Hydralazine-induced liver injury: a review and discussion

2021 ◽  
Vol 14 (8) ◽  
pp. e243278 ◽  
Author(s):  
Meeta Bhardwaj ◽  
Nakul Jay Bhardwaj ◽  
Kendra Cueto ◽  
T Colin Killeen
Keyword(s):  
Side Effects ◽  
Liver Injury ◽  
Antihypertensive Agent ◽  
Adverse Reactions ◽  
Liver Enzymes ◽  
Injury Pattern ◽  
Hypertension Management ◽  
Close Monitoring ◽  
Hepatocellular Injury ◽  
Specific Symptoms

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.

scholarly journals Enoxaparin-Induced Liver Injury

2020 ◽  
Vol 14 (2) ◽  
pp. 315-319 ◽  
Author(s):  
Shehriyar Mehershahi ◽  
Nikhitha Mantri ◽  
Aneesh Kumar ◽  
Shaikh Danial ◽  
Patel Harish
Keyword(s):  
Molecular Weight ◽  
Pulmonary Embolism ◽  
Liver Injury ◽  
Low Molecular Weight Heparin ◽  
Liver Enzymes ◽  
Low Molecular Weight ◽  
Dramatic Improvement ◽  
Hepatocellular Injury

Enoxaparin, a form of low-molecular-weight heparin, can cause a rare, underreported, and often reversible form of hepatocellular injury. This report describes a case of enoxaparin-induced hepatotoxicity in a 61-year-old male diagnosed with pulmonary embolism. Elevations of liver enzymes were noted within 1 week of starting the drug, followed by a dramatic improvement upon its discontinuation, with subsequent normalization in the following days.

scholarly journals Hepatic safety of ketoconazole in Cushing’s syndrome: results of a Compassionate Use Programme in France

2018 ◽  
Vol 178 (5) ◽  
pp. 447-458 ◽  
Author(s):  
Jacques Young ◽  
Jérôme Bertherat ◽  
Marie Christine Vantyghem ◽  
Olivier Chabre ◽  
Salima Senoussi ◽  
...  
Keyword(s):  
Liver Injury ◽  
Liver Function ◽  
Cushing’S Syndrome ◽  
Total Bilirubin ◽  
Liver Enzymes ◽  
Cushing's Syndrome ◽  
Close Monitoring ◽  
Compassionate Use ◽  
Severe Hepatotoxicity ◽  
French Cohort

ObjectiveKetoconazole (KTZ) is one of few available treatments for Cushing’s syndrome (CS). Although KTZ has been associated with severe hepatotoxicity, little information is available about hepatic safety in CS. The aim of this study was to document changes in liver function in patients with CS treated with KTZ.DesignAn observational prospective French cohort study (Compassionate Use Programme (CUP)).MethodsEnrolled patients were stratified into a KTZ-naive cohort and a cohort already treated by another formulation of ketoconazole (KTZ-switch cohort). Liver function markers (alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase, γ-glutamyltransferase and bilirubin) were monitored at regular intervals. Patients with ALT > 3 × ULN (upper limit of normal), total bilirubin > 2 × ULN or both ALP > 2 × ULN and ALT > ULN were considered to have liver injury.ResultsOverall, 108 patients were analysed (47 KTZ-naïve; 61 KTZ-switch). The median KTZ dose was 600 mg/day. Most abnormalities observed were asymptomatic mild increases of liver enzymes. Four patients in the KTZ-naïve cohort (8.5%) and two in the KTZ-switch cohort (3.3%) developed liver injury, considered related to KTZ in three cases (all KTZ-naïve in the first month of treatment). Five patients had mild liver function abnormalities at baseline and two had proven liver metastases. Two patients recovered on discontinuation of KTZ and the remaining patient died of unrelated causes.ConclusionsThese findings highlight the need for close monitoring of liver enzymes especially during the first six months of treatment. Liver enzyme abnormalities usually occurred within four weeks were asymptomatic and could be reversed on timely discontinuation of KTZ.

scholarly journals CCl4 INDUCED LIVER INJURY;

2018 ◽  
Vol 24 (05) ◽  
pp. 739-744
Author(s):  
Sana Naz ◽  
Faisal Irshad ◽  
Hina Mawani
Keyword(s):  
Carbon Tetrachloride ◽  
Liver Injury ◽  
Liver Enzymes ◽  
Isotonic Saline ◽  
Saline Group ◽  
Hepatocellular Injury ◽  
Albino Rat ◽  
Medical College ◽  
Group 2 ◽  
Animal House

Objectives: Evaluate the mitigating effect of aqueous extract of Ginkgobiloba (GkbE) on liver enzymes and histology in carbon tetrachloride (CCl4) induced liverinjury in albino rat. Study design: Experimental study. Setting and Duration: Animal house,Bhitai Dental and Medical College Mirpurkhas and Agriculture University Tando Jam fromAnimal house from May 2015 - August 2016. Subjects and Methods: Sixty rats were equallydivided into 3 groups Group 1- Controls (0.9% isotonic saline), Group 2- (CCl4 CCl4 1.0mg/kg intraperitoneal) and Group 3- (CCl4+ GkbE). Blood samples were collected at end ofexperiment from tail veins. Liver was obtained after rat sacrifice by cervical dislocation. Tissuewas fixed in formaldehyde and embedded in paraffin. Microscopy of 3μ tissue sections wasperformed after H & E staining. Statistix 10.0 (USA) software was used for data analysisat 95% confidence interval. Results: Four weeks GkbE administration in CCl4 rat showedsignificant amelioration of liver enzymes and improved liver histology (p=0.0001). In GkbEtreated rats, the histological changes of degeneration, fatty change, inflammatory cellinfiltration, sinusoid congestion and necrosis was minimal (p=0.0001). GkbE was provedof mitigating the hepatocellular injury inflicted by carbon tetrachloride. Conclusion: GkbEmitigates the carbon tetrachloride induced liver injury in rat model. GkbE may be used in drugand chemical induced liver injury.

scholarly journals Important Role of P-Selectin for Leukocyte Recruitment, Hepatocellular Injury, and Apoptosis in Endotoxemic Mice

2004 ◽  
Vol 11 (1) ◽  
pp. 56-62 ◽  
Author(s):  
Daniel Klintman ◽  
Xiang Li ◽  
Henrik Thorlacius
Keyword(s):  
Liver Injury ◽  
Liver Enzymes ◽  
Leukocyte Recruitment ◽  
Leukocyte Rolling ◽  
Hepatocellular Injury ◽  
Principal Role ◽  
Step Procedure ◽  
Pathophysiological Role ◽  
The Individual

ABSTRACT Leukocyte recruitment in the liver includes a two-step procedure in which selectin-dependent leukocyte rolling is a prerequisite for subsequent CD18-dependent leukocyte firm adhesion in postsinusoidal venules. However, the roles of the individual selectins in leukocyte rolling and adhesion, hepatocellular injury, and apoptosis remain elusive. Therefore, we examined the pathophysiological role of P-, E-, and L-selectin in male C57BL/6 mice challenged with lipopolysaccharide (LPS) and d-galactosamine (Gal) by use of intravital microscopy of the liver microcirculation. In control animals, administration of LPS-Gal provoked reproducible hepatic damage, including marked increases of leukocyte recruitment, liver enzymes, and hepatocyte apoptosis and reduced sinusoidal perfusion. Interestingly, pretreatment with an anti-P-selectin antibody (RB40.34) markedly reduced leukocyte rolling and firm adhesion by 65 and 71%, respectively. Moreover, interference with P-selectin function significantly improved sinusoidal perfusion and reduced the increase in liver enzymes by 49 to 84% in endotoxemic mice. Moreover, the activity of caspase-3 and the number of apoptotic hepatocytes were significantly reduced by 55 and 54%, respectively, in RB40.34-treated animals. In contrast, administration of an anti-E-selectin antibody (10E9.6) and an anti-L-selectin antibody (Mel-14) did not protect against endotoxin-induced leukocyte responses or hepatic injury. In conclusion, our novel findings document a principal role of P-selectin in mediating leukocyte rolling, a precondition to the subsequent firm adhesion of leukocytes in liver injury. Furthermore, our novel data demonstrate that inhibition of P-selectin function reduces hepatocellular injury and apoptosis, suggesting a causal relationship between leukocyte recruitment on one hand and hepatocellular injury and apoptosis on the other hand. Based on these findings, it is suggested that P-selectin may be an important therapeutic target in endotoxin-induced liver injury.

scholarly journals AB0287 HEMATOLOGICAL SIDE EFFECTS OF BIOLOGICAL THERAPY IN RHEUMATOLOGY: DATA FROM THE TUNISIAN REGISTER

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1442.2-1442
Author(s):  
H. Bettaieb ◽  
S. Boussaid ◽  
S. Jemmali ◽  
S. Rekik ◽  
E. Cheour ◽  
...  
Keyword(s):  
Side Effects ◽  
Biological Treatment ◽  
Blood Count ◽  
Biological Therapy ◽  
National Registry ◽  
Close Monitoring ◽  
Female Ratio ◽  
Therapy Initiation ◽  
Male Female Ratio ◽  
The Mean

Background:During the last decade, the treatment of chronic inflammatory rheumatism (CIR) has been greatly improved with the advent of biotherapy.However, the use of biological treatment can lead to a number of side effects including abnormalities in the blood count.Objectives:The aim of this study was to assess the different hematological side effects of biological treatment in patients with rheumatoid arthritis (RA) and spondyloarthitis (SA).Methods:This study included patients with RA (ACR/EULAR 2010) and SA (ASAS 2009) registred with the Tunisian Biologic National Registry (BINAR).Patients were followed and treated with biologics for 2 years of less. Clinical data relative to biological treatment, including haematological side effects, have been collected.Results:Two hundred and ninety-eight patients (178 women and 111 men) were included in the study.The mean age was 49.2 ± 14.1 years. The male/female ratio was 0.6. The mean diseases durations for RA and SA were respectively 6.7 ± 3.5 years and 6.5 ±3.6 years.Anti-TNFα agents were prescribed in 87.9% of patients (n = 263) with respectively: Infliximab (20.4%) Etanercept (23.1%), Adalimumab (24.6%) and Certolizumab (26.5%).Tocilizumab and Rituximab were prescribed in 10.4% and 5% of the patients, respectively.Blood count abnormalities were noted in 15.4 % of patients (n=46).Neutropenia was the most frequently anomaly met on the hemogram (9.1%) followed by anemia (3.4%) and thrombocytopenia (3%). Pancytopenia was found in 11.4% of patients (n=34).The median time between biological therapy initiation and the onset of hematologic manifestations was 4.8 months [1-12]. Biological treatment was interrupted in two patients.In the other cases, the biological treatment was maintained with close monitoring of blood cell count. No case of death related to these hematological disturbances has been reported.Conclusion:In our registry, hematological side effects of biological treatment were found in 15.4% of cases and were noted with a median delay of 4.8 [1-12] months after the treatment initiation. Further studies are needed to confirm our preliminary results.Disclosure of Interests:None declared

scholarly journals The Safety of COVID-19 Vaccinations—We Should Rethink the Policy

Vaccines ◽  
2021 ◽  
Vol 9 (7) ◽  
pp. 693
Author(s):  
Harald Walach ◽  
Rainer J. Klement ◽  
Wouter Aukema
Keyword(s):  
Side Effects ◽  
Confidence Interval ◽  
Field Study ◽  
Adverse Reactions ◽  
Safety Data ◽  
European Medicines Agency ◽  
Point Estimate ◽  
Drug Reactions ◽  
Vaccination Policy ◽  
Risks And Benefits

Background: COVID-19 vaccines have had expedited reviews without sufficient safety data. We wanted to compare risks and benefits. Method: We calculated the number needed to vaccinate (NNTV) from a large Israeli field study to prevent one death. We accessed the Adverse Drug Reactions (ADR) database of the European Medicines Agency and of the Dutch National Register (lareb.nl) to extract the number of cases reporting severe side effects and the number of cases with fatal side effects. Result: The NNTV is between 200–700 to prevent one case of COVID-19 for the mRNA vaccine marketed by Pfizer, while the NNTV to prevent one death is between 9000 and 50,000 (95% confidence interval), with 16,000 as a point estimate. The number of cases experiencing adverse reactions has been reported to be 700 per 100,000 vaccinations. Currently, we see 16 serious side effects per 100,000 vaccinations, and the number of fatal side effects is at 4.11/100,000 vaccinations. For three deaths prevented by vaccination we have to accept two inflicted by vaccination. Conclusions: This lack of clear benefit should cause governments to rethink their vaccination policy.

scholarly journals DIC-Like Syndrome Following Administration of ChAdOx1 nCov-19 Vaccination

Viruses ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1046
Author(s):  
Gerardo Casucci ◽  
Domenico Acanfora
Keyword(s):  
Side Effects ◽  
Disseminated Intravascular Coagulation ◽  
Adverse Reactions ◽  
Thrombus Formation ◽  
European Countries ◽  
European Medicines Agency ◽  
Safety Committee ◽  
Vectored Vaccine ◽  
Short Time ◽  
Prompt Diagnosis

In recent weeks, adverse reactions have been reported after administration of Oxford–AstraZeneca chimpanzee adenovirus vectored vaccine ChAdOx1 nCoV-19 (AZD1222), in particular thrombus formation, which has led several European Countries to discontinue administration of this vaccine. On March 8, 2021, the European Medicines Agency Safety Committee did not confirm this probable association. We report the case of a patient who developed disseminated intravascular coagulation after the first dose of Oxford-Astra Zeneca vaccine, which resolved in a few days with the administration of dexamethasone and enoxaparin. This work demonstrates the safety of the Oxford-Astra Zeneca vaccine and that any development of side effects can be easily managed with a prompt diagnosis and in a short time with a few commonly used drugs.

scholarly journals Mechanisms of Hepatocellular Injury in Hepatitis A

Viruses ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 861
Author(s):  
Minghang Wang ◽  
Zongdi Feng
Keyword(s):  
T Cells ◽  
Liver Injury ◽  
Hepatitis A ◽  
Acute Viral Hepatitis ◽  
Hepatitis A Virus ◽  
Current Knowledge ◽  
Cytotoxic T Cells ◽  
Host Factors ◽  
Hepatocellular Injury

Hepatitis A virus (HAV) infection is a common cause of acute viral hepatitis worldwide. Despite decades of research, the pathogenic mechanisms of hepatitis A remain incompletely understood. As the replication of HAV is noncytopathic in vitro, a widely accepted concept has been that virus-specific cytotoxic T cells are responsible for liver injury. However, accumulating evidence suggests that natural killer (NK) cells, NKT cells, and even non-HAV-specific CD8+ T cells contribute to liver damage during HAV infection. In addition, intrinsic death of virus-infected hepatocytes has been implicated as a cause of liver injury in a murine model of hepatitis A. Furthermore, genetic variations in host factors such as T cell immunoglobulin-1 (TIM1) and IL-18 binding protein (IL-18BP) have been linked to hepatitis A severity. This review summarizes the current knowledge of the mechanisms of hepatocellular injury in hepatitis A. Different mechanisms may be involved under different conditions and they are not necessarily mutually exclusive. A better understanding of these mechanisms would aid in diagnosis and treatment of diseases associated with HAV infection.

scholarly journals Mesalazine (5-aminosalicylic acid) induced chronic hepatitis

Gut ◽  
1999 ◽  
Vol 44 (6) ◽  
pp. 886-888 ◽  
Author(s):  
P Deltenre ◽  
A Berson ◽  
P Marcellin ◽  
C Degott ◽  
M Biour ◽  
...  
Keyword(s):  
Chronic Hepatitis ◽  
Side Effects ◽  
Adverse Effects ◽  
Liver Dysfunction ◽  
Liver Enzymes ◽  
Slow Release ◽  
Aminosalicylic Acid ◽  
Safe Alternative ◽  
Release Formulation ◽  
Slow Release Formulation

BACKGROUNDTreatment of ulcerative colitis or Crohn’s disease with sulphasalazine causes several adverse effects, including hepatitis. Sulphasalazine is cleaved by colonic bacteria into 5-aminosalicylic acid and sulphapyridine. Received wisdom was that 5-aminosalicylic acid was topically active, whereas sulphapyridine was absorbed and caused immunoallergic side effects. Mesalazine, a slow release formulation of 5-aminosalicylic acid, was expected to be a safe alternative. However, several cases of acute hepatitis have been reported.CASE REPORTA 65 year old man had increased liver enzymes, anti-nuclear and anti-smooth muscle autoantibodies and IgG levels, and lesions of chronic hepatitis after 21 months of mesalazine treatment. Although liver dysfunction had been identified eight months earlier, simvastatin rather than mesalazine had been withdrawn, without any improvement. In contrast, liver enzyme and IgG levels became normal and autoantibodies disappeared after discontinuation of mesalazine administration.CONCLUSIONContrary to initial expectations, mesalazine can cause most of the sulphasalazine induced adverse effects, and hepatic side effects may be almost as frequent. When liver dysfunction occurs, mesalazine administration should be discontinued to avoid the development of chronic hepatitis and liver fibrosis.

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