HBV Genotyping And Quantitative Analysis Of γ-GT And HBsAg In Patients With Chronic Hbv Infection With Different Degree Of Liver Fibrosis

Backgrund: Infection with hepatitis B virus(HBV)is a public health problem worldwide,and more than 240 million people are estimated to have persistent HBV infection.Chronic hepatitis B virus infection is the main cause of liver fibrosis,and thus the development of liver cirrhosis or liver decompensation.HBV genotype distribution has ethnic and regional differences,and influences the progress of liver fibrosis and anti-viral treantment response.In China,HBV genotype mainly composed by B and C genotype,which caused chronic hepatitis B is the important hazard factor for liver cirrhosis and hepatocellular carcinoma(HCC).Hepatic fibrosis is an important pathological stage of chronic hepatitis B(recurrent hepatitis)to advanced stage of liver diseases progression.Therefore,early diagnosis is not only important for guiding antiretroviral therapy,but also with the potential to reverse liver fibrosis.Although liver biopsy is the gold standard for the diagnosis of liver fibrosis and cirrhosis,it is an invasive procedure with complex process,high price and poor compliance.Thus,it is difficult to applicate in resource-constrained settings and also can not achieve early screening purpose.In view of this,a variety of noninvasive diagnostic models based on blood characteristics have been developed.Among those indices,the aspartate transaminase(AST)-to-platelet ratio index(APRI)and fibrosis index based on four factors(Fib-4)have the advantage of comprising only inexpensive laboratory tests,which are available in primary care,and have been recommended for the diagnosis of cirrhosis in resource-limited settings by the WHO guidelines.In spite of the fact that they were recommended to diagnose cirrhosis by WHO guidelines,APRI and FIB-4 have faced some problems,such as the low level of sensitivity and positive predictive value,and the lack of enough diagnostic accuracy for liver fibrosis.Objective: The aim of this study was to investigate the difference of HBV genotype,the noninvasive model of γ-glutamyl transpeptidase(γ-GT)and hepatitis B surface antigen(HBs Ag)(Gq HBs R)in the diagnosis of hepatic fibrosis in patients with chronic HBV.And then compare the diagnostic efficacy of Gq HBs R with APRI and FIB-4.Methods: Blood samples and clinical data of 317 patients with chronic hepatitis B virus infection(CHB patients)were collected from Fuyang Second People’s Hospital,affiliated to Fuyang Institute of Infectious Diseases of Anhui Medical University from may,2013 to June,2016.Fibrosis was evaluated by liver biopsy.HBV genotype of CHB patients was examined by q RT-PCR and then analyzed the relationship between genotype and liver fibrosis or HBe Ag seroconversion.The relationship between Gq HBs R,γ-GT,Hbs Ag and hepatic fibrosis staging were analyzed.The diagnostic efficacy and correlation of Gq HBs R with FIB-4 or APRI were evaluated.Results: HBV was mainly C genotype in 317 patients.The proportion of C and B genotype was statistically significant in different stages of CHB patients with liver fibrosis(P <0.01).The genotype ratio of B genotype was significantly lower in CHB patients with significant hepatic fibrosis(≥S2)than that of the patients with no obvious liver fibrosis(<S2).HBe Ag serological conversion analysis showed that the HBe Ag positive ratio was significantly higher in the C genotype than in the B genotype.The level of γ-GT,score of Gq HBs R and FIB-4 were gradually increased with the increase of liver fibrosis staging,and the level of Hbs Ag was gradually decreased(p<0.01).Gq HBs R showed a positive correlation with FIB-4 in CHB patients with liver fibrosis(R = 0.4235,P <0.0001).The value of Gq HBs R(AUC=0.860)in diagnosis of hepatic fibrosis was significantly higher than that ofγ-GT,Hbs Ag,FIB-4 and APRI,the AUC values were 0.599,0.590,0.789 and 0.775,respectively.The AUC value of Gq HBs R was about 0.9 for thediagnosis of different stages of liver fibrosis.Furthermore,Se,Sp,PPV and NPV was relatively high(>75%).Conclusions: CHB patients with significant liver fibrosis(≥S2)is mianly infected by C genotype of HBV in Anhui province.C genotype is correlated with HBe Ag serological conversion and likely to cause severe liver fibrosis than B genotype.The diagnostic value of Gq HBs R model is significantly higher than FIB-4 and APRI,and exhibits a better performance for identifying stages of liver fibrosis.Thus,to a certain extent,Gq HBs R reduce the proportion of patients undergoing liver biopsy.