HeberNasvac, a Therapeutic Vaccine for Chronic Hepatitis B, Stimulates Local and Systemic Markers of Innate Immunity: Potential Use in SARS-CoV-2 Postexposure Prophylaxis.

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.

Clinical Manifestations of Hospitalized COVID-19 Patients in Bangladesh: A 14-day Observational Study.

OBJECTIVES: Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is currently a significant public health concern and causing a pandemic in the world. Despite immense attention to the coronavirus disease 2019 (COVID-19), very little attention has been given to the kinetics of disease progression in infected patients. Therefore, in this study, we present a 14-day clinical observation of hospital-admitted COVID-19 patients. METHODS: After recording the demography of 42 COVID-19 patients on day 1, we observed the clinical progression for 14 days by investigating the hematological and biochemical responses of patients' blood and serum, respectively. RESULTS: Approximately, 62% of the hospital-admitted COVID-19 patients presented cough, followed by fever (∼52%). The top comorbidities of these patients were hypertension (30%) and diabetes mellitus (19%). The average blood hemoglobin (Hb) level was slightly low among the patients in the early days of infection and went up to the normal level on the later days. A substantial increase in the level of ALT or SGPT [up to 106 IU/L; standard error of the mean (SEM): 12.64] and AST or SGOT (up to 64.35 IU/L; SEM: 5.013) in COVID-19 patients was observed, which may suggest that infection with coronavirus is associated with the functionality of other organs of COVID-19 patients. CONCLUSION: This 14-day observational study may help clinicians to decide the choice of treatment for COVID-19 patients. HOW TO CITE THIS ARTICLE: Shaha M, Islam MA, Huq F, et al. Clinical Manifestations of Hospitalized COVID-19 Patients in Bangladesh: A 14-day Observational Study. Euroasian J Hepato-Gastroenterol 2021;11(1):14-20.

Role of Pegylated Interferon in Patients with Chronic Liver Diseases in the Context of SARS-CoV-2 Infection.

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.

Treatment of COVID-19 Patients at a Medical College Hospital in Bangladesh.

BACKGROUND AND AIM: Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has induced a sense of panic around the world as the disease is highly contagious and has been spreading in full swing during last 5 months causing millions of COVID-19 patients and hundreds of thousands of deaths. Bangladesh, a country of 170 million people, is not an exception regarding COVID-19; it has reported several thousand COVID-19 patients with several hundred of deaths. This observational study has been planned to assess the scope and limitation of management strategy against COVID-19 patients in a medical college hospital of Bangladesh with available drugs in a real-life situation. MATERIALS AND METHODS: All patients in this cohort (N: 33) were positive for SARS-CoV-2 by polymerase chain reaction (PCR) and they attended the hospital with variable presenting symptoms those ranged from cough and fever to respiratory distress and pneumonia. As per the protocol, the patients were regularly evaluated for several parameters of COVID-19-related pathology. Before discharge, they were checked for SARS-CoV-2 for 2 consecutive times. The management strategy included standard of care (SoC) and administration of hydroxychloroquine and azythromycin, available in Bangladesh. RESULTS: Out of total 33 patients, 1 patient died at day 4 day after admission. Two patients developed severe complications and were referred to tertiary hospital in Dhaka (2 and 3 days after admission), the capital of Bangladesh, where they recovered and were discharged from hospital after being SARS-CoV-2 negative. The rest 30 patients were discharged from the medical college hospital after being negative for SARS-CoV-2 in two subsequent assessments and improvement of their COVID-related symptoms. The average hospital stay of these patients was 14.5 days with a range of 10-24 days. CONCLUSION: It seems that most of the COVID-19 patients may be adequately managed by standard of care management with drug support. However, early diagnosis and hospitalization with adequate care may be important variables for better survival. These factors may be properly ensured if the patient burden remains at a palatable level in forthcoming days in Bangladesh. HOW TO CITE THIS ARTICLE: Bhuyan MAR, Al Mahtab M, Ashab E, et al. Treatment of COVID-19 Patients at a Medical College Hospital in Bangladesh. Euroasian J Hepato-Gastroenterol 2020;10(1):27-30.

Therapeutic Endoscopy during COVID-19 Pandemic: An Observational Study from Bangladesh.

How to cite this article: Al Mahtab M, Huq AKMF, Rahman MF, et al. Therapeutic Endoscopy during COVID-19 Pandemic: An Observational Study from Bangladesh. Euroasian J Hepato-Gastroenterol 2020;10(1): 47-49.

Real-life Management Strategy of COVID-19 Patients in Bangladesh with No Death: An Observational and Cohort Study.

BACKGROUND: Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been declared as pandemic by World Health Organization (WHO) with increasing morbidity (more than 4.6 million patients) and mortality (300,000 deaths). The world-wide target of management COVID-19 is to reduce complications with available management options; this become highly variable from country to country and even within different regions of the same country. AIM AND OBJECTIVE: This observational prospective study represents a single center study in which all patients in this cohort received almost similar medicines and care. MATERIALS AND METHODS: All patients in this cohort (N: 32) were positive for SARS-CoV-2 by polymerase chain reaction (PCR) with variable presenting symptoms. The management strategy included Standard of Care (SoC) and administration of hydroxychloroquine and doxycycline. Out of 32 patients, 9 patients also received favipiravir. All patients were followed until they were discharged after negativity of SARS-CoV-2 confirmed by PCR on two consecutive occasions taken within 2 days. RESULTS: No death has been recorded in this cohort of 32 patients within the study period. The average hospital staying duration was 13.9 days with a range of 8-21 days. All patients were discharged with improvement of subjective symptoms and SARS-CoV-2 negativity. The vital signs (pulse, blood pressure) as well as and levels of electrolyte and blood counts were within normal and acceptable ranges at the time of discharge. CONCLUSION: The study presented here provide and evidence of a real-life situation of management of limited numbers of COVID-19 patients at a tertiary center of Bangladesh. This study inspires optimism that proper diagnosis, establishment of effective inclusion and exclusion criteria, ensuring application of proper SoC with drugs available in Bangladesh may be a practical option for management of COVID-19 in the country. HOW TO CITE THIS ARTICLE: Huq AKMF, Rahman MF, Islam MA, et al. Real-life Management Strategy of COVID-19 Patients in Bangladesh with No Death: An Observational and Cohort Study. Euroasian J Hepato-Gastroenterol 2020;10(1):31-35.

Effect of Granulocyte Colony-stimulating Factor and Erythropoietin on Patients with Acute-on-chronic Liver Failure.

INTRODUCTION: Patients with acute-on-chronic liver failure (ACLF) have low survival without liver transplantation. Granulocyte colony-stimulating factor (G-CSF) improves survival in ACLF and erythropoietin (EPO) promotes hepatic regeneration in animal studies. The aim of this study is to determine whether coadministration of G-CSF and EPO improves the outcome in ACLF. METHODS: The study was conducted in the Department of Hepatology, Bangabandhu Sheikh Mujib Medical University, Dhaka. Consecutive patients with ACLF were randomly assigned into group A and group B. Group A patients received subcutaneous G-CSF (5 mcg/kg/d) for 6 days and subcutaneous EPO (40 mcg/wk) for 4 weeks and group B patients received only standard medical care (control group). All patients were followed up for 3 months. The primary end point was to see survival at 3 months. RESULTS: Patients had comparable baseline characteristics; hepatitis B virus infection was the commonest etiology of ACLF as both acute and chronic events. A higher proportion of patients were male in both groups. The survival was higher in group A than in group B at the end of 3 months (36.4% vs 29.4%; p = 0.457), but this was not statistically significant. Regarding complications, hepatorenal syndrome was higher in group B than in group A (36.7% vs 41.7%). In both the groups, Child-Turcotte-Pugh score and model for end-stage liver disease scores were similar before treatment and improved during follow-up. CONCLUSION: This is one of the early human studies that demonstrate potential hepatic regeneration using EPO in ACLF patients. Further study with a larger cohort will be needed to reproduce the results of the present work. HOW TO CITE THIS ARTICLE: Haque Md N, Al-Mahtab M, Das DC, et al. Effect of Granulocyte Colony-stimulating Factor and Erythropoietin on Patients with Acute-on-chronic Liver Failure. Euroasian J Hepato-Gastroenterol 2020;10(2):64-67.

Extraordinary Survival Benefits of Severe and Critical Patients with COVID-19 by Immune Modulators: The Outcome of a Clinical Trial in Bangladesh.

BACKGROUND: Coronavirus disease (COVID)-19 has devasted the healthcare delivery system as well as social establishments of almost all countries of the world. However, vaccines for containing new cases of COVID-19 are yet to be realized. Also, presently available antiviral drugs and other standard of care (SOC) management strategies could not satisfactorily control COVID-19-related mortality, which has crossed the one million mark during the last 9 months. These facts present an emergent need for developing new, novel, and evolving therapeutic strategies for the management of COVID-19. AIM AND OBJECTIVE: This cohort study represents a clinical trial in real-life situations in Bangladesh where two immune modulators were applied in patients with severe and critical COVID-19 patients. MATERIALS AND METHODS: A total of 199 confirmed patients of COVID-19 were enrolled in this study. All of them had severe and critical COVID-19 and they were hospitalized at the intensive care unit (ICU) of the Combined Military Hospital (CMH), Dhaka, Bangladesh. All patients were positive for SARS-CoV-2 by polymerase chain reaction (PCR) of the nasal swab and they were endowed with severe pneumonia, multiple organ dysfunctions, and coagulopathy. The median percentage of lung involvement was 65%. The mean oxygen saturation was 83%. The patients received two immune modulators (tocilizumab and bevacizumab) in different combinations to retrieve broader insights about the safety and efficacy of immune modulators in COVID-19 management. RESULTS: Out of the total 199 patients, 122 survived and 77 expired. A single dose of tocilizumab resulted in the survival of 71.5% (73 of 102 COVID-19 patients). On the other hand, a dramatic survival benefit was found in patients receiving bevacizumab (92%). CONCLUSION: The study indicates that active treatment should be started as early as possible for COVID-19 patients as moderate COVID-patients may progress to more severe illnesses with grave consequences. The safety of two immune modulators has been recorded in this cohort of severe and critical COVID-19 patients. In order to have a proper use of these immune modulators, there is a need to accomplish controlled, blinded, and large-scale prospective studies with at least two arms. HOW TO CITE THIS ARTICLE: Islam MA, Mazumder MA, Akhter N, et al. Extraordinary Survival Benefits of Severe and Critical Patients with COVID-19 by Immune Modulators: The Outcome of a Clinical Trial in Bangladesh. Euroasian J Hepato-Gastroenterol 2020;10(2):68-75.

Nobel Prize for the Discovery of Hepatitis B and C: A Brief History in Time.

In 2020, the Noble Prize for Medicine jointly went to three scientists for hepatitis C virus-related discoveries. Earlier in 1976, an American scientist won this award for the discovery of hepatitis B virus. The Noble Prize, constituted as per the will of Alfred Noble, is awarded every year for achievements that benefit human beings in the best possible way. Although humans have known hepatitis as a deadly disease for hundreds of years, it was the discovery of hepatitis B and C viruses that changed the way we knew the hepatitis viruses forever and paved the way for saving millions of lives all over the world, the reason why the Noble Committee has on two different occasions picked up the great minds behind the discovery of these two hepatitis viruses and recognized them by conferring them with the highest recognition that one dreams of. How to cite this article: Al-Mahtab M, Roy PP, Khan MSI, et al. Nobel Prize for the Discovery of Hepatitis B and C: A Brief History in Time. Euroasian J Hepatogastroenterol 2020;10(2):98-100.

High Prevalence of Wilson's Diseases with Low Prevalence of Kayser-Fleischer Rings among Patients with Cryptogenic Chronic Liver Diseases in Bangladesh.

BACKGROUND: Chronic liver disease (CLD) is common in Bangladesh; however, a major bulk remains as cryptogenic CLD as they remain devoid of known pathological agents leading to have a check of Kayser-Fleischer (K-F) rings for possible Wilson's disease (WD) and many of these patients develop complications such as cirrhosis of liver and hepatocellular carcinoma. However, there remains considerable proportions of CLD patients with undefined etiology (cryptogenic CLD) and these patients cannot be provided effective therapy based on etiological factors. Here, the proportion of WD among cryptogenic CLD patients in Bangladesh has been evaluated to improve the management of CLD and reduce complications. MATERIALS AND METHODS: A total of 941 patients with cryptogenic CLD [negative for hepatitis viruses, alcohol, nonalcoholic fatty liver disease (NAFLD), drug, and autoimmunity] were enrolled in the study. To assess if they have been suffering from WD, the levels of copper in 24-hour urine were evaluated. Definitive WD was diagnosed when 24-hour urinary copper output was >100 µg and strongly indicative WD patients excreted >40 µg of copper in 24 hours. RESULTS: Out of 941 patients with cryptogenic CLD, 212 patients were diagnosed as definitive WD and 239 patients as strongly indicative WD on the basis of 24-hours copper excretion. The age distribution ranging of the patients varied from 1 year to 90 years. There was a male predominance. Considerable numbers of WD patients had previous history of jaundice. Kayser-Fleischer rings were mostly uncommon and detected in five patients with WD only. DISCUSSION: Wilson's disease is not a rare entity in Bangladesh; rather, it seems to be fairly common among CLD patients. A country-wide epidemiological survey should be conducted for diagnosis of WD in Bangladesh to provide a proper management strategy for these huge numbers of WD patients. In fact, most of the WD patients are unaware of their diagnosis and the general physicians are equally unaware of diagnosis and management of WD. HOW TO CITE THIS ARTICLE: Choudhury N, Quraishi SB, Atiqullah AKM, et al. High Prevalence of Wilson's Diseases with Low Prevalence of Kayser-Fleischer Rings among Patients with Cryptogenic Chronic Liver Diseases in Bangladesh. Euroasian J Hepato-Gastroenterol 2019;9(2):67-70.

Cost Assessment of Hepatitis B Virus-related Hepatitis in Bangladesh.

Hepatitis B virus (HBV) infection is endemic in Bangladesh. Studies have indicated that HBV is the major cause of chronic hepatitis B (CHB), liver cirrhosis (LC), and hepatocellular carcinoma (HCC) in this country. Recently, HBV-related acute on chronic liver failure (HBV-ACLF) has emerged as a serious and emergent medical problem in Bangladesh. To develop a strategy to address HBV-related problems and their influence on health care delivery system, proper understandings about extent of problems and nature of economic burden should be explored. Conservative estimates indicate that about 50 million or more of Bangladeshi have been infected by HBV at some point of their life. Out of the total Bangladeshi population, about 2 to 5% is chronically infected with HBV (about 3-8 million) (1-6%) and considerable number of these patients will eventually develop LC, HCC, or ACLF (about 1 million). Although proper statistics is lacking, it is estimated that HBV-related liver diseases account for a majority of hospital admissions and around 20,000 deaths every year in Bangladesh. In addition, complex clinical features of HBV-related liver diseases have been documented in Bangladesh that show similarity and differences from HBV infection in other Asian countries. Although vaccination against HBV and containment of horizontal transmission are in progress in Bangladesh for reduction of new HBV infection, there is a lack of national strategy for treatment of millions of chronic HBV-infected subjects. This paper will provide an insight regarding the economic impact of HBV in Bangladesh that may act as a primary impetus for developing national HBV eradication program, a goal set by World Health Organization (WHO). HOW TO CITE THIS ARTICLE: Al Mahtab M, Chaudhury M, Uddin MH, Noor-E-Alam SM, Rahim MA, Alam MA, Moben AL, Khondaker FA, Choudhury MFI, Sarkar MJA, Poddar PK, Foez SA, Akbar SMF. Cost Assessment of Hepatitis B Virus-related Hepatitis in Bangladesh. Euroasian J Hepato-Gastroenterol 2016;6(2):163-166.