63rd Annual Conference of the Indian Society of Gastroenterology, ISGCON 2022

The proceedings contain 380 papers. The topics discussed include: fecal microbiota transplantation with anti-inflammatory diet followed by anti-inflammatory diet alone is effective in inducing and maintaining remission over 1 year in mild to moderate ulcerative colitis - a randomized controlled trial;gut microbial dysbiosis, gut barrier integrity, and severity of chronic pancreatitis: exploring a mechanistic link using an experimental model;acanthosis nigricans-a rare cutaneous association in progressive familial intrahepatic cholestasis type 3;liver mass presenting as acute cardiorespiratory failure;role of serum phosphate levels in acute-on-chronic liver failure patients to predict short-term mortality;association of liver dysfunction in corona virus disease-19 patients;diabetic with emphysematous liver abscess: a case report;non HFE hemochromatosis - the uncommon variant;granulomatous disease with hepatic involvement in a South Indian female;epidemiological profile of acute hepatitis patients hospitalized in a tertiary care center in Western India;and a prospective randomized comparative four arm intervention study of efficacy and safety of saroglitazar and vitamin E in patients with non-alcoholic fatty liver disease/ non-alcoholic steatohepatitis - an interim analysis.

Chronic liver disease-related mortality in diabetes before and during the COVID-19 in the United States.

BACKGROUND: Global pandemic of COVID-19 represents an unprecedented challenge. COVID-19 has predominantly targeted vulnerable populations with pre-existing chronic medical diseases, such as diabetes and chronic liver disease. AIMS: We estimated chronic liver disease-related mortality trends among individuals with diabetes before and during the COVID-19 pandemic. METHODS: Utilizing the US national mortality database and Census, we determined the quarterly age-standardized chronic liver disease-related mortality and quarterly percentage change (QPC) among individuals with diabetes. RESULTS: The quarterly age-standardized mortality for chronic liver disease and/or cirrhosis among individuals with diabetes remained stable before the COVID-19 pandemic and sharply increased during the COIVD-19 pandemic at a QPC of 8.5%. The quarterly mortality from nonalcoholic fatty liver disease (NAFLD) and alcohol-related liver disease (ALD) increased markedly during the COVID-19 pandemic. Mortality for hepatitis C virus (HCV) infection declined with a quarterly rate of -3.3% before the COVID-19 pandemic and remained stable during the COVID-19 pandemic. While ALD- and HCV-related mortality was higher in men than in women, NAFLD-related mortality in women was higher than in men. CONCLUSIONS: The sharp increase in mortality for chronic liver disease and/or cirrhosis among individuals with diabetes during the COVID-19 pandemic was associated with increased mortality from NAFLD and ALD.

Impact of the COVID-19 pandemic on liver disease-related mortality rates in the United States.

BACKGROUND: The pandemic has resulted in an increase of deaths not directly related to COVID-19 infection. We aimed to use a national death dataset to determine the impact of the pandemic on people with liver disease in the U.S, focusing on alcohol-associated liver disease (ALD) and non-alcoholic fatty liver disease (NAFLD). METHODS: Using data from the National Vital Statistic System from the CDC WONDER platform and ICD-10 codes, we identified deaths associated with liver disease. We evaluated observed versus predicted mortality for 2020-2021 based on trends from 2010-2019 with joinpoint and prediction modeling analysis. RESULTS: Among 626,090 chronic liver disease-related deaths between 2010 and 2021, Age-standardized mortality rates (ASMR) for ALD dramatically increased between 2010-2019 and 2020-2021 (annual percentage change [APC] 3.5% to 17.6%, P<0.01), leading to a higher observed ASMR (per 100,000 persons) than predicted for 2020 (15.67 vs.13.04) and 2021 (17.42 vs.13.41). ASMR for NAFLD also increased during the pandemic (APC:14.5%), while the rates for hepatitis B and C decreased. Notably, the ASMR rise for ALD was most pronounced in non-Hispanic Whites, Blacks, and Alaska Indians/Native Americans (APC: 11.7%, 10.8%, 18.0%, all P<0.05), with similar but less critical findings for NAFLD while rates were steady for non-Hispanic Asians throughout 2010-2021 (APC: 4.9%). The ASMR rise for ALD was particularly severe for the 25-44 age group (APC: 34.6%, versus 13.7% and 12.6% for 45-64 and ≥65, all P<0.01), which were also all higher than pre-COVID-19 rates (all P<0.01). CONCLUSIONS: ASMR for ALD and NAFLD increased at an alarming rate during the COVID-19 pandemic with the largest disparities among the young, non-Hispanic White, and Alaska Indian/Native American populations. LAY SUMMARY: The impact of the pandemic on people with liver disease in the U.S remains unclear. This study indicated that age-standardized mortality rates for alcohol associated liver disease and non-alcohol fatty liver disease greatly accelerated during the COVID-19 pandemic with the largest disparities among the young, non-Hispanic White, and Alaska Indian/Native American populations. Increasing awareness about the care importance of chronic liver disease in specific populations must be prioritized.

The Impact of Nonalcoholic Fatty Liver Disease on Severe Community-Acquired Pneumonia Outcomes.

Community-acquired pneumonia (CAP) is one of the leading causes of morbidity and mortality, while nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease. NAFLD is associated with systemic changes in immune response, possibly linked to CAP severity. However, the impact of NAFLD on CAP outcomes has not been determined. The aim of this study was to evaluate clinical course, complications and outcomes of severe CAP requiring ICU treatment in patients with NAFLD in the pre-COVID-19 era. A retrospective cohort study included 138 consecutively hospitalized adult patients with severe CAP admitted to the ICU during a 4-year period: 80 patients with NAFLD and 58 controls. Patients with NAFLD more frequently presented with ARDS (68.7% vs. 43.1%), and required invasive mechanical ventilation (86.2% vs. 63.8%), respiratory ECMO (50% vs. 24.1%), and continuous renal replacement therapy (62.5% vs. 29.3%). Mortality was significantly higher in the NAFLD group (50% vs. 20.7%), and the time from hospital admission to death was significantly shorter. In survival analysis, NAFLD (HR 2.21, 95%CI 1.03-5.06) was associated with mortality independently of other components of metabolic syndrome. In conclusion, our study identified NAFLD as an independent predictor of mortality in patients with severe CAP.

Nonalcoholic Fatty Liver Disease Association with Intubation and Severity of Covid-19

INTRODUCTION: Non-alcoholic fatty liver disease (NAFLD) and its hepatic manifestation, metabolic-associated fatty liver disease (MAFLD) have a rising prevalence worldwide in the background of the ongoing global pandemic. It is imperative to explore the relationship with COVID-19 to improve patient care and treatment protocols for better outcomes. This metaanalysis aims to investigate the association between NAFLD and MAFLD with the severity of COVID-19 infection and the need for mechanical ventilation. METHOD(S): A systematic review of literature across 5 databases was conducted from January 2019 to June 2022. Observational studies or clinical trials were included. Studies that evaluated NAFLD/ MAFLD using laboratory methods, non-invasive imaging, or liver biopsy were included. The study protocol was registered in Prospero and Prisma guidelines were followed (Figure 1). Meta-analysis was performed on studies with mechanical ventilation and severity of COVID-19 infection outcomes using Revman software. The Mantel- Haenszel odds ratio was generated to describe the overall effect size using random effect models. RESULT(S): Mechanical Ventilation A total of 36,817 patients from twelve studies were included in the qualitative analysis. There were 5615 patients in the NAFLD group and 31,202 patients in the Non-NAFLD group. A total of 3148 patients with COVID-19 required mechanical ventilation;778 (13.8%) in the NAFLD group and 782 (2.5%) in the Non-NAFLD group with high odds of need for mechanical ventilation (OR 2.03, 95%CI 1.06-3.88, p-value=0.03, I2=95%) (Figure 2). COVID-19 Severity A total of 5286 patients from fourteen studies were included in the qualitative analysis. 2716 patients were in the NAFLD group, while 2570 patients were in the Non-NAFLD group. A total of 1,623 patients had increased severity of COVID-19;901 (33.1%) in the NAFLD group and 722 (28.9%) in the Non-NAFLD group. COVID-19 patients with NAFLD had worse COVID-19 infection outcomes compared to those without NAFLD (OR 1.59, 95%CI 1.12-2.26, p-value=0.01, I2=81%) (Figure 4). CONCLUSION(S): Our meta-analysis suggests that NAFLD patients had higher odds of needing mechanical ventilation or ICU admission and developing more severe forms of COVID-19 than Non-NAFLD patients.

Physical Activity of Obese Children and Adolescents with the Nonalcoholic Fatty Liver Disease during the Covid-19 Pandemic

Introduction: Social isolation due to the COVID-19 pandemic leads to changes in general physical activity in children with nonalcoholic fatty liver disease (NAFLD) which may aggravate the course of the disease and alleviate the efficacy of the treatment. Aims & Methods: The aim of our study was to investigate the physical activity (PA) in children and adolescents with NAFLD during the COVID-19 pandemic and its association with liver fibrosis. 40 obese patients with NAFLD aged from 10 to 17 years (average age was 12.15 +/- 2.51 years) were examined from September-October 2021. Obesity was established by body mass index (BMI) calculation and comparison with the sigma deviations of BMI values according to age and sex. The presence of liver fibrosis and steatosis was evaluated by transient elastography (Fibroscan502touch, France). Children were divided into 4 groups according to transient elastography and BMI: 1 group - 13 children with NAFLD and liver fibrosis, 2 group - 13 children with NAFLD without fibrosis, 3 group - 14 obese children without NAFLD and fibrosis. The 4 group (control) consisted of 10 children with normal weight without NAFLD and fibrosis. The assessment of physical activity was conducted with the Physical Activity Questionnaire for older children (PAQ-C) and adolescents (PAQ-A). Result(s): The final summary score of the PA amounted to 2.4+/-0.3 in the 1 group, 2.2+/-0.2 in the 2 group, 2.2+/-0.3 in the 3 group, 2.4+/-0.2 in the 4 group without significant differences between the groups. The level of PA in spare time was the lowest in all groups compared to other types of activity. The highest rate of the PA score was observed in all groups during physical education classes, but the number of children who attended these classes not regularly was 43.9% among whom do not attend physical education classes at all 9.8%, almost never - 2.4%, from time to time - 31.7% of children. Only 26.8% of patients were active at recess while 73.2% of children stood or walked within the classroom or sat down. The level of PA of chil dren right after school increased slightly, also without significant differences between groups, but children with liver fibrosis had the lowest PA level (2.1 +/-0.2). 24.4% of children did not have any PA right after school. Free time at the weekend was not accompanied by an increase in physical activity, on the contrary, the summary score decreased in almost all groups to 1.94 points, and the portion of children without physical activity remains stable (24.4%). According to self-reports children of the 1-3 groups had a lower level of physical activity score compared to children of the control group. Almost 73.2% of interviewed children understood that their level of physical activity was low. The total level of physical activity on each day of the week was the lowest in children with liver fibrosis (1 group). The highest percentage of PA absence was on weekends. The total PA score was negatively correlated with calf circumference (r = -0.582, p = 0.018), self-report PA tended to a negative correlation with the level of alaninaminotransferase (r = - 0.372, p = 0.056). Conclusion(s): Physical activity of obese NAFLD children during the COVID- 19 pandemic is low, especially in spare time, and does not rise at the weekends. The majority of children (73.2%) are inactive at recess as well as self-reported low level of PA. NAFLD children with liver fibrosis have the lowest total level of PA right after school and generally on each day of the week, which may reflect an insufficiency of adaptation.

Trends of Cirrhosis-related Mortality in the USA during the COVID-19 Pandemic

Immunocompromised status and interrupted routine care may render patients with cirrhosis vulnerable to the coronavirus disease 2019 (COVID-19) pandemic. A nationwide data set that includes more than 99% of the decedents in the U.S. between April 2012 and September 2021 was used. Projected age-standardized mortality during the pandemic were estimated according to prepandemic mortality rates, stratified by season. Excess deaths were determined by estimating the difference between observed and projected mortality rates. A temporal trend analysis of observed mortality rates was also performed in 0.83 million decedents with cirrhosis between April 2012 and September 2021 was included. Following an increasing trend of cirrhosis-related mortality before the pandemic, with a semiannual percentage change (SAPC) of 0.54% [95% confidence interval (CI): (0.0-1.0%), p=0.036], a precipitous increase with seasonal variation occurred during the pandemic (SAPC 5.35, 95% CI: 1.9-8.9, p=0.005). Significantly increased mortality rates were observed in those with alcohol-associated liver disease (ALD), with a SAPC of 8.44 (95% CI: 4.3-12.8, p=0.001) during the pandemic. All cause mortality of nonalcoholic fatty liver disease rose steadily across the entire study period with a SAPC of 6.79 (95% CI: 6.3-7.3, p<0.001). The decreasing trend of HCV-related mortality was reversed during the pandemic, while there was no significant change in HBV-related deaths. While there was significant increase in COVID-19-related deaths, more than 55% of the excess deaths were the indirect impact of the pandemic. We observed an alarming increase in cirrhosis related deaths during the pandemic especially for ALD, with evidence in both direct and indirect impact. Our findings have implications on formulating policies for patients with cirrhosis.

A Multidisciplinary Approach and Current Perspective of Nonalcoholic Fatty Liver Disease: A Systematic Review.

In recent times, nonalcoholic fatty liver disease (NAFLD) has been considered one of the major causes of liver disease across the world. NAFLD is defined as the deposition of triglycerides in the liver and is associated with obesity and metabolic syndrome. Hyperinsulinemia, insulin resistance (IR), fatty liver, hepatocyte injury, unbalanced proinflammatory cytokines, mitochondrial dysfunction, oxidative stress, liver inflammation, and fibrosis are the main pathogenesis in NAFLD. Recent studies suggest that the action of intestinal microbiota through chronic inflammation, increased intestinal permeability, and energy uptake plays a vital role in NAFLD. Moreover, polycystic ovarian syndrome also causes NAFLD development through IR. Age, gender, race, ethnicity, sleep, diet, sedentary lifestyle, and genetic and epigenetic pathways are some contributing factors of NAFLD that can exacerbate the risk of liver cirrhosis and hepatocellular carcinoma (HCC) and eventually lead to death. NAFLD has various presentations, including fatigue, unexplained weight loss, bloating, upper abdominal pain, decreased appetite, headache, anxiety, poor sleep, increased thirst, palpitation, and a feeling of warmth. Some studies have shown that NAFLD with severe coronavirus disease 2019 (COVID-19) has poor outcomes. The gold standard for NAFLD diagnosis is liver biopsy. Other diagnostic tools are imaging tests, serum biomarkers, microbiota markers, and tests for extrahepatic complications. There are no specific treatments for NAFLD. Therefore, the main concern for NAFLD is treating the comorbid conditions such as anti-diabetic agents for type 2 diabetes mellitus, statins to reduce HCC progression, antioxidants to prevent hepatocellular damage, and bariatric surgery for patients with a BMI of >40 kg/m2 and >35 kg/m2 with comorbidities. Lifestyle and dietary changes are considered preventive strategies against NAFLD advancement. Inadequate treatment of NAFLD further leads to cardiac consequences, sleep apnea, chronic kidney disease, and inflammatory bowel disease. In this systematic review, we have briefly discussed the risk factors, pathogenesis, clinical features, and numerous consequences of NAFLD. We have also reviewed various guidelines for NAFLD diagnosis along with existing therapeutic strategies for the management and prevention of the disease.

Prognostic performance of an index based on lactic dehydrogenase and transaminases for patients with liver steatosis and COVID-19.

BACKGROUND: Metabolic associated fatty liver disease (MAFLD) is associated with complications and mortality in patients with coronavirus disease 2019 (COVID-19). However, there are no prognostic scores aimed to evaluate the risk of severe disease specifically in patients with MAFLD, despite its high prevalence. Lactate dehydrogenase, aspartate aminotransferase and alanine aminotransferase have been used as markers of liver damage. Therefore, we propose an index based on lactate dehydrogenase, aspartate aminotransferase and alanine aminotransferase for the prediction of complications and mortality in patients with MAFLD and COVID-19. AIM: To evaluate the prognostic performance of an index based on lactate dehydrogenase and transaminases (aspartate aminotransferase/alanine aminotransferase) in patients with COVID-19 and MAFLD [liver fibrosis and nutrition (LNF)-COVID-19 index]. METHODS: In this retrospective cohort study, two cohorts from two different tertiary centers were included. The first was the derivation cohort to obtain the score cutoffs, and the second was the validation cohort. We included hospitalized patients with severe COVID-19 and MAFLD. Liver steatosis was evaluated by computed tomography scan. Area under the receiver operating characteristic (ROC) curve analysis and survival analysis were used. RESULTS: In the derivation cohort, 44.6% had MAFLD; ROC curve analysis yielded a LFN-COVID-19 index > 1.67 as the best cutoff, with a sensitivity of 78%, specificity of 63%, negative predictive value of 91% and an area under the ROC curve of 0.77. In the multivariate analysis, the LFN-COVID-19 index > 1.67 was independently associated with the development of acute kidney injury (odds ratio: 1.8, 95% confidence interval: 1.3-2.5, P < 0.001), orotracheal intubation (odds ratio: 1.9, 95% confidence interval: 1.4-2.4, P < 0.001), and death (odds ratio: 2.86, 95% confidence interval: 1.6-4.5, P < 0.001) in both cohorts. CONCLUSION: LFN-COVID-19 index has a good performance to predict prognosis in patients with MAFLD and COVID-19, which could be useful for the MAFLD population.

Sars-Cov2 and Liver Damage in Pediatric Population

The Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV2) initially was perceived as a lower respiratory tract infection. However, with time coronavirus disease (COVID-19) presented with a wide variability of symptoms, including gastrointestinal and hepatic. This because the viral tropism to the angiotensin-converting enzyme 2 (ACE2) receptor found in liver and bile-duct epithelial cells. The ACE2 expression is mainly in cholangiocytes (60% of cells), minimally expressed in hepatocytes (3% of cells) and absent in Kupffer cells. Hepatic involvement can be evidenced with elevation of serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), and lactate dehydrogenase (LDH), these alterations have been evidenced in up to 43% of patients. The aim of this study is to evaluate liver damage in pediatric patients with COVID-19. Material(s) and Method(s): A retrospective cohort was carried out between March 2020 to October 2021 at the Instituto Nacional de Pediatria in Mexico City. We include all patients between 0 to 18 years with positive COVID-19 PCR test or antigen rapid test. Result(s): We had a total population of 161 subjects of which 83 had liver function tests (inflammation, excretion, or synthesis) during SARS-CoV2 infection;82 had ALT value. Mean age was 5.3 years and 56% were men (n: 47). Fifty-four patients (65%) had previous comorbidity, with oncological diseases being the most frequent (33%). Of the 54 patients with previous comorbidity, 3 had liver disease (Graft-versus-host disease, nonalcoholic fatty liver disease and autoimmune hepatitis). Regarding treatment, 32 patients did not require oxygen support, 32 patients had non-invasive devices and 19 patients required mechanical ventilation. Fifty-four percent (n = 45) were using steroid management. In relation to the outcome of the patients, 11 die and the rest were discharged. Liver function tests were submitted 2 days after admission, 51 patients (62%) presented elevation of ALT (according to age and sex). Second liver function tests were taken around day 23 53 patients. Table 1 shows the average of each of the parameters. It has been documented that severe COVID-19 is associated with higher levels of inflammatory mediators like C-reactive protein (CRP) and ferritin. Therefore, levels of this inflammatory mediators were evaluated, the average of this parameters was 1601 ng/mL and 8.19 mg/L respectively in the first test. Analysis: We evaluated the difference that existed in liver function tests by comparing the first and second determination. Regarding AST, INR and PT, a significant difference was found (p = <0.05) with improvement compared to baseline. While the ALT did not show a significant difference, there was an improvement compared to baseline. Secondary to the association described between elevation of inflammatory mediators and severity of the disease, a Pearson Correlation test was performed between liver inflammatory tests and ferritin/prealbumin. A significant correlation was obtained when comparing ALT with ferritin (r = 0.301, p = 0.033) and AST with ferritin (r = 0.311, p= 0.028), which demonstrate a weak correlation probably associated with the amount of population. The correlation between ALT/AST and prealbumin was carried out without being significant. In search of associated factors, it was found that the alteration of liver function tests is a risk factor for needing support with supplemental oxygen with an Odds Ratio of 2.007 (CI: 0.77-5.31). From 19 patients who required mechanical ventilation, 73.7% had altered liver function tests. Conclusion(s): SARS-CoV2 is a virus that has been shown to have liver involvement which can be demonstrated with elevation of liver function test. In our series, 62% had elevated ALT, being the most sensitive parameter of liver inflammation. With respect to factors associated with liver impairment, we found that higher ferritin levels are associated with greater liver involvement, as well as that having hepatic impairment is a risk factor for the use of supplemental oxygen. Therefore, it is important to consider in patients with COVID-19 liver function tests and thus make a timely detection of alterations at this level. Studies with more population are required to have external validity.

Covid-19 Mandates Associated with Increased Rate of Weight Gain and Liver Function Test Elevation in Children with Non-Alcoholic Fatty Liver Disease

Introduction: Weight management is currently the only established treatment of pediatric non-alcoholic fatty liver disease (NAFLD). Studies have shown improvements in liver histology, aminotransferase activity, and quality of life after weight loss in children with NAFLD.1 Recent studies demonstrate an accelerated rate of weight gain among children and adolescents during the COVID-19 pandemic that has been attributed to many factors, including the inability to be in a structured school setting and disruptions in family income.2,3 Objective: Our study aims to explore the effect of COVID-19 stay-at-home mandates and school closures on weight gain and liver function tests in children with NAFLD. Method(s): Following IRB approval (IRB 2021-4333), a retrospective chart review was performed on children aged 13-20 years who were seen at Lurie Children's Hospital (LCH) hepatology clinic for NAFLD and had two or more clinic visits at least three months apart during the pandemic period, defined as 3/1/20-9/1/21, and the pre-pandemic period, defined as before 3/1/20. The two most recent visits at least three months apart were the ones selected for the pre-pandemic period. Demographic and clinical data (race, ethnicity, age, BMI, height, weight, AST, ALT) were ed. Monthly BMI, AST, and ALT differences during the two periods were calculated for each patient. Paired-samples T-Tests were used to analyze differences between the two periods. Relative risks for an increase in BMI, AST, or ALT during the pandemic period compared to the pre-pandemic period were calculated. Result(s): Our cohort included 102 patients, with mean age of 14.5 (SD 1.6) during pre-pandemic period and 15.6 (SD 1.4) during pandemic period, 71 (70%) males, and 85 (83%) identifying as Hispanic or Latino. Mean BMI was 34.2 kg/m2 (SD 7.16) with mean Z-score of 2.16 (SD 0.56) during pre-pandemic period and mean BMI of 35.5 kg/m2 (SD 7.0) with mean Z-score of 2.21 (SD 0.56) during pandemic period. Seventy-seven (75%) children had a liver biopsy or other imaging consistent with their NAFLD diagnosis. There was a significant difference between monthly BMI differences during the pre-pandemic period (mean 0.0691 kg/m2/month, SD 0.271) and pandemic period (mean 0.161 kg/m2/month, SD 0.271);p=0.02. Of the 102 patients in our cohort, 75 had two or more ALT measurements at least three months apart during both time periods. There was a significant difference between monthly ALT differences during the pre-pandemic period (mean -2.39 IU/L, SD 8.67) and pandemic period (mean 1.70 IU/L, SD 11.3);p=0.01 (Figure 1). There was no significant difference between monthly AST differences during the two time periods. The relative risk of having an increase in BMI Z-score during the pandemic period compared to the pre-pandemic period was 1.37 (95% CI [1.09-1.72], p < 0.01, Figure 2). The relative risk of having an increase in ALT or AST during the pandemic period compared to the pre-pandemic period was not significant. Conclusion(s): Our cohort of children with NAFLD experienced an accelerated rate of BMI increases and ALT elevation during the COVID-19 pandemic. These findings underscore the importance of increasing access to resources for healthy behaviors during public health emergencies or extended school closures in facilitating the health and well-being of children with NAFLD.

Impact of the COVID-19 pandemic on the care and outcomes of people with NAFLD-related cirrhosis.

Background & Aims: The COVID-19 pandemic has had a major negative impact on health systems and many chronic diseases globally. We aimed to evaluate the impact of the first year of the pandemic on the outcomes of people with NAFLD cirrhosis. Methods: We conducted a before-after study in four University hospitals in Catalonia, Spain. Study subperiods were divided into Pre-pandemic (March/2019-February/2020) vs. Pandemic (March/2020-February/2021). The primary outcome was the rate of first liver-related event (LRE). Overall clinical outcomes (LREs plus cardiovascular plus all-cause mortality) were also assessed. Results: A total of 354 patients were included, all of whom were compensated at the beginning of the study period; 83 individuals (23.5%) had a history of prior hepatic decompensation. Mean age was 67.3 years and 48.3% were female. Median BMI was 31.2 kg/m2 and type 2 diabetes was present in 72.8% of patients. The rates of first LRE in the Pre-pandemic and Pandemic periods were 7.4% and 11.3% (p = 0.12), respectively. Whilst the rate of overall events was significantly higher in the Pandemic period (9.9% vs. 17.8%; p = 0.009), this was strongly associated with COVID-19-related deaths. The rate of worsened metabolic status was significantly higher in the Pandemic period (38.4% vs. 46.1%; p = 0.041), yet this was not associated with the risk of first LRE during the Pandemic period, whereas type 2 diabetes (odds ratio [OR] 3.77; 95% CI 1.15-12.32; p = 0.028), albumin <4 g/L (OR 4.43; 95% CI 1.76-11.17; p = 0.002) and Fibrosis-4 score >2.67 (OR 15.74; 95% CI 2.01-123.22; p = 0.009) were identified as risk factors in the multivariable analysis. Conclusion: Overall, people with NAFLD cirrhosis did not present poorer liver-related outcomes during the first year of the pandemic. Health system preparedness seems key to ensure that people with NAFLD cirrhosis receive appropriate care during health crises. Lay summary: Mobility restrictions and social stress induced by the COVID-19 pandemic have led to increased alcohol drinking and worsened metabolic control (e.g., weight gain, poor control of diabetes) in a large proportion of the population in many countries. We aimed to analyze whether people with cirrhosis due to non-alcoholic fatty liver disease, who are particularly vulnerable to such lifestyle modifications, were significantly impacted during the first year of the pandemic. We compared the clinical situation of 354 patients one year before the pandemic and one year after. We found that although metabolic control was indeed worse after the first year of the pandemic and patients presented worse clinical outcomes, the latter was mostly due to non-liver causes, namely COVID-19 itself. Moreover, the care provided to these patients did not worsen during the first year of the pandemic.

FATTY LIVER DISEASE IN NHS STAFF AND ROLE OF FIBROSCAN

Introduction It has never been more crucial to ensure the health and wellbeing of our colleagues. This study focuses on the impact of diet, alcohol and activity on the liver and anxiety levels were also reflected upon as a result of the Covid period on NHS staff. A Fibroscan (530, Compact, Echosens) was used as part of a staff 'Love your Liver 'clinic in a NHS general hospital, conducted by Hepatology nurses. Non-alcoholic fatty liver disease (NAFLD) is a rising health problem that can lead to non-alcoholic steatohepatitis (NASH) and cirrhosis with associated liver mortality. In the UK 63% of adults are obese and overweight, 1 in 3 people have earlystage NAFLD. In a previous study we conducted between 2018- 2020, 'NHS Biscuit Culture' 74 staff participated, 60 female and 14 male. Mean age 46.9 (range 25 -70). 59.4% had NAFLD with Controlled Attenuation Parameter (CAP) >248 dB/m with 16.2% also having associated fibrosis with Liver Stiffness Measure (LSM) >7.8 kPa. It was felt the results may act as a 'shock factor' to motivate lifestyle changes. Method 15 patients who were identified as having NAFLD were re-scanned 6 months later and were asked to follow advice on diet and lifestyle. 80% improved the CAP score with a mean reduction of 56.3dB/m. 20% CAP did not improve reported, diet was not changed. During November 2021, we offered a liver clinic to previously scanned staff to re-evaluate but many declined due to weight gain during Covid. Our event incorporated 45 staff, age range 30-71 years (mean age 42.6 years, 39 females, 6 males). Questionnaires were emailed to 45 participants. The questionnaire focused on diet, alcohol, anxiety levels and activity level at work. Results Fibroscan results 47% (n=45) fatty liver, CAP >243 dB/m and 2% (n=45) fibrosis with LSM >7.8 kPa. 9% borderline fatty liver, CAP of 231-237 dB/m and 7% borderline fibrosis LSM 6.2 -6.6 kPa. 18% staff were rescanned that previously had fatty liver in our previous liver events during 2018 to 2020, 50% (n=8) of fibroscan returned within normal range, 37.5% fat content had improved but fatty liver remained, 12.5% of the staff 's results remained the same, fatty liver, no fibrosis. Staff 's weekly diet included candy, sweetened drinks, fast food, fruit and vegetables. Candy 29%, Fast food 27%, sweetened beverages 16%, and 5 or more fruit a day 11%. 20% Staff were already on a diet. Admin staff 41% (n=45), 33% nursing staff, 22% pathology, radiology and dieticians, 2% doctors and 2% management attended the events. 11% currently drinking over 14 units a week (15-25 units), 15% drinking 10-14 units a week. Staff alcohol consumption did increase during the Covid. No alcohol consumption 47% (n=45), 1-5 units 20%, 5-10 units 9%. Mild anxiety 74% (range 0-5), moderate 15% (6-14) and severe 10% (15-21). Pre-existing high level of anxiety 2% of the staff, Covid increased anxiety levels due to increased pressures at work. 10% required further assessment. 56% had limited activity during the day due to job role and 44% regularly mobilised as part of their roles. Conclusion The study tells us that diet and lifestyle has a significant impact on hepatosteatosis. Incidence of NAFLD is considerably higher in staff members (47%) in a district general hospital as compared to the general population (25%). This could be secondary to levels of stress during the COVID pandemic. The study showed a significant reduction in CAP and LSM scores after simple lifestyle advice was given to a group of motivated healthcare workers.

Abstracts of the BSG Annual Meeting

The proceedings contain 374 papers. The topics discussed include: optical biopsy with linked color imaging accurately predicts inflammation in ulcerative colitis;predicting use of opiates in patients with inoperable pancreatic cancer: a retrospective cohort study;unbiased clustering of breath signature in NAFLD identifies disease progression high-risk patient phenotype - 5 year study;prevalence of malnutrition screening;the association between IBD and mental ill health: a retrospective primary care cohort study;the interleukin 22//neutrophil axis is associated with treatment resistance in ulcerative colitis;neuromuscular dysfunction in patients with nausea and vomiting syndrome defined by body surface gastric mapping;two-tiered liver fibrosis assessment in primary care annual diabetic screening 3 year follow up;can an algorithm help in the difficult dilemma of upper gastrointestinal bleed and anticoagulant COVID-19 pandemic and alcohol-specific hospital admissions;and upper gastrointestinal hemorrhages and COVID-19: a nationwide cohort study of the pandemic's impact on hospitalizations.

Global burden of nonalcoholic steatohepatitis-related liver cancer, 1990-2019: a systematic analysis for the GBD 2019.

With the pandemic of metabolic diseases, nonalcoholic fatty liver disease (NAFLD) prevalence has dramatically elevated. NAFLD encompasses a spectrum of diseases including simple steatosis and nonalcoholic steatohepatitis (NASH), which can further progress to cirrhosis or liver cancer (LC). However, data are lacking on the burden and trend of NASH-related LC. Here, we analyzed the trends and changes of NASH-related LC burden using Global Burden of Disease (GBD) data (1990-2019). In 2019, the global incidence, prevalence, disability-adjusted life years (DALYs) and deaths of NASH related LC were 36.3 thousand (95% UI 29.5-44.9), 46.8 thousand (38.2-57.6), 796 thousand (657-976) and 34.7 thousand (28.4-43.2), respectively. The absolute numbers and rates of NASH-related LC incidence, mortality, and DALY significantly elevated from 1990 to 2019. With the age increased, the incidences, DALYs and deaths of NASH-related LC significantly elevated. The incidence and mortality rate of NASH-related LC significantly increased from 2010 to 2019 in individuals aged from 20 to 54 and older than 55 years old. We also found that a large disparity of NASH-related LC burden in different socio-demographic index (SDI) locations. The crude number and the age-standardized rate of incidences, DALYs and deaths was highest in the middle SDI locations and high SDI locations showed the largest increase of NASH-related LC burden from 1990 to 2019. Moreover, the proportion of LC incidences, deaths and DALYs attributed to NASH were 4.74%, 5.30% and 4.25%, respectively in 1990 which were increased by 43.5%, 35.3% and 49.4%, respectively in 2019. Conclusion: The global burden of NASH-related LC and the proportion LC burden attributed to NASH are significantly increasing.

Use of a cirrhosis database can positively impact patient care in United Kingdom practice

Background and aims: Screening for oesophageal varices and surveillance for hepatocellular carcinoma (HCC) are advised for patients with cirrhosis but adherence to recommendations is poor. The study aimed to provide descriptive analysis of a new cirrhosis database and evaluate rates of surveillance in a large teaching hospital. Method: All patients diagnosed with advanced fibrosis/cirrhosis in our centre entered the database sequentially from April 2018. The service covers a population of 600000, with expected prevalence of 600 cirrhotic patients. The database-rather than clinic visits-became the primary means to monitor HCC surveillance/endoscopic screening requests. Subsequent adherence to recommendations was measured in 2021. Results: 841 patients entered the database over 3 years, with only 200 at inception-less than the predicted cirrhosis prevalence. 36 people died during follow-up and 5 left the area. Of the remaining 800 patients, median age was 60 years;40% female. 46% of patients had alcohol related disease, 21% non-alcoholic fatty liver disease, 14% viral hepatitis. 63% of the cohort had Childs-Pugh (CP) A or advanced fibrosis, 14% CP-B, 3% CP-C. 21% had no stage recorded. 157 patients (20%) were on primary prophylaxis for variceal bleeding. Of the remaining 643 patients, 237 (37%) were on active endoscopic surveillance and a further 100 (16%) had attended endoscopy in the past 3 years. 43 patients (7%) were overdue, 40 (6%) declined, and 30 (5%) had documented clinical decision not to proceed. 191 patients (24%) had no documentation about screening. 603 (78%) of appropriate patients were up to date with HCC surveillance with a further 105 (14%) awaiting scan, significantly more than our historically reported adherence of 50% (p = <0.0001). Conclusion: The database improved our knowledge of clinical characteristics of our patient population, and provided a way to readily monitor surveillance intervals. Most had appropriate HCC surveillance, surpassing our previous (or nationally reported) adherence rates. A quarter of patients had no documentation of variceal screening, highlighting an area for improvement. Given the rapid rise in cohort size, it is likely the database also reduces numbers lost to follow-up/surveillance in the event of clinic non-attendance, which may be particularly valuable in the post-Covid era of delayed appointments. This study shows the potential of a registry to improve care and outcomes in people with cirrhosis

The prevalence and prognostic significance of vitamin C deficiency in patients with cirrhosis: a prospective observational cohort study

Background and aims: Malnutrition is a common comorbidity in cirrhotic patients and confers a poorer prognosis. Vitamin C (VC) is a micronutrient essential for human health. Vitamin C deficiency (VCD) can lead to scurvy and may impair immune and liver functions. Although previously thought to be rare in developed countries, VCD is now well described in patients with pneumonia, COVID19 and upper gastrointestinal bleeding (UGIB). The prevalence and clinical significance of VCD in cirrhosis remains poorly studied. Method: Patients with cirrhosis admitted to 3 metropolitan tertiary centres in Australia were prospectively included over a 10-month period in 2021. Fasting VC levels were collected on admission and we recorded demographic data and clinical outcomes. The primary outcomes were the prevalence of VCD (defined as VC level <23 mcmol/L) and severe VCD (SVCD), defined as <11 mcmol/L. Secondary outcomes included mortality, intensive care admission, length of stay (LOS) and rate of infection. Results: 117 patients were included. Mean age was 57.1 ± 13.9 years, 59.0% were male and 23.9% belonged to the lowest socioeconomic decile. The most common aetiologies of cirrhosis were alcohol (62.4%), viral hepatitis (24.0%) and non-alcoholic fatty liver disease (18.8%). Median MELD scorewas 29 (IQR 22–36) and Child Pugh (CP) grades were 12.8% A, 46.2% B and 41.0% C. Most patients (74.4%) were hospitalised with complications of decompensated cirrhosis, including ascites (59.0%), encephalopathy (31.6%) and variceal bleeding (11.1%). Median VC level was 34mcmol/L (IQR 16–55) and did not differ with age, gender, or aetiology of cirrhosis. Increasing CP grade correlated with significantly lower median VC levels (CP-A 46.0 mcmol/L vs. CPB 36.5 mcmol/L and CP-C 20.5 mcmol/L, p = 0.026). The prevalence of VCD and SVCD were 39.3% and 17.1% respectively. SVCD was more prevalent in patients with a body mass index <25 (28.3% vs 13.0%, p = 0.036). In-hospital mortality was 12.8% and did not differ by VCD status, however in the subgroup of patients presenting with UGIB, SVCD correlated with significantly higher mortality (50% vs 4.1%, p = 0.045). Bacteraemia was more frequent in patients with VCD (13.3% vs. 1.4%, p = 0.014) and SVCD (26.3% vs 2.1%, p < 0.001), which remained significant at multivariate analysis (OR for every 1mcmol/L increase in VC, 0.91 (95% CI: 0.83–0.99), p = 0.037). Overall infection rateswere higher in patients with SVCD (40.0% vs. 27.8%) although thiswas nonsignificant (p = 0.279). Median hospital LOS was 10 (IQR 6–18) days and did not differ by VCD status. (Figure Presented) Conclusion: VCD is common in hospitalised cirrhotic patients and prevalence increases with severity of liver disease. VCD increases the risk of infective complications and higher mortality was observed in patients with UGIB and SVCD. Further studies are required to assess the significance of VCD in cirrhosis and the impacts of VC replacement.

Features of characteristics of metabolic syndrome components in covid-19 patients associated with nonalcoholic fatty liver disease

Objectives: Covid-19 was affected all over the world and caused pandemic. Compelling data suggest that Covid-19 might influence all human parts. Host of studies showed that metabolic syndrome (MetS) was associated with nonalcoholic fatty liver disease (NAFLD). Purpose of the study was to evaluate the possible impact of MetS components in the course of Covid-19 in patients with NAFLD. Materials and Methods: 192 consecutive patients (aged 37-75 years;mean age 56.2 ± 13.2 years;male = 48%) with NAFLD and MetS who underwent Covid-19 were enrolled in this study. Patients were divided into two groups by 91 in each group according to the presence or absence of MetS. All anthropometric, laboratory and instrumental data were obtained and analyzed at baseline. All statistical analysis were performed by SPSS 24.0 software. Results: Patients with concomitant MetS (Group I) had severe Covid- 19 than those without it (P<0.05). 19% out of Group I patients had severe Covid-19 whilst 12% out of Group II patients had severe course of the invective disease. Multiple regression logistic analysis showed that among MetS components having abdominal obesity (AO) (2.7;1.6-4.4;CI 95%;P<0.05), insulin resistance (IR) (2.0;1.4-3.9' CI 95%;P<0.05), hypertension (HT) (1.4;1.3-2.4;CI 95%;P<0.05) tended have a severe Covid-19 in patients with NAFLD. When we separately analyzed by gender there was not significant changes between male and female (P[0.05). Conclusion: MetS was significantly associated with severe Covid-19 in patients with NAFLD. Among MetS components AO, IR and HT independently associated with severe Covid-19 regardless of gender. Further investigations are required with large amount of participants.

The use of andrographolide and effects on liver biochemistry in patients with gastrointestinal problems amid the pandemic of COVID-19

Objectives: In the situation of COVID-19 pandemic in Thailand, healthcare facility supply and access are limited. There was an announcement promoting Andrographolide (ADG) use in treatment of mild COVID-19 patients, but misconception of taking for prevention might occur. Moreover, the effect of ADG on liver function test (LFT) has not been established. We aim to study the prevalence of ADG use and effect on LFTs in patients with gastrointestinal (GI) problems. Materials and Methods: We conducted a cross-sectional study including GI patients at our center who voluntarily filled the ADG questionnaire in Aug-Sep 2021. LFT data at that visit and at the prior visit (if available) were obtained. The changes in LFT within the same person were analyzed using Wilcoxon signed-rank test. Wilcoxon rank-sum and Chi-square test were used to compare between patients with and without ADG consumption. Results: A total of 886 patients completed the survey, 170 patients (19.2%) took ADG within the past month. Patients who took ADG were more likely to have history of COVID-19 infection in their closed companies (5.6% vs 1.5%) compared with who did not (control group). LFT data were available in 486 (54.8%) patients, the median ALT change compared with the prior visit was higher in ADG vs control group (2 vs 0, p = 0.026), and 45% had increased ALT ([3 U/L) vs 32.2% in ADG and control group, respectively (p = 0.023). Multivariable logistic regression analysis found that factors independently associated with an increased ALT were ADG exposure (adjusted OR [aOR] of 1.62, p = 0.042), and patients with NAFLD who gained weight (aOR of 2.37, p = 0.046). Conclusion: One-fifth of GI patients recently took ADG, in which currently not indicated as it has no effect on preventing COVID-19 infection. Those who took ADG are more likely to experience an increase in ALT than who did not. Warning should be made regarding this issue.