EUS Elastography for Predicting Cirrhotic-related Complications
EUS Elastography for Predicting Cirrhotic-related Complications
Evaluation of the tissue stiffness as a surrogate marker of degree of liver cirrhosis has
 gained popularity in recent decades. Current guidelines also advocate the use of Fibroscan®
 machine (EchoSens, Paris, France) to detect any advanced liver fibrosis as represented by
 high liver stiffness, for prediction of varices development.

 Apart from liver stiffness, studies have shown that spleen stiffness (SS) has been proven
 another useful parameter to severity of underlying portal hypertension and liver cirrhosis.
 However, spleen stiffness measurement by Fibroscan® is highly limited by the thickness of
 subcutaneous soft tissue or abdominal wall tissue, especially in obese subjects. It carries
 certain technical difficulty as well due to its deep-seated anatomical position.

 Recently, the technique of endoscopic ultrasound elastography (EUS-E) has been described. It
 can overcome the limitations of Fibroscan by making measurements of liver and spleen
 stiffness through the gastric wall, which has a shorter distance than the abdominal wall. It
 also allows concomitant upper GI tract luminal examination, incorporating both
 esophagogastroduodenoscopy and elastography measurements into one procedure at the same time.
 This research study aims to prospectively study the utility of EUS-E in patients with chronic
 liver diseases, both in terms of diagnostic and prognostic indications for future
 cirrhotic-related complications.
Portal hypertension is a severe consequence of chronic liver diseases and is responsible for
 multiple main clinical complications of liver cirrhosis. Gastroesophageal variceal bleeding
 is one of the notorious causes of cirrhosis-related morbidity and mortality, as a direct
 consequence of portal hypertension. Bleeding is usually major and carries 42% medical
 mortality at 6 weeks. 60% of early deaths and 40% of late deaths were attributable to
 bleeding. Approximately one-third of patients experienced rebleeding within 6 weeks and
 one-third of survivors experienced subsequent bleeds.

 Assessment for portal hypertension is therefore of paramount importance. The gold standard of
 measurement of hepatic venous pressure gradient (HPVG) requires catheterization of the portal
 vein and is rarely performed in daily clinical practice due to its high invasiveness.
 Evaluation of the tissue stiffness as a surrogate marker of degree of liver cirrhosis has
 gained popularity in the recent decade. Transient elastography (TE) is one of the well proven
 tools to obtain liver stiffness measurements, which demonstrates good direct correlation to
 liver histology fibrosis staging. It also has satisfactory diagnostic performance for the
 prediction of clinically significant portal hypertension (HVPG > 10 mmHg) in the setting of
 compensated chronic liver disease or cirrhosis, with an area under receiver operating
 characteristics (AUROC) of 0.93. The Baveno VI criteria is one of the excellent examples to
 utilize TE liver stiffness measurements, all together with consideration of the platelet
 count, to screen out low risk patients for upper endoscopy variceal screening.

 With reference to the basic anatomy, apart from liver stiffness, spleen stiffness (SS)
 becomes another potential quantitative parameter to the severity of underlying portal
 hypertension. A non-inferiority, open-label, randomized controlled trial across two hospitals
 in Hong Kong showed that high SS measurement by TE was independently associated with clinical
 significant varices. It was shown that a SSM cutoff value <41.3 kPa was sensitive and able to
 accurately rule out the presence of varices. Another study from Korea, with the use of
 acoustic radiation force impulse (ARFI) imaging, also demonstrated that SS was significantly
 higher in patients with varices than in those without varices (3.58 ± 0.47 vs 3.02 ± 0.49; P
 < 0.001). Increasing SS was observed in patients with higher grades of varices (No varix,
 3.02 ± 0.49; F1, 3.39 ± 0.51; F2, 3.60 ± 0.42; F3, 3.85 ± 0.37; P < 0.001), as well as in
 patients who experienced variceal hemorrhage than in those who did not (3.80 ± 0.36 vs 3.20 ±
 0.51; P = 0.002).

 The most common way of TE is using the Fibroscan® machine (EchoSens, Paris, France). It is
 done by placement of a machine probe at right intercostal space over the liver parenchyma,
 which delivers a vibration and determines the liver stiffness by measuring the velocity of
 the vibration wave. It is able to measure a volume of approximately 10mm (wide) x 40mm
 (length) at a 25-65mm depth below the skin surface. However, it is highly limited by the
 thickness of subcutaneous soft tissue or abdominal wall tissue, especially in obese subjects.
 The spleen stiffness measurements carry certain technical difficulty as well due to its
 deep-seated anatomical position, particularly when it is not enlarged.

 EUS elastography (EUS-E) makes use of another concept of direct tissue stiffness measurement,
 namely the real-time tissue elastography (RTE). It gauges the oscillation of tissue from
 adjacent vascular pulsation and compression, with the degree of deformation and displacement
 as an indicator of tissue stiffness. The tissue elasticity distribution is then represented
 in color superimposed on the conventional B mode image displayed. It can also be quantified
 in terms of Strain Ratio (SR) and Strain Histogram (SH) by machine calculation. Initially
 developed to differentiate benign soft tissue from malignant tumour, RTE has been used to
 characterize liver fibrosis in chronic liver disease of different aetiologies, as the liver
 is just adjacent to the stomach, which is a common scanningfield in EUS.

 With such, EUS-E may offer a better option for liver and spleen stiffness measurements with
 the following advantages:

 1. EUS is expected to have a higher success rate for LS and SS measurements, with closer
 distance through the gastric wall to the parenchyma. This can overcome the limitations
 of TE in patients with extreme body habitus, thick abdominal wall muscles and also
 normal spleen size.

 2. Forward viewing radial echoendoscope and forward oblique viewing linear echoendoscope
 allow concomitant upper GI tract luminal examination, incorporating both
 oesophagogastroduodenoscopy (OGD) and elastography measurements into one procedure at
 the same time.

 3. EUS can apply Doppler signals to allow detection of "deep" submucosal varices,
 paraesophageal and para-gastric varices that may not be routinely observed during
 conventional endoscopy at luminal view.

 Literature search reveals utilization of other means of TE measurements, such as ARFI and 2-D
 shear wave elastography in SS measurements to predict clinical outcomes, such as variceal
 bleeding. However, there are still no relevant studies on EUS-E in terms of liver and
 stiffness measurements with correlation to development of cirrhotic complications, despite
 its more popular use and availability. Thus, investigators aim to prospectively study the
 utility of EUS-E in patients with chronic liver diseases, both in terms of diagnostic and
 prognostic indications for future cirrhotic-related complications.
Inclusion Criteria:

 -  Patients with radiologic features suggestive of cirrhosis on abdominal imaging studies
 such as transabdominal ultrasound, CT or MRI and indication for variceal screening

 -  Patients with suspected advanced liver fibrosis as detected by Fibroscan

 -  Patients with clinical evidence of hypersplenism

 -  Age > 18 years

 -  Written informed consent available

 Exclusion Criteria:

 -  Patients with features of decompensated cirrhosis, such as history of ascites, prior
 variceal bleeding, hepatic encephalopathy, hepatorenal syndrome

 -  Patients with history of hepatocellular carcinoma

 -  Patients with history of liver transplant or TIPS or shunting surgery

 -  Patients with portal and/or mesenteric vein thrombosis

 -  Moribund patients from terminal illnesses

 -  Patients with terminal malignancy

 -  Contraindications for endoscopy

 -  Unable to provide written informed consent

 -  Pregnancy