WFA+M2BP in Evaluation of Portal Hypertension and Clinical Outcome in Patients With Liver Cirrhosis

Portal hypertension is a common complication of chronic liver diseases and is responsible for most clinical consequences of cirrhosis. measurement of the hepatic venous pressure gradient(HVPG) is the gold standard for evaluating the presence and severity of portal hypertension, this technique is considered invasive and is not routinely performed in all centers. Wisteria floribunda agglutinin-positive human Mac-2 binding protein (WFA+-M2BP) is a secreted N-glycoprotein, which has been reported as a novel marker in assessing liver fibrosis.However, the correlation of WFA+-M2BP with HVPG is unclear.The aim of this study was to explore the relationship between WFA+-M2BP and HVPG.

Study Overview

• Status: Unknown
• Conditions: Cirrhosis; Portal Hypertension
• Intervention / Treatment: Drug: Carvedilol

Detailed Description

Portal hypertension is a common complication of chronic liver diseases and is responsible for most clinical consequences of cirrhosis. Accurate assessment of portal hypertension is essential for strategy of treatment and judgement of prognosis. Although measurement of the hepatic venous pressure gradient(HVPG) is the gold standard for evaluating the presence and severity of portal hypertension, this technique is considered invasive and is not routinely performed in all centers. Therefore, it is urgent to explore a noninvasive assessment of portal hypertension.

Wisteria floribunda agglutinin-positive human Mac-2 binding protein (WFA+-M2BP) is a secreted N-glycoprotein, which has been reported as a novel marker in assessing liver fibrosis. Recently, a retrospective study investigated the role of WFA+-M2BP in assessing the degree of liver cirrhosis and predicting mortality. However, the correlation of WFA+-M2BP with HVPG is unclear. And the role of WFA+-M2BP in predicting the clinical outcome of liver fibrosis patients is needed to be further evaluated.

The aim of this study was to explore the relationship between WFA+-M2BP and HVPG, as well as its predictive ability of complication rate, including large varices, bleed status, and ascites, and liver disease-related mortality.

• Study Type: Observational
• Enrollment (Anticipated): 80

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

From June 2017 to March 2018, patients with cirrhosis admitted to either of the two participating hospitals were consecutively enrolled.

Hospitals: Shanghai Changzheng hospital and Shandong Provincial Hospital

Description

Inclusion Criteria:

1. Patients agreed to sign the informed consents
2. Patients aged 18-80 years,males or females
3. Patients with liver cirrhosis was diagnosed by previous liver biopsy or by compatible clinical, biochemical, and ultrasonographic/CT/MRI findings.
4. Patients were not treated with nonselective β-blockers(propranolol or carvedilol ) within previous 3 months

Exclusion Criteria:

1. Uncontrolled hypertension, diabetes or other serious cardiac problems（NYHA class IV）and pulmonary disease
2. Severe renal function injury(serum creatinine≥1.2 fold of upper limits of normal)
3. Conformed or highly suspicious diagnosis of liver malignant tumors or concomitant disease with reduced life expectancy
4. Acute hepatic failure or acute on chronic liver failure(ACLF)
5. Human immunodeficiency virus(HIV) infection
6. Previous portosystemic shunt
7. After liver transplantation
8. Pregnancy and breastfeeding
9. With contraindications of intervention surgery(hypersensitivity to iodinated contrast media, puncture site infection, severe coagulation defects, uncontrolled hyperthyroidism and multiple myeloma)
10. Participated in other drug clinical trails within 3 months
11. The researchers thought it was not suitable for this clinical trail

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

HVPG group; When HVPG > 12 mmHg, patients would be treated with carvedilol at an initial dose of 6.25 mg once-daily that was adjusted over 5-7 days to the maximum tolerated dose, keeping heart rate >55 beats per minute, or up to 12.5 mg/day. After about 8 weeks, the patients treated with carvedilol will received the second HVPG monitoring wether achieved a decrease in HVPG below 12 mm Hg or>20% from baseline.

Drug: Carvedilol; an initial dose of 6.25 mg once-daily that was adjusted over 5-7 days to the maximum tolerated dose, keeping heart rate >55 beats per minute, or up to 12.5 mg/day

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes of portal pressure (PP)	portal pressure (PP) will be estimated from the hepatic venous pressure gradient(HVPG)	3 months
serum WFA+-M2BP levels	serum WFA+-M2BP levels	3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
number of death or liver transplantation	number of death or liver transplantation	up to 1 year
complications of cirrhosis	large varices, bleed status and ascites	up to 1 year

Collaborators and Investigators

• Sponsor: Shanghai Changzheng Hospital
• Collaborators: Shandong Provincial Hospital

Study record dates

Study Major Dates

• Study Start (ANTICIPATED): June 1, 2017
• Primary Completion (ANTICIPATED): March 1, 2018
• Study Completion (ANTICIPATED): December 1, 2018

Study Registration Dates

• First Submitted: June 21, 2017
• First Submitted That Met QC Criteria: June 21, 2017
• First Posted (ACTUAL): June 22, 2017

Study Record Updates

• Last Update Posted (ACTUAL): June 22, 2017
• Last Update Submitted That Met QC Criteria: June 21, 2017
• Last Verified: June 1, 2017

More Information

Terms related to this study

• Keywords: Cirrhosis; Portal Hypertension
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Liver Diseases; Fibrosis; Hypertension; Liver Cirrhosis; Hypertension, Portal; Physiological Effects of Drugs; Adrenergic beta-Antagonists; Adrenergic Antagonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Vasodilator Agents; Protective Agents; Membrane Transport Modulators; Calcium-Regulating Hormones and Agents; Calcium Channel Blockers; Antioxidants; Adrenergic alpha-1 Receptor Antagonists; Adrenergic alpha-Antagonists; Carvedilol
• Other Study ID Numbers: CZXH0021

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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