Serum total bilirubin and aminotransferases in patients with COVID-19 in Nellore district of South Andhra Pradesh

BACKGROUND: Corona virus disease-19 (COVID -19) infection is an acute infectious disease caused by a newly discovered beta corona virus, severe acute respiratory syndrome corona virus 2 (SARS-CoV-2). While the primary target organ is the lungs, involvement of many other organs is often evident in patients with COVID-19. There is emerging evidence to suggest association of SARS-CoV-2 infection with development of many liver abnormalities. The purpose of this study was to evaluate the prevalence of abnormal liver parameters in COVID-19 patients and their variation in moderate and severe cases. METHODS: This is a retrospective study. All patients with COVID -19, between the ages 20-75 years, encountered between April and May 2021, were included for the study and compared with age-matched controls. Severity of infection was defined based on the presence of symptoms, oxygen saturation, need for respiratory and intensive care support. Liver parameters such as serum total bilirubin (TBIL), serum aminotransferases, alanine aminotransaminase (ALT) and aspartate aminotransaminase (AST) were analysed. Inflammatory markers such as C-reactive protein (CRP) and D-dimer were also included for assay. RESULTS: A total of 52 patients were encountered during the study period. Of these, 29% (15/52) required intensive care. Abnormal liver parameters were observed in 14 (27%) patients, and were significantly elevated compared to healthy controls. Liver dysfunction was markedly profound in severe infection than those with moderate disease. Higher levels of CRP and D-dimer were noted in severe patients of COVID-19. CONCLUSIONS: Mild liver abnormalities in the form of elevated ALT and AST are seen in COVID-19 patients suggesting mild or no liver injury. These abnormal parameters do not generally lead to significant liver function impairment/failure and no specific treatment is required.

Liver Damage Associated with SARS-CoV-2 Infection-Myth or Reality?

(1) Introduction: While the primary impairment in COVID-19 is pulmonary, the ubiquitous distribution of angiotensin-converting enzyme 2 (ACE2) demonstrates the possible presence of systemic disease with involvement of the heart, kidneys, liver and other organs. (2) Methods: We retrospectively studied the observation sheets of patients diagnosed with SARS-CoV-2 infection hospitalized in the "Sf. Parascheva" Clinical Hospital of Infectious Diseases from Iasi for a period of 3 months. The aim of the study was to identify the frequency of liver injury due to SARS-CoV-2 infection among patients and its impact on the course of the disease. (3) Results: Out of the total number of hospitalized cases (1552), 207 (13.34%) were the subjects of our analysis. The severe form of SARS-CoV-2 infection predominated (108 cases; 52.17%) and in terms of liver damage, in all cases increased transaminase levels predominated and were determined to be secondary to the viral infection. We divided the lot into two groups, A (23 cases; 23.19%) and B (159 cases; 76.81%), depending on the time of onset of liver dysfunction, either at the time of hospitalization or during hospitalization. The evolution of liver dysfunction was predominant in most cases, with an average time of onset at 12.4 days of hospitalization. Death occurred in 50 cases. (4) Conclusions: This study revealed that high AST and ALT at hospital admission was associated with a high mortality risk in COVID-19 patients. Therefore, abnormal liver test results can be a significant prognostic indicator of outcomes in COVID-19 patients.

High serum transaminase due to COVID-19 infection

Although COVID-19 was first described as a respiratory disease, current data has shown that it is a disease with multisystemic involvement including respiratory, cardiovascular, gastrointestinal, neurological, hematological and immune systems. COVID-19 associated liver injury may be due to various potential mechanisms. Direct viral cytotoxic effect, immun mediated injury, drugs, ischemic injury due to hypoxia-hypoperfusion are among these mechanisms. Here we present a five year-old male patient who had no known history of liver disease admitted to our clinic due to elevated transaminase during the course of COVID-19 infection.

COVID-19 Enfeksiyonuna Bağlı Gelişen Serum Transaminaz Yüksekliği

Although COVID-19 was first described as a respiratory disease, current data has shown that it is a disease with multisystemic involvement including respiratory, cardiovascular, gastrointestinal, neurological, hematological and immune systems. COVID-19 associated liver injury may be due to various potential mechanisms. Direct viral cytotoxic effect, immun mediated injury, drugs, ischemic injury due to hypoxia-hypoperfusion are among these mechanisms. Here we present a five year-old male patient who had no known history of liver disease admitted to our clinic due to elevated transaminase during the course of COVID-19 infection.

Liver tests abnormalities with licensed antiviral drugs for COVID-19: a narrative review.

INTRODUCTION: Liver involvement in COVID-19 is multifactorial, and the three potential mechanisms are direct hepatocyte viral damage, vascular or cellular damage during the cytokine storm of severe COVID-19 and drug-induced liver injury. To date, three antivirals are licensed for the treatment of COVID-19 by most guidelines: remdesivir, molnupiravir, and ritonavir-boosted nirmatrelvir. AREAS COVERED: We performed a narrative review about the hepatic safety profile of the three antivirals licensed for COVID-19 treatment. We used data about hepatobiliary adverse events from English-language randomized clinical trials (RCTs). EXPERT OPINION: Remdesivir was found to be potentially hepatotoxic, and liver biochemistry abnormalities were common (2-34%) but mild and reversible. Molnupiravir exhibits a favorable safety profile and the increase in aminotransferases was usually mild and reversible (up to 11% of patients in one study). Ritonavir-boosted nirmatrelvir is potentially hepatotoxic, but in the only phase 3 RCT there were no safety issues and aspartate aminotransferase/alanine aminotransferase levels increase did not exceed 2.4% of patients. All antivirals have a favorable safety profile, but they are not sufficiently studied in patients with underlying chronic kidney or liver disease. In this special populations, antivirals should be used with caution and careful monitoring during treatment should be pursued on a case-by-case basis.

Predictive prognostic biomarkers in patients with COVID‑19 infection

The present study aimed to identify useful biomarkers to predict deterioration in patients with coronavirus disease 2019 (COVID‑19). A total of 201 COVID‑19 patients were classified according to their disease severity into non‑severe (n=125) and severe (n=76) groups, and the behavior of laboratory biomarkers was examined according to the prognosis. Neutrophil count, aspartate aminotransferase (AST), alanine aminotransferase, lactate dehydrogenase (LDH), C‑reactive protein (CRP), sialylated carbohydrate antigen KL‑6 (KL‑6), procalcitonin (PCT), presepsin (PSP) and D‑dimer levels were significantly higher, and lymphocyte count and platelet count were significantly lower in the non‑severe group compared with the severe group. In the non‑severe group, ROC analysis demonstrated that only four biomarkers, CRP, PSP, AST and LDH were useful for differentiating the prognosis between improvement and deterioration subgroups. No strong correlation was revealed for any of the markers. Multivariate analysis identified CRP as a significant prognostic factor in non‑severe cases (odds ratio, 41.45;95% confidence interval, 4.91‑349.24;P<0.001). However, there were no blood biomarkers that could predict the outcome of patients in the severe group. Overall, several blood markers changed significantly according to disease severity in the course of COVID‑19 infection. Among them, CRP, PSP, LDH and AST were the most reliable markers for predicting the patient's prognosis in non‑severe COVID‑19 cases.

Advances in acute severe hepatitis of unknown etiology in children

Since the International Health Regulations National Focal Point for the United Kingdom alerted the WHO of ten cases of acute severe hepatitis of unknown etiology in children on April 5, 2022, relevant cases have been reported worldwide. These patients had acute hepatitis (negative for hepatitis viruses A-E) and elevated aminotransferase (AST) or alanine aminase (ALT) exceeding 500 U/L. Furthermore, severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) and/or adenovirus type F41 have been detected in some cases. This unknown hepatitis has been hypothesized to be induced by a viral reservoir of novel coronavirus superantigen, which repeatedly stimulates the intestines and leads to a multisystem inflammatory syndrome in children (MIS-C), which causes immune abnormalities in the presence of human adenovirus. Although this hypothesis has not been confirmed by any in vivo experimental or clinical studies, it may provide ideas for possible intervention strategies.

Identification of High Death Risk Coronavirus Disease-19 Patients using Blood Tests.

Background: The coronavirus disease (COVID-19) pandemic has made a great impact on health-care services. The prognosis of the severity of the disease help reduces mortality by prioritizing the allocation of hospital resources. Early mortality prediction of this disease through paramount biomarkers is the main aim of this study. Materials and Methods: In this retrospective study, a total of 205 confirmed COVID-19 patients hospitalized from June 2020 to March 2021 were included. Demographic data, important blood biomarkers levels, and patient outcomes were investigated using the machine learning and statistical tools. Results: Random forests, as the best model of mortality prediction, (Matthews correlation coefficient = 0.514), were employed to find the most relevant dataset feature associated with mortality. Aspartate aminotransferase (AST) and blood urea nitrogen (BUN) were identified as important death-related features. The decision tree method was identified the cutoff value of BUN >47 mg/dL and AST >44 U/L as decision boundaries of mortality (sensitivity = 0.4). Data mining results were compared with those obtained through the statistical tests. Statistical analyses were also determined these two factors as the most significant ones with P values of 4.4 × 10-7 and 1.6 × 10-6, respectively. The demographic trait of age and some hematological (thrombocytopenia, increased white blood cell count, neutrophils [%], RDW-CV and RDW-SD), and blood serum changes (increased creatinine, potassium, and alanine aminotransferase) were also specified as mortality-related features (P < 0.05). Conclusions: These results could be useful to physicians for the timely detection of COVID-19 patients with a higher risk of mortality and better management of hospital resources.

Impact of Liver Functions by Repurposed Drugs for COVID-19 Treatment.

Liver injury is an important complication that may arise in patients suffering from coronavirus disease 2019 (COVID-19) and is accompanied by a transient increase of transaminases and/or other liver enzymes. Liver function test (LFT) abnormalities generally disappear when the COVID-19 resolves or hepatotoxic drugs are discontinued. The LFT abnormalities are associated with drug-induced liver injury (DILI), due to the overuse of antimalarials, antivirals, and antimicrobials. Studies have reported varying levels of these liver injuries in COVID-19 patients; however, most involve elevated serum aminotransferases. Hepatic dysfunction is significantly high in patients with severe illness and has poor outcome. Normally, the liver is involved in the metabolism of many drugs, including nucleoside analogs and protease inhibitors, which are currently repurposed to treat COVID-19. In addition to the manifestation of COVID-19, drugs implemented in its treatment may aggravate liver injuries. Thus, DILI should be considered especially in those COVID-19 patients with underlying liver disease. It was unclear whether the elevated liver enzymes have originated from the underlying disease or DILI in this population. Furthermore, it is difficult to establish a direct relationship between a specific drug and liver injury. Another possible effect of liver damage may due to inflammatory cytokine storm in severe COVID-19. Liver injury can change metabolism, excretion, dosing, and expected concentrations of the drugs, which may make it difficult to achieve a therapeutic dose of the drug or increase the risk of adverse effects. These repurposed drugs have shown limited efficacy against the virus and the disease itself; however, they still pose risk of adverse effects. Careful and close monitoring of LFTs in COVID-19 patients can provide early diagnosis of liver injury, and the risk of DILI could be reduced. Also, drug interactions in liver-transplanted patients should always be kept in mind for certain immunosuppressive therapies and their known signs of DILI. Altogether, abnormal LFTs should not be regarded as a contraindication to use COVID-19 experimental therapies if needed under emergent status.

Effect of favipiravir and standard COVID-19 therapy on amino transferase in a sample of Iraqi COVID-19 patients

Background: COVID-19 is a condition that can proceed in a broad spectrum from asymptomatic moderate sickness to severe lung disease. Hepatic harm in COVID-19 may arise owing to the direct cytopathic action of the virus, uncontrolled immunological response, hypoxia related to pneumonia, and the medications used in therapy. In the literature, the rate of rise in blood transaminase levels of patients hospitalized with COVID-19 was determined to be 37.5%. Also, rise in serum transaminase levels in COVID-19 patients has been shown to be related with higher mortality in the literature. Favipiravir is a ribonucleic acid (RNA)-dependent RNA polymerase (RdRP) inhibitor antiviral drug used in the treatment of coronavirus disease-2019 (COVID-19) Aims: In this study, we investigated the changes in serum transaminase levels of patients who were hospitalized with the diagnosis of COVID-19 and underwent favipiravir therapy. Materials and methods: case-control research was done. It was done in a multi-hospital of Baghdad city over the period from November 1, 2020, to August 1, 2021. All patients in this study were hospitalized patients with polymerase chain reaction identified Coronavirus illness 2019 (severe cases) according to Iraqi criteria and supervision of a professional.

Mortality in patients hospitalized with COVID-19 in northern Peru

Background: Peru has one of the highest mortality rates due to COVID-19 in the world. Aim: To describe the clinical features, evolution and explore factors associated with mortality in patients with moderate to severe Covid-19. Material and Methods: Prospective analytical study. The clinical, laboratory, imaging, and mortality data of patients admitted at a COVID service of the Santa Rosa de Piura Hospital were recorded from April to June 2020.

Longitudinal progression of clinical variables associated with graded liver injury in COVID-19 patients.

BACKGROUND: Hospital-acquired liver injury is associated with worse outcomes in COVID-19. This study investigated the temporal progression of clinical variables of in-hospital liver injury in COVID-19 patients. METHODS: COVID-19 patients (n = 1361) were divided into no, mild and severe liver injury (nLI, mLI and sLI) groups. Time courses of laboratory variables were time-locked to liver-injury onset defined by alanine aminotransferase level. Predictors of liver injury were identified using logistic regression. RESULTS: The prevalence of mLI was 39.4% and sLI was 9.2%. Patients with escalated care had higher prevalence of sLI (23.2% vs. 5.0%, p < 0.05). sLI developed 9.4 days after hospitalization. sLI group used more invasive ventilation, anticoagulants, steroids, and dialysis (p < 0.05). sLI, but not mLI, had higher adjusted mortality odds ratio (= 1.37 [95% CI 1.10, 1.70], p = 0.005). Time courses of the clinical variables of the sLI group differed from those of the nLI and mLI group. In the sLI group, alanine aminotransferase, procalcitonin, ferritin, and lactate dehydrogenase showed similar temporal profiles, whereas white-blood-cell count, D-dimer, C-reactive protein, respiration and heart rate were elevated early on, and lymphocyte and SpO2 were lower early on. The top predictors of sLI were alanine aminotransferase, lactate dehydrogenase, respiration rate, ferritin, and lymphocyte, yielding an AUC of 0.98, 0.92, 0.88 and 0.84 at 0, - 1, - 2 and - 3 days prior to onset, respectively. CONCLUSIONS: This study identified key clinical variables predictive of liver injury in COVID-19, which may prove useful for management of liver injury. Late onset of sLI and more aggressive care are suggestive of treatment-related hepatotoxicity.

Liver injury predicts overall mortality in severe COVID-19: a prospective multicenter study in Brazil.

BACKGROUND/PURPOSE: The relationship between liver injury and mortality remains unclear in patients with COVID-19. We aimed to evaluate the prognostic value of aminotransferases levels at hospital admission to predict mortality in patients with COVID-19. METHODS AND RESULTS: This prospective study included 406 patients [57% male, aged 56 years] with COVID-19 hospitalized in 26 centers in Brazil. Overall, 36.7% (95% CI 32.1-41.5) presented at admission with severe disease requiring respiratory support. The prevalence of elevated ALT and AST levels at admission [> 2 × ULN] was 14.0% (95% CI 11.0-17.8) and 12.9% (95% CI 10.0-16.6), respectively. Sixty-two patients [15.3% (95% CI 12.1-19.1)] died during hospitalization and the overall mortality rate was 13.4 (10.5-17.2) deaths per 1000 persons-years. The 15-day-overall survival (95% CI) was significantly lower in patients with ALT levels ≥ 2 × ULN compared to those with ALT < 2 × ULN [67.1% (48.4-80.2) vs 83.4% (76.1-88.6), p = 0.001] and in those with AST levels ≥ 2 × ULN compared to those with AST < 2 × ULN [61.5% (44.7-74.6) vs 84.2% (76.5-89.5), p < 0.001]. The presence of elevated aminotransferases levels at hospital admission significantly increased the risk of in-hospital all-cause mortality adjusted for age-and-sex. Those findings were present in the subgroup of critically ill patients already admitted in need of respiratory support (n = 149), but not in patients without that requirement at admission (n = 257). CONCLUSIONS: Elevated aminotransferases at hospital admission predicted in-hospital all-cause mortality in patients with COVID-19, especially in those with severe disease. Measurement of transaminases levels at hospital admission should be integrated to the care of patients with COVID-19 as an auxiliary strategy to identify patients at higher death risk.

Aminotransferases disorders associated with venous thromboembolic events in patients infected with COVID-19.

INTRODUCTION AND OBJECTIVES: Since the outbreak of the COVID-19 pandemic, increasing evidence suggests that infected patients present a high incidence of venous thromboembolic (VTE) events and elevated aminotransferases (AT).The objective of this work was to evaluate the incidence of aminotransferases disorders in patients infected with COVID-19 and to manage the VTE events associated with elevated AT. PATIENTS OR MATERIALS AND METHODS: We report a retrospective study of 46 patients admitted for COVID-19 infection. Venous duplex ultrasound of lower limbs was performed in all patients at Day 0 and Day 5. All patients had antithrombotic-prophylaxis upon admission using low molecular weight heparin with Enoxaparin. Demographics, comorbidities and laboratory parameters were collected and analyzed. RESULTS: Elevated AT were reported in 28 patients (61%). 10 had acute VTE events of which eight (17.4%) had aminotransferases disorders. They had been treated with curative Enoxaparin. After a follow-up of 15 and/or 30 days, six of them were controlled, and treated with direct oral anticoagulant (DOACs) after normalization of aminotransferases. CONCLUSIONS: The incidence of aminotransferases disorders associated with acute VTE events in patients infected with COVID-19 is significant. The use of DOACs appear pertinent in these patients. Monitoring of the liver balance should therefore be considered at a distance from the acute episode in the perspective of DOACs relay.

A systematic review and meta-analysis of the COVID-19 associated liver injury.

INTRODUCTION AND OBJECTIVES: The novel coronavirus disease 2019 (COVID-19) has affected more than 5 million people globally. Data on the prevalence and degree of COVID-19 associated liver injury among patients with COVID-19 remain limited. We conducted a systematic review and meta-analysis to assess the prevalence and degree of liver injury between patients with severe and non-severe COVID-19. METHODS: We performed a systematic search of three electronic databases (PubMed/MEDLINE, EMBASE and Cochrane Library), from inception to 24th April 2020. We included all adult human studies (>20 subjects) regardless of language, region or publication date or status. We assessed the pooled odds ratio (OR), mean difference (MD) and 95% confidence interval (95%CI) using the random-effects model. RESULTS: Among 1543 citations, there were 24 studies (5961 subjects) which fulfilled our inclusion criteria. The pooled odds ratio for elevated ALT (OR = 2.5, 95%CI: 1.6-3.7, I2 = 57%), AST (OR = 3.4, 95%CI: 2.3-5.0, I2 = 56%), hyperbilirubinemia (OR = 1.7, 95%CI: 1.2-2.5, I2 = 0%) and hypoalbuminemia (OR = 7.1, 95%CI: 2.1-24.1, I2 = 71%) were higher subjects in critical COVID-19. CONCLUSION: COVID-19 associated liver injury is more common in severe COVID-19 than non-severe COVID-19. Physicians should be aware of possible progression to severe disease in subjects with COVID-19-associated liver injury.

Alteration of Liver Biomarkers in Patients with SARS-CoV-2 (COVID-19).

INTRODUCTION: Coronavirus disease 2019 (COVID-19) emerged in China and spread worldwide. In this study, we assessed the characteristics of markers of the liver in patients with COVID-19 to provide new insights in improving clinical treatment. PATIENTS AND METHODS: We recruited 279 patients who confirmed COVID-19 and the data of liver biomarkers and complete blood count of patients were defined as the day onset when the patients admitted to the hospital. RESULTS: The average of LDH value was 621.29 U/L in all patients with COVID-19, and CPK was 286.90 U/L. The average AST was 44.03 U/L in all patients, and ALT was 31.14 U/L. The AST/ALT ratio was 1.64 in all patients. The measurement of CRP was increased by 79.93% in all patients. Average ALT and AST values of patients with elevated ALT were significantly increased in comparison to patients with normal ALT (P-value = 0.001), while AST/ALT ratio was significantly decreased compared to patients with normal ALT (P-value= 0.014). In addition, the average LDH of patients with elevated ALT was significantly increased compared to patients with normal ALT (P-value = 0.014). CONCLUSION: Hepatic injury and abnormal liver enzymes related to COVID-19 infection is an acute non-specific inflammation alteration.