COVID-19 and liver dysfunction: Epidemiology, association and potential mechanisms

Du, Min; Song, Yang; Liu, Min; Liu, Jue

doi:10.1016/j.clinre.2021.101793

Cited by 21 publications

(19 citation statements)

References 93 publications

(199 reference statements)

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“…In addition, it is currently the largest study from Greece reflecting our experience regarding the baseline characteristics and the outcomes of the COVID-19 patients admitted and managed in our center. In agreement with data in the literature [ 13 ], we found that abnormal values in serum aminotransferases were frequently observed on admission (in our cohort 35% and 26%, respectively, of the patients had AST and ALT values >40 IU/L). However, at baseline, only 1% and 0.2% of the patients had LI (i.e., AST>200 IU/L) or AST >400 IU/L, respectively.…”

Section: Discussionsupporting

confidence: 93%

Prevalence of abnormal liver biochemistry and its impact on COVID-19 patients’ outcomes: a single-center Greek study

Cholongitas

2022

aog

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Background Abnormalities in aminotransferases are frequently observed in hospitalized COVID-19 patients, but their clinical impact is poorly characterized. Methods A total of 1046 patients hospitalized to the non-intensive care unit ward with documented COVID-19 were included retrospectively. Demographic, clinical and laboratory characteristics on admission and during hospital stay, including the presence of liver injury (LI), defined as aspartate aminotransferase (AST) >200 IU/L, were recorded. Results On admission, 363 (34.7%) and 269 (25.7%) patients had abnormal AST and ALT values (i.e., >40 IU/L), respectively, while during hospitalization 53 (5%) patients fulfilled the criteria for LI. In multivariate logistic regression analysis, AST (odds ratio [OR] 1.023, 95% confidence interval [CI] 1.016-1.029; P<0.001), and ferritin (OR 1.01, 95%CI 1.001-1.02; P<0.001) were the baseline factors independently associated with the development of LI during hospital stay. One hundred twenty-three (11.7%) patients died during hospitalization. The independent variables associated with mortality were: age (hazard ratio [HR] 1.043, 95%CI 1.029-1.056; P<0.001), ferritin (HR 1.1, 95%CI 1.05-1.2; P<0.001), platelets (HR 0.996, 95%CI 0.994-0.999; P=0.003), and administration of remdesivir (HR 0.50, 95%CI 0.30-0.85; P=0.009). The patients with abnormal baseline AST (i.e., >40 IU/L), compared to those with normal AST values, had worse outcomes (log rank test: 8.8, P=0.003). Conclusions Elevated aminotransferases are commonly seen in COVID-19 patients. They possibly reflect disease severity and may be associated with in-hospital mortality.

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Section: Discussionsupporting

confidence: 93%

Prevalence of abnormal liver biochemistry and its impact on COVID-19 patients’ outcomes: a single-center Greek study

Cholongitas

2022

aog

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“…The mechanisms of association between liver injury and SARS-CoV-2 infections are complex and the subject of current research. Direct cholangiocyte injury has been described in the context of cytokine growth triggered by SARS-CoV-2 [ 38 ]. We also confirmed these data in our study, where critically ill COVID-19 patients showed significantly increased liver enzymes.…”

Section: Discussionmentioning

confidence: 99%

Significantly Reduced Retinol Binding Protein 4 (RBP4) Levels in Critically Ill COVID-19 Patients

et al. 2022

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The SARS-CoV-2 virus is the causative agent of the COVID-19 pandemic. The disease causes respiratory failure in some individuals accompanied by marked hyperinflammation. Vitamin A (syn. retinol) can exist in the body in the storage form as retinyl ester, or in the transcriptionally active form as retinoic acid. The main function of retinol binding protein 4 (RBP4), synthesized in the liver, is to transport hydrophobic vitamin A to various tissues. Vitamin A has an important role in the innate and acquired immune system. In particular, it is involved in the repair of lung tissue after infections. In viral respiratory diseases such as influenza pneumonia, vitamin A supplementation has been shown to reduce mortality in animal models. In critically ill COVID-19 patients, a significant decrease in plasma vitamin A levels and an association with increased mortality have been observed. However, there is no evidence on RBP4 in relation to COVID-19. This prospective, multicenter, observational, cross-sectional study examined RBP4 (enzyme-linked immunosorbent assay) and vitamin A plasma levels (high-performance liquid chromatography) in COVID-19 patients, including 59 hospitalized patients. Of these, 19 developed critical illness (ARDS/ECMO), 20 developed severe illness (oxygenation disorder), and 20 developed moderate illness (no oxygenation disorder). Twenty age-matched convalescent patients following SARS-CoV-2 infection, were used as a control group. Reduced RBP4 plasma levels significantly correlated with impaired liver function and elevated inflammatory markers (CRP, lymphocytopenia). RBP4 levels were decreased in hospitalized patients with critical illness compared to nonpatients (p < 0.01). In comparison, significantly lower vitamin A levels were detected in hospitalized patients regardless of disease severity. Overall, we conclude that RBP4 plasma levels are significantly reduced in critically ill COVID-19 patients during acute inflammation, and vitamin A levels are significantly reduced in patients with moderate/severe/critical illness during the acute phase of illness.

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“…Most cases of liver involvement are mainly characterized by elevated transaminases and are thought to represent a combination of direct virus-induced cholangiocyte damage, drug-induced hepatotoxicity and cytokine storm. However, a small proportion of the patients with critical illness including ARDS may develop a rapidly progressive cholestatic liver injury reminiscent of secondary sclerosing cholangitis in critically ill patients (SSC-CIP) of other causes [ 4 – 6 ]. The etiology of this COVID-19-associated SSC is hypothesized to be multifactorial and potential inciting factors include systemic inflammatory response syndrome (SIRS) with cytokine storm, hypoxic injury to cholangiocytes, viral-induced direct cytotoxicity, micro- and macrovascular changes leading to hypercoagulability and use of hepatotoxic medications (e.g., antibiotics, ketamine) in these critically ill patients [ 7 ].…”

Section: Introductionmentioning

confidence: 99%

Imaging features of COVID-19-associated secondary sclerosing cholangitis on magnetic resonance cholangiopancreatography: a retrospective analysis

et al. 2022

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Background Despite emerging reports of secondary sclerosing cholangitis (SSC) in critically ill COVID-19 patients little is known about its imaging findings. It presents as delayed progressive cholestatic liver injury with risk of progression to cirrhosis. Diagnosis cannot be made based on clinical presentation and laboratory markers alone. Magnetic resonance imaging (MRI) and magnetic resonance cholangiopancreatography (MRCP) can aid in the diagnosis. The aim of this study was to describe MRI/MRCP imaging features of COVID-19-associated SSC. Results Seventeen patients (mean age 60.5 years, 15 male) who underwent MRI/MRCP were included. All had been admitted to intensive care unit (ICU) (median duration of ICU stay 10 weeks, range, 2–28 weeks) and developed acute respiratory distress syndrome requiring mechanical ventilation. On imaging, all patients had intrahepatic bile duct strictures and 10 (58.8%) had associated upstream dilatation. Intrahepatic bile duct beading was seen in 14 cases (82.3%). Only one patient (5.9%) had extrahepatic bile duct stricturing. Patchy arterial phase hyperenhancement and high signal on T2- and diffusion-weighted images were seen in 7 cases (53.8%) and 9 cases (52.9%), respectively. Biliary casts were seen in 2 cases (11.8%). Periportal lymphadenopathy and vascular complications were not seen. Conclusion On MRI/MRCP, COVID-19-associated SSC presents with multiple intrahepatic bile duct strictures with or without upstream dilatation and intrahepatic bile duct beading. Surrounding hepatic parenchymal changes including alterations in enhancement and T2 signal are common. The extrahepatic biliary tree was typically spared and periportal lymphadenopathy was missing in all patients.

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COVID-19 and liver dysfunction: Epidemiology, association and potential mechanisms

Cited by 21 publications

References 93 publications

Prevalence of abnormal liver biochemistry and its impact on COVID-19 patients’ outcomes: a single-center Greek study

Prevalence of abnormal liver biochemistry and its impact on COVID-19 patients’ outcomes: a single-center Greek study

Significantly Reduced Retinol Binding Protein 4 (RBP4) Levels in Critically Ill COVID-19 Patients

Imaging features of COVID-19-associated secondary sclerosing cholangitis on magnetic resonance cholangiopancreatography: a retrospective analysis

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