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.

Characteristics associated with COVID-19 vaccine uptake among adults aged 50 years and above in England (8 December 2020-17 May 2021): a population-level observational study.

OBJECTIVE: To determine characteristics associated with COVID-19 vaccine coverage among individuals aged 50 years and above in England since the beginning of the programme. DESIGN: Observational cross-sectional study assessed by logistic regression and mean prevalence margins. SETTING: COVID-19 vaccinations delivered in England from 8 December 2020 to 17 May 2021. PARTICIPANTS: 30 624 257/61 967 781 (49.4%) and 17 360 045/61 967 781 (28.1%) individuals in England were recorded as vaccinated in the National Immunisation Management System with a first dose and a second dose of a COVID-19 vaccine, respectively. INTERVENTIONS: Vaccination status with COVID-19 vaccinations. MAIN OUTCOME MEASURES: Proportion, adjusted ORs and mean prevalence margins for individuals not vaccinated with dose 1 among those aged 50-69 years and dose 1 and 2 among those aged 70 years and above. RESULTS: Of individuals aged 50 years and above, black/African/Caribbean ethnic group was the least likely of all ethnic groups to be vaccinated with dose 1 of the COVID-19 vaccine. However, of those aged 70 years and above, the odds of not having dose 2 was 5.53 (95% CI 5.42 to 5.63) and 5.36 (95% CI 5.29 to 5.43) greater among Pakistani and black/African/Caribbean compared with white British ethnicity, respectively. The odds of not receiving dose 2 was 1.18 (95% CI 1.16 to 1.20) higher among individuals who lived in a care home compared with those who did not. This was the opposite to that observed for dose 1, where the odds of being unvaccinated was significantly higher among those not living in a care home (0.89 (95% CI 0.87 to 0.91)). CONCLUSIONS: We found that there are characteristics associated with low COVID-19 vaccine coverage. Inequalities, such as ethnicity are a major contributor to suboptimal coverage and tailored interventions are required to improve coverage and protect the population from SARS-CoV-2.

Impact of the COVID-19 pandemic on Bordetella pertussis infections in England.

BACKGROUND: In March 2020, England went into its first lockdown in response to the COVID-19 pandemic. Restrictions eased temporarily, followed by second and third waves in October 2020 and January 2021. Recent data showed that the COVID-19 pandemic resulted in reduced transmission of some invasive diseases. We assess the impact of the COVID-19 pandemic on pertussis incidence and on the immunisation programme in England. METHODS: We assessed trends in pertussis cases from 2012 to 2020 by age group and month. Incidence from the time that England eased its initial lockdown measures in July 2020 through to summer 2021 was calculated and the incidence rate ratios of pertussis cases from five years prior to the pandemic (July 2014 - June 2019) compared to the same time period during the pandemic (July 2020 - June 2021). Vaccine coverage estimates for pertussis containing vaccines were reviewed for the maternal and childhood programmes. RESULTS: A substantial decline in pertussis cases was observed from April 2020 onwards, marking the lowest number of cases in the last decade. Pertussis incidence dropped in all age groups, particularly among infants less than one year old (0.50 / 100,000 during July 2020 to June 2021 compared to 24.49/ 100,000 from July 2014 to June 2019). The incidence rate ratio was 0.02 (95% CI 0.01 to 0.02) for July 2014 to June 2019 (pre-pandemic) compared to the pandemic period of July 2020 to June 2021. None of the cases had a co-infection with SARS-CoV-2. Vaccine coverage for infants born between January to March 2020 with three doses of pertussis vaccine by 12 months of age decreased by 1.1% points compared to infants born between January to March 2019 (91.6% and 92.7%, respectively). Prenatal pertussis coverage for the 2020 to 2021 financial year was 2.7% points lower than the year prior to the pandemic (70.5% and 76.8%, respectively). CONCLUSIONS: Lockdown measures due to the COVID-19 pandemic have had a significant impact on pertussis transmission. With the easing of restrictions it is important to continue monitoring pertussis cases in England alongside coverage of the maternal and childhood immunisation programmes.

Uptake of infant and preschool immunisations in Scotland and England during the COVID-19 pandemic: An observational study of routinely collected data.

BACKGROUND: In 2020, the SARS-CoV-2 (COVID-19) pandemic and lockdown control measures threatened to disrupt routine childhood immunisation programmes with early reports suggesting uptake would fall. In response, public health bodies in Scotland and England collected national data for childhood immunisations on a weekly or monthly basis to allow for rapid analysis of trends. The aim of this study was to use these data to assess the impact of different phases of the pandemic on infant and preschool immunisation uptake rates. METHODS AND FINDINGS: We conducted an observational study using routinely collected data for the year prior to the pandemic (2019) and immediately before (22 January to March 2020), during (23 March to 26 July), and after (27 July to 4 October) the first UK "lockdown". Data were obtained for Scotland from the Public Health Scotland "COVID19 wider impacts on the health care system" dashboard and for England from ImmForm. Five vaccinations delivered at different ages were evaluated; 3 doses of "6-in-1" diphtheria, tetanus, pertussis, polio, Haemophilus influenzae type b, and hepatitis B vaccine (DTaP/IPV/Hib/HepB) and 2 doses of measles, mumps, and rubella (MMR) vaccine. This represented 439,754 invitations to be vaccinated in Scotland and 4.1 million for England. Uptake during the 2020 periods was compared to the previous year (2019) using binary logistic regression analysis. For Scotland, uptake within 4 weeks of a child becoming eligible by age was analysed along with geographical region and indices of deprivation. For Scotland and England, we assessed whether immunisations were up-to-date at approximately 6 months (all doses 6-in-1) and 16 to 18 months (first MMR) of age. We found that uptake within 4 weeks of eligibility in Scotland for all the 5 vaccines was higher during lockdown than in 2019. Differences ranged from 1.3% for first dose 6-in-1 vaccine (95.3 versus 94%, odds ratio [OR] compared to 2019 1.28, 95% confidence intervals [CIs] 1.18 to 1.39) to 14.3% for second MMR dose (66.1 versus 51.8%, OR compared to 2019 1.8, 95% CI 1.74 to 1.87). Significant increases in uptake were seen across all deprivation levels. In England, fewer children due to receive their immunisations during the lockdown period were up to date at 6 months (6-in-1) or 18 months (first dose MMR). The fall in percentage uptake ranged from 0.5% for first 6-in-1 (95.8 versus 96.3%, OR compared to 2019 0.89, 95% CI 0.86- to 0.91) to 2.1% for third 6-in-1 (86.6 versus 88.7%, OR compared to 2019 0.82, 95% CI 0.81 to 0.83). The use of routinely collected data used in this study was a limiting factor as detailed information on potential confounding factors were not available and we were unable to eliminate the possibility of seasonal trends in immunisation uptake. CONCLUSIONS: In this study, we observed that the national lockdown in Scotland was associated with an increase in timely childhood immunisation uptake; however, in England, uptake fell slightly. Reasons for the improved uptake in Scotland may include active measures taken to promote immunisation at local and national levels during this period and should be explored further. Promoting immunisation uptake and addressing potential vaccine hesitancy is particularly important given the ongoing pandemic and COVID-19 vaccination campaigns.

Impact of COVID-19 Disruptions on Global BCG Coverage and Paediatric TB Mortality: A Modelling Study.

The impact of COVID-19 disruptions on global Bacillus Calmette-Guérin (BCG) coverage and paediatric tuberculosis (TB) mortality is still unknown. To fill this evidence-gap and guide mitigation measures, we estimated the impact of COVID-19 disruptions on global BCG coverage and paediatric TB mortality. First, we used data from multiple sources to estimate COVID-19-disrupted BCG vaccination coverage. Second, using a static mathematical model, we estimated the number of additional paediatric TB deaths in the first 15 years of life due to delayed/missed vaccinations in 14 scenarios-varying in duration of disruption, and magnitude and timing of catch-up. We estimated a 25% reduction in global BCG coverage within the disruption period. The best-case scenario (3-month disruption, 100% catch-up within 3 months) resulted in an additional 886 (0.5%) paediatric TB deaths, and the worst-case scenario (6-month disruption with no catch-up) resulted in an additional 33,074 (17%) deaths. The magnitude of catch-up was found to be the most influential variable in minimising excess paediatric TB mortality. Our results show that ensuring catch-up vaccination of missed children is a critical priority, and delivery of BCG alongside other routine vaccines may be a feasible way to achieve catch-up. Urgent action is required to support countries with recovering vaccination coverages to minimise paediatric deaths.

Disregarding the restrictive vial-opening policy for BCG vaccine in Guinea-Bissau: impact and cost-effectiveness for tuberculosis mortality and all-cause mortality in children aged 0-4 years.

OBJECTIVE: BCG vaccination is frequently delayed in low-income countries. Restrictive vial-opening policies, where a vial of BCG vaccine is not opened for few children, are a major reason for delay. During delays, children are unprotected against tuberculosis (TB) and deprived of non-specific effects of BCG. We assessed the potential effect and cost-effectiveness of disregarding the restrictive vial-opening policy, on TB and all-cause mortality, in children aged 0-4 years in Guinea-Bissau. METHODS: Using static mathematical models, we estimated the absolute and percentage change in TB and all-cause deaths, in children aged 0-4 years, between the current BCG vaccine restrictive-opening policy scenario, and a non-restrictive policy scenario where all children were vaccinated in the first health-facility contact. Incremental cost-effectiveness was estimated by integration of vaccine and treatment costs. FINDINGS: Disregarding the restrictive BCG vial-opening policy was estimated to reduce TB deaths by 11.0% (95% uncertainty range (UR):0.5%-28.8%), corresponding to 4 (UR:0-15) TB deaths averted per birth cohort in Guinea-Bissau, resulting in incremental cost-effectiveness of US$ 911 per discounted life-year gained (LYG) (UR:145-9142). For all-cause deaths, the estimated reduction was 8.1% (UR: 3.3%-12.7%) corresponding to 392 (UR:158-624) fewer all-cause deaths and an incremental cost-effectiveness of US$ 9 (UR:5-23) per discounted LYG. CONCLUSIONS: Disregarding the restrictive BCG vial-opening policy was associated with reductions in TB deaths and all-cause deaths and low cost-effectiveness ratios. Our results suggest that it would be cost-effective to disregard the restrictive vial-opening policy. Other settings with similar practice are also likely to gain from disregarding this policy.

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.

Potential effect of age of BCG vaccination on global paediatric tuberculosis mortality: a modelling study.

BACKGROUND: BCG has been recommended at birth in countries with a high tuberculosis burden for decades, yet delayed vaccination is widespread. To support a WHO guidance review, we estimated the potential global tuberculosis mortality benefit of administering BCG on time and consequences of later administration. METHODS: We estimated age-specific BCG coverage in 152 high-burden countries using data from large, nationally representative household surveys, to parameterise a static mathematical model, calibrated to global childhood tuberculosis deaths in 2016. 12 hypothetical scenarios explored the effect of BCG delivery at birth, 6 weeks, 6 months, or 9-12 months, on tuberculosis deaths per global birth cohort by age 15 years, including delivery at the time of the first diphtheria-tetanus-pertussis vaccine (DTP1) or the first measles-containing vaccine (MCV1). We assumed constant vaccine efficacy by age, but varied coverage and degree of vaccination delay, including no delay. FINDINGS: In 152 high-burden countries, we estimated that BCG coverage in 2016 was 37% at 1 week of age, 67% at 6 weeks, and 92% at 3 years. Modelled scenarios in which 92% BCG coverage was achieved at birth reduced tuberculosis deaths in the global birth cohort by 5449 (95% uncertainty range 218-15 071) or 2·8% (0·1-7·0) by age 15 years. 100% coverage at birth reduced tuberculosis deaths by 16·5% (0·7-41·9). Later administration increased tuberculosis deaths-eg, BCG vaccination at 6 weeks, the recommended age of DTP1, increased tuberculosis deaths by 0·2% (0-0·4), even if BCG reached DTP1 coverage levels (94% at 3 years). INTERPRETATION: Reducing delays and increasing coverage at birth would substantially reduce global paediatric tuberculosis mortality. Modelled scenarios whereby BCG was administered later in the infant schedule were all estimated to increase tuberculosis deaths, even with increased coverage. The WHO recommendation for BCG at birth should be maintained and emphasised. FUNDING: WHO.

Budd-Chiari Syndrome Due to Protein C Deficiency: A Rare Disorder to cause Chronic Liver Disease.

The Budd-Chiari syndrome (BCS) is a rare disorder due to chronic liver disease (CLD), which is caused by the obstruction of hepatic venous outflow that can be located at any place from the small hepatic venules up to the entrance of the inferior vena cava (IVC) into the right atrium. Among the causes of BCS, the rarer one is coagulation factor deficiencies. Here, we report a case of BCS associated with deficiency of protein C resulting in thrombus in IVC. The patient was a 50-year-old male, who had been suffering from recurrent abdominal and leg swelling for a long period of 7 years. He was evaluated thoroughly, and other causes of liver cirrhosis were excluded. HOW TO CITE THIS ARTICLE: Begum R, Al Mahtab M, Al Mamun A, Moben AL, Hossain SMS, Das DC, Malakar D, Rashid HO, Roy PP, Rahman S. Budd-Chiari Syndrome Due to Protein C Deficiency: A Rare Disorder to cause Chronic Liver Disease. Euroasian J Hepato-Gastroenterol 2016;6(2):194-197.

Anaesthetic management of previously non-diagnosed phaeochromocytoma: Clinical vigilance, the ultimate saviour of anaesthesiologist.

A 39-year-old male, post nephrectomy and adrenalectomy (right), was planned for adrenalectomy (left) and radiofrequency ablation of left renal mass. Clinical evaluation indicated a possibility of phaeochromocytoma, whereas biochemical parameters were found to be within normal limits. Intraoperatively, massive fluctuations in haemodynamic parameters were noticed while the tumour was being handled. Patient was stabilised with inotropes, vasopressors, fluids and careful titration of anaesthetic agents. Preoperatively diagnosed coronary disease could have complicated anaesthetic care. Optimum and modern anaesthetic care leads to safe execution of surgery.