Can disulfiram cause liver injury? How would the liver enzyme tests look like early in the developm

Fråga: Can disulfiram cause liver injury? How would the liver enzyme tests look like early in the development of liver toxicity?

Background: The patient has most probably no alcohol intake for the last 1.5 years. S-GT now 1.19 uKat/L (normally < 0.50). Also antiasthmatic treatment.

Sammanfattning: Disulfiram may cause liver toxicity, mainly of hepatocellular type, usually reversible, but in rare instances severe, even fatal. In an individual patient this reaction may be very difficult to diagnose as separate from other obvious causes of liver damage.

Svar: Some 25 cases of disulfiram-induced liver damage have been reported in the medical literature, in a few cases with fatal outcome (1-4). The latency period may be 2 weeks to 6 months, but usually the damage occurs within 8 weeks (1,2). Adverse reactions from the liver (usually so-called "hepatitisk reaktion") have also been reported in several cases to the National Board of Health and Welfare in Sweden (5). The causal relationship is debatable in alcoholic patients with underlying liver disease (1,2) but it has also been reported in patients with previous normal hepatic function during alcohol abstinence (6) and in non alcoholic patients with previous normal liver function with nickel hypersensitivity treated with disulfiram (7,8).

The damage is usually of the hepatocellular type but often also some increase in alkaline phosphatases and bilirubin is seen (8,9). In a couple of cases withdrawal and/or rechallenge with disulfiram was followed carefully with liver function tests (6,8). In those cases where cause-effect was established the rechallenge induced liver abnormality, particularly increased aminotransferases, within 3 days (original papers enclosed). A short and recent review in Swedish is also enclosed (10). Monitoring of ASAT, ALAT, ALP and GT is considered useful to follow treatment outcome as well as to discover liver toxicity of the treatment (11). 1 Side effects of drugs. Ed by MNG Dukes, Elsevier, Amsterdam. 1986; Annual 10: 438

2 Stricker BHCH, Spoelstra P: Drug-induced hepatic injury. 1985, p 302
3 Martindale, The extra pharmacopoeia. 1982; 28th ed: 579-580
4 Zimmerman HJ, Hepatotoxicity. 1978, p 547, 555
5 Socialstyrelsens biverkningsregister, 1965-1988
6 Ranek L, Andreasen PB: Disulfiram hepatotoxicity. Br Med J 1977; 2: 94-96 (bifogas)

7 Kaaber K et al: Treatment of nickel dermatitis with antabuse; a double blind study. (Contact Dermatitis 1983; 9: 297-299) Cited in reference no 2.

8 Kristensen ME: Toxic hepatitis induced by disulfiram in a non-alcoholic. Acta Med Scand 1981; 209: 335-336 (bifogas)
9 Drug interferences and drug effects in clinical chemistry. Apoteksbolaget. 1986; 4th ed: 79-80
10 Nässberger L: Disulfirambehandling kan ge leverskada. Läkartidningen 1985; 82: 4520-4521 (bifogas)

11 Kristensen H: Deterrent Drugs in Treatment of Alcoholism. In: Pharmacological Treatment of Alcoholism: Withdrawal and aversion therapy. National Board of Health and Welfare 1985:2, p 57