Twenty-five years of Nipah outbreaks in Southeast Asia: A persistent threat to global health.

Objectives: Nipah virus (NiV), a bat-borne zoonotic pathogen, poses persistent threats to global public health due to severe clinical manifestation and high case fatality rate (CFR). A critical examination of NiV outbreaks is essential for refining strategies and mitigating the impact of future infections. In this study, we provide a concise update on global NiV outbreaks that occurred during the past 25 years. Methods: In this geospatial study, we conducted an in-depth examination of the epidemiological characteristics of human NiV cases and deaths from 1998 to 2024 through multiple analyses of public data and official reports. Results: NiV emerged in 1998 in Malaysia during an outbreak among pig farmers. Since then, NiV outbreaks have been documented in five countries of South and Southeast Asia (Bangladesh, India, Malaysia, Philippines, and Singapore). As of May 2024, there have been 754 confirmed human NiV cases with 435 deaths (CFR: 58%) reported in these five countries. Bangladesh records the highest incidence (341 cases and 241 deaths; CFR: 71%) followed by Malaysia (283 cases and 109 deaths; CFR: 39%), India (102 cases and 74 deaths; CFR: 73%), the Philippines (17 cases and nine deaths; CFR: 53%), and Singapore (11 cases and one death; CFR: 9%). Conclusions: The clinical outcomes of NiV have been underscoring constant global public health threats as no effective therapies and vaccines are available. Strong global understandings, with an eye on developing vaccines and therapeutics, are required to minimize clinical outcomes and future threats of NiV.

Bangladesh records persistently increased number of dengue deaths in recent years: Dissecting the shortcomings and means to resolve.

Objectives: Dengue, a life-threatening disease caused by the mosquito-borne dengue virus, has become a severe problem in recent years in Bangladesh, a South Asian country. In this study, we have critically analyzed the factors contributing to the escalation of the dengue burden in recent years in Bangladesh and discussed the strategies for effective control. Design: This retrospective observational study analyzed the dengue data collected from the five most dengue-affected countries (Bangladesh, Brazil, Mexico, Peru, and the Philippines) from 2019 to 2023. Results: An increased number of dengue-related deaths has been recorded in Bangladesh since 2021. The year 2023 has witnessed a record high dengue-related deaths in Bangladesh, with cumulative deaths for the year surpassing all totals of the previous 23 years (2000-2022: 853 deaths vs 2023: 1705 deaths). Comparing the epidemiologic data of major dengue-endemic countries over the last 5 years, Bangladesh recorded higher dengue fatality rates consecutively for 3 years. Besides the environmental and viral host factors, which are also applicable to many other dengue-endemic countries, there is concern about the failures and mismanagement of authorities to manage dengue patients properly. Conclusion: This study provided evidence that Bangladesh recorded higher dengue fatality rates in recent years. By implementing multi-pronged proactive approaches that can ensure proper prevention programs and appropriate patient management, Bangladesh or similar other countries can significantly reduce the current dengue burden and the associated deaths.

Comprehensive analysis of antigenic variations and genomic properties of hepatitis B virus in clinical samples in the mid-north east region of Bangladesh.

This investigation delineates an exhaustive analysis of the clinical, immunological, and genomic landscapes of hepatitis B virus (HBV) infection across a cohort of 22 verified patients. The demographic analysis unveiled a pronounced male bias (77.27%), with patient ages spanning 20 to 85 years and durations of illness ranging from 10 days to 4 years. Predominant clinical manifestations included fever, fatigue, anorexia, abdominal discomfort, and arthralgia, alongside observed co-morbidities such as chronic renal disorders and hepatocellular carcinoma. Antigenic profiling of the HBV envelope proteins elucidated significant heterogeneity among the infected subjects, particularly highlighted by discordances in the detection capabilities of small and large HBsAg assays, suggesting antigenic diversity. Quantitative assessment of viral loads unveiled a broad spectrum, accompanied by atypical HBeAg reactivity patterns, challenging the reliability of existing serological markers. Correlative studies between viral burden and antigenicity of the envelope proteins unearthed phenomena indicative of diagnostic evasion. Notably, samples demonstrating robust viral replication were paradoxically undetectable by the large HBsAg ELISA kit, advocating for more sophisticated diagnostic methodologies. Genotypic examination of three HBV isolates classified them as genotype D (D2), with phylogenetic alignment to strains from various global origins. Mutational profiling identified pivotal mutations within the basic core promoter and preS2/S1 regions, associated with an augmented risk of hepatocellular carcinoma. Further, mutations discerned in the small HBsAg and RT/overlap regions were recognized as contributors to vaccine and/or diagnostic escape mechanisms. In summation, this scholarly discourse elucidates the intricate interplay of clinical presentations, antigenic diversity, and genomic attributes in HBV infection, accentuating the imperative for ongoing investigative endeavors to refine diagnostic and therapeutic modalities.

Intranasal HBsAg/HBcAg-Containing Vaccine Induces Neutralizing Anti-HBs Production in Hepatitis B Vaccine Non-Responders.

Hepatitis B vaccine induces the production of antibodies against hepatitis B surface antigen (anti-HBs) and prevents hepatitis B virus (HBV) infection. However, 5-10% of individuals cannot develop anti-HBs even after multiple vaccinations (HB vaccine non-responders). We developed an intranasal vaccine containing both HBs antigen (HBsAg) and HB core antigen (HBcAg) and mixed it with a viscosity enhancer, carboxyl vinyl polymer (CVP-NASVAC). Here, we investigated the prophylactic capacity of CVP-NASVAC in HB vaccine non-responders. Thirty-four HB vaccine non-responders were administered three doses of intranasal CVP-NASVAC. The prophylactic capacity of CVP-NASVAC was assessed by evaluating the induction of anti-HBs and anti-HBc (IgA and IgG) production, HBV-neutralization activity of sera, and induction of HBs- and HBc-specific cytotoxic T lymphocytes (CTLs). After CVP-NASVAC administration, anti-HBs and anti-HBc production were induced in 31/34 and 27/34 patients, respectively. IgA anti-HBs and anti-HBc titers significantly increased after CVP-NASVAC vaccination. HBV-neutralizing activity in vitro was confirmed in the sera of 26/29 CVP-NASVAC-administered participants. HBs- and HBc-specific CTL counts substantially increased after the CVP-NASVAC administration. Mild adverse events were observed in 9/34 participants; no serious adverse events were reported. Thus, CVP-NASVAC could be a beneficial vaccine for HB vaccine non-responders.

Development of Therapy Based on the Exploration of Biological Events Underlying the Pathogenetic Mechanisms of Chronic Hepatitis B Infection.

According to the World Health Organization (WHO), an estimated 296 million people are chronically infected with hepatitis B virus (HBV). Approximately 15-25% of these people develop complications such as advanced chronic liver diseases (ACLDs). Mortality due to HBV-related complications accounted for an estimated 882,000 deaths in 2019. Potent preventive vaccines have already restricted new HBV infections, and several drugs are available to treat chronic HBV infections. However, the positive impacts of these drugs have been recorded in only a few patients with chronic HBV infection. These drugs do not show long-term efficacy and cannot halt the progression to complications. Thus, more effective and evidence-based therapeutic strategies need to be urgently developed for patients with chronic HBV infection. CHB is a pathological entity induced by HBV that progresses due to impaired host immunity. This indicates the inherent limitations of antiviral-drug-based monotherapy for treating patients with chronic HBV infection. Additionally, commercially available antiviral drugs are not available to patients in developing and resource-constrained countries, posing a challenge to achieving the following WHO goal: "Elimination of Hepatitis by 2030". As such, this review aimed to provide insights regarding evidence-based and effective management strategies for chronic HBV infection.

Antiviral Response across Genotypes after Treatment of Chronic Hepatitis B Patients with the Therapeutic Vaccine NASVAC or Pegylated Interferon.

An open-level, randomized and treatment-controlled clinical trial has shown that a therapeutic vaccine containing hepatitis B surface antigen (HBsAg) and hepatitis B core antigen (HBcAg) (NASVAC) is endowed with antiviral and liver protecting capacity and is safer than pegylated interferon (Peg-IFN) in patients with chronic hepatitis B (CHB). The present study provides information about the role of the hepatitis B virus (HBV) genotype in this phase III clinical trial. From a total of 160 patients enrolled in this trial, the HBV genotypes of 133 patients were characterized, and NASVAC induced a stronger antiviral effect (HBV DNA reduction below 250 copies per mL) than Peg-IFN. The antiviral effects and alanine aminotransferase levels were not significantly different among different HBV genotypes in NASVAC-treated patients. However, a significantly higher proportion of genotype-D patients receiving NASVAC showed better therapeutic effects, compared to genotype-D patients receiving Peg-IFN, with a marked difference of 44%. In conclusion, NASVAC seems to be a better alternative to Peg-IFN, especially in patients with HBV genotype-D patients. This reflects the attractiveness of NASVAC in countries where genotype D is highly prevalent. The mechanisms underlying the effect of HBV genotype are being studied in a new clinical trial.

INASL-SAASL Consensus Statements on NAFLD Name Change to MAFLD.

There is an ongoing debate on the change of terminology of non-alcoholic fatty liver disease (NAFLD) to metabolic associated fatty liver disease (MAFLD). Experts from the Indian National Association for Study of the Liver (INASL) and the South Asian Association for Study of the Liver (SAASL) involved in diagnosing, managing, and preventing NAFLD met in March 2022 to deliberate if the name change from NAFLD to MAFLD is appropriate, as proposed by a group of experts who published a "consensus" statement in 2020. Proponents of name change to MAFLD opined that NAFLD does not reflect current knowledge, and the term MAFLD was suggested as a more appropriate overarching term. However, this "consensus" group which proposed the name change to MAFLD did not represent the views and opinions of gastroenterologists and hepatologists, as well as perceptions of patients across the globe, given the fact that change of nomenclature for any disease entity is bound to have multidimensional impact on all aspects of patient care. This statement is the culmination of the participants' combined efforts who presented recommendations on specific issues concerning the proposed name change. The recommendations were then circulated to all the core group members and updated based on a systematic literature search. Finally, all the members voted on them using the nominal voting technique as per the standard guidelines. The quality of evidence was adapted from the Grades of Recommendation, Assessment, Development and Evaluation system.

Cellular and Molecular Mechanisms of Pathogenic and Protective Immune Responses to SARS-CoV-2 and Implications of COVID-19 Vaccines.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has devastated the world with coronavirus disease 2019 (COVID-19), which has imparted a toll of at least 631 million reported cases with 6.57 million reported deaths. In order to handle this pandemic, vaccines against SARS-CoV-2 have been developed and billions of doses of various vaccines have been administered. In the meantime, several antiviral drugs and other treatment modalities have been developed to treat COVID-19 patients. At the end of the day, it seems that anti-SARS-CoV-2 vaccines and newly developed antiviral drugs may be improved based on various new developments. COVID-19 represents a virus-induced, immune-mediated pathological process. The severity of the disease is related to the nature and properties of the host immune responses. In addition, host immunity plays a dominant role in regulating the extent of COVID-19. The present reality regarding the role of anti-SARS-CoV-2 vaccines, persistence of SARS-CoV-2 infection even three years after the initiation of the pandemic, and divergent faces of COVID-19 have initiated several queries among huge populations, policy makers, general physicians, and scientific communities. The present review aims to provide some information regarding the molecular and cellular mechanisms underlying SARS-CoV-2 infection.

Safety profile, antiviral capacity, and liver protection of a nasal therapeutic vaccine in patients with chronic hepatitis B: Five-year-follow-up outcomes after the end of treatment.

Introduction: There is a pressing need to develop novel drugs for treating patients with chronic hepatitis B (CHB), as commercially available antiviral drugs are endowed with safety and efficacy concerns. Methods: A phase III clinical trial was conducted with a therapeutic vaccine containing two antigens of the hepatitis B virus (HBV; named NASVAC) in 78 patients with CHB expressing both HBV DNA and elevated levels of alanine aminotransferase (ALT) in the blood. Five years after the end of treatment (EOT), 60 NASVAC-recipient patients were enrolled in this long-term follow-up study to evaluate the safety, antiviral potential, and liver-protective capacity of NASVAC. Results: NASVAC exhibited an excellent safety profile 5 years after EOT. The levels of HBV DNA in the sera were reduced in 55 of the 60 patients, and 45 of them were negative for HBV DNA in the sera. ALT levels were also normalized in 40 of the 60 patients 5 years after EOT. None of the patients receiving NASVAC developed liver cirrhosis or cancer. Discussion: The present study is the first to exhibit long-term follow-up data of a finite immune therapy for CHB that is safe and endowed with potent antiviral and liver-protecting capacities.

Intranasal therapeutic vaccine containing HBsAg and HBcAg for patients with chronic hepatitis B; 18 months follow-up results of phase IIa clinical study.

AIMS: HBsAg loss with anti-HBs acquisition is considered a functional cure and ideal treatment goal for patients with CHB. Our group have reported the efficacy of therapeutic vaccine with HBsAg and HBcAg (NASVAC) by intranasal and subcutaneous injection. In this study, we investigated the safety and efficacy of newly developed CVP-NASVAC, which contained NASVAC with mucoadhesive carboxyl vinyl polymer (CVP) in the dedicated device. METHODS: A single dose, open-label, phase IIa clinical trial of CVP-NASVAC was conducted. Patients with CHB treated with nucleoside/nucleotide analogs (NAs) and HBV carriers not undergoing anti-HBV treatment were enrolled. CVP-NASVAC was injected through the nose for, in total, 10 times. Participants were followed-up for 18 months, and their HBsAg reduction and anti-HBs induction assessed as endpoints. RESULTS: Among the patients with CHB treated with NAs (n = 27) and HBV carriers without NAs (n = 36), 74.1% and 75.0% exhibited reductions in their baseline HBsAg, and the mean reductions were -0.1454 log10  IU/ml (p < 0.05) and -0.2677 log10  IU/ml (p < 0.05), respectively. Anti-HBs antibody was detected in 40.7% and 58.3% of patients treated with and without NAs, respectively. Six of 71 (9.5%) patients were functionally cured after the CVP-NASVAC treatment. CONCLUSIONS: Anti-HBs induction and HBsAg reduction was observed after CVP-NASVAC treatment in some patients with CHB. The CVP-NASVAC is a safe treatment, which might expect to achieve functional cure for patients with CHB.

Impact of the Route and Schedule of Immunization on the Serological and Virological Response of Chronic Hepatitis B Patients Treated with HeberNasvac.

HeberNasvac is a recently developed therapeutic vaccine for chronic hepatitis B (CHB) administered by intranasal (IN) and subcutaneous (SC) routes in a 14 days/10 doses schedule. To compare different schedules and routes of immunizations, a group of patients received four different vaccination regimens in a placebo-controlled factorial study. Subsequently, patients were followed for a minimum time of 48 weeks. Samples collected at the end of the follow-up were compared with initial samples. Groups I and II received the product by IN/SC routes, every 14 and 7 days, respectively. Groups III and IV were treated by SC route alone following a 14 and 7 days schedule. A group of 21 CHB patients received the vaccine in four different schedules and eight patients received placebo for a total of 29 patients enrolled. The 61.9% of vaccinees reduced their VL ≥2Log compared with baseline levels and 25% in placebo group. The 47.6% of vaccines reduced HBV levels to undetectable, 25% in placebo. HBeAg loss and seroconversion to anti-HBeAg was only achieved in vaccinees, 4 out of 9 (44.4%), and 40% (8 out of 20) developed anti-HBs response, none in placebo group. Reduction of HBsAg level in ≥1Log was achieved in the 35.0% of vaccinees and in none of the placebo-treated patients. Considering the individual and factorial analysis, significant HBV DNA reduction was detected in groups I and II, immunized by IN/SC routes. A significantly higher proportion of patients reducing VL to ≥2Log was also detected grouping the patients treated by IN/SC routes (G I + II) and grouping those inoculated every 14 days (G I + III), with 72.7% and 63.6%, respectively, compared with the placebo group (25.0%). The patients immunized every 14 days (G I + G III) also reduced the HBsAg levels compared with baseline. In conclusion, after more than 48 weeks of treatment-free follow-up, HeberNasvac-treated patients demonstrated superior responses compared with the placebo group in terms of antiviral and serological responses. The factorial analysis evidenced that the schedule combining the IN route of immunization and the frequency of 14 days resulted in the stronger antiviral and serological responses. Present results support the study of IN-only immunization schedules in future and was consistent with previous results. Long-lasting follow-ups were done to explore histological variables and the progression of serological variables in order to detect late responders. How to cite this article: Freyre FM, Aguiar JA, Cinza Z, et al. Impact of the Route and Schedule of Immunization on the Serological and Virological Response of Chronic Hepatitis B Patients Treated with HeberNasvac. Euroasian J Hepato-Gastroenterol 2023;13(2):73-78.

Identification of Leading Compounds from Euphorbia neriifolia (Dudsor) Extracts as a Potential Inhibitor of SARS-CoV-2 ACE2-RBDS1 Receptor Complex: An Insight from Molecular Docking ADMET Profiling and MD-simulation Studies.

Coronavirus disease-19 (COVID-19) are deadly and infectious disease that impacts individuals in a variety of ways. Scientists have stepped up their attempts to find an antiviral drug that targets the spike protein (S) of Angiotensin converting enzyme 2 (ACE2) (receptor protein) as a viable therapeutic target for coronavirus. The most recent study examines the potential antagonistic effects of 17 phytochemicals present in the plant extraction of Euphorbia neriifolia on the anti-SARS-CoV-2 ACE2 protein. Computational techniques like molecular docking, absorption, distribution, metabolism, excretion, and toxicity (ADMET) investigations, and molecular dynamics (MD) simulation analysis were used to investigate the actions of these phytochemicals. The results of molecular docking studies showed that the control ligand (2-acetamido-2-deoxy-ß-D-glucopyranose) had a binding potential of -6.2 kcal/mol, but the binding potentials of delphin, ß-amyrin, and tulipanin are greater at -10.4, 10.0, and -9.6 kcal/mol. To verify their drug-likeness, the discovered hits were put via Lipinski filters and ADMET analysis. According to MD simulations of the complex run for 100 numbers, delphin binds to the SARS-CoV-2 ACE2 receptor's active region with good stability. In root-mean-square deviation (RMSD) and root mean square fluctuation (RMSF) calculations, delphinan, ß-amyrin, and tulipanin showed reduced variance with the receptor binding domain subunit 1(RBD S1) ACE2 protein complex. The solvent accessible surface area (SASA), radius of gyration (Rg), molecular surface area (MolSA), and polar surface area (PSA) validation results for these three compounds were likewise encouraging. The convenient binding energies across the 100 numbers binding period were discovered by using molecular mechanics of generalized born and surface (MM/GBSA) to estimate the ligand-binding free energies to the protein receptor. All things considered, the information points to a greater likelihood of chemicals found in Euphorbia neriifolia binding to the SARS-CoV-2 ACE2 active site. To determine these lead compounds' anti-SARS-CoV-2 potential, in vitro and in vivo studies should be conducted. How to cite this article: Islam MN, Pramanik MEA, Hossain MA, et al. Identification of Leading Compounds from Euphorbia Neriifolia (Dudsor) Extracts as a Potential Inhibitor of SARS-CoV-2 ACE2-RBDS1 Receptor Complex: An Insight from Molecular Docking ADMET Profiling and MD-simulation Studies. Euroasian J Hepato-Gastroenterol 2023;13(2):89-107.

A Narrative Review on the Specific Pattern of HBV Genotype in Bangladesh: Clinical Implications for Management.

Background and aims: Bangladesh's unique epidemiological landscape presents an intriguing puzzle. This South Asian nation, with its complex sociodemographic and environmental factors, is home to a diverse array of hepatitis-B virus (HBV) genotypes, identified as Genotype C, with Genotypes D and A also making a significant contribution to the viral landscape. Reviewing such insights is necessary not only to underscore the country's regional diversity in HBV strains but also to bring into focus the clinical implications these genetic variations may have on disease progression and management. Methods: A thorough database search covered various sources using relevant keywords like "Hepatitis B virus genotypes", "HBV genotypes in Bangladesh", and "HBV clinical implications". The review synthesized findings and analyzed HBV genotype prevalence and clinical implications in Bangladesh. Results: Genotypes C and D collectively represent 82% of chronic hepatitis-B infection (CHB) cases in Bangladesh, underscoring their regional prevalence. The geographic context is pivotal in understanding HBV infection dynamics and disease progression in this area. Notably, genotype C and the presence of A1762T/G1764A mutations appear to have a distinct impact on disease development, potentially affecting the immune response in CHB patients. This highlights the need for tailored management approaches in this specific region. Further research is vital to confirm and elaborate on these findings, particularly in relation to how these mutations influence the host's immune response. Conclusion and clinical significance: In summary, studies on HBV genotypes in Bangladesh stress the need for genotype-specific clinical considerations and more research to improve diagnostics and therapies. How to cite this article: Raihan R, Akbar SMF. A Narrative Review on the Specific Pattern of HBV Genotype in Bangladesh: Clinical Implications for Management. Euroasian J Hepato-Gastroenterol 2023;13(2):152-158.

Recent Dengue Infection in Bangladesh: A Seasonal Endemic Progressing to Year-long Serious Health Concern.

Dengue represents one of the most dangerous mosquito-borne viral diseases. Although the disease has been prevalent around the globe over the centuries, recent outbreaks of dengue have devasted the healthcare delivery system of many countries. Being a global infection, dengue virus (DENV) is endemically present mainly in Latin America and Caribbean countries as well as countries in South Asia. The recent outbreak of DENV infection has indicated an exceptional outbreak of DENV in some countries in South Asia. There has been a serious endemic of DENV during 2019. After a heterogeneous pause, another severe outbreak of DENV was reported in some Asian countries in 2023. Among the Asian countries, Bangladesh has reported an acute upsurge of DENV infection in 2023 with record numbers of fatalities. However, this pattern of DENV has not been detected in neighbors of Bangladesh, such as India or other countries in Southeast Asia. This provides an emergent task of dissecting the present DENV infection in Bangladesh from different angles to get insights for future containment of the DENV infection, not only in Bangladesh but also in other DENV endemic areas or DENV-native areas. How to cite this article: Akbar SMF, Khan S, Mahtab M, et al. Recent Dengue Infection in Bangladesh: A Seasonal Endemic Progressing to Year-long Serious Health Concern. Euroasian J Hepato-Gastroenterol 2023;13(2):145-151.

Action Mechanisms and Scientific Rationale of Using Nasal Vaccine (HeberNasvac) for the Treatment of Chronic Hepatitis B.

Nasvac (HeberNasvac®) is a novel therapeutic vaccine for chronic hepatitis B (CHB). This product is a formulation of the core (HBcAg) and surface (HBsAg) antigens of the hepatitis B virus (HBV), administered by nasal and subcutaneous routes, in a distinctive schedule of immunizations. In the present review article, we discuss the action mechanisms of HeberNasvac, considering the immunological properties of the product and their antigens. Specifically, we discuss the capacity of HBcAg to activate different pathways of innate immunity and the signal transduction after a multi-TLR agonist effect, and we review the results of recent clinical trials and in vitro studies. Aimed at understanding the clinical results of Nasvac and other therapeutic vaccines under development, we discuss the rationale of administering a therapeutic vaccine through the nasal route and also the current alternatives to combine therapeutic vaccines and antivirals (NUCs). We also disclose potential applications of this product in novel fields of immunotherapy.

Treatment of Nonalcoholic Steatohepatitis by Obeticholic Acid: Current Status.

Nonalcoholic fatty liver disease (NAFLD) is one of the major and prevalent liver diseases from the national and global perspectives. It appears that considerable numbers of the general population have been suffering from NAFLD. When a patient with NAFLD also exhibits inflammation of the liver, the condition is regarded as nonalcoholic steatohepatitis (NASH). Nonalcoholic steatohepatitis is a pathological entity that may progress to cirrhosis of the liver (LC) and hepatocellular carcinoma (HCC). It is acceptable by all that the health burden of NAFLD and NASH is tremendous. Due to the increased prevalence of these pathologies, extensive research has been conducted regarding pathogenesis, diagnostic tools, and staging of the diseases. However, adequate and approved pharmacotherapy for these pathologies is lacking. The farnesoid receptor (FXR) is a bile acid-activated receptor. It regulates lipid, glucose, bile acid metabolism. Farnesoid receptor is also endowed with anti-inflammatory and anti-fibrotic properties on the liver. Obeticholic acid (OCA), a potent and selective FXR ligand, may become a promising molecule to combat NASH and advanced fibrosis. The present review briefly discusses the current recommendation of NASH management with available pharmacological treatments. The scope of OCA with a focus on recent data of major randomized controlled trials (RCTs) is discussed. On the basis of current data and recent interim analysis, OCA seems to improve insulin resistance, steatohepatitis, levels of alanine transaminase (ALT) and fibrosis in NASH. Dose-related adverse effects like pruritus and dyslipidemia may limit its usage. Also, its usage may be restricted in patients with NASH cirrhosis. More adequately powered RCTs that would contain NASH patients with different and heterogeneous properties would be required to develop consensus about these issues. The safety profile of different doses of OCA needs to be established in these patients as well as there remain considerable queries about these. How to cite this article: Roy PP, Mahtab MA, Rahim MA, et al. Treatment of Nonalcoholic Steatohepatitis by Obeticholic Acid: Current Status. Euroasian J Hepato-Gastroenterol 2022;12(Suppl 1):S46-S50.

Development of Therapeutic Vaccine for Chronic Hepatitis B: Concept, Cellular and Molecular Events, Design, Limitation, and Future Projection.

Four decades have passed since the first usage of the therapeutic vaccine in patients with chronic hepatitis B (CHB). However, there is no approved regimen of vaccine therapy for the treatment of CHB. This is mainly attributable to faulty conception, an improper understanding of the cellular and molecular mechanisms of CHB, and the impaired design of vaccine therapy for CHB. With the advent of new techniques and a better understanding of cellular and molecular mechanisms underlying the genesis of CHB, the limitations and failures of previous regimens of therapeutic vaccines have been primarily understood. Additionally, the importance of immune therapy for treating millions of CHB patients and achieving the target of "Elimination of Hepatitis by 2030" has been focused on in the international arena. This has been amplified by the apparent limitation of commercially available antiviral drugs that are infinite in duration, endowed with safety concerns, and unable to cure liver damage due to their minimal immune modulation capacities. The proposed review article comprehensively discusses each of these points and proposes evidence-based approaches for viable types of vaccine therapy for the treatment of CHB.

A comprehensive design for prevention and management of COVID-19 in a tertiary medical institution in Bangladesh.

INTRODUCTION: Containment of the further spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and reducing fatality due to coronavirus disease 19 (COVID-19) represent a pressing challenge to global health services. Here, we present a management blueprint for both the containment of SARS-CoV-2 and treatment of COVID-19 through a comprehensive approach. METHODOLOGY: A cohort of 130 consecutive patients identified as positive for SARS-CoV-2 by testing of nasal swab by polymerase chain reaction were managed at a peripheral city of Bangladesh between 1 April and 31 May, 2020. Based on their clinical status, 64 of them were initially selected for isolation (Isolation Group) and 66 recommended for hospitalization (Hospital Group) as per the direction of the "Central COVID-19 Control" Center. Both groups of patients were allocated to receive standard of care management and oxygen inhalation, and intensive care unit management as and when necessary. Based on the conditions of the COVID-19 patients, there was an active system of patients being transferred from the "Isolation Group" to "Hospital Group" and vice versa. RESULTS: Twelve patients of the "Isolation Group" were transferred to the hospital, as they exhibited symptoms of deterioration. Four patients of the "Hospital Group" died during the observation period of two months in the intensive care unit. However, there has been no fatality among the patients of the "Isolation Group". CONCLUSIONS: The concept of "Isolation" and "Hospital Management" with the participation of the community seems to be an effective management strategy for COVID-19 in developing countries.

Dengue Infections during COVID-19 Period: Reflection of Reality or Elusive Data Due to Effect of Pandemic.

The outbreak of coronavirus disease 2019 (COVID-19) devastated the overall health management strategy of most countries. In this scenario, the present study provided insights into the possible impact of the COVID-19 pandemic on dengue infection. This ecological study retrieved data from WHO/Government reporting system from 22 major dengue epidemic countries. Incidence of dengue infections during the pre-COVID-19 time (2015~2019) and COVID-19 period (2020~2021) was compared. A correlation between the dengue and COVID-19 cases and predicted dengue incidence in 2022 was calculated using the linear regression equation. Data indicated that dengue incidences across the studied area decreased by 16% during the pandemic period (2.73 million vs. 2.29 million; p < 0.05) than the same reported in pre-COVID-19 time. Although countries in Latin America reported more cases than Asia, a positive correlation (r = 0.83) between dengue and COVID-19 cases was observed in Asia. Prediction analysis warned that specific preparation for dengue management is needed in some countries of both regions in 2022 to contain the upsurge in incidences. Due to the similar nature of symptoms of dengue and COVID-19, a state of confusion will be prevailing during the ongoing pandemic. Therefore, comprehensive and evidence-based scientific approaches were warranted at all levels.

Plasma Exchange in Patients of Acute on Chronic Liver Failure: An Observational Study in Bangladesh.

Background: Therapeutic plasma exchange (PLEX) removes toxins and different mediators from plasma in patients with acute-on-chronic liver failure (ACLF). Aim: To observe the safety and outcome of PLEX in ACLF patients in Bangladesh. Materials and methods: Twenty-eight patients with ACLF attending Bangabandhu Sheikh Mujib Medical University from September 2020 to May 2021 were enrolled in the study. The patients were given different treatment modalities and followed up for 3 months or up to death. The patients were divided into two groups, each containing 14 patients of ACLF. One group of 14 patients received standard medical therapy (SMT) for ACLF and the second group of 14 patients received SMT plus PLEX. Results: At 90 days, a total of 13 patients (46.43%) survived, of them 8 (57.1%) belonged to PLEX group and 5 (35.7%) were from SMT group. Serum bilirubin and ALT declined significantly after 7 and 30 days but not after 90 days in PLEX group in comparison to SMT group (p <0.05) but other biochemical parameters were not significantly different (p >0.05) between these two groups. Significant (p <0.05) improvement of MELD, MELD-Na, and AARC scores was observed in each group from baseline to subsequent first, second, and third follow-up but no significant (p >0.05) difference was observed in between two groups. Binary logistic regression analysis found that bilirubin, MELD score, MELD-Na score, and AARC score were predictors of mortality. Conclusion: The study presented here has shown that PLEX is safe in Bangladeshi in ACLF patients, but its efficacy remains to be checked in large-scale randomized trial or in combination therapy with other procedures in ACLF patients. How to cite this article: Al Mukit A, Al Mahtab M, Rahim MA, et al. Plasma Exchange in Patients of Acute on Chronic Liver Failure: An Observational Study in Bangladesh. Euroasian J Hepato-Gastroenterol 2022;12(1):1-5.