Liver function test (SGPT) abnormality in 319 confirmed COVID-19 cases in Bangladesh

Deranged liver function abnormalities are well-recognized sequela of COVID-19 infection. Globally, there are studies dedicated to evaluate spectrum of liver injury by COVID-19. In this study, we have described the impact of COVID-19 on liver function tests in 319 confirmed COVID cases in Bangladesh. Our study aimed to determine the liver function alteration by COVID-19 in our population. This study included all adult inpatients (> 18 years old) with laboratory-confirmed (RT-PCR) COVID-19 from March to April, 2020 in a tertiary COVID-dedicated hospital. We assessed liver function test and categorized patients according to COVID severity. This was a single-center, retrospective, observational study. Among 319 patients with COVID-19, 36% had normal and 64% had abnormal liver function test. Out of this, 18% had 1–2 times, 42% had 2–3 times, and 19% had > 3 times upper limit of normal SGPT during admission. Fifty-seven (18%) patients presented with mild illness, 83 (26%) with moderate, 124 (39%) patients with severe, and 54 (17%) with critical COVID-19 during admission. Significant correlation was found between severity of COVID-19 and raised SGPT level. More than half of patients presented during admission with abnormal liver function. COVID-19 has a significant impact on liver function derangement in this population.


Background
Since 2019 COVID-19 has claimed millions of lives until now.On 11th March 2020, the World Health Organization (WHO) declared COVID-19 a pandemic [1].It has only changed its name to Omicron in 2022 while the morbidity continued.The first COVID-19 case was detected in Bangladesh on March 8, 2020 [2].Besides the involvement of the lungs, COVID-19 can involve the liver as well.COVID-19 pathophysiology, disease progression, and optimal treatment are still under evaluation.Hepatic enzyme derangement is recognized as the most frequent extra-pulmonary manifestation of COVID-19 [3].It is postulated that liver impairment may be due to the direct cytotoxic injury to hepatocyte by virus or indirectly by hypoxia, hepatotoxic drug, or severe inflammatory response [4].Also, generalized inflammation and cytokine storm can cause multi-organ dysfunction including hepatic involvement [5,6].
Recent studies suggest that more than half of patients with COVID-19 have liver injury [3,7].Elevated SGPT was reported ranging from 14 to 53% [8].In Bangladesh, there are few studies to see the clinical profile of COVID cases [9,10] and the relationship of COVID-19 hospital duration on liver enzymes [11].The aim of this study was to see the spectrum of liver function tests and their relationship with the severity of COVID-19 patients in our population.

Methods
In this retrospective, single-center, observational study, we collected data from patients with COVID-19 who were admitted between March to April 2020.Demographic and clinical data were collected from hospital records onto a pre-defined spreadsheet.Diagnosis of COVID was based on clinical features (flu-like presentation, hypoxia, tachypnea, radiological findings) and RT-PCR test positive for COVID-19.COVID cases were clinically classified as mild, moderate, severe, and critical as defined in the Bangladesh national guideline on clinical management of COVID-19, version 8 [12].
Among the spectrum of liver function tests, we have picked SGPT only to assess liver injury to be focused.A patient was considered as having liver injury when alanine aminotransferase (ALT) or Serum glutamic pyruvic transaminase (SGPT) was more than 40 mU/ml.

Exclusion criteria
1. Patient with known chronic liver disease/preexisting liver disease 2. Patient taking alcohol 3. Patient on hepatotoxic drugs 4. Pregnancy
Statistical analysis was carried out using Statistical Package for the Social Sciences (SPSS version 23.0 for Windows) and Microsoft Excel 2016.All quantitative data such as age, hemodynamic, and laboratory parameters were estimated using mean ± SD.Categorical data were analyzed as numbers and percentages.Qualitative variables were described as proportions.For normally distributed data, means were compared using independent t test.Mann-Whitney U test was applied for statistical analysis of skewed continuous variables and ordered categorical variables.χ2 test was used to compare categorical data.P values < 0.05 were considered statistically significant.

Discussion
The present study was carried out on 319 COVID-19-positive patients admitted in a COVID-dedicated hospital.Several studies have described elevated liver panel in COVID-19 patients.Among them, alanine aminotransferase (ALT), aspartate aminotransferase (AST), Fig. 1 The clinical presentation of the study population with fever (88%), cough (67%), sore throat (27%), severe weakness (31%), and breathing difficulties (17%) and gamma-glutamyl transferase (GGT) are reported to be raised [13,14].We have chosen SGPT only among the liver function panel to be more specific and precise.
There is increasing evidence of direct, virally mediated liver injury caused by COVID-19 leading to enzyme elevation.But the causes of raised liver enzyme are multi-dimensional.Sepsis, ischemia, drug-induced liver injury, and host immune response are also contributing [15].Even long-term liver injury by COVID-19 is reported [16].We have taken liver function test sample on admission so that the effect of other contributing factors (sepsis, hospital drug treatment-antiviral, antibiotics, biologics) are minimal.
In our study, we found that more than half of our patients had an increased value of liver enzymes.A cohort study on 1059 patients in New York found that 62% presented with at least 1 elevated liver enzyme [17].A high prevalence of altered liver function test was noticed in Italian patients with COVID-19 [18].We got similar findings in all these studies.Hao et al. [19] found that 28.2% of patients with COVID-19 presented with elevated liver enzyme levels on admission which was less compared to our study.
In this study, SGPT was more raised in severe patients than in mild COVID patients.In a systematic review study, liver function test elevations were more frequent in those with severe disease [20].In a retrospective USA study of 2273 patients with COVID-19, 45% had mild liver injury, which was defined as levels of alanine aminotransferase (ALT) above the limit of normal (ULN) and below 2 times ULN.Liver injury was moderate (ALT between 2 and 5 times ULN) in 21% of cases and severe (above 5 times ULN) in 6.4% of cases.Patients with severe liver injury had a higher rate of intensive care unit admission [21].Our study came out to be supportive of those studies.Eighteen percent of our study population had 1-2 times, 42% had 2-3 times and 19% had > 3 times the upper limit of normal SGPT during admission.Out of 54 patients in the critical group 31 had SGPT > 3 Fig. 5 The correlation between severity of COVID 19 and SGPT. 1 = mild, 2 = moderate, 3 = severe and 4 = critical cases.SGPT was more raised in severe and critical group of patients Fig. 6 Receiver operating characteristic (ROC) curve to detect severity of disease by SGPT.The AUC (area under curve) is 0.83 which is statistically significant times ULN.SGPT was more raised in severe and critical group of patients which was statistically significant.Significant correlation was found between COVID-19 severity and SGPT elevation.
The limitation of the study is that being an observational, retrospective, and single-center study, may not reflect the whole population.Also, the follow-up of liver function tests during hospital stay was not included in the study that preclude the spectrum of liver injury related to COVID-19 treatment or sepsis.

Conclusion
The mechanism of liver injury by COVID-19 is multifactorial.Further clinical studies are required for better insight into the mechanism of liver damage in severe to critical COVID-19 patients.This study highlighted the short-term effect of COVID on the liver.Also, more studies with long-term follow-up are needed to see long-term effect on the liver by COVID-19 in COVID long haulers.