Liver Function Tests; a Marker of Severity in COVID-19
Patients

Ahmed M; Umar M; Sufyan A; Zeb S; Ahmad H; Shahid R; Aziz Q; Akram MO; Khan MM; Ahmed H

Research Article

Austin Hepatol. 2020; 5(1): 1013.

Liver Function Tests; a Marker of Severity in COVID-19 Patientss

Ahmed M¹*, Umar M², Sufyan A¹, Zeb S³, Ahmad H¹, Shahid R⁴, Aziz Q⁵, Akram MO⁶, Khan MM⁷ and Ahmed H¹

¹MBBS, Rawalpindi Medical University, Rawalpindi, Pakistan

²Vice Chancellor, Chief of Gastroenterology and Hepatology Division, Rawalpindi Medical University, Rawalpindi, Pakistan

³Department of Medical Education, Rawalpindi Medical University, Rawalpindi, Pakistan

⁴Department of Medical Education, Rawalpindi Medical University, Rawalpindi, Pakistan

⁵Consultant Internal Medicine, Rawalpindi Medical University, Rawalpindi, Pakistan

⁶Department of Medicine, Rawalpindi Medical University, Rawalpindi, Pakistan

⁷Department of Infectious Diseases, Rawalpindi Medical University, Rawalpindi, Pakistan

*Corresponding author: Muhammad Ahmed, MBBS, Rawalpindi Medical University, Rawalpindi, Pakistan

Received: May 25, 2020; Accepted: June 16, 2020; Published: June 23, 2020

Abstract

Background: The corona virus disease 2019 (COVID-19) begun as an outbreak in China in December 2019 and soon became a pandemic. The disease was previously unknown to humanity, hence its clinical aspects key to adequate assessment and management are yet evolving. An understanding to these is essential to ensure optimal patient directed care amid high burden of disease. Clinicopathological factors as Liver Function Tests might be a cornerstone in predicting the severity of disease.

Objectives: To assess for changes in Liver Function Tests in COVID-19 patients and its association with disease severity.

Methods: PCR confirmed COVID-19 patients with Liver Function Tests on presentation were enrolled at Allied Hospitals of Rawalpindi, Pakistan. Demographic data and Liver Function Tests were entered and analyzed. Descriptive statistics were applied and statistical tests were run to check for association with disease severity.

Results: Patients with higher age and comorbidities are more likely to develop severe disease. Liver Function Tests are more likely to be deranged in severe patients with AST levels significantly associated with disease severity.

Conclusion: Deranged Liver Function tests particularly AST levels may act as a marker of predicting severe COVID-19.

Keywords: COVID-19; SARS COV 2; Severity; Liver Function Tests; AST; Pakistan; Rawalpindi

Introduction

The corona virus disease 2019 (COVID-19) began as an outbreak in December 2019 in Wuhan, China [1]. The disease reported outside of China on January 13, 2020 [2]. Severe Acute Respiratory Syndrome Corona virus 2 (SARS-COV-2) being highly contagious turned out to be a worldwide threat and declared Pandemic by WHO on March 11, 2020 [3]. Apart from having high infectivity, the disease also carries a significant mortality varying from 4.1% in USA to 14.6% in Belgium [4,5,6]. Europe and America are carrying a high disease burden and consequently having its adverse economic and health sector effects [7]. This puts the third world countries that are relatively spared so far into a risk of developing an even worse potential crisis.

The corona viruses are known to humanity for quite a few decades [8,9,10]. There have been outbreaks previously reported as Severe Acute Respiratory Syndrome (SARS) and Middle East Respiratory Syndrome (MERS) [11,12,13,14]. However, SARSCOV- 2 is a strain completely new to mankind. Its epidemiological and clinicopathological aspects are rapidly evolving with each passing day. The initial patterns of disease were understood from case reports and a few small scale studies [15,16,17,18]. New trends are being established in the light of further studies and systematic reviews [19,20]. A considerable portion of patients who develop the disease are either asymptomatic or develop mild to moderate symptoms. These patients mainly require isolation and other precautionary measures so as to contain the spread. Indoor hospitalized care is not a necessity for most of these as they are clinically stable and no specialized monitoring or intervention has been proven to any benefit [21].

COVID-19 may be severe in around 30 % of patients calling for an observation in a health facility, with a fraction potential candidate for intensive care [22,23]. Under increasingly overwhelming COVID-19 burden on health care system ensuring patient focused quality of care based on disease severity is of utmost importance. Hence clinicopathological factors predictive of severity of disease would be a cornerstone in prioritizing resources effectively. The present study is designed to assess for accuracy of Liver Function Tests in defining the severity of COVID-19 and possible need for intensive care.

Objectives

To assess various risk factors determining severity of COVID-19, to investigate changes in Liver Function Tests and to assess its association with Severity of disease.

Materials and Methods

This was a cross sectional study conducted on patients quarantined at public sector hospitals affiliated with Rawalpindi Medical University, Rawalpindi from March 24 to April 20, 2020 after ethical approval from Institutional Research Forum, Rawalpindi Medical University. Patients were enrolled in this study via non probability consecutive sampling technique.

Figure 1: A comparison of Mean values of ALT, AST and Bilirubin among ATS Severe and Non-Severe COVID-19 patients. (ALT = Alanine Aminotransferase, AST = Aspartate Aminotransferase).

    
    
    Figure 1: A comparison of Mean values of ALT, AST and Bilirubin
among ATS Severe and Non-Severe COVID-19 patients. (ALT = Alanine
Aminotransferase, AST = Aspartate Aminotransferase).

A total of 44 patients were included with PCR positive for COVID-19 based on the World Health Organization guidelines with Liver Function Tests (LFTs) including Serum Alanine Aminotransferases (ALT), Aspartate Aminotransferases (AST) and Total Bilirubin performed on presentation. Patients with preexisting Liver diseases were excluded. Data was collected using structured proforma comprising of data regarding patient gender, age, contact history, comorbidities including Diabetes and Hypertension, serum ALT, AST and Bilirubin levels. Patient anonymity was maintained. Patients were grouped into Severe and Non-Severe based on American Thoracic Society (ATS) classification of Community acquired Pneumonia [24].

Categorical variables were described as frequency and percentages, and continuous variables as mean and Standard Deviation (SD). Means for continuous variables were compared using independent group t-tests. Comparison of categorical variables was done using Fisher exact test, if the cell counts were small. Logistic Regression was applied on significant association of continuous variables with severity. Data was entered and analyzed on Intel Business Machine Statistical Package for Social Sciences (IBM SPSS) version 25.

Results

A total of 44 PCR based confirmed COVID-19 patients were included in study with Liver Function Tests (ALT, AST, Bilirubin) performed. Mean age was 50.89 ± 18.04 years. 63.6 % (N = 28) patients were Male while 36.4% (N = 16) were Female. Based on ATS Classification 18.2 % (N = 8) patients were Severe while 81.8 % (N = 36) were Non-Severe. Regarding comorbidities 68.2% (N = 30) were normotensive and normoglycemic while 31.81% (N = 14) were diabetic and/or hypertensive (Table 1).

Mean Age among Severe patients (66.625 ± 14.4611 years) was higher than that of Non-Severe patients (47.3889 ± 17.001 years) (t (42) = 2.964, p = 0.005). Gender has no significant effect in determining disease severity (p = 0.689). Patients who are Hypertensive and/or Diabetic are more likely to develop Severe disease (p = 0.001). Mean ALT, AST and Bilirubin values for Severe patients (63.75 IU/L, 76.625 IU/L, 1.0625 mg/dl) were higher as compared to that of Non-Severe patients (41.6667 IU/L, 37.9524 IU/L, 0.5194 mg/dl), the relation was significant for AST and Bilirubin (t (27) = 3.819, p = 0.001)(t (42) = 2.667 p = 0.011) (Figure 1) (Table 2). By applying Logistic Regression analysis increase in Age was significantly associated with developing Severe disease (OR = 1.077, CI = 1.015 - 1.143, p = 0.014), similarly increase in AST levels were significantly associated with Severe disease (OR = 1.060, CI = 1.006 - 1.116, p = 0.027) (Table 3).

Table 1: Characteristics of Studied Patients.




  
    Variable
    %    (N)
  
  
    Gender
    
  
  
    Male
    63.6    (28)
  
  
    Female
    18.2    (8)
  
  
    Age    (years)
    
  
  
    Mean    (SD)
    50.89    (± 18.04)
  
  
    Comorbidities
    
  
  
    No    comorbidities
    68.2    (30)
  
  
    Diabetic    and/or Hypertensive
    31.8    (14)
  
  
    Contact    History
    
  
  
    Contact    with known or suspected case
    65.9    (29)
  
  
    No    contact
    34.1    (15)
  
  
    ATS*    Classification
    
  
  
    Severe
    18.2    (8)
  
  
    Non-Severe
    81.8    (36)

*ATS = American Thoracic Society



Table 1: Characteristics of Studied Patients.

Discussion

This is a Pakistan based study conducted on the very first COVID-19 patients presenting in Allied Hospitals of Rawalpindi Medical University. Various demographic factors were studies in comparison with the Severity of disease. Hepatic clinicopathological factors as ALT, AST and Bilirubin were studied as a possible link in developing severe disease. The associations were significant for age, comorbidities and AST levels.

The present study shows that COVID-19 was more common in men; however, the association was not statistically significant. A study based in China by Huang C et al. also demonstrated the prevalence of COVID-19 being more in men than women although the mechanism is still unclear [25].

Regarding age of hospitalized COVID-19 patients, the present study shows a mean age of 50.89 years. This is quite consistent with similar studies conducted in China where mean ages were 51 and 49.5 years respectively [26,27]. However, a French study showed a bit lower mean age of 45.1 years indicating relatively younger populations being affected and hospitalized in that region [28].

In our study, majority of patients were non-severe according to the community acquired pneumonia classification of American Thoracic Society (ATS). This is in accordance with a study conducted in Wuhan, China in which 68.29% patients were non-critical [25]. Majority of patients were also non-severe in another China based study [29].

A study conducted in Wuhan, China showed 32% of COVID-19 patients having comorbidities including diabetes (20%) and hypertension (15%) [25]. This seconds our findings that 31.8% patients were having comorbidities conditions. Another study showed that the most prevalent comorbidity was hypertension (16.9%), followed by diabetes (8.2%) [29].

Our study showed increasing the age, increases the risk for developing severe disease. A report by CDC United States also suggested that older age groups are more prone in progressing towards severe disease [30]. However, a study conducted in China showed that there was no statistically significant difference in age groups between severe and non- severe patients.25 Regarding gender this study showed that there was no significant effect of gender on disease severity which is quite consistent with the results of another study conducted in China [31].

Diseases such as diabetes, hypertension, respiratory system disease, cardiovascular disease and their susceptibility conditions may be linked to the pathogenesis of COVID-19. A study by Jin JM et al. significantly correlates the severity of COVID19 with the preexisting comorbid conditions which is in accordance with the results of our study [31]. Another study conducted in China showed the prevalence of hypertension and diabetes among severe patients as 30.8% which is almost equal to 31.8% comorbidities including Diabetes and Hypertension in our study [32].

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Citation:Ahmed M, Umar M, Sufyan A, Zeb S, Ahmad H, Shahid R, et al. Liver Function Tests; a Marker of Severity in Covid 19 Patients. Austin Hepatol. 2020; 5(1): 1013.

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Variable	Severe % (N)	Non-Severe % (N)	Total % (N)	p-value*
Gender	18.2 (8)	81.8 (36)	100 (44)	0.689**
Male	21.4 (6)	78.6 (22)	100 (28)
Female	12.5 (2)	87.5 (14)	100 (16)
Age (years)
Mean (SD)	66.63 (± 14.46)	47.38 (±17.00)	50.89 (± 18.04)	0.005***
Comorbidities	18.2 (8)	81.8 (36)	100 (44)	0.001**
No comorbidities	3.3 (1)	96.7 (29)	100 (30)
Diabetic and/or Hypertensive	50 (7)	50 (7)	100 (14)
Contact History	18.2 (8)	81.8 (36)	100 (44)
Contact with known or suspected case	13.8 (4)	86.2 (25)	100 (29)	0.414**
No contact	26.7 (4)	73.3 (11)	100 (15)
ALT (IU/L)
Mean (SD)	63.75 (± 42.52)	47.38 (± 27.56)	45.68 (±31.42)	0.072***
AST (IU/L)
Mean (SD)	76.62 (± 38.55)	37.95 (± 16.78)	48.62 (±29.70)	0.001***
Bilirubin (mg/dl)
Mean (SD)	1.0625 (± 1.12)	0.5194 (±0.28)	0.6182 (±0.56)	0.011***

Variable	Odds Ratio	Confidence Interval (95%)		p-value*
Variable	Odds Ratio	Lower value	Upper value	p-value*
Age	1.077	1.015	1.143	0.014
AST (IU/L)	1.06	1.006	1.116	0.027
Total Bilirubin (mg/dl)	6.595	0.622	69.969	0.117