14 | Himalaya Livline | Vol 6 | No. 5 | Sep–Dec 2023 Technologic Advances A Novel Liquid Biopsy Approach for the Diagnosis of Nonalcoholic Steatohepatitis and Liver Fibrosis A new liquid biopsy test that uses the peripheral monocyte proteins perilipin (PLIN)-2 and Ras-related protein (RAB)- 14 and specific algorithms to detect nonalcoholic steatohepatitis (NASH) and liver fibrosis has been developed. Conventional liver biopsy is considered the gold standard for the diagnosis of NASH and its progressive forms. However, there is a need for a more reliable and noninvasive diagnostic technique to predict NASH progression. This novel liquid biopsy approach quantifies the PLIN2 protein found on isolated hepatocytes and the RAB14 protein found on hepatic stellate cells in patients with obesity and nonalcoholic fatty liver disease (NAFLD), respectively, and generates algorithms for the accurate detection and staging of NASH and liver fibrosis. Study Design and Procedure This multicenter study included a discovery cohort (n = 100; aged 46.9 ± 10.5 y) from the BRAVES trial and a validation cohort (n = 150; aged 43.4 ± 11.9 y) from the LIBRA trial. Both study groups mostly included women with histologically proven NAFLD or NASH (with or without fibrosis). NASH was detected using the PLIN2 algorithm that included parameters such as mean florescence intensity (MFI), waist circumference (WC), triglyceride, alanine transaminase (ALT), and the presence or absence of diabetes mellitus as covariates. Liver fibrosis was detected using the RAB14 algorithm that included parameters such as MFI, age, WC, high-density lipoprotein cholesterol, plasma glucose, and ALT level as covariates. The study used neural network (NN) classifiers to detect NASH and NASH stages and logistic bootstrap-based regression to measure the accuracy of predicting liver fibrosis. NASH and fibrosis predictions The NN analysis for the detection of NASH using PLIN2 showed an accuracy, sensitivity, and specificity of 93%, 95%, and 90%, respectively, in the discovery cohort and 92%, 88%, and 100%, respectively, in the validation cohort. The detection of liver fibrosis using RAB14 had an accuracy, sensitivity, and specificity of 86.4%, 96.0%, and 45.8%, respectively, in the discovery cohort, and 82.4%, 96.9%, and 34.5%, respectively, in the validation cohort. Both the PLIN2 and RAB14 biomarkers showed better efficiency than the conventional fibrosis-4 score and aspartate transaminase to platelet ratio methods and were also comparable to ultrasound 2-dimensional shear wave elastography. Thus, the detection of NASH severity and liver fibrosis using the PLIN2 and RAB14 algorithms, respectively, was accurate. Quantification of PLIN2 and RAB14 to detect NASH and liver fibrosis, respectively, is scalable to an analytical capacity of up to 800 samples per day. Therefore, PLIN2 and RAB14 have the potential to replace invasive liver biopsy– based histologic assessment for the detection of NASH and liver fibrosis. Source: Angelini G, et al. Gut. 2023;72:392–403.
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