Effect Of Entecavir Treated On Patients With Chronic Hepatitis B For 7 Years And The Value Of Hepatocyte Death Serum Markers

【Objective】To investigate the efficacy,safety and drug resistance of entecavir long-term treatment of NA-naive and NA-experienced chronic hepatitis B(CHB)patients.To investigate the changes of hepatocyte death serum markers M30 antigen and M65 antigen in CHB patients treated with entecavir and its predictive value during treatment.【Methods】1.We retrospectively analyzed 87 cases of chronic hepatitis B patients treated with entecavir monotherapy in Ruijin Hospital Infectious Clinic,and observed the liver and kidney function,HBV-DNA quantification,HBV-M and abdominal ultrasound.2.Thirty-two CHB patients treated with entecavir were enrolled.Twenty-four patients were followed up for 12 weeks and 8 patients were followed up for 24 weeks.The level of M30 antigen and the level of M65 antigen were detected and the significance of its level change during antiviral therapy was explored.【Results】1.Among the 87 patients treated with entecavir monotherapy,32 were NA-naive patients and 55 NA-experienced patients.During the 7-year follow-up,the rates of virologic response、drug resistance and HBeAg loss of naive patient treated with entecavir were 97%(31/32)、3%(1/32)、47%(9/19),respectively.The rates of virologic response、drug resistance and HBeAg loss of ADV-experienced patients were 97%(30/31)、 3%(1/31)、45%(13/29),And two patients(8%)achieved HBsAg loss.The rates of virologic response 、 drug resistance and HBeAg loss of LAM-experienced patients were 62%(13/21)、38%(8/21)、13%(2/15).Early virological response rate in naive patients treated with entecavir was higher than that of LAM-experienced and ADV-experienced patients(P = 0.0004 and P = 0.007).In all patients and naive patients,Early virological responses of HBeAg-negative patients was higher than that of HBeAg-positive patients(P = 0.012 and P = 0.001).Early virological responses of navie patiens was higher than that of ADV-experienced group and LAM-experienced group(P =0.0001).HBeAg loss had no significant difference between the three groups(P = 0.368).2.At 12 weeks of treatment with entecavir,M30 antigen level was significantly lower than baseline(P = 0.0003),M65 antigen level was also significantly dicreased(P =0.0002).The level of M30 antigen and M65 antigen in patients who received virological response at 12 weeks of treatment was significantly lower than that of patients who received partial virological response(P = 0.0162 and P <0.0001).At 24 weeks of treatment,M30 antigen levels and M65 antigen levels were also significantly lower than baseline,while ALT levels and AST levels were also significantly reduced with the duration of treatment,M30 antigen、M65 antigen and ALT decreased with a significant correlation,(r=0.69、P<0.0001 and r=0.64、P<0.0001).At the 24 th week of treatment,M30 antigen levels and M65 antigen levels were significantly correlation with HBV DNA levels.(r=0.57、P =0.0016 and r=0.65、P =0.0002).【Conclusion】1.Na-naive patients treated with entecavir have long-term efficacy,good safety and low resistance.ADV-experienced patients treated with entecavir still achieve better long-term efficacy.Because of high risk of resistance,it is not a good choice for LAM-resistant patients sequential treatmed with entecavir.2.Hepatocyte apoptosis and death levels are closely related to the degree of inflammatory necrosis of the liver after viral infection.Serum M30 antigen and M65 antigen can predict the severity of the disease.After treatmed with entecavir,M30 antigen and M65 antigen levels were significantly decreased.Patients with early virological response decreased more significantly.M30、M65 had significant correlation with ALT and HBV DNA levels.These showed significantly reduce of the liver inflammation damage.