Table 2.
Serum Biomarkers of DILI.
| Serum biomarker | Advantage | Disadvantage | Comments | Reference |
|---|---|---|---|---|
| GLDH | • Specific expression in liver. • Early recognition of DILI and not impacted by age, gender, or muscle injury. • Indicative of DILI prognosis. |
• Elevated levels without hepatotoxicity. • Controversy in predicting hepatocyte necrosis. |
• GLDH is related to DILI diagnosis and prognosis. • Possibly a specific biomarker for mitochondrial dysfunction. |
Antoine et al., 2013; Schomaker et al., 2013; Flanigan et al., 2014; McGill et al., 2014; Singhal et al., 2014; Thulin et al., 2017 |
| K18 | • K18 and ccK18 ratio could predict necrosis and apoptosis. • Early recognition of DILI. • Not affected by muscle exercise. • Indicative of DILI prognosis. |
• Not liver specific. • Also increased in other diseases. |
• In various liver diseases, elevations in K18 and ccK18 may represent liver inflammation, and their ratio could assess the extent of hepatocyte necrosis and apoptosis. | Thulin et al., 2014; Ku et al., 2016; Chu et al., 2017; Wei et al., 2017; Sugimoto et al., 2018 |
| SDH | • Early recognition of DILI could detect liver injury caused by special types of drugs. • Abundant in liver. • Short elimination half-life. |
• No indicative of DILI prognosis. | • Previous studies have shown that SDH concentration was elevated in acute and mild liver injuries, which suggested that it may be a sensitive biomarker in liver inflammation. | Harrill et al., 2012; Metushi et al., 2012; Williams et al., 2012; Metushi et al., 2014b |
| GST | • GSTM1, GSTT1, and GSTP1 associated with ATDILI. • Increased GSTα in early DILI. |
• Expensive and time-consuming genetic testing. • No reported in the prognosis of DILI. |
• The genetic polymorphism of GST is closely related to ATDILI and GSTα presents its sensitivity in DILI. | Singla et al., 2014; Cai et al., 2015; Wu et al., 2016a; Sun et al., 2017; Tsai et al., 2017 |
| BAs | • Informative about the mechanism of cholestasis caused by drugs. | • Lacking specificity in DILI. | • Elevated BA levels can be detected in various hepatobiliary diseases, which indicates its limited specificity in DILI. | Yamazaki et al., 2013; Qiu et al., 2016; Cepa et al., 2018 |
| CYP450 | • Participation in multiple drug metabolic reactions by CYP450 and its isoforms. • Poor outcome with anti-drug/anti-CYP P450 antibodies in antituberculosis drug-induced liver injury. |
• Genetic testing is expensive and time-consuming. • The mechanism between drugs and CYP is complex and remained unknown. |
• Treatment with some immune-related drugs may be effective once the role of immunity mechanism is determined. | Tang et al., 2013; Li et al., 2014; Metushi et al., 2014a; He et al., 2015; Metushi et al., 2016 |
| OPN | • Prognosis of bad outcome in DILI. • Associated with the degree of liver necrosis. |
• Not liver specific. | • OPN acts as a pro-inflammatory cytokine in inflammatory liver disease and attracts neutrophils, lymphocytes, and macrophages to hepatic injury sites. | Fan et al., 2015; Srungaram et al., 2015; Arriazu et al., 2017; Sampayo-Escobar et al., 2018 |
GLDH, glutamate dehydrogenase; K18, keratin 18; ccK18, caspase cleaves K18; SDH, sorbitol dehydrogenase; GST, glutathione S-transferase; GSTα, glutathione-S-transferase alpha; BAs, bile acids; CYP450, cytochrome P450; OPN, osteopontin.