Portosystemic Shunt-associated Pulmonary Hypertension Multi-center Prospective Cohort Study

This study aims to establish a multi-center registry cohort of portosystemic shunt-associated pulmonary hypertension, with the goal of clarifying the epidemiology, clinical features, phenotypic classification, response to targeted therapy, and prognostic outcomes in patients with portosystemic shunt-associated pulmonary hypertension.

Study Overview

• Status: Not yet recruiting
• Conditions: Pulmonary Hypertension; Portosystemic Shunt

Detailed Description

Portosystemic shunt-associated pulmonary hypertension is defined as a condition of abnormal pulmonary hemodynamics resulting from congenital or acquired portosystemic shunts. This clinical entity is common and presents with highly heterogeneous hemodynamic profiles, including pulmonary arterial hypertension, post-capillary pulmonary hypertension, and high-output pulmonary hypertension. Currently, no dedicated cohorts exist for this specific population, and targeted clinical data are lacking. Even for portopulmonary hypertension (PoPH), a more extensively studied subtype, previous studies in East Asian populations have primarily relied on small, single-center retrospective cohorts. Therefore, this study aims to establish a multi-center registry cohort of portosystemic shunt-associated pulmonary hypertension, with the goal of clarifying the epidemiology, clinical features, phenotypic classification, response to targeted therapy, and prognostic outcomes, thereby providing an evidence-based foundation for developing tailored diagnostic and therapeutic strategies for this population.

• Study Type: Observational
• Enrollment (Estimated): 300

Contacts and Locations

• Study Contact: Name: Zhihong Liu, MD, PhD; Phone Number: +86 13269276067; Email: zhihongliufuwai@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

patients with portosystemic shunt-associated pulmonary hypertension

Description

Inclusion Criteria:

1. Age ≥ 18 years.
2. Diagnosis of Portosystemic Shunts:Imaging evidence suggestive of portosystemic shunts (congenital or acquired) or unequivocal clinical signs of portal hypertension (e.g., splenomegaly, varices).

3. Diagnosis of Pulmonary Hypertension (PH):

   • Confirmed by Right Heart Catheterization (RHC): mPAP > 20 mmHg; OR
   • Highly suspected by Echocardiography: Peak TRV > 3.4 m/s or compliant with ESC/ERS guidelines for high probability of PH (Note: RHC is encouraged for all enrolled patients).
4. Signed informed consent and willingness to strictly adhere to the follow-up schedule.

Exclusion Criteria:

1. PH caused by other reasons
2. Hepatocellular carcinoma (HCC) exceeding the Milan criteria.
3. Active extrahepatic malignancy.
4. Transjugular intrahepatic portosystemic shunt (TIPS) placement within the previous month.
5. Pregnancy or lactation.
6. Participation in other interventional clinical trials (drug or device) within the last 3 months.

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
Portosystemic shunt-associated pulmonary hypertension

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical worsening	The rate of clinical worsening during the follow-up period, which is a composite endpoint comprising all-cause death, decline in exercise capacity [defined as a ≥15% reduction in 6-minute walk distance (6MWD) compared with baseline], deterioration in World Health Organization (WHO) functional class, and non-elective hospitalizations for pulmonary hypertension (due to worsening heart failure or initiation of parenteral prostanoids).	Up to 24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline in model for End-Stage Liver Disease (MELD) score	The MELD score is a reliable measure of mortality risk in patients with end-stage liver disease, calculated using serum bilirubin, serum creatinine, and the international normalized ratio (INR). The total score ranges from 6 to 40. Higher scores indicate more severe hepatic impairment and worse prognosis in patients with portosystemic shunt-associated pulmonary hypertension. The change in MELD score from baseline will be evaluated at each specified follow-up visit.	Baseline, Month 12, and Month 24
Change from baseline in Child-Pugh Score	The Child-Pugh score assesses the severity and prognosis of chronic liver disease based on five clinical measures: total bilirubin, serum albumin, prothrombin time (INR), ascites, and hepatic encephalopathy. The total score ranges from 5 to 15, where 5-6 indicates Class A (well-compensated), 7-9 indicates Class B (significant functional compromise), and 10-15 indicates Class C (decompensated). Higher scores represent worse liver function. The change in the total Child-Pugh score from baseline will be reported.	Baseline, Month 12, and Month 24
Listing for or receipt of liver transplant or lung transplant	This measure assesses the time elapsed from study enrollment to the first documented occurrence of a transplant-related event due to the progression of portosystemic shunt-associated pulmonary hypertension. A transplant-related event is strictly defined as either being officially placed on an active waiting list for a liver or lung transplant, or the actual surgical receipt of a liver or lung transplant. The time to whichever event occurs first will be recorded.	Up to 24 months
Initiation or escalation of oral pulmonary hypertension (PH)-targeted therapy	This measure assesses the time elapsed from study enrollment to the first documented initiation or escalation of oral targeted therapy for portosystemic shunt-associated pulmonary hypertension. "Initiation or escalation" is strictly defined as the sequential addition of a new class of oral PH-targeted medication. This encompasses the clinical transition from no PH therapy to oral monotherapy, from monotherapy to double combination therapy, or from double to triple combination therapy. Dose increases of pre-existing oral medications are excluded from this definition.	Up to 24 months

Collaborators and Investigators

• Sponsor: Chinese Pulmonary Vascular Disease Research Group

Study record dates

Study Major Dates

• Study Start (Estimated): April 1, 2026
• Primary Completion (Estimated): April 1, 2031
• Study Completion (Estimated): April 1, 2031

Study Registration Dates

• First Submitted: March 8, 2026
• First Submitted That Met QC Criteria: March 13, 2026
• First Posted (Actual): March 19, 2026

Study Record Updates

• Last Update Posted (Actual): March 19, 2026
• Last Update Submitted That Met QC Criteria: March 13, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Pulmonary Hypertension; Cirrhosis; Portal hypertension; Portosystemic Shunt; POPH
• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Pathologic Processes; Respiratory Tract Diseases; Digestive System Diseases; Lung Diseases; Liver Diseases; Hypertension; Pathological Conditions, Signs and Symptoms; Fibrosis; Hypertension, Portal; Hypertension, Pulmonary
• Other Study ID Numbers: PROSPECT

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