ANTIVIRAL EFFECT OF ETV COMBINED WITH PEGYLATED INTERFERON-Α-2A AND ITS EFFECT ON HEPATITIS B VIRUS SURFACE ANTIGEN AND E ANTIGEN
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Acta Medica Mediterranea, 2020, 36: 889 ANTIVIRAL EFFECT OF ETV COMBINED WITH PEGYLATED INTERFERON-Α-2A AND ITS EFFECT ON HEPATITIS B VIRUS SURFACE ANTIGEN AND E ANTIGEN Guihua Jiang1, Jinwei Guo2, Yanli Dong3, Ran Liu4, Lei Pang3, Zhenzhen Liu1, Chunmei Jiang1, * 1 Department of Infectious Diseases, People’s Hospital of Longhua, Shenzhen, PR China - 2Department of Infectious Diseases, University of Chinese Academy of Sciences Shenzhen Hospital, Shenzhen, PR China - 3Department of Hepatology Oncology, MuDanJiang KANG AN Hospital, Mudanjiang, PR China - 4Department of Non-communicable Liver Diseases, MuDanJiang KANG AN Hospital, Mudanjiang, PR China ABSTRACT Objective: To study the antiviral effect of entecavir (ETV) combined with polyethylene glycol interferon-α-2a (g-IFN-m2a) on chronic hepatitis B (CHB) and the effects of ETV on hepatitis B surface antigen and E antigen. Methods: 84 patients with HBeAg-positive CHB in our hospital were divided into control (n=42) and treatment (n=42) groups according to the random number table method. Patients in the control group were treated with ETV, whereas patients in the treatment group were given ETV and g-IFN-m2a. The levels of HBeAg and HBsAg in serum and the disappearance of both HBsAg/HBeAg and HBeAg /HBeAg serological conversion rates in both groups were compared at 24, 48 and 72 weeks, respectively. Results: The quantitative values of HBeAg and HBsAg decreased in the treatment of the two groups. The decrease of HBeAg and HBsAg in the serum of the treatment group was significantly higher than that of the control group. The serological conversion of HBsAg and HBeAg appeared in the treatment of CHB patients in both groups. The seroconversion rate of the treatment group was better than that of the control group; the HBV DNA conversion rate was significantly higher in the treatment group than in the control group; both treatment and control groups did not show serious or rare complications during the study. Conclusion: The combination of ETV and pegylated interferon-α-2a can significantly reduce the serum levels of HBeAg and HBsAg, and significantly increase the negative rate of HBV DNA. Compared with the single use of ETV, the antiviral effect is more significant. Keywords: Entecavir, pegylated interferon-α-2a, hepatitis B virus surface antigen, E antigen. DOI: 10.19193/0393-6384_2020_2_140 Received November 30, 2019; Accepted January 20, 2020 Introduction the treatment of CHB is mainly anti-viral. In the European Guidelines for the Treatment of Chron- Chronic hepatitis B (CHB) is a chronic inflam- ic Hepatitis B in 2009, it was proposed that HBV matory disease caused by hepatitis B virus (HBV) DNA response is the desired endpoint for the treat- infection and is characterized by liver lesions. It is ment of CHB. Serological conversion of HBeAg a major infectious disease that is widely prevalent is also a primary focus, as well as the disappear- in the world(1). The disease has a high incidence in ance of HBsAg and serological conversion(2). With China and is likely to develop into cirrhosis and pri- the continuous progress of detection technology, mary liver cancer. The occurrence of CHB seriously quantitative detection of HBsAg is indispensable threatens the lives of every patient. In China, there in the treatment of CHB. According to experimen- are approximately 93 million people infected with tal results, the quantification of HBsAg is closely HBV, accounting for 6.64% of the population, of related to HBV replication and indirectly reflects which about 20 million are CHB patients. So far, the level of cccDNA in hepatocytes, particularly in
890 Guihua Jiang, Jinwei Guo et Al HBeAg-positive patients with CHB(3). It has been Average Average Average Male Female found that persistent immune control has replaced Grouping Age (Case) (Case) Course of Disease BMI Value inhibition of viral replication as the main anti-viral Control measure in the continuous exploration of the natural group (n=42) 56.5±19.5 27(64.28%) 15(35.71%) 6.30±0.15 21.12±0.15 history and pathogenesis of CHB. Treatment Academic attention has focused on the quan- group 56.5±19.5 26(61.90%) 18(42.86%) 6.35±0.20 20.15±0.10 (n=42) titative level of HBsAg, and HBsAg clearance has also become an ideal substitute index for the clinical T/χ2 0 0.051 1.296 1.079 cure of CHB. To provide more effective treatment measures p >0.05 >0.05 >0.05 >0.05 for patients with chronic hepatitis B, improve the Table 1: Comparison of clinical data for both groups of clinical efficacy of CHB treatment, reduce the rate patients with hepatitis B. of disease development, improve the quality of life of patients and reduce the mortality of patients, our Method hospital observed the antiviral effects of combined The control group was given oral entecavir use of ETV and pegylated interferon-α-2a on HBV tablets (Jiangsu Zhengda Tianqing Pharmaceutical and the effects of surface antigen, anti-E, HBV Group Co. LTD production, specifications 0.5 mg/ DNA and the original DNA in this study. tablets) once a day, 0.5 mg each time. The treatment period was 72 weeks. Materials and methods The treatment group took entecavir tablets once a day, 0.5 mg each time, and injected with pe- General information gylated interferon-α-2a subcutaneously (produced Eighty-four patients with HBeAg-positive by Shanghai Roche Pharmaceutical Co. LTD, with CHB in our hospital met the diagnostic criteria of the specifications of 180 μg/ 0.5 mL/piece), 180 μg/ CHB in the Guidelines for the Prevention and Treat- time, once a week, for 72 weeks. During the treat- ment of Chronic Hepatitis B (2015 edition). ment period, blood routine and liver function were The history of CHB was clear, and the course checked regularly, and if abnormalities occurred, of disease was more than half a year. Lamivudine, timely treatment was given. Telbivudine and Adefovir were used alone in the past. Emergence of drug resistance; HBV DNA Observation indicators negative rebound, viral load increased by 1log10 • HBV DNA was measured using the CAP/ copies·mL-1 than before treatment or HBV-DNA CTM system (Roche Molecular Systems Inc.), and was higher than 4log10 copies·zAmL-1 during drug the negative rate of HBV DNA was calculated ac- treatment, and not due to poor compliance, and con- cording to the HBV DNA value in both groups of firmed by drug resistance in p-zone; Patients with patients with CHB. alanine aminotransferase (ALT) or aspartate ami- • Quantitative values of HBeAg and HBsAg in notransferase (AST) values approximately 2-fold the serum of patients before and after treatment were higher than normal values. detected by ELISA (Abbott Company's 12 000 SR There were no other serious lesions in the en- Immunoluminescence Detection System). tire body(4). Eighty-four patients with CHB were • HBeAg disappearance/HBeAg serological randomly divided into treatment and control groups. conversion rates and HBsAg disappearance/HBsAg There were 27 males and 15 females in the control serological conversion rates were calculated accord- group, aged 37-76 (average 56.5±19.5) years, with ing to quantitative values. an average course of disease of 6.3±1.5 years and Evaluation criteria(5): average BMI value of 21.12±0.15; 26 males and 18 Virologically effective, serum HBV DNA level females were in the treatment group, aged 37-76 below 500 copies/ml and negative for HBV DNA. (average 56.5±19.5) years, with an average course of disease of 6.35±1.5 years and BMI values be- Statistical method tween 21.15±0.10. The SPSS17.0 software package was used for There was no significant difference in age, sex, statistical analysis. A χ2 test was used to compare BMI value and course of disease between the two the counting data, mean ± standard deviation (x̅±s) groups (P>0.05). was used to express the results of measurement data,
Antiviral effect of ETV combined with pegylated interferon-α-2a and its effect on hepatitis B virus surface... 891 Ridit test was used to compare the grade data, and HBeAg disappearance/HBeAg seroconver- a t-test was used to compare the measurement data. sion rate, HBsAg disappearance/HBsAg serocon- Results were considered to have statistical signifi- version rate and HBV DNA negative rate in both cance if P0.05). After treatment, HBeAg disappearance/ There was no significant difference in serum HBeAg serological conversion rate and HBsAg HBsAg level between the two groups (P>0.05). Af- disappearance/HBsAg serological conversion rate ter treatment, the serum HBsAg level of the patients in the treatment group was higher than those in the with CHB in the treatment group continued to de- control group. The difference was statistically sig- cline, and was significantly lower than that in the nificant (P
892 Guihua Jiang, Jinwei Guo et Al Incidence thesis, and had a good follow-up effect. China has Headache Nausea and Abdominal Muscle Malaise Grouping vomiting pain pain and fatigue of adverse reactions approved the use of pegylated interferon-α-2a in the Treatment treatment of CHB, and it has become the first-line group (n=42) 1(2.38%) 3(7.14%) 0(0%) 0(0%) 1(2.38%) 5/42 of anti-HBV drugs. Domestic studies have illustrat- ed that entecavir combined with pegylated interfer- Control group (n=42) 1(2.38%) 0(0%) 3(7.14%) 1(2.38%) 3(7.14%) 8/42 on-α-2a in the treatment of CHB has a good effect, can effectively improve the level of liver function, χ2 0.819 delay the development of the patient's condition, and P
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