Abstract
BackgroundOccult hepatitis B virus infection (OBI) is an important risk factor of liver cirrhosis and hepatocellular carcinoma. Type 1 interferon (IFN) signaling-related miRNAs were significantly associated with hepatitis B virus (HBV) infection. However, the characteristics of serum IFN signaling-related miRNAs in OBI remain unclear. Therefore, this study aimed to analyze the expression levels of serum IFN signaling-related miRNAs in OBI and to evaluate their potential values for OBI diagnosis.MethodsTwenty serum samples for training test (10 healthy controls and 10 OBI patients) and 438 validation serum samples from healthy controls, asymptomatic HBsAg carriers (ASC), and chronic hepatitis B (CHB) and OBI patients were collected. Expression levels of 32 IFN signaling-related miRNAs were analyzed in training and validation sets of samples using RT-qPCR.ResultsAmong 32 IFN signaling-related miRNAs, decreased miR-122 levels and increased miR-130a levels were detected in training OBI samples. Furthermore, the results from validation test showed that the mean serum miR-122 and miR-130a level was 2.28 ± 0.96 and 3.11 ± 0.93 in OBI subjects, respectively. Compared to the healthy controls, ASC and CHB patients, miR-122 levels were significantly downregulated, while miR-130a levels were significantly upregulated in OBI patients. ROC analysis indicated that miR-122 + miR-130a could differentiate OBI from healthy controls, ASC, and CHB (≥ 0.87 of AUC).ConclusionsOur study suggested that decreased serum miR-122 level and increased miR-130a level were significantly associated with OBI. Moreover, a combination of miR-122 and miR-130a could be served as a potential marker for OBI diagnosis.
Highlights
Occult hepatitis B virus infection (OBI) is an important risk factor of liver cirrhosis and hepatocellular carcinoma
Serum IFN signaling-related miRNAs in OBI patients validated by qRT-PCR As the results shown in validated study (Fig 2), the mean serum miR-122 level was 2.28 ± 0.96, 3.16 ± 4.85, 3.00 ± 0.67, and 3.61 ± 0.76 in the groups of OBI, healthy controls, asymptomatic HBsAg carriers (ASC), and chronic hepatitis B (CHB), respectively
The levels of serum miR-122 were gradually increased from OBI subjects to healthy control, ASC, and CHB patients (Trends F = 4.00 and P = 0.046)
Summary
Occult hepatitis B virus infection (OBI) is an important risk factor of liver cirrhosis and hepatocellular carcinoma. Type 1 interferon (IFN) signaling-related miRNAs were significantly associated with hepatitis B virus (HBV) infection. The characteristics of serum IFN signaling-related miRNAs in OBI remain unclear. This study aimed to analyze the expression levels of serum IFN signaling-related miRNAs in OBI and to evaluate their potential values for OBI diagnosis. In a multicenter retrospective study, Lin et al reported that IFN signaling-related miRNAs such as miR-29 family, miR-130a, miR-143, and miR-145 could be used as serum markers for the early screening of HBV-related HCC [12]. The previous studies have shown that miR-122, miR-125b, miR-372/373, and miR-146 could influence HBV replication in vitro and were significantly associated with HBV-related cirrhosis and HCC [13, 14]
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