Several clinical indicators, including elevated hemoglobin and decreased fibrinogen, were associated with arsenic trioxide (ATO)-induced hepatotoxicity among patients with acute promyelocytic leukemia (APL) in a retrospective study.

In the study, which was published in the journal Biological Trace Element Research, data from a hospital in China of 122 patients with APL who were treated with ATO were evaluated for clinical indicators of hepatotoxicity. ATO-induced hepatotoxicity was defined as elevation above normal of serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), or gamma-glutamyl transferase (GGT) levels.

The median age of the cohort was 40 years and 47% of patients were female. There were 23% of patients who had received prophylactic hepatoprotective agents. ATO alone was used in 62% of patients, whereas it as combined with chemotherapy for 38%.

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During ATO induction therapy, 91.8% of patients had laboratory values that indicated hepatotoxicity. Of these, 58% developed hepatotoxicity during the first week of ATO treatment and 89.3% within the first 2 weeks of treatment. The median time to hepatotoxicity was 6 days.

The majority of cases of hepatotoxicity were mild, as 76.8% of patients had grade I or II hepatotoxicity, according to the World Health Organization grading scale. None of the patients with hepatotoxicity demonstrated obvious symptoms. Hepatoxicity was transient and resolved within 2 weeks in 89.3% of patients.

In a multivariate analysis, elevated hemoglobin levels were significantly associated with an increased risk of ATO-induced hepatotoxicity (odds ratio [OR], 8.65; 95% CI, 1.34-55.92; P =.023). The administration of prophylactic hepatoprotective agents (OR, 14.531; 95% CI, 2.35-89.88; P =.004) and treatment with ATO alone (OR, 20.11; 95% CI, 1.36-297-89; P =.029) also demonstrated a significant association with hepatotoxicity.

In addition, elevated fibrinogen levels (OR, 3.50; 95% CI, 1.23-10.85; P =.030), use of prophylactic hepatoprotective gents (OR, 36.46; 95% CI, 7.41-179.36; P <.001), and treatment with ATO alone (OR, 4.29; 95% CI, 1.36-13.50; P =.013) were associated with ATO-induced hepatotoxicity occurring during the first week of treatment.

“These findings can enhance the clinical diagnosis of hepatotoxicity,” the authors concluded in their report. “Prospective studies should be performed in the future to validate these findings.”

Zhang Z, Zhang S, Zhang F, et al. Clinical indicators of hepatotoxicity in newly diagnosed acute promyelocytic leukemia patients undergoing arsenic trioxide treatment. Biol Trace Elem Res. Published online April 25, 2023. doi: 10.1007/s12011-023-03676-2