Non-invasive Diagnosis of Portal Hypertension in Cirrhosis Based on Metabolomics Technology

April 23, 2023 updated by: Xiaolong Qi, Hepatopancreatobiliary Surgery Institute of Gansu Province

Non-invasive Diagnosis of Portal Hypertension in Cirrhosis Based on Metabolomics Technology(CHESS2207): a Prospective, Multicenter Study

Portal hypertension (PH) is a group of syndromes characterized by abnormal changes in the portal blood flow system, mostly caused by cirrhosis. It is an important factor affecting the clinical prognosis of cirrhotic patients, and its severity determines the occurrence and development of cirrhotic complications.

Clinically, measurement of portal venous pressure directly is highly invasive, and factors such as intra-abdominal pressure changes can interfere with the results, limiting its clinical application. Hepatic venous pressure gradient (HVPG) is the gold standard for assessing PH in cirrhosis. The normal range of HVPG is 3~5 mmHg, and HVPG ≥5 mmHg indicates the presence of PH. AASLD stated that HVPG ≥10 mmHg is defined as clinically significant portal hypertension (CSPH), and the risk of decompensation events is significantly increased at this stage. However, HVPG is an invasive test, which is unacceptable to some patients, such as being expensive, difficult to repeat, and poor patient compliance.

Non-invasive tests for PH include serological tests, anatomical imaging and combination models. Imaging evidence of portal collateral circulation or hepatic blood flow in the portal venous system based on ultrasound Doppler, CT or magnetic resonance imaging techniques can assist to diagnose PH. In addition, elastography techniques such as transient elastography, point shear wave elastography, two-dimensional shear wave elastography and magnetic resonance elastography can be used to measure liver stiffness and spleen stiffness to assess PH. Some biochemical markers are also considered as non-invasive tests for PH. However, the available biomarkers are not yet a substitute for the HVPG accurately, and therefore, there is an urgent need for the development of biomarkers associated with HVPG in clinical practice.

Metabolomics is a method to analyze the concentrated changes of endogenous small molecule metabolites under the combined effect of genetic, biological and environmental factors with the help of various high-throughput technologies. Metabolites are at the end of the biological information flow, and their changes are the ultimate expression of the information from the coordinated action of each group, objectively reflecting the overall changes of the organism. Currently, metabolomics techniques have been widely used in screening biomarkers of liver diseases. Wang et al. applied GC-TOF/MS and UPLC-QTOF/MS to study the urinary metabolomics of patients with hepatitis B cirrhosis and showed that α-hydroxymaurolate, tyrosine-betaine, 3-hydroxyisovaleric acid, knife-serine succinate, estrone and GUDCA were significantly altered in different Child-Pugh grades of cirrhosis, suggesting that these metabolites are potential biomarkers to identify different pathological stages of cirrhosis. Therefore, metabolomics is a reliable and valid tool for biomarker discovery.

In conclusion, this study analyzed significantly altered metabolites in patients with hepatitis B cirrhosis using metabolomics to explore potential differential metabolites that are highly correlated with HVPG. Further, serological biomarkers were identified as an alternative to HVPG testing through model construction and validation.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Portal hypertension (PH) is a group of syndromes characterized by abnormal changes in the portal blood flow system, mostly caused by cirrhosis. It is an important factor affecting the clinical prognosis of cirrhotic patients, and its severity determines the occurrence and development of cirrhotic complications.

Clinically, measurement of portal venous pressure directly is highly invasive, and factors such as intra-abdominal pressure changes can interfere with the results, limiting its clinical application. Hepatic venous pressure gradient (HVPG) is the gold standard for assessing PH in cirrhosis. The normal range of HVPG is 3~5 mmHg, and HVPG ≥5 mmHg indicates the presence of PH. AASLD stated that HVPG ≥10 mmHg is defined as clinically significant portal hypertension (CSPH), and the risk of decompensation events is significantly increased at this stage. However, HVPG is an invasive test, which is unacceptable to some patients, such as being expensive, difficult to repeat, and poor patient compliance.

Non-invasive tests for PH include serological tests, anatomical imaging and combination models. Imaging evidence of portal collateral circulation or hepatic blood flow in the portal venous system based on ultrasound Doppler, CT or magnetic resonance imaging techniques can assist to diagnose PH. In addition, elastography techniques such as transient elastography, point shear wave elastography, two-dimensional shear wave elastography and magnetic resonance elastography can be used to measure liver stiffness and spleen stiffness to assess PH. Some biochemical markers are also considered as non-invasive tests for PH. A study by Buck's team showed that serum inflammatory markers in cirrhotic patients were highly correlated with HVPG. Liver fibrosis index has been proposed for the grading and identification of fibrosis with moderate accuracy. Bone bridging protein levels were also correlated with the degree of liver fibrosis and CSPH. Overall, non-invasive serological markers have great potential in assessing PH. However, the available biomarkers are not yet a substitute for the HVPG accurately, and therefore, there is an urgent need for the development of biomarkers associated with HVPG in clinical practice.

Metabolomics is a method to analyze the concentrated changes of endogenous small molecule metabolites under the combined effect of genetic, biological and environmental factors with the help of various high-throughput technologies. Metabolites are at the end of the biological information flow, and their changes are the ultimate expression of the information from the coordinated action of each group, objectively reflecting the overall changes of the organism. Currently, metabolomics techniques have been widely used in screening biomarkers of liver diseases. Wang et al. applied GC-TOF/MS and UPLC-QTOF/MS to study the urinary metabolomics of patients with hepatitis B cirrhosis and showed that α-hydroxymaurolate, tyrosine-betaine, 3-hydroxyisovaleric acid, knife-serine succinate, estrone and GUDCA were significantly altered in different Child-Pugh grades of cirrhosis, suggesting that these metabolites are potential biomarkers to identify different pathological stages of cirrhosis. Therefore, metabolomics is a reliable and valid tool for biomarker discovery.

In conclusion, this study analyzed significantly altered metabolites in patients with hepatitis B cirrhosis using metabolomics to explore potential differential metabolites that are highly correlated with HVPG. Further, serological biomarkers were identified as an alternative to HVPG testing through model construction and validation.

Study Type

Observational

Enrollment (Anticipated)

500

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • China
    • Shanxi
      • Taiyuan, Shanxi, China, 030000
        • Recruiting
        • The Third People's Hospital of Taiyuan
        • Contact:
          • Ying Guo, M.D.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 75 years (Adult, Older Adult)

Accepts Healthy Volunteers

N/A

Sampling Method

Probability Sample

Study Population

The study intended to include patients with hepatitis B cirrhosis who underwent HVPG examination in the hepatology outpatient/inpatient department as the case group, and healthy controls from the physical examination department, including 50 patients with HVPG <10 mmHg and 50 patients with HVPG ≥10 mmHg in the case group, and 50 healthy controls in the control group.

Description

Inclusion Criteria:

  1. Case group: age 18-75 years old; patients with hepatitis B cirrhosis diagnosed by liver biopsy, or definite clinical data, or imaging findings; undergo HVPG examination; with written informed consent.
  2. Control group: no liver-related diseases, matched with the case group in terms of race, age, sex, and BMI.

Exclusion Criteria:

  1. Other etiologies caused cirrhosis, such as HCV, autoimmune hepatitis, alcoholic, non-alcoholic liver disease, etc;
  2. Patients with severe liver failure, hepatocellular carcinoma, portal vein thrombosis.
  3. Patients with recent blood transfusion due to bleeding.
  4. Patients who are pregnant or lactating.
  5. Patients with endocrine and metabolic diseases such as diabetes mellitus.
  6. Patients treated with anticoagulants, or using drugs that may affect visceral hemodynamics or portal pressure within the last 2 weeks.
  7. Severe coagulation dysfunction, international normalized ratio > 5.
  8. Those who are unable to lie flat or cannot tolerate the procedure.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Cohort
  • Time Perspectives: Prospective

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
Training cohort
Training cohort was set to develop the novel non-invasive model based on metabolomics technology for HVPG.
Procedure: Metabolites and HVPG

HVPG measurement are performed by well-trained interventional radiologists in accordance with standard operating procedures.

All enrolled patients were analyzed for potential differential metabolites using metabolomics.
Validation cohort
Validation cohort was set to validate the novel non-invasive model based on metabolomics technology for HVPG.
Procedure: Metabolites and HVPG

HVPG measurement are performed by well-trained interventional radiologists in accordance with standard operating procedures.

All enrolled patients were analyzed for potential differential metabolites using metabolomics.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Accuracy of the features of metabolomics for assessing portal hypertension in patients with hepatitis B cirrhosis
Time Frame: 12 months
With HVPG as reference standard, the overall diagnostic performance (accuracy) for cirrhosis and portal hypertension of metabolomics was assessed.
12 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Hepatopancreatobiliary Surgery Institute of Gansu Province

Collaborators

Lishui Country People's Hospital
The Third People's Hospital of Taiyuan
Shulan (Hangzhou) Hospital
QuFu People's Hospital
Shenyang Sixth People's Hospital

Investigators

  • Study Chair: Xiaolong Qi, M.D., Portal Hypertension Alliance in China
  • Principal Investigator: Ying Guo, M.D., The Third People's Hospital of Taiyuan
  • Principal Investigator: Jiaojian Lv, M.D., Lishui Country People's Hospital
  • Principal Investigator: Yang Wang, M.D., Shenyang Sixth People's Hospital
  • Principal Investigator: Shirong Liu, M.D., QuFu People's Hospital
  • Principal Investigator: Huadong Yan, M.D., Shulan (Hangzhou) hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

February 15, 2023

Primary Completion (Anticipated)

September 14, 2023

Study Completion (Anticipated)

September 14, 2023

Study Registration Dates

First Submitted

September 20, 2022

First Submitted That Met QC Criteria

September 20, 2022

First Posted (Actual)

September 23, 2022

Study Record Updates

Last Update Posted (Actual)

April 25, 2023

Last Update Submitted That Met QC Criteria

April 23, 2023

Last Verified

April 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CHESS2207

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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