Clinical trial: NCT06278701
Section: Alternatives
Subsections: 8. **Alternative Treatment Options If You Do Not Participate In The Study**

You may choose not to participate in the study, which will have no adverse effect on your access to conventional treatment. At present, the conventional treatment for your health condition is: eat small meals. The subjects eating less and more meals can reduce the postoperative abdominal distension and make it easier to consume the daily body requirement.
Clinical trial: NCT06278701
Section: Confidentiality
Subsections: 14. **Privacy Confidentiality**

Any information and data obtained about you personally during the course of the study will be kept strictly confidential. Your blood sample will be identified by a study number/number rather than your name, and information that identifies you will not be disclosed to members outside the study group unless you have given your permission. All research members are requested to keep your identity confidential. Your files will be kept in a locked cabinet and accessible only to researchers. In order to ensure that the research is carried out in accordance with the regulations, the government administration or the members of the ethics committee may consult the relevant information about your participation in the research unit as required, but they will ensure that your information will not be disclosed to other parties. Although the results of the research may be published, your identity will not be revealed in these publications. The data of this study will be stored in Drum Tower Hospital Affiliated to the School of Medicine of Nanjing University.  
By signing this written informed consent, you consent to the study pharmacist's collection and processing of your personal information for the study (" Study Data "), including your birth date, gender, race, and physical and mental health status, which means that your study data will remain available until your informed consent is withdrawn. If you withdraw your informed consent, your personal data will no longer be used by the research pharmacist, but personal data that was shared prior to the withdrawal of informed consent can still be used.  
Research pharmacists will use the study data to conduct clinical studies. You have the right to request the personal data held by the research pharmacist, and you also have the right to request the correction of inaccuracies in your personal data; You have the right to withdraw informed consent at any time, if you have the above request, please contact the research pharmacist.
Clinical trial: NCT06278701
Section: Participant Responsibilities
Subsections: 3. **Conditions To Be Fulfilled For Participation In Studies/Research Institutes** Inclusion Criteria 1) Age 18-75 Years;|Exclusion Criteria

2) Meet the diagnostic criteria of China's "Guidelines for Diagnosis and Treatment of Primary Liver Cancer (2022 Edition)", clinically diagnosed with primary liver cancer, hospitalized with radical hepatectomy as the main surgical treatment, no indication of metastasis of the tumor to extra-hepatic organs in preoperative tests and examinations, no absolute contraindications to surgery, complete resection of the liver tumor in the operation, and hepatocellular carcinoma confirmed by postoperative pathological diagnosis ; 3.  
Child-Pugh grades A and B;
4) Preoperative Eastern Cooperative Oncology Group Physical Status Score (ECOG-PS) of 0 to 2; 5) The patient is conscious, has normal verbal communication, and is able to cooperate with the relevant examinations; 6) Fully informed about the study and voluntarily signed an informed consent form.  
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1) Failure to meet selection criteria; 2) Nutritional assessment as cachexia; 3) Presence of contraindications to enteral nutrition (EN) or EN intolerance, such as acute gastrointestinal bleeding, intestinal obstruction. (≥grade 3, National Cancer Institute-Common Terminology Criteria for Adverse Events [NCINCI-CTCAE v 5.0]);
4) Simultaneous combination of malignant tumors in other parts of the body; 6) Known refractory metabolic diseases (e.g., poorly controlled diabetes mellitus or fasting glucose ≥10 mmol/L, hyperthyroidism, hypothyroidism, metabolic acidosis);
7) Decreased renal function (defined as serum creatinine Cr level ≥176.8 μmol/L); 8) Intravenous or oral nutritional supplements, such as proteins, amino acids, etc., applied within one month prior to admission to the hospital; 9) Patients with severe stress or severe complications such as respiratory failure with severe cardiac, hepatic, renal and other insufficiencies; 10) Persons with mental and neurological disorders who are unable to cooperate with a physician; 11) Alzheimer's disease, cerebral atrophy, acute stage or sequelae of cerebrovascular disease, cognitive impairment; 12) Previously poor adherence to medication and nutritional counseling; 13) Critically ill and difficult to assess; 14) On the liver transplant waiting list or under consideration for liver transplantation, as such patients may discontinue follow-up before the end of the study; 15) Less than 12 months since last localized treatment (TACE or HAIC or ablative therapy);
16) Other circumstances that the researcher considers inappropriate for participation in the study.  
Specifics of withdrawal from the study/trial: 1) The subject does not wish to continue in the clinical trial and, in accordance with the Declaration of Helsinki and the informed consent form, the subject has the right to withdraw at any stage of the trial, and his/her subsequent treatment and follow-up will not be affected as a result; 2) Disease progression/treatment failure or worsening of the disease (unless the investigator 5) Combined hepatic encephalopathy or definite infection on admission; 3 believes that there is still a potential benefit to be gained by continuing treatment);
3) the occurrence of a serious adverse event that does not improve with optimal medical therapy and is not tolerated and, in the judgment of the investigator, requires termination of treatment; 4) a general deterioration in health or, in the judgment of the Investigator, termination of the study in the best interest of the subject; 5) Use of other nutritional supplements by the subject that are not taken at the prescribed times, or other medications (other than those permitted by the protocol) that, in the judgment of the investigator, would have a greater impact on the efficacy of the treatment; 6) Postoperative pathology suggestive of non-primary or metastatic hepatocellular carcinoma; 7) Patients who did not take more than 7 additional meals before bedtime during the follow-up period.
Clinical trial: NCT06278701
Section: Participant's Rights
Subsections: 12. **Your Rights**

Participation in the study is entirely voluntary. You can withdraw your informed consent at any time without giving a reason. Whether you make a decision to participate or not to participate, it will not lead to bias against you or affect your medical care. If you do not participate in the study or drop out of the study, there are many alternative treatments that you do not have to choose to participate in the study in order to treat your disease. If you need to withdraw from the study, for your safety and objective evaluation of the effects of the drug, please cooperate with the study pharmacist to complete the relevant evaluation and laboratory examination after the study.  
If you have any questions during the study, you can always consult your research pharmacist.
Clinical trial: NCT06278701
Section: Possible Risks, Discomforts, and Inconveniences
Subsections: 9. **Possible Side Effects, Risks, And Discomfort Associated With Study Participation** For The Experimental **Group:**|For The Control Group:|13. **Costs Of Participation In This Study/Study And Treatment In The Event Of A** Research-Related Injury

Your study pharmacist will monitor side effects such as gastrointestinal discomfort caused by extra meals before bed. If you experience any side effects or discomfort during the study, it is important that you report them immediately to your study pharmacist or doctor. The research pharmacist may give you other medications to control side effects. If you or your study pharmacist believe that you cannot tolerate these side effects, late-evening snacks will be stopped completely, and you may withdraw from the study.

Your study pharmacist will monitor for side effects, such as gastrointestinal discomfort, that may occur when you need to supplement whole-protein nutritional preparations if your self-intake is insufficient. If you experience any side effects or discomfort during the study, it is important that you report them immediately to your study pharmacist or doctor. The research pharmacist may give you other medications to control side effects. If you or your study pharmacist determines that you cannot tolerate these side effects, the supplement will be discontinued and you may withdraw from the study.  
About nutrition preparations: Whole-protein enteral nutrition preparations may cause gastrointestinal symptoms such as bloating and diarrhea after taking. In order to prevent the occurrence of the above symptoms, the subject should warm the nutritional preparation in warm water and take it orally. If the above symptoms cannot be alleviated, stop taking it to observe whether it is caused by the eating pattern of late-evening snacks. If the symptoms persist, please inform the study pharmacist in time or seek medical attention nearby.  
About Blood collection: Blood samples will be collected for this study. The blood sample comes from the excess blood sample drawn during your review and will not add additional burden to you. Temporary discomfort and/or bruising may occur during blood drawing.  
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Participating in this study, we will provide you with appropriate nutrition support plan formulation and individualized diet guidance free of charge. The cost of nutritional preparations and review costs need to be paid by you. The specific amount of costs is determined by your illness and cannot be estimated. The review items and nutritional preparations included in this study are all required for the original treatment. For patients in the experimental group, we will only guide your eating pattern and eating frequency; For the 8 control group, we only instruct you on the use of nutritional preparations and your daily diet. No matter which group you choose, there will be no additional cost to you.
Clinical trial: NCT06278701
Section: Procedures
Subsections: 6. **Research/Research Process**|The Experimental **Group Treatment Protocol Is:**|The Control Group Treatment Protocol Is:

This study is a prospective cohort study using the grouping method of patients' wishes. You will learn about the 2 dietary patterns, bedtime meal and regular diet, and then choose to enter the different groups according to your wishes. Patients who volunteer for the bedtime meal diet will be in the experimental group and those who volunteer for the regular diet will be in the control group. Both groups will have dietary counseling and discharge follow-up, with or without the bedtime meal pattern being the difference.

patients were given additional meal (total calories 200-275kcal, protein 11.5g-18g, complex carbohydrates 25-55g) 1h before bedtime. the LES regimen was: ① whole protein type enteral nutrition; ② whey protein powder + bread or cookie. The addition of meals was carried out 1h before bedtime. The dietary regimen of the experimental group will be deducted from the corresponding late-evening snacks intake.  
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(1) Preoperative: ① Patients without nutritional risk: independent intake according to the issued diet program card. ② Patients with nutritional risk: daily oral whole-protein enteral nutrition on the basis of general diet after admission.  
(2) Postoperative: start drinking small amount of water on the 1st postoperative day, over to liquid diet after ventilation, and may over to autonomous semi-liquid diet + oral whole protein enteral nutrition during the day + LES program on the 2nd postoperative day. As the patient's voluntary intake meets 60% of the body's needs, the daytime oral enteral nutrition support can be gradually stopped and the LES program can be continued.  
(3) Discharge: daily intake needs to be on time according to the LES regimen.  
Subsequent night snacks until disease recurrence or gastrointestinal intolerance or the occurrence of other conditions specified in the program that require termination of treatment, whichever occurs first.

no more food 1h before bedtime. (1) Preoperative: same as the experimental group. (2) Postoperative: start drinking small amount of water on the 1st postoperative day, over to liquid diet after ventilation, and can over to autonomous semi-liquid diet + oral whole protein type enteral nutrition during the day on the 2nd postoperative day. As the patient's voluntary intake meets 60% of the body's needs, enteral nutrition support can be gradually stopped.  
(3) Discharge: Doctors judge whether the patients need to continue nutritional support according to their dietary recovery, and if they do, their nutritional supplementation should be completed before 1h before bedtime.  
The process of the entire study is the following flowchart, and the study period amounted to 6 months:  
  
7. **Participation in the study and what you need to do with your cooperation**
provides accurate past medical history and current condition information. Tell the pharmacist in charge of the study that you need to tell your doctor about any health problems you develop during the study, whether you think they are related to your treatment or not.  
Tell the pharmacist in charge of the study about any new drugs, medicines, vitamins, nutritional supplements, or herbs you are taking during the study.  
Please be sure to take your bedtime meal correctly if you are in the experimental group, or if you are in the control group if you need to take a nutritional preparation. Both groups will be visited as required and will be fasting at the time of the visit so that you can review your blood draws.  
During the study period, refer to the issued dietary guidance card intake, to ensure that the body needs daily calories.  
Follow the guidance of the researcher and research pharmacist.  
Feel free to ask if there is anything unclear at any time.
Clinical trial: NCT06278701
Section: Purpose of Research
Subsections: 2. **Research Purpose**

The aim of this study was to use LES to optimize the management of subjects' eating time and frequency with a view to reducing complications and improving clinical outcomes, and to collect blood samples remaining after the subjects' routine review tests in a one-step study to investigate the effects of LES on subjects' metabolic patterns, providing a theoretical basis for the implementation of effective nutritional strategies in clinical practice to promote the subjects' recovery.
Clinical trial: NCT06278701
Section: Voluntary Participation
Subsections: 5. **Is It Mandatory To Participate And Complete This Study?**

Your participation in this study is completely voluntary and if you decide to participate, you will be asked to sign an informed consent form and will be given a copy of this informed consent form. If you take part in this study, you can still ask to leave at any time, and your standard treatment will not be affected if you leave.