Hepatotoxicity of isotretinoin in patients with acne and Gilbert's syndrome: a comparative study

Abstract

ObjectivesThe objective of our follow-up study is to evaluate liver function tests (LFTs) and lipid profiles in patients with Gilbert's syndrome treated with isotretinoin because of severe acne.SettingDermatology outpatient clinics of three regional hospitals of Jaén (Spain).ParticipantsOver 4 years, we included all patients diagnosed with severe acne. Only 37 patients were identified, of which 11 had Gilbert's syndrome.InterventionsAll patients were treated with isotretinoin and followed-up in our outpatient clinics after 10 and 20 weeks. Patients were subjected to an interview questionnaire which included data on age, gender, complete blood count, coagulation profile, fasting blood glucose, LFTs and lipid profiles. Data and results of patients with severe acne and Gilbert's syndrome were compared with those of 26 patients with only severe acne (control group).Primary outcomeBlood analyses were repeated in the follow-up visits.ResultsIn patients with Gilbert's syndrome, bilirubin levels showed substantial decrease over the 20-week follow-up, with more decrease after 10 weeks. None of the control group patients had significant increase in total bilirubin levels after 10 and 20 weeks of follow-up. Liver enzymes were maintained within normal levels in both groups. Both study groups did not show significant pathological increase in lipid profile levels. LDL levels were increased in the two study groups, but this increase was less substantial in patients with Gilbert's syndrome.ConclusionsOur preliminary results suggest that oral isotretinoin could be an effective, safe treatment for patients with Gilbert's syndrome, and may lower bilirubin levels in the first 10 weeks of treatment. Limitations of the study include the small numbers of participants and the fact that it is restricted to one region of Spain.

Long‐term isotretinoin use does not cause parenchymal liver change: Ultrasonographic study in 50 patients

“…In a study investigating hepatotoxicity risk in 11 cases with Gilbert syndrome, who use isotretinoin for their acne, surprisingly not only an effective and safe outcomes regarding acne signs were obtained, but also bilirubin levels were found to be decreased in the patients during isotretinoin use (Fernández‐Crehuet et al, ).…”

The effects of isotretinoin therapy on the biliary system

“…Paradoxically, there are reports of substantial reduction in serum bilirubin levels in patients with Gilbert syndrome, undergoing treatment with isotretinoin for concomitant acne (Le Gal & Pauwels, ). Gilbert syndrome is a hereditary disease characterized by mild unconjugated hyperbilirubinemia with an estimated prevalence of 6% (Aiso et al, ; Fernández‐Crehuet, Fernández‐Crehuet, Allam, & Fernández‐Crehuet, ). We had the chance to observe remarkable reduction in bilirubin levels during the first month of isotretinoin therapy in one of our male patients with coexisting Gilbert syndrome and acne.…”

Significant reduction in bilirubin levels in a patient with Gilbert's Syndrome under isotretinoin treatment for acne vulgaris: A new area of use for isotretinoin?

“…Some hypotheses have been proposed about this unexpected finding. In a few studies, similar to the mechanism of some drugs such as phenobarbital and corticosteroids, inhibition of microsomal enzymes such as uridine diphosphate glucanosyltransferase (UDP-GT), and the inducing effects of reducing bilirubin conjugation by isotretinoin treatment are claimed (Fernández-Crehuet, 2014;Rademaker, 1991;Shah, 1993). Another study suggests that isotretinoin decreases serum testosterone levels that increase the activity of UDP-GT, or it induces hepatocytes to produce carrier proteins that eliminate bilirubin (Bruno, 1984;Goodman, 1984).…”

“…Gilbert's syndrome is a genetic disease characterized by nonconjugated hyperbilirubinemia and it affects 3-10% of the general population (Radoi, 2017). Owing to hepatic dysfunction, patients with Gilbert syndrome are expected to show increased sensitivity to isotretinoin, metabolized by hepatic oxidation and bile excretion (Fernández-Crehuet, 2014). Contrary to this expectation, a few studies in the literature reported paradoxical decrease in the bilirubin levels in patients with Gilbert syndrome receiving isotretinoin treatment for acne (Fernández-Crehuet, 2014;Wang, 1995).…”