The question concerns a 45-year-old man who was treated several years ago for a short time with Roa

Fråga: The question concerns a 45-year-old man who was treated several years ago for a short time with Roaccutan (isotretinoin) for acne. The treatment was stopped because of some kind of adverse effects (what kind is unclear). The patient now has dyspepsia, and increased liver transaminases (ASAT 1.02, ALAT 2.05, normal < 0.7 ukat/l) have been found. The patient is not being treated with any drugs at the moment. Can isotretinoin cause liver toxicity? Can the elevated transaminases in the present case be due to the isotretinoin treatment several years ago?

Sammanfattning: Liver enzyme elevation has been reported in 7-13 per cent of patients treated with isotretinoin. This appears in general to be transient in nature. In the present case, a causal relationship between the patient´s previous isotretinoin treatment and the aminotransferase elevation appears less probable. Other causes of increased aminotransferases should be looked for.

Svar: Isotretinoin is a synthetic retinoid available in Sweden only on licence. Its main indication is severe forms of acne, especially cystic acne.

The side-effect profile of isotretinoin has been discussed earlier in Drugline (1). The most commonly reported side-effects include mucocutaneous side-effects, irritated eyes, itching, nose bleeds, hair loss, eczema, thirst, leg and joint pain, insomnia, headache, nausea, muscle cramps, abdominal pain and fever. Isotretinoin is contraindicated during pregnancy because of risks for foetal malformations of the eye, CNS and heart (1).

Liver enzyme elevations (aminotransferases, gamma-glutamyltransferase) have been reported in patients treated with isotretinoin. As reviewed by Stricker (2) liver enzyme elevations occur in 7-13 per cent of patients, and appear to be of a mild and reversible nature. In a search in Medline, only one case report of fatty liver and ALAT elevation persisting for at least 20 months after stopping isotretinoin treatment has been found (3). A 18-year-old male patient was treated with 40 mg isotretinoin per day for four months because of nodulocystic acne. At the end of the course, serum ALAT was found to be elevated while bilirubin, alkaline phosphatase, gamma-GT, hepatitis B antigen and autoantibody screen were all normal or negative. His ALAT remained elevated during the 20 month follow-up. A liver biopsy performed six months after stopping the treatment revealed severe generalised steatosis of macrovesicular type with mild non-specific reactive inflammatory changes. No causes of hepatic steatosis other than the treatment could be found.

Eleven cases of increased transaminases and one case of increased bilirubin with possible or probable relation to isotretinoin treatment have been reported to SADRAC.