Serum MiRNA panel as potential biomarkers for chronic hepatitis B with persistently normal alanine aminotransferase.
BACKGROUND
Circulating miRNAs, a family of miRNAs existing in plasma and serum, have a great potential to serve as novel biomarkers in body fluids for non-invasive diagnosis and prognosis of many diseases.


METHODS
A multistage, case-control study was designed to establish a panel of serum miRNAs that could be surrogate markers for chronic hepatitis B with persistently normal alanine aminotransferase (ALT). A total of 295 CHB patients presenting persistently normal ALT levels with significant histological features (SPNALT group), 243 CHB patients presenting persistently normal ALT levels with no significant histological features (NSPNALT group), and 178 healthy controls (healthy group) were enrolled in the study. An initial screening of miRNAs was performed by Illumina sequencing using serum samples pooled from SPNALT patients and controls. Quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR) assay was performed to evaluate the expression of selected miRNAs. A logistic regression model was constructed using a training cohort (n=380) and validated using a cohort (n=258). The area under the receiver operating characteristic curve (AUC) was used to evaluate diagnostic accuracy.


RESULTS
We identified 9 miRNAs (hsa-miR-885-5p, hsa-miR-122-5p, hsa-miR-10a-5p, hsa-miR-511-5p, hsa-miR-574-5p, hsa-miR-98-5p, hsa-miR-26a-5p, hsa-miR-192-5p, hsa-miR-30b-5p) and established 3 miRNA panels that provided high diagnostic accuracy for SPNALT. The AUC of miRNA panels for SPNALT vs. healthy was 0.882 (95% CI=0.839 to 0.925), for SPNALT vs. NSPNALT was 0.894 (95% CI=0.857 to 0.930), and for SPNALT vs. control was 0.860 (95% CI=0.821 to 0.899).


CONCLUSIONS
We constructed serum miRNA panels with considerable clinical value in diagnosing PNALT.
Department of Hepatosis, The Third Hospital of Zhenjiang Affiliated Jiangsu University, Zhenjiang, China. Electronic address: tyw915@sina.com.
Youwen
Y
Tan
Department of Hepatosis, The Third Hospital of Zhenjiang Affiliated Jiangsu University, Zhenjiang, China.
Guohong
G
Ge
Department of Hepatosis, The Third Hospital of Zhenjiang Affiliated Jiangsu University, Zhenjiang, China.
Tengli
T
Pan
Department of Hepatosis, The Third Hospital of Zhenjiang Affiliated Jiangsu University, Zhenjiang, China.
Danfeng
D
Wen
Department of Hepatosis, The Third Hospital of Zhenjiang Affiliated Jiangsu University, Zhenjiang, China.
Jianhe
J
Gan
D000328:Adult; D000410:Alanine Transaminase / Q000378:metabolism*; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D005260:Female; D019694:Hepatitis B, Chronic / Q000097:blood* / Q000175:diagnosis* / Q000201:enzymology / Q000235:genetics; D006801:Humans; D016015:Logistic Models; D008297:Male; D035683:MicroRNAs / Q000097:blood* / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction
D015415:Biomarkers; D035683:MicroRNAs; D000410:Alanine Transaminase
Alanine aminotransferase; Biomarker; Chronic; Hepatitis B virus; Non-invasive; microRNA