Supplement Gone Wrong: Drug-Induced Liver Injury Caused by Artemisinin

Introduction: Drug-induced liver injury (DILI) is defined as hepatic dysfunction caused by prescription medications, supplements, or xenobiotics after alternative causes have been excluded. As one of the leading causes of acute liver failure, DILI should be considered when patients present with hepatic dysfunction. We present a case of symptomatic DILI secondary to artemisinin use. Case Description/Methods: A 78-year-old Chinese man with no medical history presented to the hepatology clinic with 10 weeks of jaundice, weakness, and pruritis. He started taking Artemisinin/ Bioperine 12 weeks ago to prevent COVID-19 but stopped 3 weeks ago. He denied abdominal pain, a family history of liver disease, substance/alcohol use, and taking other concomitant drugs. Physical examination revealed scleral icterus and no other signs of chronic liver disease. Laboratory studies showed total bilirubin 11 mg/dL, alkaline phosphatase 293 U/L, aspartate transaminase 170 U/L, and alanine transaminase 196 U/L with negative workup for hepatitis A, B, and C. CT abdomen and MRCP were unremarkable for liver or biliary pathology. Further serological workup was negative and follow-up labs revealed normalization of liver enzymes and bilirubin. Given the patient's improvement, liver biopsy was not pursued. The patient was instructed to avoid supplements unless prescribed by a physician. Discussion(s): DILI is a global issue with an estimated annual incidence rate of 13.9 to 24.0 per 100,000 persons. Diagnosing DILI is important as it can cause acute liver injury and liver failure in certain cases. Since COVID-19 emerged, supplement use has increased given claims of boosting the immune system. Artemisinin is an herb used in traditional Chinese medicine with antimalarial activity investigated to be a possible COVID-19 treatment, but no current evidence exists to support it being effective against COVID-193. Our patient's supplement also contained Bioperine, a black pepper extract, which is likely benign. Contrarily, artemisinin is a well-described cause of idiosyncratic acute liver injury and hepatotoxicity, causing self-limited mild to moderate transaminitis but also severe cases requiring emergent livertransplantation. Our patient's unrevealing workup, his spontaneous improvement correlating with supplement discontinuation, and RUCAM score of 7 led to high suspicion of DILI secondary to artemisinin. Providers should always ask patients about supplement use and consider DILI when patients present with liver injury. (Table Presented).

Bupivacaine-Induced Hepatotoxicity in a Healthy Patient Without Chronic Liver Disease After Shoulder Arthroscopy

Introduction: Bupivacaine is a local anesthetic which has been increasingly used in the post-operative state for pain control. Hepatotoxicity is a rare complication, and few cases are reported in patients with chronic liver disease. We present a case of acute liver injury from bupivacaine use in a healthy patient without prior history of liver disease. Case Description/Methods: A 68-year-old female with a past medical history of primary hypertension and recent nontraumatic complete tear of the right rotator cuff, presents to the hospital with fatigue, loss of appetite, and nausea. She recently underwent an arthroscopy of the right shoulder with repair of the rotator cuff two weeks prior. Her surgery was uncomplicated, and patient was started on bupivacaine ONQ pump infusion at 5 ml/hr for three days for post-operative pain. Further history reveals patient is non-alcoholic without prior liver disease, including cirrhosis. Review of systems is concerning for associated generalized abdominal discomfort. Physical exam demonstrated jaundice with scleral icterus with mild periumbilical tenderness to palpation without hepatosplenomegaly or ascites. Labs demonstrated elevated total bilirubin of 10.2 mg/dL with Alkaline phosphatase, ALT, and AST being 924 U/L, 429 U/L, and 279 U/L, respectively. Imaging studies including CT abdomen and pelvis with contrast, abdominal ultrasound, MRCP, and portal vein doppler were negative. Additional work up for underlying liver disease including acetaminophen and ethanol levels, SARS-CoV2, Hepatitis panel, EBV antigen, and urine toxicology were negative. It was determined patient had bupivacaine induced hepatotoxicity. Patient's health improved with conservative management and she was discharged with instructions for close monitoring of her LFTs. Discussion(s): Bupivacaine is an amino-amide anesthetic which binds to the intracellular portion of voltage-gated sodium channels and prevents depolarization of pain signals. It is metabolized by the liver and thus reports of hepatotoxicity, although rare, occur in patients with underlying liver pathology. Our patient became symptomatic with acute rise in LFTs. An extensive workup for other etiologies of acute liver toxicity was negative. Rapid vascular uptake of the drug is the most common reason for bupivacaine toxicity;and this remains a possibility for the mechanism of toxicity in our patient. A prior case report of bupivacaine hepatotoxicity demonstrated a cholestatic pattern, which is consistent with our findings.

Hepatotoxicity From Marijuana Gummies

Introduction: We report a case of drug-induced liver injury (DILI) induced by cannabis gummies containing Corydalis Rhizome. Case Description/Methods: A 37-year-old female presented to her primary care clinic with recurrent fevers, night sweats, and myalgias for 7 weeks accompanied by eye redness, brain fog, headache, nausea, and abdominal pain. She denied rashes, tick-bites, cough, dyspnea, chest pain, joint swelling, or genitourinary symptoms. Past medical history was notable for IBS, migraines, and anxiety. She reported edible marijuana use four times a week, rare alcohol use, and denied tobacco use. She denied a family history of liver disease. Physical exam was notable for tachycardia to 110 and scleral injection with the remainder of vitals and exam unremarkable. Initial labs were notable for AST 61, ALT 44 and CRP of 12. CBC, BMP, urinalysis, ESR, blood cultures, blood smear for parasite screen, tests for Lyme disease, Babesia, Tularemia, Anaplasma, Ehrlichia, Rickettsia, EBV, HIV, RPR, ANA, CMV, parvovirus B19, and chest x-ray were all negative. The patient was referred to infectious disease with further testing for West Nile, Leptospira, lymphocytic choriomeningitis virus, and COVID-19 returning negative. Repeat LFTs showed worsening transaminitis with ALT 979 and AST 712, alkaline phosphatase 88, total bilirubin 0.7, and albumin 4.9. Hepatitis workup including hepatitis A, B, and C, HSV, EBV, VZV serologies, AMA, ASMA, antiLKM Ab, acetaminophen level, INR, iron panel, CPK, TSH, and abdominal ultrasound were all normal. It was later discovered that her marijuana gummies contained Corydalis rhizome extract known to be hepatotoxic. Cessation of this drug was strongly advised. She was discharged with hepatology follow-up and underwent a liver biopsy showing patchy periportal and lobular inflammation with extension across the limiting plate, hepatocyte injury and apoptosis, and increased lipofuscin for age compatible with mild to moderate hepatitis. She had complete recovery after cessation of Corydalis-containing gummies. (Figure) Discussion: Our patient consumed '1906 Midnight', an American cannabis brand containing Corydalis rhizopus 100 mg, advertised to improve sleep, pain, and have a liver protective effect. A Korean systematic review on herbal-induced liver injury reported that Corydalis was the 3rd most frequent causative herb, with 36 cases. Although there are several personal accounts on social networking sites and other websites, there are no American-based publications reported on DILI from Corydalis. (Table Presented).

A Randomized Trial on Early Therapy in Covid-19 High-Risk Outpatients in Omicron Era

Background: Antivirals and monoclonal antibodies (mAbs) were approved for early treatment of COVID-19 based on data from trials conducted in unvaccinated people before the Omicron era. The comparative effectiveness of different treatments is unknown. We present the results of the interim analysis of MONET trial (EudraCT: 2021-004188-28). Method(s): In this ongoing multicenter, open-label, phase 4 trial, we randomly assigned, in a 1:1:1 ratio, non-hospitalized patients with early symptomatic Covid-19 (<=5 days after symptoms onset) and >=1 risk factor for disease progression, to receive 500 mg of intravenous sotrovimab (SOT) or 600 mg of intramuscular tixagevimab/cilgavimab (TIX/CIL) or oral 5-days course of NMV/r 300/100 mg BID. Primary outcome was hospitalization or death for any cause within 29 days after randomization, reported as cumulative incidence per 100 (95% CI), and P-value calculated by Fisher's exact test. Inflammatory marker (CRP, d-dimer, and neutrophils-to-lymphocytes ratio) and antibody level (serum anti-S IgG and anti-N IgG) analysed by mixed linear regression with random intercept and P-values for time trend calculated by ANOVA-style test with Bonferroni correction. Result(s): Prespecified interim analysis, including 400 patients (SOT =133, TIX/ CIL=130, NMV/r=137) enrolled from Mar 4 to Nov 16, 2022 (Fig.1A). Overall, 5 pts (3/5 immunosuppressed) had disease progression leading to hospitalization [1.25% (95% CI 0.4%-2.89%)], 1 in SOT (0.75%, 95% CI 0.01%-4.1%), 4 in TIX/CIL (3.08%, 95% CI 0.84%-7.69%) and none in NMV/r arm (P=0.030). No deaths or ICU admissions were observed. Among the hospitalized pts, 3 were infected with BA.2 (1 SOT, 2 TIX/CIL), one with BA.4/5, and one BQ.1.1 (both TIX/ CIL). No serious adverse events and no kidney or liver toxicity were reported. Temporal trend of inflammation markers was similar in the three arms, and their estimates are shown in Fig.1B. Kinetics of antibody was reported in Fig.1C. The plot shows a rapid increase of anti-S in both mAb arm and a linear increase of IgG in the NMV/r arm. Anti-N IgG kinetics was similar in the three arms. Conclusion(s): By these data the overall cumulative risk of clinical failure in mild Covid-19 occurring in the Omicron era is low. The hypothesis that differences in clinical progression among the three arms could be related to different activity against the Omicron subvariant observed in vitro should be further investigated. Type of treatment does not seem to influence the development of the natural antibody response.

Interpretation of Hepatotoxic Side Effects by Rcv (Reference Change Value) in Covid-19 Patients Treated with Favipiravir

Objectives: Favipiravir was first used against SARS-CoV-2 in Wuhan at the very epicenter of the pandemic. Its side effects include hyperuricemia, decreased neutrophil counts, diarrhea, and increased alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkalen phospatase ALP, bilirubin. Reference change value (RCV) represents the clinical significance of the variation between the RESULTS of two consecutive tests and laboratory test results exceeding this value are associated with the individual's disease status. In this study, we evaluated the side effects of favipiravir treatment on AST and ALT using RCV. Materials-Methods: We examined retrospectively 40 patients were administered 1600 mg of favipiravir twice daily on day 1, followed by 600 mg twice daily from day 2 to day 5 (or more if needed). The analytic coefficient of variation (CVA:0,47 for AST 0,42 for ALT) was calculated from internal quality control RESULTS. Intra-individual coefficient of variation (CVI) and inter-individual coefficient of variation (CVG) were obtained from Westgard's website, which was updated in 2014.The RCV% is calculated with the following formula Zx21/2x[CVA2+CVI2]1/2 (Using an unidirectional probability of 95%, Z=1.65). Result(s): The RCV% results were calculated as %28 for AST and % 45 for ALT.The individuality index (II) was calculated as 0.532 for AST and 0.466 for ALT. ALT and AST values were evaluated as higher than the calculated RCV value in 70%,62,5% of the patients. Conclusion(s): The use of RCV is recommended as a valuable tool in the follow-up of patient results and side effects of treatment.

Medicinal bismuth: Bismuth-organic frameworks as pharmaceutically privileged compounds

Historically organometallic compounds have been used to cure certain diseases with limited applications. Although bismuth belongs to the category of heavy metals, many of its derivatives have found applications in modern drug discovery research, mainly because of its low toxicity and higher bioavailability. Being an eco-friendly mild Lewis acid, compounds having bismuth as a central atom are capable of binding several proteins in humans and other species. Bismuth complexes demonstrated antibacterial potential in syphilis, diarrhea, gastritis, and colitis. Apart from antibacterial activities, bismuth compounds exhibited anticancer, antileishmanial, and some extent of antifungal and other medicinal properties. This article discusses major synthetic methods and pharmacological potentials of bismuth complexes exhibiting in vitro activity to significant clinical performance in a systematic and timely manner.Copyright © 2022 Elsevier Ltd

In Silico Analysis of Bioactive Compounds from Sea Urchin (Echinometra mathaei) against SARS-COV-2

SARS-CoV-2 is a kind of coronavirus that produces Covid-19 illness, which is still a public health concern in Indonesia. Meanwhile, an effective drug has not yet been found and although vaccination has been carried out, in several regions and neighboring countries there is still an increase in Covid-19 cases. This study aimed to obtain bioactive compounds from sea urchins (Echinometra mathaei) that have greater antiviral potential and lower toxicity than remdesivir. This research was started by predicting druglikeness with SwissADME, followed ADMET predicition with pkCSM online, and docking of molecule using the Molegro Virtual Docker (MVD) 5.5 software against the main protease (Mpro) target (PDB ID: 6W63). The results showed that six compounds from sea urchins (Echinometra mathaei) had antiviral activity, where the bioactive compound from sea urchins (Echinometra mathaei) with the highest affinity was shown by Spinochrome C a smaller rerank score compared with Remdesivir and native ligand (X77). So that Spinochrome C compounds are candidates as SARS-CoV-2 inhibitors potential developed drug.Copyright Published by Oriental Scientific Publishing Company © 2023.

Coagulopathies after vaccination against SARS-CoV-2: The sole solution might lead to another problem

The common reported adverse impacts of COVID-19 vaccination include the injection site's local reaction followed by various non-specific flu-like symptoms. Nevertheless, uncommon cases of vaccine-induced immune thrombotic thrombocytopenia (VITT) and cerebral venous sinus thrombosis (CVST) following viral vector vaccines (ChAdOx1 nCoV-19 vaccine, Ad26.COV2 vaccine) have been reported. This literature review was performed using PubMed and Google Scholar databases using appropriate keywords and their combinations: SARS-CoV-2, adenovirus, spike protein, thrombosis, thrombocytopenia, vaccine-induced immune thrombotic thrombocytopenia (VITT), NF-kappaB, adenoviral vector, platelet factor 4 (PF4), COVID-19 Vaccine, AstraZeneca COVID vaccine, ChAdOx1 nCoV-19 COVID vaccine, AZD1222 COVID vaccine, coagulopathy. The s and titles of each article were assessed by authors for screening and inclusion English reports about post-vaccine CVST and VITT in humans were also collected. Some SARS-CoV-2 vaccines based on viral vector, mRNA, or inactivated SARS-CoV-2 virus have been accepted and are being pragmatic global. Nevertheless, the recent augmented statistics of normally very infrequent types of thrombosis associated with thrombocytopenia have been stated, predominantly in the context of the adenoviral vector vaccine ChAdOx1 nCoV-19 from Astra Zeneca. The numerical prevalence of these side effects seems to associate with this particular vaccine type, i.e., adenoviral vector-based vaccines, but the meticulous molecular mechanisms are still not clear. The present review summarizes the latest data and hypotheses for molecular and cellular mechanisms into one integrated hypothesis demonstrating that coagulopathies, including thromboses, thrombocytopenia, and other associated side effects, are correlated to an interaction of the two components in the COVID-19 vaccine.Copyright © 2022, Iranian Pediatric Hematology and Oncology Society. All rights reserved.

A review on quality control, toxicity and clinical application of Amomum tsao-ko Crevost & Lemarie

The dried fruit of Amomum tsao-ko Crevost & Lemarie, a perennial herb of Cardamom in Zingiberaceae, has been widely used in food and as a folk medicine. It is used not only as an important food additive and spice for removing peculiar smell and improving taste, but also as a traditional Chinese medicine with significant efficacy in treating many kinds of disorders. Based on the high edible and medicinal value, large amounts of investigation have been reported for A. tsaoko in the past several years. This review specifically summarises its quality control, toxicology and clinical application, about which no literature had systematically reviewed, based on our best acknowledge. The current quality control of A. tsaoko is based on the content of volatile oil, which should be no less than 1.4% according to the Pharmacopoeia of the People's Republic of China (2020 edition), while a more possible Q-Markers should be developed to focus on either a specific bioactive ingredient or a component correlated with a certain clinical efficacy. Toxicity research suggests that A. tsaoko actually belongs to the non-toxic substance, although citral and 1,8-cineole, two main components of A. tsaoko, is hepatotoxic for the former and displays low acute toxicity and sub-chronic oral toxicity for the latter, but no obviously accumulative toxicity has so far been discovered for A. tsaoko. In clinical practice, A. tsaoko is often used in treatment of dampness/cold resistance, malaria, vomiting, fullness and epigastric distension across additional disorders, such as SARS, COVID-19 and hepatitis.Copyright © 2022 The Author(s)

Phytomedicines for Covid-19: Opportunities and Obstacles

COVID-19 is a disease caused by SARS-CoV-2 that can trigger respiratory tract infection. Due to its tendency to affect the upper respiratory tract (sinuses, nose and throat) or lower respiratory tract (windpipe and lungs), this disease is life-threatening and affects a large number of populations. This virus's unique and complex nature enhances the scope to look into the direction of herbal plants and their constituents for its prevention and treatment. The herbal remedies can have preventive as well as therapeutic actions. This review focuses on various aspects of using herbal medicines for COVID-19, as herbal constituents may also have adverse effects. Various studies revealed that some medicinal plants show life-threatening adverse effects, so selecting plants, and their related studies should be appropriate and strategic. This article includes various factors that should be considered before herbal drug use in COVID-19 patients. These are clinical trials, safety, molecular mechanism, and self-medication, which have been elaborated. This article also discusses the targets of covid-19 and different coronavirus strains. As before, treatment diagnosis of the disease is very important. Various patents have been filed and granted for its proper diagnosis so that its treatment can be easy.Copyright © 2022 Society of Pharmaceutical Sciences and Research. All rights reserved.

Not always COVID - pulmonary BCGosis as an unexpected cause of severe respiratory failure and massive ground glass opacities in the lungs

Introduction: Instillations with balcillus Calmette - Guerin (BCG) are established adjuvant therapy for superficial bladder cancer. Although generally safe and well tolerated, they may cause a range of different, local, and systemic complications. Case description: We present a patient treated with BCG instillations for three years, who was admitted to our hospital due to fever and progressive dyspnea. Blood test revealed elevated CRP and liver function tests. On CT scan massive bilateral ground glass opacities in the middle and lower parts of the lungs, parenchymal infiltrations, bronchial walls thickening, and hilar lymphadenopathy were visible. PCR test for SARS-CoV-2 as well as sputum, blood, and urine cultures were negative. Initial empiric antibiotic therapy was ineffective and respiratory failure progressed with the need of oxygen supplementation of 15l/min. Finally, positive cultures for M. tuberculosis ssp. bovis (BCG) were available from sputum and bronchoalveolar lavage fluid. Antituberculous treatment (rifampin, isoniazid, etambuthol) was implemented together with systemic corticosteroids resulting in the quick improvement of the patient's clinical condition. Due to hepatotoxicity and finally reported resistance of the BCG strain to isoniazid, it was replaced with levofloxacin with a good tolerance. Follow up CT scan showed partial resolution of the infiltrates. The patient was discharged home and continued treatment without further side effects. Conclusion(s): The diagnosis of BCG infection in the lungs must be taken into consideration in every patient treated with BCG instillations and symptoms of unexplained infection.

Hematological and hepatic alterations as predictors of mortality in patients hospitalized by SARS-COV-2

Introduction: SARS-COV-2 infection has generated high mortality. Symptomatology manifests in the respiratory, gastrointestinal tract and others, such as the hematopoietic system. Altered cell counts have been observed, such as lymphopenia standing out within hematological disorders. The cytokine storm together with the use of hepatotoxic drugs prolongs the inflammatory process and increases liver damage. Objective(s): To assess hematological and hepatic alterations in patients hospitalized for SARS-COV-2 who survived. Method(s): Cross-sectional study was conducted, including patients > 18 years, with positive test for SARS-COV-2. Serial measurements of hematological and hepatic parameters were carried out during the period of hospitalization. Those who did not require hospitalization were excluded. Result(s): Patients who died were older (62.71+/-13.52 vs 54.34+/-12.43, p=<0.001), required invasive mechanical ventilation (94.6% vs 86 78.9%, p=0.009) with peak pressure (29.27+/-5.26 vs 26.17+/-5.13, p=0.002) and showing decrease in Kirby index (128.39+/-49.14 vs 153.07+/-49.01, p=0.004) unlike those who survived. There was higher mortality in patients with lymphopenia (0.7 [0.45-1.15] vs 1 [0.7-1.5], p=<0.001), anemia (11.38+/-2.54 vs 12.38+/-2.48, p 0.018) and borderline ranges for platelets (265 vs 329, p=0.003) respectively. Regarding the liver profile, those patients who died had lower total proteins (5.38+/-0.81 vs 5.86+/-0.69, p <0.001), albumin (2.41 +/- 0.50 vs 2.83+/-0.49, p <0.001) and direct bilirubin (0.16 [0.1-0.25] vs 0.14 [0.1 - 0.23], p 0.006). Conclusion(s): Hematological and liver alterations are markers of higher mortality in patients with COVID-19 as an expression of multiorgan disease.

A case of severe increase of liver enzymes in a ATTRv patient after one year of inotersen treatment.

BACKGROUND: Inotersen is an antisense oligonucleotide used to treat hereditary transthyretin amyloidosis (ATTRv). The most common drug-related adverse effects (AEs) include thrombocytopenia and glomerulonephritis. Hepatic damage is rare, but liver enzyme monitoring is mandatory. CASE REPORT: A 70-year-old man with ATTRv (Val30Met) treated with inotersen developed a severe increase of transaminases, with normal bilirubin and cholinesterase levels, that forced us to stop therapy. At the same time, other causes of acquired hepatitis were excluded, and the hypothesis of an inotersen-related hepatic toxicity was supported by the normalization of liver enzymes after 40 days from the drug interruption. DISCUSSION: Our case showed that 1-year inotersen treatment can stabilize neurological impairment and even improve quality of life and suggests to carefully monitor liver enzymes in order to avoid an inotersen-related hepatic dysfunction.

The Problem of Comorbid Socially Significant Infections Under The Conditions of The COVID-19 Pandemic

The aim of the study. To analyze formation features of the epidemic situation for tuberculosis (TB) in the context of the COVID-19 pandemic in order to predict the further actions of medical organizations. Materials and methods. The data for the region for the last 5 years (2017-2021) were analyzed, including 1,762 newly diagnosed cases of patients with TB and comorbidities (according to the data of the Regional Public Health Organization «Regional Clinical Anti-Tuberculosis Dispensary»). All cases were verified using standard diagnostic methods, including molecular genetic methods, to determine the resistance of pathogens to antibacterial drugs. Results. It was revealed that the epidemiological situation in the region was multidirectional: thus, during the COVID-19 epidemic, the most pronounced incidence decrease was observed among cases of chronic course hepatitis (by 16.4 times), while among patients with tuberculosis the incidence decreased by 2.75 times, and among patients with acute hepatitis - only by 1.5 times (P<0.05). Among the cases of comorbid infection, the most severe course was observed in patients with combined (TB + HIV) infection: there was both a more severe general condition, and the development of adverse (undesirable) reactions to anti-TB drugs, which required an extension of maintenance therapy. Conclusions. The results of the study showed that against the background of the COVID-19 pandemic in the region, there was no tendency towards a worsening of the epidemic situation, primarily for the more socially significant infection - tuberculosis. At the same time, there was an increase in the number of cases of comorbid pathology, including HIV + TB. In the treatment of patients with comorbid forms of infection, it is necessary to take into account the possibility of developing hepatotoxic reactions and, as a result, the appointment of accompanying drugs with hepatoprotective and detoxification effects in therapy.

Qust Al Hindi (Saussurea Lappa): A Narrative Review of Its Phytochemistry and Pharmacological Potential against Covid-19

In 2020, the World Health Organization officially designated Coronavirus Disease 2019 (COVID-19) to be global pandemic. Response of immune to SARS-CoV-2 infection includes a hyper-inflammatory state. Saussurea lappa is a medical plant known in several traditional medical systems, such as Persian and Indian medicine. S. lappa has anticancer, antiviral, antirheumatic, anti-inflammatory, and hepatoprotective properties as clinically demonstrated. The purpose of this article to analyze the content of chemical compounds and possible pharmacological activities to fight COVID-19. As primary data sources for this study, researchers looked at articles about the possibility of Saussurea lappa as an alternative in the treatment of COVID-19. Data were gathered online through various academic papers published from 2012 to 2022 derived from the PubMed and Google Scholar databases. One of the components of Saussurea lappa is myrcene which might act on ACE receptors. SARS-CoV-2 enters cells via endocytosis after binding to the ACE2 receptor. The anti-inflammatory properties of Saussurea lappa can be used to treat COVID-19 by reducing inflammatory cytokinins (TNF-alpha, IL-1beta). Further study and clinical trials are needed to prove the effectiveness of Saussurea lappa against COVID-19 patients. Saussurea lappa has a important role in treating COVID-19 based on the effects of active phytochemical compounds that have anti-inflammatory activity, antioxidant, immunomodulator, antcancer, antihepatotoxic, and antihipertension. The Qust al Hindi has not yet been a final drug for the treatment of COVID-19 for it must go through clinical trials on COVID-19 patients directly. Copyright © 2022 The Authors.

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.

Characteristics of COVID-19 in pediatric patients with hematological malignancies

Introduction: As more data is collected, hematologists will be able to gain more insight into the impact of coronavirus disease 2019 (COVID-19) on pediatric patients with hematological malignancies. Material(s) and Method(s): We analysed 21 cases of COVID-19 in pediatric patients with onco-hematological diseases treated in the Western Ukrainian Pediatric Medical Center from March 2020 through May 2021. The majority of patients (71.4%) were diagnosed with acute lymphoblastic leukemia. All patients from the analyzed cohort had an asymptomatic, mild or moderate course of coronavirus-19 infection. The most common symptoms of COVID-19 were fever, cough, gastrointestinal symptoms, and dermatitis. Severe severe acute respiratory syndrome coronavirus 2 increased the risk of liver toxicity and venous thrombosis. Result(s) and Conclusion(s): Our analysis showed that pediatric patients with hematological malignancies need the same treatment approach for COVID-19 as for other infective complications. Copyright © 2022.

Evaluation of a pharmacist-led virtual thiopurine clinic

Introduction: Monitoring of patients on immunomodulator therapy for inflammatory bowel disease (IBD) and auto-immune hepatitis (AIH) significantly increases clinical workload in gastroenterology outpatient clinics owing to blood test monitoring requirements. Aim(s): This study conducted at Barnsley Hospital NHS Foundation Trust aimed to determine the clinical impact of a pharmacist-led virtual thiopurine clinic on drug monitoring, safety and quality of service in a cohort of IBD and AIH patients. Method(s): Patients attended an initial face-to-face outpatient consultation and were then followed-up via remote telephone consultations, as part of a virtual clinic, at two-week intervals. Patient biochemical data were analysed alongside anonymous postal questionnaires to provide an assessment of the quality of the service over a three-month period between 1 May and 31 July 2014. A second survey was performed in December 2019 to re-assess patient satisfaction. Result(s): 81 patients were assessed;clinical indications for thiopurines were IBD (n=75) and AIH (n=6). Overall, 39.5% (n=32) patients failed to reach the thiopurine therapeutic target (2mg/kg with normal thiopurine methyltransferase) owing to drug intolerance, lack of clinical response or hepatotoxicity. Thioguanine nucleotide analysis was performed in 29.6% (n=24) of patients who failed initial treatment, to allow dose optimisation. Hepatotoxicity developed in 9.9% (n=8) of patients, which required shunting of thiopurine metabolism with allopurinol. Myelosuppression developed in 6.9% (n=21) of the total number of blood tests performed (n=304), leading to discontinuation of thiopurines in two patients. The questionnaire response rate was 51.9% (n=42);92.9% of respondents (n=39) found the virtual clinic to be convenient;and 95.2% (n=40) were satisfied with the service. The follow-up survey included 373 patients with a 35.9% response rate (n=134);88% (n=118) found the service easily or very easily accessible, and 82% (n=109) found it very helpful or extremely helpful. Overall satisfaction was highly rated (average 4.46/5). Conclusion(s): Pharmacist-led virtual thiopurine clinics were shown to be safe and regarded favourably by patients. The clinics identified patients exposed to the risks of myelosuppression, as well as allowing thiopurine dose optimisation during the three-month period from May to July 2014. The followup survey in 2019 showed patients valued telemedicine as an alternative to face-to-face visits. Virtual clinics offer a viable alternative to traditional outpatient-driven thiopurine monitoring, especially during the ongoing COVID-19 pandemic. Copyright © 2020 Pharmaceutical Press. All rights reserved.