Multiparametric US for Identifying Patients with High-Risk NASH: A Derivation and Validation Study
Sugimoto K, Lee DH, Lee JY, Yu SJ, Moriyasu F, Sakamaki K, et al.
Radiology 2021; 000: 1-10. https://doi.org/10.1148/radiol.2021210046
Non-alcoholic fatty liver disease (NAFLD) is considered the hepatic manifestation of the metabolic syndrome and is defined as the presence of 5% or greater hepatic steatosis in the absence of competing liver disease etiologies, use of drugs causing steatosis or other chronic liver diseases (1).
It encompasses a spectrum of clinical conditions, from simple hepatic steatosis to non-alcoholic steatohepatitis (NASH). Patients with NASH have a higher risk of developing fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). NAFLD is becoming a concerning health problem worldwide and the most common cause of liver disease globally (2).
Liver biopsy is the gold standard for the diagnosis of NASH. Its histological defining features are hepatic steatosis, hepatocellular damage (ballooning degeneration), inflammation, and fibrosis (3). Two previous studies observed that NAFLD with stage 2 or higher fibrosis and liver injury have a particularly high risk to develop complications (cirrhosis and HCC). They identified these patients as having high-risk NASH and proposed them as candidates for pharmacological treatment with anti-inflammatory and anti-fibrotic agents (4,5).
In this study, the authors aimed to identify patients with high-risk NASH using noninvasive methods. This was a retrospective cross-sectional study that analyzed data collected between April 2017 and March 2019 in Japanese patients with NAFLD. Findings were validated in an independent Korean dataset. Patients with suspected NAFLD were included and were evaluated with ultrasonography (US), liver biopsy, and clinical tests. Ultrasonography was performed immediately before liver biopsy, after 6 hours of fasting. The authors chose three US markers to estimate the degree of liver steatosis, fibrosis, and inflammation: liver stiffness (LS), attenuation coefficient (AC), and dispersion slope (DS), respectively. Liver biopsy was performed in all patients to be used as a reference standard, and NASH was defined as the presence of steatosis, hepatocyte ballooning, and lobular inflammation. Each patient underwent standard clinical evaluation with biochemical testing including aspartate aminotransferase (AST), alanine aminotransferase (ALT) levels, and AST-ALT ratio.
Three multivariate regression models for high-risk NASH were built. Model 1 comprised US-based markers (LS, AC, and DS, defined as the LAD-NASH score), Model 2 serum-based markers, and Model 3 US-based and serum-based markers. Model 1 showed the second-highest area under the receiver operating characteristics (AUC) for detection of high-risk NASH, at 0.86 in the derivation study sample and 0.88 in the validation study sample. A dual cut-off approach was used to assess the diagnostic performance of Model 1 in the detection of high-risk NASH in the training cohort. With a cut-off for sensitivity greater than 90%, positive predictive value (PPV) was 69% and negative predictive value (NPV) was 87.5%. With a cut-off for specificity greater than 90%, they were 86.5% and 71.4%, respectively.
The LAD-NASH score resulted useful in both groups to identify patients with high-risk NASH, with a positive predictive value (PPV) of 86.5% and a negative predictive value (NPV) of 87.5% for respectively ruling in and ruling out patients with high-risk NASH among the population of patients with NAFLD. Having been configured to have two thresholds, a rule-in and a rule-out cut-off, the score can be used either as a screening tool or as a diagnostic test.
Using the LAD-NASH score, 59% of patients could have been diagnosed with high-risk NASH without undergoing liver biopsy.
The greatest limitation of this study (and this score) is that 26% of patients were categorized as being in a gray zone beyond PPV and NPV requiring additional, different evaluations to receive the correct diagnosis.
NAFLD is a prominent cause of liver disease. A simple screening and diagnostic tool, that takes advantage of a single, well-diffused, low-cost, non-invasive technique to detect high-risk NASH and therefore patients requiring medical treatment, is promising for the future assessment of this disease.
References:
- Younossi ZM, Koenig AB, Abdelatif D, Fazel Y, Henry L, Wymer M. Global Epidemiology of Nonalcoholic Fatty Liver Disease-Meta-Analytic Assessment of Prevalence, Incidence, and Outcomes. Hepatology 2016; 64(1): 73-84.
- Ekstedt M, Hagström H, Nasr P, Fredrikson M, Stål P, Kechagias S, et al. Fibrosis stage is the strongest predictor for disease-specific mortality in NAFLD after up to 33 years of follow-up. Hepatology 2015; 61(5): 1547–54.
- Hashimoto E, Taniai M, Tokushige K, Etsuko Hashimoto C. Characteristics and diagnosis of NAFLD/NASH. Journal of Gastroenterology and Hepatology 2013; 28(Suppl.4): 64-70.
- Sugimoto K, Moriyasu F, Oshiro H, Takeuchi H, Abe M, Yoshimasu Y, et al. The Role of Multiparametric US of the Liver for the Evaluation of Nonalcoholic Steatohepatitis. Radiology 2020; 296: 532–540.
- Lee DH, Cho E, Bae J, Lee JY, Yu S, Kim H, et al. Accuracy of Two-Dimensional Shear Wave Elastography and Attenuation Imaging for Evaluation of Patients With Nonalcoholic Steatohepatitis. Clin Gastroenterol Hepatol 2021; 19(4): 797-805.
Matilde Bariani is a third-year radiology resident at Policlinico G.B.Rossi, Verona, Italy. She graduated in 2017 in Medicine and Surgery at the University of Verona. She is affiliated to the Associazione Italiana Studio Pancreas (AISP) and European Society of Radiology (ESR). Her interests include pulmonary and gastrointestinal radiology, in particular she focused on the CT assessment of postoperative complications after DCP.
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