The diagnostic role of miR-122 in drug-induced liver injury

Abstract

Background:Drug-induced liver injury (DILI) is a potentially severe adverse drug reaction especially in susceptible patients. But there are no sensitive or specific parameters to detecting DILI. The specific expression of miR-122 in the liver has been a hotspot in the evaluation of hepatic toxicity due to its high stability and sensitivity.Methods:We performed a systematic literature review through July 31, 2017 to identify studies which evolved DILI patients testing miR-122 without limiting a certain drug. According to the PRISMA statement, a meta-analysis: the diagnostic role of miR-122 in DILI was made. QUADAS-2 quality evaluation table was used to evaluate the quality of the documentary evidence, PRISMA flowchart and quality evaluation table were drawn with RevMan, use Stata to calculate the sensitivity and specificity of miR-122 in diagnosing DILI, ROC curve and Deeks funnel plot were also drawn by STATA.Results:Eleven studies involved 194 DILI patients and 251 controls, all were tested miR-122 (fold change). Sensitivity of miR-122 in diagnosing DILI was [0.85 (95% CI, 0.75–0.91), I2 = 53.46%] and specificity was [0.93 (95% CI, 0.86–0.97), I2 = 65.10%], the area under ROC curve was 0.95 (95% CI, 0.93–0.97). While in acetaminophen (APAP)-induced liver injury, the sensitivity was [0.82 (95%CI, 0.67–0.91), I2 = 65.77%] specificity was [0.96 (95%CI, 0.88–0.99), I2 = 31.46%], AUROC was 0.97 (95% CI, 0.95–0.98).Conclusions:In this systematic review and meta-analysis, we found miR-122 have a high specificity in DILI, and a modest positive diagnostic effects. On the basis of the limited evidence, further research is needed to evaluate the long-term observation and more clinical data to testify miR-122 in diagnosing DILI.

Diagnostic Biomarkers in Liver Injury by Drugs, Herbs, and Alcohol: Tricky Dilemma after EMA Correctly and Officially Retracted Letter of Support

“…Biomarkers are defined by the National Institutes of Health Biomarkers Definitions Working Group as "a characteristic that is objectively measured and evaluated as an indicator of normal biological processes, pathogenic processes, or pharmacologic responses to a therapeutic or toxic intervention" [18]. In clinical medicine, biomarkers are used diagnostically to aid existing tools to establish the correct diagnosis of diseases that include liver injury caused preferentially by drugs and herbs [11][12][13][14][15][16][17]. Examples of biomarkers focus on the analysis of molecules such as RNA, DNA, and proteins in biological fluids [11][12][13][14][15][16][17][18][19].…”

“…Biomarkers of idiosyncratic DILI differ in their intentional use and may now best be classified as diagnostic or prognostic biomarkers [14,24]. Both biomarker types have been discussed in a variety of contexts [11][12][13][14][24][25][26][27][28][29][30][31][32][33], whereas the current analysis focuses on only diagnostic biomarkers. These must be used prior to prognostic biomarkers for DILI case evaluation since a prognosis depends on a correct diagnosis.…”

“…Krauskopf [27] Preliminary data for idiosyncratic DILI, also low case number. Liu [13] MicroRNA-192 Liver specific release from damaged hepatocytes; validation reported as ongoing.…”

“…In particular, microRNAs including microRNA-122 have been evaluated in experimental liver injury and in human intrinsic DILI caused by paracetamol, but their diagnostic value as diagnostic biomarker remains unclear due to lack of information on the method that was used to assess causality [40]. Some groups encouraged their use at least partially [5,13,28,[47][48][49], while others were more cautious and refrained from mentioning these tools [50]. It is also clear that microRNA-122 is only a simple marker of liver injury (Table 1), assessable in the capillary blood of patients with intrinsic paracetamol induced DILI, whereby causality for paracetamol was ascertained using the updated RUCAM [51].…”

“…Complex liver diseases such as autoimmune hepatitis (AIH) require a specific AIH diagnostic algorithm [10], whereas DILI and HILI need specific diagnostic algorithms including the RUCAM (Roussel Uclaf Causality Assessment Method) [8,9]. Diagnostic biomarkers play an essential role for various liver diseases including HBV and HCV infections [8,9] and are also under discussion for cases of DILI [11][12][13][14] and HILI [15,16]. Unfortunately, regulatory recommendations to use some new biomarkers in clinical trials were officially retracted due to overt misconduct in external studies.…”