Investigation Of Influence Factors Of Anti-hepatitis-B-virus Therapy And The Clinical Significance Of HBV CccDNA Detection

[Objectives] To analyze the influence factors of HBV mutation in patients with chronic hepatitis B during nucleotide analogues therapy.[Methods] The clinical data and serum of 279 chronic hepatitis B patients treated with lamivudine and 87 chronic hepatitis B patients treated with adefovir dipivoxil and 40 chronic hepatitis B patients treated with entecavir were collected. HBV mutation were determined and analyzed.[Results] None of patients who treated with adefovir dipivoxil and entecavir proceeded HBV mutation in 48 weeks. Patients with ALT<5ULN, HBV DNA≥107copies/ml and complication with liver cirrhosis of abnormal liver function at baseline had significantly higher YMDD mutation rate. There was no association between YMDD mutation rate and HBeAg status. Chronic hepatitis B patients who gained early virological response had significantly lower YMDD mutation rate than patients who did not gain early virological response.[Conclusion] HBV mutation rate induced by adefovir dipivoxil and entecavir was lower than that induced by lamivudine. Higher HBV DNA loading and complication with liver cirrhosis of abnormal liver function at baseline and no early virological response seem to be the major determinants for the YMDD mutation during lamivudine therapy.PartⅡAssociation between early virologic response(EVR) and sustained virologic response (SVR) in patients with chronic hepatitis B during nucleotide analogues therapy[Objectives] To study the association between EVR and SVR in patients with chronic hepatitis B during nucleotide analogues therapy.[Methods] The clinical data and serum of 279 chronic hepatitis B treated with lamivudine and 87 chronic hepatitis B treated with adefovir dipivoxil and 40 chronic hepatitis B treated with entecavir were collected.[Results] EVR rate in patients treated with entecavir was higher than that in patients treated with lamivudine or adefovir dipivoxil; Virological response rate,bioche- mical response rate and serological response rate in patients with HBV DNA<3 log10 copies/ml in 12 weeks after therapy were higher than those in patients with HBV DNA 3 log10 copies/ml～5 log10 copies/ml or≥5 log10 copies/ml and virologic breakthrough rate was lower.[Conclusion] EVR is a useful factor for predicting SVR in chronic hepatitis B patients treated with nucleotide analogues.PartⅢClinical significance investigation of liver biopsy in HBV DNA positive patients with normal ALT/AST level[Objective] To investigate clinical significance of liver biopsy in HBV DNA positive patients with normal ALT/AST level.[Methods] Fluorescence quantitative real-time polymerase chain reactions were used to detect quantity of serum and intrahepatic HBV DNA in 20 chronic hepatitis B patients.[Results] Histological changes had occurred in liver biopsy specimens from 20 HBV DNA positive patients with normal ALT/AST level. Serum and intrahepatic total HBV DNA levels were found to correlate directly with each other. HBeAg positive chronic hepatitis B patients had higher serum HBV DNA loading and intrahepatic HBV DNA loading than HBeAg negative chronic hepatitis B patients. Serum HBV DNA levels were significantly lower during antiviral therapy in chronic hepatitis B patients with liver inflammation and normal ALT/AST level.[Conclusion] Histological changes may occur in liver biopsy specimens from HBV DNA positive patients with normal ALT/AST level. Chronic hepatitis B patients with liver inflammation should be treated. PartⅣClinical significance investigation of HBV cccDNA detection in patients with chronic hepatitis B[Objective] To investigate clinical significance of HBV covalently closed circular (ccc) DNA detection in patients with chronic hepatitis B.[Methods] Fluorescence quantitative real-time polymerase chain reactions were used to detect quantity of HBV cccDNA in serum,peripheral blood mononuclear cell and hepatic tissue.[Results] The detection rate of serum and peripheral blood mononuclear cell HBV cccDNA was found to correlate directly with serum HBV DNA loading. HBeAg positive chronic hepatitis B patients had higher serum HBV cccDNA levels than HBeAg negative chronic hepatitis B patients. Serum HBV cccDNA levels were found to positively correlate with intrahepatic HBV cccDNA levels,intrahepatic HBV DNA levels and serum HBV DNA levels. Serum HBV cccDNA levels had significantly lower in entecavir groups.As the total HBV DNA loading decreased in peripheral blood mononuclear cell, cccDNA became the predominant form of HBV DNA.[Conclusion] Serum and peripheral blood mononuclear cell HBV cccDNA detection may provide important information on progression of chronic hepatitis B,antiviral therapeutic effect and drug withdrawal so on. PartⅤClinical characteristic analysis of hepatitis B virus infection with different genotypes and the association with anti-HBV therapy[Objective] To analyze clinical characteristic of hepatitis B virus infection with different genotypes and the association with anti-HBV therapy[Methods] Sandwith hybridization microplate and fluorescence quantitative real-time polymerase chain reaction were used to detect HBV genotypes and serum HBV DNA loading in 98 chronic hepatitis B patients.[Results] In local region, chronic hepatitis B patients is major in HBV C infection. Serum levels of HBV DNA and ALT in patients with HBV C infection are higher than those in patients with HBV B infection. Morbidity of liver cirrhosis in patients with HBV C infection was higher than those in patients with HBV B infection. Response rate to PEG IFNα-2a was higher in those patients with HBV B infection than those patients with HBV C infection, but esponse rate to nucleoside analogue was no significant difference in patients with different HBV genotypes.[Conclusion] Chronic hepatitis B patients with various HBV genotypes have different clinical significance and antiviral therapeutic effect. HBV genotype detection may provide helpful information on therapeutic regimen and longterm prognosis.