Drug–Induced Hepatitis Associated With Anticytoplasmic Organelle Autoantibodies

Abstract

A study from five hepatology units documenting 157 cases of drug-induced hepatitis and a second study from a laboratory of immunology which tested more than 100,000 sera permitted us to establish the frequency of antiorganelle antibodies and their diagnostic value in drug-induced hepatitis. In drug-induced hepatitis caused by a heterogenous group of drugs consisting of ajmaline, aminopterine, isaxonine, isoniazid, perhexiline, phenylbutazone and troleandromycine, antiorganelle antibodies were absent or rare. In drug-induced hepatitis caused by another heterogenous group of drugs, including clometacin, fenofibrate, oxyphenisatin and papaverine, antismooth muscle, antinucleus and antimitochondria antibodies were found in isolation or in different combinations in 70% of cases. From the presence of antismooth muscle antibodies in sera, we could trace 30 cases of clometacin-induced hepatitis. The third group included drug-induced hepatitis with special antibody:iproniazid-induced hepatitis with antimitochondrial antibody 6 and tienilic acid (ticrynafen)-induced hepatitis with antiliver/kidney microsome antibody 2 (anti-LKM2). These two antibodies are rare in routine sera and were absent in patients who received the drug and had no liver damage. From the presence of corresponding antibodies, we detected six cases of iproniazid-induced hepatitis and 67 cases of tienilic acid-induced hepatitis. Antiorganelle antibodies found in high titers disappeared in 2 to 24 months following withdrawal of the offending drug. The fourth group was represented by halothane-induced hepatitis; antiliver/kidney microsome antibody 1 was weak and infrequent. Similarities between drug-induced hepatitis of the second group and lupoïd hepatitis suggest that drugs may reveal this spontaneous disorder.(ABSTRACT TRUNCATED AT 250 WORDS)

Anti-liver endoplasmic reticulum autoantibodies are directed against human cytochrome P-450IA2. A specific marker of dihydralazine-induced hepatitis.

“…1 could be quite general in immunoallergic drug-induced hepatitis. 2. The evidence that P-450pA (described in reference 19 and used in this paper), the phenacetin O-deethylase, is the human P-4501A2 gene product may be summarized as follows.…”

“…Anti-LKMl antibodies were also found in children with an idiopathic type of chronic active hepatitis where a drug could not be identified in the etiology of the disease (1,2,3). The microsomal drug-metabolizing enzymes, P-45011D6 (for anti-LKM 1), P-4501IC8/ 9/10 (for anti-LKM2), trifluoroacetylated carboxylesterase, or several unidentified microsomal proteins (4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15) were found to be recognized by the various autoantibodies.…”

Human anti-endoplasmic reticulum autoantibodies appearing in a drug-induced hepatitis are directed against a human liver cytochrome P-450 that hydroxylates the drug.

“…Some drugs have been found to induce immunoallergic hepatitis in humans as well as the appearance, in human serum, of circulating antibodies that are directed against cell organelles (1,2). By using immunofluorescence techniques, it was shown that some of these antibodies specifically recognized as yet unidentified macromolecules of the endoplasmic reticulum of rat liver or kidney cells (3).…”

Probable Bexarotene Hepatotoxicity Associated With Transient Serum Antimitochondrial Antibodies

“…Transiently detectable serum antimitochondrial antibodies have also been reported in subjects with liver damage presumably induced by Teucrium chamaedrys (germander) [8] and an anticonvulsant [9]. In addition, antibodies against various cytosolic organelles, including mitochondria, have been reported in hepatitis induced by a variety of other drugs [10].…”