Fatty Liver Change in Korean Adults in a Systematic Social Distancing System Amid the COVID-19 Pandemic: A Multicenter Analysis.

In response to the COVID-19 pandemic, the Korean government implemented policies including the systematic social distancing (SSD) system which started on 28 June 2020. The present study investigated the development and aggravation of fatty liver measured using ultrasonography during the transition period (from pre-SSD to SSD) compared to the fatty liver changes during the pre-SSD period. Changes in fatty liver and liver enzymes were assessed in different groups stratified by alcohol consumption. Our retrospective cohort analysis included 5668 participants who underwent health checkups at 13 university hospitals during the SSD period and two or more checkups before the SSD period. Fatty liver developed and aggravated more in the transition period (13.6% development and 12.0% aggravation) than in the pre-SSD period (10.8% development and 10.1% aggravation) in the alcohol consumption group. This finding was more prominent in women than in men. Abnormal alanine transaminase levels were more often developed in the transition period than in the pre-SSD period, especially in men (11.1% vs. 8.6% in each period). In conclusion, the SSD system may contribute to fatty liver changes in individuals who regularly consume alcohol. Further research of the post-pandemic period is needed to assess long-term changes in fatty liver disease.

Fatty Liver and the Coronavirus Disease 2019 Pandemic: Health Behaviors, Social Factors, and Telemedicine Satisfaction in Vulnerable Populations.

The coronavirus disease 2019 (COVID-19) pandemic has impacted health-related behaviors that influence fatty liver disease (FLD) management. We evaluated the impact of the pandemic on FLD management and satisfaction with care delivery in this population. In the San Francisco safety-net hepatology clinics, we evaluated health-related behaviors and factors associated with self-reported weight gain during the COVID-19 pandemic as well as satisfaction with telemedicine in adults with FLD by using multivariable modeling. From June 1, 2020, to May 5, 2021, 111 participants were enrolled. Median age was 52 years, 30% were men, 63% were Hispanic, 21% were Asian/Pacific Islander, and 9% were White. Eating habits were unchanged or healthier for 80%, physical activity decreased in 51%, 34% reported weight gain, and 5% reported increased alcohol intake. Forty-five percent had severe depressive symptoms, 38% in those without diagnosed depression and 60% of individuals with heavy alcohol use. On multivariable analysis, decreased physical activity (odds ratio [OR], 4.8) and heavy alcohol use (OR, 3.4) were associated with weight gain (all P < 0.05). Among those with telemedicine visits (n = 66), 62% reported being very satisfied. Hispanic ethnicity was associated with a 0.8-unit decrease in the telemedicine satisfaction score (P = 0.048) when adjusting for sex, age, and pandemic duration. Conclusion: During the pandemic, decreased physical activity and heavy alcohol use were most influential on self-reported weight gain in FLD. Maintenance of healthy eating and increased physical activity, alcohol cessation counseling, and mental health services are critical in preventing poor FLD-associated outcomes during the pandemic recovery. Dissatisfaction with telemedicine should be explored further to ensure equitable care, especially among the vulnerable Hispanic population.

Role of fatty liver in coronavirus disease 2019 patients' disease severity and hospitalization length: a case-control study.

BACKGROUND AND PURPOSE: Fatty liver is one of the most common pre-existing illnesses; it can cause liver injury, leading to further complications in coronavirus disease 2019 patients. Our goal is to determine if pre-existing fatty liver is more prevalent in hospitalized COVID-19 patients compared to patients admitted before the SARS-CoV-2 pandemic and determine the disease severity among fatty liver patients. EXPERIMENTAL APPROACH: This retrospective study involves a case and a control group consisting of 1162 patients; the case group contains hospitalized COVID-19 patients with positive PCR tests and available chest CT-scan; the control group contains patients with available chest CT-scan previous to the COVID-19 pandemic. Patients' data such as liver Hounsfield unit, hospitalization length, number of affected lobes, and total lungs involvement score were extracted and compared between the patients. RESULTS: The findings indicate that 37.9% of hospitalized COVID-19 patients have a pre-existing fatty liver, which is significantly higher (P < 0.001) than the prevalence of pre-existing fatty liver in control group patients (9.02%). In comparison to hospitalized non-fatty liver COVID-19 patients, data from hospitalized COVID-19 patients with fatty liver indicate a longer hospitalization length (6.81 ± 4.76 P = 0.02), a higher total lungs involvement score (8.73 ± 5.28 P < 0.001), and an increased number of affected lobes (4.42 ± 1.2 P < 0.001). CONCLUSION: The statistical analysis shows fatty liver is significantly more prevalent among COVID-19 against non-COVID-19 patients, and they develop more severe disease and tend to be hospitalized for more extended periods.

Clinical perspectives, assessment, and mechanisms of metabolic-associated fatty liver disease in patients with COVID-19.

Metabolic diseases are highly prevalent worldwide and have been associated with adverse clinical outcomes, including mortality, in patients developing coronavirus disease (COVID-19). Because of the close relationship between metabolic diseases such as type 2 diabetes mellitus and obesity and the presence of metabolic-associated fatty liver disease (MAFLD), a high number of cases of patients affected by both MAFLD and COVID-19 would be expected, especially in high-risk populations. Some studies have shown an increased risk of adverse clinical outcomes, viral shedding, and deep vein thrombosis, especially in patients with MAFLD- related liver fibrosis. The predisposition to poor outcomes and severe acute respiratory syndrome coronavirus 2 infection in patients with MAFLD could be secondary to mechanisms common to both, including preexisting systemic chronic inflammation, endothelial dysfunction, and involvement of the renin-angiotensin system. Because of the increased risk of adverse outcomes, MAFLD should be screened in all patients admitted for COVID-19. Available computed tomography scans could be of help, assessment of liver fibrosis is also recommended, favoring noninvasive methods to limit the exposure of healthcare workers. Liver involvement in this population ranges from abnormalities in liver chemistry to hepatic steatosis in postmortem biopsies. Finally, preventive measures should be strongly advocated in patients already known to have MAFLD, including the use of telemedicine and vaccination in addition to general measures.

Hemostatic alterations linked to body fat distribution, fatty liver, and insulin resistance.

OBJECTIVE: Obesity, in particular visceral obesity, and insulin resistance emerged as major risk factors for severe coronavirus disease 2019 (COVID-19), which is strongly associated with hemostatic alterations. Because obesity and insulin resistance predispose to thrombotic diseases, we investigated the relationship between hemostatic alterations and body fat distribution in participants at risk for type 2 diabetes. SUBJECTS: Body fat distribution (visceral and subcutaneous abdominal adipose tissue) and liver fat content of 150 participants - with impaired glucose tolerance and/or impaired fasting glucose - were determined using magnetic resonance imaging and spectroscopy. Participants underwent precise metabolic characterization and major hemostasis parameters were analyzed. RESULTS: Procoagulant factors (FII, FVII, FVIII, and FIX) and anticoagulant proteins (antithrombin, protein C, and protein S) were significantly associated with body fat distribution. In patients with fatty liver, fibrinogen (298 mg/dl vs. 264 mg/dl, p = 0.0182), FVII (99% vs. 90%, p = 0.0049), FVIII (114% vs. 90%, p = 0.0098), protein C (124% vs. 111%, p = 0.0006), and protein S (109% vs. 89%, p < 0.0001) were higher than in controls. In contrast, antithrombin (97% vs. 102%, p = 0.0025) was higher in control patients. In multivariate analyses controlling for insulin sensitivity, body fat compartments, and genotype variants (PNPLA3I148MM/MI/TM6SF2E167kK/kE), only protein C and protein S remained significantly increased in fatty liver. CONCLUSIONS: Body fat distribution is significantly associated with alterations of procoagulant and anticoagulant parameters. Liver fat plays a key role in the regulation of protein C and protein S, suggesting a potential counteracting mechanism to the prothrombotic state in subjects with prediabetes and fatty liver.

Association and Interaction Between Serum Interleukin-6 Levels and Metabolic Dysfunction-Associated Fatty Liver Disease in Patients With Severe Coronavirus Disease 2019.

Background and Aim: Circulating levels of interleukin (IL)-6, a well-known inflammatory cytokine, are often elevated in coronavirus disease-2019 (COVID-19). Elevated IL-6 levels are also observed in patients with metabolic dysfunction-associated fatty liver disease (MAFLD). Our study aimed to describe the association between circulating IL-6 levels and MAFLD at hospital admission with risk of severe COVID-19. Methods: A total of 167 patients with laboratory-confirmed COVID-19 from three Chinese hospitals were enrolled. Circulating levels of IL-2, IL-4, IL-6, IL-10, tumor necrosis factor (TNF)-α, and interferon (IFN)-γ were measured at admission. All patients were screened for fatty liver by computed tomography. Forty-six patients were diagnosed as MAFLD. Results: Patients with MAFLD (n = 46) had higher serum IL-6 levels (median 7.1 [interquartile range, 4.3-20.0] vs. 4.8 [2.6-11.6] pg/mL, p = 0.030) compared to their counterparts without MAFLD (n = 121). After adjustment for age and sex, patients with MAFLD had a ~2.6-fold higher risk of having severe COVID-19 than those without MAFLD. After adjustment for age, sex and metabolic co-morbidities, increased serum IL-6 levels remained associated with higher risk of severe COVID-19, especially among infected patients with MAFLD (adjusted-odds ratio 1.14, 95% CI 1.05-1.23; p = 0.002). There was a significant interaction effect between serum IL-6 levels and MAFLD for risk of severe COVID-19 (p for interaction = 0.008). Conclusions: Patients with MAFLD and elevated serum IL-6 levels at admission are at higher risk for severe illness from COVID-19.

High prevalence of hepatic steatosis and vascular thrombosis in COVID-19: A systematic review and meta-analysis of autopsy data.

BACKGROUND: Coronavirus disease 2019 (COVID-19) disease can frequently affect the liver. Data on hepatic histopathological findings in COVID-19 is scarce. AIM: To characterize hepatic pathological findings in patients with COVID-19. METHODS: We conducted a systematic review with meta-analysis registered on PROSPERO (CRD42020192813), following PRISMA guidelines. Eligible trials were those including patients of any age and COVID-19 diagnosis based on a molecular test. Histopathological reports from deceased COVID-19 patients undergoing autopsy or liver biopsy were reviewed. Articles including less than ten patients were excluded. Proportions were pooled using random-effects models. Q statistic and I 2 were used to assess heterogeneity and levels of evidence, respectively. RESULTS: We identified 18 studies from 7 countries; all were case reports and case series from autopsies. All the patients were over 15 years old, and 67.2% were male. We performed a meta-analysis of 5 studies, including 116 patients. Pooled prevalence estimates of liver histopathological findings were hepatic steatosis 55.1% [95% confidence interval (CI): 46.2-63.8], congestion of hepatic sinuses 34.7% (95%CI: 7.9-68.4), vascular thrombosis 29.4% (95%CI: 0.4-87.2), fibrosis 20.5% (95%CI: 0.6-57.9), Kupffer cell hyperplasia 13.5% (95%CI: 0.6-54.3), portal inflammation 13.2% (95%CI: 0.1-48.8), and lobular inflammation 11.6% (95%CI: 0.3-35.7). We also identified the presence of venous outflow obstruction, phlebosclerosis of the portal vein, herniated portal vein, periportal abnormal vessels, hemophagocytosis, and necrosis. CONCLUSION: We found a high prevalence of hepatic steatosis and vascular thrombosis as major histological liver features. Other frequent findings included portal and lobular inflammation and Kupffer cell hyperplasia or proliferation. Further studies are needed to establish the mechanisms and implications of these findings.

Liver fibrosis in patients with metabolic associated fatty liver disease is a risk factor for adverse outcomes in COVID-19.

BACKGROUND: Metabolic diseases are risk factors for severe Coronavirus disease (COVID-19), which have a close relationship with metabolic dysfunction-associated fatty liver disease (MAFLD). AIMS: To evaluate the presence of MAFLD and fibrosis in patients with COVID-19 and its association with prognosis. METHODS: Retrospective cohort study. In hospitalized patients with COVID-19, the presence of liver steatosis was determined by computed tomography scan (CT). Liver fibrosis was assessed using the NAFLD fibrosis score (NFS score), and when altered, the AST to platelet ratio index (APRI) score. Mann-Whitney U, Student´s t-test, logistic regression analysis, Kaplan-Meier curves and Cox regression analysis were used. RESULTS: 432 patients were analyzed, finding steatosis in 40.6%. No differences in pulmonary involvement on CT scan, treatment, or number of days between the onset of symptoms and hospital admission were found between patients with and without MAFLD. The presence of liver fibrosis was associated with higher severity scores, higher levels of inflammatory markers, requirement of mechanical ventilation, incidence of acute kidney injury (AKI), and higher mortality than patients without fibrosis. CONCLUSION: The presence of fibrosis rather than the presence of MAFLD is associated with increased risk for mechanical ventilation, development of AKI, and higher mortality in COVID-19 patients.

Confluence of obesity and MAFLD during Covid-19 pandemic in a developing country.

The direct relation between the overweight/obesity, MAFLD and the severity SARS-CoV-2 infection. increase number of cases of obesity and MAFLD is an important risk factor for high mortality of COVID-19 patients.

MAFLD in COVID-19 patients: an insidious enemy.

The pandemic Sars-CoV-2 infection represents a dramatic health challenge worldwide. Pneumonia is considered the major damage caused by the virus. However, recent data have highlighted the impact of the Sars-CoV-2 related disease namely COVID-19 on the liver. Hepatic abnormalities significantly increase during COVID-19 and a more severe infection occurs in patients with pre-existing liver diseases, among which the most frequent is metabolic-associated fatty liver disease (MAFLD). It has been described that MAFLD patients had a higher risk of progression to severe COVID-19, higher abnormal liver tests and longer viral shedding time. The presence of fibrosis in MAFLD patients is another risk factor for severity of COVID-19. Due to the overgrowing prevalence of MAFLD, it could be speculated that a large proportion of the population might be at risk of severe COVID-19 and the identification of these patients possibly by using liver enzymes as risk predictors may be crucial for an early diagnosis and for the management of the infection.

Metabolic dysfunction associated fatty liver disease increases risk of severe Covid-19.

BACKGROUND AND AIMS: Liver involvement is common in COVID-19. Elevated aspartate and alanine amino transaminase (AST/ALT) and borderline increase in serum bilirubin and serum alkaline phosphatase (ALP) are the commonest findings. Patients with associated co morbid conditions like obesity, cardiovascular disease, renal disease, malignancy, hypertension and old age are prone to develop severe disease. Limited data is available in patients with COVID-19 and metabolic dysfunction associated fatty liver disease (MAFLD).The aim of this review is to analyse the effect of MAFLD on severity of COVID-19. METHODS: We systematically searched the PubMed database till May 20, 2020 and retrieved all the articles published on COVID-19 and fatty liver/MAFLD/NAFLD. RESULTS: Limited studies done had shown four to six fold high risk of severe COVID-19 in patients with MAFLD. Patients with MAFLD and associated obesity, severe fibrosis and age <60 yrs are more prone to develop severe COVID-19. CONCLUSION: MAFLD is associated with 4-6 fold increase in severity of COVID-19 compared to non MAFLD patients. Physician and hepatologist should follow these patients cautiously and preventive measures to be taken strictly in these high risk patients.