Real World Study on the Effect of HBV-DNA High-precision Detection Based Anti-viral Regimen Adjustment on Achieving Complete Virologic Response in Patients With Chronic Hepatitis B.(REACH)
Conditions: Sustained Virologic Response, Hepatitis B, Chronic
Sponsor: The Second Affiliated Hospital of Chongqing Medical University

Study Protocol and Statistical Analysis 
 
A. Study Protocol 
 
1. Research subjects 
The research subjects were patients with CHB receiving ETV or 
second-line NA(LAM/ADV/LdT) who were admitted to The Second Affiliated 
Hospital of Chongqing Medical University and other centers. 
 
2. Research design 
 
 
3. Research methods 
In our hospital, about 150 patients are screened for HBV-DNA every 
day. Therefore, 54 million patients will be tested for HBV-DNA within 
one year, of which 30% are estimated to be HBV-DNA ≥10 IU. These 
patients will be informed to the Department of Infectious Diseases of 
the Second Affiliated Hospital of Chongqing Medical University for 
follow-up, and will be randomly divided into three groups according to 
1:1. Patients in all three groups will be educated about hepatitis B 
virus infection and antiviral treatment, and the treatment regimen will 
be adjusted according to whether their HBV DNA is ≥10 IU/ml or not. 
Patients in group 1: patients with persistant low level HBV DNA (<10 
IU/ml). Patients in group 2: HBV-DNA≥10 IU/ml, receiving HBV-related 
education and being advised by the doctor to change or to add another 
NA. Patients in group 2: patients with persistant HBV DNA (>10 IU/ml) 
but refuse to change the regimen. Patients in group 3: patients with 
persistant HBV DNA (>10 IU/ml) and agree to change the regimen. 
Educational methods include videos, including an introduction to 
hepatitis B virus (disease profile, infection, outcome, HBV infection, 
vertical transmission and other risk factors) for 5 minutes, brochures 
with relevant information and consultations with physicians and nurses. 
All patients with CHB receiving ETV or second-line NA(LAM/ADV/LdT) 
treatment for more than six months to one year will receive HBV-DNA 

detection, and patients with HBV-DNA≥10 IU/ml will be informed and 
recommended to adjust the treatment regimen so that we could obtain 
the actual prevalence of HBV-DNA load < 10 IU/ml in Chongqing HBV 
cohort. We estimated that 30% of the patients had HBV-DNA≥ 10 IU/ml, 
so there were about 16,200 patients had HBV-DNA≥ 10 IU/ml among 54,000 
patients a year. These patients will be diagnosed with LLV and will 
undergo a treatment regimen adjustment, with a recommendation to switch 
to or use a different type of NA for viral treatment. 
 
4. Outcome indexes 
(i) The main index: 
The proportion of patients who received a complete virologic 
response (HBV DNA<10 IU/ml) at 24 weeks after therapy adjustment. 
(ii)The secondary index: 
1.The proportion of patients with complete virologic response (HBV 
DNA<10 IU/ml) at 12 weeks, 48 weeks and 96 weeks after therapy 
adjustment. 
2.The proportion of patients with normal ALT at baseline and at 
each follow-up time point. 
3.Changes of bone and kidney indicators (eGFR, SCr, BMD, etc.) 
compared with baseline at each follow-up time point. 
 
 
B.  Statistical Analysis 
1. Statistical description 
. Whether the measurement data conforms to normal distribution: the 
statistical method is modified or the data is converted when the 
measurement data does not conform to normal distribution, then it is 
managed as normal distribution when the mean and median are close due 
to the large sample size because of the opening test. Outliers: 
Statistical and professional analysis is performed to determine whether 
to keep outliers. Management of missing value in major efficacy 
indicators data: when a major efficacy data is missing in individual 
subjects, the method of filling is determined from a statistical and 
professional perspective. If the case is lost, data from the previous 
measurement shall be transferred. 
. Case analysis of unfinished tests: the reason of lost cases should 
be analyzed one by one. 
. Descriptive statistics: indicating the mean, the standard deviation, 
the maximum, the minimum, the median, the upper and lower quartile (Q1 
and Q3), the confidence interval, the frequency (composition ratio), 
etc. 
2. Statistical inference method 
. The measurement data: T test, paired T test, rank sum test, paired 

rank sum test, correlation analysis was used. The counting data: Chi-
square test, Fisher exact test, etc. The grade data were tested by CMH 
method. 
3. Statistical expression 
. The report is mainly expressed in tables, which are self-explanatory, 
that is, with headings, notes and main statistical indicators. 
. The results of repeated measurements are presented in tables with 
statistical charts for readability. F value and P value of an OVA of 
repeated measurement data are added. 
. Bilateral tests are generally used for statistical tests, and P less 
than or equal to 0.05 is considered to be statistically significant. 
 
4. Statistical software 
SPSS22.0 software will be used for analysis.