Comparative role of tenofovir versus entecavir for treating patients with hepatitis B virus-related acute on chronic liver failure.

INTRODUCTION: The aim of the study was to compare the safety and efficacy of tenofovir versus entecavir for treatment of naive acute on chronic liver failure (ACLF) due to hepatitis B virus (HBV) (ACLF-B). METHODS: Thirty-two patients aged 14-65 years were enrolled in the study. Diagnosis of ACLF was confirmed by clinical condition, biochemical analysis, and virological data. The causes of both chronic liver damages and acute insult in all patients were HBV. They were expressing HBV DNA in the sera, positive for IgM anti-HBc, had increased levels of serum bilirubin, compromised prothrombin time; and more than 50% patients had encephalopathy. The standard dose of tenofovir and entecavir was given. RESULTS: The antiviral effects of tenofovir and entecavir were evident as most patients became negative for HBV DNA in the sera after 90 days of therapy. Also, the levels of serum bilirubin, CTP (Child-Turcotte-Pugh) and MELD (model for end-stage liver disease) score exhibited significant improvement due to antiviral therapy. Although the improvement of liver functions, and liver damages were detected in patients receiving both tenofovir and entecavir, the survival of the patients was significantly higher in those receiving tenofovir compared to entecavir-treated patients. CONCLUSION: This prospective study with limited number patients provides a challenge to assess the real potential of tenofovir over entecavir as therapeutic option for ACLF-B by conducting a multicenter clinical trial enrolling patient of different races and background.

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.

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.

Stem Cell Therapy for Cirrhosis of Liver in Bangladesh: Specific Design Compatible for Developing Country.

AIMS AND OBJECTIVES: To assess the safety and efficacy of stem cell therapy in patients with cirrhosis of the liver (LC) in the context of developing country with limited facilities for cell-based therapy and advanced technologies. MATERIALS AND METHODS: A total of 34 patients received granulocyte colony-stimulating factor at a dose of 30 IU, daily for 2 to 11 days to upregulate the numbers of white blood cells and stem cells. Subsequently, stem cells were isolated from the peripheral blood of LC patients in a closed chamber using a harvesting machine. Variable amounts of autologous stem cells were injected to LC patients for once. The patients were followed for 3 months and various factors related to safety and parameters of efficacy were analyzed in this interim report. RESULTS: Out of 34 patients available for final analysis, 3 months after the start of stem therapy, 4 patients died within this period. There was no significant alteration in biochemical parameters due to stem cell therapy, and patients also did not develop any features of acute liver failure indicating that short-term safety parameters of stem cell therapy may be acceptable. Stem cell therapy had a dominant effect on ascites of in this cohort. Although 24 of 34 patients had ascites at the start of therapy,ascites were found in 11 patients after one month and only 4 patients had ascites after 3 months. The positive role of stem cell therapy on ascites in LC patients may be attributed, even in part, to increased serum levels of albumin after therapy compared to basal levels (p <0.001). CONCLUSION: This first study about stem cell therapy in Bangladesh indicates that cell therapy may be accomplished in general hospitals of developing countries if the proper design and mild to moderate types of invasive approach is utilized. The apparent safety of administered stem cells in LC patients and the observed effect on ascites of LC patients inspire optimism about the installation of new and innovative therapy in Bangladesh. Future studies with phase I/II may with stem cell and others cell may be planned at Bangladesh in patients with LC and other intractable diseases with suitable control arms.How to cite this article: Mahtab MA, Akbar SMF, Begum M, Islam MA, Rahim MA, Noor-E-Alam SM, Alam MA, Khondaker FA, Moben AL, Mohsena M, Khan SI, Huq MZ, Munshi S, Hoque A, Haque SA. Stem Cell Therapy for Cirrhosis of Liver in Bangladesh: Specific Design Compatible for Developing Country. Euroasian J Hepatogastroenterol, 2018;8(2):121-125.