A Multicenter Prospective Clinical Cohort Study on the Pathogen Spectrum of Severe Hepatitis (Liver Failure) Complicated With Infection

The goal of this observational study is to expound the population and characteristics of pathogenic microorganisms with co-infection, draw the pedigree of pathogenic microorganisms, and evaluate its influence on disease outcome in patients with severe hepatitis (liver failure). The main questions it aims to answer are:

• Mapping of infectious agents in patients with severe hepatitis (liver failure)
• Constructing early warning predictive models to explore how to give an individualized regimen of integrated immune function.

Study Overview

• Status: Not yet recruiting
• Conditions: Liver Failure

Detailed Description

Liver failure is a clinical syndrome caused by a large number of necrotic hepatocytes leading to severe liver function damage, with jaundice, coagulation dysfunction and hepatic encephalopathy as the main manifestations, which can be caused by a variety of reasons, and the liver failure caused by Hepatitis B Virus (HBV) is the first one in our country, which accounts for about 80% of the cases. Through the "Eleventh Five-Year Plan" to "Thirteenth Five-Year Plan" national scientific and technological major special projects, the death rate of patients with early and middle stage of severe hepatitis B has been significantly reduced, but the death rate of patients with advanced stage is still as high as about 60%, especially when liver failure is combined with other complications, such as This study focuses on the impact of secondary infections on the clinical prognosis of severe hepatitis (liver failure), and intends to establish a prospective, multi-center clinical cohort of secondary infections in liver failure, map the infectious pathogens, correlate the basic immune status with the characteristics of the pathogen profile of the secondary infections, and establish a monitoring and early-warning system of secondary infections, so as to explore safe and effective treatment modalities. To further reduce the mortality rate of liver failure.

• Study Type: Observational
• Enrollment (Estimated): 2000

Contacts and Locations

• Study Contact: Name: Jiajia Chen; Phone Number: +8615967109232; Email: Jiajiatale0@zju.edu.cn

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Non-Probability Sample

Study Population

Patients with severe viral hepatitis (liver failure) who met the inclusion and exclusion criteria and were hospitalized in the First Hospital Affiliated to Zhejiang University School of Medicine, Beijing Ditan Hospital Affiliated to Capital Medical University, Beijing You'an Hospital Affiliated to Capital Medical University, Huashan Hospital Affiliated to Fudan University, and Qilu Hospital of Shandong University.

Description

Inclusion Criteria:

1. Patients agreed to participate in the study and signed an informed consent form;
2. Sex is not limited and age is 18-70 years old;
3. HBsAg positive for more than 6 months, or hepatitis E IgM positive, or hepatitis E RNA positive;
4. Progressive deepening of jaundice in a short period of time (serum total bilirubin greater than 10 times the upper limit of normal or rising ≥17.1 umol/L per day);
5. Sgnificant bleeding tendency with PTA ≤ 40% and exclusion of other non-hepatic factors.

Exclusion Criteria:

1. Patients with severe hepatitis caused by other non-hepatophilic viral infections;
2. Patients who were considered by the investigator to be unsuitable for participation in the study.

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Occurrence of secondary infections in patients with severe viral hepatitis (liver failure) at 4 weeks, including site of infection and pathogen of infection.	Site of infection, pathogen results such as blood or body fluid pathogen cultures or Next-generation sequencing(NGS) results.	4 weeks
quick SEPSIS RELATED ORGAN FAILURE ASSESSMENT(qSOFA) at 4 weeks	qSOFA consists of 3 items: altered state of consciousness, systolic blood pressure ≤ 100 mmHg, and respiratory rate ≥ 22 respirations/min. 2 or more items, i.e., a qSOFA score of ≥ 2, are considered to be suspicious for sepsis.Higher qSOFA scores are associated with a higher risk of patient death.	4 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Occurrence of secondary infections in patients with severe viral hepatitis (liver failure) at 8 weeks, including site of infection and pathogen of infection.	Site of infection, pathogen results such as blood or body fluid pathogen cultures or NGS results.	8 weeks
Occurrence of secondary infections in patients with severe viral hepatitis (liver failure) at 12 weeks, including site of infection and pathogen of infection.	Site of infection, pathogen results such as blood or body fluid pathogen cultures or NGS results.	12 weeks
qSOFA score at 8 weeks	qSOFA consists of 3 items: altered state of consciousness, systolic blood pressure ≤ 100 mmHg, and respiratory rate ≥ 22 respirations/min. 2 or more items, i.e., a qSOFA score of ≥ 2, are considered to be suspicious for sepsis.Higher qSOFA scores are associated with a higher risk of patient death.	8 weeks
qSOFA score at 12 weeks	qSOFA consists of 3 items: altered state of consciousness, systolic blood pressure ≤ 100 mmHg, and respiratory rate ≥ 22 respirations/min. 2 or more items, i.e., a qSOFA score of ≥ 2, are considered to be suspicious for sepsis.Higher qSOFA scores are associated with a higher risk of patient death.	12 weeks

Collaborators and Investigators

• Sponsor: Zhejiang University
• Collaborators: Beijing YouAn Hospital; Beijing Ditan Hospital; Huashan Hospital; Qilu Hospital of Shandong University
• Investigators: Principal Investigator: Jiajia Chen, Zhejiang University

Study record dates

Study Major Dates

• Study Start (Estimated): March 1, 2024
• Primary Completion (Estimated): November 1, 2026
• Study Completion (Estimated): November 1, 2026

Study Registration Dates

• First Submitted: February 14, 2024
• First Submitted That Met QC Criteria: February 14, 2024
• First Posted (Actual): February 22, 2024

Study Record Updates

• Last Update Posted (Estimated): March 4, 2024
• Last Update Submitted That Met QC Criteria: March 1, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: cohort study; Severe hepatitis; Pathogen pedigree of infection
• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Diseases; Liver Failure; Hepatic Insufficiency; Infections; Hepatitis
• Other Study ID Numbers: 2023YFC2308802-01

Drug and device information, study documents

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