ABSTRACT
The aim of the study was to assess the association of polymorphic variants CYP3A5*3 6986 A>G rs776746 and CYP3A4*22 rs35599367 C>T with the safety parameters of remdesivir therapy in patients with COVID-19. Material and methods. The study included 156 patients admitted to the City Clinical Hospital No. 15 of the Moscow Health Department with COVID-19 diagnosis, who received remdesivir as an antiviral drug. The frequency of adverse reactions (bradycardia, dyspeptic disorders), as well as various laboratory parameters (ALT, AST, creatinine, ferritin, interleukin-6, and d-dimer levels) were compared between the carriers of wild-type and polymorphic variants of the studied genes. Results. Carriers of CYP3A5*3 polymorphic variants (GA+AA) had higher ALT levels after the treatment with remdesivir than carriers of the wild variant (GG). When comparing the level of interleukin-6 after therapy with remdesivir, carriers of the polymorphic variant of the CYP3A4*22 (CT) gene had a significantly higher level of this cytokine. Conclusion. An association between the carriage of polymorphic variants of CYP3A5*3 and an increase in the level of liver enzymes was found. Polymorphic variants of CYP3A4*22 were associated with higher levels of interleukin-6. Additional pharmacogenetic studies are required to assess the possibilities of personalizing antiviral therapy for COVID-19.Copyright © Team of Authors, 2022.
ABSTRACT
Introduction and Objectives: Identifying independent risk factors for adverse outcomes in patients infected with severe acute respiratory syndrome coronavirus 2 can support prognostication, resource utilization, and treatment. The presenting symptoms of this virus are variable and the evolution and clinical significance of abnormal liver chemistries on outcomes in patients with coronavirus disease 2019 (COVID-19) is not well characterized. This study aimed to evaluate if aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels could predict disease severity in patients with COVID-19. Material(s) and Method(s): a retrospective, observational and cross-sectional study was carried out with data from the medical records of patients who had positive SARS-CoV2 nasal swabs, were over 18 years of age and were admitted consecutively and under free demand at a Brazilian academic hospital from April 1 to May 31, 2021. The characteristics of liver abnormalities and outcomes of patients with COVID-19 were compared. Result(s): altogether, 222 patients were enrolled, three patients with cirrhosis and 82% with abnormal liver chemistries during hospitalization. Of these, 20% showed transaminases >5 times the upper limit of normal (ULN). The most prevalent liver abnormality was AST. The increase in transaminases was directly proportional to the higher rates of intensive care unit admission, longer hospital stays, higher rates of vasoactive drug use and greater pulmonary involvement in its severe forms. We found that elevations of transaminases >5 times the ULN, at any time during hospitalization were associated with increased mortality. Conclusion(s): coronavirus 2 hepatitis may lead to poor outcomes in patients who are hospitalized for the disease. Therefore, monitoring liver chemistries, especially AST is necessary for hospitalized patients with COVID-19.Copyright © 2023
ABSTRACT
Background: Abnormalities in liver function tests (LFTs) are found in 14%-53% of hospitalized COVID-19 patients. These could occur in patients with or without previous chronic liver diseases. Knowing the risk factor of liver manifestations in COVID-19 subjects is crucial for the proper management of these patients. Objective(s): We aimed to identify the risk factors for liver manifestations as well as other risk factors in COVID-19 subjects who complained of digestive manifestations. Material(s) and Method(s): COVID-19 patients with and without liver manifestations at the Emergency Department of Al Fallujah Teaching Hospital were enrolled in this study. This study covered a period from September 15, 2022, to April 22, 2022. Comparisons between patients with or without abnormal LFTs were made. The possible risk variables connected to abnormal LFTs and hepatic manifestation were investigated using univariable and multivariable logistic regression analysis. Result(s): Out of 100 COVID-19 patients, there were 64 suffering from mild gastrointestinal (GI) symptoms. There were 26 mild cases with abnormal LFTs (40.6%). Although there were nine (total number 22) and seven (total number 14) of the moderate and severe cases with liver involvement, there was no statistically significant difference between the digestive manifestations severity and liver involvement. Increased alanine aminotransferase (ALT) levels were linked to a greater incidence of LFTs, according to multivariable analysis (odds ratio [OR]: 45.05;P < 0.0001), elevated aspartate aminotransferase (AST;OR: 3.462;P = 0.00041), elevated direct bilirubin (DBIL) (OR: 3.643;P < 0.001), and elevated d-dimer levels [OR]: 2.690;P < 0.0137) in liver involvement group compared with non-involvement patients. Conclusion(s): Elevated ALT, AST, DBIL, and d-dimer are potential risk factors for liver manifestations in COVID-19 patients with digestive symptoms.
ABSTRACT
Background: Azathioprine (AZA) is a recognised treatment option for maintaining remission in IBD patients. Myelotoxicity and abnormal liver function tests may present at any stage of therapy, therefore ECCO advises practitioners to check full blood count, liver and kidney function tests at 3-monthly intervals for patients established on therapy. During the COVID-19 pandemic, UK guidance suggested reducing blood test monitoring to a minimum safe frequency to facilitate 'shielding' of vulnerable patient groups. Patients established on treatment at St Mark's Hospital for more than 12 months, on stable doses were deemed eligible for extended blood monitoring intervals of 6-monthly. The aim of this audit was to assess the impact of this extension on patient safety, by measuring outcomes against locally agreed standards. Methods: All patients on AZA were identified using the pharmacy dispensing system and patient information software for blood test results, clinic letters and notes. Outcomes for patients who had extended blood monitoring were collected retrospectively including monitoring calls to the IBD advice line and any hospital admissions associated with therapy. Subsequent blood test results were also captured. Results: A total of 92 patient records were identified and analysed. Table 1 shows the achieved compliance (%) to the audit standards compared to the target compliance (%). 54% of patients (n=50) received medication that lasted beyond the standard 12-week validity of a blood test, i.e. had extended blood monitoring. Of those 50 patients, 43 were eligible for extended blood monitoring (86%). From 50 patients with extended blood monitoring, one patient had elevated alanine aminotransferase levels which improved after a one-week treatment break. Another patient called the IBD advice line reporting nausea and abdominal cramps due to treatment and was advised to split the dose and monitor for side effects. No patients were admitted to emergency care or hospital due to deranged blood test results or adverse effects from their medication. Conclusion: Overall the findings suggest that the temporary relaxation of blood monitoring did not adversely affect patient safety. For more comprehensive results, it would be prudent to repeat the audit using a larger sample size;however the audit has established a baseline at a time of unprecedented changes in the workplace, which will be useful in guiding future practice.