RSS-Feed abonnieren
DOI: 10.1055/s-2003-39650
Medikamenten- und fremdstoffbedingte Hepatotoxizität
Drug- and Toxin-induced HepatotoxicityPublikationsverlauf
                     Manuskript-Eingang: 2. September 2002
                     
                     Annahme nach Revision: 17. Oktober 2002
                     
Publikationsdatum:
12. Juni 2003 (online)

Zusammenfassung
Die Leber ist das zentrale Organ des Fremdstoffmetabolismus. Leberschäden durch chemische Stoffe aus unserer natürlichen, häuslichen und industriellen Umwelt oder durch Medikamente sind daher häufig. Sie werden jedoch oft verkannt und falsch behandelt. Epidemiologische Daten zeigen, dass insbesondere die medikamenteninduzierten Leberschäden mit der ansteigenden Zahl der jährlich neu entwickelten und vermarkteten Medikamente zunehmen. Bei der fremdstoffinduzierten Leberschädigung werden akut verlaufende Formen von chronischen Leberschädigungen unterschieden. Ein Hepatitis-ähnliches Bild wird ebenso beobachtet wie cholestatische Formen. Außerdem kann das Bild der Leberschädigung von zusätzlichen Symptomen der Hypersensitivitätsreaktion gegenüber Fremdstoffen oder Medikamenten begleitet werden. Fremdstoffbedingte Schädigungen des Gefäßsystems der Leber werden ebenso beobachtet wie das Entstehen von Lebertumoren und die Entwicklung einer Leberzirrhose. Erste Voraussetzung der Behandlung von Leberschäden durch Fremdstoffe ist zunächst die korrekte Diagnose. Hierbei spielt die umfassende Expositionsanamnese eine entscheidende Rolle. Im Weiteren sollte die Diagnose durch zusätzliche diagnostische Schritte und durch die Beobachtung des Verlaufes der Erkrankung nach Absetzen oder Elimination des Medikamentes oder Fremdstoffes erhärtet werden. Eine gezielte Therapie ist selten möglich. Das Hauptziel muss daher die Prävention bleibender Schäden durch eine frühzeitige Diagnose sein. Bei der Vielfalt der leberschädigenden Fremdstoffe und Medikamente ist dieses Kapitel der Inneren Medizin für den behandelnden Arzt eine große Herausforderung.
Abstract
The liver is essential for metabolism of drugs and exogenous toxins. Therefore, liver toxicity due to natural, domestic and industrial toxins or drugs is common but rarely recognised. Although thorough epidemiological data are missing, the number of cases with drug-induced liver toxicity is increasing, parallel to the growing number of drugs.
Adverse hepatic reactions may present as acute or chronic liver damage. Independent from the cause and mechanism of liver damage, the clinical presentation may be either cytolytic or cholestatic. In addition, liver damage may be accompanied by a systemic hypersensitivity reaction against the applied agent. Drug- or toxin-induced liver damage includes vascular damage, induction of liver tumours and development of liver cirrhosis.
The prerequisite for specialised treatment of drug-induced adverse hepatic reactions is establishing the diagnosis which is obtained by a thorough medical history taken by an experienced physician with a special emphasis on drug or toxin exposure. The diagnosis may be confirmed by additional diagnostic measures (e. g. liver biopsy) or the clinical course after exposure to the causing agent has been stopped. Only in a minority of cases a definite treatment may be available. Therefore, the main aim is to prevent chronic liver damage through early and correct diagnosis. Due to the extensive variety of possibly liver toxic drugs and chemical agents this aspect is a major challenge to physicians.
Schlüsselwörter
Fremdstoffe - Hepatotoxizität - Medikamente - Hepatitis
Key words
Toxins - hepatotoxicity - liver - hepatitis
Literatur
- 1 
            Friis H, Andreasen P B. 
            Drug-induced hepatic injury: an analysis of 1100 cases reported to the Danish Committee
            on Adverse Drug Reactions between 1978 and 1987. 
            J Intern Med. 
            1992; 
            232 (2) 
            133-138 
            
            Reference Ris Wihthout Link
- 2 
            Sameshima Y, Shiozaki Y, Mizuno T. et al .
            Clinical statistics on drug-induced liver injuries. Drug-induced liver injuries in
            Japan in the past 30 years. 
            Nippon Shokakibyo Gakkai Zasshi. 
            1974; 
            71 (8) 
            799-807 
            
            Reference Ris Wihthout Link
- 3 
            Garcia R odriguez LA, Perez G utthann S, Walker A M. et al .
            The role of non-steroidal anti-inflammatory drugs in acute liver injury. 
            Br Med J. 
            1992; 
            305 (6858) 
            865-868 
            
            Reference Ris Wihthout Link
- 4 
            Aithal P G, Day C P. 
            The natural history of histologically proved drug induced liver disease. 
            Gut. 
            1999; 
            44 (5) 
            731-735 
            
            Reference Ris Wihthout Link
- 5 
            Neeleman J, Wessely S. 
            Drugs taken in fatal and non-fatal self-poisoning: a study in south London. 
            Acta Psychiatr Scand. 
            1997; 
            95 (4) 
            283-287 
            
            Reference Ris Wihthout Link
- 6 
            O’Grady J G, Wendon J, Tan K C. et al .
            Liver transplantation after paracetamol overdose. 
            Br Med J. 
            1991; 
            303 (6796) 
            221-223 
            
            Reference Ris Wihthout Link
- 7 
            Turvill J L, Burroughs A K, Moore K P. 
            Change in occurrence of paracetamol overdose in UK after introduction of blister packs. 
            Lancet. 
            2000; 
            355 (9220) 
            2048-2049 
            
            Reference Ris Wihthout Link
- 8 
            Cooksley W G, Cowen A E, Powell L W. 
            The incidence of oxyphenisatin ingestion in active chronic hepatitis: a prospective
            controlled study of 29 patients. 
            Aust N Z J Med. 
            1973; 
            3 (2) 
            124-128 
            
            Reference Ris Wihthout Link
- 9 
            Goldstein G B, Lam K C, Mistilis S P. 
            Drug-induced active chronic hepatitis. 
            Am J Dig Dis. 
            1973; 
            18 (3) 
            177-184 
            
            Reference Ris Wihthout Link
- 10 
            Dietrichson O, Juhl E, Nielsen J O. et al .
            The incidence of oxyphenisatin-induced liver damage in chronic non-alcoholic liver
            disease. A controlled investigation. 
            Scand J Gastroenterol. 
            1974; 
            9 (5) 
            473-478 
            
            Reference Ris Wihthout Link
- 11 
            Lindberg J, Lindholm A, Lundin P. et al .
            Trigger factors and HL-A antigens in chronic active hepatitis. 
            Br Med J. 
            1975; 
            4 (5988) 
            77-79 
            
            Reference Ris Wihthout Link
- 12 
            Scheuer P J. 
            Classification of chronic viral hepatitis: a need for reassessment. 
            J Hepatol. 
            1991; 
            13 (3) 
            372-374 
            
            Reference Ris Wihthout Link
- 13 Desmeules J, Bonabry P, Dayer P. Hepatic metabolism of drugs. Bircher J, Benhamou J, McIntyre N et al Oxford Textbook of Clinical Hepatology New York; Oxford University Press 1999: 145-164 
            Reference Ris Wihthout Link
- 14 
            Sipes I G, Slocumb M L, Perry D F. et al .
            2,4,5,2’,4’,5’-Hexachlorobiphenyl: distribution, metabolism, and excretion in the
            dog and the monkey. 
            Toxicol Appl Pharmacol. 
            1982; 
            65 (2) 
            264-272 
            
            Reference Ris Wihthout Link
- 15 
            Dianzani M U. 
            The role of free radicals in liver damage. 
            Proc Nutr Soc. 
            1987; 
            46 (1) 
            43-52 
            
            Reference Ris Wihthout Link
- 16 
            Williams A T, Burk R F. 
            Carbon tetrachloride hepatotoxicity: an example of free radical-mediated injury. 
            Semin Liver Dis. 
            1990; 
            10 (4) 
            279-284 
            
            Reference Ris Wihthout Link
- 17 
            Lindros K O, Cai Y A, Penttila K E. 
            Role of ethanol-inducible cytochrome P-450 IIE1 in carbon tetrachloride-induced damage
            to centrilobular hepatocytes from ethanol-treated rats. 
            Hepatology. 
            1990; 
            12 (5) 
            1092-1097 
            
            Reference Ris Wihthout Link
- 18 
            Persson J O, Terelius Y, Ingelman-Sundberg M. 
            Cytochrome P-450-dependent formation of reactive oxygen radicals: isozyme-specific
            inhibition of P-450-mediated reduction of oxygen and carbon tetrachloride. 
            Xenobiotica. 
            1990; 
            20 (9) 
            887-900 
            
            Reference Ris Wihthout Link
- 19 
            Recknagel R O, Glende E A. 
            Carbon tetrachloride hepatotoxicity: an example of lethal cleavage. 
            CRC Critical Reviews in Toxicology 2. 
            1973; 
            263-297 
            
            Reference Ris Wihthout Link
- 20 
            Judah J D, McLean A E, McLean E K. 
            Biochemical mechanisms of liver injury. 
            Am J Med. 
            1970; 
            49 
            609-16 
            
            Reference Ris Wihthout Link
- 21 
            Faber J, Finkelstein J D. 
            Inherited metabolic defects involving the liver. 
            Med Clin North Am. 
            1975; 
            59 (4) 
            919-925 
            
            Reference Ris Wihthout Link
- 22 
            Boll M, Weber L W, Becker E. et al .
            Mechanism of carbon tetrachloride-induced hepatotoxicity. Hepatocellular damage by
            reactive carbon tetrachloride metabolites. 
            Z Naturforsch [C]. 
            2001; 
            56 (7-8) 
            649-59 
            
            Reference Ris Wihthout Link
- 23 
            Minoda Y, Kharasch E D. 
            Halothane-dependent lipid peroxidation in human liver microsomes is catalyzed by cytochrome
            P4502A6 (CYP2A6). 
            Anesthesiology. 
            2001; 
            95 (2) 
            509-514 
            
            Reference Ris Wihthout Link
- 24 
            Bessems J G, Vermeulen N P. 
            Paracetamol (acetaminophen)-induced toxicity: molecular and biochemical mechanisms,
            analogues and protective approaches. 
            Crit Rev Toxicol. 
            2001; 
            31 (1) 
            55-138 
            
            Reference Ris Wihthout Link
- 25 
            Mitchell J R, Jollow D J, Potter W Z. et al .
            Acetaminophen-induced hepatic necrosis. I. Role of drug metabolism. 
            J Pharmacol Exp Ther. 
            1973; 
            187 (1) 
            185-194 
            
            Reference Ris Wihthout Link
- 26 
            Mitchell J R, Jollow D J, Potter W Z. et al .
            Acetaminophen-induced hepatic necrosis. IV. Protective role of glutathione. 
            J Pharmacol Exp Ther. 
            1973; 
            187 (1) 
            211-217 
            
            Reference Ris Wihthout Link
- 27 
            Corcoran G B, Mitchell J R, Vaishnav Y N. et al .
            Evidence that acetaminophen and N-hydroxyacetaminophen form a common arylating intermediate,
            N-acetyl-p-benzoquinoneimine. 
            Mol Pharmacol. 
            1980; 
            18 (3) 
            536-542 
            
            Reference Ris Wihthout Link
- 28 
            Dahlin D C, Miwa G T, Lu A Y. et al .
            N-acetyl-p-benzoquinoneimine: a cytochrome P-450-mediated oxidation product of acetaminophen. 
            Proc Natl Acad Sci U S A. 
            1984; 
            81 (5) 
            1327-1331 
            
            Reference Ris Wihthout Link
- 29 
            Jollow D J, Mitchell J R, Potter W Z. et al .
            Acetaminophen-induced hepatic necrosis. II. Role of covalent binding in vivo. 
            J Pharmacol Exp Ther. 
            1973; 
            187 (1) 
            195-202 
            
            Reference Ris Wihthout Link
- 30 
            Potter W Z, Davis D C, Mitchell J R. et al .
            Acetaminophen-induced hepatic necrosis. 3. Cytochrome P-450-mediated covalent binding
            in vitro. 
            J Pharmacol Exp Ther. 
            1973; 
            187 (1) 
            203-210 
            
            Reference Ris Wihthout Link
- 31 
            Streeter A J, Dahlin D C, Nelson S D. et al .
            The covalent binding of acetaminophen to protein. Evidence for cysteine residues as
            major sites of arylation in vitro. 
            Chem Biol Interact. 
            1984; 
            48 (3) 
            349-366 
            
            Reference Ris Wihthout Link
- 32 
            Hoffmann K J, Streeter A J, Axworthy D B. et al .
            Identification of the major covalent adduct formed in vitro and in vivo between acetaminophen
            and mouse liver proteins. 
            Mol Pharmacol. 
            1985; 
            27 (5) 
            566-573 
            
            Reference Ris Wihthout Link
- 33 
            Hongslo J K, Smith C V, Brunborg G. et al .
            Genotoxicity of paracetamol in mice and rats. 
            Mutagenesis. 
            1994; 
            9 (2) 
            93-100 
            
            Reference Ris Wihthout Link
- 34 
            Yamada T. 
            Covalent binding theory for acetaminophen hepatotoxicity. 
            Gastroenterology. 
            1983; 
            85 (1) 
            202-203 
            
            Reference Ris Wihthout Link
- 35 
            Nelson S D. 
            Mechanisms of the formation and disposition of reactive metabolites that can cause
            acute liver injury. 
            Drug Metab Rev. 
            1995; 
            27 (1-2) 
            147-177 
            
            Reference Ris Wihthout Link
- 36 
            Beitia G, Cobreros A, Sainz L. et al .
            3,4-Methylenedioxymethamphetamine (ecstasy)-induced hepatotoxicity: effect on cytosolic
            calcium signals in isolated hepatocytes. 
            Liver. 
            1999; 
            19 (3) 
            234-241 
            
            Reference Ris Wihthout Link
- 37 
            Berson A, Schmets L, Fisch C. et al .
            Inhibition by nilutamide of the mitochondrial respiratory chain and ATP formation.
            Possible contribution to the adverse effects of this antiandrogen. 
            J Pharmacol Exp Ther. 
            1994; 
            270 (1) 
            167-176 
            
            Reference Ris Wihthout Link
- 38 
            Yasuda S U, Sausville E A, Hutchins J B. et al .
            Amiodarone-induced lymphocyte toxicity and mitochondrial function. 
            J Cardiovasc Pharmacol. 
            1996; 
            28 (1) 
            94-100 
            
            Reference Ris Wihthout Link
- 39 
            Pessayre D, Mansouri A, Haouzi D. et al .
            Hepatotoxicity due to mitochondrial dysfunction. 
            Cell Biol Toxicol. 
            1999; 
            15 (6) 
            367-373 
            
            Reference Ris Wihthout Link
- 40 
            Josephson S A, Kessel E R. 
            Amiodarone hepatotoxicity. 
            Dig Dis. 
            1997; 
            15 (4-5) 
            312 
            
            Reference Ris Wihthout Link
- 41 
            Fromenty B, Fisch C, Labbe G. et al .
            Amiodarone inhibits the mitochondrial beta-oxidation of fatty acids and produces microvesicular
            steatosis of the liver in mice. 
            J Pharmacol Exp Ther. 
            1990; 
            255 (3) 
            1371-1376 
            
            Reference Ris Wihthout Link
- 42 
            Fromenty B, Fisch C, Berson A. et al .
            Dual effect of amiodarone on mitochondrial respiration. Initial protonophoric uncoupling
            effect followed by inhibition of the respiratory chain at the levels of complex I
            and complex II. 
            J Pharmacol Exp Ther. 
            1990; 
            255 (3) 
            1377-1384 
            
            Reference Ris Wihthout Link
- 43 
            Weiland T. 
            Poisonous principles of mushrooms of the genus Amanita. 
            Science. 
            1968; 
            159 
            946-952 
            
            Reference Ris Wihthout Link
- 44 
            Faulstich H. 
            New aspects of amanita poisoning. 
            Klin Wochenschr. 
            1979; 
            57 (21) 
            1143-1152 
            
            Reference Ris Wihthout Link
- 45 
            Himmelmann A, Mang G, Schnorf-Huber S. 
            Lethal ingestion of stored Amanita phalloides mushrooms. 
            Swiss Med Wkly. 
            2001; 
            131 (41-42) 
            616-617 
            
            Reference Ris Wihthout Link
- 46 
            Cochet-Meilhac M, Chambon P. 
            Animal DNA-dependent RNA polymerases. 11. Mechanism of the inhibition of RNA polymerases
            B by amatoxins. 
            Biochim Biophys Acta. 
            1974; 
            353 (2) 
            160-184 
            
            Reference Ris Wihthout Link
- 47 Zimmerman H J. Chemical hepatic injury and its detection. Plaa G, Hewitt WR Toxicology of the liver New York; Raven Press 1982: 1-45 
            Reference Ris Wihthout Link
- 48 
            Kopelman H, Robertson M H, Sanders P G. et al .
            The Epping jaundice. 
            Br Med J. 
            1966; 
            5486 
            514-516 
            
            Reference Ris Wihthout Link
- 49 
            Kopelman H. 
            The Epping jaundice after two years. 
            Postgrad Med J. 
            1968; 
            44 (507) 
            78-81 
            
            Reference Ris Wihthout Link
- 50 
            Williams S V, Bryan J A, Burk J R. et al .
            Letter: Toxic hepatitis and methylenedianiline. 
            N Engl J Med. 
            1974; 
            291 (23) 
            
            Reference Ris Wihthout Link
- 51 
            Zimmerman H J, Lewis J H. 
            Drug-induced cholestasis. 
            Med Toxicol. 
            1987; 
            2 
            112-160 
            
            Reference Ris Wihthout Link
- 52 
            Huang L, Smit J W, Meijer D K. et al .
            Mrp2 is essential for estradiol-17beta (beta-D-glucuronide)-induced cholestasis in
            rats. 
            Hepatology. 
            2000; 
            32 (1) 
            66-72 
            
            Reference Ris Wihthout Link
- 53 
            Stieger B, Fattinger K, Madon J. et al .
            Drug- and estrogen-induced cholestasis through inhibition of the hepatocellular bile
            salt export pump (Bsep) of rat liver. 
            Gastroenterology. 
            2000; 
            118 (2) 
            422-430 
            
            Reference Ris Wihthout Link
- 54 
            Schmid M. 
            Cutaneous porphyria in Turkey. 
            N Engl J Med. 
            1960; 
            272 
            546-550 
            
            Reference Ris Wihthout Link
- 55 
            Peters H A. 
            Hexachlorobenzene poisoning in Turkey. 
            Fed Proc. 
            1976; 
            35 (12) 
            2400-2403 
            
            Reference Ris Wihthout Link
- 56 
            de Matteis F, Gibbs A H, Jackson A H. et al .
            Conversion of liver haem into N-substituted porphyrins or green pigments. Nature of
            the substituent at the pyrrole nitrogen atom. 
            FEBS Lett. 
            1980; 
            119 (1) 
            109-112 
            
            Reference Ris Wihthout Link
- 57 
            Doss M O. 
            Porphyria cutanea tarda (chronic hepatic porphyria): new aspects on pathogenesis,
            diagnosis and therapy with a review of the workshop, „Cutaneous porphyrias” at the
            17th World Congress of Dermatology in Berlin 1987. 
            Z Hautkr. 
            1988; 
            63 (4) 
            282-289 
            
            Reference Ris Wihthout Link
- 58 
            De Catabbi S CB, Aldonatti C, de Viale L C. 
            Heme metabolism after discontinued hexachlorobenzene administration in rats: possible
            irreversible changes and biomarker for hexachlorobenzene persistence. 
            Comp Biochem Physiol C Toxicol Pharmacol. 
            2000; 
            127 (2) 
            165-175 
            
            Reference Ris Wihthout Link
- 59 
            Essigmann J M, Croy R G, Bennett R A. et al .
            Metabolic activation of aflatoxin B1: patterns of DNA adduct formation, removal, and
            excretion in relation to carcinogenesis. 
            Drug Metab Rev. 
            1982; 
            13 (4) 
            581-602 
            
            Reference Ris Wihthout Link
- 60 
            Alpert M E, Davidson C S. 
            Mycotoxins. A possible cause of primary carcinoma of the liver. 
            Am J Med. 
            1969; 
            46 (3) 
            325-329 
            
            Reference Ris Wihthout Link
- 61 
            Peers F G, Linsell C A. 
            Dietary aflatoxins and liver cancer-a population based study in Kenya. 
            Br J Cancer. 
            1973; 
            27 (6) 
            473-484 
            
            Reference Ris Wihthout Link
- 62 
            Enwonwu C O. 
            The role of dietary aflatoxin in the genesis of hepatocellular cancer in developing
            countries. 
            Lancet. 
            1984; 
            2 (8409) 
            956-958 
            
            Reference Ris Wihthout Link
- 63 
            Swenberg J A, Bogdanffy M S, Ham A. et al .
            Formation and repair of DNA adducts in vinyl chloride- and vinyl fluoride-induced
            carcinogenesis. 
            IARC Sci Publ. 
            1999; 
            (150) 
            29-43 
            
            Reference Ris Wihthout Link
- 64 
            Kielhorn J, Melber C, Wahnschaffe U. et al .
            Vinyl chloride: still a cause for concern. 
            Environ Health Perspect. 
            2000; 
            108 (7) 
            579-588 
            
            Reference Ris Wihthout Link
- 65 
            Pereg D, Robertson L W, Gupta R C. 
            DNA adduction by polychlorinated biphenyls: adducts derived from hepatic microsomal
            activation and from synthetic metabolites. 
            Chem Biol Interact. 
            2002; 
            139 (2) 
            129-144 
            
            Reference Ris Wihthout Link
- 66 
            O’Brien T, Babcock G, Cornelius J. et al .
            A comparison of apoptosis and necrosis induced by hepatotoxins in HepG2 cells. 
            Toxicol Appl Pharmacol. 
            2000; 
            164 (3) 
            280-290 
            
            Reference Ris Wihthout Link
- 67 
            Aguilar F, Hussain S P, Cerutti P. 
            Aflatoxin B1 induces the transversion of G->T in codon 249 of the p53 tumor suppressor
            gene in human hepatocytes. 
            Proc Natl Acad Sci U S A. 
            1993; 
            90 (18) 
            8586-8590 
            
            Reference Ris Wihthout Link
- 68 
            Guengerich F P, Watanabe P G. 
            Metabolism of [14C]- and [36C]-labeled vinyl chloride in vivo and in vitro. 
            Biochem Pharmacol. 
            1979; 
            28 (5) 
            589-596 
            
            Reference Ris Wihthout Link
- 69 
            Tamburro C H, Makk L, Popper H. 
            Early hepatic histologic alterations among chemical (vinyl monomer) workers. 
            Hepatology. 
            1984; 
            4 (3) 
            413-418 
            
            Reference Ris Wihthout Link
- 70 
            Mundt K A, Dell L D, Austin R P. et al .
            Historical cohort study of 10 109 men in the North American vinyl chloride industry,
            1942-72: update of cancer mortality to 31 December 1995. 
            Occup Environ Med. 
            2000; 
            57 (11) 
            774-781 
            
            Reference Ris Wihthout Link
- 71 
            Binetti R, Costamagna F M, Marcello I. 
            Vinyl chloride and 1,2-dichloroethane: classification and assessment of carcinogenicity,
            guidelines, threshold values, and standards developed by national and international
            entities, organizations, and agencies. 
            Epidemiol Prev. 
            2001; 
            25 (1) 
            31-39 
            
            Reference Ris Wihthout Link
- 72 
            Smela M E, Currier S S, Bailey E A. et al .
            The chemistry and biology of aflatoxin B (1): from mutational spectrometry to carcinogenesis. 
            Carcinogenesis. 
            2001; 
            22 (4) 
            535-545 
            
            Reference Ris Wihthout Link
- 73 
            Ward E, Boffetta P, Andersen A. et al .
            Update of the follow-up of mortality and cancer incidence among European workers employed
            in the vinyl chloride industry. 
            Epidemiology. 
            2001; 
            12 (6) 
            710-718 
            
            Reference Ris Wihthout Link
- 74 
            Hollstein M, Marion M J, Lehman T. et al .
            p53 mutations at A: T base pairs in angiosarcomas of vinyl chloride-exposed factory
            workers. 
            Carcinogenesis. 
            1994; 
            15 (1) 
            1-3 
            
            Reference Ris Wihthout Link
- 75 
            Kenna J G, Satoh H, Christ D D. et al .
            Metabolic basis for a drug hypersensitivity: antibodies in sera from patients with
            halothane hepatitis recognize liver neoantigens that contain the trifluoroacetyl group
            derived from halothane. 
            J Pharmacol Exp Ther. 
            1988; 
            245 (3) 
            1103-1109 
            
            Reference Ris Wihthout Link
- 76 
            Gut J, Christen U, Huwyler J. 
            Mechanisms of halothane toxicity: novel insights. 
            Pharmacol Ther. 
            1993; 
            58 (2) 
            133-155 
            
            Reference Ris Wihthout Link
- 77 
            Volpes R, van den Oord J J, Desmet V J. 
            Can hepatocytes serve as ‘activated’ immunomodulating cells in the immune response?. 
            J Hepatol. 
            1992; 
            16 (1-2) 
            228-240 
            
            Reference Ris Wihthout Link
- 78 
            Pessayre D. 
            Role of reactive metabolites in drug-induced hepatitis. 
            J Hepatol. 
            1995; 
            23 (Suppl 1) 
            16-24 
            
            Reference Ris Wihthout Link
- 79 
            Vergani D, Mieli-Vergani G, Alberti A. et al .
            Antibodies to the surface of halothane-altered rabbit hepatocytes in patients with
            severe halothane-associated hepatitis. 
            N Engl J Med. 
            1980; 
            303 (2) 
            66-71 
            
            Reference Ris Wihthout Link
- 80 
            Satoh H, Fukuda Y, Anderson D K. et al .
            Immunological studies on the mechanism of halothane-induced hepatotoxicity: immunohistochemical
            evidence of trifluoroacetylated hepatocytes. 
            J Pharmacol Exp Ther. 
            1985; 
            233 (3) 
            857-862 
            
            Reference Ris Wihthout Link
- 81 
            Loeper J, Descatoire V, Amouyal G. et al .
            Presence of covalently bound metabolites on rat hepatocyte plasma membrane proteins
            after administration of isaxonine, a drug leading to immunoallergic hepatitis in man. 
            Hepatology. 
            1989; 
            9 (5) 
            675-678 
            
            Reference Ris Wihthout Link
- 82 
            Beaune P H, Lecoeur S. 
            Immunotoxicology of the liver: adverse reactions to drugs. 
            J Hepatol. 
            1997; 
            26 (Suppl 2) 
            37-42 
            
            Reference Ris Wihthout Link
- 83 
            Dansette P M, Bonierbale E, Minoletti C. et al .
            Drug-induced immunotoxicity. 
            Eur J Drug Metab Pharmacokinet. 
            1998; 
            23 (4) 
            443-451 
            
            Reference Ris Wihthout Link
- 84 
            Satoh H, Gillette J R, Davies H W. et al .
            Immunochemical evidence of trifluoroacetylated cytochrome P-450 in the liver of halothane-treated
            rats. 
            Mol Pharmacol. 
            1985; 
            28 (5) 
            468-474 
            
            Reference Ris Wihthout Link
- 85 
            Satoh H, Gillette J R, Takemura T. et al .
            Investigation of the immunological basis of halothane-induced hepatotoxicity. 
            Adv Exp Med Biol. 
            1986; 
            197 
            657-673 
            
            Reference Ris Wihthout Link
- 86 
            Satoh H, Martin B M, Schulick A H. et al .
            Human anti-endoplasmic reticulum antibodies in sera of patients with halothane-induced
            hepatitis are directed against a trifluoroacetylated carboxylesterase. 
            Proc Natl Acad Sci U S A. 
            1989; 
            86 (1) 
            322-326 
            
            Reference Ris Wihthout Link
- 87 
            Musch E, Eichelbaum M, Wang J K. et al .
            Incidence of hepatotoxic side effects during antituberculous therapy (INH, RMP, EMB)
            in relation to the acetylator phenotype (author’s transl). 
            Klin Wochenschr. 
            1982; 
            60 (10) 
            513-519 
            
            Reference Ris Wihthout Link
- 88 
            Ohno M, Yamaguchi I, Yamamoto I. et al .
            Slow N-acetyltransferase 2 genotype affects the incidence of isoniazid and rifampicin-induced
            hepatotoxicity. 
            Int J Tuberc Lung Dis. 
            2000; 
            4 (3) 
            256-261 
            
            Reference Ris Wihthout Link
- 89 
            Huang Y S, Chern H D, Su W J. et al .
            Polymorphism of the N-acetyltransferase 2 gene as a susceptibility risk factor for
            antituberculosis drug-induced hepatitis. 
            Hepatology. 
            2002; 
            35 (4) 
            883-889 
            
            Reference Ris Wihthout Link
- 90 
            Szumlanski C L, Honchel R, Scott M C. et al .
            Human liver thiopurine methyltransferase pharmacogenetics: biochemical properties,
            liver-erythrocyte correlation and presence of isozymes. 
            Pharmacogenetics. 
            1992; 
            2 (4) 
            148-159 
            
            Reference Ris Wihthout Link
- 91 
            Dubinsky M C, Lamothe S, Yang H Y. et al .
            Pharmacogenomics and metabolite measurement for 6-mercaptopurine therapy in inflammatory
            bowel disease. 
            Gastroenterology. 
            2000; 
            118 (4) 
            705-713 
            
            Reference Ris Wihthout Link
- 92 
            Szumlanski C, Otterness D, Her C. et al .
            Thiopurine methyltransferase pharmacogenetics: human gene cloning and characterization
            of a common polymorphism. 
            DNA Cell Biol. 
            1996; 
            15 (1) 
            17-30 
            
            Reference Ris Wihthout Link
- 93 
            Evans W E, Hon Y Y, Bomgaars L. et al .
            Preponderance of thiopurine S-methyltransferase deficiency and heterozygosity among
            patients intolerant to mercaptopurine or azathioprine. 
            J Clin Oncol. 
            2001; 
            19 (8) 
            2293-2301 
            
            Reference Ris Wihthout Link
- 94 
            Bertilsson L, Dahl M L, Dalen P. et al .
            Molecular genetics of CYP2D6: clinical relevance with focus on psychotropic drugs. 
            Br J Clin Pharmacol. 
            2002; 
            53 (2) 
            111-122 
            
            Reference Ris Wihthout Link
- 95 Ishak K G. Drug-Induced Liver Injury Pathology. Bloomer JR, Goodman ZD, Ishak KG Clinical and Pathological correlations in liver disease: Approaching the next millenium Washington DC; The Armed Forces Institute of Pathology 1998: 236-251 
            Reference Ris Wihthout Link
- 96 
            Larrey D, Erlinger S. 
            Drug-induced cholestasis. 
            Baillieres Clin Gastroenterol. 
            1988; 
            2 (2) 
            423-452 
            
            Reference Ris Wihthout Link
- 97 
            Levy M, Goodman M W, Van Dyne B J. et al .
            Granulomatous hepatitis secondary to carbamazepine. 
            Ann Intern Med. 
            1981; 
            95 (1) 
            64-65 
            
            Reference Ris Wihthout Link
- 98 
            Larrey D, Hadengue A, Pessayre D. et al .
            Carbamazepine-induced acute cholangitis. 
            Dig Dis Sci. 
            1987; 
            32 (5) 
            554-557 
            
            Reference Ris Wihthout Link
- 99 
            Ishak K G, Zimmerman H J. 
            Hepatotoxic effects of the anabolic/androgenic steroids. 
            Semin Liver Dis. 
            1987; 
            7 (3) 
            230-236 
            
            Reference Ris Wihthout Link
- 100 Zimmerman H J. Drug-induced liver injury clinical. Bloomer JR, Goodman ZD, Ishak KG Clinical and pathological correlations in liver disease: Approaching the next millenium Washington DC; The Armed Forces Institute of Pathology 1998: 252-269 
            Reference Ris Wihthout Link
- 101 Farrell G C. Drug-induced liver injury. New York; Chruchill Livingstone 1994 
            Reference Ris Wihthout Link
- 102 Zimmerman H J. Hepatotoxicity. In: The adverse effects of drugs and other chemicals on the liver New York; Appleton Century Crofts 1978 
            Reference Ris Wihthout Link
- 103 Zimmerman H J, Ishak K G. Non-alcoholic steatohepatitis and other forms of pseudoalcoholic liver disease. Hall P Alcoholic liver disease. Pathology and Pathogenesis London; Arnold 1995: 175-198 
            Reference Ris Wihthout Link
- 104 
            de Knegt R J. 
            Non-alcoholic steatohepatitis: clinical significance and pathogenesis. 
            Scand J Gastroenterol Suppl. 
            2001; 
            234 
            88-92 
            
            Reference Ris Wihthout Link
- 105 
            Reid A E. 
            Nonalcoholic steatohepatitis. 
            Gastroenterology. 
            2001; 
            121 (3) 
            710-723 
            
            Reference Ris Wihthout Link
- 106 
            Poucell S, Ireton J, Valencia-Mayoral P. et al .
            Amiodarone-associated phospholipidosis and fibrosis of the liver. Light, immunohistochemical,
            and electron microscopic studies. 
            Gastroenterology. 
            1984; 
            86 (5 Pt 1) 
            926-936 
            
            Reference Ris Wihthout Link
- 107 
            Lewis J H, Ranard R C, Caruso A. et al .
            Amiodarone hepatotoxicity: prevalence and clinicopathologic correlations among 104
            patients. 
            Hepatology. 
            1989; 
            9 (5) 
            679-685 
            
            Reference Ris Wihthout Link
- 108 
            Lewis J H, Mullick F, Ishak K G. et al .
            Histopathologic analysis of suspected amiodarone hepatotoxicity. 
            Hum Pathol. 
            1990; 
            21 (1) 
            59-67 
            
            Reference Ris Wihthout Link
- 109 
            Langman G, Hall P M, Todd G. 
            Role of non-alcoholic steatohepatitis in methotrexate-induced liver injury. 
            J Gastroenterol Hepatol. 
            2001; 
            16 (12) 
            1395-1401 
            
            Reference Ris Wihthout Link
- 110 
            Seki K, Minami Y, Nishikawa M. et al .
            „Nonalcoholic steatohepatitis” induced by massive doses of synthetic estrogen. 
            Gastroenterol Jpn. 
            1983; 
            18 (3) 
            197-203 
            
            Reference Ris Wihthout Link
- 111 
            Nemoto Y, Saibara T, Ogawa Y. et al .
            Tamoxifen-induced nonalcoholic steatohepatitis in breast cancer patients treated with
            adjuvant tamoxifen. 
            Intern Med. 
            2002; 
            41 (5) 
            345-350 
            
            Reference Ris Wihthout Link
- 112 
            Rahmat J, Gelfand R L, Gelfand M C. et al .
            Captopril-associated cholestatic jaundice. 
            Ann Intern Med. 
            1985; 
            102 (1) 
            56-58 
            
            Reference Ris Wihthout Link
- 113 
            Crantock L, Prentice R, Powell L. 
            Cholestatic jaundice associated with captopril therapy. 
            J Gastroenterol Hepatol. 
            1991; 
            6 (5) 
            528-530 
            
            Reference Ris Wihthout Link
- 114 
            Nissan A, Spira R M, Seror D. et al .
            Captopril-associated „pseudocholangitis”. A case report and review of the literature. 
            Arch Surg. 
            1996; 
            131 (6) 
            670-671 
            
            Reference Ris Wihthout Link
- 115 
            Hurlimann R, Binek J, Oehlschlegel C. et al .
            Enalapril (Reniten)-associated toxic hepatitis. 
            Schweiz Med Wochenschr. 
            1994; 
            124 (29) 
            1276-1280 
            
            Reference Ris Wihthout Link
- 116 
            Dowsett J F, Gillow T, Heagerty A. et al .
            Amoxycillin/clavulanic acid (Augmentin)-induced intrahepatic cholestasis. 
            Dig Dis Sci. 
            1989; 
            34 (8) 
            1290-1293 
            
            Reference Ris Wihthout Link
- 117 
            Koek G H, Stricker B H, Blok A P. et al .
            Flucloxacillin-associated hepatic injury. 
            Liver. 
            1994; 
            14 (5) 
            225-229 
            
            Reference Ris Wihthout Link
- 118 
            Pedro-Botet J, Supervia A, Barranco C. et al .
            Intrahepatic cholestasis without hepatitis induced by amoxycillin/clavulanic acid. 
            J Clin Gastroenterol. 
            1996; 
            23 (2) 
            137-138 
            
            Reference Ris Wihthout Link
- 119 
            Desmet V J, van Eyken P, Roskams T. 
            Histopathology of vanishing bile duct diseases. 
            Adv Clin Path. 
            1998; 
            2 (2) 
            87-99 
            
            Reference Ris Wihthout Link
- 120 
            Geubel A P, Sempoux C L. 
            Drug and toxin-induced bile duct disorders. 
            J Gastroenterol Hepatol. 
            2000; 
            15 (11) 
            1232-1238 
            
            Reference Ris Wihthout Link
- 121 
            Bolton J S, Bowen J C. 
            Biliary sclerosis associated with hepatic artery infusion of floxuridine. 
            Surgery. 
            1986; 
            99 (1) 
            119-122 
            
            Reference Ris Wihthout Link
- 122 
            Aldrighetti L, Arru M, Ronzoni M. et al .
            Extrahepatic biliary stenoses after hepatic arterial infusion (HAI) of floxuridine
            (FUdR) for liver metastases from colorectal cancer. 
            Hepatogastroenterology. 
            2001; 
            48 (41) 
            1302-1307 
            
            Reference Ris Wihthout Link
- 123 
            Dikengil A, Siskind B N, Morse S S. et al .
            Sclerosing cholangitis from intraarterial floxuridine. 
            J Clin Gastroenterol. 
            1986; 
            8 (6) 
            690-693 
            
            Reference Ris Wihthout Link
- 124 
            Hohn D, Melnick J, Stagg R. et al .
            Biliary sclerosis in patients receiving hepatic arterial infusions of floxuridine. 
            J Clin Oncol. 
            1985; 
            3 (1) 
            98-102 
            
            Reference Ris Wihthout Link
- 125 
            Kemeny M M, Battifora H, Blayney D W. et al .
            Sclerosing cholangitis after continuous hepatic artery infusion of FUDR. 
            Ann Surg. 
            1985; 
            202 (2) 
            176-181 
            
            Reference Ris Wihthout Link
- 126 
            Shea W J Jr, Demas B E, Goldberg H I. et al .
            Sclerosing cholangitis associated with hepatic arterial FUDR chemotherapy: radiographic-histologic
            correlation. 
            AJR Am J Roentgenol. 
            1986; 
            146 (4) 
            717-721 
            
            Reference Ris Wihthout Link
- 127 
            Mallat A, Zafrani E S, Metreau J M. et al .
            Terbinafine-induced prolonged cholestasis with reduction of interlobular bile ducts. 
            Dig Dis Sci. 
            1997; 
            42 (7) 
            1486-1488 
            
            Reference Ris Wihthout Link
- 128 
            Valla D, Le M G, Poynard T. et al .
            Risk of hepatic vein thrombosis in relation to recent use of oral contraceptives.
            A case-control study. 
            Gastroenterology. 
            1986; 
            90 (4) 
            807-811 
            
            Reference Ris Wihthout Link
- 129 Bras G, Brandt K H. Vascular disorders. MacSween RNM, Anthony PP, Scheur PJ Pathology of the liver Edinburgh; Chruchill Livingstone 1987: 478-502 
            Reference Ris Wihthout Link
- 130 
            Zafrani E S, Pinaudeau Y, Dhumeau D. 
            Drug-induced vascular lesions of the liver. 
            Arch Intern Med. 
            1983; 
            143 
            395 
            
            Reference Ris Wihthout Link
- 131 
            Modzelewski J R Jr, Daeschner C, Joshi V V. et al .
            Veno-occlusive disease of the liver induced by low-dose cyclophosphamide. 
            Mod Pathol. 
            1994; 
            7 (9) 
            967-972 
            
            Reference Ris Wihthout Link
- 132 
            Hazar V, Kutluk T, Akyuz C. et al .
            Veno-occlusive disease-like hepatotoxicity in two children receiving chemotherapy
            for Wilms’ tumor and clear cell sarcoma of kidney. 
            Pediatr Hematol Oncol. 
            1998; 
            15 (1) 
            85-89 
            
            Reference Ris Wihthout Link
- 133 
            Chitturi S, Farrell G C. 
            Herbal hepatotoxicity: an expanding but poorly defined problem. 
            J Gastroenterol Hepatol. 
            2000; 
            15 (10) 
            1093-1099 
            
            Reference Ris Wihthout Link
- 134 
            Valla D, Benhamou J P. 
            Drug-induced vascular and sinusoidal lesions of the liver. 
            Baillieres Clin Gastroenterol. 
            1988; 
            2 (2) 
            481-500 
            
            Reference Ris Wihthout Link
- 135 
            Zafrani E S, von Pinaudeau Y, Dhumeaux D. 
            Drug-induced vascular lesions of the liver. 
            Arch Intern Med. 
            1983; 
            143 (3) 
            495-502 
            
            Reference Ris Wihthout Link
- 136 
            Edmondson H A, Henderson B, Benton B. 
            Liver-cell adenomas associated with use of oral contraceptives. 
            N Engl J Med. 
            1976; 
            294 (9) 
            470-472 
            
            Reference Ris Wihthout Link
- 137 
            Klatskin G. 
            Hepatic tumors: possible relationship to use of oral contraceptives. 
            Gastroenterology. 
            1977; 
            73 (2) 
            386-394 
            
            Reference Ris Wihthout Link
- 138 
            Metzler M, Degen G H. 
            Sex hormones and neoplasia: liver tumors in rodents. 
            Arch Toxicol Suppl. 
            1987; 
            10 
            251-263 
            
            Reference Ris Wihthout Link
- 139 
            Scott L D, Katz A R, Duke J H. et al .
            Oral contraceptives, pregnancy, and focal nodular hyperplasia of the liver. 
            JAMA. 
            1984; 
            251 (11) 
            1461-1463 
            
            Reference Ris Wihthout Link
- 140 
            Falk H, Herbert J, Crowley S. et al .
            Epidemiology of hepatic angiosarcoma in the United States: 1964-1974. 
            Environ Health Perspect. 
            1981; 
            41 
            107-113 
            
            Reference Ris Wihthout Link
- 141 
            Zafrani E S. 
            Update on vascular tumours of the liver. 
            J Hepatol. 
            1989; 
            8 (1) 
            125-130 
            
            Reference Ris Wihthout Link
- 142 van Kaick G, Wesch H. The German Thorotrast study. van Kaick G, Muth H, Kaul A Luxembourg; European Communities 1984: 190-211 
            Reference Ris Wihthout Link
- 143 
            Picciotto A, Campo N, Brizzolara R. et al .
            Chronic hepatitis induced by Jin Bu Huan. 
            J Hepatol. 
            1998; 
            28 (1) 
            165-167 
            
            Reference Ris Wihthout Link
- 144 
            Woolf G M, Petrovic L M, Rojter S E. et al .
            Acute hepatitis associated with the Chinese herbal product jin bu huan. 
            Ann Intern Med. 
            1994; 
            121 (10) 
            729-735 
            
            Reference Ris Wihthout Link
- 145 
            Strahl S, Ehret V, Dahm H H. et al .
            Necrotizing hepatitis after taking herbal remedies. 
            Dtsch Med Wochenschr. 
            1998; 
            123 (47) 
            1410-1414 
            
            Reference Ris Wihthout Link
- 146 
            Benninger J, Schneider H T, Schuppan D. et al .
            Acute hepatitis induced by greater celandine (Chelidonium majus). 
            Gastroenterology. 
            1999; 
            117 (5) 
            1234-1237 
            
            Reference Ris Wihthout Link
- 147 
            Larrey D, Vial T, Pauwels A. et al .
            Hepatitis after germander (Teucrium chamaedrys) administration: another instance of
            herbal medicine hepatotoxicity. 
            Ann Intern Med. 
            1992; 
            117 (2) 
            129-132 
            
            Reference Ris Wihthout Link
- 148 
            Mostefa-Kara N, Pauwels A, Pines E. et al .
            Fatal hepatitis after herbal tea. 
            Lancet. 
            1992; 
            340 (8820) 
            674 
            
            Reference Ris Wihthout Link
- 149 
            Kraft M, Spahn T W, Menzel J. et al .
            Fulminant liver failure after administration of the herbal antidepressant Kava-Kava. 
            Dtsch Med Wochenschr. 
            2001; 
            126 (36) 
            970-972 
            
            Reference Ris Wihthout Link
- 150 
            Lucena M I, Camargo R, Andrade R J. et al .
            Comparison of two clinical scales for causality assessment in hepatotoxicity. 
            Hepatology. 
            2001; 
            33 (1) 
            123-130 
            
            Reference Ris Wihthout Link
- 151 
            Aithal G P, Rawlins M D, Day C P. 
            Clinical diagnostic scale: a useful tool in the evaluation of suspected hepatotoxic
            adverse drug reactions. 
            J Hepatol. 
            2000; 
            33 (6) 
            949-952 
            
            Reference Ris Wihthout Link
- 152 
            Maria V A, Pinto L, Victorino R M. 
            Lymphocyte reactivity to ex-vivo drug antigens in drug-induced hepatitis. 
            J Hepatol. 
            1994; 
            21 (2) 
            151-158 
            
            Reference Ris Wihthout Link
- 153 
            Maria V A, Victorino R M. 
            Diagnostic value of specific T cell reactivity to drugs in 95 cases of drug induced
            liver injury.PG - 534-40. 
            Gut. 
            1997; 
            41 (4) 
            534-540 
            
            Reference Ris Wihthout Link
- 154 
            Smilkstein M J, Knapp G L, Kulig K W. et al .
            Efficacy of oral N-acetylcysteine in the treatment of acetaminophen overdose. Analysis
            of the national multicenter study (1976 to 1985). 
            N Engl J Med. 
            1988; 
            319 (24) 
            1557-1562 
            
            Reference Ris Wihthout Link
- 155 
            Brotodihardjo A E, Batey R G, Farrell G C. et al .
            Hepatotoxicity from paracetamol self-poisoning in western Sydney: a continuing challenge. 
            Med J Aust. 
            1992; 
            157 (6) 
            382-385 
            
            Reference Ris Wihthout Link
- 156 
            McClain C J, Price S, Barve S. et al .
            Acetaminophen hepatotoxicity: An update. 
            Curr Gastroenterol Rep. 
            1999; 
            1 (1) 
            42-49 
            
            Reference Ris Wihthout Link
- 157 
            Jacobs J, Greene H, Gendel B R. 
            Acute iron intoxication. 
            N Engl J Med. 
            1965; 
            273 (21) 
            1124-1127 
            
            Reference Ris Wihthout Link
- 158 
            Blanc P, Hryhorczuk D, Danel I. 
            Deferoxamine treatment of acute iron intoxication in pregnancy. 
            Obstet Gynecol. 
            1984; 
            64 (3 Suppl) 
            12S-14S 
            
            Reference Ris Wihthout Link
- 159 
            Mahoney J R Jr, Hallaway P E, Hedlund B E. et al .
            Acute iron poisoning. Rescue with macromolecular chelators. 
            J Clin Invest. 
            1989; 
            84 (4) 
            1362-1366 
            
            Reference Ris Wihthout Link
- 160 
            Flora K, Hahn M, Rosen H. et al .
            Milk thistle (Silybum marianum) for the therapy of liver disease. 
            Am J Gastroenterol. 
            1998; 
            93 (2) 
            139-143 
            
            Reference Ris Wihthout Link
- 161 
            Floersheim G L, Weber O, Tschumi P. et al .
            Clinical death-cap (Amanita phalloides) poisoning: prognostic factors and therapeutic
            measures. Analysis of 205 cases. 
            Schweiz Med Wochenschr. 
            1982; 
            112 (34) 
            1164-1177 
            
            Reference Ris Wihthout Link
- 162 
            Mills R M Jr. 
            Severe hypersensitivity reactions associated with allopurinol. 
            JAMA. 
            1971; 
            216 (5) 
            799-802 
            
            Reference Ris Wihthout Link
- 163 
            Lang P G Jr. 
            Severe hypersensitivity reactions to allopurinol. 
            South Med J. 
            1979; 
            72 (11) 
            1361-1368 
            
            Reference Ris Wihthout Link
- 164 
            Al-Kawas F H, Seeff L B, Berendson R A. et al .
            Allopurinol hepatotoxicity. Report of two cases and review of the literature. 
            Ann Intern Med. 
            1981; 
            95 (5) 
            588-590 
            
            Reference Ris Wihthout Link
- 165 
            Iveson T J, Ryley N G, Kelly P M. et al .
            Diclofenac associated hepatitis. 
            J Hepatol. 
            1990; 
            10 (1) 
            85-89 
            
            Reference Ris Wihthout Link
- 166 
            Sallie R W, McKenzie T, Reed W D. et al .
            Diclofenac hepatitis. 
            Aust N Z J Med. 
            1991; 
            21 (2) 
            251-255 
            
            Reference Ris Wihthout Link
- 167 
            O’Grady J G, Alexander G J, Hayllar K M. et al .
            Early indicators of prognosis in fulminant hepatic failure. 
            Gastroenterology. 
            1989; 
            97 (2) 
            439-445 
            
            Reference Ris Wihthout Link
- 168 
            Katsinelos P, Vasiliadis T, Xiarchos P. et al .
            Ursodeoxycholic acid (UDCA) for the treatment of amoxycillin-clavulanate potassium
            (Augmentin)-induced intra-hepatic cholestasis: report of two cases. 
            Eur J Gastroenterol Hepatol. 
            2000; 
            12 (3) 
            365-368 
            
            Reference Ris Wihthout Link
- 169 
            Cicognani C, Malavolti M, Morselli-Labate A M. et al .
            Flutamide-induced toxic hepatitis. Potential utility of ursodeoxycholic acid administration
            in toxic hepatitis. 
            Dig Dis Sci. 
            1996; 
            41 (11) 
            2219-2221 
            
            Reference Ris Wihthout Link
- 170 
            Prince M I, Burt A D, Jones D E. 
            Hepatitis and liver dysfunction with rifampicin therapy for pruritus in primary biliary
            cirrhosis. 
            Gut. 
            2002; 
            50 (3) 
            436-439 
            
            Reference Ris Wihthout Link
- 171 
            Taillan B, Chichmanian R M, Fuzibet J G. et al .
            Jaundice caused by rifampicin: 3 cases. 
            Rev Med Interne. 
            1989; 
            10 (5) 
            409-411 
            
            Reference Ris Wihthout Link
- 172 
            Poupon R Y, Meyniel D, Petit J. et al .
            Cholestatic hepatitis during treatment with I.N.H. and rifampicin: arguments in favour
            of the hepatotoxicity of rifampicin (author’s transl). 
            Ann Med Interne (Paris). 
            1979; 
            130 (6-7) 
            371-375 
            
            Reference Ris Wihthout Link
Priv.-Doz. Dr. med. Christoph Reichel
         Universitätsklinikum Bonn, Medizinische Klinik und Poliklinik I
         
         Sigmund-Freud-Straße 25
         
         53105 Bonn
         
         eMail: c.reichel@uni-bonn.de
         
         
 
     
      
    