Diagnostic accuracy of Ultrasound (US) Shear Wave Elastography (SWE) for ‘at-risk NASH’, and for significant liver fibrosis (histologic fibrosis stage equal to or greater than 2), in NAFLD: A protocol for a systematic review and meta-analysis
Creators: name: Sirlin, Claude B.
name: Fladger, Anne
name: Pasek, Alex
name: Weeks, James
name: Samir, Anthony
name: Shabanan, Sedighe Hosseini
name: Rohit Loomba
name: Bain, Paul A.
name: Arinc Ozturk
name: Pierce, Theodore
name: Sherlock, Sarah P.
name: Sertic, Madeleine
name: Middleton, Michael
name: Fowler, Kathryn J.
Publisher: name: Open Science Framework
Year: 2023
Subjects: subject: Medical Specialties
subject: Gastroenterology
subject: Medicine and Health Sciences
subject: Radiology
subject: liver fibrosis
subject: ultrasound
subject: Non-alcoholic steatohepatisis
subject: Non-alcoholic fatty liver disease
subject: shear wave ultrasonography

description: Nonalcoholic fatty liver disease (NAFLD) affects 30% of adults in the United States and is characterized by accumulation of excess triglycerides in the liver (Younossi et al. 2016). NAFLD is also a common problem worldwide, affecting an estimated 1 billion or more people (Loomba et al, 2018). NAFLD can present as simple hepatic steatosis (i.e., nonalcoholic fatty liver (NAFL)), or as nonalcoholic steatohepatitis (NASH); the more advanced subtype, where inflammation, fibrosis, and histologic evidence of hepatocyte injury [e.g., ballooning] can be present. NASH, especially in those who have developed stage 2 or 3 fibrosis, can progress to cirrhosis, end-stage liver disease, liver transplantation, hepatocellular carcinoma, and death (Tong et al, 2022). The identification of patients with NASH and who are at risk for progression to cirrhosis and clinically meaningful adverse outcomes, and the development of effective therapies for these patients are public health priorities. NAFL is asymptomatic, and NASH is asymptomatic until advanced disease is present; these conditions cannot be readily diagnosed, or distinguished from each other clinically, or by routine laboratory testing. Diagnosis and staging of NASH therefore currently rely on liver biopsy with histologic assessment. However, liver biopsy is invasive and painful, and it carries a non-zero risk of catastrophic complication, including death. Further, histologic evaluation of liver biopsy is limited by moderate accuracy, sampling variability due to the small amount of material gathered for examination relative to the size of, and histologic diversity within the liver, and interpretation variability. Although biopsy is being used as the reference standard for diagnosis and staging of NASH in drug development clinical trials, and clinically, it has imperfect accuracy and precision. There is widely-recognized need to aid, improve, or augment liver biopsy acquisition and interpretation, or to develop non-invasive biomarkers to replace liver biopsy, or both. Ultrasound shear wave elastography (SWE) is an imaging based method to assess liver stiffness, a known surrogate marker for liver fibrosis. This imaging technology has emerged recently, but is now widely available clinically. However, there is a critical lack of consensus on diagnostic thresholds which vary widely based on hardware, context of use, and fibrosis level. The primary goal of this review is to synthesize the existing literature on ultrasound shear wave elastography and provide optimal thresholds for the diagnosis of clinically significant liver fibrosis (stage ≥ F2) and at-risk NASH via meta-analysis. SWE is a subset of ultrasound elastography imaging techniques, of which there are four. Strain elastography is a semi-quantitative elastographic technique that generates a relative tissue stiffness map. As this is non-quantitative, it will not be considered for this review. Vibration controlled transient elastography (VCTE), also known as Fibroscan, uses a vibrating probe tip to generate shear waves and ultrasound to measure tissue stiffness. This device does not generate traditional B-mode ultrasound images, is primarily used in gastroenterology clinics, and will not be included in this review. 2D-SWE and point-SWE are the two SWE techniques; they utilize an acoustic radiation force impulse (ARFI), a focused ultrasound pulse, to generate shear waves and high resolution B-mode imaging to estimate liver stiffness. This technology is deployed within radiology imaging centers and is often performed in conjunction with diagnostic ultrasound imaging. The test output is an estimate of liver stiffness reported in kPa (representing Young’s modulus) or m/s (representing shear wave speed). These values are interconvertible algebraically. Determining the diagnostic threshold for these two SWE techniques will be the focus of this review.