Background & aims: Non-alcoholic steatohepatitis (NASH), a subtype of non-alcoholic fatty liver disease (NAFLD) that can lead to fibrosis, cirrhosis, and hepatocellular carcinoma, is characterized by hepatic inflammation. Despite evolving therapies aimed to ameliorate inflammation in NASH, the transcriptional changes that lead to inflammation progression in NAFLD remain poorly understood. The aim of this pilot study was to define transcriptional changes in early, non-fibrotic NAFLD using two independent biopsy-proven NAFLD cohorts.

Methods: We extracted RNA from liver tissue of 40 patients with biopsy-proven NAFLD based on NAFLD Activity Score (NAS) (23 patients with NAS ≤3, 17 with NAS ≥5) and 21 healthy controls, and we compared changes in expression of 594 genes involved in innate immune function. Using plasma from an independent cohort of 67 patients with NAFLD and 15 healthy controls, we validated the gene changes observed using a multiplex protein assay.

Results: Compared to healthy controls, NAFLD patients with NAS ≥5 had differential expression of 211 genes, while those with NAS ≤3 had differential expression of only 14 genes. Notably, osteopontin (SPP1) (3.74-fold in NAS ≤3, 8.28-fold in NAS ≥5) and CXCL10 (2.27-fold in NAS ≤3, 8.28-fold in NAS ≥5) gene expression were significantly upregulated with histologic progression of NAFLD. Plasma osteopontin (SPP1) and CXCL10 are significantly increased in the presence of NAFLD, regardless of histologic grade. In addition, the plasma levels of these two proteins distinguish clearly between the presence or absence of NAFLD (AUC>0.90).

Conclusions: Osteopontin (SPP1) and CXCL10 are upregulated early in non-fibrotic NAFLD and may serve as valuable non-invasive biomarkers.

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乐备实（上海优宁维生物科技股份有限公司旗下全资子公司），是国内专注于提供高质量蛋白检测以及组学分析服务的实验服务专家，自2018年成立以来，乐备实不断寻求突破，公司的服务技术平台已扩展到单细胞测序、空间多组学、流式检测、超敏电化学发光、Luminex多因子检测、抗体芯片、PCR Array、ELISA、Elispot、PLA蛋白互作、多色免疫组化、DSP空间多组学等30多个，建立起了一套涵盖基因、蛋白、细胞以及组织水平实验的完整检测体系。

 
我们可提供从样本运输、储存管理、样本制备、样本检测到检测数据分析的全流程服务。凭借严格的实验室管理流程、标准化实验室操作、原始数据储存体系以及实验项目管理系统，已经为超过3000家客户单位提供服务，年检测样本超过100万，受到了广大客户的信任与支持。