Drug-induced liver injury more severe in African-Americans than whites

Comparative data from the Drug-Induced Liver Injury Network Prospective Study showed that the most common drug-induced liver injury causative agents differ between African-Americans and Caucasians and that African-Americans were more likely to have severe cutaneous reactions and more severe liver injury.

“There is a suggestion in the literature that certain adverse drug reactions (ADRs) have different frequency and clinical phenotypes in different racial and ethnic groups,” Naga Chalasani, MD, from the Indiana University School of Medicine, and colleagues wrote. “This prompted us to carefully analyze DILI in self-reported African-Americans enrolled in the DILIN Prospective Study.”

The DILIN Prospective Study comprised 1,182 individuals who scored as definite, highly likely or probable for DILI. Self-reported ethnicity among this cohort included 841 as non-Hispanic white or Caucasian and 144 as non-Hispanic black or African-American.

Compared with Caucasian individuals, African-Americans with DILI had higher peak levels of alanine aminotransferase (1,117 vs. 930 U/L; P = .01) and international normalized ratio (1.9 vs. 1.6; P < .001), were more likely to be younger (46.9 vs. 50.7 years; P = .005), more likely to have a higher BMI (29.9 vs 27.3 kg/m²; P < .001), diabetes (31% vs. 22%; P = .03) and severe skin reactions (2.1% vs. 0.4%; P = .04), and less likely to have a high school or higher level of education (83% vs. 93%; P < .001), health insurance (88% vs. 95%; P = .005), previous drug allergies (38% vs. 49%; P = .02) or history of alcohol use (32% vs. 55%; P < .001).

While there were no significant differences in the classes of agents implicated between the two groups, the most common agent implicated for African-Americans was combined trimethoprim and sulfamethoxazole and its frequency was significantly higher compared with Caucasians (7.6% vs. 3.6%; P = .04). Conversely, the most common agent indicated among Caucasians was combined clavulanic acid and amoxicillin and its frequency was significantly higher compared with African-Americans (13.4% vs. 4.1%; P < .001).

African-Americans also had significantly higher frequency of DILI due to phenytoin (4.8% vs. 0.8%; P = .002), methyldopa (4.1% vs. 0.5%; P = .001) and allopurinol (2.7% vs. 0.4%; P = .01).

Regarding liver injury severity, African-Americans had a higher mean severity score compared with Caucasians (3 vs. 2.6; P < .001), more severe or fatal cases of DILI (34% vs. 24%; P < .001) and more frequent severe cutaneous reactions (2.1% vs. 0.36%; P = .048).

After controlling for BMI, the researchers found a significant association between African-American ethnicity and DILIN severity score (OR = 1.98; 95% CI, 1.42–2.75). The researchers also found a significant association between African-American ethnicity and the likelihood of death or liver transplantation after controlling for age and BMI (OR = 2.12; 95% CI, 1.12–3.9).

“The liver injury in African-Americans was more severe as reflected by higher DILIN severity scores and more frequent hospitalization and was associated with higher frequency of worse outcomes such as liver related mortality/liver transplantation and chronic DILI. The reasons for this phenomenon are unclear,” the researchers wrote. “The duration between earliest DILI symptoms and stopping the implicated agent was comparable between the two groups and similarly liver biochemistries at DILI presentation were not different between two groups. This suggests that greater severity and worse outcomes associated with DILI in African-Americans is not likely due to a delay in seeking care by African-Americans.” – by Talitha Bennett

Disclosure: Chalasani reports he is a consultant for NuSirt, AbbVie, Eli Lilly, Afimmune (DS Biopharma), Tobira (Allergan), Madrigal, Shire, Cempra, Ardelyx, Gen Fit and Amarin; and received research grant support from Intercept, Lilly, Gilead, Galectin Therapeutics and Cumberland. Please see the full study for the other researchers’ relevant financial disclosures.