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INTRODUCTION: More than 180 million people have been infected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and more than 4 million coronavirus disease-2019 (COVID-19) patients have died in 1.5 years of the pandemic. A novel therapeutic vaccine (NASVAC) has shown to be safe and to have immunomodulating and antiviral properties against chronic hepatitis B (CHB). MATERIALS AND METHODS: A phase I/II, open-label controlled and randomized clinical trial of NASVAC as a postexposure prophylaxis treatment was designed with the primary aim of assessing the local and systemic immunomodulatory effect of NASVAC in a cohort of suspected and SARS-CoV-2 risk-contact patients. A total of 46 patients, of both sexes, 60 years or older, presenting with symptoms of COVID-19 were enrolled in the study. Patients received NASVAC (100 µg per Ag per dose) via intranasal at days 1, 7, and 14 and sublingual, daily for 14 days. RESULTS AND DISCUSSION: The present study detected an increased expression of toll-like receptors (TLR)-related genes in nasopharyngeal tonsils, a relevant property considering these are surrogate markers of SARS protection in the mice model of lethal infection. The HLA-class II increased their expression in peripheral blood mononuclear cell's (PBMC's) monocytes and lymphocytes, which is an attractive property taking into account the functional impairment of innate immune cells from the periphery of COVID-19-infected subjects. NASVAC was safe and well tolerated by the patients with acute respiratory infections and evidenced a preliminary reduction in the number of days with symptoms that needs to be confirmed in larger studies. CONCLUSIONS: Our data justify the use of NASVAC as preemptive therapy or pre-/postexposure prophylaxis of SARS-CoV-2 and acute respiratory infections in general. The use of NASVAC or their active principles has potential as immunomodulatory prophylactic therapies in other antiviral settings like dengue as well as in malignancies like hepatocellular carcinoma where these markers have shown relation to disease progression. HOW TO CITE THIS ARTICLE: Fleites YA, Aguiar J, Cinza Z, et al. HeberNasvac, a Therapeutic Vaccine for Chronic Hepatitis B, Stimulates Local and Systemic Markers of Innate Immunity: Potential Use in SARS-CoV-2 Postexposure Prophylaxis. Euroasian J Hepato-Gastroenterol 2021;11(2):59-70.
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INTRODUCTION: HBV is major health problem globally due to complications, including ACLF, cirrhosis and hepa¬tocellular carcinoma. ACLF due to exacerbation of CHB is associate with 30%-70% mortality. Reduction of HBV-DNA is therefore a target of therapy in ACLF-B. METHODS: Patients with spontaneous reactivation of HBV [(ALT >5×ULN or >2× baseline) and HBV-DNA >20,000 IU/ml] were randomized to Tenofovir mono therapy (300 mg/day) or Tenofovir plus Telbivudine (600 mg/day) dual therapy with standard care. Clinical and biochemical parameters were evaluated at baseline, 1 week, 4 weeks and at 3 months. Virological evaluation was done at baseline and at 3 months. Primary end points were reduction of HBV-DNA and resolution of ascites, as applied. Secondary end point was reduction of liver related complications, therapy related adverse effects and survival at 3 months. RESULTS: 27 patients were enrolled. 15 received mono therapy with Tenofovir and 12 received dual therapy (Tenofovir plus Telbivudine). Baseline parameters in 2 groups had no significant difference. In both groups there was significant improvement of S. bilirubin, ALT, INR, CTP score and MELD score. Only MELD score showed significant improvement in patient with dual therapy at 3 months in comparison to mono therapy. 11 patients on Tenofovir mono therapy (n=15) showed undetected HBV-DNA (91.7%) at 3 months and one patient had detectable HBV-DNA (<2,000 IU/ml). 10 patients on dual therapy (n=12) had undetectable HBV-DNA (100%). Ascites resolved in 3 patients in both groups. Patients receiving dual therapy showed significant improvement in AKI on follow up compared to those on Tenofovir mono therapy. Among 5 deaths, 3 received mono therapy with Tenofovir and 2 dual therapy. Predictors of mortality had high S. bilirubin, HBV-DNA, MELD score and CTP score. CONCLUSION: In spontaneous reactivation of HBV presenting as ACLF, combination of Telbivudine plus Tenofovir is safer with less nephrotoxicity and better outcomes.
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The coronavirus 2019 (COVID-19) pandemic has resulted in 168 million cases and about 3.5 million deaths (as of May 26, 2021) during the last 18 months. These 18 months of the COVID-19 pandemic have been characterized by phases or waves of new cases, the emergence of new variants of the deadly virus, and several new complications. After providing emergency approval to several drugs and adherence to several public health measures with frequent full and partial lockdowns, the incidence of new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) could not be contained till now on a global basis. Although prophylactic vaccines have inspired optimism, the scarcity of vaccines and several vaccine-related regulations indicate that the vaccine's benefit would not be reaching the people of developing countries anytime soon. In the course of our clinical practice, we used pegylated interferon (Peg-IFN) in 35 patients with chronic liver diseases (CLD), and we found that only two of them were infected with SARS-CoV-2 that was mild in nature. These two patients with CLD have a mild course of disease cured without any specific therapy. Patients with CLD are usually immune-compromised. However, three CLD patients remained free of SARS-CoV-2 although they had COVID-19 patients among their family members. Next, we accomplished two studies for assessing the immune-modulatory capacities of Peg-IFN, 1 and 12 injections following administration of Peg-IFN. The data revealed that peripheral blood mononuclear cells (PBMCs) of Peg-IFN-administered CLD patients produced significantly higher levels of some cytokines of innate immunity in comparison with the cytokines produced by PBMC of CLD patients before Peg-IFN intake. The pattern of cytokine responses and absence of infection of SARS-CoV-2 in 33 of 35 CLD patients represent some preliminary observations indicating a possible role of Peg-IFN in patients with CLD. The study may be extended to other chronic infections and cancers in which patients receive Peg-IFN. The role of Peg-IFN for pre- or postexposure prophylaxis in the acquisition of SARS-CoV-2 infection and influencing the natural course of COVID-19 remains to be clarified. HOW TO CITE THIS ARTICLE: Akbar SMF, Mahtab MA, Aguilar JC, et al. Role of Pegylated Interferon in Patients with Chronic Liver Diseases in the Context of SARS-CoV-2 Infection. Euroasian J Hepato-Gastroenterol 2021;11(1):27-31.