapy (HR: 7.206, p =0.005) and longer time taken for HBV-DNA to become undetectable while on antivirals (HR: 1.030, p=0.037) were found to be the 2 independent predictors of relapse after stopping antiviral treatment. Conclusion: Discontinuation of antiviral treatment in children with CHB resulted in relapse in one third of the patients. Relapse was more common in those with HBeAg positivity at the time of stopping therapy and in those with longer time taken for HBV-DNA to become undetectable on antivirals.

Pegylated Interferon Alpha-2b in Patients With Polycythemia Vera and Essential Thrombocythemia in the Real World

Several clinical trials have shown promising efficacy of pegylated interferon (Peg-IFN) in the first- and second-line polycythemia vera (PV) and essential thrombocythemia (ET). However, the efficacy and safety of Peg-IFN in the real world have rarely been reported. Hence, we conducted a prospective, single-center, single-arm, open exploratory study, which aimed to explore the hematologic response, molecular response, safety, and tolerability of patients with PV and ET treated with Peg-IFN in the real world. This study included newly diagnosed or previously treated patients with PV and ET, aged 18 years or older, admitted to the Department of Hematology of the First Affiliated Hospital of Soochow University from November 2017 to October 2019. The results revealed that complete hematological response (CHR) was achieved in 66.7% of patients with PV and 76.2% of patients with ET, and the molecular response was obtained in 38.5% of patients with PV and 50% of patients with ET after 48 weeks of Peg-IFN treatment. Peg-IFN is safe, effective and well tolerated in most patients. In the entire cohort, 4 patients (9.1%) discontinued treatment due to drug-related toxicity. In conclusion, Peg-IFN is a promising strategy in myeloproliferative neoplasms (MPNs), and Peg-IFN alone or in combination with other drugs should be further explored to reduce treatment-related toxicity and improve tolerability.

Case Report: Clinical Features of a COVID-19 Patient With Cirrhosis

Coronavirus disease 2019 (COVID-19) was first reported in Wuhan, Hubei Province, China in December 2019. At present, COVID-19 has emerged as a global pandemic. The clinical features of this disease are not fully understood, especially the interaction of COVID-19 and preexisting comorbidities and how these together further impair the immune system. In this case study, we report a COVID-19 patient with cirrhosis. A 73-year-old woman with cirrhosis reported a fever and cough on February 6, 2020. CT of the chest indicated an infection in her bilateral lungs. She tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. The woman was treated with lopinavir and ritonavir tablets and interferon alpha-2b injection, but there was no obvious effect. Although this patient was basically asymptomatic after 2 days in the hospital, the inflammation of the bilateral lungs was slow to subside as shown in CT of the chest. In addition, the white blood cell count (WBC), absolute neutrophil count, and absolute lymphocyte count remained decreased and the result of real-time reverse transcription polymerase chain reaction (PCR) (rRT-PCR) assay was still positive for SARS-CoV-2 on hospital day 28. After infusion of plasma from a recovered COVID-19 patient four times, the patient tested negative for SARS-CoV-2. She was discharged on March 13, 2020. This patient tested negative for SARS-CoV-2 after infusion of plasma from a recovered COVID-19 patient four times. Cirrhosis could impair the homeostatic role of the liver in the systemic immune response, which may affect the removal of SARS-CoV-2. This could lead to a diminished therapeutic effect of COVID-19. Thus, clinicians should pay more attention to COVID-19 patients with cirrhosis.

Complex treatment of acute respiratory viral infections with bacterial exacerbation in preschool children

Представлены результаты проспективного сравнительного клинического исследования эффективности и безопасности применения ректальных суппозиториев, содержащих рекомбинантный интерферон альфа-2b в сочетании с антиоксидантами – витаминами Е и С, в комплексной терапии острых респираторных вирусных инфекций среднетяжелого и тяжелого течения с бактериальными осложнениями (пневмония, бронхит, синусит, отит, фаринготонзиллит). Обследованы 60 детей от 1 месяца до 6 лет из II-IV групп здоровья, которые были госпитализированы не позднее третьих (80%) и пятых-шестых (20% больных) суток с момента начала острой респираторно-вирусной инфекции. Из них пациенты с патологией нижних дыхательных путей составили 68,3%; внебольничная пневмония, ассоциированная с ОРВИ, в половине случаев (55,6% и 66,6% соответственно) протекала с синдромом бронхиальной обструкции. Терапевтическая эффективность применения рекомбинантного интерферона альфа-2b в сочетании с антиоксидантами – витаминами Е и С по 150 000 МЕ 2 раза в сутки с интервалом 12 часов в течение 5 дней на фоне стандартной терапии основного заболевания у детей с бактериальными осложнениями острой респираторно-вирусной инфекции проявлялась в виде значимых различий по показателю синдрома бронхиальной обструкции начиная с первого дня терапии и значимого уменьшения симптома кашля и суммарного балла основных клинических симптомов заболевания к четвертому дню терапии по сравнению с группой пациентов, получавших только стандартную терапию респираторного заболевания. В связи с тем, что средняя длительность острой респираторно-вирусной инфекции с осложнениями составила 8 койко-дней (7,8 ± 2,37 и 8,77 ± 2,6 койко-дня соответственно), получение значимо лучших результатов в группе пациентов, применявших рекомбинантный интерферон альфа-2b в сочетании с антиоксидантами – витаминами Е и С, доказывает эффективность данной лечебной схемы терапии. The article presents the results of a prospective comparative clinical study of the efficacy and safety of rectal suppositories containing recombinant interferon alfa-2b in combination with antioxidants vitamins E and C in the complex therapy of acute respiratory viral infections (ARVI) with moderate and severe course with bacterial complications (pneumonia, bronchitis, sinusitis, otitis media, pharyngotonsillitis). The research examined 60 children at the age of 1 month to 6 years from II-IV health status groups, which were hospitalized not later than 3 days after coming down with ARVI (80% of patients) or 5-6 days after coming down with ARVI (20% of patients). 68,3% of patients came with lower respiratory tract impairment; the ARVI-associated community-acquired pneumonia in half the cases (55,6% and 66,6%, respectively) proceeded with bronchial obstruction syndrome. Results: the therapeutic efficacy of recombinant interferon alfa-2b in combination with antioxidants E and C 150 000 ME administration 2 times a day with an interval of 12 hours for 5 days, with underlying routine treatment of primary disease in children with bacterial exacerbation of ARVI, manifested itself in significant difference in bronchial obstruction syndrome indicator starting from the 1st day of treatment, and in significant decrease of cough syndrome and main clinical syndromes total score by the 4th day of treatment, compared to the group of patients treated with a standard ARVI therapy. Due to the fact that the average duration of ARVI disease with complications was 8 bed days (7,80 + 2,37 bed days and 8,77 + 2,60, respectively), the presence of significantly better results in the group of patients who used recombinant interferon alpha-2b in combination with antioxidants vitamins E and C shows the effectiveness of this treatment regimen.

Anti-Lethal Therapy of COVID-19 for Home Health Outpatient Therapy

The article presents the rationale for a new therapeutic strategy for treatment of patients with COVID-19, based on the combined use of biologic response modifiers and drugs targeting etiology and pathophysiology of the novel coronavirus infection, excluding disadvantages of polypharmacy, and providing a high clinical effect. This approach has been predominantly used in home health outpatient treatment of 324 patients with COVID-19 of variable severity using the biologic response modifiers “double drug cocktail” made of recombinant human interleukin-2 and recombinant human interferon alpha-2b in combination with alimemazine, nimesulide, rivaroxaban and antibiotic therapy (co-amoxiclav, or ceftriaxone) if secondary bacterial pneumonia was diagnosed. The results obtained indicate a dramatic improvement in the condition of patients, even with a severe COVID-19, which made possible to avoid artificial ventilation and prevent deaths.

Novel drug for COVID-19: Virafin a therapeutic breakthrough

Background: Pegylated Interferon Alpha-2b is synthesized via the use of PEG (polyethylene glycol). It is formulated via attaching a 12kDa mono methoxy polyethylene glycol moiety to the recombinant human Interferon Alpha-2b protein. Pegylated Interferon Alpha-2b acts via binding to the (JAK/STAT) Janus kinase signal transducer and activator of the transcription interferon receptor. The Pegylated Interferon Alpha-2b /Virafin binds to the (IFNAR1/2) alpha interferon receptor 1 and 2. Pegylated Interferon Alpha-2b better known as Virafin has been approved by the Drugs Controller General of India. This therapeutic agent is currently under a multicentric phase 3 trial with very promising results being reported. A single subcutaneous dose of Virafin has been shown to decrease the need for oxygen therapy in patients. This reduction in the need for oxygen therapy is a vital factor needed to provide relief to the Indian medical system in light of the recent oxygen shortages faced due to India’s worst wave of COVID-19 cases since the onset of the global pandemic. Pegylated Interferon Alpha-2b/ Virafin confers enhanced viral clearance and bolsters the immune response to induce a quicker recovery in patients with mild to moderate symptoms. Conclusion: It is of paramount importance that further research on Virafin is undertaken as it can hinder the progression of COVID-19, reduce pressure on the inundated health systems, and save countless lives.

Interferon-alpha 2b: An Effective Treatment for Hepatic Epithelioid Hemangioendothelioma

Background: Hepatic epithelioid hemangioendothelioma (HEH) is a rare tumor and no standard treatment has been established. This study was aimed to prospectively investigate the effect of interferon-alpha 2b (IFN-a 2b) for HEH patients.Methods: Since March 2014, a total of 62 pathologically diagnosed HEH patients were followed up regularly. IFN-a 2b was suggested to HEH patients with progressed disease. Safety was assessed each month and tumor assessment scan was performed every 3 months. The primary end point was objective response rate (ORR) and disease control rate (DCR). Results: A total of 42 HEH patients were finally included in this study. Median patient age was 35.5 years (range 18-65 years old). No severe (grade ≥3) adverse event (AE) of IFN-a 2b was reported in the whole group. The most common treatment-related AEs were fever (50.0%) and fatigue (21.4%). Two patients had grade 2 level hypothyroidism and 1 patient had grade 2 level of leukopenia and thrombocytopenia. Partial response and complete response were achieved in 20 (47.6%) and 2 (4.8%) patients, respectively, and the ORR was 52.4%. Stable disease was observed in 12 (28.6%) patients and the DCR was 81.0%. Progressive disease was observed in 8 (19.0%) patients. The 1, 3 and 5-year progression free rate were 81.0%, 69.2% and 62.3%, respectively. Only 1 patient died due to the progression of disease during the study. The1, 3 and 5-year overall survival rate were 100%, 97.2% and 97.2%, respectively.Conclusion: IFN-a 2b is a safe and effective treatment for HEH patients.