One-year Efficacy Of Peg-interferon Alpha A Sequential Combinated With Nucleoside Drugs Therapy With High Viral Load And E Antigen-positive Of Hepatitis B

Objective:Research the clinical curative effect of Peg-interferon alpha a(Peg-interferon alpha a-2a and Peg-interferon alpha a-2b) sequential combinated with a kind of Nucleos (t) ide analogues (Lamivudine or Adefovir or Entecavir) on e antigen-positive chronic hepatitis B patients with high serum hepatitis B viral loads(HBVDNA>1×107 IU/ml) compared with Peg-interferon alpha a alone under response-guided therapy. To assess 48 weeks of treatment virological response rate, rate of liver function after often, serological conversion rate and quantitative HBeAg and HBsAg declines etc, and to explore the clinical curative effect of sequential combination therapy, to provide more economic and safe and effective antiviral therapies for clinical refractory chronic hepatitis B patients with high viral load and e antigen-positive.Methods:Research 47 cases of high viral load (HBVDNA> 1×107IU/ml) and e antigen-positive Chronic hepatitis B patients those who aged 19 to 40 years old, hospitalized treated in Liver Diseases Branch of Hangzhou Xixi Hospital (Hangzhou Sixth People’s Hospital) from September 2012 to September 2014,conforms to the diagnostic criteria of "Chinese chronic hepatitis B prevention and treatment guidelines of 2010" and did not receive antiviral and immunomodulatory therapy within 6 months. Patients enrolled herein are Peg-interferon alpha a (Pegasys 180ug or PegIntron 1.0-1.5 mg/kg subcutaneous inject once a week) treatment for 12 weeks, then evaluate response effect according to HBV DNA decline is greater than 2 1g IU/ml or not. In consideration of the patient affordability conditions, poor response (HBV DNA decline≤2 1g IU/ml) were added with an NUCs (entecavir or lamivudine or adefovir) is the combination group (among them Lamy 7 cases, Adelaide 2 cases, entecavir 7 cases), good response (HBV DNA decline> 2 1g IU/ml) were used as a single group, continue to use Peg-interferon alpha a alone (Pegasys 180ug or PegIntron 1.0-1.5 mg/kg subcutaneous inject once a week). All patients were treated for 48 weeks in a row, and during treatment does not use other antiviral drugs and liver-protecting drugs. Detect blood routine, liver and kidney function, blood lipids, blood glucose, stool and urine routine, myocardial enzyme spectrum, electrolyte, hepatitis B three-line, HBVDNA and HBV genotypes, A、C、D、 E、G hepatitis virus, transfusion transmitted virus (TTV), cytomegalovirus (CMV), EV virus (EBV), HIV antibodies, thyroid function, autoantibody series, chest X-ray, electrocardiogram, B ultrasonic indicators before treatment. Exclude patients infected A、C、D、E hepatitis virus, EB virus, cytomegalovirus, human immunodeficiency virus (HIV)etc, and those associated with drug induced liver disease, autoimmune liver disease, alcoholic liver disease, hereditary metabolic liver disease, cirrhosis, etc, and those combined with other serious infections, basic medical diseases, cancer, pregnancy or planned pregnancy in the short term and lactating women, immunosuppressive drugs, alcoholism, drug abuse, etc,and patients with malignant tumor, serious blood diseases, uncontrolled diabetes, thyroid disease,etc, and patients have previous history of mental illness and other drug contraindications, the previously treated with antiviral or immune modulators. Regular monitoring blood routine,liver and kidney function, myocardial enzymes, electrolytes, hepatitis B three-line, HBVDNA, thyroid function, autoantibodies,etc during treatment. All patients are adopted electrochemiluminescence method for quantitative determination of hepatitis B three-line, use 1-2000 operating system by US abbott laboratories, and the kit provided by abbott laboratories. Automatic biochemical analyzer (Model LX-20, Beckman, USA) was used to detect liver function measured. Quantitative determination of serum HBV DNA was measured by quantitative real-time PCR technology, using PE-7900HT real-time PCR instrument type (manufactured by ABI, USA) detection,kit provided by Guangzhou Da An Gene Co., detection of baseline value is 1×103 IU/ml.Observed ALT normalization, HBVDNA negative rate, HBeAg seroconversion, HBsAg seroconversion as well as HBeAg and HBsAg declines of two groups of patients after treating for 48 weeks,and then evaluated antiviral effect of peg-interferon alpha a sequential combinated with a kind of Nucleos (t) ide analogues on e antigen-positive chronic hepatitis B patients with high serum hepatitis B viral loads.Results:47 cases of HBeAg-positive and with high viral load chronic hepatitis B patients are han nationality, of which 35 males and 12 females, aged 19 to 40 years, average age is 28.19±5.49 years. After pegylated interferon a (Pegasys or PegIntron 180ug 80ug) subcutaneous injected once a week for 12 weeks, ALT normalization 27 cases (57.45%), HBV DNA negative 9 cases (19.15%), HBeAg negative 3 cases (6.38%), HBsAg conversion 0 cases among 47 patients. There were 31 patients in 47 cases with HBV DNA decline> 2 1g copies/mL (good response), the 31 patients continued with Peg-IFN treatment alone, as alone group; other 16 cases of patients with HBV DNA decline< 2 1g copies/mL (poor response), combined with the patient’s own economic conditions considering on the basis of a polyethylene glycol interferon plus with a nucleoside drugs [lamivudine (7 cases) or entecavir (7 cases) or adefovir (2 cases)], this is a joint group. Patients of two groups both treated to 24 weeks,16 patients in the joint group, ALT normalization 10 cases (62.50%), HBV DNA negative 9 cases (56.25%), HBeAg negative 0 cases, HBsAg conversion 0 cases and HBeAg decrease> 100 S/CO 15 cases, accounting for 93.75%, HBsAg decline> 31g IU/ml 16 patients (100%);while 31 patients in the alone group,ALT normalization 19 cases (61.29%), HBV DNA negative 13 cases (41.94%), HBeAg negative 4 cases (12.90%), HBeAg seroconversion 3 cases (9.68%), HBsAg conversion 0 cases and HBeAg decrease> 100 S /CO 25 cases, accounting for 80.65%, HBsAg decline> 31g IU/ml 28 cases, accounting for 90.32%, there was no significant difference between the two groups (P values were 0.93557、 0.35137、0.13305、0.19842、0.23179、0.19842). When treated for 48 weeks, there were 1 patient combined with lamivudine turned out HBsAg seroconversion, accounting for 6.25%,2 cases HBeAg seroconversion, accounting for 12.50%,15 patients HBV DNA undetectable, accounting for 93.75%,11 cases of patients with ALT normalization, accounting 68.75%, HBsAg decline> 41g IU/ml 12 patients (80%) of 16 patients in the joint group; 31 patients in the alone group,there were no patients turned out HBsAg negative or seroconversion, HBeAg negative occurred in 5 cases, accounting for 16.13%, and HBeAg seroconversion occurred in 4 cases, accounting for 12.90%;22 patients with undetectable HBV DNA, accounting for 70.97%,26 patients with ALT normalization, accounting for 83.87%, HBsAg decline> 41g IU/ml in 16 cases, accounting for 51.61%, there was no significant difference between the two groups too(P values were 0.15943、0.74054、0.96869、0.07055、0.23005、0.121588). While there were 14 patients occurred HBsAg decline> 500 S/CO in the joint group, accounting for 87.50%,15 patients of that in the alone group, accounting for 48.39%, the difference between the two groups was statistically significant (P=0.008954).Conclusion:Under the guidance of treatment response (RGT),a sequential strategy of peg-interferon alpha a in combination with one nucleoside drug can increase the virological and serological response effect of e antigen-positive chronic hepatitis B patients with high viral load who have poor treatment with peg-interferon alpha a alone, but its long-term effect remains further observation and verification.