Cyproterone acetate induces a broad spectrum of acute liver damage including corticosteroid-responsive hepatitis: report of 22 cases

ROMA M.G.; FRIDER B.; BRUGUERA M.; MONTERO J.; COLOMBATO L.; ZENO J.; LUCENA M.I.; BESSONE F.; MEDINA-CÁLIZ I.; STEPHENS C.; HERNÁNDEZ N.; TSARIKTSIAN G.; FASSIO E.; GUALANO G.; FERRETTI S.; REGGIARDO M.V.; FERRER J.; TANNO F.; ANDRADE R.J.; TANNO H.

LIVER INTERNATIONAL

WILEY-BLACKWELL PUBLISHING, INC

Año: 2016 vol. 36 p. 302 - 310

1478-3223

Background and aims: Cyproterone acetate (CPA), anantiandrogenic drug for prostate cancer, has been associated with drug-inducedliver injury (DILI). We aim to expand the knowledge on the spectrum ofphenotypes and outcomes of CPA-induced DILI.Methods: Twenty-two males (70±8 years; range54-83) developing liver damage due to CPA therapy (dose: 150±50 mg/day; range50-200) were included. Severity index and causality by RUCAM were assessed.Results: From 1993 to 2013, 22 patients wereretrieved. Latency was 163±97 days. Most patients were symptomatic, showing hepatocellularinjury (91%) and jaundice. Liver tests at onset were: ALT 18±13 x ULN, ALP 0.7±0.7x ULN, and total serum bilirubin 14±10 mg/dL. International normalized ratiovalues higher than 1.5 were observed in 14 (66%) patients. Severity was mild in1 case (4%), moderate in 7 (32%), severe in 11 (50%), and fatal in 3 (14%).Five patients developed ascitis, and 4 encephalopathy. One patient had a liverinjury that resembled autoimmune hepatitis. Eleven (50%) were hospitalized.Nineteen patients recovered after CPA withdrawal, although 3 required steroidtherapy (2 of them had high ANA titres). Liver biopsy was performed in 7patients (2 hepatocellular collapse, 1 submassive necrosis, 2 cholestatichepatitis, 1 cirrhosis with iron overload, and 1 autoimmune hepatitis). RUCAM categorywas "highly probable" in 19 (86%), "probable" in 1 (4%),and "possible" in 2 (9%).Conclusions: CPA-induced liver injury is severeand can be fatal, and may occasionally resemble autoimmune DILI. The benefit/riskratio of this drug should be thoroughly assessed in each patient.