Study design and subjects
This was an exploratory clinical trial on simple fatty liver disease patients diagnosed at the Health Administration Center of a tertiary hospital in Zhangjiagang City from July to December 2019. All simple fatty liver disease patients diagnosed in the study period were enrolled. This study was approved by the Hospital of Nanjing University of Traditional Chinese Medicine, with the serial number of 2020-5-2. All patients signed the informed consent.
The inclusion criteria were as follows: (1) Aged between 18 and 60; (2) Patients diagnosed with simple fatty liver disease according to ultrasound imaging (3) Basic ability in reading, writing and understanding. The exclusion criteria were: (1) Women during pregnancy or breastfeeding; (2) Patients with anxiety, depression and mental illness history; (3) Patients with motor dysfunction; (4) Patients who were taking liver-protecting drugs and lipid-lowering drugs; (5) Liver function was normal or basically normal, that is, alanine aminotransferase (ALT), aspartate aminotransferase [11], γ-glutamyl transpeptidase (GGT) did not exceed the normal range of 10u/L.
Generally, the diagnostic criteria for NAFLD are most accurately assessed by liver biopsy for evidence of the degree of liver steatosis, liver cell damage, inflammatory necrosis and fibrosis. However, because liver puncture is an invasive operation, with some adverse events, it is not universally recommended for patients with suspected steatosis. Therefore, this study applied ultrasound imaging standards as the diagnostic basis of simple fatty liver disease if item (a) was met and at the same time anyone or two of item (b) or item (c) was met as follows: (a) The echo from the front field of the liver was enhanced, showing a “bright liver”, which was stronger than the echoes from the spleen and the kidney; (b) The echo from the distant field of the liver was weakened; (c) The structure of the intrahepatic biliary tract was unclear [11]. In addition, the following definitions of “non-alcoholic” and “non-alcoholic fatty liver disease” were combined: (1) In the past 12 months, the amount of ethyl alcohol consumed by the patient was less than 210 g per week for men and less than 140 g for women; (2) Diseases such as viral hepatitis, autoimmune hepatitis, hepatolenticular degeneration, congenital lipid atrophy, hypothyroidism, celiac disease and other specific diseases that can lead to fatty liver were excluded; (3) The patients were not taking medicines such as amiodarone, methotrexate, sodium valproate, glucocorticoids; (4) Bullous or bullous dominating steatosis had affected more than 5% of hepatic cells, with or without mild non-specific inflammation [12].
Interventions
The patients were randomized into two groups by the patient’s physical examination numbers through a random number table method. The transtheoretical model group received lifestyle modification based on Transtheoretical Model and Stages of Change, and the control group received routine health guidance and follow-up intervention (described below). To ensure the uniformity of the analysis of the 2 groups of patients, before the start of the study, 3 members of the research team were trained in relation to the unification of the instructions for filling in the scale, the instruction language, and the evaluation methods, and whether the investigators had concealed the grouping of patients. The investigator (without knowing the behavior change stage of the patient) explained the survey questions to the patient one by one, asked the patient to fill it out and retrieve it on the spot. If the patient could not fill it out, the investigator would ask for the patient’s permission and filled it out on their behalf and give them feedback.
For the patients in the transtheoretical model group, a transtheoretical model-oriented lifestyle amendment plan was formulated. The transtheoretical Model and Stages of Change believes that individual behavior changes can be divided into 5 stages [13]: (1) Pre-intention stage: The patient has poor knowledge of healthy lifestyles, is not aware of the harm caused by the unhealthy lifestyles, and has no plan to change within 6 months; (2) Intention stage: The patient has realized the shortcomings in his/her daily lifestyle and plans to change it within 6 months; (3) Preparation stage: The patient has established a goal for changing his/her lifestyle, and occasionally controls diet and strengthens exercise, which has not been regular; (4) Action stage: The patient has been able to observe a healthy lifestyle, but this has been no more than 6 months; (5) Maintaining phase: The patient has gotten through behavioral changes, which means they are strictly abiding by the principles of diet and exercise for more than 6 months. Ten intervention strategies can be implemented corresponding to these 5 stages. Pre-intention stage: (1) Awareness awakening, (2) Vivid relief, (3) Self-efficacy; Intention stage: (4) Self-reassessment, (5) Environmental reassessment; Preparation stage: (6) Self-liberation, (7) Helping relationships; Action stage: (8) Counter-condition; Maintaining phase: (9) Strengthen management, (10) Stimulus control. For these 10 intervention strategies, there are a series of matching intervention measures, which can be modified according to the actual situation during the implementation process. See Supplementary Table 1.
The patient’s behavioral transition stage was assessed in combination with the different performances at each stage of the Transtheoretical Model and Stages of Change. A behavioral change assessment questionnaire was used for evaluation [14], which was developed by the Cancer Prevention and Research Center of the United States and translated into Chinese by Guo Zhiping et al. In order to ensure the uniformity of the survey of the two groups of patients’ scales, the instructions, guiding terms, and evaluation methods were filled in uniformly before the survey. The investigators distributed them to the patients on the spot and explained them one by one. The patients filled them out and returned them directly. If the patients could not fill them out, the investigators consulted the patients, and their relatives filled them out, and checked them back with the patients for confirmation. The content of the questionnaire was “Please tell us your actual status truthfully according to the options”. Before starting the intervention, the definition of each stage was explained to the patient. The investigator evaluated it accordingly and divided the patient into the pre-intent stage group, the intention stage group, the preparation stage group, the action stage group, and the maintaining stage group according to the behavior change stage they are in. During the first 6 months of the study, the evaluation was conducted once every month, and once every 2 months for the next 6 months. Patients were graded as good behavioral changes if transformation of thought and behavior met the criteria for entering the next stage; medium behavioral change if after the intervention, thought and behavior changed only a little and stay at the original stage; and bad behavioral changes if the patient’s behavior regressed instead of being paid attention to. For patients with good behavioral changes, encouragement and affirmation were given, and they proceeded to the next stage in order. For patients who had remained in a stage over two evaluations, the reasons for not progressing were analyzed and interventions were performed again until the patient reached the maintaining stage. Evaluation and grouping ran throughout the entire research stage.
Different intervention measures were implemented for patients at different stages, including WeChat groups, lectures, model demonstration, consultation with an expert, group discussions, peer education, telephone follow-ups, and introductory visits. The research team consisted of 1 expert in gastroenterology, 1 expert in sports medicine, and 1 expert in nutrition, and 5 experts in nursing. All members of the team received training on Transtheoretical Model and Stages of Change related content and implementation methods through lectures, seminars and out-of-office learning.
For patients in the control group, routine health guidance and follow-up intervention were adopted. After the physical examination results were issued, materials relating to healthy lifestyle publicity for fatty liver disease were distributed to the patients, lectures for health education were held, and WeChat groups were organized to give guidance and consultations on disease knowledge, diet types, exercise plans, and emotional psychology. The patients were advised to quit smoking and limit alcohol, maintain a good life schedule and mood. Follow-ups by phone were performed for 12 months, once each month for the first 6 months and once every 2 months in the last 6 months, which were mainly intended to follow the patients’ lifestyles -including their smoking and alcohol habits- and give instructions, and provide help when patients met any difficulties.
Baseline collection
Baseline information of all the patients included gender, age, degree of education, profession, residence, concomitant symptoms of diabetes, impaired fasting glucose/impaired glucose tolerance, and high blood pressure, liver function indexes, and imaging diagnosis were collected after patients’ enrollment.
The diagnostic criteria of diabetes were having typical symptoms of diabetes, plus fasting blood glucose ≥ 7.0mmol/l, or random blood glucose ≥ 11.1mmol/l, or oral glucose tolerance test (OGTT) 2 h blood glucose ≥ 11.1mmol/l, or HbA1c ≥ 6.5%. The diagnostic criteria for impaired fasting blood glucose were fasting blood glucose 6.1 ~ < 7.0mmol/l, OGTT 2 h blood glucose < 7.8mmol/l. Diagnostic criteria of abnormal glucose tolerance: fasting blood glucose < 7.0mmol/l, OGTT 2 h blood glucose 7.8 ~ < 11.1mmol/l. High blood pressure was defined as systolic blood pressure ≥ 140mmHg, diastolic blood pressure ≥ 90mmhg.