Liver Biochemical Abnormalities Among COVID-19 Patients Liver Biochemical Abnormalities Among COVID-19 Patients

Background : The sever acute respiratory syndrome corona virus-2 (SARS_CoV-2) is a novel Corona virus that causes Corona virus disease 2019 (COVID-19). Except for respiratory symptoms, COVID-19 patient often develop different degrees of liver injury. Notably, COVID-19 patients with pre-existing liver diseases, especially liver cirrhosis, have higher incidence of liver biochemical abnormality, liver injury, and even hepatic decompensation event. Aim : To determine the liver biochemistry changes in COVID-19 patients. Patients and methods : In this retrospective study was conducted in quarantine department, Assuit Chest Hospital was conducted on 761 COVID-19 patients. Patients were divided into 2 groups: hepatic and non-hepatic groups. Results : Hepatic patients showed signi ﬁ cant elevation in AST and ALT compared to non hepatic patients. There was statistically signi ﬁ cant difference between COVID-19 patients with normal and altered liver function regarding treat-ment. Patients with altered liver function tests showed signi ﬁ cant elevation in INR compared to patients with normal liver function tests. There was no statistically signi ﬁ cant difference between COVID-19 patients with normal and altered liver function regarding mortality. There was no statistically signi ﬁ cant difference between them regarding pH, PCO2, HCO3, SO2, Na and K. Conclusion : Liver biochemical abnormality is more common in COVID-19 patients with liver cirrhosis. However, liver cirrhosis patients without COVID-19 have more hepatic decompensation events, so they should not be delayed from their hospitalization management during the COVID-19 pandemic. The presence of abnormal liver tests on admission was not associated with COVID-19 severity


Introduction
T he sever acute respiratory syndrome corona virus-2 (SARS_CoV-2) is a novel Corona virus that causes Corona virus disease 2019 (COVID-19) which first appeared in Wuhan city in Hubei province in central China, It is highly contagious and is rapidly spreading around the world. 1 (see Tables 1e25) The clinical severity of COVID-19 varies from asymptomatic to fatal.Some cases are only accompanied by mild respiratory symptoms without fever and recover spontaneously. 2 In contrast, others suffer from systemic symptoms including fever, chest pain, myalgia, shortness of breath and coughing associated with pneumonia, which contribute in part to the development of sever complications such as acute respiratory distress syndrome, and even death. 3xcept for respiratory symptoms, COVID-19 patient often develop different degrees of liver injury.Notably, COVID-19 patients with pre-existing liver diseases, especially liver cirrhosis, have higher incidence of liver biochemical abnormality, liver injury, and even hepatic decompensation events. 4herefore; this study aim to determine the liver biochemistry changes in COVID-19 patient.

Patients and methods
In this retrospective study was conducted in quarantine department, Assuit Chest Hospital was conducted on 761 COVID-19 patients was carried out in the period from January to July 2021 (3rd Wave) & from August to October 2021 (4th Wave).Patients were divided into 2 groups: hepatic and non-hepatic groups.All patients subjected to the following: Full history taking, Laboratory data was

Results
This retrospective study was conducted on 761 patients (500 patients in third wave &261 patients in  In patients with altered liver function tests, albumin was significantly higher in 4th wave compared to results in 3rd wave (p ¼ 0.039).In patients with normal liver function tests, AST & ALT were significantly higher in 4th wave compared to results in 3rd wave (p < 0.001).

Third wave
Third wave was carried out in the period from January to July 2021 and conducted on 500 Patients.

Fourth wave
Fourth wave was carried out in the period from August to October 2021 and conducted on 261 Patients.

Discussion
Liver injury in SARS-CoV-2 infection may be caused by either systemic inflammation response or drug hepatotoxicity, which is supported by the first autopsy pathological analysis of a COVID-19 patient showing moderate microvesicular steatosis and mild lobular and portal activity in the liver tissue. 5egarding in our study, No statistically significant difference between the hepatic (n ¼ 20) and nonhepatic (n ¼ 241) groups regarding age, gender and hypertension.
The current results were supported by Wang et al., 6 who compared 64 (41%) patients with COVID-19 and elevated aminotransferases versus 92 (59%) patients with COVID-19 and normal aminotransferases, the study found that was no statistically significant difference between the studied groups regarding age, gender, and comorbidities.The most common comorbidities were DM and hypertension.
In our study, at third and fourth wave, no statistically significant difference between hepatic and non hepatic groups regarding clinical presentation (p > 0.05).
Our results were supported by An et al., 7 who revealed that there was no statistically significant difference between COVID-19 patients with normal and altered liver function regarding clinical presentation (p > 0.05).The most common symptoms were fatigue, fever, cough and shortness of breath.The same was reported by Garrido et al., 8 In our study, third and fourth waves showed significant decrease in platelets count compared to non hepatic patients (p < 0.001).No statistically significant difference between hepatic and non hepatic groups regarding Hb., WBCs, lymphocytes in third and fourth waves (p > 0.05).
In agreement with the current study An et al., 7 revealed that Patients with altered liver function tests showed significant decrease in platelets count compared to patients with normal liver function tests (p < 0.001), but other CBC results and inflammatory markers were comparable between the studied groups.
In harmony with our results Voiosu et al., 9 who enrolled 1207 patients, 134 patients (11%) with abnormal liver functions test.Patients with altered liver function tests showed significant decrease in platelets count compared to patients with normal liver function tests (p < 0.001).Meanwhile, there was no statistically significant difference between COVID-19 patients with normal and altered liver function regarding Hb and WBC.
In the current study, during the third and fourth wave, no statistically significant difference between hepatic and non hepatic groups regarding serum urea and creatinine (p > 0.05).No statistically significant difference between them regarding pH, PCO2, HCO3, SO2, Na and K (p > 0.05).
In agreement with the current study An et al., 7 reported that there was no statistically significant difference between the studied groups regarding creatinine, sodium, and potassium.
Furthermore, Garrido et al., 8 reported that there was no statistically significant difference between COVID-19 patients with normal and altered liver function groups regarding creatinine, Alkaline phosphatase and Sodium.
In the current study the third and fourth wave, no statistically significant difference between hepatic and non hepatic groups regarding random blood sugar, ferritin, D-dimer and CRP (p > 0.05).
In agreement with the current study An et al., 7 reported that there was no statistically significant difference between COVID-19 patients with normal and altered liver function regarding Fasting Blood Glucose, and CRP.Patients with altered liver function tests showed significant elevation in INR compared to patients with normal liver function tests (p < 0.001).
Furthermore, Garrido et al., 8 reported that there was no statistically significant difference between COVID-19 patients with normal and altered liver function groups regarding CRP, D-dimer, Ferritin and INR.
At the third wave, hepatic patients showed significant elevation in AST and ALT compared to non hepatic patients (p < 0.001).No statistically significant difference between the two groups regarding serum albumin (p > 0.05).Results still the same during the fourth wave.
As well, Ferreira et al., 10 revealed that patients with altered liver function tests showed significant increase in AST compared to patients with normal liver function tests.There was no statistically significant difference between COVID-19 patients with normal and altered liver function regarding ALT and serum albumin (p > 0.05).The disagreement regarding ALT was due to the difference in inclusion criteria.
During the third wave, clexan was the most frequent drug used in 70.2% patients followed by dexamethasone in 55.6% patients then ceftriaxone in 44.4% patients.There was statistically significant difference between hepatic and non hepatic groups regarding treatment (p ¼ 0.033).
The study by Mendizabal et al., 11 revealed that a higher proportion of patients presenting abnormal liver biochemistry parameters on admission were under antibiotic treatment (P < .0001).During hospitalization, specific COVID-19 treatment was prescribed in 43.8% of the cohort (n ¼ 705) and was more commonly administered to patients with abnormal liver tests on admission (p < 0.0001).Other drugs frequently used for hospitalized patients with COVID-19, were also significantly more commonly prescribed to patients who presented abnormal liver biochemistry values on admission.
In our study, ground glass appearance was present in 64% patients for the third waves and 99.6% patients for the fourth waves.No statistically significant difference between the two groups regarding CT findings for third and fourth waves (p > 0.05).
An Egyptian review by Hefeda, 12 stated that CT plays a pivotal role in the diagnosis and management of COVID-19 pneumonia.The typical appearance of COVID-19 pneumonia is bilateral patchy areas of ground glass infiltration, more in the lower lobes.The appearance of other signs like consolidation, air bronchogram, crazy pavement appearance, and air bubble signs appear during the course of the disease.
Regarding third wave, 47% patients had mild to moderate symptoms while 53% of them had severe manifestation, during the fourth wave 10.3% patients had mild to moderate symptoms while 89.7% of them had severe manifestation.No statistically significant difference between the two groups regarding severity of COVID-19 for third and fourth waves (p > 0.05).
In agreement with our results Garrido et al., 9 revealed that there was no statistically significant difference between COVID-19 patients with normal and altered liver function regarding severity of COVID-19 (p > 0.05).Also, Marín-Dueñas et al., 13 there was no statistically significant difference between COVID-19 patients with normal and altered liver function regarding severity of COVID-19 (p > 0.05).
Regarding, No statistically significant difference between hepatic and non hepatic groups regarding mortality during third and fourth waves (p > 0.05).
In agreement with our results Garrido et al., 9 revealed that there was no statistically significant difference between COVID-19 patients with normal and altered liver function regarding mortality (p > 0.05).The total mortality rate was 22.8%.

Conclusion
Liver biochemical abnormality is more common in COVID-19 patients with liver cirrhosis.However, liver cirrhosis patients without COVID-19 have more hepatic decompensation events, so they should not be delayed from their hospitalization management during the COVID-19 pandemic.The presence of abnormal liver tests on admission was not associated with COVID-19 severity and mortality.Further well-designed large-scale studies should be necessary to validate these findings and establish the strategy for managing patients with SARS-CoV-2 infection and liver cirrhosis.

Table 2 .
Clinical history among the studied groups.
P 0.05 is considered statistically significant, P 0.01 is considered high statistically significant, SD ¼ standard deviation, comparison between groups done by ManneWhitney test and Chi-square test.

Table 3 .
Clinical presentation among the studied groups.

Table 1 .
Demographic characteristics among the studied groups.

Table 4 .
Comparison between the studied groups regarding vital signs.

Table 5 .
Comparison between the studied groups regarding CBC in 3rd wave.

Table 6 .
Comparison between the studied groups regarding renal function tests, ABG and serum electrolytes.

Table 7 .
Comparison between the studied groups regarding inflammatory markers.

Table 8 .
Urine analysis among the studied groups.

Table 9 .
Comparison between the studied groups regarding liver function in 3rd wave.

Table 10 .
CT among the studied groups.

Table 11 .
Management among the studied COVID-19 groups in 3rd wave.
P 0.05 is considered statistically significant, P 0.01 is considered high statistically significant, SD ¼ standard deviation, comparison between groups done by Chi-square test.

Table 12 .
Severity of COVID-19 among the studied groups.

Table 13 .
outcome of COVID-19 among the studied groups.

Table 14 .
Demographic characteristics among the studied groups.Table15.Clinical history among the studied groups in 4th wave.
P 0.05 is considered statistically significant, P 0.01 is considered high statistically significant, SD ¼ standard deviation, comparison between groups done by Chi-square test Table16.Clinical presentation among the studied groups in 4th wave.

Table 17 .
Distribution of the studied patients as per vital signs.

Table 18 .
Comparison between the studied groups regarding CBC in 4th wave.

Table 19 .
Comparison between the studied groups regarding renal function tests, ABG and serum electrolytes.

Table 20 .
Comparison between study group regarding other lab in 4th wave.

Table 21 .
Distribution of the studied patients as per liver functions.

Table 22 .
CT among the studied groups.
groups regarding mortality (p > 0.05).Significantly higher in 4th wave compared to results in 3rd wave (p ¼ 0.039).Normal liver function tests, AST & ALT were significantly higher in 4th wave compared to results in 3rd wave (p < 0.001).

Table 23 .
Severity of COVID-19 among the studied groups.

Table 25 .
Comparison between 3rd and 4th waves regarding liver function.