Meta-analysis Of Correlation Between Serum MiR-122 And Stages Of Hepatic Fibrosis

BACKGROUND:Liver fibrosis is caused by various pathogenic factors,such as viral infection,alcohol,cholestasis,drug poisons,parasites,etc.,which cause abnormal proliferation of connective tissue caused by liver injury.At present,liver biopsy pathology is the golden standard for diagnosing liver fibrosis and evaluating its severity.However,this diagnosis method is easy to be affected by sampling differences or errors,because of the location,number and size of different liver samples,and the differences in diagnostic level among pathological observers.This invasive diagnosis is prone to post-operative complications,with high risk and cost,and at the same time,because puncture biopsy cannot be monitored in real time,it cannot dynamically evaluate the curative effect,prognosis and other aspects of patients,which makes puncture biopsy less acceptable in patients and plays a limited role in the detection and diagnosis of early liver fibrosis.MicroRNA is a small non-coding endogenous RNA that regulates 60%of human gene expression.Different small RNA groups are associated with liver fibrosis and inflammatory liver disease induced by chronic hepatitis B(CHB)and chronic hepatitis C(CHC).MicroRNA-122 is a rich liver-specific microRNA,accounting for about 70%of the total liver microRNA.Studies have shown that microRNA-122 plays an important role in the occurrence and development of liver fibrosis.The level of serum microRNA-122 in patients with liver fibrosis was higher than that in control.However,whether the expression level of microRNA-122 in serum is related to the degree of fibrosis is still controversial.Whether microRNA-122 can be used as an index for detecting fibrosis and predicting the severity of fibrosis deserves further study.Objective:Collecting the articles which evaluate the staging of liver fibrosis by liver biopsy and detect the level of serum microRNA-122 in different stages of liver fibrosis.To systematically evaluate the correlation between microRNA-122 and liver fibrosis stages by meta-analysis,so as to explore and discuss the role of microRNA-122 in the occurrence and development of liver fibrosis and whether the microRNA-122 can be used as an index for detecting fibrosis and predicting the severity of fibrosis deservesMETHODS:PubMed?Embase?Ovid?CNKI and Wanfang databases were used to retrieve published articles on the correlation between microRNA-122 and liver fibrosis staging.Two researchers screened the articles according to inclusion and exclusion criteria,and evaluated the articles using quality assessment tool Newcastle-Ottawa Scale(NOS score).RevMan 5.3 software was used to evaluate the included articles,testing the bias of identification,analyze the sources of heterogeneity and draw forest maps.Result:1.Literature retrieval results:After Endnote and manual de-duplication,reading title?abstracts and full-text,11 papers were finally included in this study,including 5 Chinese papers and 6 English papers.A total of 1296 patients were included in this study.2.Statistical results:(1).Six studies also studied the level of serum microRNA-122 in patients with fibrosis stage FO and F1.A total of 238 patients had standardized mean difference(SMD)of 0.33,95%confidence interval(95%CI)of 0.04-0.61,Z=2.24 P=0.03.(2)Eight studies also studied the expression of serum microRNA-122 in patients with hepatic fibrosis stage F1 and F2.There were 579 patients with standardized mean deviation(SMD)of 0.27,95%confidence interval(95%CI)-0.04-0.57,Z=1.69 P=0.09.(3)A total of 9 studies were conducted to study the expression of serum microRN A-122 in patients with F2 and F3 stages of liver fibrosis.513 patients had standardized mean deviation(SMD)of 0.38,95%confidence interval(95%CI)-0.08-0.85,Z=1.62,P=0.11.(4)Six studies also studied the expression of serum microRNA-122 in patients with fibrosis stage F3 and F4.There were 341 patients with standardized mean difference(SMD)of 0.47,95%confidence interval(95%CI)of 0.24-0.70 and Z=4.02 P<0.0001.(5)A total of 10 studies were conducted to study the expression of serum microRNA-122 in patients with mild hepatic fibrosis(F<3)and significant hepatic fibrosis(F?3).A total of 1295 patients were enrolled.The standardized mean difference(SMD)was 0.77,95%confidence interval(95%CI)0.10-1.44,Z=2.27,P=0.02.(6)Three studies also studied the expression of serum microRNA-122 in patients with liver fibrosis and normal control group.There were 904 patients with standardized mean difference(SMD)of 2.01,95%confidence interval(95%CI)of 0.74-3.28,Z=3.11,P=0.002.(7)Four studies were conducted to study the expression of serum microRNA-122 in patients with mild hepatic fibrosis(F<3)and normal control group.A total of 763 patients had standardized mean difference(SMD)of 2.57,95%confidence interval(95%CI)of 0.21-4.92,Z=2.14,P=0.03.(8)Four studies were conducted to study the expression of serum microRNA-122 in patients with significant hepatic fibrosis(F?3)and normal controls.There were 581 patients with standardized mean deviation(SMD)of 2.01,95%confidence interval(95%CI)-0.69-4.71,Z=1.46,P=0.14.3.Heterogeneity test results:(1)Heterogeneity exists in liver fibrosis stage F1 and F2 control group,mild fibrosis and advanced fibrosis control group,mild fibrosis and normal control group,advanced fibrosis and normal control group.Subgroup analysis shows that the heterogeneity originates from the race included in the patients.After differentiating different studies of Asian and Caucasian descendants,Caucasian descendants I2=0%in subgroup.(2)Heterogeneity existed in F2 and F3 control groups.After sensitivity analysis and subgroup analysis,it was found that the heterogeneity decreased after deleting one of the articles,and I2=0%.Subgroup analysis also found that I2=0%in Caucasian subgroup after differentiating between Asian and Caucasian studies,probably because Caucasian subgroup did not contain this article.The high heterogeneity may be related to the clinical diversity of the sample included in this literature.(3)Heterogeneity analysis of the etiology included in the study showed that HBV and HCV infection were not the source of heterogeneity.Some subgroup analysis showed that the heterogeneity was reduced because the subgroups with reduced heterogeneity were also included the studies of single race.Conclusion:1.The level of serum microRNA-122 expression was significantly correlated with the degree of liver fibrosis.2.Serum microRNA-122 plays an important role in differentiating normal people and patients with hepatic fibrosis,mild hepatic fibrosis and advanced hepatic fibrosis,mild hepatic fibrosis and normal people.3.MiR-122 may be a potential marker for diagnosing hepatic fibrosis and evaluating the severity of liver fibrosis.