2022 PeDRA Annual Conference

The proceedings contain 90 papers. The topics discussed include: characterization of nonalcoholic fatty liver disease in children with psoriasis: a pilot study;management of pediatric psoriasis: a representative US survey;severity and patient-related outcomes in atopic dermatitis do not correlate with deprivation index as an indicator of socioeconomic setting in a US metropolitan area;pediatric atopic dermatitis: assessment of burden based on lesional morphology;metered dose applicators: a potential solution for improving topical medication adherence in atopic dermatitis patients;serial staged punch excision technique for linear epidermal nevus and nevus sebaceous;the molecular basis of superficial vascular lesions of the skin: genotype-phenotype correlation of capillary malformations;utilization and effect of telehealth for the treatment of hemangioma before and after COVID;image analysis of port wine birthmarks using optical coherence tomography;image analysis of port wine birthmarks using optical coherence tomography;and responsiveness to change of the morphea activity measure.

Italian Association of Clinical Endocrinologists (AME) 20th National Congress

The proceedings contain 9 papers. The topics discussed include: dulaglutide and NAFLD risk reduction;correlation between plasmatic long pentraxin PTX3 and nodular thyroid disease: a preliminary report;the fructose-bisphosphate aldolase a act as autoantigen in primary autoimmune hypophysitis;cortisol deficiency in Lenvatinib treatment;side effects of mitotane treatment: a retrospective study in 35 patients with adrenocortical carcinoma in adjuvant therapy;non-functioning pituitary adenoma: do predictor factors exist?;incidence and features of adrenal crisis in a series of 133 patients with Addison's disease;serological evidence and self-reported outcomes in patients with adrenal insufficiency during the first waves of COVID-19 in the North-East Italy;and persistent effects of spironolactone after its withdrawal in patients with hyperandrogenic skin disorders.

Management of patients with liver derangement during the COVID-19 pandemic

COVID-19 pandemic has been affecting the whole world for more than 3 years since late 2019. It is often to encounter COVID-19 patients with abnormal liver function, either in the form of hepatitis, cholestasis or both. The clinical implication of such liver derangement may be variable in different clinical scenarios. With the growing evidence of the clinical significance of such liver derangement, it would be clinically helpful to provide practice recommendations to various common clinical scenarios of liver derangement during COVID-19 pandemic. The Asia-Pacific Working Group for Liver Derangement during the COVID-19 Pandemic was formed to systematically review the literature on specified domains of interest, with special focus on clinical management of patients who have been or are at risk of developing liver derangement during COVID-19 pandemic. This Asia-Pacific position statement reports an in-depth review and a position statement on liver derangement during COVID- 19 pandemic. Ten clinical scenarios covering the use of pharmacological treatment for COVID-19 in case of liver derangement, assessment and management of patients with chronic hepatitis B or C, nonalcoholic fatty liver disease (NAFLD), liver cirrhosis, liver transplantation are discussed. Specifically, some treatments target the patient's dysregulated inflammatory response during COVID-19 infection and may cause hepatitis B reactivation (HBVr) in patients with current or past hepatitis B virus (HBV) infection. Current evidence suggests that current or past HBV infection is not associated with an increased risk of liver injury and severe disease in COVID-19 patients. Among patients who received high-dose corticosteroids, various immunosuppressive monoclonal antibodies and inhibitors of Janus kinase, the risk of HBVr exists, especially among those without antiviral prophylaxis.

Pre-existing chronic liver disease is associated with poor outcome in patients with SARS-CoV2 infection

COVID-19 is characterized by predominant respiratory and gastrointestinal symptoms. Liver enzymes derangement is seen in 15-55% of the patients. Cirrhosis is characterized by immune dysregulation, leading to concerns that these patients may be at increased risk of complications following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Patients with metabolic dysfunction-associated fatty liver (MAFLD) had shown a 4-sixfold increase in severity of COVID-19, and its severity and mortality increased in patients with higher fibrosis scores. Patients with chronic liver disease had shown that cirrhosis is an independent predictor of severity of COVID-19 with increased hospitalization and mortality. An international European registry study included 756 patients with chronic liver disease from 29 countries reports high mortality in patients with cirrhosis (32%). Data of 228 patients collected from 13 Asian countries on patients with CLD, known or newly diagnosed, with confirmed COVID-19 (APCOLIS study) showed that SARSCoV- 2 infection produces acute liver injury in 43% of CLD patients without cirrhosis. Additionally, 20% of compensated cirrhosis patients develop either ACLF or acute decompensation. In decompensated cirrhotics, the liver injury was progressive in 57% of patients, with 43% mortality. Patients with CLD and associated diabetes and obesity had a worse outcome. Liver related complications were seen in nearly half of the decompensated cirrhotics, which were of greater severity and with higher mortality. Increase in Child Turcotte Pugh (CTP) score and model for end-stage liver disease (MELD) score increases the mortality in these patients. In a subsequent study of 532 patients from 17 Asian countries was obtained with 121 cases of cirrhosis. An APCOLIS risk score was developed, which included presence of comorbidity, low platelet count, AKI, HE and respiratory failure predicts poor outcome and an APCOLIS score of 34 gave a sensitivity and specificity of 79.3%, PPV of 54.8% and NPV of 92.4% and predicted higher mortality (54.8% vs 7.6%, OR = 14.3 [95 CI 5.3-41.2], p<0.001) in cirrhosis patients with Covid-19. The APCOLIS score is helpful in triaging and prognostication of cirrhotics with Coivd-19. The impact of COVID-19 on patients with cirrhosis due to non-alcoholic fatty liver disease (NASH-CLD) was separately studied in 177 NASH-CLD patients. Obese patients with diabetes and hypertension had a higher prevalence of symptomatic COVID. Presence of diabetes [HR 2.27], fraility [HR 2.68], leucocyte counts [HR 1.69] and COVID-19 were independent predictors of worsening liver functions in patients with NASH-CLD. Severity of Covid in Cirrhosis could also be assessed by measuring ICAM1 the Intercellular Adhesion Molecule, an indicator of Endothelial Injury Marker. in Cirrhosis with Covid 19 Immunosuppression should be reduced prophylactically in patients with autoimmune liver disease and post-transplantation with no COVID-19. Hydroxychloroquine and remdesivir are found to be safe in limited studies in a patient with cirrhosis and COVID-19. And is safe in cirrhosis patients. However, flare of AIH has been reported in AIH patients. For hepatologists, cirrhosis with COVID-19 is a pertinent issue as the present pandemic cause severe disease in patients with chronic liver disease leading to more hospitalization and decompensation.

Liver injury in COVID-19 patients with non-alcoholic fatty liver disease: an update.

The coronavirus disease 2019 (COVID-19) pandemic has revolutionized the priorities of the medical society worldwide. Although most patients infected with SARS-CoV-2 exhibit respiratory symptoms, other organs may also be involved, including the liver, often resulting in liver injury. Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in the world, and its prevalence is expected to increase together with the epidemics of type 2 diabetes and obesity. Data about liver injury during COVID-19 are numerous, while overviews of this infection in patients with NAFLD, both in terms of respiratory and liver, are emerging. In this review, we summarise the current research focusing on COVID-19 in NAFLD patients and discuss the association between liver injury in COVID-19 subjects and non-alcoholic fatty liver disease.

Solid organ graft-versus-host disease in a recipient of a COVID-19 positive liver graft

A 66-year-old male with end-stage liver disease (ESLD) secondary to non-alcoholic fatty liver disease (NAFLD), complicated by hepatocellular carcinoma (HCC), underwent deceased donor liver transplantation from a Coronavirus disease 2019 (COVID-19) positive donor. He presented a month later with fever, diarrhea and pancytopenia which led to hospitalization. The hospital course was notable for respiratory failure, attributed to invasive aspergillosis, as well as a diffuse rash. A bone marrow biopsy revealed hypocellular marrow without specific findings. In the following days, laboratory parameters raised concern for secondary hemophagocytic lymphohistiocytosis (HLH). Clinical concern also grew for solid organ transplant graft-versus-host-disease (SOT-GVHD) based on repeat marrow biopsy with elevated donor-derived CD3+ T cells on chimerism. After, a multidisciplinary discussion, the patient was started on ruxolitinib, in addition to high dose steroids, to address both SOT-GVHD and secondary HLH. Patient developed symptoms concerning for hemorrhagic stroke and was transitioned to comfort care. Although GVHD has been studied extensively in hematopoietic stem cell transplant (HSCT) patients, it is a rare entity in SOT with a lack of guidelines for management. Additionally, whether COVID-19 may play a role in development of SOT-GVDH has not been explored.Copyright © 2023 The Authors

Hyperammonemia is a risk factor for poor outcomes in patients with COVID-19.

Objective. We analyzed clinical features and laboratory markers of COVID-19 patients according to favorable outcomes versus fatal outcomes. Material and methods. The medical history of 80 patients was analyzed: 51 patients with favorable outcomes were included in group 1, 29 patients with a fatal outcome were included in group 2. Demographic data, duration of the disease, comorbid-ities, laboratory markers, and results of the instrumental studies were included. The ammonia level in the peripheral blood was de-termined by the express method using a PocketChem BA 4140 photometric portable analyzer. Results. Patients in group 2 were older (68+/-11 years) had hypertension stage 3 with high cardiovascular risk;every third had a history of myocardial infarction. At admission, patients from group 2 were most likely with febrile fever and high levels of inflammatory markers - predictors of a cytokine release syndrome. In addition, 71% of patients at admission had elevated ammonia levels. Hyperammonemia correlated with high ferritin levels, leukopenia, non-alcoholic fatty liver disease in patients, and lethal outcomes. Conclusions. The risks of poor COVID-19 outcomes are higher in comorbid patients of the older age group. Hyperammonemia may be one of the predictors of poor COVID-19 outcomes.Copyright © 2022, Media Sphera Publishing Group. All rights reserved.

Nonalcoholic fatty liver disease and non-liver comorbidities.

Non-alcoholic fatty liver disease (NAFLD) is a chronic liver disease characterized by excess fat accumulation in the liver. It is closely associated with metabolic syndrome, and patients with NAFLD often have comorbidities such as obesity, type 2 diabetes mellitus, and dyslipidemia. In addition to liver-related complications, NAFLD has been associated with a range of non-liver comorbidities, including cardiovascular disease, chronic kidney disease, and sleep apnea. Cardiovascular disease is the most common cause of mortality in patients with NAFLD, and patients with NAFLD have a higher risk of developing cardiovascular disease than the general population. Chronic kidney disease is also more common in patients with NAFLD, and the severity of NAFLD is associated with a higher risk of developing chronic kidney disease. Sleep apnea, a disorder characterized by breathing interruptions during sleep, is also more common in patients with NAFLD and is associated with the severity of NAFLD. The presence of non-liver comorbidities in patients with NAFLD has important implications for the management of this disease. Treatment of comorbidities such as obesity, type 2 diabetes mellitus, and dyslipidemia may improve liver-related outcomes in patients with NAFLD. Moreover, treatment of non-liver comorbidities may also improve overall health outcomes in patients with NAFLD. Therefore, clinicians should be aware of the potential for non-liver comorbidities in patients with NAFLD and should consider the management of these comorbidities as part of the overall management of this disease.

Liver and COVID-19 - A Review and Clinical Approach

Liver enzyme abnormalities occur frequently in patients diagnosed with Coronavirus disease 2019 (COVID-19). It has been suggested that patients with severe acute liver injury are more likely to be admitted to intensive care, require intubation or renal replacement therapy and their mortality rate is higher than patients without severe acute liver injury. This review article explores the possible aetiologies of liver dysfunction seen in patients with COVID-19 and also the effect of COVID-19 on patients with pre-existing liver disease. Finally, we suggest clinical approaches to treating a patient with liver enzyme disturbance and COVID-19 and also caring for patients who require liver transplantation in the COVID-19 era.Copyright © 2022 Bentham Science Publishers.

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 dataset 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.

Nonalcoholic fatty liver disease and diabetes.

Nonalcoholic fatty liver disease (NAFLD) is the most prevalent chronic liver disease in the world and represents a clinical-histopathologic entity where the steatosis component may vary in degree and may or may not have fibrotic progression. The key concept of NAFLD pathogenesis is excessive triglyceride hepatic accumulation because of an imbalance between free fatty acid influx and efflux. Strong epidemiological, biochemical, and therapeutic evidence supports the premise that the primary pathophysiological derangement in most patients with NAFLD is insulin resistance; thus the association between diabetes and NAFLD is widely recognized in the literature. Since NAFLD is the hepatic manifestation of a metabolic disease, it is also associated with a higher cardio-vascular risk. Conventional B-mode ultrasound is widely adopted as a first-line imaging modality for hepatic steatosis, although magnetic resonance imaging represents the gold standard noninvasive modality for quantifying the amount of fat in these patients. Treatment of NAFLD patients depends on the disease severity, ranging from a more benign condition of nonalcoholic fatty liver to nonalcoholic steatohepatitis. Abstinence from alcohol, a Mediterranean diet, and modification of risk factors are recommended for patients suffering from NAFLD to avoid major cardiovascular events, as per all diabetic patients. In addition, weight loss induced by bariatric surgery seems to also be effective in improving liver features, together with the benefits for diabetes control or resolution, dyslipidemia, and hypertension. Finally, liver transplantation represents the ultimate treatment for severe nonalcoholic fatty liver disease and is growing rapidly as a main indication in Western countries. This review offers a comprehensive multidisciplinary approach to NAFLD, highlighting its connection with diabetes.

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.

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.

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.

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.

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.