Chronic active hepatitis caused by benzarone

doi:10.1016/S0168-8278(87)80039-9

Journal of Hepatology

Volume 5, Issue 3, 1987, Pages 332-335

https://doi.org/10.1016/S0168-8278(87)80039-9 Get rights and content

Summary

We report a case of chronic active hepatitis caused by benzarone, a benzofuran derivative used in Europe for the treatment of peripheral venous disorders. Jaundice and serum alanine aminotransferase activity increased while drug administration was continued, but promptly decreased when it was eventually interrupted. Liver lesions were those of chronic active hepatitis. Anti-smooth muscle antibodies were present at a titer of 1:500 and disappeared 8 months after withdrawal of benzarone.

References (26)

BonkowskyHL et al.
Chronic hepatic inflammation and fibrosis due to low doses of paractamol
Lancet
(1978)
MaddreyWC et al.
Severe hepatitis from methyldopa
Gastroenterology
(1975)
UtiliR et al.
Dantrolene-associated hepatic injury. Incidence and character
Gastroenterology
(1977)
BlackM et al.
Isoniazid-associated injury in 114 patients
Gastroenterology
(1975)
PessayreD et al.
Perhexiline maleate-induced cirrhosis
Gastroenterology
(1979)
BabanyG et al.
Chronic liver disease after low daily doses of amiodarone. Report of three cases
J Hepatol
(1986)
DeltourG et al.
Recherches dans la série des benzofurannes. X. Etude pharmacologique et toxicologique de l'éthyl-2-(hydroxy-4-benzoyl)-3-benzofuranne
Arch Int Pharmacodyn
(1965)
FelixVW
Über den Einfluss des Benzarons auf das Polidocanol- und Thiopental-Ödem am Hinterlauf der Katze
Arzneim-Forsch
(1978)
PoucellS et al.
Amiodarone-associated phospholipidosis of the liver. Light, immunohistochemical, and electron microscopic studies
Gastroenterology
(1984)
SimonJB et al.
Amiodarone hepatotoxicity simulating alcoholic liver disease
N Engl J Med
(1984)

PevnyI

Benzaron allergy

Contact Dermatitis

(1984)

SeamanWE et al.

Aspirin-induced hepatotoxicity in patients with systemic lupus erythematosus

Ann Intern Med

(1974)

PessayreD et al.

Chronic active hepatitis and giant multinucleated hepatocytes in adults treated with clometacin

Digestion

(1981)

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Drug-induced liver injury (DILI) can mimic almost all other liver disorders. A phenotype increasingly ascribed to drugs is autoimmune-like hepatitis (ALH). This article summarises the major topics discussed at a joint International Conference held between the Drug-Induced Liver Injury consortium and the International Autoimmune Hepatitis Group. DI-ALH is a liver injury with laboratory and/or histological features that may be indistinguishable from those of autoimmune hepatitis (AIH). Previous studies have revealed that patients with DI-ALH and those with idiopathic AIH have very similar clinical, biochemical, immunological and histological features. Differentiating DI-ALH from AIH is important as patients with DI-ALH rarely require long-term immunosuppression and the condition often resolves spontaneously after withdrawal of the implicated drug, whereas patients with AIH mostly require long-term immunosuppression. Therefore, revision of the diagnosis on long-term follow-up may be necessary in some cases. More than 40 different drugs including nitrofurantoin, methyldopa, hydralazine, minocycline, infliximab, herbal and dietary supplements (such as Khat and Tinospora cordifolia) have been implicated in DI-ALH. Understanding of DI-ALH is limited by the lack of specific markers of the disease that could allow for a precise diagnosis, while there is similarly no single feature which is diagnostic of AIH. We propose a management algorithm for patients with liver injury and an autoimmune phenotype. There is an urgent need to prospectively evaluate patients with DI-ALH systematically to enable definitive characterisation of this condition.
Benzarone-induced liver injury: First case report in Asia
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Chronic liver disease from drugs
2013, Drug-Induced Liver Disease
In general, if a patient survives idiosyncratic DILI, then no long-term consequences on liver function are to be expected. However, severe DILI associated with jaundice may induce progressive liver disease in a small proportion of individuals despite drug withdrawal. A number of drugs have been shown to induce autoimmune hepatitis. In addition, the development of liver cirrhosis has been reported for several different drugs. Some drugs with a cholestatic type of injury have been associated with the development of vanishing bile duct syndrome, with long-term persistent liver injury. Although it seems well documented that chronic liver injury can occur after DILI and discontinuation of drug therapy, the long-term consequences in terms of liver-related morbidity and mortality are unclear. It has been shown that chronic liver disease including cirrhosis is very rare but chronic liver disease due to drugs can occur and may contribute to cases of cryptogenic cirrhosis.
Anti-inflammatory and antipyretic analgesics and drugs used in gout
2010, Side Effects of Drugs Annual
Citation Excerpt :
It causes diarrhea (in 3–4% of patients), urate and oxalate stones, urinary sand, renal colic, and allergic reactions in a small number of patients (63R, 64R). Several cases of benzbromarone-induced hepatotoxicity have been published (65A–72A). It causes a chronic active hepatitis, which can be fatal (73A).
This chapter provides an update on cardiovascular and gastrointestinal adverse effects of non-selective non-steroidal anti-inflammatory agents/analgesics (NSAIDs) and coxibs are presented. The risk of upper gastrointestinal bleeding is increased about four-fold by non-selective NSAIDs. There is a substantial body of evidence that coxibs cause fewer gastrointestinal adverse effects than non-selective NSAIDs. Knowing mortality rates associated with adverse events allows an estimation of their significance and can also help in explaining the risks to patients. It is suggested, the choice between non-selective NSAIDs and coxibs, given similar efficacy, is likely to be determined by considerations about their cardiovascular and gastrointestinal adverse effects. The dextrorotatory stereoisomers of some arylpropionic acids, ibuprofen, indoprofen, and ketoprofen, have been marketed as individual compounds, affording extension of patent life to their manufacturers. A review of these drugs is presented.
The long-term follow-up after idiosyncratic drug-induced liver injury with jaundice
2009, Journal of Hepatology
Citation Excerpt :
Chronic liver disease, including the development of cirrhosis, has been reported with a suspect causality to a number of different drugs [1–11].
Chronic evolution after drug-induced liver injury (DILI) has been reported. How often this leads to liver-related morbidity and mortality is unexplored.
Patients who survived DILI and concomitant jaundice reported to the Swedish Adverse Drug Reaction Advisory Committee (1970–2004) were linked to the Swedish Hospital Discharge and Cause of Death Registries.
Among the 712 survivors, 27 could not be retrieved but 685 patients could be linked to the registries, 392 females (57.2%) and 293 males (42.8%) median age 58 (41–74), a mean follow-up of 10 years. A total of 23/685 (3.4%) patients had been hospitalized for liver disease and 5 had liver-related mortality. Eight patients developed cirrhosis (7 decompensated, 5 died), 5 had “cryptogenic” cirrhosis in which DILI might have played a role in this development. Duration of therapy before DILI was longer in patients with liver-related morbidity/mortality (135 ± 31 days vs. 53 ± 3; p < 0.0001). Autoimmune hepatitis developed in 5/23 (22%), all of female gender after a mean of 5.8 years.
Development of clinically important liver disease after severe DILI associated with jaundice is rare after acute DILI. However decompensated “cryptogenic” cirrhosis developed in some patients with fatal outcome in which DILI might have played a role in this development.
Toxicity of amiodarone and amiodarone analogues on isolated rat liver mitochondria
2001, Journal of Hepatology
Background: Amiodarone is a well-known mitochondrial toxin consisting of a benzofuran ring (ring A) coupled to a p-OH-benzene structure substituted with 2 iodines and a diethyl-ethanolamine side chain (ring B).
Aim: To find out which part of amiodarone is responsible for mitochondrial toxicity.
Methods: Amiodarone, ring A and B without the ethanolamine side-chain and iodines (B0), ring A and B with iodines but no ethanolamine (B2), ring B with 1 iodine and no ethanolamine (C1) and ring B with ethanolamine and 2 iodines (D2) were studied.
Results: In freshly isolated rat liver mitochondria, amiodarone inhibited state 3 glutamate and palmitoyl-CoA oxidation and decreased the respiratory control ratios. B0 and B2 were more potent inhibitors than amiodarone and B2 more potent than B0. C1 and D2 showed no significant mitochondrial toxicity. After disruption, mitochondrial oxidases and complexes of the electron transport chain were inhibited by amiodarone, B0 and B2, whereas C1 and D2 revealed no inhibition. Beta-oxidation showed a strong inhibition by amiodarone, B0 and B2 but not by C1 or D2. Ketogenesis was almost unaffected.
Conclusions: Amiodarone, B0 and B2 are uncouplers of oxidative phosphorylation, and inhibit complexes I, II and III, and β-oxidation. The benzofuran structure is responsible for mitochondrial toxicity of amiodarone and the presence of iodine is not essential.

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Research PaperChronic active hepatitis caused by benzarone

Summary

Lancet

Gastroenterology

Gastroenterology

Gastroenterology

Gastroenterology

J Hepatol

Recherches dans la série des benzofurannes. X. Etude pharmacologique et toxicologique de l'éthyl-2-(hydroxy-4-benzoyl)-3-benzofuranne

Arch Int Pharmacodyn

Über den Einfluss des Benzarons auf das Polidocanol- und Thiopental-Ödem am Hinterlauf der Katze

Arzneim-Forsch

Amiodarone-associated phospholipidosis of the liver. Light, immunohistochemical, and electron microscopic studies

Gastroenterology

Amiodarone hepatotoxicity simulating alcoholic liver disease

N Engl J Med

Benzaron allergy

Contact Dermatitis

Aspirin-induced hepatotoxicity in patients with systemic lupus erythematosus

Ann Intern Med

Chronic active hepatitis and giant multinucleated hepatocytes in adults treated with clometacin

Digestion

Research Paper
Chronic active hepatitis caused by benzarone