Tinospora cordifolia (Guduchi/Giloy)-Induced Liver Injury: A Case Review.

Tinospora cordifolia (Guduchi/Giloy) is a relatively common herbal supplement whose use has recently become prominent in Southeast Asia. It was promoted to the public in India as an immunity booster, especially against the novel COVID-19. There have been reports, mostly from India, of an association between Guduchi/Giloy and liver injury. We present a 50-year-old female with a history of Hashimoto thyroiditis, who presented with abdominal discomfort and nausea of two weeks duration, which coincided with starting HistaEzeTM supplement containing Tinospora cordifolia. The vital signs upon presentation showed no significant abnormalities. Labs were significant for severely elevated transaminases; however, viral panels, autoimmune serologies, and imaging studies were unremarkable. Roussel Uclaf causality assessment method (RUCAM) score was at 6, which was indicative of probable drug/herb-induced liver injury. HistaEzeTM was discontinued, and the patient took a three-day course of oral steroids with significant interval improvement in clinical status, as evidenced by progressive normalization of the transaminases level. The transaminases decreased by greater than 50% within two weeks of discontinuation and trended back to baseline within three months. This case highlights the worldwide availability and use of Tinospora cordifolia, which can cause liver injury that appears to be idiosyncratic and possibly immune-mediated. Further research on the precise mechanism of its hepatotoxicity is warranted.

COVID-19 Presenting With Acute Anicteric Hepatitis in Pediatric Patient: A Case Report.

The impact that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has on the hepatobiliary system is poorly described in the pediatric population compared with the adult population. In adults, gastrointestinal symptoms and marked elevation in liver enzymes in the setting of coronavirus disease 2019 (COVID-19) has been directly correlated with disease severity. This case is a unique presentation of a pediatric patient with a relatively mild disease course despite the presence of gastrointestinal symptoms and marked elevation in transaminases, suggesting that SARS-CoV-2 virus may cause isolated acute hepatitis in pediatric patients.

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 Transaminases in Pediatric Adenovirus Infection-A Five-Year Study in Two Major Reference Centers from Romania.

Human adenovirus causes infections with a very heterogeneous clinical picture, and children are often the most frequently affected group. Interest in adenovirus has increased with the 2022 outbreak of severe acute hepatitis of unknown etiology as human adenovirus was considered as one of the possible etiological agents. We conducted a retrospective study over a 5-year period in two major tertiary hospitals in the Romanian capital with the aim to characterize the clinical picture and the dynamics of liver function tests in children with confirmed adenovirus infection. The study included 1416 children with a median age of 1.1 years (IQR: 0.3, 2.3 years). Digestive symptoms were predominant in 95.2% of children, mainly diarrhea (90.5%) and vomiting (50.5%), and 38.0% had respiratory symptoms. Increased transaminases were identified in 21.5% of patients. Age over 1 year, lethargy, vomiting and dehydration significantly increased the odds of liver cytolysis independent of other risk factors such as chronic conditions or co-infections. Aspartate aminotransferase (AST) was more commonly increased compared to alanine aminotransferase (ALT). Only six children had transaminase increases above 500 U/L, three of which had co-infections with rotavirus, Epstein-Barr virus (EBV), or respiratory syncytial virus (RSV). Liver function tests should be part of routine monitoring for pediatric patients with adenovirus infection. The current study fills a gap in current knowledge related to the frequency and the extent of liver involvement in human adenovirus infection among pediatric patients.

COVID-19-induced transaminitis and hyperbilirubinemia: Presentation and outcomes.

The risk of liver injury in patients with coronavirus disease 2019 (COVID-19) infection is quite evident. Furthermore, liver function test abnormalities are still detected in COVID-19 patients despite the development of antivirals and the availability of several types of vaccines. This editorial describes liver involvement during COVID-19 infection in patients with or without preexisting liver injury, such as chronic liver disease, to elucidate COVID-19-induced liver function abnormalities and their severity, pathophysiology, clinical manifestations, and clinical and laboratory outcomes. We also discuss the effect of vaccination against COVID-19 to better understand host factors, such as age, gender, and race, on the incidence and severity of liver dysfunction at initial presentation and during the illness. Finally, we summarize the results of relevant meta-analyses published to date and highlight the importance of adequate liver function monitoring in the current climate of the overwhelming COVID-19 pandemic.

COVID-19 and the liver: Are footprints still there?

The coronavirus disease 2019 (COVID-19) hit the entire world as a global pandemic and soon became the most important concern for all patients with chronic diseases. An early trend in higher mortality in patients with acute respiratory distress attracted all researchers to closely monitor patients for the involvement of other systems. It soon became apparent that patients with chronic liver diseases are at increased risk of mortality given their cirrhosis-associated immune dysfunction. Additionally, liver function abnormalities were noted in patients with severe COVID-19. Profound cytokine storm, direct viral infection, drugs and reactivation of viral infections were causes of deranged liver functions. Here, we discuss the relation between COVID-19 and chronic liver disease, specifically cirrhosis, hepatitis B, hepatitis C, and non-alcoholic fatty liver disease (NAFLD), as well as the liver manifestations of COVID-19. The metabolic syndrome, obesity, diabetes mellitus and NAFLD were found to worsen outcome in different studies reported worldwide. Decompensated cirrhosis should be considered a risk factor for death and severe COVID-19. Recently, COVID-19 related cholangiopathy has also been reported with changes of secondary sclerosing cholangitis. The long-term persistence of viral antigens in gut epithelia raises concern regarding the future risk of autoimmune liver diseases.

Prognostic performance of an index based on lactic dehydrogenase and transaminases for patients with liver steatosis and COVID-19.

BACKGROUND: Metabolic associated fatty liver disease (MAFLD) is associated with complications and mortality in patients with coronavirus disease 2019 (COVID-19). However, there are no prognostic scores aimed to evaluate the risk of severe disease specifically in patients with MAFLD, despite its high prevalence. Lactate dehydrogenase, aspartate aminotransferase and alanine aminotransferase have been used as markers of liver damage. Therefore, we propose an index based on lactate dehydrogenase, aspartate aminotransferase and alanine aminotransferase for the prediction of complications and mortality in patients with MAFLD and COVID-19. AIM: To evaluate the prognostic performance of an index based on lactate dehydrogenase and transaminases (aspartate aminotransferase/alanine aminotransferase) in patients with COVID-19 and MAFLD [liver fibrosis and nutrition (LNF)-COVID-19 index]. METHODS: In this retrospective cohort study, two cohorts from two different tertiary centers were included. The first was the derivation cohort to obtain the score cutoffs, and the second was the validation cohort. We included hospitalized patients with severe COVID-19 and MAFLD. Liver steatosis was evaluated by computed tomography scan. Area under the receiver operating characteristic (ROC) curve analysis and survival analysis were used. RESULTS: In the derivation cohort, 44.6% had MAFLD; ROC curve analysis yielded a LFN-COVID-19 index > 1.67 as the best cutoff, with a sensitivity of 78%, specificity of 63%, negative predictive value of 91% and an area under the ROC curve of 0.77. In the multivariate analysis, the LFN-COVID-19 index > 1.67 was independently associated with the development of acute kidney injury (odds ratio: 1.8, 95% confidence interval: 1.3-2.5, P < 0.001), orotracheal intubation (odds ratio: 1.9, 95% confidence interval: 1.4-2.4, P < 0.001), and death (odds ratio: 2.86, 95% confidence interval: 1.6-4.5, P < 0.001) in both cohorts. CONCLUSION: LFN-COVID-19 index has a good performance to predict prognosis in patients with MAFLD and COVID-19, which could be useful for the MAFLD population.

Hepatic Disorders in Adults Associated with the Use of Ivermectin for SARS-CoV-2 Infection: A Pharmacovigilance Study in VigiBase: An International Journal of Medical Toxicology and Drug Experience

Introduction: In the face of the global health emergency due to SARS-CoV-2, Ivermectin has been, among other drugs, repurposed in some Latin American countries to treat COVID-19 [1]. Studies are needed on the safety of Ivermectin for this new indication. VigiBase is the WHO pharmacovigilance database that registers all Individual Case Safety Reports (ICSRs) from more than 130 countries. Objective: To review in VigiBase the reports of serious hepatic disorders in adults associated with the use of Ivermectin for COVID19. Methods: We extracted, in men or women aged > 18 years between 1 January 2020 and 7 march 2021, all ICSRs registered as serious associated with the use of ivermectin, and established the prevalence of serious hepatic disorders when Ivermectin was indicated for COVID-19 Results: During the study period, there were 1,393 ICSRs in VigiBase associated with Ivermectin, of which 60 (4.3%) were registered as serious;in 25 of those, Ivermectin had been used for COVID-19. Out of those 25, five reported serious cases of hepatic disorders (hepatitis, hepatocellular injury, cholestasis, increased alanine aminotransferase and aspartate aminotransferase, abnormal liver function test). Three patients were male and overall mean age was 59.2 ± 9.7 years. Ivermectin was administered during a mean of 2.5 ± 2.4 days, and the mean daily dose was 14.3 ± 2.9 mg. Two patients simultaneously received other drugs (Remdesivir, Hydroxychloroquine, Azithromycin). Two patients had concurrent conditions (strongyloidiasis, diabetes mellitus). Only in 2 patients liver enzyme data were reported. In all patients the evolution was favorable after stopping the drug (de-challenge), and no patient was re-exposed (rechallenge). Causality analysis was reported in 3 cases, qualifying as possible or probable. Conclusion: The safety of the use of Ivermectin should be studied more exhaustively, especially as regards the probability of hepatic disorders when used for COVID-19

Cytolytic Hepatitis Following mRNA Vaccination: An International Journal of Medical Toxicology and Drug Experience

Introduction: A few months after the commercialization of the COVID-19 mRNA vaccine, published case reports started to open-eyed concerns about patients who presented autoimmune hepatitis (AIH) after receiving a COVID-19 vaccine [1-3]. Objective: We aim to describe cytolytic hepatitis following administration of the COVID-19 mRNA vaccine. Methods: We report a case of cytolytic hepatitis following administration of the COVID-19 mRNA vaccine notified to the National Center of Pharmacovigilance. Results: A 37-year-old man with no notable medical history was incidentally diagnosed with cytolytic hepatitis during his preoperative lab tests for acute appendicitis. Liver transaminases were thrice the upper limit. He had received his two doses of mRNA vaccine Moderna® two months before getting his lab tests. His serum immunoglobulins G, A, and M levels were within the normal range, and his immune lab tests were normal. Hepatitis serologies were negative. The abdominal ultrasound didn't demonstrate any abnormalities. The liver biopsy has revealed chronic active hepatitis lesions classified as F1A2. The patient had recovered spontaneously and had a normal liver transaminase level within 10 days. This case was scored I3 according to the french imputability updated method. Conclusion: Hepatitis following COVID-19 vaccination is an uncommon condition. Even if causality is still not proven clinicians must be vigilant for liver injuries in patients who have received COVID-19 vaccination.

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.

A Systematic Review of SARS-CoV-2-Associated Hepatic Dysfunction and the Impact on the Clinical Outcome of COVID-19.

Coronavirus disease 2019 (COVID-19) has rapidly spread across the globe since December 2019. The spectrum of clinical manifestations of COVID-19 ranges from mild to life-threatening forms. Alteration of hepatic function in COVID-19 is multifactorial. The objective of this systematic review is to assess the relationship between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-induced hepatic dysfunction and the clinical outcome in patients infected with COVID-19. We methodically explored several electronic databases (PubMed, PubMed Central, MEDLINE, and Google Scholar) in April 2022 using focused words and terms of medical subject headings for appropriate studies. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines for conducting our systematic review. Hepatic dysfunction was identified as elevation of liver function tests (LFTs) above the upper limit of normal. The clinical outcome was described as a combination of mortality, intensive care unit (ICU) transfer, and the need for mechanical ventilation (MV). The initial search yielded a total of 7187 studies. After elimination of duplicates, exclusion of studies based on irrelevant titles and abstracts, comprehensive analysis of full-text formats, and evaluation of quality, a total of 16 studies were eligible to be included in our systematic review. In the 16 selected studies, there were 23,962 patients. The SARS-CoV-2 virus can negatively affect several organ systems by interacting with specific receptors widely expressed in the human body. A multifactorial etiology of hepatic dysfunction is observed in COVID-19. SARS-CoV-2 infection is associated with abnormal LFTs. Significantly higher mortality, ICU admissions, and requirement for MV are associated with LFT alterations. For this reason, patients infected with COVID-19 must have their hepatic function closely monitored.

Serum hepatic biomarkers in women with obstetric cholestasis and a concurrent SARS-CoV-2 infection.

AIM: The aim of the study was to evaluate the association between SARS-CoV-2 infection and serum hepatic biomarker levels among women with obstetric cholestasis. METHODS: In this prospective study, we recruited all pregnant women admitted in our hospital with obstetric cholestasis. Among those with a concurrent SARS-CoV-2 infection, we evaluated the following serum hepatic biomarkers: aspartate aminotransferase (AST), alanine aminotransferase (ALT), and biliar acids (BA). RESULTS: Among the 88 women enrolled in the study, 20 presented with a SARS-CoV-2 infection while 68 were negative. SARS-CoV-2 infected women were younger (mean age 30.5 ± 5.7 vs. 34.3 ± 5.4; p < 0.01) and in a greater percentage of non-Caucasian ethnicity when compared to noninfected women (60.0% vs. 17.6%; p < 0.01). Regarding levels of hepatic biomarkers, they showed higher levels of AST (111.5 ± 134.1 vs. 37.3 ± 43.4 UI/L; p = 0.02), ALT (132.2 ± 115.7 vs. 50.5 ± 73.173.1 UI/L; p < 0.01), and BA (41.4 ± 46.8 vs. 18.4 ± 13.4 µmol/L; p = 0.04) compared to noninfected patients. No significant differences in maternal or fetal outcomes were found between infected and noninfected women. CONCLUSION: SARS-CoV-2 infection was associated with higher levels of liver enzymes in patients with obstetric cholestasis. This could be the result of a possible hepatic involvement in patients with SARS-CoV-2 infection.

COVID-19 and liver diseases, what we know so far.

Coronavirus disease 2019 (COVID-19) pneumonia outbreak started in December 2019. On March 12, 2020, the World Health Organization (WHO) declared that the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) constitutes a pandemic, and as of May 2021, SARS-CoV-2 has infected over 167.3 million patients, including 3.4 million deaths, reported to WHO. In this review, we will focus on the relationship between SARS-CoV-2 infection and the liver. We will discuss how chronic liver diseases affect the COVID-19 disease course and outcomes. We will also discuss the SARS-CoV-2 effects on the liver, mechanisms of acute liver injury, and potential management plans.

Elevated Transaminases as Predictors of COVID-19 Pneumonia Severity.

BACKGROUND: This study aimed to calculate the frequency of elevated liver enzymes in hospitalized patients with coronavirus disease 2019 (COVID-19) infection and to test if liver enzyme biochemistry levels on admission could predict the computed tomography (CT) scan severity score of bilateral interstitial pneumonia. METHODS: This single-center study comprised of 323 patients including their demographic data, laboratory analyses, and radiological findings. All the information was taken from electronic health records, followed by statistical analysis. RESULTS: Out of 323 patients, 115 of them (35.60%) had aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) over 40 U/L on admission. AST was the best predictor of CT scan severity score of bilateral interstitial pneumonia (R2 = 0.313, Adjusted R2 = 0.299). CT scan severity score in the peak of the infection could be predicted with the value of AST, neutrophils, platelets, and monocytes count (R2 = 0.535, Adjusted R2 = 0.495). CONCLUSION: AST, neutrophils, platelets, and monocytes count on admission can account for almost half (49.5%) of the variability in CT scan severity score at peak of the disease, predicting the extensiveness of interstitial pneumonia related to COVID-19 infection. Liver enzymes should be closely monitored in order to stratify COVID-19 patients with a higher risk of developing severe forms of the disease and to plan the beforehand step-up treatment.

Prognostic Value of Transaminases and Bilirubin Levels at Admission to Hospital on Disease Progression and Mortality in Patients with COVID-19-An Observational Retrospective Study.

INTRODUCTION: Given the impact of COVID-19 on the world healthcare system, and the efforts of the healthcare community to find prognostic factors for hospitalization, disease progression, and mortality, the aim of the present study was to investigate the prognostic impact of transaminases and bilirubin levels at admission to hospital on disease progression and mortality in COVID-19 patients. METHODS: Using the CoviCamp database, we performed a multicenter, observational, retrospective study involving 17 COVID-19 Units in southern Italy. We included all adult patients hospitalized for SARS-CoV-2 infection with at least one determination at hospital admission of aminotransaminases and/or total bilirubin. RESULTS: Of the 2054 patients included in the CoviCamp database, 1641 were included in our study; 789 patients (48%) were considered to have mild COVID-19, 347 (21%) moderate COVID-19, 354 (22%) severe COVID-19, and 151 patients (9%) died during hospitalization. Older age (odds ratio (OR): 1.02; 95% confidence interval (CI) 1.01-1.03), higher Charlson comorbidity index (CCI) (OR 1.088; 95%CI 1.005-1.18), presence of dementia (OR: 2.20; 95% CI: 1.30-3.73), higher serum AST (OR: 1.002; 95% CI: 1.0001-1.004), and total bilirubin (OR: 1.09; 95% CI: 1.002-1.19) values were associated with a more severe clinical outcome. Instead, the 151 patients who died during hospitalization showed a higher serum bilirubin value at admission (OR 1.1165; 95% CI: 1.017-1.335); the same did not apply for AST. DISCUSSION: Patients with COVID-19 with higher levels of AST and bilirubin had an increased risk of disease progression.

Elevated Liver Aminotransferases Level and COVID-19 Prognosis in Hospitalized Patients: A Prospective Study from Iran.

BACKGROUND: Considering the conflicting results and limited studies on the association between elevated liver enzyme levels and COVID-19 outcomes, in the present study, we aimed to investigate the association between hepatic enzyme changes and the prognosis of COVID-19 during hospital admission. METHODS: In this prospective study, 1017 consecutive patients with COVID-19 participated and were followed up from admission until they were discharged or deceased. The liver enzyme levels were recorded on admission. The patient/disease-related information was recorded by trained nurses using questionnaires. The primary endpoint was the association between elevated liver enzymes and liver injury and mortality from COVID. RESULTS: The mean age of the participants was 62.58±17.45 years; 55.4% of them were male. There was no significant difference between groups regarding the COVID-19 outcomes except for the need for ICU admission (P=0.02). Moreover, all COVID-19 outcomes were significantly higher in patients with liver injury compared with other patients except for the quick sequential organ failure assessment (qSOFA) score. After adjusting for covariates, the patients with Alanine aminotransferase (ALT) and Aspartate aminotransferase (AST) levels of more than 40 (IU/L) and participants with liver injury on admission had significantly greater odds of death, ICU admission, and mechanical ventilation requirements. CONCLUSION: The results of the present study support the hypothesis that poor outcomes of COVID-19 infection were higher in patients with elevated liver enzyme levels and liver injury. Therefore, liver chemicals should be closely monitored during the illness and hospital admission, and patients with COVID-19 and an elevated level of transaminases should be followed up carefully, and necessary interventions should be considered to prevent poor outcomes.

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.

COVID-19 and liver disease: Are we missing something?

Since the coronavirus disease 2019 (COVID-19) has hit the world as a pandemic, researchers all over the world have worked on its diagnostics, prognosticating factors, etc. The present study showed liver enzymes, especially aspartate aminotransferase (AST) levels, to be high in non-survivors with raised AST/alanine aminotransferase ratio. Considering the non-specific nature of AST with its presence in organs other than liver such as muscle, heart, kidney and brain makes it difficult to interpret. Even pre-existing metabolic syndrome and non-alcoholic fatty liver disease are confounding factors for deranged liver functions detected during COVID-19 disease. Therefore, the results of the study should be taken with caution.