Effects of Oral Isotretinoin on Lipids and Liver Enzymes in Acne Patients
Isotretinoin has been used to treat severe inflammatory acne that is resistant to antibiotics or topical agents; however, it also may cause alterations in lipids and liver enzymes. In this retrospective study, we evaluated changes in lipids and liver enzymes in 322 acne patients who had been treated with oral isotretinoin at our institution over a 3-year period. Each patient’s medical records were evaluated to determine baseline triglyceride (TG), low-density lipoprotein (LDL), high-density lipoprotein (HDL), aspartate aminotransferase (AST), and alanine aminotransferase (ALT) levels compared to levels recorded at 3 and 6 months following initiation of treatment with oral isotretinoin. Overall, statistically significant increases in TG and LDL levels were noted following treatment with isotretinoin (P<.001, respectively), while HDL levels were shown to decrease (P=.016). Although ALT levels also increased, the changes were not statistically significant increases in AST levels also were noted (P=.72). In our study, isotretinoin appeared to have a greater effect on lipids than liver enzymes. Dermatologists should not avoid isotretinoin use for appropriate indications, but close follow-up is important.
Practice Points
- Isotretinoin is recommended for treatment of severe inflammatory acne and for cases resistant to prior treatment with antibiotics or topical agents; however, it may cause alterations in lipids and liver enzymes.
- In our study, liver enzymes were less affected than lipids in patients who were treated with isotretinoin.
- Use caution when administering isotretinoin in patients with a history of abnormal findings.
High-Density Lipoprotein Analysis
High-density lipoprotein levels were classified as low, normal, and high. At baseline, mean (SD) HDL levels were 52.4 (16) mg/dL, with low levels in 60 (18.6%) patients, normal in 173 (53.7%) patients, and high in 71 (22%) patients. At 3-month follow-up, mean (SD) HDL levels were 48 (12) mg/dL, with low levels in 63 (19.6%) patients, normal in 154 (47.8%) patients, and high in 41 (12.7%) patients. At 6-month follow-up, mean (SD) HDL levels were 47.6 (12) mg/dL, with low levels in 48 (14.9%) patients, normal in 117 (36.3%) patients, and high in 33 (10.2%) patients. Overall, statistically significant decreases were noted in HDL levels (F2,384=19, P<.001). Differences between baseline HDL levels compared to 3-month follow-up were statistically significant (P<.001). Differences between baseline HDL levels compared to 6-month follow-up were statistically significant (P<.001). Differences in HDL levels at 3- and 6-month follow-up were statistically significant (P<.001). Differences between HDL classifications at each time point were statistically significant (F2,384=5.2, P=.006). Overall, there were statistically significant decreases in HDL levels during isotretinoin treatment from baseline and this decrease was above normal range; however, HDL levels did not decrease at 3- and 6-month follow-up.
Comment
Studies in the literature evaluating the effects of isotretinoin on liver enzymes and lipids suggested that oral isotretinoin may cause alterations in liver aminotransferases (AST and ALT), TGs, HDL, and LDL in various degrees.1 Zane et al4 studied 13,772 patients with acne undergoing oral isotretinoin therapy between March 1995 and September 2002. The investigators found increased liver transaminase and serum lipid levels. They suggested that these abnormalities were generally transient and reversible.4 Bershad et al5 reported an increase in LDL and TG but a decrease in HDL during isotretinoin therapy. These changes in the lipid profile also appeared to be transient and returned to baseline level 2 months following the end of treatment.5 In another study of 130 patients who were treated with isotretinoin, Vieira et al1 noted an increase in AST, ALT, and TG levels. Most of the studies in the literature that reported effects of isotretinoin on liver enzymes and lipids suggested that the effects were reversible.
Although many studies reported alterations in serum transaminase and lipid levels, other studies reported no effect. In one study of 150 participants, Brito et al2 found no statistically significant changes in liver transaminase, TG, HDL, or LDL levels following treatment with isotretinoin. In another study of 1292 participants by Alcalay et al,6 serum levels of liver enzymes were not elevated to a degree necessitating discontinuation of isotretinoin treatment. In another study of 30 participants, Baxter et al7 reported no significant changes in TG, LDL, or HDL levels measured at baseline or during treatment with isotretinoin.
Some studies suggest that routine laboratory tests are needed when treating patients with isotretinoin due to severe alterations in serum liver transaminase and lipid levels, while other studies conclude that the effects are minimal and laboratory tests are not needed. In the current study, we found that there were statistically significant increases in TG and LDL levels in patients who underwent treatment with isotretinoin. We also found statistically significant decreases in HDL levels. In our study, liver enzymes were less affected than lipids in patients who underwent treatment with isotretinoin. There were statistically significant increases in AST levels, but the clinical classification was not affected. There also were increases in ALT levels, but the changes were not statistically significant.
Overall, we advise dermatologists that isotretinoin can be administered with minimal concern regarding changes in serum transaminase and lipid levels; however, although severe laboratory alterations were not noted in our study, we advise physicians to use caution when administering isotretinoin in patients with a history of abnormal findings.
