Surrogate Markers of Portal Pressure

VA Connecticut Healthcare System41 enrolled

Overview

This is a prospective longitudinal study that will evaluate if changes (pre and post therapy) in indocyanine green (ICG) retention test and liver stiff ness (LS) and spleen stiffness (SS) as measured by acoustic radiofrequency impulse (ARFI) correlate with changes in portal pressure as determined by the hepatic vein pressure gradient (HVPG) in patients with compensated hepatitis C virus (HCV) cirrhosis undergoing antiviral therapy.

Subjects will be recruited from the outpatient setting of the West Haven VA Medical Center and the Yale Liver Clinic. Subjects between 18-85 years of age with compensated cirrhosis due to chronic hepatitis C virus (HCV) infection who will be starting anti-viral therapy to treat HCV within the next 3 months will be eligible for this study. 33 subjects (assuming 10% loss to follow-up) will be recruited and their participation will last from 6-12 months. The expected duration of the study is 2 years. The primary end point of the study is to correlate the change (from baseline to after completing anti-HCV therapy) in ICG retention test, LS and SS as measured by ARFI with HVPG. After consent has been obtained, subjects will undergo ICG retention test, ARFI imaging and HVPG measurements before and after HCV therapy. Blood samples, demographic and clinical data will be collected before and after HCV therapy. Correlations between changes in HVPG and changes in ICG, LS and SS will be assessed. With 30 patients , we will have 80% power to perform a hypothesis test of the Pearson correlation assuming an observed correlation of 0.70 and a two-sided type I error rate of 0.05.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

DIAGNOSTIC

Masking

NONE

Enrollment

Conditions

Portal Hypertension Cirrhosis

Interventions

HVPGPROCEDURE

HVPG will be performed by placing a placing a 7F venous catheter into a supra-hepatic vein and then advancing a 5F balloon-tipped catheter into the right hepatic vein. Wedged hepatic venous pressure (WHVP) and free hepatic venous pressure (FHVP) will be measured by connection to an external transducer and polygraph (PowerLab, ADInstruments Inc., Colorado Springs, CO). After inflating the balloon catheter, adequacy of the occlusion will be established by injection of a small amount of radiologic contrast medium. Hepatic Venous Pressure gradient (HVPG) will be calculated as the difference between WHVP and FHVP.

Indocyanine Green Retention testDRUG

As decribed in arm descriptions

Liver stiffness measurementDEVICE

Eligibility

Sex: ALLMin age: 18 YearsMax age: 85 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Age 18-85 * HCV infection (HCV-RNA positive) * Compensated cirrhosis will be defined histologically and/or clinically (presence of compatible lab findings (platelet count ≤ 150,000, total bilirubin ≥ 2, serum albumin ≤ 3.5, INR ≥ 1.2) PLUS compatible physical exam features (cutaneous stigmata, gynecomastia in men, or splenomegaly) OR compatible radiological findings (nodular liver surface, splenomegaly, and/or collaterals). (The ultimate confirmation of the diagnosis of cirrhosis will be a baseline HVPG \> 5 mmHg) * Planned anti-HCV therapy in the next 3 months Exclusion Criteria: * Any clinically-evident complication of cirrhosis that defines decompensation : jaundice, ascites, variceal hemorrhage, overt hepatic encephalopathy) * Hepatocellular carcinoma * Co-infection with HBV or HIV * Ongoing alcohol abuse * Occlusive portal thrombosis, * Presence of comorbid conditions conferring a life expectancy\<1 year, history of allergy to iodides, pregnancy

Locations (2)

Yale-New Haven Hospital

New Haven, Connecticut, United States

VA Connecticut Healthcare System

West Haven, Connecticut, United States

Outcomes

Primary Outcomes

Indocyanine Green before and after treatment of hepatitis c

Indocyanine Green will be obtained , this will be conducted before and after treatment for hepatitis c and is measured in mg/dl

Time frame: 2 years

Secondary Outcomes

Spleen stiffness before and after treatment of hepatitis c

Spleen stiffness will be obtained by ARFI, this will be conducted before and after treatment for hepatitis c and is measured in m/sec

Time frame: 2 years

Liver stiffness before and after treatment of hepatitis c

Liver stiffness will be obtained by ARFI, this will be conducted before and after treatment for hepatitis c and is measured in m/sec

Time frame: 2 years

Hepatic venous pressure gradient before and after treatment of hepatitis c

Hepatic venous pressure gradient would be obtained by catheterization of the hepatic vein, this will be conducted before and after treatment for hepatitis c and is measured in mmHg

Time frame: 2 years

Data from ClinicalTrials.gov

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