Endo-hepatology

Introduction

Endo-hepatology is broadly defined as the integration of endoscopic procedures within the practice of hepatology. When we first coined this term in 2012, we emphasized that while the GI endoscopist has had endoscopic control of imaging (EUS, ERCP), tissue acquisition (EUS, ERCP), and intervention (EUS, ERCP) as a pancreatico-biliary specialist, the same has not been the case in the liver, where endoscopy has been limited to the diagnosis and treatment of varices. Since then, there has been a groundswell of endoscopic ultrasound (EUS) procedures and technological advancements with diagnostic, prognostic, and therapeutic applications to the liver ( Table 28.1 ). The endosonographer can assess the liver surface (nodular vs. smooth), liver edge (blunted vs. sharp), liver parenchyma (heterogeneity), and even liver stiffness by “palpating” the liver ( Fig. 28.1 ). A recent advancement has been the incorporation of shear-wave elastography (SWE) to the newest EUS processors—enabling quantitative measurements of both liver lobes as well as the spleen. For focal lesion assessment, EUS with contrast enhancement is now available in most countries, including the United States. Moreover, EUS-guided liver biopsy (EUS-bx) has come of age, and EUS-guided portosystemic pressure gradient (PPG) measurement has emerged as a powerful prognostic tool. Taken together, the practice of endo-hepatology offers liver patients a true “one-stop-shop” evaluation consisting of a combination of the following: endoscopic and EUS assessment of portal hypertensive gastropathy and esophageal/gastric varices, EUS-SWE of liver and spleen, EUS-bx of one or both lobes, and EUS-PPG. This chapter will highlight the diagnostic EUS procedures in endo-hepatology. The endo-hepatology therapeutic procedures are covered in Chapter 27 , Endoscopic Ultrasonography-Guided Vascular Interventions.

EUS-guided shear-wave elastography

The accurate staging of fibrosis or cirrhosis is critical to the diagnosis, treatment, and prognosis for patients with chronic liver disease (CLD). However, both laboratory biomarkers of cirrhosis and abdominal imaging suggesting a nodular or cirrhotic liver are often nonspecific and oftentimes misleading. Liver biopsy, the gold standard for diagnosing liver disease and staging fibrosis, has been challenged by the advent of ultrasound-based transient elastography (TE) using Fibroscan and two-dimensional (2D) shear-wave elastography (SWE). The arguments for shifting away from liver biopsy to elastography includes its invasiveness, costliness, sampling error, and the difficulty of monitoring the progression of fibrosis over time. Liver stiffness measurement using transient elastography (TE) has been shown to predict liver-related events and all-cause mortality. It is a noninvasive, swift bedside screening for hepatic fibrosis with an excellent interobserver variability, small sampling error, and good reproducibility.

However, TE has limitations including difficulty in assessing obese patients and in those with ascites, lacking 2D image guidance of the measurement, and the inability for the left side of the liver to be examined. Recent studies have shown that SWE is just as effective or even superior to TE with higher technical success rate and reproducibility. Overall, SWE allows ultrasound imaging to provide quantitative assessment of liver stiffness as an addition to a purely morphological imaging system. MR elastography (MRE) appears to outperform SWE in the detection of advanced fibrosis in nonalcoholic fatty liver disease (NAFLD) on a recent meta-analysis but is limited in its current availability and cost. Finally, controlled attenuation parameter (CAP) score—a semi-quantification of hepatic steatosis during TE—is emerging but requires further validation. Thus far, CAP does not always correlate well with hepatic fibrosis stage on liver biopsy, particularly when the CAP score is high or with an increased body mass index and may not be optimal for differentiating between higher grades of steatosis. ^,

EUS-SWE holds promise, as it facilitates quantitative measure­ments not limited by ascites, abdominal obesity, or interposing structures. ^, In addition, while TE is limited to the right lobe of the liver and displays histological variability between the right and left lobes, ^, EUS-SWE can perform bilobar liver assessment, as well as evaluate spleen stiffness. A recent pilot study of 27 subjects demonstrated the feasibility, safety, and the superiority of EUS-SWE compared to several other noninvasive clinical assessments in predicting hepatic fibrosis stage. EUS-SWE of the left lobe (LL) ≥ 12.5 kPa (compared to <12.5 kPa) was strongly associated with fibrosis stage ≥3 on Lbx (85.7% vs 20%, P = .001). EUS-SWE of the right lobe (RL) ≥12.5 kPa was also strongly associated with fibrosis stage ≥3 on liver biopsy (83.3% vs 40%, P = .035). Overall, EUS-SWE LL measurements were moderately superior but comparable to RL measurements. EUS-SWE LL ≥12.5kPa had the highest combined sensitivity and specificity (85.7%, 80%) in predicting histological stage ≥3 fibrosis, compared to EUS-SWE RL ≥12.5 kPa (83.3%, 69%), clinical cirrhosis (80%, 66.7%), INR ≥1.05 (80%, 50%), EV/GV on EGD (87.5%, 46.2%), APRI >2 (83.3%, 50%), and Fib-4 >3.25(71.4%, 44.4%). Schulman and colleagues computed a liver fibrosis index (LFI) from EUS real-time elastography images (strain elastography), which strongly correlated with abdominal imaging and could distinguish normal, fatty, and cirrhotic-appearing livers. Liver fibrosis index (LFI) greater than 2.56 correlated with METAVIR scores of F4. Transient elastography reading ≥ 12.5 kPa is well associated with stage 3–4 hepatic fibrosis. More studies are needed to determine the appropriate threshold for EUS-SWE in classifying stage 3–4 hepatic fibrosis.

EUS strain elastography can also be a valuable tool in detecting, characterizing, and differentiating between benign and malignant focal liver lesions with sensitivity of 92.5%, specificity of 88.8%, diagnostic accuracy of 88.6%, positive predictive value of 86.7%, and negative predictive value of 92.3%. ^, Benign liver lesions such as hemangiomas presented hue histograms with significantly lower stiffness values than neoplastic lesions such as HCC, cholangiocarcinoma, and metastases. Malignant neoplasms are significantly harder compared to benign lesions and about 100 times stiffer than the surrounding normal parenchyma.

The spleen is the largest lymphatic organ in the human body, is superficially located (similar to the liver), and the splenic vein is directly connected to the portal vein. Therefore, the spleen can provide useful information in assessing liver fibrosis, portal hypertension, and presence of esophageal varices. Several studies have shown that spleen stiffness correlates with liver fibrosis and is helpful in determining the level of fibrosis in the METAVIR scoring system. ^, The spleen can detect subclinical portal hypertension because spleen stiffness increases even when liver elasticity remains unaltered in patients infected with hepatitis B or hepatitis C virus. MRE has also been applied to assess both spleen stiffness (MRE-SS) and liver stiffness (MRE-LS). One retrospective study of 263 patients showed that the MRE-SS showed significant association with esophageal varices whereas MRE-LS did not. Similarly, spleen elastography appears to be superior to liver elastography in the identification and prediction of esophageal varices in those with various CLDs (odds ratio 25.73 vs 9.54, P < .05, pooled sensitivity 88%, and pooled specificity of 78%). Spleen elastography can also be used to diagnose and evaluate other clinical conditions such as biliary atresia after Kasai portoenterostomy, selecting patients for liver transplantation, choosing the best strategy for portal vein reconstruction before liver transplantation, assessing response to treatment for myelofibrosis (spleen stiffness correlates with bone marrow fibrosis), and monitoring of transjugular intrahepatic portosystemic shunt function. Other clinical applications also include nonalcoholic steatohepatitis (NASH), hepatic congestion, inflammation, and hepatic tumors.

The superiority of spleen elastography over liver elastography may be explained by the fact that the spleen is not affected by the disease that is the primary cause of portal hypertension. Therefore, the fact that EUS-SWE can be applied to both liver lobes and spleen, that it is not limited by abdominal fat, and that it can be done simultaneously with other Endo-Hepatology procedures, makes a compelling value proposition. Robles-Medranda and colleagues found that EUS elastography of the liver and spleen were useful for the diagnosis of portal hypertension in patients with cirrhosis. Furthermore, combining EUS elastography parameters for the liver and spleen predicted liver cirrhosis and portal hypertension with high sensitivities and negative predictive values (both >90%).

Technical considerations

We routinely perform EUS-SWE on both right and left lobes of the liver ( Fig. 28.2 A and B) as well as the spleen ( Fig. 28.2 C). The left lobe is imaged through the stomach, and typically there is more respiratory motion, which can create instability during the shear-wave measurement ( Video 28.1 ). One may be tempted to compensate for this by further pressing the transducer against the liver (big wheel up on the echoendoscope). However, any undue compression of the liver by the transducer can result in a falsely elevated E value.

In order to find the “sweet spot” where the transducer is making good acoustic coupling with the liver without actually compressing the liver itself, we typically move the transducer more proximally along the stomach, with minimal elevation of the big wheel. For the right lobe, the most stable and precise measurements can be made by placing the transducer in the second portion of the duodenum, with the big wheel relaxed, left arm down, and imaging liver segments 5 or 6. On the Olympus Arietta 850 console, start by pressing the SWM button. Place the center of the region of interest (ROI) box approximately 1.5 to 2 cm below the liver capsule, and avoid large vessels, ducts, or fluid. Adjust the pressure of the transducer against the liver to optimize imaging while minimizing compression. Press the “Update” button. The system will automatically freeze. Then evaluate the measurements to determine whether they meet the criteria for a high-quality assessment. Each measurement should have a VsN (a reliability index, indicating the percentage of the net amount of effective shear wave velocity) ≥60%. This indicates that at least 60% of the velocity (Vs) values acquired were accepted per the system’s defined criteria. If the SWM is acceptable, unfreeze the image and press Update again. An image will be automatically stored. If the SWM is unacceptable, delete the measurement from the touch screen and begin again. Repeat until 10 acceptable measurements from the same area are achieved. Review your 10 samples on the report page and store an image of the results.