Evaluation of liver stiffness using ultrasonic shear wave elastography in patients with COVID-19 induced pneumonia.

In patients with COVID-19-induced pneumonia, shear wave elasticity (SWE) was used to assess liver stiffness. This study included 48 cases of COVID-19-induced pneumonia and 48 cases of normal physical examination. Basic and clinical data, including aspartate aminotransferase (AST), were evaluated. Color ultrasonography was used to test the liver's SWE. A biopsy of the liver was also performed. In patients with COVID-19-induced pneumonia, AST and alanine aminotransferase (ALT) levels were higher than those in the control group. Liver SWE showed that liver stiffness is hard (8.745 ± 0.2104) compared with the control group (7.386 ± 0.1521) (P < 0.0001). Pathological biopsy showed that liver inflammation accounted for 89.58%, steatosis accounted for 81.25%, necrosis accounted for 10.42%, and fibrosis accounted for 33.33% in patients with COVID-19-induced pneumonia. ROC curve analysis showed that the SWE is highly sensitive and specific for the diagnosis of liver inflammation and steatosis. The sensitivity was 88.76% and the specificity was 77.01% for the evaluation of liver inflammation. For steatosis, the sensitivity was 90.20%, and the specificity was 78.40%. The SWE of liver is useful to assess liver function and pathological status in COVID-19 patients.

Correlation between COVID-19 severity, body mass index and radiological hepatic morphology / Correlación entre la gravedad de COVID-19, el índice de masa corporal y la morfología hepática radiológica

SUMMARY: Obesity and fatty liver steatosis are already considered metabolic risk factors which may aggravate the severity of COVID-19. This study aims to investigate the correlation between COVID-19 severity, obesity, and liver steatosis and fibrosis. 230 consecutive patients with laboratory-confirmed COVID-19 aged between 15 and 84? years, admitted to a hospital devoted to COVID-19 patients, were enrolled in the study. COVID-19 severity was classified as severe versus non-severe based on admission to ICU. Obesity was assessed by Body Mass Index (BMI). CT-scan was used to check for the liver steatosis. Fibrosis-4 score was calculated. The study was conducted in March-May 2020. Obesity strongly and positively correlated with severe COVID-19 illness r: 0.760 (P<0.001). Hepatic steatosis had rather less of a correlation with COVID-19 severity r: 0.365 (P<0.001). Multivariable-adjusted association between hepatic steatosis or obesity, or both (as exposure) and COVID-19 severity (as the outcome) revealed increased risk of severe COVID-19 illness with obesity (Adjusted model I OR: 465.3, 95 % CI: 21.9-9873.3, P<0.001), with hepatic steatosis (Adjusted model I OR: 5.1, 95 % CI: 1.2-21.0, P<0.025), and with hepatic steatosis among obese patients (Adjusted model I OR: 132, 95 % CI: 10.3-1691.8, P<0.001). Obesity remained the most noticeable factor that strongly correlated with COVID-19 severity, more than liver steatosis. However, the risk to COVID-19 severity was greater in those with both factors: obesity and liver steatosis.

RESUMEN: La obesidad y la esteatosis del hígado graso ya se consideran factores de riesgo metabólico que pueden empeorar la gravedad de la COVID-19. Este estudio tiene como objetivo investigar la correlación entre la gravedad de COVID- 19, la obesidad y la esteatosis y fibrosis hepática. El estudio se realizó en 230 pacientes consecutivos entre 15 y 84 años con COVID-19 confirmado por laboratorio, ingresados en un hospital dedicado a pacientes con COVID-19. La gravedad de COVID-19 se clasificó como grave, versus no grave según el ingreso a la UCI. La obesidad se evaluó mediante el índice de masa corporal (IMC). Se utilizó una tomografía computarizada para verificar la esteatosis hepática. Se calculó la puntuación de Fibrosis-4. El estudio se realizó entre marzo-mayo de 2020. La obesidad se correlacionó fuerte y positivamente con la enfermedad grave de COVID-19 r: 0,760 (P <0,001). La esteatosis hepática tuvo una correlación bastante menor con la gravedad de COVID-19 r: 0.365 (P <0.001). La asociación ajustada multivariable entre la esteatosis hepática u obesidad, o ambas (como exposición) y la gravedad de COVID-19 (como resul- tado) reveló un mayor riesgo de enfermedad grave por COVID- 19 con obesidad (OR del modelo ajustado I: 465,3, IC del 95%: 21,9 -9873,3, P <0,001), con esteatosis hepática (OR del modelo I ajustado: 5,1, IC del 95 %: 1,2-21,0, P <0,025) y con esteatosis hepática entre los pacientes obesos (OR del modelo I ajustado: 132, IC del 95 % : 10,3-1691,8, P <0,001). La obesidad siguió siendo el factor más notable que se correlacionó significativamente con la gravedad de COVID-19, más que la esteatosis hepática. Sin embargo, el riesgo de gravedad de COVID-19 fue mayor en aquellos con ambos factores: la obesidad y esteatosis hepática.

Innate and Adaptive Immunity Alterations in Metabolic Associated Fatty Liver Disease and Its Implication in COVID-19 Severity.

The coronavirus infectious disease 2019 (COVID-19) pandemic has hit the world, affecting health, medical care, economies and our society as a whole. Furthermore, COVID-19 pandemic joins the increasing prevalence of metabolic syndrome in western countries. Patients suffering from obesity, type II diabetes mellitus, cardiac involvement and metabolic associated fatty liver disease (MAFLD) have enhanced risk of suffering severe COVID-19 and mortality. Importantly, up to 25% of the population in western countries is susceptible of suffering from both MAFLD and COVID-19, while none approved treatment is currently available for any of them. Moreover, it is well known that exacerbated innate immune responses are key in the development of the most severe stages of MAFLD and COVID-19. In this review, we focus on the role of the immune system in the establishment and progression of MAFLD and discuss its potential implication in the development of severe COVID-19 in MAFLD patients. As a result, we hope to clarify their common pathology, but also uncover new potential therapeutic targets and prognostic biomarkers for further research.

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.

New Mexico's COVID-19 Experience.

ABSTRACT: The 2019 novel coronavirus disease (COVID-19) has spread worldwide, infiltrating, infecting, and devastating communities in all locations of varying demographics. An overwhelming majority of published literature on the pathologic findings associated with COVID-19 is either from living clinical cohorts or from autopsy findings of those who died in a medical care setting, which can confound pure disease pathology. A relatively low initial infection rate paired with a high biosafety level enabled the New Mexico Office of the Medical Investigator to conduct full autopsy examinations on suspected COVID-19-related deaths. Full autopsy examination on the first 20 severe acute respiratory syndrome coronavirus 2-positive decedents revealed that some extent of diffuse alveolar damage in every death due to COVID-19 played some role. The average decedent was middle-aged, male, American Indian, and overweight with comorbidities that included diabetes, ethanolism, and atherosclerotic and/or hypertensive cardiovascular disease. Macroscopic thrombotic events were seen in 35% of cases consisting of pulmonary thromboemboli and coronary artery thrombi. In 2 cases, severe bacterial coinfections were seen in the lungs. Those determined to die with but not of severe acute respiratory syndrome coronavirus 2 infection had unremarkable lung findings.

Pathological findings in the postmortem liver of patients with coronavirus disease 2019 (COVID-19).

Although coronavirus disease 2019 (COVID-19) is transmitted via respiratory droplets, there are multiple gastrointestinal and hepatic manifestations of the disease, including abnormal liver-associated enzymes. However, there are not many published articles on the pathological findings in the liver of patients with COVID-19. We collected the clinical data from 17 autopsy cases of patients with COVID-19 including age, sex, Body mass index (BMI), liver function test (alanine aminotransaminase (ALT), aspartate aminotransaminase (AST), alkaline phosphatase (ALP), direct bilirubin, and total bilirubin), D-dimer, and anticoagulation treatment. We examined histopathologic findings in postmortem hepatic tissue, immunohistochemical (IHC) staining with antibody against COVID-19 spike protein, CD68 and CD61, and electron microscopy. We counted the number of megakaryocytes in liver sections from these COVID-19-positive cases. Abnormal liver-associated enzymes were observed in 12 of 17 cases of COVID-19 infection. With the exception of three cases that had not been tested for D-dimer, all 14 patients' D-dimer levels were increased, including the cases that received varied doses of anticoagulation treatment. Microscopically, the major findings were widespread platelet-fibrin microthrombi, steatosis, histiocytic hyperplasia in the portal tract, mild lobular inflammation, ischemic-type hepatic necrosis, and zone 3 hemorrhage. Rare megakaryocytes were found in sinusoids. COVID-19 IHC demonstrates positive staining of the histiocytes in the portal tract. Under electron microscopy, histiocyte proliferation is present in the portal tract containing lipid droplets, lysosomes, dilated ribosomal endoplasmic reticulum, microvesicular bodies, and coronavirus. The characteristic findings in the liver of patients with COVID-19 include numerous amounts of platelet-fibrin microthrombi, as well as various degrees of steatosis and histiocytic hyperplasia in the portal tract. Possible mechanisms are also discussed.

Hepatic Steatosis Is Associated with Increased Disease Severity and Liver Injury in Coronavirus Disease-19.

BACKGROUND: Coronavirus disease-2019 (COVID-19) is a global pandemic. Obesity has been associated with increased disease severity in COVID-19, and obesity is strongly associated with hepatic steatosis (HS). However, how HS alters the natural history of COVID-19 is not well characterized, especially in Western populations. AIMS: To characterize the impact of HS on disease severity and liver injury in COVID-19. METHODS: We examined the association between HS and disease severity in a single-center cohort study of hospitalized COVID-19 patients at Michigan Medicine. HS was defined by either hepatic steatosis index > 36 (for Asians) or > 39 (for non-Asians) or liver imaging demonstrating steatosis > 30 days before onset of COVID-19. The primary predictor was HS. The primary outcomes were severity of cardiopulmonary disease, transaminitis, jaundice, and portal hypertensive complications. RESULTS: In a cohort of 342 patients, metabolic disease was highly prevalent including nearly 90% overweight. HS was associated with increased transaminitis and need for intubation, dialysis, and vasopressors. There was no association between HS and jaundice or portal hypertensive complications. In a sensitivity analysis including only patients with liver imaging > 30 days before onset of COVID-19, imaging evidence of hepatic steatosis remained associated with disease severity and risk of transaminitis. CONCLUSIONS: HS was associated with increased disease severity and transaminitis in COVID-19. HS may be relevant in predicting risk of complications related to COVID-19.