Amiodarone-induced Liver Injury Research Articles

Amiodarone induced liver injury in a patient with Metabolic dysfunction-associated steatotic liver disease

Amiodarone induced liver injury in a patient with Metabolic dysfunction-associated steatotic liver disease

S3773 Should We Start Treating Intravenous Amiodarone-Induced Liver Injury With N-Acetylcysteine? A Successful Treatment Case Report

S3773 Should We Start Treating Intravenous Amiodarone-Induced Liver Injury With N-Acetylcysteine? A Successful Treatment Case Report

Risk factors for amiodarone-induced liver injury: A retrospective analysis of medical records.

This study identified risk factors for drug-induced liver injury (DILI) based on patient information before the administration of amiodarone. A retrospective analysis was performed on patients who had received amiodarone treatment. Data from patients with and without DILI were compared immediately before the start of amiodarone treatment. An elevated C-reactive protein level (odds ratio (OR) 1.119; 95% confidence interval (CI) 1.009 - 1.241; p = 0.033) before amiodarone administration was a significant risk factor for DILI. Possible treatment with alternative drugs should be considered in patients with elevated C-reactive protein levels. Moreover, close monitoring of liver function when amiodarone is administered may prevent the onset and exacerbation of DILI.

Development of a Scoring System to Differentiate Amiodarone-Induced Liver Injury From Alcoholic Steatohepatitis

Amiodarone-induced liver injury (AILI) is histopathologically similar to alcoholic steatohepatitis (ASH). We sought to elucidate their histologic differences and develop a scoring system to differentiate these two entities. A cohort of 17 AILI and 17 ASH cases was included in the initial study. Cases from three different institutions were included for further validation. Macrovesicular steatosis was usually below 10% of the liver parenchyma in AILI. Hepatocyte ballooning degeneration was more common in ASH than in AILI. "Balloon-like" hepatocyte was more common in AILI than in ASH. Lobular neutrophilic inflammation, satellitosis, and cholestasis were more common in ASH. Mallory-Denk bodies and pericellular fibrosis in AILI were mainly located in zone 1 compared with a panacinar or zone 3 distribution in ASH. A scoring system was developed in which points were assigned to different histologic features; a total sum of less than 5 suggests AILI, more than 5 is ASH, and 5 is equivocal. This scoring system was then evaluated on a test cohort comprising 14 AILI cases, in which 13 cases were correctly assigned with a score less than 5. The sensitivity, specificity, and accuracy for diagnosing AILI in the test cohort were 92.9%, 91.7%, and 92.3%, respectively. This scoring system can aid pathologists to differentiate AILI from ASH.

3181 Intravenous Amiodarone: An Uncommon Culprit of Reversible Hyper-Acute Liver Injury

INTRODUCTION: Amiodarone is a commonly used anti-arrhythmic agent and it is important that physicians are familiar with the toxicity profile. We are reporting a case of intravenous (IV) amiodarone induced hyper-acute liver injury. CASE DESCRIPTION/METHODS: 62-year-old man with history of atrial fibrillation, non-ischemic cardiomyopathy and tobacco abuse, was admitted with atrial fibrillation and rapid ventricular response related to medication non-adherence. Patient was given IV amiodarone (total of 1050 mg) over 24-hour period, following which patient developed marked elevation of aspartate aminotransferase/AST (4021 U/L) and alanine aminotransferase/ALT (3000 U/L) with mild elevation of alkaline phosphatase/ALP (218 U/L) and total bilirubin (2.0 mg/dL). International Normalized Ratio (INR) - 5.3. Viral hepatitis panel, acetaminophen and drug toxicology screen - negative. Ceruloplasmin – normal. Ultrasound abdomen – normal liver and CBD diameter 4 mm. Portal venous duplex – no thrombosis. Patient denied use of over the counter medications or herbal supplements. No hypotensive episodes or evidence of cardiogenic shock. Due to the temporal relationship between the use of intravenous amiodarone and the development of liver injury, amiodarone-induced liver injury was suspected. Amiodarone was immediately discontinued and patient was given IV N-acetylcysteine (NAC). 24 hours later, AST fell by 50% to 2167 U/L. Liver enzymes continued to decrease and on day 4 (day of discharge), AST and ALT levels were 212 U/L and 929 U/L. After the liver enzymes normalized, our patient was started on oral amiodarone without recurrence of liver injury. DISCUSSION: IV amiodarone is typically used as a short-term therapy for various arrhythmias and is primarily eliminated by biliary excretion. Acute hepatitis due to parenteral therapy is extremely rare and can develop within 1 day of administration. Amiodarone should be immediately discontinued in those cases. The different mechanisms suspected to cause acute liver toxicity due to IV amiodarone are ischemic liver injury due to relative hypotension, hypersensitivity reaction, toxicity of the vehicle (polysorbate-80), and idiosyncratic toxicity. Limited evidence is available about the use of NAC in amiodarone induced liver injury.

Hepatic Amiodarone Lipotoxicity Is Ameliorated by Genetic and Pharmacological Inhibition of Endoplasmatic Reticulum Stress.

Amiodarone is a commonly used antiarrhythmic drug and can cause liver steatosis. We investigated the role of endoplasmic reticulum (ER) stress/unfolded protein response in the pathogenesis of amiodarone-induced steatosis. Amiodarone-induced liver injury was obtained by 1 intraperitoneal injection to wild-type (WT) or C/EBP homologous protein knock-out mice (Ddit3-/-). Amiodarone directly reduced intracellular ATP and Ca2+ in hepatocytes invitro, inducing ER stress and lipid accumulation. In vivo, amiodarone-driven liver damage and lipid accumulation was accompanied by activation of ER stress/unfolded protein response, as demonstrated by up-regulation of genes encoding key ER stress mediators and by phosphorylation of eIF2α. In contrast to WT mice, Ddit3-/- mice were protected from amiodarone-induced ER stress and lipid accumulation. Importantly, amiodarone-induced lipid accumulation was not mediated by de novo hepatic lipogenesis, increased adipose tissue lipolysis or increased hepatic uptake of triglycerides or free fatty acids. Rather, amiodarone strongly increased hepatic mRNA expression of lipid droplet proteins, particularly Cidea and Cidec, in WT, but less so in Ddit3-/- mice, suggesting a link between ER stress and increased triglyceride storage. Moreover, while insulin attenuated amiodarone-induced phosphorylation of hormone sensitive lipase (HSL) in WT, it did not affect pHSL in Ddit3-/-, indicating increased lipolysis and therefore reduced lipid accumulation in these mice. Finally, ER stress attenuation using 2 different pharmacological chaperones reduced lipid accumulation, accompanied by reduced mRNA expression of Cidec. In conclusion, amiodarone-induced ER stress drives liver steatosis and may be considered for therapeutic targeting.

Two Cases of Amiodarone-induced Liver Injury and Cirrhosis

Two Cases of Amiodarone-induced Liver Injury and Cirrhosis

Oral Amiodarone-induced liver Injury, especially Gamma Glutamyl Transferase Elevation: A Case Report

Oral Amiodarone-induced liver Injury, especially Gamma Glutamyl Transferase Elevation: A Case Report

Predictors of intravenous amiodarone induced liver injury.

BackgroundIntravenous (IV) amiodarone may be associated with liver injury that may necessitate drug discontinuation. The prediction of amiodarone induced liver injury (AILI) and its severity may help careful patient monitoring or the choice of other measures alternative to amiodarone in high risk patients. Little is known regarding predictors of AILI.ObjectivesTo address the predictors of AILI and its severity.MethodsThe study included 180 patients indicated for IV amiodarone therapy who were divided into 2 groups: cases (90 patients) who developed AILI, and controls (90 patients) who did not develop AILI. AILI was defined as aminotransferase (ALT and AST) elevation by ⩾2 folds of baseline levels. Severe AILI was defined as enzyme elevation by >5 folds of baseline values.ResultsMultivariate analysis showed that the presence of cardiomyopathy (P = 0.032), congestive hepatomegaly (P = 0.001), increasing baseline total bilirubin (P < 0.0001), direct current cardioversion (P = 0.015), and increasing dose of amiodarone (P = 0.014) to be independent predictors for AILI. Regarding severity of AILI, inotropic support (P = 0.034), congestive hepatomegaly (P = 0.012), increasing baseline total bilirubin (P = 0.001), and increasing dose of amiodarone (P = 0.002) were found to be independent predictors for severe AILI. Among cases, linear regression analysis showed that baseline ALT was the only significant independent predictor of post-amiodarone ALT (P < 0.0001), while baseline AST (P < 0.0001) and EF (P = 0.012) were the only significant independent predictors of post-amiodarone AST.ConclusionsCompromised cardiac, hepatic, and hemodynamic conditions, with increasing dose of IV amiodarone were associated with AILI. Severity of liver injury had linear relationship with baseline aminotransferase levels and left ventricular systolic function.

Effect of stem cell therapy on amiodarone-induced liver injury in albino rats

Introduction Sustained liver injury causes the development of fibrosis. For patients with end-stage fibrosis (cirrhosis) with subsequent portal hypertension, liver failure, and hepatocellular cancer, liver transplantation is the only effective method of treatment. However, it is associated with several complications and side effects. Aim of the work The present study aimed to determine the possible effect of human cord blood mesenchymal stem cell therapy on liver injury using amiodarone as a model of induced liver damage in albino rats. Materials and methods Twenty-three adult male albino rats were divided into three groups: group I (control) included six rats that were given 0.5ml Tween 80 orally for 2 weeks, group II included 10 rats that were given 5.4mg of amiodarone orally for 2 weeks, and group III included seven rats that were injected with stem cells in the tail vein following confirmation of liver damage and held for 4 weeks before sacrifice. Liver specimens were processed. Sections were subjected to the following stains: H&E, Masson's trichrome, and Prussian blue. Immunohistochemical studies were carried out for CD44 and human APF. Digital image analysis was used to determine the area % of collagen fibers and the optical density of α-fetoprotein-positive cells. The results were compared statistically. Results In group II, congested dilated blood sinusoids were observed. Some hepatocytes showed dark nuclei. Some hepatocytes appeared with dark nuclei and a strong acidophilic cytoplasm; others were ballooned. Mallory bodies were observed. Some portal areas showed intense mononuclear cellular infiltration. Extensive collagen fibers existed around some central veins and portal tracts and increased area % of collagen fibers was observed. Most histological findings were improved in group III. In addition, multiple-positive α-fetoprotein immunostained cells were detected and proved morphometrically by their increased mean optical density in comparison with group II. Conclusion It can be concluded that cord blood mesenchymal stem cell therapy induces amelioration in morphological changes associated with amiodarone-induced liver injury, provided therapy is initiated early in the development of the injury.

Causality assessment of liver injury after chronic oral amiodarone intake

The number of patients receiving amiodarone will increase in future years. As clinically significant hepatotoxicity associated with oral amiodarone is infrequent and difficult to predict, a new Bayesian-developed model is proposed to help in the causality assessment of amiodarone-induced liver injury. Incidence of abnormal liver enzymes in patients receiving amiodarone was obtained from placebo controlled clinical trials. Published case reports of amiodarone-induced hepatotoxicity were identified through a literature search. Maximum number of expected hepatotoxicity cases in amiodarone and placebo-treated patients was calculated using Poisson distribution. The calculated odds ratio was used as a Prior Odds (PrO) to subsequent quantification, using a Bayesian-approach, of individual amiodarone-induced hepatotoxicity likelihood. PrO of amiodarone-induced hepatotoxicity was 0.48. Thirty nine amiodarone-associated hepatotoxicity case reports were retrieved. Half of published case reports developed an irreversible damage. The amiodarone Bayesian model combining information about latency period and period of remission, together with analytical parameters properly defines the toxicity profile shown in published case reports. The analytical pattern defined by this model is different from the one expected if liver injury in published cases was caused by other etiologies. A method based on a Bayesian-approach, which links information from clinical trials with clinical hepatotoxicity profile from published case reports can be a useful tool for amiodarone-induced liver injury causality assessment. At present, this method is limited due to scarcity and quality of available data. Further efforts are needed to improve model ability in order to identify amiodarone-induced liver injury.