TIPS for Platinum-Related Porto-Sinusoidal Vascular Disease With Variceal Bleeding

Case-Control Study of Transjugular Intrahepatic Portosystemic Shunt in Treating Platinum-Related Porto-Sinusoidal Vascular Disease With Esophagogastric Variceal Bleeding

Platinum-based compounds are associated with several adverse effects, including Porto-Sinusoidal Vascular Disease (PSVD). Therapeutic strategies for platinum-related PSVD are based on the management of complications seen in cirrhotic portal hypertension. Currently, a combination of non-selective beta-blockers (NSBB) and endoscopic therapies, such as endoscopic band ligation and endoscopic cyanoacrylate injection, is recommended as the primary approach for the secondary prevention of variceal rebleeding, with Transjugular Intrahepatic Portosystemic Shunt (TIPS) reserved for cases in which first-line treatments fail.

However, previous research indicates that endoscopic treatments for the secondary prevention of esophagogastric variceal bleeding show suboptimal efficacy in PSVD patients. In contrast, TIPS has demonstrated comparable rebleeding control but with a lower incidence of liver-related complications and reduced mortality in PSVD patients compared to cirrhotic patients with similar liver function. Based on these findings, the investigators hypothesize that TIPS may be a safer option for this cohort, offering lower rebleeding rates than endoscopic therapy, reduced incidences of hepatic encephalopathy and liver insufficiency, and improved survival rates compared to patients with cirrhosis.

Study Overview

• Status: Active, not recruiting
• Conditions: Porto-Sinusoidal Vascular Disease; Cirrhosis Due to Hepatitis B; Gastric Variceal Bleeding; Esophageal Variceal Rebleeding
• Intervention / Treatment: Procedure: Transjugular intrahepatic portosystemic shunt; Procedure: Endoscopic treatment

Detailed Description

Platinum-based compounds are widely employed in chemotherapy regimens, yet they are associated with a range of adverse effects, most notably Porto-Sinusoidal Vascular Disease (PSVD). PSVD can trigger portal hypertensive complications, including esophagogastric varices and ascites.

Platinum-related PSVD constitutes a variant of intrahepatic presinusoidal portal hypertension, manifesting clinical symptoms analogous to those of liver cirrhosis. There is a scarcity of clinical data pertaining to these patients, and therapeutic strategies should be extrapolated from the management of complications associated with cirrhotic portal hypertension. Presently, the combination of non-selective beta-blockers (NSBB) with endoscopic therapies is advocated as the primary therapeutic modality for the secondary prevention of variceal bleeding, with transjugular intrahepatic portosystemic shunt (TIPS) being employed subsequent to the failure of firstline treatments.

A study by Shanghai Zhongshan Hospital revealed that patients with gastroesophageal variceal bleeding following oxaliplatin-based chemotherapy required more frequent endoscopic treatments to prevent rebleeding compared to those with cirrhosis, and exhibited higher rates of rebleeding and mortality. This suggests the suboptimal efficacy of endoscopic treatments for secondary prevention in this patient population. Additionally, findings from a retrospective study conducted by our institution demonstrated that PSVD patients treated with TIPS for variceal bleeding achieved rebleeding control comparable to cirrhotic patients with similar liver function. However, PSVD patients experienced a lower incidence of liver-related complications, such as overt hepatic encephalopathy and hepatic insufficiency, along with a reduced mortality rate.

Therefore, it is postulated that patients with platinum-related PSVD and esophagogastric varices may experience a lower rebleeding rate following TIPS intervention compared to those receiving endoscopic treatment, without an increased risk of hepatic encephalopathy. TIPS may present a safer treatment option for this cohort, with a reduced incidence of hepatic encephalopathy and liver insufficiency, and improved survival rates compared to patients with cirrhosis.

• Study Type: Observational
• Enrollment (Estimated): 150

Contacts and Locations

Study Locations

• China
  • Shaanxi
    • Xi'an, Shaanxi, China, 710032
      • Air Force Military Medical University

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Non-Probability Sample

Study Population

Patients confirmed diagnosis of Platinum-Related Porto-Sinusoidal Vascular Disease or Cirrhosis Due to Hepatitis B in Xijing Hospital and Shanghai Zhongshan Hospital during Jan 2010 to Jun 2024

Description

Inclusion Criteria:

• Patients aged 18 to 75 years and confirmed diagnosis of Platinum-Related Porto-Sinusoidal Vascular Disease or Cirrhosis Due to Hepatitis B
• Acute esophagogastric variceal bleeding or history of gastroesophageal variceal bleeding episodes
• The patients was received endoscopic variceal ligation/histoacryl injection therapy or TIPS treatment
• At least one postoperative follow-up data

Exclusion Criteria:

• Primary tumor recurrence and metastasis
• Hepatocellular carcinoma or other malignant tumors
• Common contraindications of TIPS
• HIV, AIDS, Serious acute and chronic disease
• Pregnant or breast-feeding woman
• Without postoperative follow-up data

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Experimental group: TIPS for PSVD; This group of PSVD patients received TIPS treatment.TIPS is an artificial channel within the liver that establishes communication between the inflow portal vein and the outflow hepatic vein.	Procedure: Transjugular intrahepatic portosystemic shunt; Transjugular intrahepatic portosystemic shunt (TIPS) is a procedure that uses imaging guidance to connect the portal vein to the hepatic vein in the liver. The TIPS-dedicated stent (Gore, Arizona, USA)was emplaced within the liver and gradually expanded utilizing a balloon with a diameter ranging from 6 to 10 millimeters, aiming for a decrease in portal-venous pressure gradient to less than 12 mmHg or achieve a reduction of 25 to 50% relative to the baseline pressure.
Control group: Endoscopic therapy for PSVD; This group of PSVD patients received endoscopic treatment.Endoscopic treatment includes endoscopic variceal ligation, endoscopic injection sclerotherapy and endoscopic variceal histoacryl injection therapy	Procedure: Endoscopic treatment; Endoscopic variceal ligation, endoscopic injection sclerotherapy, endoscopic variceal histoacryl injection therapy , or a combination of several methods were selected according to the location, size, and shape of the patient's varicose veins.Treatment failure can be transferred to TIPS therapy.
Control Group: TIPS for Cirrhosis Due to Hepatitis B; This group of Cirrhosis Due to Hepatitis B patients received TIPS treatment.	Procedure: Transjugular intrahepatic portosystemic shunt; Transjugular intrahepatic portosystemic shunt (TIPS) is a procedure that uses imaging guidance to connect the portal vein to the hepatic vein in the liver. The TIPS-dedicated stent (Gore, Arizona, USA)was emplaced within the liver and gradually expanded utilizing a balloon with a diameter ranging from 6 to 10 millimeters, aiming for a decrease in portal-venous pressure gradient to less than 12 mmHg or achieve a reduction of 25 to 50% relative to the baseline pressure.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cumulative incidence of clinically significant variceal rebleeding	Recurrent melena or hematemesis resulting in either hospital admission, blood transfusion, drop in hemoglobin of at least 3 g/L, or death within 6 weeks after rebleeding.	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cumulative incidence of hepatic encephalopathy (HE)	HE is classified as covert HE and overt HE	12 months
Cumulative incidence of death	all cause mortality	12 months
Cumulative incidence of patients with other decompensation events	Decompensation was defined as hepatic ascites, abdominal ascites jaundice and infection	12 months
Cumulative incidence of liver function damage		12 months
Cumulative incidence of treatment related complications		12 months

Collaborators and Investigators

• Sponsor: Air Force Military Medical University, China
• Collaborators: Shanghai Zhongshan Hospital
• Investigators: Principal Investigator: Jun Tie, M.D.,Ph.D., Air Force Military Medical University, China

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2024
• Primary Completion (Estimated): October 31, 2024
• Study Completion (Estimated): October 1, 2025

Study Registration Dates

• First Submitted: October 5, 2024
• First Submitted That Met QC Criteria: October 9, 2024
• First Posted (Actual): October 10, 2024

Study Record Updates

• Last Update Posted (Actual): October 15, 2024
• Last Update Submitted That Met QC Criteria: October 10, 2024
• Last Verified: August 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Cardiovascular Diseases; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Liver Diseases; Hepatitis, Viral, Human; Hepadnaviridae Infections; DNA Virus Infections; Hepatitis; Vascular Diseases; Hepatitis B; Hemorrhage
• Other Study ID Numbers: KY20242274-C-1

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
• product manufactured in and exported from the U.S.: No