Liver chemistries in severe or non-severe cases of COVID-19: A systematic review and meta-analysis.

BACKGROUND: Coronavirus disease (COVID-19) patients exhibit different patterns of liver impairment, according to growing evidence. AIM: In this study, we sought to provide a comprehensive analysis of liver test parameters in patients with severe and non-severe COVID-19. METHODS: We performed a meta-analysis of published liver manifestations and described the liver damage in COVID-19. We searched PubMed, Google Scholar, Embase, Cochrane Library, medRxiv, bioRxiv, and three Chinese electronic databases through April 18, 2020, in accordance with the Preferred Reporting Items for Meta-Analyses. We analyzed pooled data on liver chemistries stratified by COVID-19 severity using a fixed or random-effects model. RESULTS: A meta-analysis of 56 studies, including 11052 patients, found that the pooled mean alanine aminotransferase (ALT) in severe COVID-19 cases was 35.9 IU/L whereas in non-severe COVID-19 cases was 27.3 IU/L. Average aspartate aminotransferase (AST) levels were 44.3 IU/L in severe cases compared to 27.9 IU/L in non-severe cases. In addition, AST levels are often higher than ALT levels regardless of disease severity. The severe cases tended to have a higher gamma-glutamyltransferase level but a lower albumin level than the non-severe cases. CONCLUSION: Severe COVID-19 was more likely to be associated with abnormal liver test results. Monitoring liver chemistry closely can help detect disease progression early.

Age-adjusted mortality and predictive value of liver chemistries in a Viennese cohort of COVID-19 patients.

BACKGROUND AND AIMS: The coronavirus disease of 2019 (COVID-19) causes considerable mortality worldwide. We aimed to investigate the frequency and predictive role of abnormal liver chemistries in different age groups. METHODS: Patients with positive severe acute respiratory distress syndrome-coronavirus-2 (SARS-CoV-2) polymerase chain reaction (PCR) test between 03/2020-07/2021 at the Vienna General Hospital were included. Patients were stratified for age: 18-39 vs. 40-69 vs. ≥70 years (y). Aspartate aminotransferase (AST), alanine-aminotransferase (ALT), alkaline phosphatase (ALP), gamma-glutamyl transferase (GGT) and total bilirubin (BIL) were recorded. RESULTS: 900 patients (18-39 years: 32.2%, 40-69 years: 39.7%, ≥70 years: 28.1%) were included. Number of comorbidities, median D-dimer and C-reactive protein increased with age. During COVID-19, AST/ALT and ALP/GGT levels significantly increased. Elevated hepatocellular transaminases (AST/ALT) and cholestasis parameters (ALP/GGT/BIL) were observed in 40.3% (n  = 262/650) and 45.0% (n  = 287/638) of patients respectively. Liver-related mortality was highest among patients with pre-existing decompensated liver disease (28.6%, p < .001). 1.7% of patients without pre-existing liver disease died of liver-related causes, that is consequences of hepatic dysfunction or acute liver failure. Importantly, COVID-19-associated liver injury (16.0%, p < .001), abnormal liver chemistries and liver-related mortality (6.5%, p < .001) were most frequent among 40-69 years old patients. Elevated AST and BIL after the first positive SARS-CoV-2 PCR independently predicted mortality in the overall cohort and in 40-69 years old patients. CONCLUSIONS: Almost half of the COVID-19 patients exhibit abnormal hepatocellular and cholestasis-related liver chemistries with 40-69 years old patients being at particularly high risk for COVID-19-related liver injury and liver-related mortality. Elevated AST and BIL after SARS-CoV-2 infection are independent predictors of mortality, especially in patients aged 40-69 years.

Evaluation of Liver Histopathological Findings of Coronavirus Disease 2019 by Minimally Invasive Autopsies.

AIM: The severe acute respiratory syndrome coronavirus 2 outbreak resulted in severe health impact with the loss of many lives across the world. Pulmonary parenchyma suffers the most from the brunt of the infection. However, evidence suggested a systemic involvement during the course of illness. Information on morphological changes of the liver is sparse in the literature. We aimed to evaluate the pathological findings in the liver by minimally invasive autopsies. METHODS: Postmortem core biopsies of the liver obtained from patients who succumbed to coronavirus disease 2019 disease were studied. Demographic findings, comorbidities, and relevant laboratory tests were collected. Detailed histopathological changes were assessed. RESULTS: Liver function tests were available in 40 cases, and it was deranged in 80% cases. A spectrum of histological changes was observed. Macrovesicular steatosis and nonspecific portal inflammation of mild degree were the common morphological changes. Features suggestive of vascular alteration were noted in more than half of the cases. These included increased portal vein branches, irregular luminal dilation, and herniation of portal veins into the periportal hepatocytes. In addition, we observed morphological changes attributed to terminal shock-related changes. CONCLUSION: The present study results highlight that liver parenchyma changes may be related to multiple pathogenic mechanisms. The presence of vascular alteration in portal tracts suggests derangement of hepatic vasculature related to systemic hypercoagulable state induced by the viral infection. It remains to be established if the histological changes are related to direct viral insult or to the systemic response caused by the viral attack.

Risk factors and outcomes for acute-on-chronic liver failure in COVID-19: a large multi-center observational cohort study.

OBJECTIVE: Coronavirus disease 2019 [COVID-19] infection in patients with chronic liver disease [CLD] may precipitate acute-on-chronic liver failure [ACLF]. In a large multi-center cohort of COVID-19-infected patients, we aim to analyze (1) the outcomes of patients with underlying CLD [with and without cirrhosis] and (2) the development and impact of ACLF on in-hospital mortality. DESIGN: We identified 192 adults with CLD from among 10,859 patients with confirmed COVID-19 infection (admitted to any of 12 hospitals in a New York health care system between March 1, 2020 and April 27, 2020). ACLF was defined using the EASL-CLIF Consortium definition. Patient follow-up was through April 30, 2020, or until the date of discharge, transfer, or death. RESULTS: Of the 84 patients with cirrhosis, 32 [38%] developed ACLF, with respiratory failure [39%] and renal failure [26%] being the most common. Hispanic/Latino ethnicity was particularly at higher risk of in-hospital mortality [adjusted HR 4.92, 95% 1.27-19.09, p < 0.02] in cirrhosis despite having lower risk of development of ACLF [HR 0.26, 95% CI 0.08-0.89, p = 0.03]. Hypertension on admission predicted development of ACLF [HR 3.46, 95% CI 1.12-10.75, p = 0.03]. In-hospital mortality was not different between CLD patients with or without cirrhosis [p = 0.24] but was higher in those with cirrhosis who developed ACLF [adjusted HR 9.06, 95% CI 2.63-31.12, p < 0.001] with a trend for increased mortality by grade of ACLF [p = 0.002]. There was no difference in in-hospital mortality between the CLD cohort compared to matched control without CLD (log rank, p = 0.98) and between the cirrhosis cohort compared to matched control without cirrhosis (log rank, p = 0.51). CONCLUSION: Development of ACLF is the main driver of increased in-hospital mortality in hospitalized patients with COVID-19 infection and cirrhosis.

Serum Activity of Liver Enzymes Is Associated With Higher Mortality in COVID-19: A Systematic Review and Meta-Analysis.

Background: Abnormal liver chemistries are common findings in patients with COVID-19. It is unclear whether abnormal liver chemistries can predict the severity of COVID-19. Therefore, we compared the serum liver chemistries such as hepatic transaminases, total bilirubin, albumin, and prothrombin time to evaluate whether they can predict severity and mortality in COVID-19. Methods: An electronic search was performed on PubMed/Medline, EMBASE, and Google Scholar for studies comparing liver chemistries in severe and mild COVID-19. The literature search was performed using keywords "COVID-19," "Liver," Aspartate Aminotransferase (AST)," and "Alanine Aminotransferase (ALT)," "AST," and "ALT," in various combinations of "AND/OR" from December 1, 2019, till May 8, 2020. The pooled weighted mean difference (WMD) and 95% confidence interval (CI) were calculated for each component of liver chemistries. Results: Twenty-two studies were eligible, with 3,256 patients (54.57% males). Seventeen studies compared liver chemistries for severe vs. mild COVID-19, whereas five studies compared liver chemistries in survival vs. non-survival groups. The pooled WMD of AST and ALT in severe vs. mild COVID-19 were 12.23 (95% CI; 8.07, 16.39; p < 0.01) and 8.07 (95% CI 2.55, 11.91; p < 0.01), respectively. The pooled WMD for AST in survivors vs. non-survivors analysis was 8.82 (n = 789; 95% CI; 2.27, 15.37; p < 0.01) and that of ALT was 4.70 (n = 340; 95% CI 0.04,9.35; p = 0.05). Conclusion: Our meta-analysis shows that deranged liver chemistries may indicate severe COVID-19 and could also predict mortality. Larger studies are needed to evaluate the relationship between derangement in liver chemistries and mortality in COVID-19.

Increased Serum Aminotransferase Activity and Clinical Outcomes in Coronavirus Disease 2019.

AIM: Elevation of hepatic aminotransferases (aspartate aminotransferase [AST]/alanine aminotransferase [ALT]) is commonly noted among COVID-19 patients. It is unclear if they can predict the clinical outcomes among hospitalized COVID-19 patients. We aim to assess if elevations in AST/ALT were associated with poor outcomes in hospitalized COVID-19 patients. METHODS: We retrospectively evaluated hospitalized COVID-19 patients with clinically significant elevated aminotransferases (defined as >2 times upper limit of normal) and compared them with COVID-19 patients without an elevation in aminotransferases. RESULTS: The prevalence of elevation in AST/ALT was found to be 13.7% (20/145). The two groups were similar in baseline demographics, comorbidities, and the majority of laboratory tests. There was no difference in the mortality (50% vs. 36.8%, P = 0.32) and median hospital stay (7 days vs. 7 days, P = 0.78). However, there was a statistically significant increase in the rates of mechanical ventilation among elevated aminotransferases group compared with individuals without elevation (50% vs. 24%, P = 0.028). However, this difference was not observed after adjusting for inflammatory markers such as ferritin, lactate dehydrogenase, and lactic acid levels. CONCLUSION: Elevated aminotransferases among hospitalized COVID-19 patients is associated with higher rates of mechanical ventilation but did not achieve statistical significance after controlling for inflammatory markers. Also, patients with elevated aminotransferases did not have higher rates of mortality or prolonged length of stay.