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

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

Interventions

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.

Sponsors & Collaborators

• The Third People's Hospital of Taiyuan

  collaborator OTHER

• Lishui Country People's Hospital

  collaborator OTHER

• Shenyang Sixth People's Hospital

  collaborator OTHER

• QuFu People's Hospital

  collaborator INDIV

• Shulan (Hangzhou) Hospital

  collaborator OTHER

• Hepatopancreatobiliary Surgery Institute of Gansu Province

  lead OTHER

Principal Investigators

• Xiaolong Qi, M.D. · Portal Hypertension Alliance in China

• Ying Guo, M.D. · The Third People's Hospital of Taiyuan

• Jiaojian Lv, M.D. · Lishui Country People's Hospital

• Yang Wang, M.D. · Shenyang Sixth People's Hospital

• Shirong Liu, M.D. · QuFu People's Hospital

• Huadong Yan, M.D. · Shulan (Hangzhou) Hospital

Eligibility

Min Age

18 Years

Max Age

75 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2023-02-15

Primary Completion

2023-09-14

Completion

2023-09-14

Countries

• China

Study Locations