Abstract
Aims
Liver-enriched microRNA-122 (miR-122) is a novel circulating biomarker for drug-induced liver injury (DILI). To date, miR-122 has been measured in serum or plasma venous samples. If miR-122 could be measured in capillary blood obtained from a finger prick it would facilitate point-of-care testing, such as in resource-limited settings that have a high burden of DILI.
Methods
In this study, in healthy subjects, miR-122 was measured by polymerase chain reaction in three capillary blood drops taken from different fingers and in venous blood and plasma (n = 20). miR-122 was also measured in capillary blood obtained from patients with DILI (n = 8).
Results
Circulating miR-122 could be readily measured in a capillary blood drop in healthy volunteers with a median (interquartile range) cycle threshold (Ct) of 32.6 (31.1–34.2). The coefficient of variation for intraindividual variability across replicate blood drops was 49.9%. Capillary miR-122 faithfully reflected the concentration in venous blood and plasma (Pearson R = 0.89, P < 0.0001; 0.88, P < 0.0001, respectively). miR-122 was 86-fold higher in DILI patients [median value 1.0 × 108 (interquartile range 1.89 × 107–3.04 × 109) copies/blood drop] compared to healthy subjects [1.85 × 106 (4.92 × 105–5.88 × 106) copies/blood drop]. Receiver operator characteristic analysis demonstrated that capillary miR-122 sensitively and specifically reported DILI (area under the curve: 0.96, P = 0.0002).
Conclusion
This work supports the potential use of miR-122 as biomarker of human DILI when measured in a capillary blood drop. With development across DILI aetiologies, this could be used by novel point-of-care technologies to produce a minimally invasive, near-patient, diagnostic test.
Liver-enriched microRNA-122 (miR-122) is a novel circulating biomarker for drug-induced liver injury (DILI). To date, miR-122 has been measured in serum or plasma venous samples. If miR-122 could be measured in capillary blood obtained from a finger prick it would facilitate point-of-care testing, such as in resource-limited settings that have a high burden of DILI.
Methods
In this study, in healthy subjects, miR-122 was measured by polymerase chain reaction in three capillary blood drops taken from different fingers and in venous blood and plasma (n = 20). miR-122 was also measured in capillary blood obtained from patients with DILI (n = 8).
Results
Circulating miR-122 could be readily measured in a capillary blood drop in healthy volunteers with a median (interquartile range) cycle threshold (Ct) of 32.6 (31.1–34.2). The coefficient of variation for intraindividual variability across replicate blood drops was 49.9%. Capillary miR-122 faithfully reflected the concentration in venous blood and plasma (Pearson R = 0.89, P < 0.0001; 0.88, P < 0.0001, respectively). miR-122 was 86-fold higher in DILI patients [median value 1.0 × 108 (interquartile range 1.89 × 107–3.04 × 109) copies/blood drop] compared to healthy subjects [1.85 × 106 (4.92 × 105–5.88 × 106) copies/blood drop]. Receiver operator characteristic analysis demonstrated that capillary miR-122 sensitively and specifically reported DILI (area under the curve: 0.96, P = 0.0002).
Conclusion
This work supports the potential use of miR-122 as biomarker of human DILI when measured in a capillary blood drop. With development across DILI aetiologies, this could be used by novel point-of-care technologies to produce a minimally invasive, near-patient, diagnostic test.
Original language | English |
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Pages (from-to) | 2027-2033 |
Number of pages | 7 |
Journal | British Journal of Clinical Pharmacology |
Volume | 83 |
Issue number | 9 |
Early online date | 3 Mar 2017 |
DOIs | |
Publication status | Published - Sept 2017 |