MedPath

A New Screening Strategy for Varices

Completed
Conditions
Liver Cirrhosis
Registration Number
NCT02024347
Lead Sponsor
Chinese University of Hong Kong
Brief Summary

Liver cirrhosis is an advanced stage of chronic liver diseases, which is often associated with various complications, namely esophageal and/or gastric varices, ascites, hepatocellular carcinoma (HCC). It is well known that the risk of complications varies even among cirrhotic patients, as those with more advanced disease would have more complications and poorer survival rates. Liver stiffness measurement (LSM) with transient elastography is found useful to identify cirrhotic patients with higher risk of portal hypertension and presence of varices . Recently, spleen stiffness measurement (SSM) with the same machine was found accurate to predict portal hypertension and esophageal varices.

Investigators hypothesized that a new screening strategy guided by LSM and SSM (LSSM) values (LSSM-guided) is non-inferior to conventional strategy in terms of detection rate of clinically significant esophageal and/or gastric varices for patients with liver cirrhosis in an open-labeled randomized controlled trial.

Consecutive patients with compensated liver cirrhosis will be invited for the study. Patients fulfilling the study criteria will be randomized into LSSM arm (upper endoscopy only performed to patients with high LSM or SSM values), and control arm (upper endoscopy performed to all patients). Patients randomized into LSSM arm will undergo transient elastography examination; those with high LSM or SSM results will be referred for upper endoscopy examination for to screen varices. Patients randomized into control arm will be directly referred for upper endoscopy examination.

Detailed Description

Liver cirrhosis is an advanced stage of chronic liver diseases, which is often associated with various complications, namely esophageal and/or gastric varices, ascites, hepatocellular carcinoma (HCC). It is well known that the risk of complications varies even among cirrhotic patients, as those with more advanced disease would have more complications and poorer survival rates. Liver stiffness measurement (LSM) with transient elastography is found useful to identify cirrhotic patients with higher risk of portal hypertension and presence of varices at cross-sectional basis. LSM cutoff values of 17.6 kPa and 21.0 kPa would have the sensitivity ≥ 90% in order to detect patients with hepatic venous pressure gradient (HVPG) above 10-12mmHg , while the presence of varices could be confidently excluded with a liver stiffness below 12.5-19.8 kPa. However, these suggested cutoff values overlap with those for detecting histologic cirrhosis in most chronic liver diseases. Hence there seems no significant additional information provided by LSM regarding screening endoscopy for varices among cirrhotic patients.

Recently, spleen stiffness measurement (SSM) with the same machine was found accurate to predict portal hypertension and esophageal varices. An SSM cutoff value \<41.3 kPa is sensitive and seems able to accurately rule out the presence of varices. This supports a possible screening strategy, reserving upper endoscopy only for patients with an SSM ≥41.3kPa.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
548
Inclusion Criteria
  • Age 18 years or above
  • Known chronic liver diseases
  • Radiological evidence of liver cirrhosis, defined as coarse liver echotexture and/or nodularity & small liver size noted on liver imaging
  • Informed written consent obtained
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Exclusion Criteria
  • Absence of chronic liver diseases (i.e. acute liver diseases in the absence of chronic components e.g. acute hepatitis A)
  • Decompensated liver cirrhosis, i.e. Child's B or C liver cirrhosis
  • Hepatocellular carcinoma
  • Portal vein thrombosis
  • Previous liver surgery
  • Liver transplantation
  • Recent upper endoscopy within last 36 months
  • Recent transient elastography within last 24 months
  • Current use of beta-blockers
  • Known varices of grade II or above diagnosed from previous endoscopic examination, and/or previous history of variceal bleeding
  • Previous endoscopic treatment to varices (e.g. banding ligation, sclerotherapy)
  • Serious concurrent illness (e.g. malignancy) leading to a life expectancy shorter than 6 months
  • Contraindications to transient elastography (e.g. pregnancy, previous pacemaker implantation)
  • Refusal to consent
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Study & Design

Study Type
OBSERVATIONAL
Study Design
Not specified
Primary Outcome Measures
NameTimeMethod
Clinically significant esophageal and/or gastric varicesAt time of upper endoscopy, up to 5 years

Number of participants who develop large varices warranting pharmacological and/or endoscopic therapy according to the indications mentioned below:

* Varices of any size which is actively bleeding;

* Varices of any size identified in the presence of blood in the esophagus and/or stomach;

* Varices of any size with the presence of red-wale signs and/or fibrin plugs;

Secondary Outcome Measures
NameTimeMethod
Variceal bleedingAt last visit, up to 5 years

Number of participants who develop variceal bleeding, the diagnosis of which is made when diagnostic upper endoscopy shows one of the following: active bleeding from a varix, a "white nipple" overlying a varix, clots overlying a varix, or varices with no other potential source of bleeding.

hepatic eventsAt last visit, up to 5 years

Number of participants who develop ascites, spontaneous bacterial peritonitis, hepatorenal syndrome, hepatic encephalopathy, hepatic decompensation to Child's B or C cirrhosis

HospitalizationAt last visit, up to 5 years

Number of participants who are admitted to hospital for emergency medical problems. This exclude hospitalizations which are scheduled electively.

MortalityAt last visit, up to 5 years

Number of participants who die because of any causes.

Trial Locations

Locations (1)

Prince of Wales Hospital

🇭🇰

Hong Kong, Hong Kong

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