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.

Progress in understanding of association between metabolic associated fatty liver disease and viral infectious diseases.

Metabolic associated fatty liver disease (MAFLD) is a chronic liver disease with the highest incidence in the world, which affects 1/4-1/3 of the world population and has a serious effect on people's health. As is a multi-systemic disease, MAFLD is closely related to the occurrence and prognosis of many diseases. Studies have shown that MAFLD is associated with viral infectious diseases, and their interaction affects the prognosis of the disease. This paper reviews the research progress in this field in recent years.Copyright © The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.

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.

Metabolic associated fatty liver disease is highly prevalent in the post-acute COVID syndrome

Background and Aims : Recently a proposal has been advanced to change the traditional definition of Non-Alcoholic Fatty Liver Disease to Metabolic Associated Fatty Liver Disease (MAFLD), to reflect the cluster of metabolic abnormalities that may be more closely associated with cardiovascular risk. Long COVID is a smoldering inflammatory condition, characterized by a number of symptom clusters. This study aims to determine the prevalence of MAFLD in patients with post-acute COVID syndrome (PACS) and its association with other PACS-cluster phenotypes. Method(s): We included 235 patients followed at a single university outpatient clinic. The diagnosis of PACS was based on >=1 cluster of symptoms: respiratory, neurocognitive, musculoskeletal, psychological, sensory, dermatological. The outcome was prevalence of MAFLD detected by transient elastography during the first post-discharge follow-up outpatient visit. The prevalence of MAFLD at the time of hospital admission was calculated retrospectively using the hepatic steatosis index. Result(s): Of 235 patients, 162 (69%) were men (median age 61). The prevalence of MAFLD was 55.3% at follow-up and 37.3% on admission (P<0.001). Insulin resistance (OR=1.5, 95%CI: 1.14-1.96), body mass index (OR=1.14, 95%CI: 1.04-1.24), and the metabolic syndrome (OR=2.54, 95%CI: 1.13-5.68), were independent predictors of MAFLD. The number of PACS clusters was inversely associated with MAFLD (OR=0.86, 95%CI: 0.76-0.97). Thirty-one patients (13.2%) had MAFLD with no other associated PACS clusters. All correlations between MAFLD and other PACS clusters were weak. Conclusion(s): MAFLD was highly prevalent after hospital discharge and may represent a specific PACS-cluster phenotype, with potential long-term metabolic and cardiovascular health implications. Copyright © 2022

Stoppage of exercise during the COVID-19 pandemic results in worsening liver enzymes in patients with metabolic associated fatty liver disease

Objectives: Worldwide, the COVID-19 pandemic has resulted in lifestyle disruptions, with lockdowns and curtailed activities. This was acutely felt in Asia from February 2020 onwards. Such drastic changes in lifestyle habits may impact negatively on metabolic related diseases. We explored these changes and their effects in patients with metabolic associated fatty liver disease (MAFLD). Materials and Methods: The data of MAFLD patients who were prospectively enrolled from eleven Asian centres in a longitudinal cohort study were analyzed. The data from 1st January 2019 (pre- COVID-19), were compared with the data from 1st February 2020 onwards (during COVID-19). Patients were stratified by physical activity level and whether they met target recommendation of[ 150 min of moderate/vigorous exercise per week. Results: A total of 229 patients were evaluated. Mean age was 59 ± 9.6 years with 136 (59.4%) males. During the COVID-19 pandemic, 50 (21.8%) patients maintained moderate/vigorous exercise, while 28 (12.2%) and 33 (14.4%) patients started and stopped moderate/vigorous exercising respectively. 118 patients (51.5%) did not participate in moderate/vigorous exercise either before or during the pandemic. Seventy-eight (34.1%) patients achieved[150 min moderate/vigorous exercise per week at the last visit. With the onset of COVID-19, reduction of physical activity of any kind was demonstrated in the majority (65.9%) of patients. There was a reduction of any physical activity including walking amongst those who stopped moderate/vigorous exercise and those without moderate/ vigorous exercise throughout. No significant changes in BMI, waist or hip circumference were observed in any activity level group. In patients who stopped moderate/vigorous exercise, alanine transaminase and aspartate transaminase significantly increased by 18.5% and 14.8% respectively. Conclusion: Stoppage of moderate/vigorous exercise leads to worsening of liver enzymes in patients with MAFLD and may have deleterious effects long term. As we adapt to live with COVID endemicity, novel modified healthy lifestyle habits would be needed to manage MAFLD.

Metabolic dysfunction-associated fatty liver disease and liver fibrosis score in patients with COVID-19 as predictors of adverse clinical outcomes: an artificial intelligent application through machine learning

Introduction and aims. Patients with coronavirus disease-2019 (COVID-19) and metabolic-dysfunction associated fatty liver disease (MAFLD) appear to be at higher risk for severe manifestations like acute respiratory distress syndrome, especially in the youngest decades. Our aim was to examine whether patients with imaging-defined MAFLD and/or with increased non-invasive liver fibrosis scores (FIB-4) are at higher risk for severe illness from COVID-19, using a machine learning model. Methods. In this retrospective cohort study, we included 672 patients admitted for SARS-CoV-2 pneumonia between February the 28th 2020 and May the 1st 2021. Hepatic steatosis was detected by ultrasound or computed tomography (CT), whereas FIB-4 score was used to define the risk of advanced liver fibrosis. We used a machine learning (ML) model to evaluate the risks of both in-hospital death and prolonged hospitalizations (>28 days), considering MAFLD, a set of blood tests (hepatic profile;HP), and the FIB-4 score, either separately and together. Results. Three hundred-thirty-three (49.6% of total) had imaging-defined MAFLD. The accuracy in predicting in-hospital death in the whole sample was 0.709 for the HP alone, and 0.721 for HP+FIB-4 combined together;in the 55-to-75 age subgroup, the accuracies were respectively 0.842 and 0.855 for HP alone and HP+FIB-4 together. In the MAFLD subgroup, the accuracy in predicting death was 0.739 considering HP alone, and 0.772 when considering HP+FIB-4 together;whereas in the MAFLD 55-to-75 years cohort, the accuracies were respectively 0.825 for HP and 0.833 for HP+FIB-4. Similar results were obtained both in the entire cohort and in MAFLD patients when considering the accuracy in predicting prolonged hospitalization (>28 days). Conclusions. In our cohort of COVID-19 patients, the presence of a worse HP and a higher FIB-4 correlated with a higher risk of death and prolonged hospitalization, regardless of the presence of MAFLD. These findings could improve the clinical risk stratification of patients diagnosed with SARS-CoV-2 pneumonia.