Skip to main content
SpringerLink
Log in

Drug-Induced Liver Disease

  • Review Article
  • Published:
Drugs Aims and scope Submit manuscript

Summary

The large number of chemical agents administered for therapeutic or diagnostic purposes can produce various types of hepatic injury by several mechanisms. Acute injury may be cytotoxic, cholestatic or mixed. Cytotoxic injury may consist of necrosis or steatosis. Cholestatic injury may be cholangiolitic (hepatocanalicular) or bland (canalicular). Chronic hepatic lesions caused by medicinal agents include chronic active hepatitis, steatosis, cirrhosis, fibrosis, hepatoportal sclerosis (non-cirrhotic portal hypertension), hepatic vein thrombosis, peliosis hepatis, adenoma, carcinoma, and angiosarcoma. There is a useful relationship between the type of hepatic injury and the chemical setting in which the drugs are employed.

Some agents produce the liver damage because they are intrinsic (true, predictable) hepatotoxins. Others (non-predictable ‘hepatotoxins’), produce hepatic injury only in the rare and unusually susceptible individual (idiosyncratic injury). Hepatotoxic agents can be recognised by their dose-dependent and experimental reproducibility, properties which are not shared by agents which produce hepatic injury only in idiosyncratic hosts.

Intrinsic hepatotoxins may be categorised as direct or indirect. Direct hepatotoxins injure the hepatocyte by direct physiochemical alteration and as a consequence produce metabolic defects. Indirect hepatotoxins selectively block metabolic pathways and, by producing a precise biochemical lesion, lead to structural changes. They may lead to hepatic steatosis or necrosis (cytotoxic indirect hepatotoxins) or block bile flow (cholestatic indirect hepatotoxins). Direct hepatotoxins are rarely encountered as drugs.

Overdoses of some drugs and antineoplastic agents appear to be indirect cytotoxic hepatotoxins, and the C-17 alkylated anabolic and contraceptive steroids are indirect, cholestatic hepatotoxins. Idiosyncracy of the host is the mechanism for most types of drug-induced hepatic injury. It may reflect allergy to the drug or a metabolic aberration of the host permitting the production of hepatotoxic metabolites.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Adlercreutz, H. and Tenhunen, R.: Some aspects of the interaction between natural and synthetic female sex hormones and the liver. American Journal of Medicine 49: 630 (1970).

    PubMed  CAS  Google Scholar 

  • Alpers, D.H. and Isselbacher, K.J.: Fatty liver: Biochemical and clinical aspects; in Schiff (Ed) Diseases of the Liver, 4th ed, pp.815–832 (Lippincott, Philadelphia 1975).

    Google Scholar 

  • Baghesi, S.A. and Byer, J.L.: Peliosis hepatis associated with androgenic-anabolic steroid therapy: A severe form of hepatic injury. Annals of Internal Medicine 81: 610 (1974).

    Google Scholar 

  • Baker, R.D. and Handler, P.: Animal experiments with tannic acid suggested by the tannic acid treatment of burns. Annals of Surgery 118: 417 (1943).

    PubMed  CAS  Google Scholar 

  • Batlifora, H.A.: Thorotrast and the tumors of the liver; in Okuda and Peters (Eds) Hepatocellular Carcinoma pp.83–93 (Wiley, New York 1976).

    Google Scholar 

  • Bjornboe, M.; Iverson, O. and Olsen, S.: Infective hepatitis and toxic jaundice in a municipal hospital during a 5-year period. Acta Medica Scandinavica 182: 491 (1967).

    Google Scholar 

  • Black, M.; Mitchell, J.R.; Zimmerman, H.J. et al.: Isoniazid-associated hepatitis in 114 patients. Gastroenterology 69: 289 (1975).

    PubMed  CAS  Google Scholar 

  • Bloodworth, J.M.B. Jr.: Morphologic changes associated with sulfonylurea therapy. Metabolism 12: 287 (1963).

    PubMed  Google Scholar 

  • Bottinger, L.E.; Dalen, E. and Hallin, U.: Halothane-induced liver damage: An analysis of the material reported to the Swedish Adverse Drug Reaction Committee, 1966–1973. Acta Anaesthesiologica Scandinavica 20: 40 (1976).

    Google Scholar 

  • Boyer, T.D.; Sun, N. and Reynolds, T.B.: Allopurinol hypersensitivity and liver damage. Western Journal of Medicine 126: 143 (1977).

    PubMed  CAS  Google Scholar 

  • Brodsky, I.; Johnson, H.; Killman, S.A. et al.: Fibrosis of central and hepatic veins and perisinusoidal spaces of the liver following prolonged administration of urethane. American Journal of Medicine 30: 976 (1961).

    Google Scholar 

  • Burl-Andreassen, P.; Lyngbye, J. and Trolle, E.: Abnormalities in liver function during long-term diphenylhydantoin therapy in epileptic outpatients. Acta Medica Scandinavica 194: 261 (1973).

    Google Scholar 

  • Butler, R.C.; Shah, S.M.; Gurnow, W.A. et al.: Massive hepatic necrosis in a patient receiving allopurinol. Journal of the American Medical Association 237: 473 (1977).

    PubMed  CAS  Google Scholar 

  • Clark, R.; Boriakchanyavat, V.; Davidson, A.R. et al.: Hepatic damage and death from overdose of paracetamol. Lancet 1: 66 (1973).

    PubMed  CAS  Google Scholar 

  • Cohn, H.O.: Clinical studies with new rifamycin derivative. Journal of Clinical Pharmacology and Journal of New Drugs 9: 48 (1969).

    Google Scholar 

  • Cuthbert, M.B.: Adverse reactions to non-steroidal anti-inflammatory drugs. Current Medical Research and Opinion 2: 12 (1974).

    Google Scholar 

  • Dahl, M.G.C.; Gregory, M.M. and Scheuer, P.J.: Liver damage due to methotrexate in patients with psoriasis. British Medical Journal 1: 625 (1971).

    PubMed  CAS  Google Scholar 

  • Dahl, M.G.C.; Gregory, M.M. and Scheuer, P.J.: Methotrexate hepatotoxicity in psoriasis — Comparison of different dose regimen. British Medical Journal 1: 654 (1972).

    PubMed  CAS  Google Scholar 

  • Davis, J.: Liver damage due to tetracycline and its relationship to pregnancy; in Meyler and Peck (Eds) Drug-Induced Diseases, pp. 103–110 (Excerpta Medica, Amsterdam 1968).

    Google Scholar 

  • Davies, G.E. and Holmes, J.E.: Drug-induced immunological effects on the liver. British Journal of Anesthesiology 44: 941 (1972).

    CAS  Google Scholar 

  • Delage, C. and Lagace, R.: La peliose hepatique: Role etiologique possible des medicaments. L’Union Medicale de Canada 102: 1888 (1973).

    CAS  Google Scholar 

  • Despopoulus, A.: Hepatic and renal excretory metabolism of bile salts: A background for understanding steroid-induced cholestasis. Journal of Pharmacology and Experimental Therapeutics 176: 273 (1971).

    Google Scholar 

  • Ebert, M.H. and Shader, R.I.: Hepatic effects; in Shader and DiMascio (Eds) Psychotropic Drug Side Effects: Clinical and Theoretical Considerations, pp. 175–197 (Williams and Wilkins, Baltimore 1970).

    Google Scholar 

  • Edmondson, H.A.; Henderson, B. and Benton, B.: Liver-cell adenomas associated with use of oral contraceptives. New England Journal of Medicine 294: 470 (1976).

    PubMed  CAS  Google Scholar 

  • Edmondson, H.A.; Reynolds, T.B.; Henderson, B. et al.: Regression of liver cell adenomas associated with oral contraceptives. Annals of Internal Medicine 86: 180 (1977).

    PubMed  CAS  Google Scholar 

  • Eisen, H.J. and Ginsberg, A.L.: Disulfiram hepatotoxicity. Annals of Internal Medicine 83: 673–674 (1975).

    PubMed  CAS  Google Scholar 

  • Esperitu, C.R.; Alain, J.; Glueckauf, L.G. et al.: Allopurincl-induced granulomatous hepatitis. American Journal of Digestive Diseases 21: 804 (1976).

    Google Scholar 

  • Farber, E.: On the pathogenesis of experimental hepatocellular carcinoma; in Okuda and Peters (Eds) Hepatocellular Carcinoma, pp. 3–24 (Wiley, New York 1976).

    Google Scholar 

  • Farrell, C.G.; Joshua, D.E.; Uren, R.F. et al.: Androgen-induced hepatoma. Lancet 1: 685 (1975).

    Google Scholar 

  • Farrell, G.C.; Joshua, D.E.; Uren, R.F.; Baird, P.J.; Perkins, K.W. and Kronenberg, H.: Androgen-induced hepatoma. Lancet 1: 685 (1975).

    Google Scholar 

  • Fox, K.A. and Lachen, R.B.: Liver cell adenomas and peliosis hepatitis in mice associated with oxazepam. Research Communications, Chemical Pathology and Pharmacology 8: 481 (1974).

    CAS  Google Scholar 

  • French, A.J.: Hypersensitivity in pathogenesis of the histopathologic changes associated with sulfonamide chemotherapy. American Journal of Pathology 22: 679 (1946).

    CAS  Google Scholar 

  • Garibaldi, R.A.; Drusin, R.E.; Ferebee, S.H. et al.: Isoniazid-associated hepatitis: Report of an outbreak. American Review of Respiratory Disease 106: 357 (1972).

    PubMed  CAS  Google Scholar 

  • Goldstein, G.: Sarcoid reaction associated with phenylbutazone sensitivity. Annals of Internal Medicine 59: 97 (1963).

    PubMed  CAS  Google Scholar 

  • Goldstein, L.I.; Ishak, K.G. and Burns, W.: Toxic hepatitis, secondary to chronic nitrofurantoin therapy. American Journal of Digestive Diseases 19: 987 (1974).

    PubMed  CAS  Google Scholar 

  • Goldstein, G.B.; Lam, K.C. and Mistiiis, S.P.: Drug-induced active chronic hepatitis. American Journal of Digestive Diseases 18: 177 (1973).

    PubMed  CAS  Google Scholar 

  • Griner, P.F.; El-Badawi, A. and Parkman, H.: Veno-occlusive disease after chemotherapy for acute leukemia. Annals of Internal Medicine 85: 573 (1976).

    Google Scholar 

  • Gross, M.A.; Speen, R.J. and Hill, J.M.: Hepatic lipidosis associated with L-asparaginase treatment. Proceedings of the Society for Experimental Biology and Medicine 130: 733 (1967).

    Google Scholar 

  • Gumucio, J.J. and Valdivieso, V.D.: Studies on the mechanism of the ethynylestradiol impairment of bile flow and bile salt excretion in the rat. Gastroenterology 61: 339 (1971).

    PubMed  CAS  Google Scholar 

  • Hardin, B.L. Jr.: Carbon tetrachloride poisoning — A review. Industrial Medicine and Surgery 23: 93 (1954).

    PubMed  CAS  Google Scholar 

  • Hargreaves, T. and Lathe, G.H.: Inhibitory aspects of bile secretion. Nature 200: 1172 (1963).

    PubMed  CAS  Google Scholar 

  • Heath, C.W. Jr. and Falk, H.: Characteristics of cases of angiosarcoma of the liver among vinyl chloride workers in the United States. Annals of the New York Academy of Science 246: 231 (1975).

    Google Scholar 

  • Himsworth, H.P.: Lectures on the liver and its diseases (Harvard University Press, Cambridge, Massachusetts 1947).

    Google Scholar 

  • Hoekenga, M.T.; Bunde, C.A.; Cho, Y.W. et al.: Double-blind multicenter evaluation of a new anti-anginal drug: Perihexilene Maleate. Clinical Pharmacology and Therapeutics 13: 140 (1972).

    Google Scholar 

  • Hoyumpa, A.M.; Green, H.L.; Dunn, G.D. et al.: Fatty liver: Biochemical and clinical considerations. American Journal of Digestive Diseases 20: 1142 (1975).

    PubMed  CAS  Google Scholar 

  • Hueper, W.E.: Cinchophen (Atophan): A critical review. Medicine 27: 43 (1948).

    PubMed  CAS  Google Scholar 

  • Hurst, P. and Paget, G.E.: Protophorphyrine, cirrhosis and hepatomata in livers of mice given griseofulvin. British Journal of Dermatology 75: 105 (1963).

    Google Scholar 

  • Inman, W.H.W. and Mushin, W.M.: Jaundice after repeated exposure to halothane: An analysis of reports of the Committee on Safety of Medicine. British Medical Journal 1: 5010 (1974).

    Google Scholar 

  • Ishak, K.G.: Tumors of the liver associated with anabolic and contraceptive steroids; in Ligeman and D’Aguanno (Eds) Carcinogenesis of Some Hormonally Active Compounds (Springer-Verlag, Berlin In press 1978).

    Google Scholar 

  • Ishak, K.G. and Irey, W.S.: Hepatic injury associated with the phenothiazines: Clinicopathologic and follow-up studies of 36 patients. Archives of Pathology 93: 283 (1972).

    PubMed  CAS  Google Scholar 

  • Ishak, K.G.; Kirschner, J.P. and Dhar, J.K.: Granulomas and cholestatic hepatocellular injury associated with phenylbutazone. Report of two cases. American Journal of Digestive Diseases 22: 611 (1977).

    PubMed  CAS  Google Scholar 

  • Ishak, K.G. and Rabin, L.: Benign tumors of the liver. Medical Clinics of North America 59: 995 (1975).

    PubMed  CAS  Google Scholar 

  • Iuel, A.J.: Didsfeld ved guldenhandking i. Denmark 1960–1969. Ugeskr. Laeger 135: 1639 (1973).

    PubMed  CAS  Google Scholar 

  • Jalota, R. and Freston, J.A.: Severe intrahepatic cholestasis due to thiabendazole. American Journal of Tropical Medicine 23: 676 (1974).

    CAS  Google Scholar 

  • Joshi, P.H. and Conn, H.O.: The syndrome of methoxyflurane-associated hepatitis. Annals of Internal Medicine 80: 395 (1974).

    PubMed  CAS  Google Scholar 

  • King, J.A. and Blount, R.E.: An unexpected reaction to procainamide. Journal of the American Medical Association 186: 603 (1963).

    PubMed  CAS  Google Scholar 

  • Klatskin, G.: Toxic and drug-induced hepatitis; in Schiff (Ed) Diseases of the Liver, 4th ed, pp.604–710 (Lippincott, Philadelphia 1975).

    Google Scholar 

  • Klatskin, G.: Hepatic tumors: Possible relationship to use of oral contraceptives. Gastroenterology 73: 386 (1977).

    PubMed  CAS  Google Scholar 

  • Klatskin, G. and Smith, D.P.: Halothane induced hepatitis; in Gerohand Sickinger (Eds) Drugs and the Liver, pp.289–296 (Schattauer-Verlag, Stuttgart 1975).

    Google Scholar 

  • Klemola, H.; Pentilla, O.; Runeberg, L. et al.: Anicteric liver damage during nitrofurantoin medication. Scandinavian Journal of Gastroenterology 10: 501 (1975).

    PubMed  CAS  Google Scholar 

  • Koch, M.J.; Seeff, L.B.; Crumley, CE. et al.: Quinidine-toxicity: A report of a case and a review of the literature. Gastroenterology 70: 1136 (1976).

    PubMed  CAS  Google Scholar 

  • Koff, R.S.; Gardner, R.; Harinasuta, U. et al.: Profile of hyperbilirubinemia in three hospital populations. Clinical Research 18: 680 (1970).

    Google Scholar 

  • Lieber, C.S.: Alcohol and the liver. Transition from adaption to tissue injury; in Khuana, Israel and Kalant (Eds) Alcoholic Liver Pathology, pp.171–189 (Addiction Research Foundation, Ontario 1975).

    Google Scholar 

  • Little, D.M.: Effects of halothane on liver function; in Greene (Ed) Clinical Anesthesia: Halothane, pp.85–137 (Davis, Philadelphia 1968).

    Google Scholar 

  • Little, D.M. and Whetstone, H.J.: Anesthesia and the liver. Anesthesiology 25: 815 (1964).

    PubMed  CAS  Google Scholar 

  • Maddrey, W.C. and Boitnott, J.K.: Isoniazid hepatitis. Annals of Internal Medicine 79: 1 (1973).

    PubMed  CAS  Google Scholar 

  • Maddrey, W.C. and Boitnott, J.K.: Severe hepatitis from methyldopa. Gastroenterology 68: 351 (1975).

    PubMed  CAS  Google Scholar 

  • Maddrey, W.C. and Boitnott, J.K.: Drug-induced chronic liver disease. Gastroenterology 72: 1348 (1977).

    PubMed  CAS  Google Scholar 

  • Mays, E.T.; Christopherson, W.M.; Mahr, M.M.; et al.: Hepatic changes in young women ingesting contraceptive steroids. Hepatic hemorrhage and primary hepatic tumors. Journal of the American Medical Association 235: 730 (1976).

    PubMed  CAS  Google Scholar 

  • McAlister, W.H.; Anderson, M.S.; Bloomberg, G.R. et al.: Lethal effects of tannic acid in the barium enema: Report of three fatalities and experimental studies. Radiology 80: 765 (1963).

    Google Scholar 

  • McCann, J.; Choi, E.; Yamasaki, E. et al.: Detection of carcinogens as mutagens in the Salmonella/microsome test-Assay of 300 chemicals (rapid in-vitro, screening of environmental carcinogens and mutagens). Proceedings of the National Academy of Science 72: 5135 (1975).

    CAS  Google Scholar 

  • Metreau, J.M.; Dhumeaux, D. and Bethelot, P.: Oral contraceptives and the liver. Digestion 7: 318 (1972).

    PubMed  CAS  Google Scholar 

  • Mihas, A.A.; Holley, P.; Koff, R.S. et al.: Fulminant hepatitis and lymphocyte sensitization due to propylthiouracil. Gastroenterology 70: 770 (1976).

    PubMed  CAS  Google Scholar 

  • Miller, P.R. and Miller, J.A.: Hepatocarcinogenesis by chemicals; in Popper and Schaffner (Eds) Progress in Liver Disease, vol. V, pp.699–711 (Grune and Stratton,New York 1976).

    Google Scholar 

  • Mistilis, S.P.: Chronic active hepatitis; in Schiff (Ed) Diseases of the Liver 4th Ed, pp.787–814 (Lippincott, Philadelphia 1975).

    Google Scholar 

  • Mitchell, J.R.; Potter, W.Z.; Hinson, J.A.; Snodgrass, W.R.; Timbrell, J.A. and Gillette, J.R.: Toxic drug reactions; in Eichler et al. (Eds) Handbook of Experimental Pharmacology, New Series. Vol. XXVIII/3, pp.282–419 (Springer-Verlag, Berlin 1975).

    Google Scholar 

  • Mitchell, J.R.; Zimmerman, H.J.; Ishak, K.G. et al.: Isoniazid liver injury: Clinical spectrum, pathology and probable pathogenesis. Annals of Internal Medicine 84: 181 (1976).

    PubMed  CAS  Google Scholar 

  • Nadel, J. and Kosek, J.: Peliosis hepatis. Twelve cases associated with oral androgen therapy. Archives of Pathology and Laboratory Medicine 101: 405 (1977).

    Google Scholar 

  • Parker, L.N.: Hepatitis and propylthiouracil. Annals of Internal Medicine 82: 228 (1975).

    PubMed  CAS  Google Scholar 

  • Perkins, J.: Phenindione jaundice. Lancet 1: 125 (1962a).

    PubMed  CAS  Google Scholar 

  • Perkins, J.: Phenindione sensitivity. Lancet 1: 127 (1962b).

    PubMed  CAS  Google Scholar 

  • Peters, R.L.; Edmondson, H.A.; Mikkelsen, W.P. et al.: Tetracycline induced fatty liver in non-pregnant patients. American Journal of Surgery 113: 622 (1967).

    PubMed  CAS  Google Scholar 

  • Phillips, M.J.; Oda, M.; Mak, E. et al.: Microfilament dysfunction as a possible cause of intrahepatic cholestasis. Gastroenterology 69: 48 (1975).

    PubMed  CAS  Google Scholar 

  • Pietsch, J. and Meakins, J.L.: Complications of povidone-iodine absorption in topically treated burn patients. Lancet 1: 280–282 (1976).

    PubMed  CAS  Google Scholar 

  • Popper, H.; Schaffner, F. and Kenk, H.: Molecular pathology of cholestasis; in Taylor (Ed) The Hepatobiliary System. Fundamental and Pathological Mechanisms, pp.605–629 (Plenum Press, New York 1976).

    Google Scholar 

  • Popper, H. and Thomas, L.B.: Alterations of liver and spleen among workers exposed to vinyl chloride. Annals of the New York Academy of Science 246: 172 (1975).

    CAS  Google Scholar 

  • Pratt, C.B. and Johnson, W.W.: Duration and severity of fatty metamorphosis of the liver following L-asparaginase therapy. Cancer 28: 361 (1971).

    PubMed  CAS  Google Scholar 

  • Recknagel, R.O. and Glende, E.A. Jr.: Carbon tetrachloride hepatotoxicity: An example of lethal cleavage. CRC Critical Review of Toxicology 2: 263 (1973).

    Google Scholar 

  • Reed, C.B. and Cox, A.J. Jr.: The human liver after radiation injury. American Journal of Pathology 48: 597 (1965).

    Google Scholar 

  • Rees, L.: Drugs used in the treatment of psychiatric disorders. Abstracts of World Medicine 39: 129 (1966).

    Google Scholar 

  • Reynolds, T.B.: Laxative liver disease; in Gerok and Sickinger (Eds) Drugs and the Liver, pp.319–325 (Schattauer-Verlag, Stuttgart 1975).

    Google Scholar 

  • Rigberg, L.A.; Robinson, M.J. and Esperitu, C.: Chlorpropamide-induced granulomas. A probable hypersensitivity in liver and bone-marrow. Journal of the American Medical Association 235: 409 (1976).

    PubMed  CAS  Google Scholar 

  • Rodman, J.S.; Deutsch, D.J. and Gutman, S.I.: Methyldopa hepatitis. A report of six cases in the literature. American Journal of Medicine 60: 941 (1976).

    PubMed  CAS  Google Scholar 

  • Rosenblum, L.E.; Korn, R.J. and Zimmerman, H.J.: Hepatocellular jaundice as a complication of iproniazid therapy. Archives of Internal Medicine 105: 583 (1960).

    PubMed  CAS  Google Scholar 

  • Rosenkrantz, H.S. and Carr, H.S.: Hydrazine antidepressants and isoniazid: Potential carcinogens. Lancet 1: 1354 (1971).

    Google Scholar 

  • Russell, R.I.; Allan, J.G. and Patrick, R.: Active chronic hepatitis after chlorpromazine ingestion. British Medical Journal 1: 655 (1973).

    PubMed  CAS  Google Scholar 

  • Russell, R.M.O.; Bagheri, S.A. and Boyer, J.L.: The hepatic lesion of hypervitaminosis A. A unique pattern of hepatic fibrosis with portal hypertension and ascites. Gastroenterology 65: 568 (1973a).

    Google Scholar 

  • Schaffner, F. and Raisfield, I.H.: Drugs and the liver. A review of metabolism and adverse reactions. Advances Internal Medicine 115: 221 (1969).

    Google Scholar 

  • Schenker, S.; Olson, K.N.; Dunn, D. et al.: Intrahepatic cholestasis due to therapy of rheumatoid arthritis. Gastroenterology 64: 622 (1973).

    PubMed  CAS  Google Scholar 

  • Schenker, S.; Breen, K.J. and Heimberg, M.: Pathogenesis of tetracycline-induced fatty liver; in Gerok and Sickinger (Eds) Drugs and the Liver, pp.269–280 (Schattauer-Verlag, Stuttgart 1975).

    Google Scholar 

  • Scheuer, P.J.: Chronic hepatitis. A problem for the pathologist. Histopathology 1: 5 (1977).

    PubMed  CAS  Google Scholar 

  • Scheuer, P.J.: Liver Biopsy Interpretation, 2nd ed, pp.40–55 (Williams and Wilkins, Baltimore 1973).

    Google Scholar 

  • Schiff, L.: Personal communication (1976).

  • Schweitzer, I.L. and Peters, R.L.: Acute submassive hepatic necrosis due to methyldopa: A case demonstrating possible induction of chronic liver disease. Gastroenterology 66: 1203 (1974).

    PubMed  CAS  Google Scholar 

  • Seaman, W.E.; Ishak, K.G. and Plotz, P.H.: Aspirin-induced hepatotoxicity in patients with systemic lupus erythematosus. Annals of Internal Medicine 80: 1 (1974).

    PubMed  CAS  Google Scholar 

  • Seiinger, M. and Koff, R.S.: Thorotrast and the liver: A reminder. Gastroenterology 68: 799–803 (1975).

    Google Scholar 

  • Sherlock, S.: Diseases of the Liver and Biliary System, 5th Ed, pp.340–382 (Blackwell, Oxford 1975a).

    Google Scholar 

  • Sherlock, S.: Hepatic adenomas and oral contraceptives. Gut 16: 753 (1975b).

    PubMed  CAS  Google Scholar 

  • Shikata, T.; Oda, T.; Naito, C. et al.: Phospholipid fatty liver: A proposal of a new concept and its electron microscopical study. Acta Pathologica Japonica 20: 467 (1970).

    PubMed  CAS  Google Scholar 

  • Simmonds, F.; Feldman, B. and Gerety, D.: Granulomatous hepatitis in a patient receiving allopurinol. Gastroenterology 62: 101 (1972).

    Google Scholar 

  • Stafford, A.: Drugs acting on the heart; in Meyler and Herxheimer (Eds) Side Effects of Drugs, Vol. III, pp.277–279 (Excerpta Medica, Amsterdam 1971).

    Google Scholar 

  • Sterup, K. and Mosbech, J.: Budd-Chiari syndrome after taking oral contraceptives. British Medical Journal 4: 660 (1967).

    PubMed  CAS  Google Scholar 

  • Teller, D.N.: Phenothiazines and butyrophenones in relation to neurochemistry and pharmacology in Denbar (Ed) Psycho-pharmacological Treatment: Theory and Practice pp. 28–42 (Marcel Dekker, New York 1975).

    Google Scholar 

  • Thomas, F.B.: Chronic aggressive hepatitis induced by halothane. Annals of Internal Medicine 81: 487 (1974).

    PubMed  CAS  Google Scholar 

  • Ticktin, H.E. and Zimmerman, H.J.: Hepatic dysfunction and jaundice in patients receiving triacetyloleandomyoin. New England Journal of Medicine 267: 964 (1962).

    CAS  Google Scholar 

  • Tonder, M.; Nordoy, A. and Elgio, K.: Sulfonamide-induced chronic liver disease. Scandinavian Journal of Gastroenterology 9: 23 (1974).

    Google Scholar 

  • Trey, C.; Lipworth, L.; Chalmers, T. et al.: Fulminant hepatic failure. Presumable contribution of halothane. New England Journal of Medicine 279: 798 (1968).

    PubMed  CAS  Google Scholar 

  • Utili, R.; Boitnott, J. and Zimmerman, H.J.: Dantrolene-associated hepatic injury. Incidence and character. Gastroenterology 72: 610 (1976).

    Google Scholar 

  • Van Thiel, D.H.; DeBelle, R.; Mellow, M. et al.: Tolazamide hepatotoxicity. A case report. Gastroenterology 67: 506 (1974).

    PubMed  Google Scholar 

  • Vester, J.W.; Sunder, J.H.; Aarons, J.H. et al.: Long-term monitoring during Clofibrate therapy. Clinical Pharmacology and Therapeutics 11: 689 (1971).

    Google Scholar 

  • Weir, J.F. and Comfort, M.W.: Toxic cirrhosis caused by cinchophen. Archives of Internal Medicine 28: 476 (1933).

    Google Scholar 

  • Wheeler, H.O.: Secretion of bile; in Schiff (Ed) Diseases of the Liver 4th Ed, pp.87–110 (Lippincott, Philadelphia 1975).

    Google Scholar 

  • Wildhirt, E.: Therapie chronische Leberkrankheiten Mit D-Pencillamin. Munchener Medisinische Wochenschrift 116: 217–220 (1974).

    CAS  Google Scholar 

  • Yanoff, M. and Rawson, A.J.: Peliosis hepatis. An anatomic study with demonstration of two varieties. Archives of Pathology 77: 159 (1964).

    PubMed  CAS  Google Scholar 

  • Zimmerman, H.J.: Clinical and laboratory manifestations of hepatotoxicity. Annals of New York Academy of Science 104: 954 (1963).

    Google Scholar 

  • Zimmerman, H.J.: The spectrum of hepatotoxicity. Perceptives in Biology and Medicine 12: 135 (1968).

    Google Scholar 

  • Zimmerman, H.J.: Liver injury induced by chemicals and drugs; in Bockus (Ed) Gastroenterology, 3rd ed., Vol. III. Ch. 105, pp.299–341 (W.B. Saunders, Philadelphia 1976a).

    Google Scholar 

  • Zimmerman, H.J.: Experimental hepatotoxicity; in Born et al. (Eds) Handbook of Experimental Pharmacology, Vol. XVI/5, Ch. 1, pp.1–120 (Springer-Verlag, Berlin 1976b).

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Medical Service, Veterans Administration Hospital and George Washington University School of Medicine, 50 Irving Street NW, Washington DC, 20422, USA

    Hyman J. Zimmerman

Authors
  1. Hyman J. Zimmerman
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Zimmerman, H.J. Drug-Induced Liver Disease. Drugs 16, 25–45 (1978). https://doi.org/10.2165/00003495-197816010-00002

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2165/00003495-197816010-00002

Keywords

Search

Navigation