Liver Damage And Its Relavant Factors Of Patients With Persistent Hepatitis B Virus Infection

OBJECTIVE: To investigate hepatic damage in patients with persistent hepatitis B virus(HBV) infection and its relationships with HBV genotype,viral load,and viral antigen expression in liver.To investigate the spontaneous occurrence of 2-amino-3-p-hydroxyphenyprop acid-methionine-aminosuccinic acid-aminosuccinic acid(YMDD) mutation in patients with persistent HBV infection without antiviral therapy.Method:Liver biopsy was conducted and serum samples was collected from 37 patients from Xinjiang province with serum HBV DNA positive and alanine aminotransferase(ALT) level less than 1.5up limited normal (ULN) and without antiviral therapy. HBV genotype was tested by type specific primers- polymerse chain reaction(PCR) and YMDD mutation by polymerse chain reaction restriction fragment length polymorphism(PCR-RFLP). serum HBV maker was tested by ELESA and quantitive HBV DNA was tested by real-time quantitive fluorescent PCR.Hepatic histological activity index was assayed after HE staining.Expression of hepatitis B surface antigen(HBsAg) and hepatitis B core antigen(HBcAg) was detected by immunal historychemical method.Results:1.Most of the patients with normal ALT level showed some extent hepatic damage.The hepatic inflammation usually was G₁ G₂,and the fribosis staged S₁ S₂ while S3 S4 was observed occasionly.2.The difference of hepatic inflammation among the groups of different age was significant. The hepatic inflammation of patients younger than 30 years old usually was G₁ G₂, The hepatic inflammation of patients older than 30 was more serious,6 was G₂,2 was G3,even 4 was G4.3. BC mixing type was dominated, 22 out of 37 account for 59.46%.B type 10 for 27.03%, C type 5 for 13.51%. No A , D , E , F type was detected .4. Genotype distribution was different between male and female. mixing BC type was dominated in male(12/15,accout for 80.00%)while in female both BC mixing type and B type were dominant(both were 10 in 22,accout for 45.45% respectively).5. Among 37 patients,81.82% (30/37) was hepatitis B e antigen(HBeAg) positive and 18.92% (7/37) was HBeAg negative.Serum viral loads is significantly higher in HBeAg positive patients than in HBeAg negative patients.6.Serum viral load was correlated with age.viral loads was significant higher in patients less of 30 years old than in patients older than 30 .viral load of 13 patients were more than 1.0×108 among 24 patients younger than 30 . viral load of 13 patients older than 30 were mostly less than 1.0×108.7.There was no difference of the positive rates of HBsAg in liver among groups of different viral load.while expression of HBcAg in liver was higher in petients with high viral load.No difference of the positive rates of hepatic viral antigen was observed among groups of different genotype.8.Hepatic fribosis is more gently in group of BC mixing type,while there was no correlations between hepatic imflammation and HBV genotype,as liver damage and viral load.9.YMDD mutation was identified in 2 among 37 (spontaneous mutation rate is 5.45%), one existed as YMDD+YVDD+YIDD , while the other was YMDD +YIDD.Conclusions:1. Varied extent hepatic damage is a common feature of patients with persistent HBV infection.the extent of hepatic damage is correlated with age but not with viral load,genotype and viral protein expression in liver. 2. Liver biopsy should be considered in patients with persistent HBV infection with normal ALT level especially in elder for respective evaluation and treatment.3. There is BC mixing type, B type ,C type in patients with persistent HBV infection from Xinjiang, the dominant genotype is BC mixing type.Genotype distribution is different between male and female, BC mixing type was dominated in man, while both BC mixing type and B type was dominated in woman.4. Serum viral load is correlated with e antigen state and age.Patients with HBeAg positive and younger patients have higher viral load in serum.5. The YMDD motif mutation occurs spontaneously in patients of chronic hepatitis B without antiviral therapy.