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

NCT ID: NCT05551884

Last Updated: 2023-04-25

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

UNKNOWN

Total Enrollment

500 participants

Study Classification

OBSERVATIONAL

Study Start Date

2023-02-15

Study Completion Date

2023-09-14

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

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.

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

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.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Cirrhosis, Liver Portal Hypertension

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Observational Model Type

COHORT

Study Time Perspective

PROSPECTIVE

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

Training cohort

Training cohort was set to develop the novel non-invasive model based on metabolomics technology for HVPG.

Metabolites and HVPG

Intervention Type PROCEDURE

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.

Metabolites and HVPG

Intervention Type PROCEDURE

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.

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

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.

Intervention Type PROCEDURE

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

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.
Minimum Eligible Age

18 Years

Maximum Eligible Age

75 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

The Third People's Hospital of Taiyuan

OTHER

Sponsor Role collaborator

Lishui Country People's Hospital

OTHER

Sponsor Role collaborator

Shenyang Sixth People's Hospital

OTHER

Sponsor Role collaborator

QuFu People's Hospital

INDIV

Sponsor Role collaborator

Shulan (Hangzhou) Hospital

OTHER

Sponsor Role collaborator

Hepatopancreatobiliary Surgery Institute of Gansu Province

OTHER

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Xiaolong Qi

Prof.

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

Xiaolong Qi, M.D.

Role: STUDY_CHAIR

Portal Hypertension Alliance in China

Ying Guo, M.D.

Role: PRINCIPAL_INVESTIGATOR

The Third People's Hospital of Taiyuan

Jiaojian Lv, M.D.

Role: PRINCIPAL_INVESTIGATOR

Lishui Country People's Hospital

Yang Wang, M.D.

Role: PRINCIPAL_INVESTIGATOR

Shenyang Sixth People's Hospital

Shirong Liu, M.D.

Role: PRINCIPAL_INVESTIGATOR

QuFu People's Hospital

Huadong Yan, M.D.

Role: PRINCIPAL_INVESTIGATOR

Shulan (Hangzhou) Hospital

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

The Third People's Hospital of Taiyuan

Taiyuan, Shanxi, China

Site Status RECRUITING

Countries

Review the countries where the study has at least one active or historical site.

China

Central Contacts

Reach out to these primary contacts for questions about participation or study logistics.

Xiaolong Qi, M.D.

Role: CONTACT

+8618588602600

Ruiling He, M.D.

Role: CONTACT

18153674392

Facility Contacts

Find local site contact details for specific facilities participating in the trial.

Ying Guo, M.D.

Role: primary

References

Explore related publications, articles, or registry entries linked to this study.

Wang X, Lin SX, Tao J, Wei XQ, Liu YT, Chen YM, Wu B. Study of liver cirrhosis over ten consecutive years in Southern China. World J Gastroenterol. 2014 Oct 7;20(37):13546-55. doi: 10.3748/wjg.v20.i37.13546.

Reference Type BACKGROUND
PMID: 25309085 (View on PubMed)

Groszmann RJ, Wongcharatrawee S. The hepatic venous pressure gradient: anything worth doing should be done right. Hepatology. 2004 Feb;39(2):280-2. doi: 10.1002/hep.20062. No abstract available.

Reference Type BACKGROUND
PMID: 14767976 (View on PubMed)

Abraldes JG, Sarlieve P, Tandon P. Measurement of portal pressure. Clin Liver Dis. 2014 Nov;18(4):779-92. doi: 10.1016/j.cld.2014.07.002. Epub 2014 Aug 21.

Reference Type BACKGROUND
PMID: 25438283 (View on PubMed)

de Franchis R, Bosch J, Garcia-Tsao G, Reiberger T, Ripoll C; Baveno VII Faculty. Baveno VII - Renewing consensus in portal hypertension. J Hepatol. 2022 Apr;76(4):959-974. doi: 10.1016/j.jhep.2021.12.022. Epub 2021 Dec 30.

Reference Type BACKGROUND
PMID: 35120736 (View on PubMed)

Zhang CE, Niu M, Li Q, Zhao YL, Ma ZJ, Xiong Y, Dong XP, Li RY, Feng WW, Dong Q, Ma X, Zhu Y, Zou ZS, Cao JL, Wang JB, Xiao XH. Urine metabolomics study on the liver injury in rats induced by raw and processed Polygonum multiflorum integrated with pattern recognition and pathways analysis. J Ethnopharmacol. 2016 Dec 24;194:299-306. doi: 10.1016/j.jep.2016.09.011. Epub 2016 Sep 9.

Reference Type BACKGROUND
PMID: 27620661 (View on PubMed)

Wang X, Wang X, Xie G, Zhou M, Yu H, Lin Y, Du G, Luo G, Jia W, Liu P. Urinary metabolite variation is associated with pathological progression of the post-hepatitis B cirrhosis patients. J Proteome Res. 2012 Jul 6;11(7):3838-47. doi: 10.1021/pr300337s. Epub 2012 Jun 7.

Reference Type BACKGROUND
PMID: 22624806 (View on PubMed)

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

CHESS2207

Identifier Type: -

Identifier Source: org_study_id

More Related Trials

Additional clinical trials that may be relevant based on similarity analysis.