MicroRNA-122 and cytokeratin-18 have potential as a biomarkers of drug-induced liver injury in European and African patients on treatment for mycobacterial infection.
Br J Clin Pharmacol
; 87(8): 3206-3217, 2021 08.
Article
en En
| MEDLINE
| ID: mdl-33432705
ABSTRACT
AIMS:
Patients on antituberculosis (anti-TB) therapy are at risk of drug-induced liver injury (DILI). MicroRNA-122 (miR-122) and cytokeratin-18 (K18) are DILI biomarkers. To explore their utility in this global context, circulating miR-122 and K18 were measured in UK and Ugandan populations on anti-TB therapy for mycobacterial infection.METHODS:
Healthy subjects and patients receiving anti-TB therapy were recruited at the Royal Infirmary of Edinburgh, UK (ALISTER-ClinicalTrials.gov Identifier NCT03211208). African patients with human immunodeficiency virus-TB coinfection were recruited at the Infectious Diseases Institute, Kampala, Uganda (SAEFRIF-NCT03982277). Serial blood samples, demographic and clinical data were collected. In ALISTER samples, MiR-122 was quantified using polymerase chain reaction. In ALISTER and SAEFRIF samples, K18 was quantified by enzyme-linked immunosorbent assay.RESULTS:
The study had 235 participants (healthy volunteers [n = 28]; ALISTER active TB [n = 30], latent TB [n = 88], nontuberculous mycobacterial infection [n = 25]; SAEFRIF human immunodeficiency virus-TB coinfection [n = 64]). In the absence of DILI, there was no difference in miR-122 and K18 across the groups. Both miR-122 and K18 correlated with alanine transaminase (ALT) activity (miR-122 R = .52, 95%CI = 0.42-0.61, P < .0001. K18 R =0.42, 95%CI = 0.34-0.49, P < .0001). miR-122 distinguished those patients with ALT>50 U/L with higher sensitivity/specificity than K18. There were 2 DILI cases baseline ALT, 18 and 28 IU/L, peak ALT 431 and 194 IU/L; baseline K18, 58 and 219 U/L, peak K18 1247 and 3490 U/L; baseline miR-122 4 and 17 fM, peak miR-122 60 and 336 fM, respectively.CONCLUSION:
In patients treated with anti-TB therapy, miR-122 and K18 correlated with ALT and increased with DILI. Further work should determine their diagnostic and prognostic utility in this global context-of-use.Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
MicroARNs
/
Enfermedad Hepática Inducida por Sustancias y Drogas
Tipo de estudio:
Etiology_studies
Límite:
Humans
País/Región como asunto:
Africa
Idioma:
En
Revista:
Br J Clin Pharmacol
Año:
2021
Tipo del documento:
Article
País de afiliación:
Reino Unido