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1.
Int J Mol Sci ; 23(9)2022 Apr 27.
Article in English | MEDLINE | ID: covidwho-1809943

ABSTRACT

Patients with coronavirus disease 19 (COVID-19) commonly show abnormalities of liver tests (LTs) of undetermined cause. Considering drugs as tentative culprits, the current systematic review searched for published COVID-19 cases with suspected drug-induced liver injury (DILI) and established diagnosis using the diagnostic algorithm of RUCAM (Roussel Uclaf Causality Assessment Method). Data worldwide on DILI cases assessed by RUCAM in COVID-19 patients were sparse. A total of 6/200 reports with initially suspected 996 DILI cases in COVID-19 patients and using all RUCAM-based DILI cases allowed for a clear description of clinical features of RUCAM-based DILI cases among COVID-19 patients: (1) The updated RUCAM published in 2016 was equally often used as the original RUCAM of 1993, with both identifying DILI and other liver diseases as confounders; (2) RUCAM also worked well in patients treated with up to 18 drugs and provided for most DILI cases a probable or highly probable causality level for drugs; (3) DILI was preferentially caused by antiviral drugs given empirically due to their known therapeutic efficacy in other virus infections; (4) hepatocellular injury was more often reported than cholestatic or mixed injury; (5) maximum LT values were found for alanine aminotransferase (ALT) 1.541 U/L and aspartate aminotransferase (AST) 1.076 U/L; (6) the ALT/AST ratio was variable and ranged from 0.4 to 1.4; (7) the mean or median age of the COVID-19 patients with DILI ranged from 54.3 to 56 years; (8) the ratio of males to females was 1.8-3.4:1; (9) outcome was favorable for most patients, likely due to careful selection of the drugs and quick cessation of drug treatment with emerging DILI, but it was fatal in 19 patients; (10) countries reporting RUCAM-based DILI cases in COVID-19 patients included China, India, Japan, Montenegro, and Spain; (11) robust estimation of the percentage contribution of RUCAM-based DILI for the increased LTs in COVID-19 patients is outside of the current scope. In conclusion, RUCAM-based DILI with its clinical characteristics in COVID-19 patients and its classification as a confounding variable is now well defined, requiring a new correct description of COVID-19 features by removing DILI characteristics as confounders.


Subject(s)
Antiviral Agents , COVID-19 , Chemical and Drug Induced Liver Injury , Alanine Transaminase , Antiviral Agents/adverse effects , Aspartate Aminotransferases , COVID-19/drug therapy , Chemical and Drug Induced Liver Injury/diagnosis , Chemical and Drug Induced Liver Injury/epidemiology , Chemical and Drug Induced Liver Injury/etiology , Female , Humans , Male , Middle Aged , Publications
2.
BMJ Case Rep ; 14(8)2021 Aug 17.
Article in English | MEDLINE | ID: covidwho-1361973

ABSTRACT

Hydralazine is a commonly prescribed antihypertensive agent. Some of its labelled adverse reactions include lupus-like syndrome, tachycardia, headache and fever. Despite its well-known side effects, little is known about hydralazine's hepatotoxic effects. We report the case of a 54-year-old female patient who was started on hydralazine for hypertension management but later presented with hydralazine-induced liver injury. Her initial presentation consisted of non-specific symptoms and a hepatocellular injury pattern. Liver biopsy revealed hepatic steatosis. Three weeks after discontinuation of hydralazine, the patient's liver enzymes normalised, and her symptoms resolved. Few studies have examined the incidence and mechanism by which hydralazine induces a liver injury pattern. With this case, we review the literature, the pathogenesis involved and the eventual management of hydralazine-induced liver injury. We propose close monitoring of liver enzymes for patients on hydralazine throughout their treatment course.


Subject(s)
Chemical and Drug Induced Liver Injury, Chronic , Chemical and Drug Induced Liver Injury , Hypertension , Antihypertensive Agents/adverse effects , Chemical and Drug Induced Liver Injury/diagnosis , Chemical and Drug Induced Liver Injury/drug therapy , Chemical and Drug Induced Liver Injury/etiology , Chemical and Drug Induced Liver Injury, Chronic/drug therapy , Female , Humans , Hydralazine/adverse effects , Hypertension/drug therapy , Middle Aged
4.
J Gastrointestin Liver Dis ; 29(3): 473-475, 2020 Sep 09.
Article in English | MEDLINE | ID: covidwho-1005155
5.
Dig Liver Dis ; 53(2): 146-152, 2021 02.
Article in English | MEDLINE | ID: covidwho-807581

ABSTRACT

The coronavirus pandemic has changed the priorities of the whole medical society. During the clinical course of COVID-19, it has been observed that hepatic injury occurs in a significant proportion of patients, particularly in those with severe or critical illness. In this literature review, we summarize the most recent studies, which covered the pathophysiology of COVID-19 induced liver injury including; hepatic pathological findings, therapy related liver damage, and the effects of the viral infection on pre-existing liver diseasesin context of the most recent recommendations. Conclusions: This review sheds light on the impact of COVID-19 infection on the liver, as well as the prognostic effect of liver laboratory markers on disease outcome. Temporal variations in liver parameters during disease course as well as different patterns of derangement are depicted. More intensive surveillance and individualized therapeutic approaches should be tailored for immunocompromised patients with advanced liver disease, hepatocellular carcinoma, and liver transplant patients. Despite the limited studies on COVID-19 infected patients with preexisting liver disease, this comprehensive overview provides a perspective on the management of liver disease during COVID-19.


Subject(s)
Antiviral Agents/pharmacology , COVID-19 , Liver Diseases , Liver , Patient Care Management/methods , SARS-CoV-2/physiology , COVID-19/drug therapy , COVID-19/physiopathology , Chemical and Drug Induced Liver Injury/diagnosis , Chemical and Drug Induced Liver Injury/etiology , Chemical and Drug Induced Liver Injury/prevention & control , Humans , Liver/metabolism , Liver/pathology , Liver Diseases/diagnosis , Liver Diseases/etiology , Liver Diseases/therapy , Liver Diseases/virology , Liver Function Tests/methods , Prognosis
7.
United European Gastroenterol J ; 8(7): 814-819, 2020 08.
Article in English | MEDLINE | ID: covidwho-617210

ABSTRACT

BACKGROUND: Reports of liver injury in patients with novel coronavirus disease 2019 (COVID-19) are emerging from China and the USA. A wide variety of liver function test abnormalities and few cases of severe liver failure have been reported. No data on the hepatic phenotype from Europe are available at current. METHODS: We report a case series of 44 consecutive patients hospitalized for COVID-19 in Germany. RESULTS: At the time of admission, aspartate aminotransferase greater than the upper limit of normal was present in 70%, while alanine aminotransferase was elevated in 15.8%. Markers of cholestatic liver injury were altered only in a minority of patients. During hospitalization, 31% and 22% experienced increasing aspartate aminotransferase and alanine aminotransferase, respectively, when transaminases were normal at admission. Severe liver injury defined by 3×> upper limit of normal was observed in 9.1% over a mean time of 10.5 days. Importantly, patients exhibited cytotoxicity including lactate dehydrogenase and creatinine kinase elevations, but no signs of relevant liver function impairment. CONCLUSION: In summary, in a case series of hospitalized patients in Germany, cytotoxicity in the absence of severe liver dysfunction at admission and only few cases suggestive of severe liver injury during hospital were observed.


Subject(s)
Antiviral Agents/adverse effects , Betacoronavirus/pathogenicity , Chemical and Drug Induced Liver Injury/epidemiology , Coronavirus Infections/complications , Liver Failure, Acute/epidemiology , Pneumonia, Viral/complications , Adult , Aged , Aged, 80 and over , Alanine Transaminase/blood , Aspartate Aminotransferases/blood , Biomarkers/blood , COVID-19 , COVID-19 Testing , Chemical and Drug Induced Liver Injury/blood , Chemical and Drug Induced Liver Injury/diagnosis , Chemical and Drug Induced Liver Injury/etiology , Clinical Laboratory Techniques/statistics & numerical data , Coronavirus Infections/diagnosis , Coronavirus Infections/drug therapy , Coronavirus Infections/epidemiology , Coronavirus Infections/virology , Electronic Health Records/statistics & numerical data , Female , Germany/epidemiology , Humans , Liver/drug effects , Liver/virology , Liver Failure, Acute/blood , Liver Failure, Acute/diagnosis , Liver Failure, Acute/virology , Liver Function Tests/statistics & numerical data , Male , Middle Aged , Pandemics , Pneumonia, Viral/drug therapy , Pneumonia, Viral/epidemiology , Pneumonia, Viral/virology , Retrospective Studies , SARS-CoV-2 , Young Adult
8.
Infection ; 48(5): 779-782, 2020 Oct.
Article in English | MEDLINE | ID: covidwho-276775

ABSTRACT

At present, there is no definitive antiviral treatment for coronavirus disease 2019 (COVID-19). We describe our early experience with remdesivir in four critically ill COVID-19 patients. Patients received a 200 mg loading dose, followed by 100 mg daily intravenously for up to 10 days. All patients had been previously treated with other antivirals before remdesivir initiation. One patient experienced a torsade de pointes requiring cardiac resuscitation and one died due to multiple organ failure. Three patients showed biochemical signs of liver injury. Lymphocyte count increased in all patients soon after remdesivir initiation. Nasal swab SARS-CoV-2 RNA became negative in three of four patients after 3 days of therapy. We observed an in vivo virological effect of remdesivir in four critically ill, COVID-19 patients, coupled with a significant burden of adverse events. Although limited by the low number of subjects studied, our preliminary experience may be relevant for clinicians treating COVID-19.


Subject(s)
Adenosine Monophosphate/analogs & derivatives , Alanine/analogs & derivatives , Antiviral Agents/administration & dosage , Betacoronavirus/drug effects , Coronavirus Infections/drug therapy , Pneumonia, Viral/drug therapy , RNA, Viral/blood , Adenosine Monophosphate/administration & dosage , Adenosine Monophosphate/adverse effects , Alanine/administration & dosage , Alanine/adverse effects , Antiviral Agents/adverse effects , Betacoronavirus/immunology , COVID-19 , Chemical and Drug Induced Liver Injury/diagnosis , Chemical and Drug Induced Liver Injury/etiology , Chemical and Drug Induced Liver Injury/physiopathology , Chemical and Drug Induced Liver Injury/virology , Convalescence , Coronavirus Infections/virology , Critical Illness , Darunavir/administration & dosage , Darunavir/adverse effects , Drug Administration Schedule , Drug Combinations , Fatal Outcome , Humans , Hydroxychloroquine/administration & dosage , Hydroxychloroquine/adverse effects , Lopinavir/administration & dosage , Lopinavir/adverse effects , Multiple Organ Failure/chemically induced , Multiple Organ Failure/diagnosis , Multiple Organ Failure/physiopathology , Multiple Organ Failure/virology , Pandemics , Pneumonia, Viral/virology , Ritonavir/administration & dosage , Ritonavir/adverse effects , SARS-CoV-2 , Torsades de Pointes/chemically induced , Torsades de Pointes/diagnosis , Torsades de Pointes/physiopathology , Torsades de Pointes/virology
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