Working with the Drug Induced Liver Injury Network (DILIN), an international research group funded by the National Institute of Health (NIH), Dellinger and others searched for the cause of liver injury due to a common antibiotic. This antibiotic goes by names such as Bactrim, Septra, Sulfatrim, SMZ-TMP, and sulfamethoxazole with trimethoprim.

A set of 61 patients were studied whose medical records were evaluated and expertly determined that the cause of their liver injury was Bactrim. Genetic data was obtained using microarrays and DNA sequencing. A previous study of over 2,000 cases and over 12,000 controls indicated that the HLA region of chromosome 6 significantly influenced liver damage regardless of the particular medication, herbal ingredient, or supplement causing the damage. Therefore, the HLA region was the focus of the analysis.

Allele 14:01 of the HLA-B gene (B*14:01) was found to be significantly associated with liver injury due to Bactrim in European American patients. People in this population with this allele are at greater risk for liver injury when taking Bactrim. Haplotype analysis found that alleles B*14:01 and C*08:02 together were more strongly associated with liver injury in this population than B*14:01 alone.  From amino acid analysis, it is believed that the Sulfamethoxazole medication in Bactrim binds to an amino acid called cysteine in position 67 of the B*14:01 protein.

Allele 35:01 of the HLA-B gene was found to be significantly associated with liver injury due to Bactrim in African American patients. People in this population with this allele are at greater risk for liver injury when taking Bactrim. In this population, it is believed that the Sulfamethoxazole medication in Bactrim binds to an amino acid called phenylalanine in position 67 of the B*35:01 protein.

The research was e-published in the journal Hepatology () on April 9 ahead of the printed paper.

This research was presented in April 2019 at the EASL (European Association for the Study of the Liver) International Liver Congress in Vienna, Austria. The work was produced in collaboration with colleagues at Duke University, Mount Sinai Hospital, UNC-Chapel Hill, University of Michigan, Vanderbilt University and Indiana University.

The antibiotic Trimethoprim-Sulfamethoxazole (brand names Bactrim and Septra) is a common cause of drug-induced liver injury, but the genetics behind the injury are unknown. The most likely culprits are the HLA genes, which are known causes of liver injury with other medications.

Each HLA gene tested in this research has many different alleles- the same gene with different DNA sequences. The alleles for each patient with Trimethoprim-Sulfamethoxazole drug-induced liver injury (cases) and for each person from the general population without Trimethoprim-Sulfamethoxazole drug-induced liver injury (controls) were determined.

The frequencies of each allele in cases and controls were compared. Separate analyses were required for each race or ethnicity considered. Among White/Caucasian patients, those with the HLA-B*14:01 allele had approximately 8 times the risk of liver injury from Trimethoprim-Sulfamethoxazole compared to a person without this allele.