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      Amiodarone-induced Hepatitis and Polyneuropathy

      case-report

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          Abstract

          Amiodarone chlorhydrate is a diiodated benzofuran derivative, and it is used to treat cardiac rhythm abnormalities. Hepatotoxicity is a relatively uncommon side effect of amiodarone, and symptomatic hepatic dysfunction occurs in fewer than 1% of the patients taking amiodarone. Cirrhosis is a rare complication that's been confirmed in 12 cases. Peripheral neuropathy occurs in 10% of patients taking aminodarone. We report here on an unusual case of amiodarone-induced hepatotoxicity and peripheral neurotoxicity. A 75 year old man with normal liver function was given amiodarone for treating his atrial fibrillation and heart failure. He developed nausea, vomiting, muscle weakness and wasting after 17.8 months therapy with amiodarone (400 mg orally once per day). Liver biopsy showed the presence of foam cells in the hepatic sinusoids and Mallory bodies in the periportal hepatocytes on light microscopy. Sural nerve biopsy showed demyelination, and nerve conduction studies showed mixed sensorimotor polyneuropathy. These observations show the necessity of monitoring the hepatic function and conducting neurologic examination of the patients treated with amiodarone.

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          Most cited references16

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          Amiodarone hepatotoxicity: prevalence and clinicopathologic correlations among 104 patients.

          The prevalence of apparent amiodarone-related hepatic injury in 104 patients followed prospectively is compared to that reported in the literature. Asymptomatic elevation of serum aminotransferase levels was detected in approximately one-fourth of the patients, a figure similar to the average of reported cases. The frequency of extrahepatic organ toxicity was increased in patients with elevated levels. Symptomatic "hepatitis" developed in 3% of this series and in less than 1% of cases in the literature. Evidence of hepatic phospholipidosis and the development of pseudoalcoholic liver injury is most likely due to the biochemical effects of the drug and to possible metabolic idiosyncrasy, respectively. Serial blood enzyme measurements, as recommended by the manufacturer, may offer some protection against the development of more serious liver injury. However, levels of amiodarone may persist in various tissues for weeks to months following withdrawal, and stopping the drug does not guarantee the prompt reversal of any organ toxicity. Accordingly, the risks posed and benefits offered by amiodarone should be carefully weighed prior to discontinuing the drug, as the risk of sudden cardiac death may outweigh the hazards of ongoing hepatic, pulmonary or other toxicity.
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            Histopathologic analysis of suspected amiodarone hepatotoxicity.

            This analysis of the morphology of suspected amiodarone (AD) liver disease is based on a study of liver specimens from 17 individuals. Changes similar to alcoholic liver injury were commonly seen. Steatosis, both macrovesicular and microvesicular, was the most frequent histopathologic feature. Ballooning of hepatocytes, Mallory bodies, and fibrosis were also common. Other changes included nuclear unrest, acidophilic bodies, foam cells, glycogenated nuclei, and portal inflammation. Characteristic lamellar lysosomal inclusion bodies representing phospholipidosis were found in two of 14 specimens studied ultrastructurally. These changes of pseudoalcoholic hepatitis and/or phospholipidosis were present in liver specimens from asymptomatic, anicteric patients with mild elevations in serum aminotransferase or alkaline phosphatase values with or without hepatomegaly, as well as in patients with clinically overt symptoms of hepatotoxicity. Phospholipidosis appears to be a generalized systemic effect of cationic amphophilic compounds, such as AD. The cytotoxic pseudoalcoholic changes appear to be an independent phenomenon in susceptible patients, whom we speculate may have been unable or less able to metabolize AD through normal pathways. The true incidence of hepatic injury from AD remains to be determined from prospective evaluations of pretreatment and follow-up liver biopsies.
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              Amiodarone: reevaluation of an old drug.

              P J Podrid (1995)
              To review the pharmacology, electrophysiology, and toxicity of amiodarone and to discuss the clinical results produced when amiodarone is used as therapy for patients with atrial fibrillation, patients with nonsustained ventricular tachycardia and cardiomyopathy, patients who have recently had myocardial infarctions, and patients who have survived out-of-hospital cardiac arrest caused by ventricular tachycardia or ventricular fibrillation. Animal and clinical studies involving the pharmacology and electrophysiology of amiodarone and clinical trials in which amiodarone was used as therapy for the arrhythmias noted above were reviewed. Relevant studies that reported on the efficacy and toxicity of amiodarone and on long-term therapy using amiodarone were reviewed, and their data were summarized. Reports of ongoing trials using amiodarone were also reviewed and summarized. Amiodarone is useful for the treatment of many rhythm disturbances. Although side effects from this agent are common, serious toxicity necessitating discontinuation of therapy is infrequent. Unlike other antiarrhythmic agents, amiodarone has not been shown to increase mortality in any population studied. Amiodarone, a unique antiarrhythmic agent with many pharmacologic actions, is effective in the treatment of a wide range of rhythm abnormalities. Several large, randomized trials will provide further information about the clinical usefulness of this agent.
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                Author and article information

                Journal
                Korean J Intern Med
                KJIM
                The Korean Journal of Internal Medicine
                The Korean Association of Internal Medicine
                1226-3303
                2005-6648
                September 2007
                30 September 2007
                : 22
                : 3
                : 225-229
                Affiliations
                Department of Internal Medicine, Chungnam National University College of Medicine, Daejeon, Korea.
                [2 ]Department of Pathology, Chungnam National University College of Medicine, Daejeon, Korea.
                Author notes
                Correspondence to: Byung Seok Lee, M.D., Department of Internal Medicine, Chungnam National University College of Medicine, 640, Daesa-dong, Jung-gu, Daejeon 301-721, Korea. Tel: 82-42-220-7125, Fax: 82-42-254-4553, gie001@ 123456cnuh.co.kr
                Article
                10.3904/kjim.2007.22.3.225
                2687697
                17939344
                b54c9408-831e-4d99-809a-5dbc4ef864f4
                Copyright © 2007 The Korean Association of Internal Medicine
                History
                : 03 January 2007
                : 30 May 2007
                Categories
                Case Report

                Internal medicine
                hepatitis,amiodarone,polyneuropathy
                Internal medicine
                hepatitis, amiodarone, polyneuropathy

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