Liver ultrasound evaluation of acutely increased liver function tests of COVID-19 hospitalized patients

Background The incidence of hepatic abnormalities has been notably higher following the coronavirus disease 2019 (COVID-19) infection, attributed to the virus’s entry into cells via angiotensin-converting enzyme 2 (ACE2) surface expression. The gastrointestinal tract’s significant ACE2 expression, alongside a lesser degree in the biliary epithelium, has been implicated in gastrointestinal symptoms and liver injury. Purpose The aim of this study was to determine whether specific ultrasonographic findings in the liver correlate with acute increases in liver function tests (LFTs) among hospitalized patients. Methods A retrospective analysis was conducted on hospitalized COVID-19 patients at Hazem Mebaireek General Hospital in Qatar, from March 1, 2020, to June 30, 2020. The study focused on patients who experienced acute increases in LFTs, excluding those with chronic liver disease. Ultrasound imaging and patient records were reviewed to gather data. Results Out of 223 ultrasound studies of COVID-19 patients, 158 met the inclusion criteria. The majority were male, with a mean age of 47.76 ± 13.76 years. Ultrasound results showed 43.7% normal liver parenchyma, while 56.3% exhibited nonspecific abnormalities such as diffuse liver hyperechogenicity (39.2%), enlargement with diffuse hyperechogenicity (12.7%), and other findings (4.4%). The biliary tree was predominantly normal (96.2%), with 3.8% showing abnormalities, including intrahepatic (2.5%) and extrahepatic (1.3%) dilatation. Gallbladder evaluations were normal in 60.1% of cases, with 39.9% showing abnormalities like stones (6.3%), stones with sludge (13.3%), polyps (6.3%), wall thickening (1.9%), and other conditions (12%). A significant correlation was found between abnormal liver parenchyma findings and elevated levels of bilirubin (total and direct) and alkaline phosphatase, with p-values < 0.05. Only aspartate aminotransferase levels showed a significant correlation with biliary tree abnormalities. Conclusion The most common ultrasonographic finding associated with acute increases in LFTs among hospitalized COVID-19 patients was diffuse liver hyperechogenicity, with or without enlargement. These findings suggest a nonspecific yet significant association with liver function anomalies in the context of COVID-19.

Purpose: The aim of this study was to determine whether specific ultrasonographic findings in the liver correlate with acute increases in liver function tests (LFTs) among hospitalized patients.
Methods: A retrospective analysis was conducted on hospitalized COVID-19 patients at Hazem Mebaireek General Hospital in Qatar, from March 1, 2020, to June 30, 2020.The study focused on patients who experienced acute increases in LFTs, excluding those with chronic liver disease.Ultrasound imaging and patient records were reviewed to gather data.

INTRODUCTION
At the end of 2019, a new coronavirus, severe acute respiratory syndrome coronavirus (SARS-CoV-2), was identified as the culprit behind a series of pneumonia cases in Wuhan, within China's Hubei Province. 1 Coronavirus disease 2019 (COVID- 19), the disease caused by this virus, predominantly affects the lungs, presenting symptoms that range from mild respiratory issues to severe pneumonia, acute respiratory distress syndrome, and even death. 2Healthcare professionals, notably those in gastroenterology and hepatology, are revising their practices to mitigate COVID-19's spread while continuing to provide patient care. 3Although primarily a respiratory illness, COVID-19 also impacts multiple organs, including the heart, kidneys, and liver. 4otably, up to 11% of COVID-19 patients experience liver-related comorbidities, and 14%-53% exhibit elevated levels of liver enzymes (alanine aminotransferase [ALT] and aspartate aminotransferase [AST]) as well as the other parameters of liver function tests (LFTs) such as bilirubin total and direct and alkaline phosphatase (ALP) as the disease progresses, underscoring a Liver ultrasound evaluation of acutely increased liver function tests of COVID-19 hospitalized patients criteria, aiming to isolate the impact of COVID-19 on liver function as evidenced through ultrasound imaging and LFT results.

Exclusion criteria
• Patients with a negative COVID-19 PCR test result.• Individuals with a pre-existing history of chronic liver disease, including features of chronic liver conditions or focal lesions on the liver.• Cases where the ultrasound study was incomplete or lacked sufficient detail for analysis.Through this methodology, the study aims to identify specific ultrasonographic findings associated with acute liver function alterations in COVID-19 patients, thereby contributing valuable insights into the broader spectrum of the virus's systemic effects.

Statistical analysis
In this study, statistical analysis was carried out to evaluate the relationship between COVID-19 infection and liver function abnormalities as detected through ultrasound imaging and LFTs.The analysis began with descriptive statistics to summarize the demographic characteristics of the study population, including means and standard deviations for continuous variables like age and LFT levels, and frequencies and percentages for categorical variables such as gender and ultrasound findings.Inferential statistics were then employed to identify any significant associations between the ultrasound findings and elevated LFTs.Chi-square tests were used for categorical variables to compare the prevalence of abnormal ultrasound findings among different patient groups, while t-tests or ANOVA were applied for continuous variables to compare mean LFT levels across groups with varying ultrasound results.A significance level of p < 0.05 was adopted for all tests to determine statistical significance.Additionally, logistic regression analyses may have been conducted to adjust for potential confounders and assess the strength of associations between significant findings and COVID-19 severity, although the specifics of such analyses would depend on the data available, and the hypotheses being tested.

RESULTS
The study encompassed 158 participants, of whom 151 (95.6%) were male and the remainder were female.The majority, 81 individuals (51.3%), fell within the age range of 41-60 years, with an average age of 47.76 ± 13.76 years (Table 1).
LFTs were extensively analyzed, documenting both the initial elevation levels and the peak levels of LFTs.The mean levels of LFTs among participants are detailed in Table 2. Ultrasound examinations focused on liver parenchyma, which appeared normal in 69 cases (43.7%), although these patients have abnormal LFTs.Notably, among those with abnormal US findings, 39.2% of ultrasounds exhibited diffuse liver hyperechogenicity.The biliary tree was predominantly normal, with exceptions being mild intrahepatic dilatation in four cases (2.5%) and mild extrahepatic dilatation in two cases (1.3%).Gallbladder assessments revealed stones in 10 participants (6.3%) and stones with well as initial ALP levels, all with p-values < 0.05.Other LFT parameters did not show statistical significance.Similarly, abnormalities in the biliary tree correlated significantly with total and direct bilirubin levels (both initial and peak), with p-values < 0.05, while other parameters were not sludge in 21 participants (13.3%), as summarized in Table 3.
Upon comparing ultrasound findings with LFT results, a significant correlation was observed between liver parenchyma abnormalities and total and direct bilirubin levels (both initial and peak) as    significantly affected.Gallbladder findings showed significant correlations only with peak ALT and ALP levels (p < 0.05) (Table 4).Not all patients exhibited elevated LFTs in correlation with ultrasound findings, indicating variability among individuals (Table 5).The most commonly elevated LFT parameter was AST (94.3%), followed by ALT (88%), total bilirubin (57.6%),ALP (51.9%), and direct bilirubin (41.8%).Abnormal total bilirubin was noted in 91 participants, direct bilirubin in 66, ALP in 82, ALT in 139, and AST in 149.
When examining the correlation of abnormal LFTs with gender and age, no statistical significance was found for any LFT parameter across these demographics (Table 6).However, a gender-specific analysis of ultrasound findings indicated a higher prevalence of abnormalities among male patients, though no significant age-related trends were observed, despite the 41-60-year age group being most represented (Table 7).Finally, a significant association was found between abnormal ultrasound findings and elevated levels of total and direct bilirubin and ALP, with p-values < 0.05.For the biliary tree, only AST levels were significantly correlated (Table 8).

DISCUSSION
In the context of the ongoing COVID-19 pandemic, there is a pressing need for research into various treatment and intervention strategies.The susceptibility of patients with chronic liver diseases to COVID-19 remains unclear.][10][11] This connection implies a potential association between liver enzyme levels and SARS-CoV-2 infection.Our research focused on exploring liver pathology and abnormalities in LFTs, using ultrasound imaging as a diagnostic tool in COVID-19 patients.Of the 223 ultrasound examinations reviewed, 158 patients met the inclusion criteria for our study.The findings revealed a predominance of male patients, with an average age of 47.76 ± 13.76 years, aligning with previous research. 123][14] LFTs, which include measurements of AST and ALT, are crucial for detecting hepatocyte injury.These enzymes are key indicators of liver function and are closely related to the permeability of the hepatocyte membrane. 13It is important to note that increased levels of ALT and AST are not exclusive to liver damage and have also been linked to myositis. 15Generally, liver failure or impairment in patients with SARS-CoV-2 infection does not correlate with abnormal LFTs, and liver-focused treatments are often not required.The mechanisms underlying abnormal LFTs in COVID-19 patients remain largely undefined.
Our study assessed LFTs for both lower and peak levels, identifying a statistically significant elevation in total bilirubin and ALT among COVID-19 patients, which is consistent with previous findings. 16Ultrasound examinations most commonly identified hepatobiliary abnormalities, with 62 of 158 patients displaying diffuse liver hyperechogenicity and 20 of 158 showing an enlarged liver with diffuse hyperechogenicity.These findings are consistent with Abdelmohsen's 2020 study, 17 which reported that most cases of hepatomegaly showed elevated LFTs and a bright echo pattern in the hepatic parenchyma.This observation is also detailed in the overview of liver involvement in COVID-19 infection done by Ippolito et al.

CONCLUSION
Ultrasound findings, while helpful, should be interpreted with caution due to their nonspecific nature, as liver parenchyma abnormalities can occur in various conditions, with fatty liver (steatosis) appearance being a common causative feature.The ongoing evolution of COVID-19 underscores the critical need for further research to deepen our understanding of its impact on liver health and the optimal management of patients with liver diseases.Given the common observation of liver impairment in COVID-19 patients, future studies should include comprehensive evaluations, such as serology tests, to better understand the causes of liver failure and impairment.Additionally, as new antiviral vaccines are developed, it may be necessary to update recommendations to ensure their safety and efficacy in patients with liver diseases.

Table 1 . Demographic data of the participants (n = 158).
VOL. 2024 / ART.46 Liver ultrasound evaluation of acutely increased liver function tests of COVID-19 hospitalized patients

Table 4 . Correlation of ultrasound findings with liver function test (n = 158).
VOL. 2024 / ART.46 Liver ultrasound evaluation of acutely increased liver function tests of COVID-19 hospitalized patients

Table 5 . Percentage of normal to abnormal LFTs.
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Table 8 . Correlation of abnormal ultrasound findings with abnormal LFTs.
Liver ultrasound evaluation of acutely increased liver function tests of COVID-19 hospitalized patients ultrasound findings and LFT elevations specifically attributable to COVID-19.