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

NCT05551884 | Unknown

• 1 other identifier: CHESS2207
• Study Type: observational
• Target: 500
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Cirrhosis, Liver; Portal Hypertension

Keywords

Portal hypertension; Hepatic venous pressure gradient; Non-invasive diagnostics; metabolomics

Outcome Measures

Primary Outcomes (1)

• Accuracy of the features of metabolomics for assessing portal hypertension in patients with hepatitis B cirrhosis

  With HVPG as reference standard, the overall diagnostic performance (accuracy) for cirrhosis and portal hypertension of metabolomics was assessed.

  12 months

Study Arms (2)

Training cohort

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

Procedure: Metabolites and HVPG

Validation cohort

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

Procedure: Metabolites and HVPG

Interventions

Metabolites and HVPG 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.

Training cohort; Validation cohort

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Age Groups: Adult (18-64), Older Adult (65+)
• 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.

You may qualify if:

• 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.
• Control group: no liver-related diseases, matched with the case group in terms of race, age, sex, and BMI.

You may not qualify if:

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

Sponsors & Collaborators

• Hepatopancreatobiliary Surgery Institute of Gansu Province: lead
• The Third People's Hospital of Taiyuan: collaborator
• Lishui Country People's Hospital: collaborator
• Shenyang Sixth People's Hospital: collaborator
• QuFu People's Hospital: collaborator
• Shulan (Hangzhou) Hospital: collaborator

Study Sites (1)

The Third People's Hospital of Taiyuan

Taiyuan, Shanxi, 030000, China

RECRUITING

Related Publications (6)

• 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.

  PMID: 25309085 BACKGROUND

• 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.

  PMID: 14767976 BACKGROUND

• 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.

  PMID: 25438283 BACKGROUND

• 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.

  PMID: 35120736 BACKGROUND

• 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.

  PMID: 27620661 BACKGROUND

• 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.

  PMID: 22624806 BACKGROUND

MeSH Terms

Conditions

Liver Cirrhosis; Hypertension, Portal

Condition Hierarchy (Ancestors)

Liver Diseases; Digestive System Diseases; Fibrosis; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Xiaolong Qi, M.D.

  Portal Hypertension Alliance in China

  STUDY CHAIR

• 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

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Xiaolong Qi, M.D.

CONTACT

+8618588602600; qixiaolong@vip.163.com

Ruiling He, M.D.

CONTACT

18153674392; 1037039754@qq.com

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof.

Study Record Dates

• First Submitted: September 20, 2022
• First Posted: September 23, 2022
• Study Start: February 15, 2023
• Primary Completion: September 14, 2023
• Study Completion: September 14, 2023
• Last Updated: April 25, 2023

Record last verified: 2023-04

Locations

CN (1)