Antiviral Therapy For Chronic Hepatitis B Patients And Correlation Studies With T Helper Cell17Related Cytokines

Hepatitis B virus (HBV) infection is common worldwide (about350~400millioncarriers), and there are15%-40%population develop into liver cirrhosis, liver failure andhepatocellular carcinoma, these end-stage liver diseases seriously affect the outcome ofchronic hepatitis B (CHB) patients. Effective anti-viral therapy can delay or prevent thedevelopment of liver diseases. But effective anti-viral therapy is correlated with the type ofanti-viral drugs, the time to begin anti-viral therapy, the time to withdraw and host immunereaction. Anti-viral response are divided as follows: virological response; serologicalresponse; drug resistance. In recent years, nucleot(s)ide analogs (NUCs) are widely used forits specific anti-viral efficacy, convenience and few side effects. Especially lamivudine(LAM) and adefovir (ADV), these two drugs are most widely used for its cheap price andearlier appearance. In order to obtain satisfied efficacy, not only do initial time need furtherinvestigation, but also the CHB population who are resistant to anti-viral drugs and thosewho need to maintain long time virological response after drug withdraw. Immune responseis also important in the clearance of HBV. Th17cell is a kind of T helper cell found inrecent years, and gain importance for its role in preventing infection and regulating autoimmune diseases. IL-17A is secreted by Th17cell, and exist in almost all kinds of cells inliver. But its role in virological response is not clear.Our study planned to retrospectively collect the data of CHB patients who receiveantiviral therapy at our department, and record the initial time to receive antiviral therapy inthose patients who obtained long time virological response to find the best time to initiateantiviral therapy. The same work was done for patients with drug resistance to seek the bestmethod for rescue therapy. For patients who obtained clinical response using NUCs, longterm outcomes were observed to investigate risk factors for withdrawal rebound and thebest time for drug withdraw. Protein microarray was applied to compare the differencebetween different kinds of patients who had diverse antiviral responses, and the difference of Th17cell related cytokine levels between different time were measured to investigate thepattern of Th17cell related cytokine in the process of antiviral therapy, aiming to offer cluesfor predicting different anti-viral response types and for regulating immune state for patientswho are resistant to anti-viral therapy.Results1. To LAM and ADV, initial combined therapy are better than sequential combinedtherapy.2. To CHB patients with drug resistance, ADV20mg is a considerable choice, andETV plus TDF is the best choice for rescue therapy, while interferon is not recommended.3. Preliminary prediction can be made according to HBeAg state for long tern clinicaloutcome.4. A duration of more than96-week consolidation therapy after serological response isrecommended for HBeAg-positive patients; a duration of more than144-week consolidationtherapy after serum HBV DNA undetectable is recommended for HBeAg-negative patients.5. A sustained response of more than96weeks is a good predictive indicator for longtern response.6. Moderate elevation of IL-17A is correlated with serological response of CHBpatients.7. A regularly measurement of IL-17A level is beneficial to the assessment ofserological response in the process of anti-viral therapy.