Relationship Between MicroRNA-122 And Virological Response In Chronic Hepatitis B Patients

BackgroundAt present,chronic hepatitis B infection still remains an imperative worldwide health problem.According to World Health Organization,over 240 million people worldwide are living with chronic hepatitis B virus(HBV)infection,and China is one of the countries with the highest population of HBsAg-positive individuals.Chronic HBV infection can lead to fatal complications including liver cirrhosis,liver failure,and hepatocellular carcinoma,resulted from repeated flares and continuous inflammation.Currently,antiviral treatment options for chronic hepatitis B(CHB)patients include nucleos(t)ide analogues(NAs)and interferon.Multiple previous studies have identified several predictors for treatment response to NA therapy,such as alanine aminotransferase(ALT),interferon-inducible protein 10(IP-10),hepatitis B surface antigen(HBsAg)and hepatitis B core antibody(HBcAb)levels.However,as is known to all that the clinical outcome of virus infection is dependent on a complex interaction between viral factors and host immune response.And yet,most of the current predictors are virus-dependent,moreover,only a handful are performed in CHB patients with high viral load at baseline.MicroRNAs(miRNAs)are a large class of small non-coding RNAs.These approximately 22-nucleotides long RNAs post-transcriptionally regulate one third of human genes.In mammals,microRNA-122(miR-122)is the most abundant liver-specific miRNA,almost undetectable in other tissues.This miRNA has been identified involved in multiple liver physiology and pathology process.It also plays a role in hepatotropic virus infection as well as occurrence and development of hepatocellular carcinoma.Currently,these small RNAs are increasingly studied in circulating system and are widely identified as potential biomarker because of their stability,easy access to measurement and noninvasive measuring.And miR-122 is also identified to have the ability to serve as a biomarker in HBV-related liver diseases.However,whether the circulating miR-122 has the prognostic value of treatment response to NA therapy in non-neoplastic and non-fibrotic CHB patients remains unknown.AimsThe aim of this study was to identify the role of serum miR-122 levels as predictors for treatment response in CHB patients with pre-treatment high viral load treated with NAs.Secondary,we aim to explore the dynamic changes of miR-122 during antiviral treatment.MethodsA total of 80 naive CHB patients with pretreatment high viral load and positive hepatitis B e antigen(HBeAg),willing to receive NA therapy,were enrolled in this study.The serum of every patient collected at baseline,week 12 and week 24 were used.The total RNA was isolated and real-time quantitative PCR was performed to obtain relative miR-122 level.Differences between subgroups were analyzed by Mann-Whitney U-test and Chi-squared test.Receiver operating characteristic(ROC)cxurve and logistic regression were performed to determine the prognostic value of serum miR-122 levels for treatment response to NAs.Dynamic changes in serum miR-122 level were evaluated by repeated measures analysis.ResultsWe found that serum miR-122 levels at the early phase of treatment,like week 12 and week 24,were significantly lower in patients who developed a virological response at week 96,compared with those who did not achieve a virological response.Levels of miR-122 at week 12 and week 24 were determined to be effective prognostic indicators for a VR with satisfactory AUROC values at 0.812 and 0.749 respectively.Moreover,the multivariate analysis also showed that serum miR-122 level at week 12 is still an independent protective factor for virological response.Then we firstly identified the dynamic change of serum miR-122 level during the antiviral treatment with NAs.During the antiviral therapy,serum miR-122 level deceased steadily and an earlier reduction was observed in patients with a virological response.ConclusionWe firstly identified serum miR-122 level at week 12 of NA treatment as an independent predictor for the virological response in CHB patients with high viral load.We also firstly identified the dynamic change of serum miR-122 level during the antiviral treatment with NAs.