Development of a Risk Prediction Model for Immune-Targeted Therapy-Related Diarrhea in Patients With Hepatocellular Carcinoma Based on TCM Constitutional Types: A Prospective Cohort Study

Immune checkpoint inhibitors combined with anti-angiogenic targeted agents have become the first-line standard therapeutic regimen for advanced hepatocellular carcinoma (HCC). Nevertheless, the high incidence rate of therapy-related diarrhea severely impairs patients' quality of life and treatment adherence, and may even result in treatment discontinuation. Current studies mostly focus on symptomatic intervention after diarrhea onset, while few tools are available for upfront risk screening prior to treatment initiation. According to the theory of traditional Chinese medicine (TCM) constitutional types, individuals with different constitutions exhibit discrepant disease susceptibility and drug responses. Based on a prospective cohort design, this study aims to explore the correlation between TCM constitutional types and immune-targeted therapy-related diarrhea in HCC patients, and further construct a risk prediction model integrated with both western medical and TCM indicators.

This study is designed as a multicenter prospective observational cohort study. A total of 350 primary HCC patients receiving combined immunotherapy and targeted therapy at the Affiliated Hospital of Chengde Medical University from January 2027 to December 2028 will be enrolled into the model development cohort. Another 150 patients from Chengde Central Hospital and Chengde Hospital of Traditional Chinese Medicine between January 2029 and January 2030 will be recruited as the external validation cohort. Baseline data will be collected before treatment, including sociodemographic and general clinical information, tumor and treatment-related data, laboratory test results, TCM constitutional assessment, nutritional risk screening, physical function and psychological status evaluation. All participants will be followed up regularly for one year to record the occurrence of diarrhea.

Samples in the development cohort will be randomly divided into a training set and an internal validation set at a stratified ratio of 7:3. Lasso regression will be applied to screen predictive factors, and multivariate Logistic regression will be adopted to establish a nomogram prediction model. Receiver operating characteristic (ROC) curves, calibration curves and decision curve analysis (DCA) will be used to assess the discrimination, calibration and clinical net benefit of the established model, respectively. The independent multicenter data of the external validation cohort will adopt consistent variable criteria, outcome definitions and the prediction model from the development cohort to evaluate the cross-center generalizability, stability and clinical applicability of the model for comprehensive efficacy verification.

The study protocol has been approved by the Medical Ethics Committee of the Affiliated Hospital of Chengde Medical University. Written informed consent will be obtained from all subjects before enrollment. The research findings will be disseminated via academic journal publications, web-based assessment tools and clinical promotion. The established TCM constitution risk screening tool can be directly applied to routine admission assessment in the hepatology department.

Study Overview

• Status: Not yet recruiting
• Conditions: Liver Cancer

• Study Type: Observational
• Enrollment (Estimated): 500

Contacts and Locations

• Study Contact: Name: Liyang Liu; Phone Number: 18232242016; Email: 519151381@qq.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

January 2027 - January 2030: Implementation of immunotherapy combined with targeted therapy for patients with primary hepatocellular carcinoma

Description

Inclusion Criteria:

1. Pathologically or radiologically confirmed primary hepatocellular carcinoma (HCC);
2. Scheduled to receive combined immune checkpoint inhibitor (ICI) and anti-angiogenic targeted therapy;
3. Aged ≥ 18 years, able to complete questionnaire assessment independently;
4. Normal hearing, speaking, reading and writing ability; Voluntary participation and signed written informed consent.

Exclusion Criteria:

1. Pre-existing underlying intestinal diseases such as chronic diarrhea, inflammatory bowel disease (IBD), or intestinal metastasis before enrollment;
2. History of long-term laxative use;
3. Cognitive dysfunction or mental illness that prevents cooperation with questionnaire assessment;
4. Severe multiple organ failure that precludes completion of full follow-up.

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Incidence of diarrhea associated with combined immunotherapy and targeted therapy for liver cancer	one year

Collaborators and Investigators

• Sponsor: Affiliated Hospital of Chengde Medical University

Study record dates

Study Major Dates

• Study Start (Estimated): January 1, 2027
• Primary Completion (Estimated): January 1, 2030
• Study Completion (Estimated): January 1, 2030

Study Registration Dates

• First Submitted: July 22, 2026
• First Submitted That Met QC Criteria: July 27, 2026
• First Posted (Actual): August 3, 2026

Study Record Updates

• Last Update Posted (Actual): August 3, 2026
• Last Update Submitted That Met QC Criteria: July 27, 2026
• Last Verified: July 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Liver Diseases; Liver Neoplasms
• Other Study ID Numbers: CYFYLL2026030

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No