Permission was obtained from the Ethics Committee of Qilu Hospital of Shandong University, China. The date of approval by the ethics committee was 2018-02-12. Given that centers were governmental, participation in our study was completely voluntary, and patients provided written informed consent.
2.2.1 Sample sources
People who participated in a NAFLD screening and physical examination at the health management center, Qilu Hospital of Shandong University from March 2018 to June 2018 with complete information were recruited.
The inclusion criteria for the study were as follows:
⑴ Age 18-55 years.
(2) NAFLD diagnosis based on two of the following three abdominal ultrasonographic findings:
①The near-field echo of the liver was diffuse and stronger than that of the kidney.
② The structure of the intrahepatic duct was not clearly displayed.
③ The far-field echo of the liver gradually attenuated.
(3) Clear consciousness and ability to answer questions correctly and act freely.
(4) Use of a smart phone.
(5) No other Internet-based health management use.
(6) Voluntary participation in this study and provision of informed consent.
The exclusion criteria for the study were as follows:
(1) Alcohol consumption history or equivalent alcohol intake of > 140 g/week for men and > 70 g/week for women;
(2) Viral hepatitis, drug-induced liver disease, total parenteral nutrition, hepatolenticular degeneration, hemochromatosis, autoimmune liver disease, primary sclerosing cholangitis, primary biliary cirrhosis and other specific diseases that can cause fatty liver.
(3) Pregnant, lactating and reproduction-aged women who lack effective birth control.
(4) Patients with unstable angina pectoris, myocardial infarction, stroke or any serious adverse event within the first three months of the study.
(5) The use of any treatment that may affect liver function.
(6) Infectious diseases such as active pulmonary tuberculosis, AIDS or cancer.
(7) Diabetic individuals insulin or hypoglycemic drugs.
(8) Physical disability, mental illness or an inability to provide written informed consent.
(9) Over the past three months or currently taking weight loss drugs or undergoing surgical treatment.
Termination or discontinuation of study:
(1) Participants who cannot attend follow-up or cooperate with the platform management and those lost to follow-up
(2) The subjects who asked to withdraw.
(3) The development of other diseases that may affect the outcome of the patient's treatment.
2.2.2 Sample size calculation
The calculation of sample size was based on the following formulas:
[Please see the supplementary files section to view this formula.]
Considering sampling error of 0.05 and power of 80%, non-response rate of 10.0% and assuming 15% score difference before and after the intervention. 250 patients were calculated as the sample size, and the same number as the control group. Based on the above assumptions, the minimum sample size for this study was calculated to be 500 patients.
2.2.3 Research design
According to the inclusion and exclusion criteria, the research participants were strictly screened. The present study was a randomized, controlled, parallel-group comparison trial, with evaluators blinded to the allocation. The participants were randomly assigned to the routine health education group or the health management platform group, and stratifed by gender. To reduce potential contamination, any couples enrolled in the present study were randomized into the same group. The course was managed by an independent staff member not involved in the study. The patients in the routine health education group received health education management from clinicians according to the American Association for the Study of Liver Diseases (AASLD) the Practice Guidance for the Prevention and Treatment of Non-alcoholic Fatty Liver Disease (2017 edition)[27]. In addition to routine management, the health management platform group also received guidance and support from the health management platform, and the management norms were formulated by the platform expert group. The health management platform was developed on the basis of electronic health records by Beijing Medical Star Company. The Software as a Service (SaaS) mode was mainly adopted. Patient could use mobile phones to login to the patient-side app. Health management platform group members needed to first install the health management app on their mobile phones and receive relevant training. The platform model adopted a unified management of membership by establishing a digitized database to collect the information of the participants, formulate the individual therapeutic schedule for each participant and monitor their conditions. The subjects of the health management platform group were treated for NAFLD for 24 weeks. To encourage participants to complete the platform health management protocols, we offer a 10% discount on medical examination fees. All subjects were required to complete an examination of relevant observation and evaluation indicators and fill in the scale the 24th week after baseline regarding chronic disease management.
The technical roadmap is shown in Figure 1.
In this study, the service flow was divided into three steps: group archiving evaluation, intervention phase planning, and evaluation, providing closed-loop services for the prevention and rehabilitation of NAFLD. After introducing the new management model and service, patients were registered on the health management platform, and the management service package to be introduced was initially selected. The health management content accepted by the members of the platform management team mainly included the following parts:
(1) Establishment of electronic health records.
The collected baseline health information and related examination results were recorded in the health management files to provide the basis for health assessment and health intervention. The related management team includes chief experts, attending doctors, medical consultants, health consultants and so on.
(2) Individualized health assessment management.
According to the data of relevant indicators in health records, the health status of the subjects was evaluated, the main problems of the subjects were analyzed, the disease risks were determined, and the aspects to be improved and the matters needing attention were analyzed. Informing patients of the results of the examination and communicating and explaining them face to face can help the patients understand the significance of health indicators and encourage the subjects to actively manage their own health according to their health records.
(3) Health intervention management
① Dietary intervention management
According to the specific conditions of the study subjects, dietary guidance was provided to encourage the study subjects to change their bad eating habits; eat more vegetables, fruits and grains regularly; strictly control the intake of animal fat and cholesterol; limit sweets; control salt intake; avoid fried food and high-calorie foods; quit smoking and consuming alcohol; and avoid overeating.
②Sports Intervention Management
According to the physical activity level and physical condition of the subjects, the types, frequency and time of exercise were suggested. Adjustment suggestions were made in stages. The subjects were asked to perform aerobic exercises, such as jogging, walking, swimming and so on, at least four times a week for at least 40 minutes each time. The participants were shown various online videos, pictures and text so the subjects could learn and practice by themselves.
③ Cognitive intervention management
Relevant NAFLD text-, film- and television-based guidance and other materials to publicize NAFLD-related knowledge and self-management-related knowledge were provided to participants. The content included the knowledge of NAFLD's etiology, prognosis, treatment principles and preventive measures and enabled the subjects to quickly acquire relevant knowledge using their free time.
④ Care
Once a day, the health platform automatically sends out a form inquiring whether the participant was experiencing any discomfort symptoms. If the patient did not answer, the round was completed. If the answer was yes, the platform automatically sent out the inquiry form for the patient to complete. The content of the inquiry form was determined by the patient's current health status or illness, and the management team checked and completed the inquiry form for timely processing. In addition, weather change care, recent epidemic reminders, exercise, diet, exercise, psychological care, sleep care and so on were systematically promoted.
⑤Appointment
When the patient suffered from diseases, acute episodes of chronic diseases, complications, etc., general practitioners and hepatologists who treat patients with NAFLD determined whether hospitalization was necessary. The doctor confirmed the patients’ applications for appointments regularly according to his or her working schedule.
(4) The patient carried out the plan and uploaded it to receive feedback guidance.
(5) The team of doctors regularly evaluated and adjusted the plan according to the patient's health data.
(6) Follow-up.
Through the management platform for real-time online consultation (words, pictures, voice, etc.), patients carry out online follow-up; understand their diet, exercise, and psychological situation; facilitate timely detection of problems; and provide reminders and corrections. Moreover, according to the frequency of follow-up determined by the health plan, the system automatically sends reminders to patients. The health consultant checks the unfinished follow-up scale at any time and urges patients to complete the scale. This method can establish a closer relationship between the research object and the researchers and reduce the dropout rate.
2.3 Basic demographic information survey
The basic demographic information collected through questionnaires included name, sex, birth date, education level, marital status, employment, lifestyle factors (smoking, alcohol consumption), medication use and disease history.
2.4 Observation and evaluation index
2.4.1 Safety indicators
(1) The blood tests included hemoglobin (Hb), red blood cell count (RBC), leukocyte count (WBC), platelet count (PLT), lymphocyte proportion (Lym), neutrophil ratio (Neu) and other items.
(2) The renal function test included serum creatinine (Scr) blood urea nitrogen (BUN), blood uric acid (BUA) and other indices.
2.4.2 Basic indicators
(1) Weight
The subjects removed their coats and shoes, stood naturally on an automatic body mass index (BMI) measuring stadiometer (BSM370, Korea), kept their body stable, waited for the reading to be stable and read the weight (kg); the data were accurate to 0.1 kg.
(2) Waist circumference (WC)
An anthropometric tape was used to measure waist circumference (WC). WC was measured at the level midway between the lowest rib margin and the iliac crest. During the measurement, the subjects stood upright, relaxed their abdominal, relaxed their arms, stood with their feet together, breathed gently, and did not hold their breath; the data were accurate to 0.1 cm.
(3) Hip circumference (HIPS)
An anthropometric tape was used to measure hip circumference. Hip circumference was measured at the maximum protuberance of the buttocks in a standing position, and the data were accurate to 0.1 cm.
(4) Body mass index (BMI)
Standing height without shoes was measured to the nearest 0.1 cm using an automatic BMI measuring stadiometer (BSM370, Korea) with a precision of 0.1 cm. BMI was calculated as weight (kg) / [height (m)]2, and the data were accurate to 0.01. BMI was categorized as follows: slim, BMI <18.5; normal weight, 18.5 ≤ BMI < 22.9; overweight, 23 ≤ BMI ≤ 27.9; and obesity, BMI ≥ 28.
(5) Blood pressure (BP)
Blood pressure, including systolic blood pressure (SBP) and diastolic blood pressure (DBP). Blood pressure was measured twice in a comfortable quiet sitting position with their right arm supported at the level of the heart by a calibrated mercury Omron electronic sphygmomanometer (model: HBP-1300) after at least 5 minutes rest.
All equipment that used in the study are calibrated. And by the same person to measure, reduce the system error.
2.4.3 Laboratory parameters
The examinees fasted for at least 8 hours; blood was taken from the cubital vein in the morning and was tested immediately after centrifugation with a Hitachi 7600 automatic biochemical analyzer.
(1) Liver function tests included alanine aminotransferase (ALT), aspartate aminotransferase (AST), and AST/ALT values.
(2) Four lipid indicators including triglycerides (TGs), total cholesterol (CHOL), high-density lipoprotein (HDL-C), low-density lipoprotein (LDL-C) were assessed in addition to other parameters.
(3) Fasting plasma glucose (FPG)
All of the above clinical parameters were assessed at the Department of Laboratory Medicine, Qilu Hospital, Shandong University, China.
2.4.4 Body composition
The analysis of body composition was performed using a body composition analyzer (InBody) with multifrequency. Bioelectrical impedance measurement technology can provide detailed analysis reports of human body water, fat and protein components and is the most effective new indicator for analyzing and managing the nutrition and water status of patients. The measured indices included body fat content (kg), skeletal muscle content (kg), and visceral fat area (cm2).
2.4.5 Controlled attenuation parameter (CAP)
The CAP is a system that measures the degree of ultrasound attenuation by hepatic fat using a process based on vibration control transient elastography [28-29]. CAP was measured by one experienced technician using the FibroScan-502 ultrasound diagnostic instrument (Echosens, Paris, France). During the test, the subjects lie on their backs and hold their heads in their right hands. The measurement points are usually between the axillary midline of the right 7-9 rib space and the axillary front line. Keeping the M probe perpendicular to the skin surface and avoiding the structure of large blood vessels, each subject was successfully measured more than 10 times. After the measurement, the instrument automatically took the median of the measurement as the final measurement result. An effective measurement was considered when the ratio of interquartile range to the median of all measurements (IQR/med) was less than 30%. The success rate (number of successful tests/total tests) should be more than 60%.
2.4.6 Quality of life assessment
The Quality of Life and Health Survey Scale (SF-36) is also called the Medical Outcomes Study Short-form 36 (MOSSF-36). General health status parameters designed for population surveys or evaluative studies of health policies are also used to measure outcomes associated with certain diseases in clinical practice and research. The scale includes 36 items, including physiological function (PF), role physical (RP), role emotional (RE), vitality (VT), mental health (MH), social functioning (SF), body pain (BP), general health status (GH) and 8 other categories involving physical and mental health. Each domain was scored on a standardized scale with values ranging between 0 and 100, where 0 represents the lowest, and 100 represents the highest, quality of life.Sf-36 is one of the most commonly used international standardized measurement tools to assess quality of life. The Chinese version of SF-36 has been translated and applied for many years, and its reliability and validity have been verified. In a previous study, the Cronbach's alpha reliability coeffcients ranged between 0.72 and 0.88, and the test‑retest correlation coeffcients ranged between 0.66 and 0.94 [30]. Before using the Chinese version of the SF-36 scale, 32 participants were randomly selected from the included subjects for the preliminary experiment to test the reliability and validity of the SF-36 scale in NAFLD patients. The preliminary results showed that Cronbach's alpha = 0.720, KMO = 0.647, Bartlett sphericity test = 0.000, and three common factors produced by factor analysis could explain 67.67% of the total variation. The overall reliability and validity of the scale were tested. The scale can be used to investigate the quality of life and health status of patients with NAFLD. In this study, eight dimensions of the SF-36 scale were included in the score; the higher the score, the better the quality of life in the corresponding dimensions.
2.5 Quality Control
Participants needed to undergo unified training; after the training, the researchers were assessed, and the consistency of the researchers was tested by the kappa test. Only when kappa > 0.6 could the research be carried out. The participants’ unified criteria for judgment confirm the consistency of the selection of research subjects; the intervention and program; and the consistency, reliability and integrity of the outcome evaluation indicators. The researchers were responsible for monitoring and reducing the rate of missing visits. The research data and summary materials are being managed by the health management center of Qilu Hospital, Shandong University. The center is subordinate to the third class hospital of the government, authenticity and reliability were ensured.
2.6. Statistical analysis
Data were collected and a database was established. SPSS 22.0 software was used to analyze the data. The counting data are expressed as the constituent ratio and rate (%). Metrological data are expressed as the mean ± standard deviation (X± S), and categorized variables are expressed as numbers. According to the specific data type, the corresponding analysis methods were adopted. Measurement data that satisfied both normal distribution and homogeneity of variance were analyzed by a t-test or analysis of variance. If data is not normally distributed, their natural logarithms will be used for further analysis, if the data did not satisfy the requirements, a rank sum test was used. The counting data were tested by the χ2-test or Fisher exact test, and the comparison between groups was performed by one-way ANOVA or Nemenyi test.