Suspected cholestatic liver injury induced by favipiravir in a patient with COVID-19

Yamazaki, Shingo; Suzuki, Takaaki; Sayama, Misa; Nakada, Taka‐aki; Igari, Hidetoshi; Ishii, Itsuko

doi:10.1016/j.jiac.2020.12.021

Cited by 47 publications

(51 citation statements)

References 13 publications

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“…After 5 days of favipiravir treatment, liver function test (AST and ALT) levels of our patient were found to be doubled. This may be due to the use of the hepatotoxic effect of paracetamol and/or favipiravir [ 16 ].…”

Section: Discussionmentioning

confidence: 99%

COVID-19-Related Pneumonia in an Adolescent Patient with Allergic Asthma

Özdemir

Engin

Yılmaz

2021

Case Reports in Medicine

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Background. The latest coronavirus infection due to SARS-CoV-2, which started in China in December 2019, was announced as a pandemic by the World Health Organization (WHO) in March 2020. All epidemiological data so far show us that SARS-CoV-2 infection is less serious in children than in adults. Allergic asthma, the most common chronic disease in children, is usually not to be related to greater risk or severity for COVID-19 in pediatric populations. Although reports/research on asthma and COVID-19 in children have thus far been comforting, when coming across an asthma patient with any lower airway infection, attention should be given to evaluate their asthma control level and the possibility of SARS-CoV-2 infection. Case Report. Here, we report a rare adolescent case of COVID-19-related pneumonia development with underlying asthma. A 16-year-old male patient has been followed up by the pediatric allergy outpatient clinic with the diagnosis of asthma for the last 5 years. He was thought to have typical clinical and laboratory findings for SARS-CoV-2 infection combined with underlying pediatric (allergic) asthma. Pulmonary CT showed findings consistent with COVID-19-related pneumonia. He was discharged after 1 week when all his complaints regressed, his examination became normal, and 5-day favipiravir treatment was completed. Conclusion. When a physician comes across an asthma patient with any lower airway infection, attention should be given to evaluate their asthma control level and possibility of SARS-CoV-2 infection.

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Section: Discussionmentioning

confidence: 99%

COVID-19-Related Pneumonia in an Adolescent Patient with Allergic Asthma

Özdemir

Engin

Yılmaz

2021

Case Reports in Medicine

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“…This case report described a patient who developed cholestatic liver injury caused by favipiravir. However, based on the author's view, the administration of antibacterial treatment triggered the liver injury, and a high dose of favipiravir worsened the liver function ( 41 ).…”

Section: Resultsmentioning

confidence: 99%

Drug-Induced Liver Injury in COVID-19 Patients: A Systematic Review

et al. 2021

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Introduction: The severity of COVID-19 may be correlated with the risk of liver injury development. An increasing number of studies indicate that degrees of hepatotoxicity has been associated with using some medications in the management of COVID-19 patients. However, limited studies had systematically investigated the evidence of drug-induced liver injury (DILI) in COVID-19 patients. Thus, this study aimed to examine DILI in COVID-19 patients.Methods: A systematic search was carried out in PubMed/Medline, EMBASE, and Web of Science up to December 30, 2020. Search items included “SARS-CoV-2”, “Coronavirus,” COVID-19, and liver injury.Results: We included 22 related articles. Among included studies, there was five case report, five case series, four randomizes control trial (RCT), seven cohort studies, and one cross-sectional study. The drugs included in this systematic review were remdesivir, favipiravir, tocilizumab, hydroxychloroquine, and lopinavir/ritonavir. Among included studies, some studies revealed a direct role of drugs, while others couldn't certainly confirm that the liver injury was due to SARS-CoV-2 itself or administration of medications. However, a significant number of studies reported that liver injury could be attributable to drug administration.Discussion: Liver injury in COVID-19 patients could be caused by the virus itself or the administration of some types of drug. Intensive liver function monitoring should be considered for patients, especially patients who are treated with drugs such as remdesivir, lopinavir/ritonavir, and tocilizumab.

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“…Elevated liver function tests and/or liver injury are important adverse effects of favipiravir observed frequently in clinical trials [5, 6]. Since abnormal liver function tests (LFTs) are affected by various factors, including concomitantly administered drugs, underlying liver disease, and disease severity, case reports of favipiravir-induced liver injury are still few [7] and no previous study has reported an association between favipiravir-induced liver injury and serum concentrations.…”

Section: Discussionmentioning

confidence: 99%

“…To the best of our knowledge, there is only one case report of favipiravir-induced liver injury, despite the high frequency of abnormal LFTs and/or liver injury in clinical studies of favipiravir among patients with COVID-19 [7]. Yamazaki et al [7] reported that a 73-year-old patient with a history of alcoholic hepatitis received favipiravir at 6000 mg/day on the first day and 2400 mg/day from the second day for 14 days; however, subsequently developed a favipiravir-induced cholestatic liver injury with a score of 6 (possible) based on the R factor and CIMOS/RUCAM scoring system [9]. This case report also suggested that favipiravir exposure may have contributed to drug-induced liver injury; however, favipiravir concentrations were not measured.…”

Section: Discussionmentioning

confidence: 99%

“…However, blood uric acid levels normalize quickly after discontinuation of favipiravir, and few symptoms due to hyperuricemia have been observed in most studies [4]. Subsequently, abnormal liver tests and/or liver injury are also important adverse effects observed frequently in some clinical trials [5, 6], which sometimes lead to discontinuation of therapy; however, case reports on favipiravir-induced liver injury are limited, and no previous study has reported an association between favipiravir-induced liver injury and serum concentrations [7].…”

Section: Introductionmentioning

confidence: 99%

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Association between high serum favipiravir concentrations and drug-induced liver injury

Kawasuji

Tsuji

Ogami

et al. 2021

Preprint

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ObjectivesThis study aimed to evaluate the incidence and pattern of favipiravir-induced liver injury and the potential association between serum concentrations in hospitalized COVID-19 patients.Patients and methodsWe retrospectively reviewed laboratory-confirmed patients with COVID-19 for whom serum favipiravir trough concentration (Cmin) was measured under steady-state conditions during treatment. All patients were administered 1800 mg of favipiravir twice daily on the first day and 800 mg twice daily from the second day.ResultsThirty observed favipiravir concentrations were collected from nine patients. Of these, favipiravir-induced liver injury developed in three patients after 13 (11–14) days from the initiation of therapy, with two classified as cholestatic and one hepatocellular injury, with a score of four (possible), seven (probable), and three (possible) based on the CIMOS/RUCAM scoring system. Median (range) favipiravir Cmin at steady state was found to be significantly higher in patients with liver injury at 66.4 (47.8–72.4) mg/L than in those without injury at 12.8 (9.4–21.8) mg/L (P = 0.028).ConclusionsHigher favipiravir serum concentrations were observed in patients who developed favipiravir-induced liver injury than in those who did not. As the variations in favipiravir concentrations between patients were large, personalized optimal dosing strategies may be needed for safe use.

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Suspected cholestatic liver injury induced by favipiravir in a patient with COVID-19

Cited by 47 publications

References 13 publications

COVID-19-Related Pneumonia in an Adolescent Patient with Allergic Asthma

COVID-19-Related Pneumonia in an Adolescent Patient with Allergic Asthma

Drug-Induced Liver Injury in COVID-19 Patients: A Systematic Review

Association between high serum favipiravir concentrations and drug-induced liver injury

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