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
Antiviral effect of ETV combined with pegylated interferon-α-2a and its effect on hepatitis B virus surface...   893

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